Reconstructing population exposures to environmental chemicals from biomarkers: challenges and opportunities.

Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101262796 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-064X (Electronic) Linking ISSN: 15590631 NLM ISO Abbreviation: J Expo Sci Environ Epidemiol Subsets: MEDLINE

Original Publication: New York, NY : Nature Pub. Group, c2006-

Biopharmaceutics*/methods ; Biopharmaceutics*/statistics & numerical data; Biomarkers/*analysis ; Environmental Exposure/*analysis ; Environmental Pollutants/*administration & dosage; Algorithms ; Bayes Theorem ; Biomarkers/chemistry ; Biomarkers/urine ; Environmental Pollutants/chemistry ; Environmental Pollutants/pharmacokinetics ; Environmental Pollutants/urine ; Humans ; Monte Carlo Method ; Population Groups/classification ; Population Groups/statistics & numerical data ; Risk Assessment ; Stochastic Processes ; Time Factors

A conceptual/computational framework for exposure reconstruction from biomarker data combined with auxiliary exposure-related data is presented, evaluated with example applications, and examined in the context of future needs and opportunities. This framework employs physiologically based toxicokinetic (PBTK) modeling in conjunction with numerical "inversion" techniques. To quantify the value of different types of exposure data "accompanying" biomarker data, a study was conducted focusing on reconstructing exposures to chlorpyrifos, from measurements of its metabolite levels in urine. The study employed biomarker data as well as supporting exposure-related information from the National Human Exposure Assessment Survey (NHEXAS), Maryland, while the MENTOR-3P system (Modeling ENvironment for TOtal Risk with Physiologically based Pharmacokinetic modeling for Populations) was used for PBTK modeling. Recently proposed, simple numerical reconstruction methods were applied in this study, in conjunction with PBTK models. Two types of reconstructions were studied using (a) just the available biomarker and supporting exposure data and (b) synthetic data developed via augmenting available observations. Reconstruction using only available data resulted in a wide range of variation in estimated exposures. Reconstruction using synthetic data facilitated evaluation of numerical inversion methods and characterization of the value of additional information, such as study-specific data that can be collected in conjunction with the biomarker data. Although the NHEXAS data set provides a significant amount of supporting exposure-related information, especially when compared to national studies such as the National Health and Nutrition Examination Survey (NHANES), this information is still not adequate for detailed reconstruction of exposures under several conditions, as demonstrated here. The analysis presented here provides a starting point for introducing improved designs for future biomonitoring studies, from the perspective of exposure reconstruction; identifies specific limitations in existing exposure reconstruction methods that can be applied to population biomarker data; and suggests potential approaches for addressing exposure reconstruction from such data.

Comment in: J Expo Sci Environ Epidemiol. 2008 Nov;18(6):535; author reply 536-7. (PMID: 18936758)

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P30 ES005022 United States ES NIEHS NIH HHS; P30 ES005022-22 United States ES NIEHS NIH HHS; P30 ES 005022 United States ES NIEHS NIH HHS

0 (Biomarkers)
0 (Environmental Pollutants)

Date Created: 20080328 Date Completed: 20090615 Latest Revision: 20211020

20240628

PMC3068528

10.1038/jes.2008.9

18368010