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Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic

Journal of Exposure Science & Environmental Epidemiology volume 18, pages 462–476 (2008)Cite this article

Abstract

This article presents an integrated, biologically based, source-to-dose assessment framework for modeling multimedia/multipathway/multiroute exposures to arsenic. Case studies demonstrating this framework are presented for three US counties (Hunderton County, NJ; Pima County, AZ; and Franklin County, OH), representing substantially different conditions of exposure. The approach taken utilizes the Modeling ENvironment for TOtal Risk studies (MENTOR) in an implementation that incorporates and extends the approach pioneered by Stochastic Human Exposure and Dose Simulation (SHEDS), in conjunction with a number of available databases, including NATA, NHEXAS, CSFII, and CHAD, and extends modeling techniques that have been developed in recent years. Model results indicate that, in most cases, the food intake pathway is the dominant contributor to total exposure and dose to arsenic. Model predictions are evaluated qualitatively by comparing distributions of predicted total arsenic amounts in urine with those derived using biomarker measurements from the NHEXAS — Region V study: the population distributions of urinary total arsenic levels calculated through MENTOR and from the NHEXAS measurements are in general qualitative agreement. Observed differences are due to various factors, such as interindividual variation in arsenic metabolism in humans, that are not fully accounted for in the current model implementation but can be incorporated in the future, in the open framework of MENTOR. The present study demonstrates that integrated source-to-dose modeling for arsenic can not only provide estimates of the relative contributions of multipathway exposure routes to the total exposure estimates, but can also estimate internal target tissue doses for speciated organic and inorganic arsenic, which can eventually be used to improve evaluation of health risks associated with exposures to arsenic from multiple sources, routes, and pathways.

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References

  • ATSDR. Toxicological Profile for Arsenic (Draft for Public Comment). 2005: http://www.atsdr.cdc.gov/toxprofiles/tp2.html.

  • Buchet J.P., Lauwerys R., and Roels H. Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int Arch Occup Environ Health 1981: 48 (1): 71–79.

    Article  CAS  Google Scholar 

  • Buck R.J., Ozkaynak H., Xue J., Zartarian V.G., and Hammerstrom K. Modeled estimates of chlorpyrifos exposure and dose for the Minnesota and Arizona NHEXAS populations. J Expo Anal Environ Epidemiol 2001: 11 (3): 253–268.

    Article  CAS  Google Scholar 

  • Burke J.M., Zufall M.J., and Ozkaynak H. A population exposure model for particulate matter: case study results for PM2*5 in Philadelphia, PA. J Expo Anal Environ Epidemiol 2001: 11 (6): 470–489.

    Article  CAS  Google Scholar 

  • Calderon R.L., Hudgens E., Le X.C., Schreinemachers D., and Thomas D.J. Excretion of arsenic in urine as a function of exposure to arsenic in drinking water. Environ Health Perspect 1999: 107 (8): 663–667.

    Article  CAS  Google Scholar 

  • Dabeka R.W., McKenzie A.D., Lacroix G.M., Cleroux C., Bowe S., Graham R.A., Conacher H.B., and Verdier P. Survey of arsenic in total diet food composites and estimation of the dietary intake of arsenic by Canadian adults and children. J AOAC Int 1993: 76 (1): 14–25.

    CAS  PubMed  Google Scholar 

  • El-Masri H.A., and Kenyon E.M. Development of a human physiologically based pharmacokinetic (PBPK) model for inorganic arsenic and its mono- and di-methylated metabolites. J Pharmacokinet Pharmacodyn 2007; Advance Online Publication (DOI:10.1007/s10928-007-9075-z).

    Article  Google Scholar 

  • Frey M.M., and Edwards M.A. Surveying arsenic occurrence in US drinking water. J Am Water Works Assoc 1997: 89 (3): 105–117.

    Article  CAS  Google Scholar 

  • Gallegos A.F., and Wenzel W.J. HUMTRN: documentation and verification for an ICRP-based age- and sex-specific human simulation model for radionuclide dose assessment, Los Alamos National Laboratory, Los Alamos, NM, 1984.

  • Georgopoulos P. A multiscale approach for assessing the interactions of environmental and biological systems in a holistic health risk assessment framework. Water Air Soil Pollut Focus 2007, Advance online publication (DOI:10.1007/s11267-007-9137-7).

    Article  Google Scholar 

  • Georgopoulos P.G., Bandi S., Efstathiou C., Li W., Shade P., Tan H., Tanwar S., Tong S., Vyas V.M., Wang S.W., and Yang Y.C. Infrastructure for an Arsenic Exposure Information System, CERM: 2006:01, Prepared by Computational Chemodynamics Laboratory for USEPA, 2006a: http://ccl.rutgers.edu/reports/cerm/Georgopoulos-etal_CERM2006-report_ArsenicEXIS.pdf.

  • Georgopoulos P.G., and Lioy P.J. From theoretical aspects of human exposure and dose assessment to computational model implementation: the MOdeling ENvironment for TOtal Risk studies (MENTOR). J Toxicol Environ Health B Crit Rev 2006: 9 (6): 457–483.

    Article  CAS  Google Scholar 

  • Georgopoulos P.G., Wang S.W., Georgopoulos I.G., Yononne-Lioy M.J., and Lioy P.J. Assessment of human exposure to copper: a case study using the NHEXAS database. J Expo Sci Environ Epidemiol 2006b: 16: 397–409.

    Article  CAS  Google Scholar 

  • Georgopoulos P.G., Wang S.W., Vyas V.M., Sun Q., Burke J., Vedantham R., McCurdy T., and Ozkaynak H. A source-to-dose assessment of population exposures to fine PM and ozone in Philadelphia, PA, during a summer 1999 episode. J Expo Anal Environ Epidemiol 2005: 15 (5): 439–457.

    Article  CAS  Google Scholar 

  • Gunderson E.L. Dietary intakes of pesticides, selected elements, and other chemicals: FDA Total Diet Study, June 1984–April 1986. J AOAC Int 1995a: 78 (4): 910–921.

    CAS  PubMed  Google Scholar 

  • Gunderson E.L. FDA Total Diet Study, July 1986–April 1991, dietary intakes of pesticides, selected elements, and other chemicals. J AOAC Int 1995b: 78 (6): 1353–1363.

    CAS  PubMed  Google Scholar 

  • Hays A.M., Srinivasan D., Witten M.L., Carter D.E., and Lantz R.C. Arsenic and cigarette smoke synergistically increase DNA oxidation in the lung. Toxicol Pathol 2006: 34 (4): 396–404.

    Article  CAS  Google Scholar 

  • ICRP. ICRP Publication 89: Basic Anatomical and Physiological Data for Use in Radiological Protection: Reference Values. Elsevier Publishing Company, New York, 2003.

  • Johnson L.R., and Farmer J.G. Use of human metabolic studies and urinary arsenic speciation in assessing arsenic exposure. Bull Environ Contam Toxicol 1991: 46 (1): 53–61.

    Article  CAS  Google Scholar 

  • Lowney Y.W., Ruby M.V., Wester R.C., Schoof R.A., Holm S.E., Hui X.Y., Barbadillo S., and Maibach H.I. Percutaneous absorption of arsenic from environmental media. Toxicol Ind Health 2005: 21 (1–2): 1–14.

    Article  CAS  Google Scholar 

  • Mann S., Droz P.O., and Vahter M. A physiologically based pharmacokinetic model for arsenic exposure II: Validation and application in humans. Toxicol Appl Pharmacol 1996: 140: 471–486.

    Article  CAS  Google Scholar 

  • Maslia M.L., Sautner J.B., Aral M.M., Reyes J.J., Abraham J.E., and Williams R.C. Using water-distribution system modeling to assist epidemiologic investigations. J Water Resour Plann Manag 2000: 126 (4): 180–198.

    Article  Google Scholar 

  • McCurdy T., Glen G., Smith L., and Lakkadi Y. The national exposure research laboratory's consolidated human activity database. J Expo Anal Environ Epidemiol 2000: 10 (6 Part 1): 566–578.

    Article  CAS  Google Scholar 

  • Meacher D.M., Menzel D.B., Dillencourt M.D., Bic L.F., Schoof R.A., Yost L.J., Eickhoff J.C., and Farr C.H. Estimation of multimedia inorganic arsenic intake in the U.S. population. Hum Ecol Risk Assess 2002: 8 (7): 1697–1721.

    Article  CAS  Google Scholar 

  • Meza M.M., Yu L., Rodriguez Y.Y., Guild M., Thompson D., Gandolfi A.J., and Klimecki W.T. Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children. Environ Health Perspect 2005: 113 (6): 775–781.

    Article  CAS  Google Scholar 

  • Munoz O., Bastias J.M., Araya M., Morales A., Orellana C., Rebolledo R., and Velez D. Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study. Food Chem Toxicol 2005: 43 (11): 1647–1655.

    Article  CAS  Google Scholar 

  • NRC. Arsenic in Drinking Water: 2001 Update. National Academy Press, Washington, DC, 2001, 244.

  • Pellizzari E.D., and Clayton C.A. Assessing the measurement precision of various arsenic forms and arsenic exposure in the National Human Exposure Assessment Survey (NHEXAS). Environ Health Perspect 2006: 114 (2): 220–227.

    Article  CAS  Google Scholar 

  • Peterson B., Berry M., and Elkins A. Assessment of ingestion exposures in the residential environment. In: Baker S., Driver J., McCallum D.B. (Eds.). Residential Exposure Assessment, A Sourcebook. Kluwer Academic/Plenum, New York, 2001 pp. 131–160.

    Google Scholar 

  • Pomroy C., Charbonneau S.M., McCullough R.S., and Tam G.K. Human retention studies with 74As. Toxicol Appl Pharmacol 1980: 53 (3): 550–556.

    Article  CAS  Google Scholar 

  • Rossman L.A. EPANET 2 Users Manual. EPA/600/R-00/057, U.S. Environmental Protection Agency, Cincinnati, OH, 2000.

  • Roy A., Ouyang M., Freeman N., Georgopoulos P.G., and Lioy P.J. Environmental, dietary, demographic, and activity variables associated with biomarkers of exposure for benzene and lead. J Expo Anal Environ Epidemiol 2003: 13 (6): 417–426.

    Article  CAS  Google Scholar 

  • Schoof R.A., Yost L.J., Eickhoff J., Crecelius E.A., Cragin D.W., Meacher D.M., and Menzel D.B. A market basket survey of inorganic arsenic in food. Food Chem Toxicol 1999: 37 (8): 839–846.

    Article  CAS  Google Scholar 

  • Stallings C., Tippett J.A., Glen G., and Smith L. CHAD User's Guide — Extracting Human Activity Information from CHAD on the PC, Written for USEPA National Exposure Research Laboratory by ManTech Environmental Technologies, 2002: http://www.epa.gov/chadnet1/reports/CHAD_Manual.pdf.

  • Suzuki K.T. Metabolomics of arsenic based on speciation studies. Anal Chim Acta 2005: 540 (1): 71–76.

    Article  CAS  Google Scholar 

  • Tao S.S.H., and Bolger P.M. Dietary arsenic intakes in the United States: FDA Total Diet Study, September 1991–December 1996. Food Addit Contam 1999: 16 (11): 465–472.

    Article  CAS  Google Scholar 

  • Thomas D.J., Styblo M., and Lin S. The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol 2001: 176 (2): 127–144.

    Article  CAS  Google Scholar 

  • Thomas D.J., Waters S.B., and Styblo M. Elucidating the pathway for arsenic methylation. Toxicol Appl Pharmacol 2004: 198 (3): 319–326.

    Article  CAS  Google Scholar 

  • Thomas K.W., Pellizzari E.D., and Berry M.R. Population-based dietary intakes and tap water concentrations for selected elements in the EPA region V National Human Exposure Assessment Survey (NHEXAS). J Expo Anal Environ Epidemiol 1999: 9 (5): 402–413.

    Article  CAS  Google Scholar 

  • Tippett K.S., Enns C.W., and Moshfegh A.J. Food consumption surveys in the US Department of Agriculture. Nutr Today 1999: 34 (1): 33–46.

    Article  Google Scholar 

  • USEPA. Research plan for arsenic in drinking water. EPA/600/R-98/042, U.S. Environmental Protection Agency, Cincinnati, OH, 1998.

  • USEPA. Arsenic occurrence in public drinking water supplies. EPA-815-R-00-02, U.S. Environmental Protection Agency, Washington, DC, 2000: http://www.epa.gov/OGWDW/arsenic/pdfs/occurrence.pdf.

  • USEPA. About the National Emission Inventory Database, 2006a, http://www.epa.gov/air/data/neidb.html.

  • USEPA. NHEXAS — National Human Exposure Assessment Survey, 2006b: http://www.epa.gov/nerl/research/nhexas/nhexas.htm.

  • USEPA. Technology Transfer Network — National Air Toxics Assessment, 2006c: http://www.epa.gov/ttn/atw/nata/natsaov.html.

  • USGS. NWISWeb Data for the Nation, 2002: http://waterdata.usgs.gov/nwis.

  • Valenzuela O.L., Borja-Aburto V.H., Garcia-Vargas G.G., Cruz-Gonzalez M.B., Garcia-Montalvo E.A., Calderon-Aranda E.S., and Del Razo L.M. Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic. Environ Health Perspect 2005: 113 (3): 250–254.

    Article  CAS  Google Scholar 

  • Velez D., Ybanez N., and Montoro R. Monomethylarsonic and dimethylarsinic acid contents in seafood products. J Agric Food Chem 1996: 44: 859–864.

    Article  CAS  Google Scholar 

  • Wester R.C., Maibach H.I., Sedik L., Melendres J., and Wade M. In vivo and in vitro percutaneous absorption and skin decontamination of arsenic from water and soil. Fundam Appl Toxicol 1993: 20 (3): 336–340.

    Article  CAS  Google Scholar 

  • WHO. Gomez-Caminero A., Howe P., Hughes M., Kenyon E., Lewis D.R., Moore M., and Ng J. Arsenic and Arsenic Compounds (updated November 2004), Environmental Health Criteria 224, World Health Organization. 2001: http://www.who.int/ipcs/publications/ehc/ehc_224/en/.

  • Xue J., Zartarian V.G., Ozkaynak H., Dang W., Glen G., Smith L., and Stallings C. A probabilistic arsenic exposure assessment for children who contact chromated copper arsenate (CCA)-treated playsets and decks, Part 2: sensitivity and uncertainty analyses. Risk Anal 2006: 26 (2): 533–541.

    Article  Google Scholar 

  • Yost L.J., Schoof R.A., and Aucoin R. Intake of inorganic arsenic in the North American diet. Hum Ecol Risk Assess 1998: 4 (1): 137–152.

    Article  CAS  Google Scholar 

  • Yu D.H. A pharmacokinetic modeling of inorganic arsenic: a short-term oral exposure model for humans. Chemosphere 1999a: 39 (15): 2737–2747.

    Article  CAS  Google Scholar 

  • Yu D.H. A physiologically based pharmacokinetic model of inorganic arsenic. Regul Toxicol Pharmacol 1999b: 29 (2): 128–141.

    Article  CAS  Google Scholar 

  • Zartarian V.G., Ozkaynak H., Burke J.M., Zufall M.J., Rigas M.L., and Furtaw E.J. A modeling framework for estimating children's residential exposure and dose to chlorpyrifos via dermal residue contact and nondietary ingestion. Environ Health Perspect 2000: 108 (6): 505–514.

    Article  CAS  Google Scholar 

  • Zartarian V.G., Xue J., Ozkaynak H., Dang W., Glen G., Smith L., and Stallings C. A probabilistic arsenic exposure assessment for children who contact CCA-treated playsets and decks, part 1: model methodology, variability results, and model evaluation. Risk Anal 2006: 26 (2): 515–531.

    Article  Google Scholar 

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Acknowledgements

The USEPA has supported this work through the Center for Exposure and Risk Modeling (CERM — EPAR827033) and the Environmental Bioinformatics and Computational Toxicology Center (ebCTC — GAD R 832721-010). Additional support has been provided by the NIEHS sponsored UMDNJ Center for Environmental Exposures and Disease (Grant #: NIEHS P30ES005022). We acknowledge contributions of Elaina Kenyon, Ted Palma, Andrew Schullman, and David Thomas (USEPA); Karen Feld (NJDEP); Eric Vowinkel (USGS); Ming Ouyang, Linda Everett, and Alan Sasso (EOHSI); and numerous EOHSI collaborators.

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  1. Environmental and Occupational Health Sciences Institute (EOHSI), A Joint Institute of UMDNJ — R.W. Johnson Medical School and Rutgers University, 170 Frelinghuysen Road, Piscataway, 08854, New Jersey, USA

    Panos G Georgopoulos, Sheng-Wei Wang & Yu-Ching Yang

  2. National Exposure Research Laboratory — USEPA, Research Triangle Park, 27711, North Carolina, USA

    Jianping Xue, Valerie G Zartarian, Thomas Mccurdy & Halûk Özkaynak

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  1. Panos G Georgopoulos
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  2. Sheng-Wei Wang
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  3. Yu-Ching Yang
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  5. Valerie G Zartarian
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Correspondence to Panos G Georgopoulos.

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Georgopoulos, P., Wang, SW., Yang, YC. et al. Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic. J Expo Sci Environ Epidemiol 18, 462–476 (2008). https://doi.org/10.1038/sj.jes.7500637

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