TY - JOUR
T1 - Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic
AU - Georgopoulos, Panos G.
AU - Wang, Sheng Wei
AU - Yang, Yu Ching
AU - Xue, Jianping
AU - Zartarian, Valerie G.
AU - McCurdy, Thomas
AU - Özkaynak, Halûk
N1 - Funding Information:
The USEPA has supported thi s work through the Center for Exposure and Ri sk Modeli ng (CERM F EPAR827033) and the Environmental Bioinformatics and Computational Toxi cology Center (ebCTC F GAD R 832721-010). Addi - tional support has been provided by the NIEHS sponsored UMDNJ Center for Envi ronmental Exposures and Di sease (Grant #: NIEHS P30ES005022). We acknowledge contri bu-ti ons of Elai na Kenyon, Ted Palma, Andrew Schullman, and David Thomas (USEPA); Karen Feld (NJDEP); Eric Vowi nkel (USGS); Mi ng Ouyang, Li nda Everett, and Alan Sasso (EOHSI); and numerous EOHSI collaborators.
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
KW - Arsenic
KW - Dose
KW - Exposure
KW - Exposure biology
KW - Modeling
KW - Multimedia
KW - PBPK
UR - http://www.scopus.com/inward/record.url?scp=45349089576&partnerID=8YFLogxK
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U2 - 10.1038/sj.jes.7500637
DO - 10.1038/sj.jes.7500637
M3 - Article
C2 - 18073786
AN - SCOPUS:45349089576
SN - 1559-0631
VL - 18
SP - 462
EP - 476
JO - Journal of Exposure Science and Environmental Epidemiology
JF - Journal of Exposure Science and Environmental Epidemiology
IS - 5
ER -