Using publicly available data, a physiologically-based pharmacokinetic model and Bayesian simulation to improve arsenic non-cancer dose-response

Dong, Zhaomin and Liu, CuiXia and Liu, Yanju and Yan, Kaihong and Semple, Kirk Taylor and Naidu, Ravi (2016) Using publicly available data, a physiologically-based pharmacokinetic model and Bayesian simulation to improve arsenic non-cancer dose-response. Environment International, 92-93. pp. 239-246. ISSN 0160-4120

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Abstract

Publicly available data can potentially examine the relationship between environmental exposure and public health, however, it has not yet been widely applied. Arsenic is of environmental concern, and previous studies mathematically parameterized exposure duration to create a link between duration of exposure and increase in risk. However, since the dose metric emerging from exposure duration is not a linear or explicit variable, it is difficult to address the effects of exposure duration simply by using mathematical functions. To relate cumulative dose metric to public health requires a lifetime physiologically-based pharmacokinetic (PBPK) model, yet this model is not available at a population level. In this study, the data from the U.S. total diet study (TDS, 2006–2011) was employed to assess exposure: daily dietary intakes for total arsenic (tAs) and inorganic arsenic (iAs) were estimated to be 0.15 and 0.028 μg/kg/day, respectively. Meanwhile, using National Health and Nutrition Examination Survey (NHANES, 2011–2012) data, the fraction of urinary As(III) levels (geometric mean: 0.31 μg/L) in tAs (geometric mean: 7.75 μg/L) was firstly reported to be approximately 4%. Together with Bayesian technique, the assessed exposure and urinary As(III) concentration were input to successfully optimize a lifetime population PBPK model. Finally, this optimized PBPK model was used to derive an oral reference dose (Rfd) of 0.8 μg/kg/day for iAs exposure. Our study also suggests the previous approach (by using mathematical functions to account for exposure duration) may result in a conservative Rfd estimation.

Item Type:
Journal Article
Journal or Publication Title:
Environment International
Additional Information:
This is the author’s version of a work that was accepted for publication in Environment International. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Environment International, 92-93, 2016 DOI: 10.1016/j.envint.2016.03.035
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2300
Subjects:
ID Code:
79255
Deposited By:
Deposited On:
27 Apr 2016 14:06
Refereed?:
Yes
Published?:
Published
Last Modified:
04 Aug 2020 03:46