Bayesian Hierarchical Structure for Quantifying Population Variability to Inform Probabilistic Health Risk Assessments

Human variability is a very important factor considered in human health risk assessment for protecting sensitive populations from chemical exposure. Traditionally, to account for this variability, an interhuman uncertainty factor is applied to lower the exposure limit. However, using a fixed uncertainty factor rather than probabilistically accounting for human variability can hardly support probabilistic risk assessment advocated by a number of researchers; new methods are needed to probabilistically quantify human population variability. We propose a Bayesian hierarchical model to quantify variability among different populations. This approach jointly characterizes the distribution of risk at background exposure and the sensitivity of response to exposure, which are commonly represented by model parameters. We demonstrate, through both an application to real data and a simulation study, that using the proposed hierarchical structure adequately characterizes variability across different populations.

[1]  D Krewski,et al.  A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty/safety factors. , 1999, Regulatory toxicology and pharmacology : RTP.

[2]  Tracey J. Woodruff,et al.  Estimating Risk from Ambient Concentrations of Acrolein across the United States , 2006, Environmental health perspectives.

[3]  Nazmul Sohel,et al.  Arsenic in Drinking Water and Adult Mortality: A Population-based Cohort Study in Rural Bangladesh , 2009, Epidemiology.

[4]  S. Arifeen,et al.  Prevalence of arsenic exposure and skin lesions. A population based survey in Matlab, Bangladesh , 2006, Journal of Epidemiology and Community Health.

[5]  Kan Shao,et al.  Potential Uncertainty Reduction in Model‐Averaged Benchmark Dose Estimates Informed by an Additional Dose Study , 2011, Risk analysis : an official publication of the Society for Risk Analysis.

[6]  Weihsueh A. Chiu,et al.  A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects , 2015, Environmental health perspectives.

[7]  Richard N Hill,et al.  Risk Assessment For Benefits Analysis: Framework for Analysis of A Thyroid-Disrupting Chemical , 2005, Journal of toxicology and environmental health. Part A.

[8]  Robert Goble,et al.  A STRAW MAN PROPOSAL FOR A QUANTITATIVE DEFINITION OF THE RfD , 2002, Drug and chemical toxicology.

[9]  Wout Slob,et al.  Shape and steepness of toxicological dose–response relationships of continuous endpoints , 2014, Critical reviews in toxicology.

[10]  Sumio Watanabe,et al.  Asymptotic Equivalence of Bayes Cross Validation and Widely Applicable Information Criterion in Singular Learning Theory , 2010, J. Mach. Learn. Res..

[11]  X. Le,et al.  Increased Mortality Associated with Well-Water Arsenic Exposure in Inner Mongolia, China , 2009, International journal of environmental research and public health.

[12]  J. Evans,et al.  Reproductive and Developmental Risks from Ethylene Oxide: A Probabilistic Characterization of Possible Regulatory Thresholds , 2001, Risk analysis : an official publication of the Society for Risk Analysis.

[13]  D. Rubin,et al.  Inference from Iterative Simulation Using Multiple Sequences , 1992 .

[14]  Kan Shao,et al.  Model Uncertainty and Bayesian Model Averaged Benchmark Dose Estimation for Continuous Data , 2014, Risk analysis : an official publication of the Society for Risk Analysis.

[15]  Mengling Liu,et al.  Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study , 2011, BMJ : British Medical Journal.

[16]  Jiqiang Guo,et al.  Stan: A Probabilistic Programming Language. , 2017, Journal of statistical software.

[17]  Kan Shao,et al.  A comparison of three methods for integrating historical information for Bayesian model averaged benchmark dose estimation. , 2012, Environmental toxicology and pharmacology.