Citation:

Setzer, Woodrow, R. Pearce, B. Wetmore, AND J. Wambaugh. An Upper Bound for Population Exposure Variability (SOT). Presented at Society of Toxicology Annual Meeting, San Diego, CA, March 22 - 26, 2015. https://doi.org/10.23645/epacomptox.5178697

Impact/Purpose:

The ExpoCast project has developed models that predict median population exposure from minimal chemical property and use information. This presentation describes research to estimate upper quantile population exposure with the same information.

Description:

Tools for the rapid assessment of exposure potential are needed in order to put the results of rapidly-applied tools for assessing biological activity, such as ToxCast® and other high throughput methodologies, into a quantitative exposure context. The ExpoCast models (Wambaugh et al, 2013 ) comprise such a tool, predicting population median exposures and their confidence intervals for the total population and for defined subgroups. However, even if the population median exposure is so low that effects appear unlikely, as predicted by in vitro assays, upper quantiles of the exposure distribution may be large enough to be of concern, so it would be extremely helpful to be able to put an upper bound on the likely population variability. We used an analysis of data on urine analytes collected as part of the NHANES (National Health and Nutrition Examination Survey) program to estimate the total variance among individuals of log transformed urinary analyte concentration (creatinine adjusted) for environmental chemicals. This analysis suggested that, for 95% of chemicals like those assayed for in NHANES, the exposure to 95% of the population is less than two-orders of magnitude greater than the median exposure. However, the variance on which this is based is known to overestimate the actual exposure variability (Aylward, et al, 2014), and we showed numerical simulations whose results help to quantify the degree of this overestimate. Finally, we showed the application of this methodology to over 400 chemicals from ToxCast Phase I and II. We compared in vitro concentrations that result in biological activity, converted to equivalent human steady-state exposures (Wetmore et al, 2012), and exposure predictions adjusted for population variability. The comparison showed that, while the quantitative uncertainties were large, the tools described here can be useful in narrowing the range of chemicals needing further, more detailed evaluation. This abstract does not necessarily reflect U.S. EPA policy.

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