Citation:

Blackwell, B., A. Schroeder, G. Ankley, S. Corsi, L. DeCicco, J. Swintek, AND Dan Villeneuve. Predicting biological effects of environmental mixtures using exposure:activity ratios (EAR) derived from US EPA’s ToxCast data: Retrospective application to chemical monitoring data. SETAC North America, Salt Lake City, UT, November 01 - 05, 2015.

Impact/Purpose:

not applicable

Description:

Chemical monitoring has been widely used in environmental surveillance to assess exposure to environmental contaminants which could represent potential hazards to exposed organisms. However, the ability to detect chemicals in the environment has rapidly outpaced assessment of potential adverse ecological effects from these emerging contaminants. Recent advances in the arena of high throughput toxicology allow for the screening of large numbers of chemicals for a wide array of biological activity in a rapid, low cost manner. Data generated from these assays can provide benchmark effect concentrations and relative potencies for interaction with various biological targets, which in turn can be compared with available chemical occurrence data. These data can be used to calculate an exposure:activity ratio (EAR) to prioritize specific chemicals for further testing or to identify biological pathways most likely to be impacted at specific environmental sites. The US EPA’s ToxCast Program has generated a unique publically accessible dataset with over 1,800 individual chemicals screened through more than 800 assays. Chemical concentrations from composite water samples were compared to AC50 values from ToxCast to generate EARs for sites sampled along a gradient of wastewater discharge in the St. Louis River, MN, USA. Composite water samples collected from these sites in 2012 had been analyzed for 137 chemicals including wastewater indicators, pharmaceuticals, and steroid hormones. A conservative EAR threshold of 0.1 was set to screen for chemicals with potential biological activity. Locations nearest to the wastewater discharge generally showed higher EARs indicating a greater likelihood of biological impact. Chemicals interacting with estrogen receptor alpha (ERá), pregnane X receptor (PXR), and aryl hydrocarbon receptor (AhR), among others, were frequently observed with EAR>1. EARs will be used to prioritize further chemical monitoring of specific analytes and for subsequent targeted effects monitoring of biological pathways with predicted interactions.

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