Citation:

Blackwell, B., G. Ankley, S. Corsi, L. DeCicco, K. Houck, R. Judson, S. Li, M. Martin, E. Murphy, A. Schroeder, E. Smith, J. Swintek, AND Dan Villeneuve. An "EAR" on environmental surveillance and monitoring: A case study on the use of exposure-activity ratios (EARS) to prioritize sites, chemicals, and bioactivities of concern in Great Lakes waters. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 51(15):8713–8724, (2017).

Impact/Purpose:

Anthropogenic contaminants are frequently reported in environmental media at concentrations that could potentially affect ecological or human receptors. For many contaminants, including industrial use compounds, pharmaceuticals, and personal care products, extensive hazard testing has not been performed, thus the potential biological effects of exposure to these compounds are not well characterized. The US EPA’s ToxCast program has currently screened thousands of chemicals through hundreds of in vitro assays, providing a unique effects database that characterizes the potential molecular interactions for many chemicals lacking traditional toxicity data. By comparing environmental concentrations of contaminants with concentrations known to activate molecular targets in vitro, an exposure-activity ratio (EAR) can be calculated. Compounds present at concentrations near that which are biologically active show higher EAR values and can be prioritized for future follow-up assessments. As a case study, chemical occurrence data from a 2012 study in the Great Lakes Basin along with the ToxCast effects database were used to calculate EARs as a prioritization tool to identify sites, chemicals, and biological pathways of potential concern. Highlighted biological targets were linked to the AOPWiki to identify potential targets for future monitoring or verification of predicted hazards. The case study demonstrates the utility of using high content, high-through toxicology databases (i.e., the ToxCast database) to screen environmental monitoring datasets, which will aid managers in identifying potential concerns and prioritizing future monitoring needs. This case study and the development of the EAR prioritization approach directly supports the Great Lakes Restoration Initiative, Action Plan II focus area on Toxic Substances and Areas of Concern. The approach has broader application as a demonstration of the application of the AOP framework and AOP-based tools in the context of environmental assessment and monitoring (CSS Project 17.01, Task 2.2).

Description:

Current environmental monitoring approaches focus primarily on chemical occurrence. However, based on chemical concentration alone, it can be difficult to identify which compounds may be of toxicological concern for prioritization for further monitoring or management. This can be problematic because toxicological characterization is lacking for many emerging contaminants. New sources of high throughput screening data like the ToxCast™ database, which contains data for over 9,000 compounds screened through up to 1,100 assays, are now available. Integrated analysis of chemical occurrence data with HTS data offers new opportunities to prioritize chemicals, sites, or biological effects for further investigation based on concentrations detected in the environment linked to relative potencies in pathway-based bioassays. As a case study, chemical occurrence data from a 2012 study in the Great Lakes Basin along with the ToxCast™ effects database were used to calculate exposure-activity ratios (EARs) as a prioritization tool. Technical considerations of data processing and use of the ToxCast™ database are presented and discussed. EAR prioritization identified multiple sites, biological pathways, and chemicals that warrant further investigation. Biological pathways were then linked to adverse outcome pathways to identify potential adverse outcomes and biomarkers for use in subsequent monitoring efforts.

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