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

Abstract

Current environmental monitoring approaches focus primarily on chemical occurrence. However, based on concentration alone, it can be difficult to identify which compounds may be of toxicological concern and should be prioritized for further monitoring, in-depth testing, or management. This can be problematic because toxicological characterization is lacking for many emerging contaminants. New sources of high-throughput screening (HTS) data, such as the ToxCast database, which contains information for over 9000 compounds screened through up to 1100 bioassays, 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. Prioritized bioactivities from the EAR analysis were linked to discrete adverse outcome pathways to identify potential adverse outcomes and biomarkers for use in subsequent monitoring efforts.

Exposure and potential effects of pesticides and pharmaceuticals in protected streams of the US National park Service southeast region

“…4; Table S7) and median ( Figure S3; Table S8) exposure conditions support this conclusion. The in vitro ToxCast EAR approach informs the potential for sub-lethal effects at an observed concentration (Becker et al, 2015;Blackwell et al, 2017), provides probable effects screening consistent with traditional in vivo water-quality benchmark-based toxicity quotient (TQ) approaches (EAR = 0.001 comparable to commonly employed TQ = 0.1 effects threshold (Corsi et al, 2019)), and supports cumulative effects ( P EAR ) estimation (CA-model (Ankley et al, 2010;Conolly et al, 2017;Judson et al, 2014;Villeneuve et al, 2014)). Although sometimes restricted only to chemicals with a common mode of action, CApredicted toxicities typically agree with observed toxicities within a factor of 2-4, regardless of recognized mode of action (Belden et al, 2007;Boobis et al, 2011;Cedergreen et al, 2008;Ermler et al, 2011;Faust et al, 2003;Rodney et al, 2013;Thrupp et al, 2018;Warne, 2003;Zhang et al, 2011).…”

“…Table S3c contains median concentrations (all samples) by compound and site and only includes target analytes that were detected in at least half of the samples at one or more sites. Integrated effects of detected pesticide and pharmaceutical contaminants in water were estimated using the toxEval R-program (De Cicco et al, 2018) to sum (concentration addition (CA) model (Altenburger et al, 2013;Altenburger et al, 2012;Cedergreen et al, 2008;Ermler et al, 2011;Kortenkamp et al, 2009;Thrupp et al, 2018)) individual EAR (ratio of detected maximum or median concentration to activity concentration at cutoff (ACC) from Toxicity ForeCaster (ToxCast TM ; U.S. Environmental Protection Agency, 2019) high-throughput screening data (U.S. Environmental Protection Agency, 2018a, 2018b) to provide site-specific cumulative EAR ( P EAR ) (Becker et al, 2015;Blackwell et al, 2017;Li et al, 2017;Schroeder et al, 2016). EAR !…”

“…Sediment pesticide (119 unique analytes) concentrations were also assessed once (2017) in select locations. Two lines of evidence were employed to assess the potential for cumulative contaminant effects (hazard) to in-stream biota: 1) occurrence and cumulative concentrations of designed-bioactives, and 2) cumulative Exposure Activity Ratios ( P EAR ) (Blackwell et al, 2017;Bradley et al, 2019;Bradley et al, 2018b) based on high-throughput screening data in Toxicity Forecaster (ToxCast TM , U.S. Environmental Protection Agency, 2019). Table 1 2.…”

Risk assessment for pesticide mixtures on aquatic ecosystems in China: a proposed framework

“…Data gaps in hazard assessment can be numerous in many cases which can lead to many uncertainties and sometimes can make accurate assessment impossible. In recent years, high‐throughput assay methods have been developed actively, and many of them have been used in large‐scale prioritization and evaluation on environmental mixtures, such as those research activities under the Great Lakes Restoration Initiative . However, low cost and high‐throughput assays or platforms for representative aquatic toxicity test organisms are often lacking.…”

The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

“…Measurements from HTP assays often correspond to MIEs or early KEs (e.g., receptor activation, enzyme inhibition, etc. ), so it is possible to query/cross-reference knowledgebases such as the AOP Wiki to translate bioactivity data generated from complex mixtures into potential hazards in exposed organisms, such as fish [35,36]. The AOP framework also can serve as the basis for translating molecular/biochemical data from field-collected animals exposed to complex mixtures into endpoints useful for inferring hazard/risk [37].…”