Prioritizing chemicals of ecological concern in Great Lakes tributaries using high-throughput screening data and adverse outcome pathways

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).…”

“…However, 80 pesticides and pharmaceuticals were detected across all sites, with detection frequencies for individual compounds ranging up to 100% (18) of sites for nicotine (median: 3 sites; 17%). Frequent detections of pesticide and pharmaceutical contaminant mixtures and common exceedance of the 0.001 EAR effects-screening threshold (Corsi et al, 2019) in NPS SER protected-stream systems raise concerns for potential adverse effects to aquatic and associated terrestrial foodwebs and illustrate the opportunity for improved direct and indirect management actions. Visitors and proximal property owners are often heavily vested in preserving the health and beauty of NPS SER protected streams, potentially increasing the efficacy of public outreach efforts, particularly those posted at stream access points.…”

“…1 indicate exposures demonstrated to modulate molecular targets in vitro, whereas EAR 1 suggest proportionately lower probability of biological activity. A recent cross-examination of surface-water contaminants, for which both ToxCast and aquatic-toxicity benchmark data were available, indicated correspondence between the commonly employed 0.1 benchmark-based Toxicity Quotient threshold of concern and EAR = 0.001 (Corsi et al, 2019). Non-specificendpoint, baseline, and unreliable response-curve assays were excluded (as described in Becker et al, 2015; Blackwell et al, Table 1 Site name, unit code ( Fig.…”

“…Environmental Protection Agency, 2018a), but does include a suite of zebrafish (ZF; Danio rerio) embryonic-exposure endpoints that provide useful models of organism-level as well as vulnerable, early-life-cycle effects in fish (Padilla et al, 2012;Truong et al, 2013). Given the diversity of organisms and respective contaminant vulnerabilities extant in southeastern stream foodwebs (Lydeard and Mayden, 1995;McKinney, 2006;Scott, 2006;Warren et al, 2000), we employed the conservative (protective) effects-screening threshold of 0.001 suggested recently (Corsi et al, 2019) as described (Bradley et al, 2019). Of the 80 pesticides and pharmaceuticals detected at least once in this study, 56% (45) had acceptable exposure-effects relation data at the time of Tox-Cast access (see Table S6 for ToxCast exclusions).…”

Pathway‐Based Approaches for Assessing Biological Hazards of Complex Mixtures of Contaminants: A Case Study in the Maumee River

“…One challenge associated with this chemical–gene network modeling approach is that it is based on the presence or absence of chemicals rather than concentrations in samples, so the ability to quantitatively consider exposure as part of the complex mixture analysis is limited (Schroeder et al 2016, 2017; Blackwell et al 2017). To help address this shortcoming, we recently utilized single‐chemical dose–response data generated from a large‐scale high‐throughput screening (HTS) program supported through the US Environmental Protection Agency (USEPA) and other Federal partners (ToxCast; US Environmental Protection Agency 2020b), to generate exposure–activity ratios (EARs) based on concentrations of chemicals measured in an environmental sample (Blackwell et al 2017, 2019; Corsi et al 2019). The ToxCast program has generated in vitro dose–response data capturing hundreds of biological pathways and processes for >9000 chemicals, many of which have limited or no in vivo toxicity information.…”