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Evaluation of Complex Mixture Toxicity: An Effects-Driven Analysis in the Milwaukee Estuary Area of Concern (Milwaukee, WI)
Citation:
Maloney, E., G. Ankley, B. Blackwell, J. Cavallin, D. Feifarek, M. Kahl, S. Poole, E. Randolph, K. Jensen, C. LaLone, D. Blatz, C. Schaupp, AND Dan Villeneuve. Evaluation of Complex Mixture Toxicity: An Effects-Driven Analysis in the Milwaukee Estuary Area of Concern (Milwaukee, WI). SETAC North America 42nd Annual meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17100254
Impact/Purpose:
Presentation to the SETAC North America 42nd Annual Meeting November 2021. Understanding potential impacts of complex mixtures of contaminants has long been one of the most challenging aspects of environmental toxicology and ecological risk assessment. To help address aims under Focus area 1 (Toxic Substances and Areas of Concern) of the Great Lakes Restoration Initiative (GLRI), the present study integrated chemical, biological, and computational approaches to evaluate the potential toxicity associated with complex mixtures of contaminants present in the Milwaukee estuary area of concern. This research aids Region 5, GLNPO, in addressing specific aims and objectives under the GLRI and illustrates general strategies that may be employed by other EPA regions needed to consider impacts of complex contaminant mixtures.
Description:
A wide range of anthropogenic activities result in release of complex contaminant mixtures into associated watersheds. To protect organisms inhabiting these aquatic environments, it is important to account for mixture toxicity during ecotoxicological effects assessment. Here, we present several different strategies to evaluate complex mixture toxicity and identify individual constituents, contaminant groups, and mixtures of greatest concern within the Milwaukee Estuary Area of Concern (AOC; Milwaukee, WI). To evaluate potential in vivo effects of contaminant mixtures, adult fathead minnows (Pimephales promelas) were caged at 8-11 study sites across the AOC in 2017 and 2018. Following 96-h of exposure, fish tissues were sampled and used for targeted effects analyses (e.g., sex steroid concentrations, gene expression). Concurrently, composite water samples were collected and analyzed for nutrients and 178 wastewater indicators and pharmaceuticals, and characterized for in vitro bioactivity that might lead to adverse effects (e.g., endocrine related and pathway-specific effects; Attagene cis- and trans-Factorial and T47-Kbluc assays). Chemicals were subsequently grouped based on putative mode of action (MOA), and susceptibility of local fish species to potential adverse effects mediated through chemical interactions with specific proteins using the US EPA SeqAPASS tool and data from the Map of Life Project. Individual constituents, chemical groups, and mixtures potentially contributing to integrated biological effects were identified using multiple lines of evidence including occurrence at impacted sites (qualitative analysis), contribution to cumulative toxic units (maximum cumulative ratio; ECOTOXicology Knowledgebase, ToxCast database), and covariance with measured effects (randomForest regression). Overall, this study demonstrates multiple strategies that can be employed to evaluate complex mixture toxicity, and highlights the utility of integrating chemical, biological, and computational techniques for cumulative effect analysis. The contents of this abstract neither constitute nor necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Evaluation of Complex Mixture Toxicity: An Effects-Driven Analysis in the Milwaukee Estuary Area of Concern (Milwaukee, WI)
SETAC_2021_MILWAUKEE_MIXTURES.PDF (PDF, NA pp, 3133.183 KB, about PDF)