Citation:

Maloney, E., D. Villeneuve, K. Jensen, B. Blackwell, M. Kahl, S. Poole, K. Vitense, D. Feifarek, G. Patlewicz, Kenneth Dean, C. Tilton, E. Randolph, J. Cavallin, C. Lalone, D. Blatz, C. Schaupp, AND G. Ankley. Evaluation of Complex Mixture Toxicity in the Milwaukee Estuary (WI, USA) Using Whole-Mixture and Component-Based Evaluation Methods. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 42(6):1229-1256, (2023). https://doi.org/10.1002/etc.5571

Impact/Purpose:

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:

Anthropogenic activities introduce complex mixtures into aquatic environments, necessitating mixture toxicity evaluation during risk assessment. There are many alternative approaches that can be used to complement traditional techniques for mixture assessment. Our study aimed to demonstrate how these approaches could be employed for mixture evaluation in a target watershed. Evaluations were carried out over 2 years (2017–2018) across 8–11 study sites in the Milwaukee Estuary (WI, USA). Whole mixtures were evaluated on a site-specific basis by deploying caged fathead minnows (Pimephales promelas) alongside composite samplers for 96 h and characterizing chemical composition, in vitro bioactivity of collected water samples, and in vivo effects in whole organisms. Chemicals were grouped based on structure/mode of action, bioactivity, and pharmacological activity. Priority chemicals and mixtures were identified based on their relative contributions to estimated mixture pressure (based on cumulative toxic units) and via predictive assessments (random forest regression). Whole mixture assessments identified target sites for further evaluation including two sites targeted for industrial/urban chemical mixture effects assessment; three target sites for pharmaceutical mixture effects assessment; three target sites for further mixture characterization; and three low-priority sites. Analyses identified 14 mixtures and 16 chemicals that significantly contributed to cumulative effects, representing high or medium priority targets for further ecotoxicological evaluation, monitoring, or regulatory assessment. Overall, our study represents an important complement to single-chemical prioritizations, providing a comprehensive evaluation of the cumulative effects of mixtures detected in a target watershed. Furthermore, it demonstrates how different tools and techniques can be used to identify diverse facets of mixture risk and highlights strategies that can be considered in future complex mixture assessments.

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