Evaluation of Complex Mixture Toxicity in the Milwaukee Estuary (WI, USA) Using Whole‐Mixture and Component‐Based Evaluation Methods

Abstract

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. Environ Toxicol Chem 2023;42:1229–1256. © 2023 SETAC

Estrogenic activity and acute toxicity assessments of sediments from a chronically polluted estuarine area in southeastern Brazil

“…The estrogenic activities detected herein for Guanabara Bay sediments were close to those reported at the Santa Lucia Basin, ranging from non‐detected (ND) to 8.49 ngg −1 (Griffero et al., 2018), corroborating the relationship between estrogenicity and urban‐industrial land use postulated by those authors and other literature assessments (Griffero et al., 2018; Maloney et al., 2023). Studies in other countries have reported variable values, such as in samples from the Rhine River in Germany, which ranged from 1.03 to 5.14 ng g −1 (Schulze‐Sylvester et al., 2016).…”

“…between estrogenicity and urbanindustrial land use postulated by those authors and other literature assessments(Griffero et al, 2018;Maloney et al, 2023). Studies in other countries have reported variable values, such as in samples from the Rhine River in Germany, which ranged from 1.03 to 5.14 ng g −1(Schulze-Sylvester et al, 2016).…”

Assessing Contaminants of Emerging Concern in the Great Lakes Ecosystem: A Decade of Method Development and Practical Application

“…Understanding biological consequences in such a complex system is challenging for many reasons, including data limitations and lack of knowledge concerning potential interactions among contaminants (Nilsen et al, 2019). One approach to assessing mixture effects explored by scientists involved in the GLRI‐CEC project focused on the use of various types of available effects/bioactivity data in conjunction with models to forecast possible interactive risks of chemicals detected in environmental samples (Maloney et al, 2023b). However, not every contaminant present will or can be detected, and for many compounds that are detected, no biological effects data exist.…”

“…When co-located with in situ deployment of fish (e.g., fathead minnows [Pimephales promelas]) or potentially other organisms, this provides a basis for connecting a range of biological responses in the organisms (e.g., changes in gene, protein, or metabolite expression; altered sex steroid concentrations) to the time-averaged concentrations of tens to hundreds of contaminants present in the same water over the same time. This linked caged fish-composite sampler approach was employed at many of the GLRI study sites (e.g., Ankley et al, 2021;Davis et al, 2016;Garcia-Reyero et al, 2022;Li et al, 2017;Maloney et al, 2023aMaloney et al, , 2023b, thereby enhancing the ability to associate exposures with effects.…”

“…This provides a basis for translation of the HTP information into potential apical effects in organisms in the field. Insights derived from HTPderived single-chemical data and/or direct HTP assays have been integral to interpretation of many of the field studies conducted through the GLRI-CEC work, several of which used their results to inform AOP-based predictions of effects (Alvarez et al, 2021;Ankley et al, 2021;Baldwin et al, 2022;Blackwell et al, 2017;Corsi et al, 2019;Li et al, 2017;Loken et al, 2023;Maloney et al, 2023aMaloney et al, , 2023bOliver et al, 2023;Pronschinske et al, 2022). Mosley et al (2018) describe another application of a NAM to better understand exposure and effects of complex mixtures in fish.…”