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

G. T. Ankley, J. P. Berninger, B. R. Blackwell, J. E. Cavallin, T. W. Collette, D. R. Ekman, K. A. Fay, D. J. Feifarek, K. M. Jensen, M. D. Kahl, J. D. Mosley, S. T. Poole, E. C. Randolph, D. Rearick, A. L. Schroeder, J. Swintek, D. L. Villeneuve

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Assessment of ecological risks of chemicals in the field usually involves complex mixtures of known and unknown compounds. We describe the use of pathway-based chemical and biological approaches to assess the risk of chemical mixtures in the Maumee River (OH, USA), which receives a variety of agricultural and urban inputs. Fathead minnows (Pimephales promelas) were deployed in cages for 4 d at a gradient of sites along the river and adjoining tributaries in 2012 and during 2 periods (April and June) in 2016, in conjunction with an automated system to collect composite water samples. More than 100 industrial chemicals, pharmaceuticals, and pesticides were detected in water at some of the study sites, with the greatest number typically found near domestic wastewater treatment plants. In 2016, there was an increase in concentrations of several herbicides from April to June at upstream agricultural sites. A comparison of chemical concentrations in site water with single chemical data from vitro high-throughput screening (HTS) assays suggested the potential for perturbation of multiple biological pathways, including several associated with induction or inhibition of different cytochrome P450 (CYP) isozymes. This was consistent with direct effects of water extracts in an HTS assay and induction of hepatic CYPs in caged fish. Targeted in vitro assays and measurements in the caged fish suggested minimal effects on endocrine function (e.g., estrogenicity). A nontargeted mass spectroscopy-based analysis suggested that hepatic endogenous metabolite profiles in caged fish covaried strongly with the occurrence of pesticides and pesticide degradates. These studies demonstrate the application of an integrated suite of measurements to help understand the effects of complex chemical mixtures in the field. Environ Toxicol Chem 2021;40:1098–1122.

    Original languageEnglish (US)
    Pages (from-to)1098-1122
    Number of pages25
    JournalEnvironmental Toxicology and Chemistry
    Volume40
    Issue number4
    DOIs
    StatePublished - Apr 2021

    Bibliographical note

    Funding Information:
    We thank S. Corsi and E. Maloney for helpful comments on an earlier draft of the manuscript. We also thank J. Gottgens and colleagues at the University of Toledo for providing laboratory space and T. Jicha for providing critical technical support. Portions of the study were supported through the Great Lakes Restoration Initiative administered through the US Environmental Protection Agency Great Lakes National Program Office (GLNPO). We thank E. Smith, E. Murphy, and D. Ager from GLNPO for their contributions to our study.

    Funding Information:
    We thank S. Corsi and E. Maloney for helpful comments on an earlier draft of the manuscript. We also thank J. Gottgens and colleagues at the University of Toledo for providing laboratory space and T. Jicha for providing critical technical support. Portions of the study were supported through the Great Lakes Restoration Initiative administered through the US Environmental Protection Agency Great Lakes National Program Office (GLNPO). We thank E. Smith, E. Murphy, and D. Ager from GLNPO for their contributions to our study.

    Publisher Copyright:
    © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

    Keywords

    • Adverse outcome pathways
    • Field
    • Mixture
    • Toxicity

    PubMed: MeSH publication types

    • Journal Article

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