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

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.

Pesticide Prioritization by Potential Biological Effects in Tributaries of the Laurentian Great Lakes

“…The Maumee River watershed has a history of environmental contamination related to urban (Toledo) and agricultural influences, and surface waters in the Maumee River Basin are contaminated by pesticides (Weaver et al, 1965) and pharmaceuticals (see Ankley et al, 2021; Baldwin et al, 2016). The pesticides with the most benchmark exceedances (either from the parent or a transformation product) at this site were the herbicides acetochlor, atrazine, and metolachlor, which had EAR chem or TQ chem exceedances in all 18 samples taken from the Maumee River, and the insecticide imidacloprid, which had TQ chem exceedances in all samples.…”

“…Streams in the Great Lakes Basin (USA/Canada) are of particular interest regarding pesticides due to a combination of substantial urban and agricultural inputs. Urban and agricultural streams have distinct pesticide signatures, and variability in land use can be a strong driver in the variability of occurrence and concentration of pesticides across the Basin (Ankley et al, 2021 ; Baldwin et al, 2016 ; Hladik & Kolpin, 2016 ). For example, herbicides like atrazine and metolachlor, which are used in Midwestern corn and soybean production, are frequently detected at concentrations above benchmark values in agricultural streams (Hladik et al, 2018 ; Nowell et al, 2018 ).…”

Prioritizing Pharmaceutical Contaminants in Great Lakes Tributaries Using Risk‐Based Screening Techniques

“…Fipronil is toxic to fish and aquatic invertebrates and has been reported to elicit adverse effects at concentrations below USEPA chronic benchmarks for invertebrates (Gibbons et al, 2015; Miller et al, 2020). Atrazine is an herbicide that has a wide range of potential adverse effects to aquatic life, including reproductive dysfunction in fish and reduced growth in algal species (Richter et al, 2016; Stratton, 1984), and it has previously been identified as a chemical of concern in Great Lakes tributaries (Ankley et al, 2021; Corsi et al, 2019). As an herbicide, atrazine has the potential to impact aquatic and wetland vegetation and inhibit water‐quality improvements from wetland ecosystems (Graymore et al, 2001).…”

Identifying Chemicals and Mixtures of Potential Biological Concern Detected in Passive Samplers from Great Lakes Tributaries Using High‐Throughput Data and Biological Pathways

“…Two approaches were used to gain insight into potential adverse outcomes and biological pathways: the adverse outcome pathway (AOP) and functional annotations associated with ToxCast assay gene targets. The AOP framework has previously been used in assessment of water quality data to help interpret the significance of EAR results for estimation of potential ecological impact (Corsi et al 2019 ; Ankley et al 2021 ) and is briefly described in the present study. The ToxCast assays have been mapped to corresponding key events and molecular initiating events in AOPs defined in the AOP‐Wiki (Fay et al 2018 ; Pittman et al 2018 ; Society for the Advancement of Adverse Outcome Pathways 2018 ; Corsi et al 2019 ).…”