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Evaluation of in vitro bioactivity of surface waters from a nationwide assessment of United States streams
Citation:
Blackwell, B., G. Ankley, P. Bradley, K. Houck, J. Swintek, AND Dan Villeneuve. Evaluation of in vitro bioactivity of surface waters from a nationwide assessment of United States streams. SETAC Focused Topic Meeting, Durham, NC, April 16 - 18, 2018.
Impact/Purpose:
In vitro bioassays can be used to evaluate the integrated effects of complex mixtures. In the current study, surface waters samples from 38 sites were screened through two multiplexed in vitro assays as part of a nationwide stream assessment. Between both assays, 69 target endpoints were screened covering 59 unique gene targets. Eleven commonly activated pathways were identified. Chemicals measured at environmental sites did not explain the biological activity for most endpoints, indicating that even robust chemical monitoring may not be adequate to describe potential biological effects. Land use characteristics indicative of anthropogenic inputs were correlated with bioeffects, suggesting point and non-point anthropogenic sources as contributors to observed bioactivity. Overall, the results highlight the applicability of multiplexed in vitro bioassays to environmental monitoring and identify biological targets on which to focus subsequent monitoring efforts.
Description:
Bioassays can be used to evaluate the integrated effects of complex mixtures of both known and unidentified contaminants present in environmental samples. Most bio-monitoring approaches have historically focused only on one or a few pathways (e.g. estrogen receptor, androgen receptor) despite the fact that the chemicals in a mixture may exhibit a range of biological activities. High-throughput screening approaches that can rapidly assess samples for a broad diversity of biological activities offer a means to provide a more comprehensive characterization of complex mixtures. In the current study, surface waters samples from 38 sites were screened through two multiplexed in vitro assays as part of a nationwide stream assessment. Between both assays, 69 target endpoints were screened covering 59 unique gene targets. In total, 26 endpoints demonstrated borderline activity above extract blanks (>1.25-fold induction), and 11 of these endpoints were active above baseline (>1.5-fold induction) in two or more samples. Active biological targets include aryl hydrocarbon receptor, estrogen receptor, glucocorticoid receptor, and pregnane X receptor. The number of registered National Pollution Discharge Elimination System (NPDES) sources and percent of watershed classified as “developed, low intensity” were both significantly correlated with bioactivities, suggesting point and non-point anthropogenic sources as contributors to observed bioactivity. Reported contaminant concentrations and assay bioactivity were further evaluated to identify potential associations between bioactivity and specific chemicals. Estrogen receptor activity was the only endpoint well predicted through exposure-activity analysis. Sparse partial least squares (SPLS) analysis identified 48 unique contaminants associated with bioactivity, suggesting potential surrogates of biological effect that could be used to prioritize locations with available chemical monitoring data for subsequent bioeffects monitoring. Overall, the results highlight the applicability of multiplexed in vitro bioassays to environmental monitoring and identify biological targets to focus development of adverse outcome pathways (AOPs) to better understand the consequence of increased biological activity in surface waters.