Potential toxicity of complex mixtures in surface waters from a nationwide survey of United States streams: Identifying in vitro bioactivities and causative chemicals
Citation:
Blackwell, B., G. Ankley, P. Bradley, K. Houck, S. Makarov, A. Medvedev, J. Swintek, AND Dan Villeneuve. Potential toxicity of complex mixtures in surface waters from a nationwide survey of United States streams: Identifying in vitro bioactivities and causative chemicals. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 53(2):973-983, (2019). https://doi.org/10.1021/acs.est.8b05304
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:
While chemical analysis of contaminant mixtures remains an essential component of environmental monitoring, bioactivity-based assessments using in vitro systems increasingly play a role in the detection of possible biological effects. Historically, in vitro assessments focused on a few prominent biological pathways, such as aryl hydrocarbon receptor (AhR) or estrogen receptor (ER) activities. Over the past decade, novel test systems and high-throughput screening (HTS) technologies have greatly increased the number of biological targets and processes that can be rapidly assessed. Here we screened surface waters collected in a nationwide survey of United States (US) streams for activities associated with about 69 different endpoints (mostly vertebrate, nuclear receptor-mediated) using two different HTS assays. Bioactivity of extracts of surface water from 38 different streams was evaluated and compared with concentrations of over 700 analytes measured in split samples, in order to identify potential chemicals or sources contributing to observed effects. Eleven primary biological were detected. Pregnane X receptor (PXR) and AhR-mediated activities associated with regulation of xenobiotic metabolism were the most commonly detected. Measured chemicals did not completely account for the magnitude of AhR and PXR responses, but surface waters with detected effects were often associated with low intensity, developed land-cover. Likewise, elevated bioactivities frequently associated with wastewater treatment plant discharges included two involved in endocrine signalingthe ER and glucocorticoid receptor (GR). Steroidal estrogens (estrone, estradiol) were identified as the likely primary contributors to ER activity, but no known GR active compounds were identified. These results underscore the value of bioassay-based monitoring of environmental contaminant mixtures for detecting the occurrence of biological effects that could not be ascertained solely through chemical analyses.
URLs/Downloads:
DOI: Potential toxicity of complex mixtures in surface waters from a nationwide survey of United States streams: Identifying in vitro bioactivities and causative chemicals