Potential Toxicity of Complex Mixtures in Surface Waters from a Nationwide Survey of United States Streams: Identifying in Vitro Bioactivities and Causative Chemicals

While chemical analysis of contaminant
mixtures remains an essential
component of environmental monitoring, bioactivity-based assessments
using in vitro systems increasingly are used in the detection of biological
effects. Historically, in vitro assessments focused on a few biological
pathways, for example, aryl hydrocarbon receptor (AhR) or estrogen
receptor (ER) activities. High-throughput screening (HTS) technologies
have greatly increased the number of biological targets and processes
that can be rapidly assessed. Here we screened extracts of surface
waters from a nationwide survey of United States streams for bioactivities
associated with 69 different end points using two multiplexed HTS
assays. Bioactivity of extracts from 38 streams was evaluated and
compared with concentrations of over 700 analytes to identify chemicals
contributing to observed effects. Eleven primary biological end points
were detected. Pregnane X receptor (PXR) and AhR-mediated activities
were the most commonly detected. Measured chemicals did not completely
account for AhR and PXR responses. Surface waters with AhR and PXR
effects were associated with low intensity, developed land cover.
Likewise, elevated bioactivities frequently associated with wastewater
discharges included endocrine-related end points ER and glucocorticoid
receptor. These results underscore the value of bioassay-based monitoring
of environmental mixtures for detecting biological effects that could
not be ascertained solely through chemical analyses.