High-throughput in Vitro Data To Inform Prioritization of Ambient Water Monitoring and Testing for Endocrine Active Chemicals

The presence of industrial chemicals,
consumer product chemicals,
and pharmaceuticals is well documented in waters in the U.S. and globally.
Most of these chemicals lack health-protective guidelines and many
have been shown to have endocrine bioactivity. There is currently
no systematic or national prioritization for monitoring waters for
chemicals with endocrine disrupting activity. We propose ambient water
bioactivity concentrations (AWBCs) generated from high throughput
data as a health-based screen for endocrine bioactivity of chemicals
in water. The U.S. EPA ToxCast program has screened over 1800 chemicals
for estrogen receptor (ER) and androgen receptor (AR) pathway bioactivity.
AWBCs are calculated for 110 ER and 212 AR bioactive chemicals using
high throughput ToxCast data from in vitro screening assays and predictive
pathway models, high-throughput toxicokinetic data, and data-driven
assumptions about consumption of water. Chemical-specific AWBCs are
compared with measured water concentrations in data sets from the
greater Denver area, Minnesota lakes, and Oregon waters, demonstrating
a framework for identifying endocrine bioactive chemicals. This approach
can be used to screen potential cumulative endocrine activity in drinking
water and to inform prioritization of future monitoring, chemical
testing and pollution prevention efforts.