Comprehensive Nontargeted Analysis of Drinking Water Supplies to Identify Chemicals Associated with Estrogen Receptor Agonism or Present in Regions of Elevated Breast Cancer Occurrence

To explore the hypothesis that differential exposures
to estrogen
active chemicals may contribute to regional disparities in cancer
incidence, a comprehensive targeted and nontargeted analysis was conducted
over two seasons (2020) for drinking water samples from 120 households
served by 8 public water systems (4 with historically elevated breast
cancer incidence) and from 15 brands of retail water. All samples
were analyzed using gas and liquid chromatography with high-resolution
mass spectrometry and a bioassay for estrogen receptor agonism. Target
compounds included disinfection byproducts, per- and polyfluoroalkyl
substances (PFAS), trace elements, and compounds selected for their
possible relation to breast cancer. Over 7500 GC and LC nontargeted
molecular features passed all quality control filters in each sampling
season and were prioritized for identification if they were related
to measured estrogen receptor agonism or were present at higher levels
in areas with high breast cancer incidence (n = 1036).
Benzothiazole-2-sulfonic acid, acetyl tributyl citrate, and diphenyl
sulfone were among the prioritized and confirmed nontarget compounds.
Nine polycyclic aromatic hydrocarbons and two ketone derivatives displayed
significant negative correlations with estrogen receptor agonism.
Many prioritized compounds remained unidentified, as 84.4% of the
LC features and 77.5% of the GC features could not be annotated with
high confidence.