Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River

Since
a large number of contaminants are detected in source waters
(SWs) and tap waters (TWs), it is important to perform a comprehensive
effect evaluation and key contributor identification. A reduced human
transcriptome (RHT)-based effect-directed analysis, which consisted
of a concentration-dependent RHT to reveal the comprehensive effects
and noteworthy pathways and systematic identification of key contributors
based on the interactions between compounds and pathway effects, was
developed and applied to typical SWs and TWs along the Yangtze River.
By RHT, 42% more differentially expressed genes and 33% more pathways
were identified in the middle and lower reaches, indicating heavier
pollution. Hormone and immune pathways were prioritized based on the
detection frequency, sensitivity, and removal efficiency, among which
the estrogen receptor pathway was the most noteworthy. Consistent
with RHT, estrogenic effects were widespread along the Yangtze River
based on in vitro evaluations. Furthermore, 38 of
100 targets, 39 pathway-related suspects, and 16 estrogenic nontargets
were systematically identified. Among them, diethylstilbestrol was
the dominant contributor, with the estradiol equivalent (EEQ) significantly
correlated with EEQwater. In addition, zearalenone and
niclosamide explained up to 54% of the EEQwater. The RHT-based
EDA method could support the effect evaluation, contributor identification,
and risk management of micropolluted waters.