Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source...

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 EEQ_water. In addition, zearalenone and niclosamide explained up to 54% of the EEQ_water. The RHT-based EDA method could support the effect evaluation, contributor identification, and risk management of micropolluted waters.