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

Abstract

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 concentrationdependent 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.

Niclosamide Exposure at Environmentally Relevant Concentrations Efficaciously Inhibited the Growth and Disturbed the Liver-Gut Axis of Adult Male Zebrafish

“…7 Recently, up to 1.8 tons of NIC were discharged in tributaries and lentic areas of the Laurentian Great Lakes to protect fisheries in 2020. 8 As a result, NIC residuals have been detected in various environment media, such as waters, 9 soils, 10 and even in milk, 11 and relatively high levels of NIC have been detected in surface water (38 μg/L) and sediments (474 μg/kg) from Poyang Lake of China. 7 Additionally, NIC can be accumulated in nontarget animals such as fish, 12 where the residuals can exist for quite a long time.…”

Identification and Prioritization of Environmental Organic Pollutants: From an Analytical and Toxicological Perspective

“…It features a formalized and rational integration of information from different domains (e.g., data from exposure status, chemical properties, in vitro assays, and biological pathways), and thus, more robust conclusions are expected to be obtained than any data source used alone . In particular, the accurately quantified concentration was illustrated to be a replaceable variable in case studies. , With reasonable selection and evaluation procedures, alternative variables in mass spectrometry data such as detection frequency and instrument response can be used to characterize the ecological risks of all detected chemicals beyond the scope of commercially available standards. It will significantly increase the likelihood of identifying causative pollutants corresponding to an adverse effect in complex samples. TEF i = AC 50 false( normalmin false) AC 50 false( normali false) TEQ i = TEF i × C i TEQ i % = TEQ i TEQ total EAR i = Exposure false( environmental concentration , μ normalM false) Activity ( activity concentration at cutoff , μ M ) …”

“…It is generally accepted that introducing NTS analytical techniques into EDA workflows can expand the range of chemicals monitored and increase the likelihood of identifying main effect-contributing pollutants. ,, For instance, a data set of estrogenic suspects was established based on the ToxCast database and Hallmark Gene Sets, which was then utilized in an EDA study to elucidate the monitored estrogenic potency of water samples. An additional 54% of the estradiol equivalent in samples was further explained by identifying the contributions of zearalenone and niclosamide to the effect . The suspect list generated by a predictive estrogenic activity model within the scope of chemicals in the NORMAN Substance Database was further used to identify contaminants in sewage sludge in California.…”

Methodology for Effect-Based Identification of Bioconcentratable Endocrine Disrupting Chemicals (EDCs) in Water: Establishment, Validation, and Application

“…Field water samples were extracted by solid phase extraction using a previously published method. 37 Briefly, the samples were loaded on glass HLB columns at a flow rate of 3−5 mL/min, which were activated by 10 mL of nhexane, dichloromethane, methanol, and Milli-Q water in advance. The cartridges were dried and eluted sequentially with 5 mL of methanol, 5 mL of dichloromethane, and 5 mL of n-hexane.…”

“…Qualitative analysis of Microcosm samples was performed on quadrupole time-of-flight mass spectrometry (QTOF-MS, TripleTOF 5600, AB Sciex, USA) coupled with HPLC (Agilent 1260, Agilent, USA) with an Agilent C18 column (2.1 × 150 mm, 2.5 μm) using a previously published method. 37 Full-scan MS profiles were acquired by informationdependent acquisition with electrospray ionization (ESI) in positive and negative modes. Details on the qualitative methods are provided in the SI.…”