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Background: The pollution of organophosphate flame retardants (OPFRs) is of global concern, but the site-specific data of OPFR concentrations in drinking water are scarce for many areas of the world outside of Europe and the US. This study aimed to investigate the occurrence and profiles of OPFRs in the tap water treatment and delivery process in Shanghai. Methods: In total, 106 samples were analyzed for 10 OPFRs, which were collected periodically from monitoring points of drinking water treatment plants and piped water between November 2021 and July 2023. The average daily doses of OPFRs through the ingestion of tap water were calculated by multiplying nominal volumes of water ingestion rates with the measured concentrations of OPFRs. Hazard quotients, the hazard index, and the carcinogenic risks of OPFRs via drinking water were used to estimate the health risks. Results: Tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris (1-chloro-2-propyl) phosphate (TCIPP) were found in >90% of the tap water samples, whereas triethyl phosphate (TEP) and tris (2,3-dibromopropyl) phosphate (TDBPP) were not found in any samples. The concentrations of Σ10OPFRs were found at part-per-trillion ranges, with average concentrations that ranged from 86.0 ng/L in February 2023 (dry season) to 218 ng/L in July 2022 (wet season). TCIPP was the most abundant compound among the investigated OPFRs. The average daily dose of Σ10OPFRs via the ingestion of tap water was up to 20.4 ng/kg body weight/day. The hazard quotients of OPFRs through drinking water were in the range of 10−5–10−4, indicating low risk levels. Moreover, the hazard index of OPFRs indicated that the risk for children (2 × 10−4) was higher than adults (7 × 10−5). Conclusion: Tap water intake may be an important source of OPFRs exposure. But the risk of OPFRs for local residents is at a low level through drinking water. [ABSTRACT FROM AUTHOR]

Variants in the genes encoding gamma‐aminobutyric acid type A (GABAA) receptor subunits are associated with epilepsy. To date, over 1000 clinical variants have been identified in these genes. However, the majority of these variants lack functional studies and their clinical significance is uncertain although accumulating evidence indicates that proteostasis deficiency is the major disease‐causing mechanism. Here, we apply two state‐of‐the‐art modeling tools, namely AlphaMissense and Rhapsody to predict the pathogenicity of saturating missense variants in genes that encode the major subunits of GABAA receptors in the central nervous system, including GABRA1, GABRB2, GABRB3, and GABRG2. We demonstrate that the predicted pathogenicity correlates well between AlphaMissense and Rhapsody. In addition, AlphaMissense pathogenicity score correlates modestly with plasma membrane expression, peak current amplitude, and GABA potency of the variants that have available experimental data. Furthermore, almost all annotated pathogenic variants in the ClinVar database are successfully identified from the prediction, whereas uncertain variants from ClinVar partially due to the lack of experimental data are differentiated into different pathogenicity groups. The pathogenicity prediction of GABAA receptor missense variants provides a resource to the community as well as guidance for future experimental and clinical investigations. [ABSTRACT FROM AUTHOR]