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基于体外多毒性试验对双酚A及其类似物安全性的综合评估

Comprehensive assessment of the safety of bisphenol A and its analogs based on multi-toxicity tests in vitro.

作者信息

Wang Juan, Hong Xiangsheng, Liu Wang, Zhang Le, Yan Saihong, Li Zhitong, Zha Jinmiao

机构信息

National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; National Joint Research Center for Ecological Conservation and High Quality Development of the Yellow River Basin, Beijing 100012, China; University of Chinese Academy of Sciences, Beijing 100049, China.

National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

出版信息

J Hazard Mater. 2025 Mar 15;486:136983. doi: 10.1016/j.jhazmat.2024.136983. Epub 2024 Dec 25.

DOI:10.1016/j.jhazmat.2024.136983
PMID:39742861
Abstract

As substitutes for bisphenol A (BPA), bisphenol analogs (BPs) have raised concerns due to their frequent environmental detection and unclear safety. Here, the cytotoxicity, endocrine disruption, neurotoxicity, aryl hydrocarbon receptor (AhR) activity, and genotoxicity of nine BPs and BPA were evaluated in three types of cell lines. Over half of the tested BPs exhibited greater cytotoxicity than BPA, with IC50 values showing a linear correlation with Log (R²=0.69). All tested BPs exhibited at least one endocrine-disrupting effect, notably estrogenic, which was observable even at 0.01-0.1 μM. Importantly, BPAF and BPAP exposure had widespread endocrine-suppressing effects. Moreover, all BPs (except BPP) and BPA increased SH-SY5Y cells apoptosis at 1-10 μM. Only BPF and BPP significantly increased 7-ethoxyresorufin-O-deethylase levels, highlighting their notable effects on AhR activity. BPAF significantly induced DNA damage at 1.25 μM, whereas BPA, BPF, and BPP induced damage at 20, 25, and 25 μM, respectively. Finally, ToxPi, a weighted scoring system, was used to rank the comprehensive toxicity of BPs, with 7 of 9 BPs showing higher scores than BPA. Collectively, BPs generally exhibited stronger comprehensive toxicity compared with BPA, emphasizing the urgent need for further research to confirm their potential health implications.

摘要

作为双酚A(BPA)的替代品,双酚类似物(BPs)因其在环境中频繁被检测到且安全性不明而引发关注。在此,对9种双酚类似物和双酚A在三种细胞系中的细胞毒性、内分泌干扰作用、神经毒性、芳烃受体(AhR)活性及遗传毒性进行了评估。超过半数的受试双酚类似物表现出比双酚A更强的细胞毒性,其半数抑制浓度(IC50)值与Log呈线性相关(R² = 0.69)。所有受试双酚类似物均表现出至少一种内分泌干扰效应,尤其是雌激素效应,即使在0.01 - 0.1 μM时也可观察到。重要的是,双酚AF(BPAF)和双酚AP(BPAP)暴露具有广泛的内分泌抑制作用。此外,所有双酚类似物(除双酚P(BPP)外)和双酚A在1 - 10 μM时均增加了SH - SY5Y细胞的凋亡。只有双酚F(BPF)和双酚P显著提高了7 - 乙氧基异吩唑酮 - O - 脱乙基酶水平,突出了它们对AhR活性的显著影响。双酚AF在1.25 μM时显著诱导DNA损伤,而双酚A、双酚F和双酚P分别在20、25和25 μM时诱导损伤。最后,使用加权评分系统ToxPi对双酚类似物的综合毒性进行排名,9种双酚类似物中有7种得分高于双酚A。总体而言,与双酚A相比,双酚类似物通常表现出更强的综合毒性,强调了进一步研究以确认其对健康潜在影响的迫切需求。

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