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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2021 · IF 6.291

Individual and combined effects of BPA, BPS and BPAF on the cardiomyocyte differentiation of embryonic stem cells

Ren Zhou,Ming Xia,Lei Zhang,Wei Cheng,Jia Yan,Yu Sun,Yan Wang,Hong Jiang

Exposure to many kinds of bisphenols (BPs) is common, and the effects of BP mixtures may differ from those of individual BPs. Therefore, evaluating combined exposure effects is necessary. Our study evaluated the individual and combined exposure effects of bisphenol A (BPA), bisphenol S (BPS) and bisphenol AF (BPAF) on embryonic development using an embryonic stem cell test (EST) and a concentration additive (CA) model at relatively high doses to uncover the interaction model of the three BPs. Environmentally relevant concentrations were then used to evaluate the possible effects of the individual and combined BPs at actual human exposure levels. Exposure to relatively high-dose BPA, BPS and BPAF inhibited embryonic stem cell differentiation into cardiomyocytes and exhibited weak embryo toxicity. Individually, BPA, BPS and BPAF inhibited endoderm, mesoderm and ectoderm marker expression but enhanced pluripotency marker expression. Combined exposure to BPs had an additive effect on cardiomyocyte differentiation and embryonic stem cell proliferation based on the CA model. Environmentally relevant individual or combined BP doses (10 ng/ml individual BPA, BPS and BPAF doses or 1 ng/ml and 10 ng/ml BP mixture doses) failed to cause oxidative stress, DNA damage or apoptosis changes in stem cell differentiation. The cardiomyocyte differentiation ratio also did not change significantly. Individual and combined exposure to environmentally relevant BP doses led to a significant increase in collagen expression. BPAF and the combination of BPs increased the type 1 collagen level, while the combination also increased the type 3 collagen level, which may be related to p38 pathway activation. The p38 pathway inhibitor SB203580 inhibited the increase in collagen during cardiomyocyte differentiation caused by low-dose BPs. These results suggest that relatively high-dose BPs in combination have an additive effect on cardiomyocyte differentiation. Low-dose BPs individually and in combination may affect cardiomyocyte collagen through the p38 pathway.

CAS / MDL: 1478-61-1
研究领域: 毒理学 · 发育生物学 · 细胞生物学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Maternal BPAF exposure impaired synaptic development and caused behavior abnormality in offspring

Xiaorong Wu,Shiqi Li,Yangyue Ni,Caoyan Qi,Shengjun Bai,Qiaoqiao Xu,Yun Fan,Xuan Ma,Chuncheng Lu,Guizhen Du,Zhipeng Xu,Yufeng Qin

Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4 + T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.

CAS / MDL: 1478-61-1
研究领域: 毒理学 · 神经科学 · 发育生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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WATER AIR AND SOIL POLLUTION · 2026 ·Vol. 237 ·期 10 ·572 · IF 3.5

Efficiency and Mechanism of Peroxymonosulfate Activation by MnaCo(1–a)Ox for BPAF Degradation

Zhang Jian,Wang Ningruo,Xie Xuewen,Liao Siyi,Zhong Biao,Feng Bo,Tian Chunxiang,Xu Yajun,Chen Yuhan,Xiao Jiewen

This study systematically evaluates the efficiency and mechanism of Mn–Co bimetallic oxides for peroxymonosulfate (PMS) activation to degrade bisphenol AF (BPAF). A series of spherical Mn a Co (1-a) O x catalysts were synthesized via a facile hydrothermal method. Among them, Mn 0.2 Co 0.8 O x exhibited the highest catalytic activity, outperforming other ratios. Under optimized conditions ([BPAF] = 5 mg/L, [PMS] = 0.2 mM, [Mn 0.2 Co 0.8 O x ] = 400 mg/L, pH = 7.85), the Mn 0.2 Co 0.8 O x /PMS system achieved 97.7% BPAF removal. Quenching tests and EPR spectroscopy confirmed SO 4 •⁻ and •OH as the predominant reactive oxygen species, with SO 4 •⁻ playing the dominant role. XPS and mechanism analysis indicated that the synergistic Co(III)/Co(II) and Mn(III)/Mn(II) redox cycles drive the efficient PMS activation and BPAF degradation.

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Toxics · 2026 ·Vol. 14 ·期 1 ·97 · IF 4.1

Perinatal BPAF Exposure Reprograms Offspring’s Immune–Metabolic Axis: A Multi-Omics Investigation of Intergenerational Hepatotoxicity

Shengjun Bai,Xiaorong Wu,Wei Mao,Mengan Guo,Yufeng Qin,Guizhen Du

Bisphenol AF (BPAF), a prevalent bisphenol A (BPA) substitute, raises concerns due to its environmental persistence and endocrine-disrupting potency. While metabolic effects of direct exposure are documented, its intergenerational consequences remain unclear. Here, we demonstrated that perinatal BPAF exposure induced persistent metabolic syndrome in offspring, including glucose intolerance, hepatic steatosis, and adipose hypotrophy. Integrating multi-omics data, we observed that BPAF exposure shaped offspring’s hepatic epigenome, as demonstrated by genome-wide alterations in H3K27ac-marked regulatory elements. This epigenetic rewiring indicated a dual regulatory effect on transcriptomes that suppressed interferon-γ responses while activating sterol biosynthesis, ultimately perturbating hepatic metabolome, including depleted pantothenate levels and accumulation of pro-inflammatory eicosanoids. Our findings suggest that BPAF may act as a developmental toxicant capable of persistently disrupting the immune–metabolic axis through epigenomic mechanisms, highlighting the need for careful re-evaluation of its use as a BPA substitute in consumer products.

CAS / MDL: 1478-61-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Environmental Chemical Engineering · 2024 · IF 7.4

Enhanced degradation of bisphenol AF (BPAF) by visible light irradiated zero valent iron activated persulfate system

Cheng Qin,Yumeng Qi,Qing Zheng,Xiaolei Teng,Ahmed A. Allam,Ahmed Rady,Zunyao Wang,Ruijuan Qu

In this study, we conducted a systematic study of bisphenol AF (BPAF) removal by visible light coupled zero valent iron activated persulfate (Vis/Fe 0 /PS) system. The results showed that in Fe 0 /PS system, the removal rate of BPAF increased by 46.4% with the addition of Vis. New mechanisms were proposed: that PS became excited under Vis irradiation, which favored its reaction with Fe 2+ to produce more free radicals. Moreover, Fe 3+ could form complex with mono-hydroxylated and mono-carboxylated intermediate of BPAF, and the photoinduced ligand-metal charge transfer (LMCT) process could effectively transfer the charge to the metal ion, accelerating the reduction of Fe 3+ to Fe 2+ to enhance the generation of free radicals. The generation of hydroxylation products of bisphenol AF in the Vis/Fe 0 /PS system was greatly increased compared to the Fe 0 /PS system. The Vis/Fe 0 /PS system had a great application prospect, as it reduced the economic cost of treating bisphenol AF by at least 49.5% compared to other methods. Moreover, 99.6% of bisphenol AF was degraded after 45 min of reaction under natural light. Findings of this study provides new insights into the synergistic role of Vis in Fe 0 /PS systems and may advance the practical application of Vis/Fe 0 /PS system in water and wastewater treatment.

研究领域: 环境科学 · 化学工程
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ANALYTICA CHIMICA ACTA · 2024 · IF 5.7

Single atom nanozyme sensing platform for simultaneous rapid detection of multiple bisphenols

Mengqiong Zhang,Guowen Wang,Jiping Chen,Xianbo Lu

Bisphenol compounds (BPA, BPS, BPAF, etc.) are one class of the most important and widespread pollutants that poses severe threat to human health and the ecological environment. Because of the presence of multiple bisphenols in environmental and food samples, it is urgent and challenging to develop a rapid and cheap technique for simultaneously detecting BPA and its analogues. In this study, a series of M - N -C (M = Cu, Mg, Ni, Co, Fe, K) single-atom nanozymes (SAzymes) were created by simulating the structure of natural enzyme molecules, which were used as novel sensing platform for the fabrication of electrochemical sensors. Through systematic screening and characterization, it was interestingly discovered that the electrochemical sensor based on Cu- N -C SAzymes exhibited the best sensing performance for bisphenols among all SAzymes, which catalyzed not only BPA like tyrosinase, but also showed excellent catalytic capacity beyond tyrosinase (tyrosinase has no catalytic activity for BPS, BPAF, etc.), and achieved potential-resolved simultaneous rapid detection of BPA, BPS and BPAF. Further structure-activity relationship and catalytic mechanism characterizations of Cu- N -C SAzymes revealed that the presence of single atom Cu was predominantly in the form of Cu + and Cu 2+ , which were anchored onto graphene nanosheet support through four coordination bonds with pyridinic N and pyrrolic N and acted as highly efficient active centers for electrocatalytic oxidation of bisphenols. The developed electrochemical sensing method exhibited excellent selectivity, sensitivity, and reliability for the rapid detection of multiple bisphenols in actual samples.

研究领域: 分析化学 · 环境科学 · 材料科学 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2020 · IF 5.778

Heterogeneous catalytic oxidation degradation of BPAF by peroxymonosulfate active with manganic manganous oxide: Mineralization, mechanism and degradation pathways

Ningruo Wang,Jian Zhang,Yongli Zhang,Peng Zhou,Jingquan Wang,Yang Liu

In this study, the catalytic ability and mechanisms involved in activating peroxymonosulfate (PMS) with Mn 3 O 4 and the degradation pathways of bisphenol-AF (BPAF) removal was investigated. SO 4 −• and · OH which were explored by and scavenging tests were the major reactive radicals in the Mn 3 O 4 /PMS system. A simple simulation algorithm was also used to calculate the relative concentrations of SO 4 −• ([SO 4 −• ]) and · OH ([ · OH]) which were 8.39 × 10 −15  M and 6.96 × 10 −13  M, respectively. The mechanism for the electron transfer between the Mn (II) and Mn (III) species was discussed. Three degradation pathways of BPAF were determined by the GC/MS and LC/MS technology , including chemical mechanism of oxidation, hydroxylation, electron transfer, polymerization, and ring-cleavage. In addition, the results suggested that the Mn 3 O 4 /PMS system had an efficient total organic carbon (TOC) removal rate and excellent environmental adaptability, the removal rate of TOC being as high as 73.2% in the control condition. Furthermore, the reuse experiments and the comparison on the structural and componential changes of Mn 3 O 4 powder before and after reaction demonstrated that the Mn 3 O 4 catalyst possessed excellent stability and reusability. Finally, a maximum BPAF degradation of approximately 90.0% was achieved on the optimal conditions for 500 mg/L Mn 3 O 4 dosage, 4 mM PMS concentration, 7.0 ± 0.2 initial pH, and 5 mg/L BPAF concentration respectively. And the effect of the coexisting anions and natural environmental water quality were also considered. This study demonstrated the Mn 3 O 4 /PMS system can be considered as a green approach for the removal of environmental reluctant pollutants.

研究领域: 环境科学 · 催化化学
✓ 已验证 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2026 · IF 6.6

Curcumin alleviates BPAF-induced ferroptosis in caprine endometrial epithelial cells through inhibition of endoplasmic reticulum stress and autophagy

Ming Liu,Cheng-Fang Gao,Jing-Jing Wang,Sheng-Ji Yang,Yin-Qing Li,Lei Sang,Li-Jun Huo

Bisphenol AF (BPAF) is widely used as a substitute for bisphenol A (BPA) in the plastics industry. However, it is known to cause reproductive toxicity in both humans and animal models. Curcumin, a polyphenolic compound from turmeric, is known for its potent anti-inflammatory and antioxidant effects. We previously showed that curcumin alleviates BPAF-induced apoptosis in caprine endometrial epithelial cells (EECs). However, the underlying mechanisms of BPAF toxicity remain unclear. The aim of this study was to investigate whether ferroptosis contributes to BPAF-induced injury in EECs and to assess the protective role of curcumin. We demonstrate that BPAF triggers ferroptosis in EECs: ferroptosis-related factors (COX2, FACL4, and NCOA4 ) were upregulated, and GSH content was increased. These effects were significantly reversed by the ferroptosis inhibitor Fer-1, which restored cell viability and reduced MDA accumulation. Mechanistically, BPAF-induced ferroptosis was autophagy-dependent, as evidenced by upregulated ATG5, Beclin1, and LC3, and enhanced autophagic flux. Inhibition of autophagy by CQ significantly attenuated ferroptosis and improved cell viability. Furthermore, ER stress acted as an upstream regulator, as its inhibitor 4-PBA alleviated both autophagy and ferroptosis. BPAF also disrupted cellular iron homeostasis by promoting NCOA4-mediated ferritinophagy, resulting in intracellular iron accumulation. Curcumin pretreatment alleviated BPAF-induced ferroptosis by suppressing ferritinophagy and restoring iron homeostasis. Moreover, activation of the PI3K/AKT/mTOR and Nrf2/HO-1 pathways may exert protective effects by suppressing autophagy and lipid peroxidation. In conclusion, this study indicates that ferroptosis is a key mechanism underlying BPAF-induced cytotoxicity in EECs. Curcumin protects against this damage by inhibiting ER stress and autophagy, providing a potential therapeutic strategy for BPAF-related uterine diseases.

✓ 已验证 DOI PubMed 高影响因子
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WATER RESEARCH · 2024 · IF 11.4

Cotransport of nanoplastics and plastic additive bisphenol AF (BPAF) in unsaturated hyporheic zone: Coupling effects of surface functionalization and protein corona

Xin Ling,Guanghua Lu,Leibo Zhang,Jiaqi Zhang,Heyun Fu,Zhenhua Yan

The ecological risk of combined pollution from microplastics (MPs) and associated contaminants usually depends on their interactions and environmental behavior, which was also disturbed by varying surface modifications of MPs. In this study, the significance of surface functionalization and protein-corona on the cotransport of nanoplastics (NPs; 100 nm) and the related additive bisphenol AF (BPAF) was examined in simulated unsaturated hyporheic zone (quartz sand; 250–425 μm). The electronegative bovine serum albumin (BSA) and electropositive trypsin were chosen as representative proteins, while pristine (PNPs), amino-modified (ANPs), and carboxyl-modified NPs (CNPs) were representative NPs with different charges. The presence of BPAF inhibited the mobility of PNPs/CNPs, but enhanced the release of ANPs in hyporheic zone, which was mainly related to their hydrophobicity changes and electrostatic interactions. Meanwhile, the NPs with high mobility and strong affinity to BPAF became effective carriers, promoting the cotransport of BPAF by 16.4 %–26.4 %. The formation of protein-coronas altered the mobility of NPs alone and their cotransport with BPAF, exhibiting a coupling effect with functional groups. BSA-corona promoted the transport of PNPs/CNPs, but this promoting effect was weakened by the presence of BPAF via increasing particle aggregation and hydrophobicity. Inversely, trypsin-corona aggravated the deposition of PNPs/CNPs, but competition deposition sites and increased energy barrier caused by coexisting BPAF reversed this effect, facilitating the cotransport of trypsin-PNPs/CNPs in hyporheic zone. However, BPAF and protein-coronas synergistically promoted the mobility of ANPs, owing to competition deposition sites and decreased electrostatic attraction. Although all of the NPs with two protein-coronas reduced dissolved BPAF in the effluents via providing deposition sites, the cotransport of total BPAF was improved by the NPs with high mobility (BSA-PNPs/CNPs) or high affinity to BPAF (BSA/trypsin-ANPs). However, the trypsin-PNPs/CNPs inhibited the transport of BPAF due to their weak mobility and adsorption with BPAF. The results provide new insights into the role of varying surface modifications on NPs in the vertical cotransport of NPs and associated contaminants in unsaturated hyporheic zone.

CAS / MDL: 75-05-8 9002-07-7
研究领域: 环境科学 · 生态学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2018 · IF 4.427

Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring

Zhiyuan Meng,Dezhen Wang,Sen Yan,Ruisheng Li,Jin Yan,Miaomiao Teng,Zhiqiang Zhou,Wentao Zhu

The widespread application of bisphenols (BPs) makes them ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of perinatal exposure to BPA and its 3 alternatives (BPS, BPF, and BPAF) on lipid and glucose homeostasis in female mice adolescent offspring . Specifically, BPA exposure promoted the expression of hepatic lipid synthesis and fatty acid accumulation genes, resulting in a significant increase in 2 free fatty acids contents. BPS exposure caused an increase in 6 free fatty acids and triglyceride contents through promoting the expression of fatty acid synthesis, triglyceride synthesis and fatty acid accumulation genes and inhibiting the expression of fatty acid β-oxidation genes. Interestingly, BPAF exposure showed completely opposite effects on hepatic lipid metabolism compared to BPS exposure. 9 free fatty acids and triglycerides contents in the liver were significantly reduced. In particular, BPF exposure caused decreases in 2 free fatty acids contents, but no significant changes were found in the genes for lipid metabolism. In addition, unlike BPA and BPF exposure, BPS and BPAF exposure also resulted in significant increases in glucose and glycogen contents in the liver by activation of Fxr-Sh p pathway and glycolysis, and inhibition of gluconeogenesis. The results showed that compared to BPA and BPF exposure, BPS and BPAF exposure significantly regulated the expression of genes related to glucose and lipid metabolism and severely interfered with hepatic lipid and glucose homeostasis. This suggested that we should thoroughly evaluate the potential health risks of BPA and its alternatives.

CAS / MDL: 7789-20-0
研究领域: 环境科学 · 分子生物学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2019 ·Vol. 26 ·期 6 ·5804-5813 · IF 2.914

1H NMR-based serum metabolomics analysis of the age-related metabolic effects of perinatal exposure to BPA, BPS, BPF, and BPAF in female mice offspring

Meng Zhiyuan,Zhu Wentao,Wang Dezhen,Li Ruisheng,Jia Ming,Yan Sen,Yan Jin,Zhou Zhiqiang

The widespread application of bisphenols (BPs) in the industry has made them ubiquitous in the environment, causing potential environmental risks. Its unknown impacts on human being have received more and more attention. In this study, we have assessed the metabolic effects of perinatal exposure to bisphenol A (BPA) and its substitutes (bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF)) in female mice adolescent offspring and female mice adulthood offspring. 1 H NMR-based serum metabolomics showed that metabolic profiles were disturbed with BPA and its three substitutes exposure in female mice adolescent offspring and female mice adulthood offspring. In addition, age-related metabolic effects were found based on changes in serum endogenous metabolites and metabolic pathways. Specifically, metabolic pathway analysis showed that major disturbed metabolic pathways in female mice adulthood offspring compare with female mice adolescent offspring also changed significantly. With the increase of age of the female mice offspring, changes in the metabolic pathways became more obvious in the BPA treatment group. Conversely, partially disturbed metabolic pathways were restored in the BPS, BPF, and BPAF treatment groups. In conclusion, perinatal exposure to BPA and its three substitutes significantly interferes with metabolic profiles and metabolic pathways, and this metabolic effects were age-related. These results offer more detailed information about the age-related metabolic effects of perinatal exposure to BPA, BPS, BPF, and BPAF in female mice offspring and provide data for systematic evaluation of the health risk assessment of BPA and its substitutes.

研究领域: 环境毒理学 · 代谢组学 · 发育生物学 · 生殖毒理学 · 分子毒理学 · 环境健康 · 生命早期暴露
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