Bisphenol analogues (BPs), a prominent group of endocrine-disrupting compounds, are widely used in the production of epoxy resins and polycarbonate plastics, leading to their inevitable release into aquatic environments. However, limited data exists on the occurrence of BPs in drinking water sources and upstream rivers. In this study, we developed and validated a solid-phase extraction method coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the trace-level detection and simultaneous quantification of 19 BPs in surface water. Seventeen BPs were detected in the Taipu River with concentrations ranging from non-detectable to 38.2 ng L-1 and industrial discharges may be a primary source of BPs contamination. For the first time, the presence of bisphenol C-dichloride (BPC-di) and tetrachlorobisphenol A in surface water was reported, with mean concentrations of 11.5 ng L-1 and 2.0 ng L-1, respectively. In drinking source water, 15 BPs were found, with bisphenol A, bisphenol B, and BPC-di being the most abundant ones. Additionally, a comprehensive toxicity assessment was performed to evaluate the ecological risks associated with these BPs. Although risk quotient values indicated negligible ecological risk for these BPs, estrogen equivalence values suggested potential estrogenic risks in the river. This study provides new insights into the occurrence, ecological risks, and estrogenic effects of BPs in source water and its upstream river systems.

Bisphenol AF (BPAF) is a widespread endocrine disruptor in the environment, and the use of BPAF has been strongly associated with the development of several diseases. In this study, we investigated the effects of BPAF on growth, development, oxidative stress and lipid metabolism in zebrafish. We chose the concentrations based on the measured LC50 at 96 h post-fertilization (96 hpf), and the zebrafish embryos were exposed to three different concentrations (0.125, 0.5 and 2 μmol/L). The findings indicated that BPAF exposure in zebrafish leaded to alterations in heart rate, body length and hatching rate, as well as an accumulation of red blood cells in the heart. Additionally, BPAF exposure resulted in increased levels of neutrophils, reactive oxygen species (ROS) and malondialdehyde (MDA), and decreased activity of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), thus disturbing the balance between oxidative and antioxidative systems. BPAF promoted fatty acid catabolism and inhibited fatty acid synthesis, ultimately leading to a reduction in fatty acid content. Mechanistically, RNA-seq analysis and RT-qPCR revealed a significant upregulation of heat shock protein 70 (hsp70) after BPAF exposure. Inhibition of hsp70 with VER-155008 ameliorated BPAF-induced oxidative stress. These data provided a novel approach to investigate BPAF-induced oxidative stress and suggested that regulation of hsp70 is a crucial target for alleviating this process.

Bisphenol AF (BPAF), a polyfluorinated compound and widely used substitute for bisphenol A, is ubiquitous in the environment. However, the fate of BPAF in soil is still obscure. Here, we used [ring-U-14C]-labeled BPAF to investigate its fate in three agricultural soils for 240 days, based on a four-compartment fate model. BPAF dissipated in the soils with a half-life of 35-110 days, accompanied by low mineralization (8.5-11.3% of the initial radioactivity). The main fate of BPAF in the soils was formation of nonextractable residues (NERs) (44.2-65.3%), mostly (>90%) via physicochemical sequestration (31.2-42.7%) and ester bonds (10.0-22.6%). Notably, the sequestered free BPAF in the NERs increased the half-life by 1.4-2.5 times. Six transformation products (TPs) were identified, including BPAF mono- and dimethyl ethers, monosulfate ester, and three single-ring monophenolic compounds. BPAF monomethyl ether was the predominant extractable TP, while the polar TPs were the predominant physico-chemically sequestered and ester-linked TPs in the NERs. Three transformation pathways for BPAF in the soils are proposed, including type II ipso-substitution, O-methylation, and sulfate conjugation. Our study provides the first quantitative information on the fate of BPAF in soil, and highlights the importance of NERs in determining the persistence of BPAF.

Due to the growing environmental and health concerns surrounding bisphenol S (BPS) as a common bisphenol A (BPA) substitute, this study investigated the metabolic pathways and tissue-specific accumulation of BPS in flowering cabbage under hydroponic conditions, revealing key insights into plant detoxification processes and potential human health risks. Over a 32-day exposure of 5 mg L-1 14C-BPS, 60.2 ± 3.0 % of 14C in the nutrient solution was taken up, with the 14C-radioactivity accounting for 40.2 ± 2.6 %, 5.3 ± 0.3 %, and 14.5 ± 0.6 % in roots, stems, and leaves, respectively. Older leaves retained higher levels of BPS and/or its metabolites. Using HPLC-LSC, LC-MS/MS, and subcellular fractionation, we identified four metabolites, characterized by glycosylation, malonylation, sulfation, and amino acid conjugation pathways. BPS and its metabolites were primarily located in the cell wall, plastid, and soluble component. The segregation of BPS and metabolites into the cell wall and plastid resulted in the formation of large amounts of non-extractable residues in roots. Results highlight that BPS metabolites, particularly glycosylated forms like M526, may accumulate in edible plant parts. These findings advance understanding of BPS metabolism in plants, underlining the potential food safety risks posed by its uptake and metabolism in agricultural systems.

Following the restrictions on bisphenol A (BPA), the production and environmental release of bisphenol analogues (BPs) have increased. However, knowledge about the occurrence of bisphenol analogues other than BPA, especially in farmland soils and edible plants, remains limited. This study investigated the occurrence, contamination characteristics, and human health risks of eight bisphenol analogues in paired soil-plant samples from areas near factories in eastern China. Results indicated that the concentrations of Σ8BPs in the collected soil and plant samples ranged from 1.4 to 897.1 ng/g dw and 2.5 to 586.2 ng/g dw, respectively. BPA, bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) were the primary components of BPs, with BPA having the highest detection frequency (74 %). In addition, a positive correlation was observed between the root concentration factor and the log Kow of BPs (R2 = 0.471, P < 0.05), whereas the translocation factor exhibited a negative correlation with the log Kow (R2 = 0.405, P < 0.05). The hazard index (HI) values of BPs in paired soil-plant samples were <1, suggesting that the current contamination levels of BPs in soils and plants are unlikely to pose significant health risks to humans. However, potential risks from long-term exposure require careful monitoring. This study offers new insights into the spatial distributions and contamination status of BPs in farmland soils and plants, highlighting the environmental behavior and health risks of other bisphenol analogues.

Bisphenol AF (BPAF), one of the most common bisphenol analogues, has been reported to exhibit higher estrogenic activity compared to bisphenol A (BPA) due to the presence of additional hydrophobic groups. To comprehensively understand the male reproductive toxicity of BPAF, TM3 Leydig cells were used to investigate the effects of BPAF on cell proliferation, apoptosis, and cell cycle arrest. The underlying mechanisms of cellular responses induced by BPAF were examined through analysis of target mRNA and protein expression. Results showed that BPAF treatment reduced cell viability and induced both G2/M cell cycle arrest and apoptosis in a time- and dose-dependent manner in TM3 Leydig cells. RNA sequencing analysis and experimental verification further revealed that the p53 signaling pathway was involved in BPAF-induced cytotoxicity. Furthermore, Pifithrin-α (PFT-α), a p53 inhibitor, attenuated BPAF-induced G2/M cell cycle arrest and apoptosis. These results demonstrate that the p53 signaling pathway mediates BPAF-induced cell cycle arrest and apoptosis in Leydig cells, providing mechanistic insights into BPAF's toxicological effects on the male reproductive system.

The extensive usage of bisphenols in the production of plastics and other materials has raised concerns about their potential adverse effects on human and marine ecosystems. This comprehensive review paper aims to provide insights into the various types of bisphenols and their derivatives, as well as the multiple pathways through which human and marine life can be exposed to these compounds. Additionally, it highlights the growing importance of developing effective detection methods for bisphenols and their derivatives due to their potential health and environmental implications. The focus then shifts towards metal-organic frameworks (MOFs) as promising materials for the detection of bisphenols. We delve into the characteristic properties of MOFs and their potential and limitations in the detection of bisphenols and their derivatives. This paper also addresses the significance of pristine MOFs and explores the potential of MOF-based composites for achieving enhanced detection performance. Subsequently, various detection techniques utilizing MOFs and their composites are reviewed. In the final sections, the recent strategic developments and challenges in this field, offering a concise summary of the principal findings of this review, novel approaches, limitations of current methodologies, and emerging trends for future directions, are discussed. This comprehensive exploration of the subject matter not only illuminates the current state of research on the detection of bisphenols but also provides valuable insights into the opportunities and challenges in this evolving field. In conclusion, this review underscores the critical importance of advancing the detection of bisphenols and their derivatives, with MOFs and their composites emerging as promising candidates for more efficient and sensitive detection. The potential for their applications in diverse fields, coupled with ongoing research efforts, suggests a bright future for MOF-based bisphenol detection technologies.

High doses of bisphenol AF (BPAF), a widely used chemical in many products, has been reported to exert adverse effects on lipid or glucose metabolism, but whether low-dose exposure, especially in combination with a high-sugar, high-fat diet (Western diet, WD), has unacceptable effects remains unexplored. Here, we investigated the effects of postnatal exposure to 50 μg/kg/d (low) BPAF on glycolipid homeostasis in mice receiving administration through drinking water under the WD stress after weaning or not, in comparison with the effects 5000 (high) BPAF without stress. After approximately 8-week exposure, blood tests of glucose metabolism revealed that high-dose BPAF caused insulin resistance and elevated insulin levels in a normal diet (ND)-fed mice; low-dose BPAF exerted slight effects in ND-fed mice but caused significant glucose metabolic impairment under the WD stress. Also, low-dose BPAF exerted limited effects on pancreas islets as well as hepatic histology and metabolic homeostasis in ND-fed mice, but aggravated pancreatic and hepatic impairments caused by the WD stress. We also conducted cell culture experiments using β-TC-6 and HepG2 cells to explore whether BPAF could directly interfere with pancreatic cells and hepatocytes. In vitro assays showed that BPAF affected insulin secretion of pancreatic β-TC-6 cells in a glucose-dependent manner and glucose sensitivity of HepG2 cells, with slight effects on lipid metabolism in HepG2 cells. All results collectively demonstrate that low-dose BPAF caused metabolic disorders under the WD stress, highlighting its health risks. Besides, in vitro data suggest that BPAF may directly affect glucose metabolism rather than lipid metabolism.

In this study, the genotoxic effects of three different bisphenols (BPAF, BPF and BPS) and their mixture were assessed in the crab Carcinus aestuarii. Crabs were exposed for 7 and 14 days to 300 ng/L of BPA analogues, alone or as a mixture (100 ng/L for each compound). After 7- and 14-day exposure, gills and hepatopancreas were sampled from crabs to evaluate damage to DNA by quantifying the levels of DNA single- and double-strand breaks. Results indicated that BPA analogues increased the DNA damage in both gills and hepatopancreas. In detail, BPAF, the most hydrophobic compound tested, exerted a marked effect on DNA. Overall, results suggest that such relatively new compounds can cause damage to DNA in crabs, raising doubts about the toxicological profile of BPA analogues, at least in the species studied and under the conditions tested in this study.

Bisphenol AF (BPAF) has been widely used as a main alternative to bisphenol A (BPA), and previous in vitro studies have shown that BPAF has higher reproductive toxicity potentials than BPA. However, data on in vivo toxicity of BPAF is still limited. In this study, Sprague Dawley rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to study toxicokinetics and reproductive toxicity in offspring. The results showed that plasma concentrations BPAF peaked within 6 h after birth, followed by a two-phase decay, with clearance rates of approximately 3.0 l/h and terminal half-life values ranging from 77 h to 114 h, suggesting fast absorption and high persistence of BPAF. At postnatal day 21 (PND21), BPAF was found to be bioaccumulated in reproductive organs (testes and ovaries) of the offspring, resulting in adverse effects on reproduction in both sexes. Lower anogenital distance, reduced relative testicular weight, dissolved interstitial cells, fewer primary spermatocytes, decreased testosterone levels, and increased luteinizing hormone levels were detected in male offspring. In female offspring, vacuolization in follicular antrum, fewer follicles, increased 17β-estradiol levels, and increased luteinizing hormone levels in female offspring were found. Gene expression of scavenger receptor class B type I (SR-B1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), sterol regulatory element-binding protein-1c (SREBP-1c), and several steroidogenic enzymes was significantly decreased in male offspring following maternal exposure to BPAF, suggesting that the decreases in testosterone levels is a result of inhibited cholesterol uptake, cholesterol de novo synthesis, and steroidogenesis. In addition, inhibition of pathways of phagosome and cell adhesion molecules might be the underlying molecular mechanism involved in BPAF-induced reproductive disorders in male offspring. This study provides the scientific basis for a comprehensive assessment of the safety of BPAF.

Due to the established endocrine-disrupting effects of Bisphenol A (BPA), alternative bisphenols entered the market. Bisphenol AF (BPAF) is now commonly used in the industrial manufacturing of polycarbonate plastics and epoxy resins. However, BPAF's effects on reproduction and development have not been thoroughly reviewed. We investigated the relationship between BPAF exposure and reproduction and early development. We performed a literature review of studies on BPAF and reproductive physiology. Using keywords, we searched PubMed, Medline, Cochrane Library Database, Embase, and ClinicalTrials.gov for English language literature available until December 2024; we additionally identified and included studies from bibliographies. We included 125 articles, spanning in vitro and in vivo model organism and human studies. BPAF is a selective estrogen receptor modulator and an androgen receptor antagonist and is more potent than BPA. It is detected in urine, blood products, saliva, amniotic fluid, and breast milk. In vitro and in vivo studies demonstrate a spectrum of BPAF-induced endocrine and reproductive changes in both sexes. There is strong evidence of alterations in the hypothalamic-pituitary-gonadal axis and of altered steroidogenesis pathways. Multiple studies using zebrafish, Xenopus, chickens, and rodents, show BPAF's effects on embryogenesis, morphology, and sexual differentiation. Decreased serum testosterone and impaired spermatogenesis and oocyte viability have been demonstrated. The current literature shows clear disruptive effects of BPAF on reproductive health and embryonic development. Though further investigation is warranted, there is ample converging evidence to support limiting the use of BPAF and other similar bisphenols.

Bisphenols (BPs) are pervasive environmental contaminants extensively found in indoor environments worldwide. Despite their ubiquitous presence and potential health risks, there remains a notable gap in the comprehensive reviews focusing on BPs in indoor dust. Existing literature often addresses specific aspects such as exposure pathways, transformation products, or biomonitoring techniques, but lacks a consolidated, in-depth review encompassing all these facets. This review provides a comprehensive overview of the global distribution of BPs, emphasizing their prevalence in diverse indoor settings ranging from households and workplaces to public areas. Variations in BP concentrations across these environments are explored, influenced by factors such as industrial activities, consumer product usage patterns, and geographical location. Exposure assessments highlight ingestion, inhalation, and dermal contact as primary pathways for BP exposure, with ingestion being particularly significant for vulnerable groups such as infants and young children. Studies consistently reveal higher concentrations of BPs in urban indoor dust compared to rural settings, reflecting the impact of urbanization and intensive consumer practices. Moreover, BPs from mobile sources like vehicles contribute significantly to overall human exposure, further complicating exposure assessments. The review also delves into the transformation of BPs within indoor environments, emphasizing the diverse roles of physical, chemical, and biological processes in generating various transformation products (TPs). These TPs can exhibit heightened toxicity compared to their parent compounds, necessitating deeper investigations into their environmental fate and potential health implications. Critical examination of biomonitoring techniques for BPs and their metabolites underscores the importance of non-invasive sampling methods, offering ethical advantages and practicality in assessing human exposure levels. The emerging use of bioindicators, encompassing plants, animals, and innovative approaches like spider webs, presents promising avenues for effectively monitoring environmental contamination.

The fluorinated bisphenol A (2,2-bis[4-hydroxyphenyl]propane, BPA) substitute bisphenol AF (BPAF) could be more persistent and toxic than BPA, but little is known about its environmental fate. In this study, we established a co-metabolic BPAF-degrading bacterial enrichment culture with BPA as the growth substrate. BPAF degradation by the enrichment culture was dependent on BPA, and BPAF could be eliminated to below the detection limit with successive additions of BPA. BPAF was mainly degraded via phenolic ring hydroxylation and sequential ring cleavage, which are minor BPA transformation pathway. Conjugated BPAF products were also identified based on the characteristic CF3- fragment and were found to accumulate during BPAF degradation. Sphingopyxis was the key BPA and BPAF degrader in the aerobic enrichment cultures, which was the most abundant genera in only BPA-added and BPA and BPAF-added cultures and was proven to be able to degrade BPA and BPAF by isolation. The aerobic co-metabolic BPAF degrading community also contain non-BPA and BPAF degraders, such as Pandoraea, which may play a supporting role in the community.

Bisphenol AF (BPAF), a substitute for bisphenol A (BPA), exhibits potent endocrine-disrupting properties that pose a serious health hazard to organisms. This study employed marine medaka as a model, subjecting them to different concentrations of BPAF (0.61, 6.65, and 91.88 μg/L) from the embryonic stage for a period of 160 days. Findings showed that 91.88 μg/L BPAF reduced survival rates and altered sex ratios. Furthermore, exposure to BPAF at all concentrations led to a significant increase in body length and weight. Behavioral analysis revealed that BPAF exposure impaired the swimming ability of the medaka. Histological changes included disrupted ovarian development, reduced sperm count, liver inflammation, and intestinal damage. Gene expression analysis revealed impacts on nervous system (e.g., gap43, itr, elavl3), HPG axis (e.g., gthα, erα, 3βhsd), and liver genes (e.g., chgl, vtg2). Additionally, BPAF altered the diversity and richness of gut microbes in marine medaka, leading to significant changes in specific bacterial species and intestinal functions. In conclusion, long-term BPAF exposure induced neurotoxicity, reproductive toxicity, and impaired digestive and immune systems in marine medaka, with sex-specific effects. These results provide further evidence of the potential hazards of BPAF as an environmental pollutant.

Bisphenol AF (BPAF) is degraded through the ultrasound-assisted in situ generation and activation of hydrogen peroxide (H2O2) by the copper(II) catalysed oxidation of hydroxylamine (NH2OH) with dioxygen (O2). Compared to added H2O2, in situ generated H2O2 significantly improves the degradation of BPAF from 46.7% to 94.8% in ∼15 min. The reaction follows a pseudo-first-order kinetic model. This study examines the influence of solution pH, anions, humic acid, and different concentrations of the reactants on BPAF degradation. Mass spectrometry was used to identify the BPAF degradation products, and a degradation pathway is proposed. This work advances the understanding of in situ hydrogen peroxide generation and activation in advanced oxidation (Fenton-like) processes (AOPs).

Bisphenol A analogues are largely used plasticisers that are going to replace bisphenol A in many sectors. Due to this replacement, their discharge and presence in the marine coastal areas are increasing, with unknown consequences for organisms and the trophic chain. This study assessed the effects of three different bisphenols (BPAF, BPF and BPS) - alone or as a mixture - provided via food (exposed clams) to the crab Carcinus aestuarii. First, clams were exposed for two weeks to 300 ng/L of each of the three bisphenols and their mixture (100 ng/L of each) to allow the bioaccumulation of the contaminants in bivalves. Then, crabs were fed for two weeks with BPA analogue-exposed clams, while unexposed clams were used to feed control crabs. After 7 and 14 days, haemolymph, gills and hepatopancreas were collected from crabs to measure a battery of biomarkers indicative of cytotoxicity, oxidative stress and damage, neurotoxicity, physiological performance (respiration and excretion rate) and electron transport system activity. Lastly, bioaccumulation of BPA analogues was assessed by UHPLC-HRMS in crabs. Our findings revealed that BPA analogue-exposed clams were able to alter total haemocyte count, haemocyte size and their proliferation. The activity of immune enzymes, such as phosphatases and phenoloxidase was altered. Moreover, we observed an impairment of antioxidant and detoxifying enzymes like SOD, CAT, GST and GPX activities. Alterations of metabolism-involved enzymes and physiological parameters and increased oxidative damage to macromolecules like proteins, lipids, and DNA were also observed in crabs. Among BPA analogues, only bioaccumulation of BPAF, which has the highest Logkow value among the tested bisphenols, was evidenced in crabs. Overall, the obtained results indicated that crabs, under the tested experimental conditions at least, underwent alterations in cellular, biochemical and physiological responses following a diet of bisphenol-exposed clams, suggesting a potential ecotoxicological risk in the marine food chain.

Bisphenol AF (BPAF) and TGSA are analogues of Bisphenol A (BPA). BPAF is used in polymer synthesis, while TGSA is applied in thermal papers. The EU classifies BPAF as toxic to reproduction and TGSA as a skin sensitizer. However, TGSA's other health effects remain unclear. BPAF contamination has been noted among electronic waste workers, and TGSA exposure is documented in various professions. Despite the significance of skin contact, data on skin permeation rates for BPAF and TGSA are limited. This study aimed to generate percutaneous absorption data for BPAF and TGSA following OECD guidelines. [14C]-labeled BPAF or TGSA was applied to human skin samples in vitro using Franz diffusion cells for 20 and 40 h, respectively. Key parameters such as steady-state flux, lag time, and skin permeability coefficient (Kp) were calculated. Furthermore, the distribution of the dose across different compartments, particularly within the skin, was evaluated at the conclusion of the experiment. Sequential strippings and epidermis-dermis separation were conducted for BPAF to predict the potential absorption of the remaining dose present within the skin. The permeability coefficients for BPAF and TGSA were found to be 1.9 E-03 and 1.6 E-03 cm/h, with 22% and 23% of the applied doses absorbed, respectively. Both chemicals are classified as "fast" penetrants based on their Kp values. These findings suggest that BPAF and TGSA are absorbed through the skin, highlighting potential occupational risks through dermal exposure. The new percutaneous absorption data will enhance the assessment of the occupational risks.

The presence and distribution of toxic organic compounds in soil pose significant challenges. Whether their distributional characteristics are more complex, especially in arid and semi-arid regions with harsh climatic conditions? This study analyzed the composition, classification, spatial distribution, and sources of 123 toxic organic compounds in 56 soil samples of coal-electricity production base. Those compounds were classified into 11 categories, mainly pesticides (41 compounds), organic synthesis intermediates (31 compounds), and drugs (23 compounds). Seventeen of those compounds were detected over the rate of 30 %, with 13 of them being under the Toxic Substances Control Act (TSCA) inventory. The primary sources of toxic organic compounds were determined using Principal Component Analysis (PCA) and Positive Matrix Factorization (PMF), including the degradation of pesticide residues (22.03 %), emissions of plastic pellets (16.64 %), industrial waste emissions (12.80 %), emissions from livestock (12.74 %), plastic films (11.22 %) and coal-to-liquid projects (10.78 %). This research underscores the widespread presence of toxic organic compounds in soil, highlighting their origins and distribution patterns, which are essential for developing targeted environmental management strategies in arid and semi-arid regions.

Bisphenol AF (BPAF) is found in high concentrations in aquatic environments due to the increased use of thermal paper and food packaging. However, there have been relatively few toxicological studies and potential risk assessments of BPAF. In this study, the risk quotient (RQ) and hazard quotient (HQ) of BPAF were derived to present the safety standards for environmental risk management and protection in lakes, rivers, bays, and Italian regions. We applied the species sensitivity distribution (SSD) method based on the previous ecotoxicological data and the results of supplementary toxicity tests on BPAF. From the SSD curves, the hazardous concentration for 5 % of the species (HC5) values for the acute and chronic toxicity data were 464.75 µg/L and 3.59 µg/L, respectively, and the acute- and chronic-based predicted no-effect concentration were derived as 154.92 µg/L and 1.20 µg/L, respectively. The acute-based RQ (RQA)values of BPAF in all regions were negligible (RQ < 0.1). The chronic-based RQ (RQC) in the Xitang River (XR) and the Central Italy (CI) showed a considerably high ecological risk (12.77 and 1.29) and the Hangzhou Bay (0.21), the South and North Italy (0.79 and 0.27), and the Tamagawa River (0.13) had a medium ecological risk (0.1 < RQ < 1.0). However, the HQ values based on the tolerable daily intake for BPAF over all age groups in these regions was < 0.1, indicating the low health risk. Nonetheless, the result of this study indicates that BPAF contamination is serious in XR and CI, and their use and emissions require continuous monitoring.

This study explored the levels, distribution, potential sources, ecological risks and estrogenic activities of 14 bisphenol analogues (BPs) in soil under eight land-use types in the megacity of Chengdu, China. Eleven BPs were detected in the soil samples and the total concentrations ranged from 32.3 to 570 ng/g d.w. Levels of bisphenol BP (BPBP) in the soil (up to 208 ng/g d.w.) only second to the most dominant compound bisphenol A (BPA) were found. Relatively higher Σ14BP accumulation in the soil was observed in the commercial and residential areas (median: 136 ng/g d.w. and 131 ng/g d.w.) compared with agricultural area (median: 67.5 ng/g d.w.). Source identification indicated the role of atmospheric particulate deposition and consecutive anthropogenic activities in BP emission. The ecotoxicity assessment implied that BPA, bisphenol S (BPS), bisphenol F (BPF) and bisphenol PH (BPPH) might pose low to medium risk to the ecosystem due to their extensive use and biological effects. The calculated 17β-estradiol equivalents of BPs were in the range of 0.501-7.74 pg E2/g d.w, and the estrogenic activities were inferior to those contributed by natural estrogens in the soil.

Bisphenols are emerging endocrine disrupting pollutant, and several studies have reported that they are already ubiquitous in various environmental matrices and intend to deposit in sediment. The primary sources of bisphenols are river and sewage discharge. Sea cucumber (Apostichopus japonicus), a typical deposit feeder, is one of the most important commercial marine species in Aisa. However, the effects of the bisphenol A (BPA) and its analogues bisphenol AF (BPAF) on sea cucumber was unclear. In this study, we carried out field survey in major sea cucumber farming areas in northern China, with the aim of determining which bisphenol analogue is the major bisphenol contamination in this aquaculture area. The results showed that the presence of BPAF was detected in four sampling sites (Dalian, Tangshan, Laizhou, and Longpan). The mean level of BPAF in Laizhou sediment samples was the highest which reached to 9.007 ± 4.702 μ g/kg. Among the seawater samples, the BPAF only have been detected in the samples collected at Longpan. (0.011 ± 0.003 μ g/L). Furthermore, we conducted an experiment to evaluate the single and combined toxicity of BPA and BPAF on sea cucumbers. The concentrations were informed by the findings based on the results of field research. (0.1, 1.0, and 10 μ g/L). After exposure, the body weight gain, and specific growth rate showed no significant changes (P > 0.05). We observed the histological alterations in respiratory tree of treated sea cucumbers including the fusion and detachment of lining epithelial tissue, and increase of lumen space. However, the catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) activity was not significantly changed (P > 0.05). We evaluated the effects of BPA and BPAF through calculating the integrated biomarker response index (IBR), and the results indicated that the toxicity of combined treatment was higher than single treatment. Additionally, BPAF exposure to A. japonicus was more toxic than BPA.

Bisphenol A (BPA) is an endocrine disruptor strongly associated with ovarian dysfunction. BPA is being substituted by structurally similar chemicals, such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF). However, the toxicity of these analogues in female reproduction remains largely unknown. This study evaluated the effects of BPA and its analogues BPS, BPF, and BPAF on the mitochondrial mass and function, oxidative stress, and their potential to induce apoptosis of human granulosa cells (KGN cells). BPA and its analogues, especially BPA and BPAF, significantly decreased mitochondrial activity and cell viability. The potential of bisphenols to reduce mitochondrial mass and function differed in the following order: BPAF > BPA > BPF > BPS. Flow cytometry revealed that exposure to bisphenols significantly increased mitochondrial ROS levels and increased mitochondrial Ca2+ levels. Thus, bisphenols exposure causes mitochondrial stress in KGN cells. At the same time, bisphenols exposure significantly induced apoptosis. These results thus emphasize the toxicity of these bisphenols to cells. Our study suggests the action mechanism of BPA and its analogues in damage caused to ovarian granulosa cells. Additionally, these novel analogues may be regrettable substitutes, and the biological effects and potential risks of BPA alternatives must be evaluated.

Bisphenol AF (BPAF) is a novel environmental endocrine disruptor, and is widely detected in the aquatic environment, which is a potential threat to the health of fish. In this study, male Oryzias curvinotus were exposed to environmental concentrations (0.93 and 9.33 μg/L) of BPAF for 21 days. The effects of BPAF on survival, growth, reproduction, liver and testis histology, and gene transcriptional profiles of O. curvinotus were investigated. The results showed that the survival rate of male O. curvinotus slight decrease with increasing BPAF concentration, and there was no significant effect on body length, body weight, and K-factor. BPAF (9.33 μg/L) caused significant changes in testicular structure and reduced spermatid count in O. curvinotus. Changes in transcript levels of some antioxidant-related genes in gills and liver following BPAF exposure, imply an effect of BPAF on the immune system. After BPAF exposure, chgs and vtgs were up-regulated, validating the estrogenic effect of BPAF. In the hypothalamic - pituitary - gonadal axis (HPG) results, erα, erγ and cyp19a1b were all up-regulated in the brain, and the 0.93 μg/L BPAF group was more up-regulated than the 9.33 μg/L BPAF group. In testis, BPAF significantly up-regulated the mRNA expression level of cyp17a1 and cyp11b, while significantly down-regulated mRNA expression level of cyp11a, and cyp19a1 was significantly down-regulated only in the 0.93 μg/L BPAF group. In conclusion, environmental levels of BPAF have adverse effects on the survival and reproduction of O. curvinotus, and the potential toxic effects of environmental levels of BPAF cannot be ignored.

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.

Bisphenol analogues (BPs) have gained increasing attention in recent years due to their ubiquitousness and potential endocrine disrupting properties in environments. However, little information is available on their spatiotemporal distribution, source apportionment and ecological risk in river sediments, especially the case in river basins with a high population density and those typical regions with agricultural-urban gradient, where land use patterns and intensity of human activity are varying. In this study, field investigations of BPs in the sediment of the entire Qinhuai River Basin, a typical agricultural-suburban agricultural-urban gradient area, were conducted before and after the flood period. Thirty-two sites were sampled for six types of BPs, resulted in no significant difference in the concentration of ΣBPs between the two periods, with ΣBPs ranging from 3.92 to 151 ng/g and 2.16-59.0 ng/g, respectively. Bisphenol A (BPA) was the main contributor. Whereas a multivariate analysis of variance (MANOVA) suggested that the composition structure of BPs had been influenced by water periods. The land use patterns had an impact on the distribution of ΣBPs in river sediments, which was more significant in after the flood period, with ΣBPs in urban rivers was 1.85 times, 3.44 times, and 3.08 times higher than the suburban rivers, agricultural rivers, and reservoirs, respectively. Yet land use types did not significantly alter the composition structure of BPs. The correlation analysis between BPs and the physicochemical properties of sediments showed a significant positive correlation between BPA and total organic carbon (TOC). The positive matrix factorization model (PMF) suggested that BPs in sediments of the basin might be influenced by industrial coatings, textiles, electronics and biopharmaceuticals, as well as urban wastewater or solid waste generated from daily life. The ecological risk assessment posed by BPA, based on the risk quotient, indicated that the ecological risk of BPA in sediments was low for three indicator benthic organisms: crustaceans, worms, and mollusks. However, the risk of BPA in river sediments varied among different land use patterns, with the risk ranking as follows: reservoirs < agricultural rivers < suburban rivers < urban rivers.

Bisphenol A (BPA) and its analogues have been proved to be harmful to human reproduction, endocrine and nervous system. But information on the occurrence and human exposure to bisphenol compounds (BPs) in dust (especially outdoor dust) is limited. In this study, 14 BPs were determined in 174 indoor dust samples and 202 outdoor dust samples from Chinese mainland, Hong Kong, Macau and Taiwan. BPA, BPS, BPAF, BPF, BPAP and BPE were widely detected with detection frequencies of 98.94 %, 98.67 %, 97.87 %, 95.21 %, 87.23 % and 71.54 %, respectively. The median total concentrations of the most detected six BPs in the dust were in the order of south urban indoors (556 ng/g) > south rural outdoors (438 ng/g) > south urban outdoors (432 ng/g) > south rural outdoors (418 ng/g) > north rural indoors (412 ng/g) > north urban outdoors (341 ng/g) > north urban indoors (311 ng/g) > north rural outdoors (246 ng/g). The amounts of garbage incineration, plastic output and recycled paper may have influence on the BPs levels. Some BPs (BPAF, BPAP, BPF and BPS) in the indoor and outdoor samples were significantly positively correlated. In addition, the BPs in the indoor dust from different indoor micro environments in Chengdu were investigated. BPA (median concentration: 571.2 ng/g) and BPF (median concentration: 114.3 ng/g) were the two primary BPs, accounting for 78.1 % of the median total concentrations of the investigated BPs. High concentration of BPA appeared in printing workshops and offices, while high concentration of BPAP, BPC, BPE and BPF appeared in electronic repair shops. Occupational exposure to BPs deserves attention in the future. ΣBPs exposure risk for children and adults in the urban areas of southern China was the highest. To our knowledge, this is the first report in China to study BPs in outdoor dust sample.

Exposure to bisphenols has been found to have adverse effects on male reproductive function in animals. Human exposure to bisphenols is widespread. Bisphenol A (BPA) and its analogues, including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) are utilized in various consumer products such as food contact materials and dental resins. The effects of these compounds on male fertility and spermatogenesis are unclear and findings from human studies are inconsistent. In this cross-sectional study, we evaluated the influence of BPA, BPS, BPF, BPAF (BPs) measured in semen on number of spermatozoa, total motility, progressive motility, morphology, and DNA fragmentation. We also examined the association of bisphenols (BPs) exposure with patients' occupation. A total of 358 patients aged 17-62 years with BMI 18-42 were included in the study from 2019 to 2021. BPs were extracted using solvent extraction followed by preconcentration step and determined by high-performance liquid chromatography and tandem mass spectrometry (LC/MSMS). Bisphenols were detected in 343 from 349 analysed samples (98.3% of all the samples). In 6 samples, the concentration of all BPs was under the limit of detection and in 20 samples under the limit of quantification. We did not find a statistically significant relationship between occupation and BPs. However, we observed significant correlations between the concentration of BPA and a lower motility and normal morphology. For BPS, a significant correlation with a lower ejaculate volume and a lower total sperm count was found. BPF and BPAF were detected only in 14.3% and 23.9% of samples, respectively. For BPF and BPAF, no significant correlations with spermiogram parameters were observed. Our results show that BPs are widespread in the male population (more than 90% of analysed samples), independently of an occupation and in case of BPA and BPS having a negative impact on spermiogram parameters.

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

Widespread occurrences of various poly- and perfluoroalkyl substances (PFAS) in terrestrial environment calls for the growing interest in their transport behaviors. However, limited studies detected PFAS with structural diversity in tree barks, which reflect the long-term contamination in atmosphere and play a vital role in air-soil exchange behaviors. In this study, 26 PFAS congeners and typical branched isomers were investigated in surface soils and tree barks at 28 sites along the Taihu Lake, Taipu River, and Huangpu River. Concentrations of total PFAS in soils and tree barks were 0.991-29.4 and 7.99-188 ng/g dw, with PFPeA and PFDoA were the largest contributors in the two matrices. The highest PFAS levels were found in the Taihu Lake watershed, where textile manufacturing and metal plating activities highly prosper. With regard to the congener and isomer signatures, short-chain homologs dominated in soils (65.5%), whereas long-chain PFAS showed a major proportion in barks (41.9%). The composition of linear isomers of PFOS, PFOA and PFHxS implied that precursor degradation might be an important source of PFAS in addition to the 3M electrochemical fluorination (ECF). Additionally, the distance from the emission source, total organic carbon (TOC), logKOA and logKOW were considered potential influencing factors in PFAS distributions. Based on the multi-media fugacity model, about 71% of the fugacity fraction (ffs) values of the PFAS were below 0.3, indicating the dominant deposition from the atmosphere to the soil. The average fluxes of air-soil exchange for PFAS were -0.700 ± 11.0 ng/(m2·h). Notably, the estimated daily exposure to PFAS ranged from 9.57 × 10-2 to 8.59 × 10-1 ng/kg·bw/day for children and 3.31 × 10-2 to 3.09 × 10-1 ng/kg·bw/day for adults, suggesting low risks from outdoor inhalation and dermal uptake. Overall, results from distribution with structural diversity, air-soil exchange and preliminary risk assessment. This study provided in-depth insight of PFAS in multi-medium environment and bridged gaps between field data and policy-making for pollution control.

In this study, a novel functionalized magnetic composite (MNCGC) for magnetic solid-phase extraction of bisphenols from environmental and food samples was developed, featuring a multistep synthesis with Fe3O4, chitosan, graphene oxide, and β-cyclodextrin, crosslinked by glutaraldehyde. Characterization confirmed its advantageous morphology, intact crystal structure of the magnetic core, specific surface area, and magnetization, enabling efficient adsorption and separation via an external magnetic field. The optimized MSPE-HPLC-FLD method demonstrated excellent sensitivity, linearity, and recovery rates exceeding 80% for bisphenol pollutants, validating the method's effectiveness in enriching and detecting trace levels of bisphenols in complex matrices. This approach offers a new avenue for analyzing multiple bisphenol residues, with successful application to environmental water and food samples, showing high recovery rates.

Bisphenol analogues (BPs) are commonly used as modifiers, stabilizers and photo-initiators in polymer materials, including those used in food packaging. Compared to adults, infants are more sensitive to chemicals because their bodies are growing and not fully developed. Therefore, it is essential to determine the concentrations of BPs in common infant foods to assess infant exposure and prevent hazards. We collected 54 infant formula (IF) samples, 90 complementary food (CMF) samples and 62 breastmilk samples from breastfeeding women in south China. Tandem mass spectrometry coupled to liquid chromatography separation (HPLC-MS/MS) was used to detect the concentrations of 8 BPs in the three types of food samples. The estimated daily intake (EDI) of infants was also assessed. The results showed that the detection frequency of bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF) and bisphenol AP (BPAP) were relatively high among the different infant foods. BPF, BPP and BPS were predominant among the detected BPs. The lowest 95th EDI for BPA was 0.67 ng kg-bw-1 day-1, exceeding the tolerable daily intake (TDI) limit for BPA set by the European Food Safety Authority in 2023. Thus, BP exposure is a significant risk to infants. More attention should be paid to the presence of BPs in daily use products and food, and intake limits should be set for BPs other than BPA.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 μg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 μg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

There is evidence in humans that endocrine disrupting chemicals exposure, such as bisphenol A (BPA), is tied to social behavior impacts when evaluated in early life stage. However, the potential social impact of BPA alternatives and its association with central nervous system (CNS) is poorly understood. Here, we performed behavioral test for zebrafish that are continuously exposed to environmental relevant concentrations (5 and 500 ng/L) of BPA, BPF, and BPAF since embryonic stage. Surprisingly, significant social behavior defects, including increased social distance and decreased contact time, were identified in zebrafish treated by 500 ng/L BPAF and BPA. These behavioral changes were accompanied by apparent histological injury, microglia activation, enhanced apoptosis and neuron loss in brain. The gut-brain transcriptional profile showed that genes involved in neuronal development pathways were up-regulated in all bisphenol analogs treatments, indicating a protective phenotype of CNS; however, these pathways were inhibited in gut. Besides, a variety of key regulators in the gut-brain regulation were identified based on protein interaction prediction, such as rac1-limk1, insrb1 and fosab. These findings implicated that the existence of bisphenol analogues in water would influence the social life of fish, and revealed a potential role of gut-brain transcriptional alteration in mediating this effect.

Plant accumulation of phenolic contaminants from agricultural soils can cause human health risks via the food chain. However, experimental and predictive information for plant uptake and accumulation of bisphenol congeners is lacking. In this study, the uptake, translocation, and accumulation of five bisphenols (BPs) in carrot and lettuce plants were investigated through hydroponic culture (duration of 168 h) and soil culture (duration of 42 days) systems. The results suggested a higher bioconcentration factor (BCF) of bisphenol AF (BPAF) in plants than that of the other four BPs. A positive correlation was found between the log BCF and the log Kow of BPs (R2carrot = 0.987, R2lettuce = 0.801, P < 0.05), while the log (translocation factor) exhibited a negative correlation with the log Kow (R2carrot = 0.957, R2lettuce = 0.960, P < 0.05). The results of molecular docking revealed that the lower binding energy of BPAF with glycosyltransferase, glutathione S-transferase, and cytochrome P450 (-4.34, -4.05, and -3.52 kcal/mol) would be responsible for its higher accumulation in plants. Based on the experimental data, an attention mechanism multi-layer perceptron (AM-MLP) model was developed to predict the BCF of eight untested BPs by machine learning, suggesting the relatively high BCF of bisphenol BP, bisphenol PH, and bisphenol TMC (BCFcarrot = 1.37, 1.50, 1.03; BCFlettuce = 1.02, 0.98, 0.67). The prediction of BCF for ever-increasing varieties of BPs by machine learning would reduce repetitive experimental tests and save resources, providing scientific guidance for the production and application of BPs from the perspective of priority pollutants.

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 μg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.

Bisphenol AF (BPAF) is a newly identified contaminant in the environment that has been linked to impairment of the male reproductive system. However, only a few studies have systematically studied the mechanisms underlying BPAF-induced toxicity in testicular Sertoli cells. Hence, this study primarily aims to explore the toxic mechanism of BPAF on the porcine Sertoli cell line (ST cells). The effects of various concentrations of BPAF on ST cell viability and cytotoxicity were evaluated using the Counting Kit-8 (CCK-8) assay. The results demonstrated that exposure to a high concentration of BPAF (above 50 μM) significantly inhibited ST cell viability due to marked cytotoxicity. Flow cytometry analysis further confirmed that BPAF facilitated apoptosis and induced cell cycle arrest in the G2/M phase. Moreover, BPAF exposure upregulated the expression of pro-apoptotic markers BAD and BAX while downregulating anti-apoptotic and cell proliferation markers BCL-2, PCNA, CDK2, and CDK4. BPAF exposure also resulted in elevated intracellular levels of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside reduced activities of the antioxidants glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Furthermore, the ROS scavenger N-acetyl-L-cysteine (NAC) effectively blocked BPAF-triggered apoptosis and cell cycle arrest. Therefore, this study suggests that BPAF induces apoptosis and cell cycle arrest in ST cells by activating ROS-mediated pathways. These findings enhance our understanding of BPAF's role in male reproductive toxicity and provide a foundation for future toxicological assessments.

Plastic-related contaminants in the environment have attracted increasing attention, with plastic pollution becoming a serious issue globally. The present study investigated the potential bioaccumulation and biotransfer of bisphenol (BP) compounds that are widely added in various products such as plastics and other products in a freshwater ecosystem, China. Among commonly applied 14 BP analogues, bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) were predominant, representing 64%-100% of the total concentrations of BPs (ΣBPs) in freshwater wildlife. Both the concentrations and analogue profiles in the fish showed seasonal differences and species dependence. Higher BP concentrations were observed in fish collected during the dry season than the wet season. Higher percentages of non-BPA analogues (e.g., BPS and BPF) were observed in fish collected during the wet season. Pelagic species accumulated notably higher levels of BPs than midwater and bottom species. The liver generally contained the highest ΣBPs, followed successively by the swim bladder, belly fat, and dorsal muscle. The analogue profile also showed some differences among tissues, varying by species and season. Lower ΣBPs but higher percentages of non-BPA analogues were observed in female than male common carp. Time trends of the BPA concentration in fish varied by species, probably related to habitats and diets of the fish. Habitats, feeding behaviors, and trophic transfer may have significant impacts on exposure of wildlife to BPs in natural ecosystems. The BPs did not demonstrate strong potential for bioaccumulation. More research is warranted about metabolism and transgenerational transfer of BPs in wildlife to fully reveal the bioaccumulation and consequently ecological risks of these chemicals in the environment. Environ Toxicol Chem 2023;42:2130-2142. © 2023 SETAC.

Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. In recent years, its connection with environmental pollutants, such as bisphenol A (BPA), has been demonstrated; consequently, new structurally similar molecules are used to replace BPA in the plastics industry (BPS, BPF and BPAF).

To carry out a systematic review to allow coherent evaluation of the state of the art. Subsequently, a meta-analysis was performed to unify the existing quantitative data.

Firstly, a systematic review was carried out, using the terms "(bisphenol) AND (Diabetes OR Hyperglycemia)", to maximize the number of results. Subsequently, three authors analyzed the set of articles. Finally, a meta-analysis was performed for each BP, using RevMan software. In addition, funnel plots were developed to study publication bias.

The systematic analysis of the literature revealed 13 recent articles (2017-2023) related to the study paradigm. The qualitative analysis showed interesting data linking diabetes to the three most widely used substitute BPs in the industry: BPS, BPF and BPAF. Finally, the meta-analysis determined a positive relationship with BPS, BPF and BPAF, which was only statistically significant with BPS.

There is a need to apply the precautionary principle, regulating the use of new BPs. Therefore, replacing BPA with BPS, BPF or BPAF is unlikely to protect the population from potential health risks, such as DM.

Bisphenol AF (BPAF) is an emerging endocrine-disrupting chemical (EDC) prevalent in the environment as one of the main substitutes for bisphenol A. Sex-specific effects of EDCs have been commonly reported and closely linked to sexually dimorphic patterns of hormone metabolism and related gene expression during different exposure windows, but our understanding of these mechanisms is still limited. Here, following 28-day exposure of adult zebrafish to an environmentally relevant concentration of BPAF at 10 μg/L, the global transcriptional networks applying RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were respectively investigated in the male and female fish liver, connecting the sex-dependent toxicity of the long-term exposure of BPAF to molecular responses. As a result, more differentially expressed genes (DEGs) were detected in males (811) than in females (195), and spermatogenesis was the most enriched Gene Ontology (GO) functional classification in males, while circadian regulation of gene expression was the most enriched GO term in females. The expression levels of selected DEGs were routinely verified using qRT-PCR, which showed consistent alterations with the transcriptional changes in RNA-seq data. The causal network analysis by IPA suggested that the adverse outcomes of BPAF in males including liver damage, apoptosis, inflammation of organ, and liver carcinoma, associated with the regulation of several key DEGs detected in RNA-seq, could be linked to the activation of upstream regulatory molecules ifnα, yap1, and ptger2; while, the inhibition of upstream regulators hif1α, ifng, and igf1, leading to the down-regulated expression of several key DEGs, might be involved in BPAF's effects in females. Furthermore, BPAF exposure altered hepatic histological structure and inhibited antioxidant capability in both male and female livers. Overall, this study revealed different regulation networks involved in the sex-dependent effects of BPAF on the fish liver, and these detected DEGs upon BPAF exposure might be used as potential biomarkers for further assessing sex-specific hepatotoxicity following environmental EDC exposure.