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Bisphenol A (BPA) is an emerging organic compound used in the production of epoxy resin, polycarbonate plastics and thermal paper. Following the restrictions on the use of bisphenol A, many substitutes have been produced as its replacement in several consumer products. The main task of this research was to examine the toxic effects of single bisphenol analogues and their mixtures against freshwater microalgae Chlorella vulgaris and Desmodesmus armatus. The findings suggest that bisphenol B, bisphenol C, bisphenol PH (EC50 (14 day): 33.32-43.32 mg L-1) and bisphenol B, bisphenol C, bisphenol FL, bisphenol PH (EC50 (14 day): 30.49-64.54 mg L-1) show strong toxic effects towards C. vulgaris and D. armatus, respectively. In turn, the research results indicate that the toxicity of a mixture of examined bisphenol analogs on both species of green algae is much higher (EC50 (14 day): 24.55-32.68 mg L-1) than the individual toxicity of each component of the mixture. Therefore, it can be concluded that mixtures lead to the occurrence of synergistic effects. The toxicity of the individual bisphenol analogues and their mixture by EC50 (14 day) values in descending order, was as follows: mixture>bisphenol PH> bisphenol B> bisphenol C> bisphenol FL> bisphenol F> bisphenol E for C. vulgaris and bisphenol B> mixture> bisphenol FL> bisphenol C> bisphenol PH> bisphenol E> bisphenol F for D. armatus, respectively. Moreover, the present research expands current knowledge of the ecotoxicological risks of bisphenol analogues to aquatic organisms. [ABSTRACT FROM AUTHOR]

Copyright of Ege Journal of Fisheries & Aquatic Sciences (EgeJFAS) / Su Ürünleri Dergisi is the property of Ege Journal of Fisheries & Aquatic Sciences (EgeJFAS) / Su Urunleri Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Plastics, while providing modern conveniences, have become an inescapable source of global concern due to their role in environmental pollution. Particularly, the focus on bisphenol A (BPA) reveals its biohazardous nature and association with liver issues, specifically steatosis. However, research indicates that BPA is just one facet of the problem, as other bisphenol analogues, microplastics, nanoplastics and additional plastic derivatives also pose potential risks. Notably, BPA is implicated in every stage of non‐alcoholic fatty liver disease (NAFLD) onset and progression, surpassing hepatitis B virus as a primary cause of chronic liver disease worldwide. As plastic contamination tops the environmental contaminants list, urgent action is needed to assess causative factors and mitigate their impact. This review delves into the molecular disruptions linking plastic pollutant exposure to liver diseases, emphasizing the broader connection between plastics and the rising prevalence of NAFLD. [ABSTRACT FROM AUTHOR]

Copyright of Journal of South China Normal University (Natural Science Edition) / Huanan Shifan Daxue Xuebao (Ziran Kexue Ban) is the property of Journal of South China Normal University (Natural Science Edition) Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives.

Bisphenol S (BPS) is a novel bisphenol A (BPA) analogue, a ubiquitous environmental pollutant that disrupts male reproductive system. Whether BPS affects Leydig cell maturation in male puberty remains unclear. Male Sprague–Dawley rats (age of 35 days) were daily gavaged to 0, 1, 10, 100, and 200 mg/kg/day from postnatal days 35–56. BPS at 1–10 mg/kg/day and higher doses markedly reduced serum testosterone and progesterone levels but it at 200 mg/kg/day significantly increased estradiol level. BPS at 100 and 200 mg/kg/day significantly elevated serum luteinizing hormone (LH) levels. BPS at 1–10 mg/kg/day and higher doses significantly reduced inhibin A and inhibin B levels. BPS at 100 and 200 mg/kg/day markedly increased CYP11A1+ Leydig cell number, but did not affect HSD11B1+ (a mature Leydig cell marker) cell number. BPS at 10 mg/kg/day and higher doses significantly downregulated the expression of Cyp11a1 and at 100 and 200 mg/kg/d significantly lowered Cyp17a1, Hsd11b1, and Nr5a1 in the testes. BPS at 100 and/or 200 mg/kg/day significantly elevated Lhb in the pituitary. BPS at 100 and 200 mg/kg/day significantly increased the phosphorylation of AKT1, AKT2, and CREB without affecting total AKT1, AKT2, and CREB levels. BPS at 1–100 μM significantly suppressed testosterone production and induced proliferation of primary immature Leydig cells after 24 h of treatment and these actions were reversed by estrogen receptor α antagonist, ICI 182780, and partially reversed by vitamin E. BPS at 0.1–10 μM significantly increased oxidative stress of Leydig cells in vitro. BPS also directly inhibited 17β‐hydroxysteroid dehydrogenase 3 activity at 10–100 μM. In conclusion, BPS causes hypergonadotropic androgen deficiency in male rats during pubertal exposure via activating ESR1 and inducing ROS in immature Leydig cells and directly inhibiting 17β‐hydroxysteroid dehydrogenase 3 activity. [ABSTRACT FROM AUTHOR]

This study investigated concentration levels of ten bisphenols (BPs) in 13 Chinese commercial fresh low temperature dairy milk samples (fresh milk) of main local and national brands with or without enzyme hydrolysis. The results showed that at least two BPs were detected in each fresh milk sample without enzyme hydrolysis and the respective mean concentrations of bisphenol AF (BPAF), bisphenol B (BPB), bisphenol C (BPC), bisphenol F (BPF), bisphenol A (BPA), bisphenol S (BPS), bisphenol AP (BPAP), bisphenol PP (BPP), bisphenol Z (BPZ), and bisphenol E (BPE) were 0.73, 0.61, 1.86, 0.87, 0.42, 0.11, 1.06, 1.42, 1.5, and 0.04 ng/mL, while their respective detection frequencies ranged from 23.1–92.3%. These results indicated the frequent detection of BPs in fresh milk samples. With enzyme hydrolysis, the respective mean concentrations of BPAF, BPA, BPB, BPC, BPF, BPS, and BPAP were increased 7.1–107.1%, indicating the long-ignored importance of enzyme hydrolysis. The respective average estimated daily intakes (EDIs) of BPA by adult and children in China via fresh milk were 32.5 and 37.5 ng/kg bw/d, indicating that BPA in fresh milk was a crucial source to human. Six out of nine other BPs had higher average EDIs than that of BPA, among which the EDI of BPAP was almost three times that of BPA, suggesting the widespread contamination of other BPs in Chinese fresh milk. [ABSTRACT FROM AUTHOR]

Exposure to bisphenol analogues can occur in several ways throughout the food production chain, with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC, and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22), including canned pineapples, ravioli, and beer, were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient simultaneous quantitative analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested, with the most frequent analytes at higher concentrations: BPA and BPS were discovered in 78% and 48% of cases, respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity. [ABSTRACT FROM AUTHOR]

Copyright of Asian Journals of Ecotoxicology is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bisphenol A (BPA) is a well-known endocrine-disrupting compound that causes several toxic effects on human and aquatic organisms. The restriction of BPA in several applications has increased the substituted toxic chemicals such as bisphenol F (BPF) and bisphenol S (BPS). A native tropical freshwater cladoceran, Moina micrura, was used as a bioindicator to assess the adverse effects of bisphenol analogues at molecular, organ, individual and population levels. Bisphenol analogues significantly upregulated the expressions of stress-related genes, which are the haemoglobin and glutathione S-transferase genes, but the sex determination genes such as doublesex and juvenile hormone analogue genes were not significantly different. The results show that bisphenol analogues affect the heart rate and mortality rate of M. micrura. The 48-h lethal concentration (LC50) values based on acute toxicity for BPA, BPF and BPS were 611.6 µg L−1, 632.0 µg L−1 and 819.1 µg L−1, respectively. The order of toxicity based on the LC50 and predictive non-effect concentration values were as follows: BPA > BPF > BPS. Furthermore, the incorporated method combining the responses throughout the organisation levels can comprehensively interpret the toxic effects of bisphenol analogues, thus providing further understanding of the toxicity mechanisms. Moreover, the output of this study produces a comprehensive ecotoxicity assessment, which provides insights for the legislators regarding exposure management and mitigation of bisphenol analogues in riverine ecosystems. [ABSTRACT FROM AUTHOR]

Bisphenol A is the most studied compound due to its adverse effects on human health and is one of the most widely used products in contact materials worldwide. However, in recent years, due to stringent restrictions on the use of BPA, structural analogues are substituting BPA in the production of some consumer products. A method based on the Micro-QuEChERS technique and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was proposed, derived from a previous method based on standard QuEChERS and HPLC-MS/MS. The proposed method was compared with the previous method using the analytical Eco-scale as a verification tool. The results highlight that the proposed method achieved a metric value of 79 points, higher than the required value of 75 points for 'excellent green analysis'. The method was then tested on Algerian and Tunisian honey samples of different floral origins. The results showed that the developed method was satisfactory in terms of recovery, sensitivity, and analysis time, showing good applicability even in a complex matrix such as honey. Low levels of contamination of residues of bisphenol-analogues were found and it can therefore be concluded that the samples analysed do not pose a health risk to consumers with regard to these compounds.

• This study used DES to help MWCNTs complete solid-phase extraction. • This study allows simultaneous detection of nine bisphenol compounds. • The magnetic soft materials makes extraction process simple and efficient. • This study used fewer extractants for the detection of BPs in a large volume sample. Bisphenol analogues (BPs) are a class of typical environmental endocrine disruptors (EDCs) that have recently attracted increasing attention with regard to their potential effects on human health. The objective of this study was to develop a method using a magnetic soft material, which consisted of hydrophilic deep eutectic solvent (DES) and magnetic multi-walled carbon nanotubes (MMWCNTs), for the dispersive solid-phase extraction (d-SPE), coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), for the determination of the levels of nine BPs in bottled water. The hydrophilic DES enable the rapid dispersion of MMWCNTs when the material is injected rapidly into the sample solution using a pipette gun. This process can therefore be completed in a relatively short period of time, resulting in an efficient extraction. Under optimal conditions, the limit of detections (LODs) of the method were 0.0003–0.003 μg/L and the limit of quantifications (LOQs) were 0.001–0.01 μg/L. The relative standard deviations (RSDs) of the method were only 2.42–7.59 % for inter-day and 3.71–9.67 % for intra-day. The method demonstrated good reproducibilities and recoveries, rendering it suitable for the determination of BPs in large-volume water samples. [ABSTRACT FROM AUTHOR]

Animal studies indicated that Bisphenol analogues (BPs) exhibited potential thyroid toxicity. However, little is known of the associations between maternal BPs exposure and offspring’s thyroid related hormones in humans. On the basis of Shanghai-Minhang Birth Cohort study, we analyzed BPs in maternal urine collected at the third trimester of pregnancy. Thyroid related hormones (THs), including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured in cord blood samples. We performed multiple linear regression and Bayesian kernel machine regression (BKMR) models to explore the single and joint effects of gestational BPs exposure on thyroid related hormones in cord blood among 258 mother-child pairs. Statistically significant inverse associations of categorized BPA with FT3 and TT4 concentrations were observed. We also found a significant association between the mixture of BPs in maternal urine and increased concentration of TT3 in cord blood and a marginally significant association between BPs mixture and increased FT3 concentrations. Further associations of BPA with lower TT4/FT4 and of Bisphenol AF (BPAF) with higher TT3/FT3 were also suggestive, by BKMR model, when other BPs were fixed at 25th percentiles. It was concluded that prenatal BPs exposure was associated with THs in cord blood. Exposure to BPA and BPAF might have large contributions to the effects on thyroid function than other bisphenols.

Bisphenol analogs (BPs) are widely used as industrial alternatives for Bisphenol A (BPA). Their toxicity assessment in humans has mainly focused on estrogenic activity, while other toxicity effects and mechanisms resulting from BPs exposure remain unclear. In this study, we investigated the effects of three BPs (Bisphenol AF (BPAF), Bisphenol G (BPG) and Bisphenol PH (BPPH)) on metabolic pathways of HepG2 cells. Results from comprehensive cellular bioenergetics analysis and nontarget metabolomics indicated that the most important process affected by BPs exposure was energy metabolism, as evidenced by reduced mitochondrial function and enhanced glycolysis. Compared to the control group, BPG and BPPH exhibited a consistent pattern of metabolic dysregulation, while BPAF differed from both, such as an increased ATP: ADP ratio (1.29-fold, p

Bisphenols (BPs) as endocrine-disrupting compounds have drawn attention to their health hazards. Whether a BP interferes with glucocorticoid metabolism remains unclear. 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) is a key glucocorticoid-metabolizing enzyme that controls fetal glucocorticoid levels across the placental barrier and mineralocorticoid receptor specificity in the kidney. In this study, 11 BPs were tested to inhibit human placental and rat renal 11β-HSD2 and were analyzed for inhibitory potency, mode action, and docking parameters. BPs had inhibitory potency against human 11β-HSD2: BPFL>BPAP>BPZ>BPB>BPC>BPAF>BPA>TDP and the IC10 values were 0.21, 0.55, 1.04, 2.04, 2.43, 2.57, 14.43, and 22.18 μM, respectively. All BPs are mixed inhibitors except BPAP, which is a competitive inhibitor for human 11β-HSD2. Some BPs also inhibited rat renal 11β-HSD2, with BPB (IC50, 27.74 ± 0.95) > BPZ (42.14 ± 0.59) > BPAF (54.87 ± 1.73) > BPA (77.32 ± 1.20) > other BPs (about 100 μM). Docking analysis showed that all BPs bound to the steroid-binding site, interacting with the catalytic residue Tyr232 of both enzymes and the most potent human 11β-HSD2 inhibitor BPFL acts possibly due to its large fluorene ring that has hydrophobic interaction with residues Glu172 and Val270 and π-stacking interaction with catalytic residue Tyr232. The increase in the size of substituted alkanes and halogenated groups in the methane moiety of the bridge of BPs increases its inhibitory potency. Regressions of the lowest binding energy with inhibition constant indicated that there was an inverse regression. These results indicated that BPs significantly inhibited human and rat 11β-HSD2 activity and that there were species-dependent differences.

The prevalence of bisphenols (BPs) has been well documented in the aquatic environment of many countries, but such studies from India are quite limited. The present work aimed to determine the occurrence of BPs in surface water (n = 96), tap water (n = 172), and packaged drinking water (n = 42) and estimate their exposure to humans. For this, a simple, sensitive, cost-effective, and green analytical chemistry method based on dispersive liquid-liquid microextraction (DLLME) was employed. Bisphenol A (BPA) was found as the most prevalent bisphenol (mean concentration range = 980–6470 ng/L) in all the water samples, with a % detection frequency of 17–39%. Bisphenol S (BPS) and bisphenol Z (BPZ) were also detected in all types of water samples. The mean estimated daily intake (EDI) for total BPs (tap water and packaged drinking water) was found to be 474.37 ng/kg b.w./day in adults and 665.65 ng/kg b.w./day in children, respectively. This indicated that the total exposure to all the detected BPs obtained for adults and children was lower than the temporary tolerable daily intake (t-TDI) recommended by the European Food Safety Authority (EFSA) (4 μg/kg b.w./day), thereby posing no substantial risks to humans from consuming water from the tap and/or packaged drinking water. [ABSTRACT FROM AUTHOR]

Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives. The zebrafish embryonic acute toxicity, behavioral effects, and concentration-dependent transcriptome analysis of 17 BP analogues were tested, and the chemical structure characteristics and key biological activities-induced embryonic toxicity were explored. BPE, BPF, BPP, BPBP, and BPS induced lower embryonic lethality than BPA. And, 8 BP analogues triggered hyperactive behavior at environmentally and human relevant concentrations. BP analogues with phenol rings linked via hydrophobic segments ("chain:alkaneBranch&#95;neopentyl&#95;C5") disturbed stress response, leading to embryonic lethality, and introducing hydrophobic groups on the meta position of bisphenol structure augmented their embryonic lethality effects. "3DACorr&#95;TotChg&#95;3" of BP analogues is a key physicochemical feature for behavioral disorders, and BP analogues with 3DACorr&#95;TotChg&#95;3 value < 0.11 could induce hyperactive behavior by perturbing neurodevelopment relevant biological pathways. This study provides an integrated strategy, combining data-driven profiling and mechanism-based analysis for safer chemical alternatives.

Exposure to bisphenol analogues can occur in several ways throughout the food production chain, with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC, and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22), including canned pineapples, ravioli, and beer, were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient simultaneous quantitative analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested, with the most frequent analytes at higher concentrations: BPA and BPS were discovered in 78% and 48% of cases, respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity.

Because of its toxicity and impacts on the environment and human health, bisphenol A (BPA) has been controlled in numerous industrialized nations, increasing demand for bisphenol analogues (BP) for its replacement. However, the consequences of these chemicals on the environment and the health of persons exposed to their emissions are still being researched. The emissions from polypropylene manufacturing facilities in Colombia and Brazil were evaluated in this study, and the presence of bisphenol A and four BPs was detected among the gaseous compounds released, with total concentrations of BPs (∑BP) between 92 and 1565 ng g−1. As the melt flow index (MFI) of the polymer rises, so does the quantity of volatiles in its matrix that are eliminated during deodorization, indicating that the MFI and the amount of bisphenol released have a directly proportional connection. [ABSTRACT FROM AUTHOR]

Bisphenol analogues (BPs) have been widely used in industrial production, and caused harmful effects on biological reproduction and development. The occurrence characteristics of six BPs in multi-matrices, including truly dissolved phase, colloids, suspended particulate matter (SPM), sediment and fish samples from urban river were investigated. Bisphenol A (BPA) and bisphenol S (BPS) were the mostly detected in six BPs in the Yangtze River (Nanjing section). The total average concentration of BPs was 393.8 ng/L in truly dissolved phase, 57.4 ng/L in colloids, 255.2 ng/g in SPM and 34.5 ng/g in sediment. The adsorption capacity of SPM and sediment to BPs were weaker than that of colloids. For the spatial variation, the concentrations of BPs in the surface water of the downstream of urban rivers were 1.3–1.6 times higher than that of the upstream, and the BPs concentrations in the sediments downstream of the sewage treatment plant were significantly higher than that in other sites. In wild fish, muscle has a high accumulative potential for BPs, followed by brain and liver tissues, and BPA was the dominant BPs in brain tissues. Furthermore, BPs concentration in muscle of wild fish with different feeding habits was in the following order: filter-feeding fish > omnivorous fish > herbivorous fish, and which was significantly positively correlated with BPs concentration in traditionally dissolved phase and colloidal phase. Meanwhile, BPs concentration in benthic herbivorous fish might be also controlled by the BPs adsorbed in the sediment. Ecological risk assessment was conducted and demonstrated that BPs might pose a moderate risk to fish, a low risk to algae and daphnias. The detected BPs does not pose a health risk to human trough drinking water and eating fish alone. [Display omitted] [ABSTRACT FROM AUTHOR]

The metabolic effects of endocrine-disrupting chemicals, such as bisphenol analogues, have drawn increasing attention. Bisphenol A (BPA) usage is associated with the occurrence of many metabolic diseases. With the restricted use of BPA, alternatives like bisphenol F (BPF) and bisphenol AF (BPAF) have been greatly introduced for industrial manufacture, and brings new hazard to public health. To understand how bisphenol analogues induced metabolic effects, zebrafish are continuous exposed to environmental level (0.5 μg/L) of BPA, BPF and BPAF since embryonic stage, and identified hepatic steatosis and insulin resistance at 60-day post fertilization. Hepatic transcriptional profile indicated that pancreatic disease pathways were activated by BPA, but were inhibited by BPF. At the same time, increased lipid secretion and gluconeogenesis pathways in zebrafish liver was found post BPAF exposure. Significant inflammatory response, histological injury and increased mucus secretion was detected in zebrafish intestine post exposure of three bisphenol analogues. Single-cell RNA sequencing of zebrafish intestinal cells revealed activation of lipid uptake and absorption pathways in enterocyte lineages, which well explained the hepatic steatosis induced by BPA and BPF. Besides, genes related to carbohydrate metabolism, diabetes and insulin resistance were activated in intestinal immune cell types by three bisphenol analogues. These findings indicated that BPA and its alternatives could lead to abnormal lipid and carbohydrate metabolism of zebrafish through inducing cell heterogeneous changes in gut, and revealed both molecular and cellular mechanism in mediating this effect.

Bisphenol A (BPA) is a high production volume (HPV) chemical used to make polycarbonate (PC) plastics and epoxy resins. Due to its potential adverse health effects, BPA has been restricted or banned in some products and thus many alternatives to BPA have been introduced into the market. Most of these alternatives such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol M (BPM), have similar chemical structures to BPA and termed as BPA analogues (BPAAs). In this study, a method was developed for the simultaneous determination of 16 BPAAs in indoor dust by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The method was sensitive, with method detection limits (MDLs) ranging from 0.001 μg/g to 0.017 μg/g. The method demonstrated good recoveries (>80%) for the majority of the target compounds and was applied to the analysis of dust samples collected from 2007 to 2010 in 13 cities across Canada under the Canadian House Dust Study (CHDS). Samples were collected using two different techniques: household vacuum dust samples collected from household vacuum bags (HD); fresh vacuum dust (FD) samples collected by a trained technician from dry floor surfaces. In addition to BPA with 100% detection in 119 HD samples, BPS, BPF, and BPM were detected with high detection frequencies (>75%) with median (range) concentrations of 0.242 (

Bisphenol analogues (BPs) including bisphenol a (BPA) have been broadly utilized as industrial feedstocks and unavoidably discharged into water bodies. However, there is little published data on the occurrence, distribution, and environmental risks of other BPs in surface water. In this study, ten BPs besides BPA were analyzed in surface water from the Pearl River, South China. Among these detected BPs, BPA, bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol S (BPS) were the most frequently detected compounds. The median concentrations of the measured BPs were ranked in the order of BPA (34.9 ng/L) > BPS (24.8 ng/L) > BPAF (10.1 ng/L) > bisphenol F (BPF) (9.0 ng/L) > bisphenol B (BPB) (7.6 ng/L) > bisphenol C (BPC) (1.2 ng/L). Among them, BPA and BPS were predominant BPs, contributing 68% of the total ten BPs in surface water of the Pearl River. These results demonstrated that BPA and BPS were the most extensively utilized and manufactured BPs in this region. The source analysis of BPs suggested that the BPs may be originated from domestic wastewater, wastewater treatment plant (WWTP) effluent, and the leaching of microplastic in surface water of the Pearl River. The calculated BP-derived estrogenic activity exhibited low to medium risks in surface water, but their combined estrogenic effects with other endocrine disrupting compounds should not be ignored. [ABSTRACT FROM AUTHOR]

Bisphenol analogs (BPs) are widely used in industrial and commercial products and have been detected in surface water, sediment, sewage, and sludge. The presence of BPs in the natural environment poses threats to the aquatic ecosystem and human health. The concentration, distribution, seasonal variation, and risk assessment of BPA and BPA structural analogs including BPB, BPF, BPS, BPZ, BPAF, and BPAP in surface water and sediment during dry season and flood season in Luoma Lake and its inflow rivers in Jiangsu Province, China, were investigated in this study. The detection frequency of BPA and BPF was 100%. Although the use of BPA is restricted, BPA is still the dominant BPs in surface water and sediment. The concentration of BPs in surface water during flood season was higher than that in dry season. The concentrations of BPs in Fangting River, Zhongyun River, and Bulao River were higher than those in Luoma Lake. The average concentrations of BPs in surface water were in the order of BPA > BPF> BPS> BPB > BPZ > BPAF> BPAP. Compared with other studies, the concentration of BPs in Luoma Lake was moderate. There is no significant spatial distribution and difference in seasonal variation of BPs concentration in sediment (p > 0.05). Compared with other studies, the contamination of BPs in sediment of Luoma Lake was relatively low. Risk quotient (RQ) was used to evaluate the ecological risk of BPs in water environment, and the 17β estradiol equivalent (EEQ) method was used to estimate the estrogenic activity of BPs. The risk assessment showed no high ecological risk (RQ < 1.0) and estrogenic risk (EEQ < 1.0 ng/L) in dry season and flood season. The estimated RQ and EEQt indicated that the ecological and human health impacts were negligible in the short term. [ABSTRACT FROM AUTHOR]

Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, we found for the first time that PPARβ/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARβ/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARβ/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARβ/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARβ/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARβ/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARβ/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARβ/δ pathway.

• Simultaneous detection of nine bisphenol analogues (BPs) in human urine. • Using 96-well solid phase extraction as purification. • The procedures are suitable for the batch detection of BPs in urine. • The MRM-IDA-EPI mode can effectively identify the target bisphenols. • The analytical method has high accuracy and sensitivity. Bisphenol analogues (BPs) are a class of typical environmental endocrine-disrupting chemicals (EDCs). This study aimed to establish a highly sensitive and high-throughput method utilizing 96-well solid-phase extraction (96-well SPE) in conjunction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) employing multiple reaction monitoring (MRM), information-dependent acquisition (IDA), and enhanced product ion (EPI) scan modes for the identification and quantitative analysis of nine BPs in human urine. Urine samples were initially thawed to room temperature, followed by digestion using β-glucuronidase in an ammonium acetate buffer solution at 37 °C overnight. Subsequently, they were purified using 96-well SPE and finally analyzed by UHPLC-MS/MS. The limits of detection (LOD) for the nine BPs ranged from 0.05 μg∙kg−1 to 0.3 μg kg−1. Average recoveries fell within the range of 92.8 % to 111.7 %. Moreover, both the intra-day and inter-day precisions were satisfactory, with relative standard deviations (RSDs) ranging from 2.2 % to 6.7 % and 3.5 % to 6.3 %, respectively. The targets in the samples exhibited a perfect match, with a purity fit value exceeding 70 % from the self-built library. The analytical method developed in this study demonstrates high accuracy and sensitivity. In addition, the MRM-IDA-EPI mode can effectively identifies the target BPs and prevents false positive detection of analytes in the urine. [ABSTRACT FROM AUTHOR]

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development. [Display omitted] • Urinary BPA and BPF levels were higher in SLE patients than controls. • High exposure to BPA and BPF associated with increased SLE risk. • Bisphenol analogues may be environmental triggers for autoimmunity disorders. [ABSTRACT FROM AUTHOR]

Due to the strict control on bisphenol A (BPA) in many countries, bisphenol analogues (BPs) are being widely used as alternative materials to manufacture epoxy resins and polycarbonate plastics, resulting in their occurrence in sewage treatment plants (STPs). In this study, the occurrence and distribution of 7 BPs in a large-scale STP in Beijing China was investigated. Wastewater samples were collected from the influents and effluents of each processing unit, and extracted by solid-phase extraction. Target compounds were quantified by ultra-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS). The total concentrations of seven BPs (ΣBPs) were 400.42 ± 48.12 ng/L in the raw sewage, 438.60 ± 46.50 ng/L in the primary effluent, 17.21 ± 13.12 ng/L in the secondary effluent, and 11.33 ± 4.84 ng/L in the tertiary effluent, respectively. Bisphenol S (BPS) and BPA were the predominant congener in raw sewage with an overall contribution of 29.32% and 70.22% to the ΣBPs, indicating that there was a large amount of BPS and BPA consumption in the study area. During a one-week sampling period, ΣBPs changed slightly at the same sampling site. It was found that high removal efficiencies were achieved for BPs in anoxic and oxic secondary clarifier treatment units, suggesting that biodegradation and sorption played major roles in BPs elimination in the STP. After tertiary treatment, all BPs except BPA were completely removed, suggesting the necessity to investigate the fate and toxicity of BPA in the aquatic environment. [ABSTRACT FROM AUTHOR]

The most prevalent exposure of bisphenol A (BPA) to biological systems has directed health organizations to reduce its safe dosage and the stringent regulation by developed countries that led to ban of BPA-based (Bisphenol analogues) baby bottles. This in turn has opened a new window for ongoing entry of bisphenol analogues into consumer market. Recently, there has been tremendous growth in both production and application of bisphenol analogues to achieve the "BPA-free" claim. Nevertheless, due to growing epidemiological evidence concerning the toxicological effects of these bisphenol analogues in both in vivo and in vitro systems, the debate regarding the safety concerns over bisphenols is back. Structural analogues of bisphenol A had been identified in food products, human and environment matrices. Present review is an attempt to recapitulate the presence of bisphenols in food and environment matrices as well as their concerning physiological effects in animal models and human groups. But, due to structural analogy of these substitutes, their endpoints on biological functions are comparable to original compound or in certain situations, more harmful than original compound. Unfortunately, other potentially harmful alternatives are emerging and it is therefore advised that the replacement of bisphenol A with other structural analogues must be executed with great care. [ABSTRACT FROM AUTHOR]

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children's digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 ( PCDH8 ), RBMX Like 2 ( RBMXL2 ), and Sperm Acrosome Associated 1 ( SPACA1 ), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 ( FGF13 ). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

Bisphenol analogues (BPs) have been widely applied to industry as the substitutes for bisphenol A (BPA), which have been detected frequently in surface water, sediment, sewage and sludge. The presence of BPs in natural environment could pose risks to the aquatic ecosystem and human health. This study outlined the occurrence, toxicity of BPs in aquatic environment and manifested their potential ecological risk to the aquatic ecosystem throughout the world. As for occurrence, BPA was losing its dominance, while BPs were occupying a large part, especially for bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). In some heavily polluted areas, BPs concentration reached µg/L in aquatic environment, which in the effluent of sewage plants was higher than that in the surface water. BPs content in sludge and sediment was more than that in the aqueous phase. All BPs other than BPS and Bisphenol P (BPP) had moderate toxicity. The current data supports that exposure to BPs may have adverse effects on dysfunction of endocrine system such as thyroid hormone concentration, enzyme activity, and even cell dysfunction, gene damage and chromosomal abnormalities. According to the risk quotient (RQ), BPF shows the highest ecological risk in China, Japan and South Korea, followed by BPA and BPS. The occurrence of bisphenols and their neurotoxicity on aquatic organisms merit further investigation.

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brain-derived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.

The environmental fate and persistence of bisphenol S (BPS), a substitute for bisphenol A (BPA), are unclear. This study used 14C-labeled BPS to examine the fate, biodegradation, and residue properties of BPS incubated in an oxic soil for 28 days. BPS dissipated quickly, with a half-life of 2.8 days. Most of the BPS was mineralized (53.6 ± 0.2% of initial amount by day 28) or transformed into non-extractable residues (NERs) (45.1 ± 0.3%), with generation of minor extractable residues (3.7 ± 0.2%) containing two metabolites. NERs were formed mainly via physico-chemical entrapment (51.1 ± 2.4% of the total NERs, consisting almost exclusively of BPS) and ester-linkages (31.5 ± 3.0% of the total NERs, consisting of both BPS and polar metabolites). When mixed with fresh soil, BPS-derived NERs became unstable and bioavailable. Subsequent mineralization was determined for 19.5 ± 1.1% of the total NERs and 35.5 ± 2.6% of the physico-chemically entrapped BPS. A fate model was used to describe the kinetics of NER formation, which indicated that microbial activity in soil could have strongly reduced the kinetic rate of the release of physico-chemically entrapped NERs into free form and therefore increased the stability of this type of NERs in soil. Our results provide unique insights into the fate of BPS in soil and suggest that while BPS is biodegradable, it includes the formation of large amounts of reversibly physico-chemically entrapped and covalently bound ester-linked NERs. The instability of these NERs should be considered in assessments on environmental persistence and risks of BPS. Our study also points out the environmental importance of NERs of agrochemicals.

For non-occupationally exposed adults, dietary intake is the main route of exposure to bisphenols (BPs), with canned foodstuffs playing a key role. This study was aimed at biomonitoring bisphenol A (BPA) and 5 more BP analogues (BPB, BPE, BPF, BPAF and BPZ) in spot urine and blood samples of a cohort of adults, who followed a diet based on a high consumption of canned food. To the best of our knowledge, this is the first study aimed at assessing the co-exposure of BP analogues in food and biological samples after a two-day duplicate diet study. The estimated total dietary exposure was 0.37 and 0.045 µg/kg body weight/day, for the canned-diet and control groups, respectively. BPA was the compound with the highest concentration in urine in comparison with the values of the remaining BP analogues. A high detection rate of BPA was noted in urine for both groups, 96% for the canned-diet group and 90% for the control group, while in blood it could be only quantified in 6% of the samples. The identification of other analogues was hardly related to diet, so it could be the result of other potential exposure sources, such as personal care products (PCPs) or air inhalation. After 2 days, the excretion of BPA was considerably higher in the canned-diet group subjects than those in the control group (7.02 vs. 1.89 µg/day), confirming that diet and canned foodstuffs are the main route of exposure to BPA. Anyhow, the temporary tolerable daily intake (t-TDI) established by the EFSA was not exceeded, even by those consumers with a diet rich in canned food. Moreover, spot urine samples provided accurate information about exposure and excretion of BPA, being the 4 h, instead of 24 h, the optimal sampling interval, when the collection of spot urine samples is not possible.

Bisphenols (BPs), which act as endocrine disruptors, are extensively used in epoxy resin and polycarbonate plastic production and are found in various environmental media. This study investigated the occurrence and distribution of seven BPs in water and sediment samples from the Lanzhou section of the Yellow River, China. Previous studies have focused on the southern and more developed regions in China. Paired water and sediments were collected in the Yellow River from August 2016 to March 2017. Bisphenol A (BPA), bisphenol AF (BPAF) and bisphenol S (BPS) were measured in the study samples. Mean concentrations of BPs were 88 and 61.2 ng/L in the rainy and dry seasons, respectively, in water samples. The concentrations were 40.4 and 29.9 ng/g in the rainy and dry seasons, respectively, in sediment samples. BPA accounted for the largest proportion in ∑BPs, followed by BPAF and BPS, which indicates that BPA and BPAF have been widely used and discharged in this region. 17β-estradiol equivalents for BP analogues were 21.57–203.83 pg/L and 13.06–185.30 pg/L in the dry and rainy seasons, respectively, in water samples. BPAF had the highest mean estrogenic activity (> 80%) amongst the study samples. The concentration of ∑BPs was lower than those in previous studies; however, the concentration of BPAF was high. The present study also surveyed the estrogenicity of BPs from the samples, and BPAF contributed the highest mean estrogenic activity. The results of this study demonstrate that BP pollution exists to some degree, and the use and discharge of BPAF should be monitored. [ABSTRACT FROM AUTHOR]

The study focused on the application of GC in the quantitative analysis of bisphenols and their analogues (12 analytes), and the improvement of solid-phase extraction for the whole water analysis of complex water samples. The role of silylation in the qualitative and quantitative analysis of bisphenols was investigated. Partial degradation occurred for selected targets during hot injection with the presence of a silylation agent. A PSA (primary and secondary amines) sorbent placed on the top of the solid-phase extraction (SPE) column sorbent was found to be a matrix component trap, mostly for humic acids. The whole water analysis was performed by washing the filters with methanol and recycling the extract to the sample. The validation of SPE-GC/MS(SIM) gave limits of detection of 1–50 ng/L for ten target bisphenols with a method recovery of between 87 and 133%. The application of the method was tested by the analysis of wastewater sampled from three wastewater treatment plants located in Poland, and municipal surface waters. The only analytes found were BPA and BPS, within the range of 16–1465 ng/L and < MDL-1249 ng/L in wastewater, and 170–3113 ng/L and < MDL-1584 ng/L in surface water, respectively. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • ΣBPs was no significantly between the two periods, BPA was the main contributor. • The land use patterns had an impact on the distribution of BPs in river sediments. • ΣBPs, BPA, and total organic carbon observed a significant positive correlation. • Three key sources of BPs were identified in the QRB based on the PMF model. • BPA posed low risk for benthic animals but varied across land use patterns. [ABSTRACT FROM AUTHOR]

The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives. • Evaluation of bisphenols using hiPSC-CMs and MEA-based dual-cardiotoxicity assessment method. • Reduced electrophysiological signals and contractility by Bisphenol A, AF, C, E, and F exposure. • Among analogues, acute exposure to BPS does not cause cardiotoxicity. [ABSTRACT FROM AUTHOR]

Bisphenol Z (BPZ), bisphenol S (BPS), bisphenol C (BPC), and bisphenol F (BPF) had been widely used as alternatives to bisphenol A (BPA), but the toxicity data of these bisphenol analogues were very limited. In this study, the joint toxicity of BPZ, BPS, BPC, and BPF to zebrafish (Danio rerio) was investigated. The median half lethal concentrations (LC50) of BPZ, BPS, BPC, and BPF to zebrafish for 96 h were 6.9 × 105 µM, 3.9 × 107 µM, 7.1 × 105 µM, and1.6 × 106 µM, respectively. The joint toxicity effect of BPF–BPC (7.7 × 105–3.4 × 105µM) and BPZ–BPC (3.4 × 105–3.5 × 105µM) with the same toxic ratio showed a synergistic effect, which may be attributed to enzyme inhibition or induction theory. While the toxicity effect of the other two bisphenol analogue combined groups and multi-joint pairs showed an antagonistic effect due to the competition site, other causes need to be further explored. Meanwhile, the expression levels of the estrogen receptor genes (ERα, ERβ1) and antioxidant enzyme genes (SOD, CAT, GPX) were analyzed using a quantitative real-time polymerase chain reaction in zebrafish exposure to LC50 of BPZ, BPS, BPC, and BPF collected at 24, 48, 72, and 96 h. Relative expression of CAT, GPX, and ERβ1 mRNA declined significantly compared to the blank control, which might be a major cause of oxidant injury of antioxidant systems and the disruption of the endocrine systems in zebrafish.

Bisphenol analogues and alkyl esters of p -hydroxybenzoic (parabens) can be defined as emerging endocrine-disrupting compounds (EDCs) due to their similar characteristics. This study analyzed eight bisphenol analogues, six parabens, and five paraben metabolites in seawater (including aqueous and suspended particle matter (SPM)), as well as organism samples from the Pearl River Estuary, in order to determine their occurrence, distribution, bioaccumulation, and ecological and human health risk in South China's marine environment. The aggregation concentrations of bisphenol analogues, parabens, and paraben metabolites were 106 ng/L, 4.53 ng/L, and 231 ng/L in aqueous samples, 868 ng/g, 173 ng/g, and 9320 ng/g in SPM samples, 41.6 ng/g, 6.46 ng/g, and 460 ng/g in marine organisms, respectively. This study identified significantly higher concentrations of paraben metabolites than their parent parabens in the marine environment, which has not yet been reported in previous studies. These findings call for greater attention on the contamination of paraben metabolites in marine environments. Moreover, the median values of the logarithm of bioaccumulation factors (BAF) for the detected 20 target compounds ranged from 0.11 to 5.07. Bisphenol analogues including bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), bisphenol P (BPP), and Fluornen-9-bisphenol (BPFL) (3.3 < lg BAF < 3.7), and three paraben metabolites including 4-hydroxybenzoic acid (4-HB) (3.3 < lg BAF < 3.7), methyl protocatechuate (OH-MeP), and ethyl protocatechuate (OH-EtP) (Log BAF > 3.7), exhibited varying degrees of potential bioaccumulation effect in the majority of organism samples. Furthermore, all tested chemicals in this study were at low risk quotient (RQ) levels for acute and chronic toxicity in seawater. However, the target hazard quotient (THQ) values of two paraben metabolites, 4-HB and benzoic acid (BA), were higher than 1, which indicates that paraben metabolites have the potential to adsorb into organisms, and their associated human health risks should be of great concern. Overall, the study results suggest that the occurrence and risks of emerging EDCs in coastal waters are deserving of further studies, especially in densely populated regions of the world. Image 1 • 19 target emerging EDCs were studied in aqueous, SPM and organism in Pearl River Estuary. • Six bisphenols and three paraben metabolites exhibited potential bioaccumulation effect. • All tested chemicals were at low risk quotient levels for acute and chronic toxicity. • Two paraben metabolites (4-HB and BA) present high target hazard quotient values. Capsule: Bisphenol analogues, parabens, and their metabolites were frequently detected in the Pearl River Estuary, South China. [ABSTRACT FROM AUTHOR]

Bisphenol analogues including bisphenol A and its derivatives are ubiquitous environmental contaminants and have been linked to adverse neurodevelopment effects on animals and humans. Most toxicological research focused on estrogen receptor mediated pathways and did not comprehensively clarify the observed toxicity. O-GlcNAcase (OGA), the highest level in brain, plays a critical role in controlling neuronal functions at multi-levels from molecule to animal behaviors. In this work, we intend to investigate the underlying molecular mechanisms for the neurotoxicity of bisphenol analogues by identifying their cellular targets and the resultant effects. The inhibitory actions of seven bisphenol analogues on the OGA activity at molecular level were investigated by our developed electrochemical biosensor. We found that their potency varied with substituent groups, in which tetrabromo bisphenol A (TBBPA) was the strongest. The seven bisphenol analogues (0–100 μM exposure) significantly inhibited OGA activity and up-regulated protein O-GlcNAcylation level in PC12 cells. Inhibition of OGA by bisphenol analogues further induced intracellular calcium, ROS, inflammation, repressed proliferation, interfered with cell cycle, induced apoptosis. And especially, 10 μM tetrabromo bisphenol A (TBBPA) exposure could impair the growth and development of neurite in human neural stem cells (hNSCs). Molecular docking for OGA/bisphenol analogue complexes revealed the hydrophobicity-dominated inhibition potency. OGA, as a new cellular target of bisphenol analogues, would illuminate the molecular mechanism of bisphenol analogues neurotoxicity. [ABSTRACT FROM AUTHOR]

Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7–15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPF > BPA > BPAF > BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment. Unlabelled Image • The rank order of metabolomic disturbances of four bisphenol analogues in HepG2 cells was BPF > BPA > BPAF > BPS. • BPAF increased the pyruvate kinase (PKLR) and pyruvate level indicated enhanced glycolysis. • BPA, BPF, and BPS decreased the glucokinase (GCK) level implied an impaired glucose sensing. [ABSTRACT FROM AUTHOR]