In order to understand the negative effects of bisphenol A (BPA) alternatives comprehensively, zebrafish embryos were used to assess the lethality, developmental effects, and estrogenic activity of ...bisphenol analogues. The in silico estrogenic activities of bisphenol analogues were assayed by binding simulation. According to our results, the lethality of bisphenol analogues decreased in order of bisphenol AF (BPAF) > BPA > bisphenol F (BPF) > bisphenol S (BPS). BPAF and BPF induced significant effects on zebrafish embryos, including decreased heart rate, hatching inhibition, and teratogenic effects. The binding potentials of bisphenol analogues toward zebrafish ERs (zfERS) decreased in the following order: BPAF > BPA > BPF > BPS. Among the three subtypes of zfERs, zfERβ2 showed the highest binding activity toward the bisphenols, followed by zfERα and zfERβ1. In vivo estrogenic activity tests showed that BPAF, BPA, and BPF significantly enhanced the protein levels of ERα along with the mRNA levels of esr1, esr2a, esr2b, and vtg1 in zebrafish embryos. Esr2b showed the strongest response to BPAF and BPA exposure among the three esrs. In contrast, BPS did not significantly regulate ER protein level or ER transcription. In conclusion, BPAF showed the highest lethality, developmental effects, and estrogenic activity (both in silico and in vivo) followed by BPA and BPF. BPS showed the weakest toxicity and estrogenic activity. zfERβ2 might act as the main target among the three ER subtypes of zebrafish after exposure to BPAF and BPA.
Bisphenol A (BPA), a reprotoxic and endocrine-disrupting chemical, has been substituted by alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) in the plastic industry. Despite ...their detection in placenta and amniotic fluids, the effects of bisphenols on human placental cells have not been characterized. Our objective was to explore in vitro and to compare the toxicity of BPA to its substitutes BPF and BPS to highlight their potential risks for placenta and then pregnancy.
Human placenta cells (JEG-Tox cells) were incubated with BPA, BPF, and BPS for 72 h. Cell viability, cell death, and degenerative P2X7 receptor and caspases activation, and chromatin condensation were assessed using microplate cytometry and fluorescence microscopy.
Incubation with BPA, BPF, or BPS was associated with P2X7 receptor activation and chromatin condensation. BPA and BPF induced more caspase-1, caspase-9, and caspase-3 activation than BPS. Only BPF enhanced caspase-8 activity.
BPA, BPF, and BPS are all toxic to human placental cells, with the P2X7 receptor being a common key element. BPA substitution by BPF and BPS does not appear to be a safe alternative for human health, particularly for pregnant women and their fetuses.
Background: Bisphenol A (BPA) is the principal constituent of baby bottles, reusable water bottles, metal cans, and plastic food containers. BPA exerts estrogen-like activity by interacting with the ...classical estrogen receptors (ERα and ERß) and through the G protein-coupled receptor (GPR30/GPER). In this regard, recent studies have shown that GPER was involved in the proliferative effects induced by BPA in both normal and tumor cells. Objectives: We studied the transduction signaling pathways through which BPA influences cell proliferation and migration in human breast cancer cells and cancer-associated fibroblasts (CAFs). Methods and results: We used as a model system SKBR3 breast cancer cells and CAFs that lack the classical ERs. Specific pharmacological inhibitors and gene-silencing procedures were used to show that BPA induces the expression of the GPER target genes c-FOS, EGR-1, and CTGF through the GPER/EGFR/ERK transduction pathway in SKBR3 breast cancer cells and CAFs. Moreover, we observed that GPER is required for growth effects and migration stimulated by BPA in both cell types. Conclusions: Results indicate that GPER is involved in the biological action elicited by BPA in breast cancer cells and CAFs. Hence, GPER-mediated signaling should be included among the transduction mechanisms through which BPA may stimulate cancer progression.
The present work deals with the development of bisphenol‐BA based benzoxazines and to study their behavior toward utilization for thermal, high‐dielectric, low‐dielectric, and anti‐corrosion ...applications. A new type of bifunctional benzoxazine resins were synthesized using bisphenol‐BA with different types of amines and characterized using FTIR, 1H‐NMR spectra, DSC, and TGA techniques. In the present study, thermally stable bisphenol‐BA with trifluoromethylaniline benzoxazine (BBA‐tfma) and bisphenol‐BA with furfurylamine benzoxazine (BBA–ffa) were selected as matrices for the preparation of composites with SBA‐15, bio‐silica (from Bermuda grass) and reduced graphene oxide. The results indicated that the poly(BBA‐tfma) with 5 wt% SBA‐15 composites and poly(BBA‐ffa) with 10 wt% bio‐silica composites showed the lowest dielectric constant value of 1.71 and 1.87, respectively. While in contrast, the 5 wt% of reduced graphene oxide (rGO) reinforced poly(BBA‐tfma) exhibits highest value of dielectric constant (k = 8.49). Results from corrosion studies ascertain that the bisphenol‐BA with aminoethoxyethanol benzoxazine, that is, poly(BBA‐aee) possess better mild steel corrosion protection behavior than that of other benzoxazines. Data resulting from different studies indicate that the bisphenol‐BA‐based benzoxazines and their composites can be effectively used for different industrial applications.
Development of new bisphenol‐BA‐based polybenzoxazine composites and to study their behavior toward utilization of thermal, high‐dielectric, low‐dielectric, and anti‐corrosion applications.
Bisphenols, estrogenic endocrine-disrupting chemicals, disrupt at least one of three endocrine pathways (estrogen, androgen, and thyroid). 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is a ...steroidogenic enzyme that catalyzes the activation of estradiol from estrone in human placenta and rat ovary. However, whether bisphenols inhibit 17β-HSD1 and the mode of action remains unclear. This study we screened 17 bisphenols for inhibiting human 17β-HSD1 in placental microsomes and rat 17β-HSD1 in ovarian microsomes and determined 3D-quantitative structure-activity relationship (3D-QSAR) and mode of action. We observed some bisphenols with substituents were found to significantly inhibit both human and rat 17β-HSD1 with the most potent inhibition on human enzyme by bisphenol H (IC50 = 0.90 μM) when compared to bisphenol A (IC50 = 113.38 μM). Rat enzyme was less sensitive to the inhibition of bisphenols than human enzyme with bisphenol H (IC50 = 32.94 μM) for rat enzyme. We observed an inverse correlation between IC50 and hydrophobicity (expressed as Log P). Docking analysis showed that they bound steroid-binding site of 17β-HSD1. The 3D-QSAR models demonstrated that hydrophobic region, hydrophobic aromatic, ring aromatic, and hydrogen bond acceptor are key factors for the inhibition of steroid synthesis activity of 17β-HSD1.
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•BPA analogues have been widely used but disrupt at least one of three endocrine pathways.•Bisphenols inhibit both human and rat 17β-HSD1. Rat enzyme was less sensitive than human enzyme.•Docking analysis showed that they bound steroid-binding site of 17β-HSD1.•3D-QSAR models demonstrated HBA, HY, RA, HYA are key factors.•An inverse correlation between IC50 and hydrophobicity (expressed as Log P).
An efficient g-C3N4/Cu2O@Cu plasmonic Step-scheme (S-scheme) heterojunction photocatalyst was successfully designed and used for the degradation of pollutants and energy generation. The removal of ...Bisphenol-S pollutants and catalytic reduction of CO2 for hydrocarbon fuel production experiments under the visible light irradiation showed that the catalyst displayed good stability and perfect photocatalytic performance. Among the prepared samples, g-C3N4/Cu2O@Cu-4 displayed the highest catalytic performance, which was attributed to the high light absorption capacity and the efficient interfacial charge separation in the S-scheme heterojunction. From the viewpoint of practical wastewater treatment, a series of the effects of environmental factors, such as initial pollutant concentration, inorganic salts, organic compounds and various water sources on the photocatalytic performance were investigated. Eight intermediate products formed in the photocatalytic oxidation of Bisphenol-S were confirmed by the GC-MS, and the proposed photocatalytic degradation pathway of Bisphenol-S was suggested according to the intermediate products. Importantly, the charge density difference of the interface between g-C3N4 and Cu2O (g-C3N4/Cu2O) as well as the interface between Cu and Cu2O (Cu/Cu2O heterostructures) was calculated, respectively. The calculated results verified that the built-in electric field had been established at their interface. Spatial separation of photogenerated electron-hole pairs in the S-scheme g-C3N4/Cu2O@Cu heterojunction was realized through the built-in electric field.
The charge density difference verified the internal electric field (E) had been established, and the spatial separation of photogenerated electron and holes followed Step-scheme heterojunction mechanism. Display omitted
•g-C3N4/Cu2O@Cu was synthesized for pollutants degradation and energy generation.•A built-in electric field was fabricated in the g-C3N4/Cu2O@Cu.•The proposed photocatalytic degradation pathway of Bisphenol-S was suggested.•Comparative experiment and DFT study of g-C3N4/Cu2O@Cu were performed.
Phthalates and bisphenol A (BPA) have received special attention in recent years due to their frequent use in consumer products and potential for adverse effects on human health. BPA is being ...replaced with a number of alternatives, including bisphenol S, bisphenol B, bisphenol F and bisphenol AF. These bisphenol analogues have similar potential for adverse health effects, but studies on human exposure are limited. Accurate measurement of multiple contaminants is important for estimating exposure. This paper describes a sensitive and automated method for the simultaneous determination of 14 phthalate metabolites, BPA and four bisphenol analogues in urine using online solid phase extraction coupled with high-performance liquid chromatography/tandem mass spectrometry using a hybrid triple-quadrupole linear ion trap mass spectrometer (LC-QTRAP-MS/MS), requiring very little sample volume (50µL). Quantification was performed under selected reaction monitoring (SRM) mode with negative electrospray ionization. The use of SRM combined with an enhanced product ion scan within the same analysis was examined. Unequivocal identification was provided by the acquisition of three SRM transitions per compound and isotope dilution. The analytical performance of the method was evaluated in synthetic and human urine. Linearity of response over three orders of magnitude was demonstrated for all of the compounds (R2>0.99), with method detection limits of 0.01–0.5ng/mL and limits of reporting of 0.07–3.1ng/mL. Accuracy ranged from 93% to 113% and inter- and intra-day precision were <22%. Finally, the validated method has been successfully applied to a cohort of pregnant women to measure biomarker concentrations of phthalates and bisphenols, with median concentrations ranging from 0.3ng/mL (bisphenol S) to 18.5ng/mL (monoethyl phthalate).
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•First reported method for 14 phthalate metabolites and 5 bisphenol analogues.•Low-volume method requires only 50µL urine.•Detection limits consistent with or lower than previously published methods.
Abstract Although much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile ...is lacking. Here the possible effects of BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated structural analogue and widely used flame retardant tetrabromobisphenol A (TBBPA) on human glucocorticoid and androgen receptor (GR and AR) activation were assessed. BPA, BPF, and TBBPA showed clear GR and AR antagonism with IC50 values of 67 μM, 60 μM, and 22 nM for GR, and 39 μM, 20 μM, and 982 nM for AR, respectively, whereas BPS did not affect receptor activity. In addition, murine MA-10 Leydig cells exposed to the bisphenol analogues were assessed for changes in secreted steroid hormone levels. Testicular steroidogenesis was altered by all bisphenol analogues tested. TBBPA effects were more directed towards the male end products and induced testosterone synthesis, while BPF and BPS predominantly increased the levels of progestagens that are formed in the beginning of the steroidogenic pathway. The MA-10 Leydig cell assay shows added value over the widely used H295R steroidogenesis assay because of its fetal-like characteristics and specificity for the physiologically more relevant testicular Δ4 steroidogenic pathway. Therefore, adding an in vitro assay covering fetal testicular steroidogenesis, such as the MA-10 cell line, to the panel of tests used to screen potential endocrine disruptors, is highly recommendable.
Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), ...bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (
R
2
= 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.
Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, ...have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown.
Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth.
The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile.
Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend
-values (
) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome.
Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.
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