Bisphenol a (BPA) is a high production volume chemical that is frequently used to manufacture epoxy resins and polycarbonate plastics. BPA-containing products are now pervasive, and as a result, ...biomonitoring studies report widespread exposure in > 90% of adults, adolescents, and children. Both epidemiological and experimental studies have reported associations between BPA exposure and adverse cardiovascular health outcomes. With increasing concerns regarding BPA exposure, a few structurally similar bisphenol chemicals have been introduced as replacements, including bisphenol s (BPS) and bisphenol f (BPF). In accordance with the recently established “
Key characteristics of cardiovascular toxicants
”, we reviewed the literature to highlight the immediate effects of bisphenol chemicals on (1) cardiac excitability, and (2) contractility and relaxation. BPA inhibits key cardiac ion channels, impairs cardiac excitability, and acts as a more potent inhibitor as compared to BPF and BPS. Through the inhibition of calcium current, some studies report that bisphenol chemicals can act as negative inotropic agents. Yet, others suggest that low dose exposures may increase contractility and precipitate triggered arrhythmias via the phosphorylation of key calcium handling proteins. Accordingly, we propose additional considerations for future work to comprehensively address the cardiac safety profile of BPA, as compared to replacement chemicals.
BACKGROUND: Experimental laboratory evidence suggests that bisphenol A (BPA), an endocrine disruptor, is a neurodevelopmental toxicant However) there have been limited and inconclusive results with ...respect to sex-specific BPA effects on child behavior. OBJECTIVE: We examined the association between prenatal BPA exposure and child behavior, adjusting for postnatal BPA exposure and hypothesizing sex-specific effects. METHODS: We followed African-American and Dominican women and their children from pregnancy to child's age 5 years, collecting spot urine samples from the mothers during pregnancy (34 weeks on average) and from children between 3 and 4 years of age to estimate BPA exposure. We assessed child behavior between 3 and 5 years of age using the Child Behavior Checklist (CBCL) and used generalized linear models to test the association between BPA exposure and child behavior, adjusting for potential confounders. RESULTS: The analysis was conducted on 198 children (87 boys and 111 girls). Among boys, high prenatal BPA exposure (highest quartile vs. the lowest three quartiles) was associated with significantly higher CBCL scores (more problems) on Emotionally Reactive 1.62 times greater; 95% confidence interval (CI): 1.13, 2.32 and Aggressive Behavior syndromes (1.29 times greater; 95% CI: 1.09,1.53). Among girls, higher exposure was associated with lower scores on all syndromes, reaching statistical significance for Anxious/Depressed (0.75 times as high; 95% CI: 0.57, 0.99) and Aggressive Behavior (0.82 times as high; 95% CI: 0.70, 0.97). CONCLUSION: These results suggest that prenatal exposure to BPA may affect child behavior, and differently among boys and girls.
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.
Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic ...environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka (
). In the acute toxic exposure, the LC
of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.
Due to the potential toxicity of bisphenol A (BPA), several bisphenols (BPs), including bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF), have been gradually used as its main substitutes, ...and the levels of these alternatives in different environmental media have been constantly increasing. Although some previous studies have shown that bisphenol substitutes have similar or greater acute toxicity and estrogenic effects than BPA, comparative studies on the cardiovascular toxicity of BPs have not been evaluated. In this study, the developmental vascular toxicity of BPA and three predominant substitutes (BPF, BPS and BPAF) were evaluated using zebrafish embryos and human vascular endothelial cells (HUVECs). BP exposure at a sublethal concentration of 1/10 96 h median lethal concentration (96 h-LC50) significantly hindered intersegmental vessel (ISV) growth, delayed common cardinal vein (CCV) remodeling and decreased subintestinal vessels (SIVs) in Tg (fli1:EGFP) zebrafish embryos. Meanwhile, the results of the endothelial tube formation assay showed that in vitro angiogenesis was inhibited by BP exposure. Mechanistically, BP exposure increased oxidative stress characterized by a significant decrease in superoxide dismutase (SOD) and catalase (CAT) activity, accompanied by increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in both zebrafish and HUVECs. Therefore, the vascular toxicity and oxidative stress potency of the BPs were compared and evaluated, ranking as follows: BPAF > BPF > BPA > BPS. To the best of our knowledge, the present work, for the first time, systematically provides direct evidence for BPA and its alternatives on developmental vascular toxicity in vitro and in vivo. Therefore, these findings will provide insight into the rational and safe application of BPA substitutes.
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•BPs induced vascular toxicity in zebrafish in vivo.•BPs exposure significantly inhibited angiogenesis in vitro.•BPs exposure dramatically increased the oxidative stress.•The vascular toxicity of BPs: BPAF > BPF > BPA > BPs.
Bisphenol A (BPA) is a well-known endocrine disruptor that imperfectly mimics the effects of physiologic estrogens via membrane-bound estrogen receptors (mERα, mERβ, and GPER/GPR30), thereby ...initiating nongenomic signaling. Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper.
To characterize the nongenomic activities of BPS, we examined signaling pathways it evoked in GH3/B6/F10 rat pituitary cells alone and together with the physiologic estrogen estradiol (E2). Extracellular signal-regulated kinase (ERK)- and c-Jun-N-terminal kinase (JNK)-specific phosphorylations were examined for their correlation to three functional responses: proliferation, caspase activation, and prolactin (PRL) release.
We detected ERK and JNK phosphorylations by fixed-cell immunoassays, identified the predominant mER initiating the signaling with selective inhibitors, estimated cell numbers by crystal violet assays, measured caspase activity by cleavage of fluorescent caspase substrates, and measured PRL release by radioimmunoassay.
BPS phosphoactivated ERK within 2.5 min in a nonmonotonic dose-dependent manner (10-15 to 10-7 M). When combined with 10-9 M E2, the physiologic estrogen's ERK response was attenuated. BPS could not activate JNK, but it greatly enhanced E2-induced JNK activity. BPS induced cell proliferation at low concentrations (femtomolar to nanomolar), similar to E2. Combinations of both estrogens reduced cell numbers below those of the vehicle control and also activated caspases. Earlier activation of caspase 8 versus caspase 9 demonstrated that BPS initiates apoptosis via the extrinsic pathway, consistent with activation via a membrane receptor. BPS also inhibited rapid (≤ 1 min) E2-induced PRL release.
BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E2-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release.
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•Amorphous boron exhibited outstanding catalytic activity and superior stability for peroxymonosulfate activation.•Effective degradation of bisphenol S was achieved in the amorphous ...boron/peroxymonosulfate oxidative system.•The corresponding catalytic oxidation mechanism was elucidated.
Recently, tremendous efforts have been devoted to developing carbon-based metal-free catalysts as an alternative to metal-based catalysts for remediation of emerging contaminants. However, further investigations have demonstrated that the durability of carbocatalysts is poor. Therefore, it is extremely desirable to seek a novel metal-free catalyst with high efficiency and superb stability. Herein, we first discovered that amorphous boron (A-boron) can be used as a metal-free catalyst for peroxymonosulfate (PMS) activation to produce free radicals for effective degradation of bisphenol S (BPS), which is a newly-occurring estrogenic endocrine-disrupting chemical. It exhibited outstanding catalytic activity and superior stability as comparing to metal-based and metal-free carbon-based catalysts. Moreover, many other typical organic pollutants in water such as bisphenol F, sulfamethoxazole, rhodamine B and methyl orange can also be effectively decomposed in A-boron/PMS oxidative system. The effects of reaction parameters on BPS degradation were systematically investigated. The catalytic oxidation mechanism was proposed. The intriguing catalytic feature of A-boron discovered in this study will provide new opportunities for the future development of A-boron based materials with promising applications in water remediation.
Bisphenol A (BPA), a chemical incorporated into plastics and resins, has estrogenic activity and is associated with adverse health effects in humans and wildlife. Similarly structured BPA analogues ...are widely used but far less is known about their potential toxicity or estrogenic activity in vivo. We undertook the first comprehensive analysis on the toxicity and teratogenic effects of the bisphenols BPA, BPS, BPF, and BPAF in zebrafish embryo-larvae and an assessment on their estrogenic mechanisms in an estrogen-responsive transgenic fish Tg(ERE:Gal4ff)(UAS:GFP). The rank order for toxicity was BPAF > BPA > BPF > BPS. Developmental deformities for larval exposures included cardiac edema, spinal malformation, and craniofacial deformities and there were distinct differences in the effects and potencies between the different bisphenol chemicals. These effects, however, occurred only at concentrations between 1.0 and 200 mg/L which exceed those in most environments. All bisphenol compounds induced estrogenic responses in Tg(ERE:Gal4ff)(UAS:GFP) zebrafish that were inhibited by coexposure with ICI 182 780, demonstrating an estrogen receptor dependent mechanism. Target tissues included the heart, liver, somite muscle, fins, and corpuscles of Stannius. The rank order for estrogenicity was BPAF > BPA = BPF > BPS. Bioconcentration factors were 4.5, 17.8, 5.3, and 0.067 for exposure concentrations of 1.0, 1.0, 0.10, and 50 mg/L for BPA, BPF, BPAF, and BPS, respectively. We thus show that these BPA alternatives induce similar toxic and estrogenic effects to BPA and that BPAF is more potent than BPA, further highlighting health concerns regarding the use of BPA alternatives.
Background: Human exposure to bisphenol A (BPA) is widespread. After exposure, BPA is rapidly metabolized and eliminated in urine. Therefore, there is considerable within-person and betweenperson ...variability of BPA concentrations in spot urine samples. However, no information exists on the within-day variability of urinary BPA concentrations. Objectives: We examined the between-person and within-person and between-day and withinday variability in the urinary BPA concentrations of eight adults who collected all voids for 1 week to investigate the impact of sampling strategy in the exposure assessment of BPA using spot, first morning, or 24-hr urine collections. Methods: We determined the urinary concentrations of BPA using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography/tandem mass spectrometry. Results: The between-day and within-person variability was the primary contributor to the total variance both for first morning voids (77%) and 24-hr urine collections (88%). For the spot collections, we observed considerable within-day variance (70%), which outweighed the between-person (9%) and between-day and within-person (21%) variances. Conclusions: Regardless of the type of void (spot, first morning, 24-hr collection), urinary BPA concentrations for a given adult changed considerably—both within a day and for the 7 days of the study period. Single 24-hr urine collections accurately reflect daily exposure but can misrepresent variability in daily exposures over time. Of interest, when the population investigated is sufficiently large and samples are randomly collected relative to meal ingestion times and bladder emptying times, the single spot—sampling approach may adequately reflect the average exposure of the population to BPA.
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.
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