Abstract
Comparative analyses determined the relationship between the structure of bisphenol A (BPA) as well as of seven bisphenol analogues (bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), ...bisphenol F (BPF), bisphenol Z (BPZ), bisphenol AP (BPAP), bisphenol PH (BPPH)) and their biotransformability by the biphenyl-degrading bacterium
Cupriavidus basilensis
SBUG 290
.
All bisphenols were substrates for bacterial transformation with conversion rates ranging from 6 to 98% within 216 h and 36 different metabolites were characterized. Transformation by biphenyl-grown cells comprised four different pathways: (a) formation of
ortho-
hydroxylated bisphenols, hydroxylating either one or both phenols of the compounds; (b) ring fission; (c) transamination followed by acetylation or dimerization; and (d) oxidation of ring substituents, such as methyl groups and aromatic ring systems, present on the 3-position. However, the microbial attack of bisphenols by
C. basilensis
was limited to the phenol rings and its substituents, while substituents on the carbon bridge connecting the rings were not oxidized. All bisphenol analogues with modifications at the carbon bridge could be oxidized up to ring cleavage, while substituents at the 3-position of the phenol ring other than hydroxyl groups did not allow this reaction. Replacing one methyl group at the carbon bridge of BPA by a hydrophobic aromatic or alicyclic ring system inhibited both dimerization and transamination followed by acetylation. While most of the bisphenol analogues exhibited estrogenic activity, four biotransformation products tested were not estrogenically active.
•The highest concentrations in surface waters were for BPA, BPS, and BPF.•For several surface waters the concentrations of analogues BPs were greater than BPA.•High environmental risks were found for ...BPA, BPAF, BPB, BPF, and BPF.•The risk of estrogenic activity was high for BPA, BPAF, and BPB.•Hybrid MBR and biologically modified MBR can be effective for BPs removal.
The presence of bisphenols (BPs) in surface water is a recent environmental concern due to their potential adverse effects on ecosystem. As an aggravating factor, the monitoring and regulations of BPs in aquatic matrices are rare or nonexistent. Therefore, the present article reviewed and deeply discussed the occurrence of BPs in surface water worldwide and their effects on waterbodies, including acute and chronic toxicity and estrogenicity. In sequence, the environmental risks of BPs were calculated for the context of several countries. Also, the removal of BPs and their related risks were evaluated for several configurations of membrane bioreactors (MBR). The results showed that the highest concentrations in surface waters were for BPA, BPF, and BPS; for surface waters of several countries, the concentrations of analogues BPs were greater than BPA. Besides, many BPs were classified with high toxicity, and high environmental risks were found for BPA, BPAF, BPB, BPF, and BPS. Countries such as China, India, Portugal, and Taiwan had surface waters with high risks related to BPs. In addition, the risk of estrogenic activity was high for BPA, BPAF, and BPB. Finally, hybrid MBR, hybrid anaerobic MBR, and modification in biological MBR can be effective alternatives for BPs and risk removal; however, more investigations are necessary, mainly for analogue BPs.
•Synthesis of C-3-O-labeled BODIPY–estradiol conjugates.•Labeling via C4–C8-long alkyl linkers based on CuAAC reaction or etherification.•Molecular docking calculations on two binding sites of human ...ERα.•Retained estrogenic activity, direct interaction and activation of ERα.•Induction of cellular fluorescence and co-localisation with ERα.
Novel BODIPY–estradiol conjugates have been synthesized by selecting position C-3-O for labeling. The conjugation strategy was based on Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) or etherification. Estradiol derivatives used as azide partners bearing an ω-azidoalkyl function through C4–C8-long linkers have been prepared. CuAAC reactions of estradiol azides with BODIPY alkyne furnished fluorescent 3-O-labeled conjugates bearing the triazole ring as a coupling moiety. Williamson etherifications of 3-O-(ω-bromoalkyl)-17β-estradiol derivatives with BODIPY-OH resulted in labeled conjugates connected with an ether moiety. Interactions of the conjugates with estrogen receptor (ER) were investigated using molecular docking calculations in comparison with estradiol. The conjugates occupied both the classical and alternative binding sites on human ERα, with slightly lower binding affinity to references estradiol and diethystilbestrol. All compounds have displayed reasonable estrogenic activity. They increased the proliferation of ER-positive breast cancer cell line MCF7 contrary to ER-negative SKBR-3 cell line. The most potent compound 13a induced the transcriptional activity of ER in dose-dependent manner in dual luciferase recombinant reporter model and increased progesterone receptor's expression, proving the retained estrogenic activity. The fluorescence of candidate compound 13a co-localised with the ERα. The newly synthesized labeled compounds might serve as good starting point for further development of fluorescent probes for modern biological applications. In addition to studying steroid uptake and transport in cells, e.g. in the processes of biodegradation of estrogen-hormones micropollutants, they could also be utilized in examination of estrogen-binding proteins.
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Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity ...of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings.
•The fragmentation of PC MPs was accompanied with the decline of molecular weight.•Dropped intermediates were trapped in the particles or released to the leachate.•The amount of BPA (369.57 ± 5.47 ...μg/g) occupied 2.7 % of the TOC leached out.•The integral estrogenic activity of leachates from aged MPs should be highlighted.
Bisphenol A polycarbonate (BPA-PC) is a kind of widely used engineering plastics. However, excessive usage causes the production of plastic wastes, following property changes of polymers and high risks of released chemicals during outdoor weathering. In this study, we systematically investigated the photoaging behavior of PC microplastics (MPs) in aquatic environment and evaluated the potential risk of released intermediates. Light irradiation along with mechanical abrasion facilitated the fragmentation of PC MPs and stimulated photooxidative modification during 640 h of ultraviolet (UV) exposure. Continuous degradation of the polymer was accompanied with dramatic decline of molecular weight. Also, BPA was released from irradiated PC MPs with a trend of an initial rapid increase followed by a decrease versus the irradiation time, and the maximum concentration of dropped BPA was detected up to 652.80 ± 72.89 μg/g (43.39% and 56.61% respectively in particles and leachates). However, the releasing amount of BPA in the leachate merely occupied 2.7% of the total organic carbon (TOC) leached out, suggesting that a great number of unknown organic products were produced other than BPA. Liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) analysis showed that these organic compounds forming MPs-derived dissolved organic matter (MPs DOM) were partly composed of 4,4’-dihydroxybenzophenone (DHB), p-hydroxybenzoic acid (p-HBA) and methyparaben (MeP), which would also contribute to the estrogenic activity. The degradation pathway of PC MPs was elaborated with the photolysis process of PC dimer and BPA, and the remarkable photoaging of PC MPs was mainly dominated by the generated reactive oxygen species (ROS). The findings of this study indicated that understanding the photoaging process of PC MPs was vital to evaluate their integral cumulative estrogenic activity in aquatic environment, and further highlighted the notable possible risks of plastic leachates to exposed biota.
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Bisphenol (BP) analogues are widely used as industrial materials and various product additives and are inevitably released into environment. However, knowledge on the sources of different BPs, ...especially those from urban rainfall runoff to the receiving rivers is very limited. In this study, 15 BPs were determined in surface water, sediments, wastewater treatment plant (WWTP) and rainfall runoff samples in the Pearl River region, South China. Eleven BPs were detected in surface water and sediments of the Pearl Rivers. BPA was the dominant compound up to 2080 ng/L in surface and 1970 ng/g in sediments, followed by BPF, BPS, BPTMC and BPAF. In WWTPs, 10, 9 and 8 BPs were detected in influents, effluents and excess sludges, respectively, with total BPs (ΣBPs) concentrations in effluents still at thousands ng/L, suggesting incompletely removal of BPs. Five BPs were detected in urban rainfall runoff samples, with the ΣBPs concentrations up to 7740 ng/L. Mass loads of ΣBPs from the rainfall runoff (5800 kg/y) were almost equivalent to the source from WWTPs (7370 kg/y) in the region, implying that the urban rainfall runoff was a potential source for BPs into the receiving river. The calculated estrogenic activity contributed by BPs showed low to median risks in sources and receiving rivers. But BPs are always as mixtures with other potential endocrine disrupting chemicals (EDCs) which probably pose high estrogenic activity risks. Hence, effective measures should be taken to decrease the input of EDCs from sources to receiving rivers.
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•15 Bisphenol (BP) analogues in river, WWTPs and rainfall runoff were investigated.•BPA was the dominant, followed by BPF, BPS, BPTMC and BPAF in most inputs.•The mean ΣBPs in street and courtyard runoff were 2410 and 232 ng/L, respectively.•The mass load of BPs from rainfall runoff was almost equal to WWTP effluents.•BPs posed low to median estrogenic risks in the Pearl River Delta region.
This study showed the wide detections of bisphenol analogues from different sources to the Pearl River system, and emphasizes the importance of considering urban rainfall runoff as a potential source of bisphenols for the receiving rivers.
The estrogenic activity of the chemical UV-filters, 4-methylbenzylidene camphor (4-MBC) and octyl methoxy cinnamate (OMC) was investigated in an in vivo rainbow trout (Oncorhynchus mykiss) assay. ...Plasma vitellogenin concentrations were quantified by means of an Enzyme Linked Immuno Sorbent Assay (ELISA) in juvenile rainbow trout before and after intraperitoneal injection of the test compounds. Injection of 4-MBC on day 0, 3, 6 and 10 in the exposure period caused dose and time dependent increases in the concentration of plasma vitellogenin. Significant elevation of vitellogenin concentrations in plasma was demonstrated from 151 mg 4-MBC kg−1 injection−1. Logistic regression analysis relating the percentage of responding fish to the injected dose of 4-MBC resulted in ED10, ED50 and ED90 values of 37, 115 and 194 mg kg−1 injection−1, respectively, after 14 days of exposure (4 injections). Injections with OMC (up to 202 mg kg−1 injection−1) did not result in a statistically significant response in groups of exposed fish, although some individual fish showed elevated concentrations of vitellogenin in plasma. The results confirm that 4-MBC is estrogenic in fish in vivo.
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•The estrogenic effect of 4-MBC and OMC was tested in a rainbow trout in vivo assay.•Vitellogenin induction was used as biomarker after intraperitoneal injection.•4-MBC induced vitellogenin synthesis with an ED50 of 115 mg 4-MBC/kg/injection.•202 mg OMC/kg did not result in increased average vitellogenin concentrations.•However, a few individual fish responded to 202 mg OMC/kg.
Lignin-derivable bisguaiacols/bissyringols are viable alternatives to commercial bisphenols; however, many bisguaiacols/bissyringols (e.g., bisguaiacol F BGF) have unsubstituted bridging carbons ...between the aromatic rings, making them more structurally similar to bisphenol F (BPF) than bisphenol A (BPA) – both of which are suspected endocrine disruptors. Herein, we investigated the estrogenic activity (EA) and developmental toxicity of dimethyl-substituted bridging carbon-based lignin-derivable bisphenols (bisguaiacol A BGA and bissyringol A BSA). Notably, BSA showed undetectable EA at seven test concentrations (from 10−12 M to 10−6 M) in the MCF-7 cell proliferation assay, whereas BPA had detectable EA at five concentrations (from 10−10 M to 10−6 M). In silico results indicated that BSA had the lowest binding affinity with estrogen receptors. Moreover, in vivo chicken embryonic assay results revealed that lignin-derivable monomers had minimal developmental toxicity vs. BPA at environmentally relevant test concentrations (8.7–116 μg/kg). Additionally, all lignin-derivable compounds showed significantly lower expression fold changes (from ∼1.81 to ∼4.41) in chicken fetal liver tests for an estrogen-response gene (apolipoprotein II) in comparison to BPA (fold change of ∼11.51), which was indicative of significantly reduced estrogenic response. Altogether, the methoxy substituents on lignin-derivable bisphenols appeared to be a positive factor in reducing the EA of BPA alternatives.
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•Bissyringol A had undetectable estrogenic activity in MCF-7 cell assays.•Lignin-derivable monomers had reduced estrogenic responses vs. bisphenol A and F.•Developmental toxicity of lignin-derivable monomers was tested for the first time.•Lignin-derivable monomers had minimal developmental toxicity in chicken embryos.
Extensive use of endocrine disruptor compounds (EDCs) and their release through various pathways into the environment are emerging environmental concerns. In this context, H2O2 and chlorine UV-based ...treatments were carried out to evaluate their efficiency in the removal of the bisphenol A (BPA), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) at 100 μg L−1 from ultrapure water and from wastewater treatment plants (WWTP). Photolysis was performed under different irradiation sources, i.e. UVC and UVA. The effect of H2O2 (3 and 30 mg·L−1), free chlorine concentrations (1 and 2 mg·L−1) and pH (5, 7 and 9) were also investigated. Toxicity (Raphidocelis subcapitata) and estrogenic activity (yeast estrogen screen - YES assay) were assessed during the processes. Compound removal at optimal operating parameters reached 100% after 15 and 2 min for UVC/H2O2 (pH 9 and 3 mg L−1 of H2O2), and UVC/Cl (pH 9 and 2 mg L−1 of chlorine), respectively. Total organic carbon (TOC) removal achieved 37% and 45% for the H2O2 and Cl-UV based process, respectively. The in vitro YES assay indicated that the formed by-products were non-estrogenic compounds, while the toxicity evaluation revealed high cell growth inhibition due to UVC/Cl byproducts. During the UV-based processes, 30 transformation products (TPs) were identified, in which three new chlorinated TPs from E2 and EE2 may be responsible for toxicity effects. EDC degradation by UV/Cl is faster than by UV/H2O2, although chlorinated toxic byproducts were also formed during the UV/Cl process.
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•The Cl/UV process is more efficient than H2O2/UV in removing E2, EE2 and BPA.•Both processes are capable of removing WWTP EDCs.•EDC degradation products do not display estrogenic activity.•The Cl/UV process produces high toxicity TPs.•Three new TPs were identified during the Cl/UV process.
The flavone apigenin is widely distributed in vegetables and fruits and has a variety of pharmacological effects. However, there is no definitive scientific evidence that apigenin could act as a ...phytoestrogen and exert exerting estrogenic or antiestrogenic efficacy in vivo. Therefore, this study was established an ovariectomy (OVX) and estrogenized mouse model to evaluate the effects of apigenin on reproductive target tissues. Our data demonstrated that apigenin could exert a double-directional adjusting estrogenic effect in vivo. Specifically, treatment with apigenin reversed the weight changes caused by abnormal estrogen levels and altered the status of vaginal epithelial cells via the estrogen receptors. In addition, we found that apigenin exhibited a significant estrogenic activity, as indicated by the reversal of uterine atrophy. Apigenin treatment could also regulate the target tissue coefficient changes and estrogen disorders caused by excessive estrogen. Importantly, the administration of apigenin could upregulated the estrogen receptor (ER) α and ER β expression as a partial agonist. Our results demonstrate that apigenin has a double directional adjusting function in different physiological environments.
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