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.
•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.
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.
•Steroids and BPA had a higher removal than phthalates in STPs, and mainly by biodegradation.•The estrogenic activity of steroids in effluents were higher than that of BPA and phthalates.•Tertiary ...treatment effectively reduced the discharge of steroids and BPA in STPs.•E2 contributed more estrogenic activity in effluents based on chemEEQ results.•E2 and EE2 in the tertiary effluent posed a moderate risk to the aquatic ecosystem.
Effluents of sewage treatment plants (STPs) are an important source of estrogenic substances to the receiving water bodies affecting their ecological safety. In this study, steroids, bisphenol A (BPA) and phthalates were assessed in the secondary (SE) and tertiary effluent (TE) of three typical urban STPs in Beijing (China). In addition, the overall estrogenic activity in these effluents was assessed by an in-vitro bioassay (ERE-CALUX). Results showed that the concentrations and activities of estrogenic compounds in TE were lower than those in SE. The residual concentration of 17β-estradiol (E2) was the highest among the detected steroids, accounting for 51.6 ± 5.1% in SE and 57.5 ± 24.8% in TE. The residual level (25.2–41.6 ng/L) of BPA in effluents was significantly higher than that of steroids (0.2–28.8 ng/L). The residual concentration of diethyl phthalate was the highest among the detected phthalates accounting for 47.1 ± 5.1% in SE and 37.6 ± 11.5% in TE. Steroids and BPA had a higher removal rate (83.5% and 96.7%) in secondary and tertiary treatment than phthalates (68.8% and 83.1%). The hydrophobic characteristics of these estrogenic compounds determined the removal mechanism. The removal of steroids, BPA, dimethyl phthalate and diethyl phthalate (LogKow= 1.61–4.15) mainly occurred through biodegradation in the water phase, while the removal of dibutyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate (LogKow= 4.27–7.50) mainly occurred in the solid phase after adsorption on and sedimentation of the suspended particulate matter. According to ERE-CALUX, the estrogenic activity in the final STP effluents was 3.2–45.6 ng E2-equivalents/L, which is higher than reported levels in the effluents of European STPs. Calculation of estrogenic equivalents by using substance specific chemical analysis indicated that the dominant contributor was E2 (56.4–88.4%), followed by 17α-ethinylestradiol (EE2) (4.1–34.8%), both also exerting a moderate risk to the aquatic ecosystem. While the upgrade of treatment processes in STPs has efficiently reduced the emission of estrogenic substances, their ecological risk was not yet phased out.
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The adverse effects of fine atmospheric particulate matter with aerodynamic diameters of ≤2.5 μm (PM2.5) are closely associated with particulate chemicals. In this study, PM2.5 samples were collected ...from highway and industry sites in Hangzhou, China, during the autumn and winter, and their cytotoxicity and pulmonary toxicity and endocrine-disrupting potential (EDP) were evaluated in vitro and in vivo; the particulate polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and heavy metals were then characterized. The toxicological results suggested that the PM2.5 from highway site induced higher cytotoxicity (cell viability inhibition, intracellular oxidative stress, and cell membrane injury) and pulmonary toxicity (inflammatory response (IR) and oxidative stress (OS)) than the samples from industry site, while the PM2.5 from industry site exhibited higher EDP (estrogenic and anti-androgenic activity). The cytotoxicity and pulmonary toxicity of PM2.5 in the winter were higher than those in the autumn, while no seasonal difference in the endocrine-disrupting potential was observed (p > 0.05). The Pearson correlation analysis between the biological effects and particulate chemicals revealed that the PM2.5-induced inflammatory response and oxidative stress were closely associated with the particulate PAHs and heavy metals (Pearson correlation coefficients: rIR, PAHs = 0.822–0.988, rIR, heavy metals = 0.895–0.971, rOS, PAHs = 0.843–0.986, and rOS, heavy metals = 0.887–0.933), while particulate di (2-ethylhexyl)phthalate (DEHP) substantially contributed to the EDP of PM2.5 (rEDP, DEHP = 0.981). This study indicated that the toxicity and EDP of PM2.5 could vary with the surrounding environment and season, which was closely associated with the variations of particulate chemicals. Further studies are needed to clarify the associations between the harmful effects of PM2.5 and other contributing factors.
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•PM2.5 from highway site induced higher cytotoxicity and pulmonary toxicity.•PM2.5 from industry site had higher endocrine-disrupting potential.•PM2.5 in the winter induced higher cytotoxicity and pulmonary toxicity.•Toxicity of PM2.5 was closely associated with particulate PAHs and heavy metals.•Di (2-ethylhexyl) phthalate substantially contributed to endocrine-disrupting potential of PM2.5.
•Concentration of PAEs was determined in highly acidic juice kept in PET container.•DEHP was the major compound with the median value of 8.1, 10.5 and 9.8 μg/L for lemon juice, verjuice and ...vinegar.•DEHP concentration has exceeded the WHO (8 μg/L) and EPA (6 μg/L) allowable limit.•PAEs concentrations had significant correlation with storage time and storage temperature.•Significant but negative correlations were obtained between PAEs concentrations and pH.•PAEs in iranian highly acidic juice may pose estrogenic-based health risks.
The present study aimed to investigate the concentration of PAEs, their migration from the walls of PET containers into highly acidic juices (such as lemon juice, vinegar, and verjuice) and the risk assessment based on the estrogenic potential of these widespread pollutants. We analyzed and quantified six priority compounds of PAEs, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n‑butyl phthalate (DnBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP) in 40 samples of aforementioned juices packed in PET containers. The results showed that DEHP and DnBP were the major compounds with the median value of 8.1 and 6.8 µg/L, 10.5 and 7.2 µg/L, and 9.8 and 6.7 µg/ L, in lemon juice, vinegar, and verjuice, respectively. The results also showed that ∑PAEs concentration was higher in juices packed in PET containers than in glass containers (two sample t-test, pvalue < 0.05). A significant and positive correlation was observed between the concentration of PAEs and the storage temperature, storage time, and sun exposure of containers of juices (Pearson correlation test, pvalue <0.05). However, there was a significant and negative correlation between pH and the concentration of these pollutants (pvalue < 0.05). The human daily intake-based risk assessment showed that the safety factor (SF) calculated for all PAEs was much higher than 1. This indicates that the consumption of these acidic juices would not put consumers at the risk of these compounds. However, the risk assessment based on the estrogenic potential of PAEs compounds showed that the average of estrogen equivalence (EEQ) calculated for the ∑PAEs was higher than 1 ng E2/L and could have long-term adverse effects on human health.
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•Caffeine, an indicator of anthropogenic waste, was associated with estrogenic activity.•Predominance of DnBP at tourist destinations may have plastic litter as its source.•Dominance of BPA in the ...lower stretch of Ganga is due to industrial effluents.•Only two sites had estrogenic activity that exceeded the pNEC for E2 in fish species.
The transboundary River Ganga serves as a conduit for meltwater from the Himalayas and is a major freshwater source for two thirds of Indian population before emptying into the Sundarban Delta, the largest estuary in the Bay of Bengal. Endocrine disrupting compounds (EDCs) such as phthalic acid esters (PAEs) and bisphenol A (BPA) used as organic plastic additives can pollute the aquatic environment receiving plastic litter. Hence, we have investigated these EDCs in water samples from Ganga and Sundarban wetland of India. Since these compounds exhibit estrogenic potential, we have further measured steroids and evaluated the estrogenic activity (estradiol equivalents, BioE2Eqs) using an in-vitro bioassay (E-Screen). Further BioE2Eqs were compared with the sum of predicted estradiol equivalents based on the chemical concentrations of PAEs and BPA by E-Screen (ChemE2Eq) and YES factors (ChemYES). Caffeine was measured as a marker for anthropogenic wastewater discharge. Results showed that the highest BioE2Eq (below the lowest observable effect of E2 on fish) was associated with sites having sewer outfalls in the middle stretch of the river, and concomitantly coinciding with the elevated concentrations of caffeine. Neither ChemE2Eq nor ChemYES correlated with measured BioE2Eqs. River concentrations of BPA (0.04–4.46 µg/L) and ∑7plasticizers (0.43–7.63 µg/L) were higher than BPA (0.21–2.82 µg/L) and ∑7plasticizers (0.85–2 µg/L) in the Sundarban wetland. The only steroids detected were androgens, found at four sites in Ganga (0.007 µg/L± 0.003, mean ± S.D.). The highest estimated ecotoxicological risk to aquatic insect and fish stemmed from BPA. A secondary effect, and a potential impact on human health could be reflected via fish consumption from the productive fisheries region along the lower stretch of River Ganga. Identification of areas of elevated estrogenicity, plasticizer and steroid concentrations in River Ganga can be used to design and implement interventions for the remediation of such emerging contaminants.
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Polycyclic aromatic hydrocarbons (PAHs) are often detected in the environment and are regarded as endocrine disruptors. We here designated mixtures of PAHs in the environment as environmental PAHs ...(ePAHs) to discuss their effects collectively, which could be different from the sum of the constituent PAHs. We first summarized the biological impact of environmental PAHs (ePAHs) found in the atmosphere, sediments, soils, and water as a result of human activities, accidents, or natural phenomena. ePAHs are characterized by their sources and forms, followed by their biological effects and social impact, and bioassays that are used to investigate their biological effects. The findings of the bioassays have demonstrated that ePAHs have the ability to affect the endocrine systems of humans and animals. The pathways that mediate cell signaling for the endocrine disruptions induced by ePAHs and PAHs have also been summarized in order to obtain a clearer understanding of the mechanisms responsible for these effects without animal tests; they include specific signaling pathways (MAPK and other signaling pathways), regulatory mechanisms (chromatin/epigenetic regulation, cell cycle/DNA damage control, and cytoskeletal/adhesion regulation), and cell functions (apoptosis, autophagy, immune responses/inflammation, neurological responses, and development/differentiation) induced by specific PAHs, such as benzaanthracene, benzoapyrene, benzlaceanthrylene, cyclopentac,dpyrene, 7,12-dimethylbenzaanthracene, fluoranthene, fluorene, 3-methylcholanthrene, perylene, phenanthrene, and pyrene as well as their derivatives. Estrogen signaling is one of the most studied pathways associated with the endocrine-disrupting activities of PAHs, and involves estrogen receptors and aryl hydrocarbon receptors. However, some of the actions of PAHs are contradictory, complex, and unexplainable. Although several possibilities have been suggested, such as direct interactions between PAHs and receptors and the suppression of their activities through other pathways, the mechanisms underlying the activities of PAHs remain unclear. Thus, standardized assay protocols for pathway-based assessments are considered to be important to overcome these issues.
•Over 250 references are reviewed to understand the current status of studies about ePAHs.•Bioassays for the study of ePAHs are summarized.•A total of 41 cell signaling pathways are discussed in association with ePAHs.•A comprehensive list of estrogenic/antiestrogenic PAHs and ePAHs is provided.
Environmental polycyclic aromatic hydrocarbons.
•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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Personal-care products (PCPs) involve a variety of chemicals whose persistency along with their constant release into the environment raised concern to their potential impact on wildlife and humans ...health. Regarded as emergent contaminants, PCPs demonstrated estrogenic activity leading to the need of new methodologies to detect and remove those compounds from the environment.
Molecular imprinting starts with a complex between a template molecule and a functional monomer, which is then polymerized in the presence of a cross-linker. After template removal, the polymer will contain specific cavities. Based on a good selectivity towards the template, molecularly imprinted polymers (MIPs) have been investigated as efficient materials for the analysis and extraction of the so called emergent pollutants contaminants.
Rather than lowering the limit of detections, the key theoretical advantage of MIP over existing methodologies is the potential to target specific chemicals. This unique feature, sometime named specificity (as synonym to very high selectivity) allows to use cheap, simple and/or rapid quantitative techniques such as fast separation with ultra-violet (UV) detection, sensors or even spectrometric techniques. When a high degree of selectivity is achieved, samples extracted with MIPs can be directly analyzed without the need of a separation step. However, while some papers clearly demonstrated the specificity of their MIP toward the targeted PCP, such prove is often lacking, especially with real matrices, making it difficult to assess the success of the different approaches.
This review paper focusses on the latest development of MIPs for the analysis of personal care products in the environment, with particular emphasis on design, preparation and practical applications of MIPs.
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•Evaluation of key parameters used for imprinted polymers selective to EP.•Practical applications of MIP in the analysis of contaminants release by PCP.•Application of MIP for the removal of contaminants in wastewater.
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