bisphenols
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Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- buňky Hep G2 MeSH
- diacylglycerol-O-acyltransferasa genetika metabolismus MeSH
- diethylhexylftalát toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- sloučeniny bisfenolu A MeSH
- viabilita buněk účinky léků MeSH
- ztučnělá játra * chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).
Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.
- MeSH
- androgeny * krev metabolismus MeSH
- benzhydrylové sloučeniny krev MeSH
- cytokiny krev metabolismus MeSH
- dospělí MeSH
- endokrinní disruptory * krev MeSH
- fenoly MeSH
- hirzutismus * krev etiologie chemicky indukované MeSH
- hyperandrogenismus krev MeSH
- lidé MeSH
- mladý dospělý MeSH
- obezita krev metabolismus MeSH
- syndrom polycystických ovarií * krev metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: A novel supported liquid extraction approach using small polymeric nanofibrous discs was demonstrated and applied to the analysis of real river water. Nanofibrous discs were tested to extract model mixture of 9 common water contaminants 4-nitrophenol, various chlorophenols, bisphenol A, permethrin, and fenoxycarb featuring a wide range of log P values (1.9-6.5). Polyacrylonitrile, polyhydroxybutyrate, and polylactic acid nanofibers were selected as adsorptive materials. One-step desorption was performed directly in HPLC vials, to avoid time-consuming evaporation and reconstitution steps. The discs were allowed to sediment to the bottom of the vial before injection into the chromatographic system. RESULTS: Various parameters affecting the extraction efficiency including 1-octanol volume, extraction time, ionic strength, and sample volume were investigated and optimized. Wetting the nanofiber discs with 1-octanol resulted in up to 20-fold increase in enrichment factor when compared to non-wetted polymer counterparts. The highest enrichment factors were observed for analytes with a log P range of 3.3-4.5. Our developed method showed good linearity in the range 20-200 μg/L for all analytes tested. Satisfactory repeatability with RSD <13 % were achieved covering all steps including disc preparation, wetting, extraction/elution, and chromatography analysis, and recoveries ranged from 58.93 to 121.43 %. SIGNIFICANCE: This work represents novel simple supported liquid extraction approach using impregnated polymer nanofiber discs. Using only 50 μL 1-octanol, we reduced the organic solvent compared to other extraction methods. There was no need for any plastic cartridge to hold the sorbent and direct in-vial desorption reduced the unnecessary, time-consuming steps and simplified the sample preparation protocol.
- Publikační typ
- časopisecké články MeSH
A novel sorbent for solid phase extraction (SPE) based on hybrid nanofibrous polycaprolactone containing graphene nanoparticles has been prepared. The preparation of hybrid polymer nanofibers with a very high 1:1 polymer/graphene ratio was achieved for the first time using alternating current electrospinning. The final appearance of these nanofibers was a thick porous layer that was cut into the shape of easy-to-handle extraction discs. Based on the preliminary study in which the graphene content varied, 30% graphene-doped nanofibers (w/w) exhibited the highest recoveries and enabled a significant increase in the retention of analytes, 2-25 times in comparison to PCL. The incorporation of graphene resulted in a higher surface area of 12 g/m2 compared to 2 g/m2 determined for the native polycaprolactone (PCL) nanofibers. This unique material was applied for a simple stirred disc sorptive extraction and preconcentration of trace levels of emerging organic environmental contaminants, bisphenols A, AF, AP, C, S, Z, 3-chlorophenol, and pesticides fenoxycarb, deltamethrin, and kadethrin from surface waters prior to HPLC-DAD determination. This was accomplished by stirring the unsupported nanofiber disc in a large-volume sample with RSD of five extractions of 3-15%. Recoveries yielded 87-120%, except 52% for bisphenol S due to its high polarity. Optimization of the extraction procedure included conditioning, sample volume, extraction time, and elution solvent. Our novel desorption procedure carried out in a vial used for the direct injection into the HPLC system significantly reduced sample handling and minimized potential human error.
- Publikační typ
- časopisecké články MeSH
Exposure to bisphenols has been found to have adverse effects on male reproductive function in animals. Human exposure to bisphenols is widespread. Bisphenol A (BPA) and its analogues, including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) are utilized in various consumer products such as food contact materials and dental resins. The effects of these compounds on male fertility and spermatogenesis are unclear and findings from human studies are inconsistent. In this cross-sectional study, we evaluated the influence of BPA, BPS, BPF, BPAF (BPs) measured in semen on number of spermatozoa, total motility, progressive motility, morphology, and DNA fragmentation. We also examined the association of bisphenols (BPs) exposure with patients' occupation. A total of 358 patients aged 17-62 years with BMI 18-42 were included in the study from 2019 to 2021. BPs were extracted using solvent extraction followed by preconcentration step and determined by high-performance liquid chromatography and tandem mass spectrometry (LC/MSMS). Bisphenols were detected in 343 from 349 analysed samples (98.3% of all the samples). In 6 samples, the concentration of all BPs was under the limit of detection and in 20 samples under the limit of quantification. We did not find a statistically significant relationship between occupation and BPs. However, we observed significant correlations between the concentration of BPA and a lower motility and normal morphology. For BPS, a significant correlation with a lower ejaculate volume and a lower total sperm count was found. BPF and BPAF were detected only in 14.3% and 23.9% of samples, respectively. For BPF and BPAF, no significant correlations with spermiogram parameters were observed. Our results show that BPs are widespread in the male population (more than 90% of analysed samples), independently of an occupation and in case of BPA and BPS having a negative impact on spermiogram parameters.
- MeSH
- benzhydrylové sloučeniny * toxicita analýza MeSH
- fenoly * MeSH
- fluorokarbony * MeSH
- lidé MeSH
- průřezové studie MeSH
- sperma * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The aim of the study was to examine the potential impacts of bisphenol A (BPA) and its analogues BPB, BPF, and BPS on mice TM3 Leydig cells, with respect to basal cell viability parameters such as metabolic activity, cell membrane integrity, and lysosomal activity after 48-h exposure. In addition, monitoring of potential bisphenol ́s actions included evaluation of ROS production and gap junctional intercellular communication (GJIC) complemented by determination of testosterone secretion. Obtained results revealed significant inhibition in mitochondrial activity started at 10 microg/ml of bisphenols after 48-h exposure. Cell membrane integrity was significantly decreased at 5 microg/ml of BPA and BPF and 10, 25, and 50 microg/ml of BPA and BPS. The lysosomal activity was significantly affected at 10, 25, and 50 microg/ml of applied bisphenols. A significant overproduction of ROS was recorded mainly at 5 and 10 microg/ml of tested compounds. In addition, significant inhibition of GJIC was observed at 5 microg/ml of BPB followed by a progressive decline at higher applied doses. In the case of testosterone production, a significant decline was confirmed at 10, 25 and 50 microg/ml.
- MeSH
- benzhydrylové sloučeniny metabolismus MeSH
- endokrinní disruptory * farmakologie MeSH
- Leydigovy buňky * MeSH
- myši MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sulfony farmakologie MeSH
- testosteron metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.
- Publikační typ
- časopisecké články MeSH
Advanced solid phase extraction (SPE) fibrous sorbents including polyethylene, polypropylene poly (hydroxybutyrate), and polyamide 6 nanofibers, polycaprolactone microfibers/nanofibers, polycaprolactone microfibers/polyvinylidene difluoride nanofibers, and poly (hydroxybutyrate) microfibers/polypropylene microfibers composites, as well as commercial molecularly imprinted polymers and restricted access media sorbent were compared in terms of bisphenols extraction from milk and their clean-up efficiency. Three on-line SPE-HPLC methods were completely validated for the extraction and detection of bisphenols A, AF, C, A diglycidyl ether, and F diglycidyl ether in bovine milk. Polycaprolactone composite nanofibers compared favorably to restricted access media, enabled excellent clean-up of bisphenols from the proteinaceous matrix, and yielded recoveries 98.0-124.5% and 93.0-115.0%, respectively, with RSD less than 10%. Total analysis time including on-line SPE step lasted only 12 min, which represents a significant reduction in time compared with previously reported as well as official European Union and AOAC methods defined for the determination of bisphenols in various matrices.
- MeSH
- adsorpce MeSH
- ethery MeSH
- extrakce na pevné fázi metody MeSH
- hydroxybutyráty MeSH
- mléko MeSH
- molekulárně imprintované polymery MeSH
- molekulový imprinting * metody MeSH
- nanovlákna * chemie MeSH
- polypropyleny MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A novel method for the extraction of river water contaminants as model analytes of ranging polarities, including bisphenols A, C, S, Z, fenoxycarb, kadethrin, and deltamethrin, using small compact fibrous disks has been developed and validated. Polymer nanofibers and microfibers prepared from poly(3-hydroxybutyrate), polypropylene, polyurethane, polyacrylonitrile, poly(lactic acid), and polycaprolactone doped with graphene were evaluated in terms of extraction efficiency, selectivity, and stability in organic solutions. Our novel extraction procedure comprised preconcentration of analytes from 150 mL river water to 1 mL of eluent using a compact nanofibrous disk freely vortexed in the sample. Small nanofibrous disks with a diameter of 10 mm were cut from a compact and mechanically stable 1-2 mm thick micro/nanofibrous sheet. After 60 min extraction in a magnetically stirred sample located in a beaker, the disk was removed from the liquid and washed with water. Then, the disk was inserted into a 1.5 mL HPLC vial and extracted with 1.0 ml methanol upon short intensive shaking. Our approach avoided the undesired problems related to the manual handling typical of "classical" SPE procedure since the extraction was carried out directly in the HPLC vial. No sample evaporation, reconstitution, or pipetting was required. The nanofibrous disk is affordable, needs no support or holder, and its use avoids creation of plastic waste originating from disposable materials. Recovery of compounds from the disks was 47.2-141.4% depending on the type of polymer used and the relative standard deviations calculated from 5 extractions ranged from 6.1 to 11.8% for poly(3-hydroxybutyrate), 6.3-14.8% for polyurethane, and 1.7-16.2% for polycaprolactone doped with graphene. A small enrichment factor was obtained for polar bisphenol S using all sorbents. A higher preconcentration reaching up to 40-fold was achieved for lipophilic compounds such as deltamethrin when using poly(3-hydroxybutyrate) and graphene-doped polycaprolactone.
- Publikační typ
- časopisecké články MeSH
