Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of mice.Methods We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 days.Fecal samples from the colon were analyzed using 16S rRNA sequencing.Results Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or BPF.This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus.Additionally,pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic pathways.Considering the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

Fabrication of a novel electrochemical sensor based on MnFe_(2)O_(4)/graphene modified glassy carbon electrode for the sensitive detection of bisphenol A

Manganese ferrite(MnFe_(2)O_(4))has the advantages of simple preparation,high resistivity,and high crystal symmetry.Herein,we have developed an electrochemical sensor utilizing graphene and MnFe_(2)O_(4) nanocomposites modified glassy carbon electrode(GCE),which is very efficient and sensitive to detect bisphenol A(BPA).MnFe_(2)O_(4)/graphene(GR)was synthesized by immobilizing the MnFe_(2)O_(4) microspheres on the graphene nanosheets via a simple one-pot solvothermal method.The morphology and structure of the MnFe_(2)O_(4)/GR nanocomposite have been characterized through scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS).In addition,electrochemical properties of the modified materials are comparably explored by means of cyclic voltammetry(CV),electrochemical impedance spectroscopy(EIS)and differential pulse voltammetry(DPV).Under the optimal conditions,the proposed electrochemical sensor for the detection of BPA has a linear range of 0.8-400μmol/L and a detection limit of 0.0235μmol/L(S/N=3)with high sensitivity,good selectivity and high stability.In addition,the proposed sensor was used to measure the content of BPA in real water samples with a recovery rate of 97.94%-104.56%.At present,the synthesis of MnFe_(2)O_(4)/GR provides more opportunities for the electrochemical detection of BPA in practical applications.

Garcinia Kola and Kolaviron Attenuates Bisphenol A-Induced Memory Impairment and Hippocampal Neuroinflammation in Male Wistar Rats

Bisphenol A (BPA), a toxicant which can leach into food from plastic containers, is reported to induce neurotoxicity among others via oxidative mechanisms. However, antioxidant compounds have been suggested to mitigate BPA-induced toxicities. Garcinia kola (GK) and its bioactive compound, kolaviron, are well-established natural antioxidants, which can exert protective effects against BPA-induced toxicities. This study was designed to investigate the likely mitigating effect of GK and kolaviron on BPA-induced memory impairment and hippocampal neuroinflammation in male Wistar rats. Thirty-five rats were equally grouped and treated as follows: I and II received distilled water and corn oil, respectively at 0.2 mL, while III - VII received BPA (50 mg/kg), BPA + GK (200 mg/kg), BPA + kolaviron (200 mg/kg), GK and kolaviron, respectively for 28 days p.o. Thereafter, behavioral studies were done using the Novel Object Recognition and Y maze tests. Subsequently under anaesthesia, the hippocampus in each animal was dissected out, homogenized and analysed for malondialdehyde, superoxide dismutase, catalase, reduced glutathione, glutathione transferase, nitrites, interleukin-6, tumour necrosis factor-α, acetylcholinesterase, glutamate acid decarboxylase, and arginase activity. Data were analyzed by ANOVA and Tukey Post-hoc test at p p Garcinia kola and Kolaviron mitigate bisphenol A-induced memory impairment and neuroinflammation via antioxidant potentiation and neurotransmitter balance.

Detection of Bisphenol A (BPA) in Plastic Bottles Using Vertical Cultivation at Various Temperatures

Polycarbonate plastics containing bisphenol A (BPA) used to manufacture drinking water bottles. Kurdistan region in northern Iraq is a developed area with increased pollution from plastic bottles. Trace amounts of BPA have been detected in bottled water samples. The absorption of BPA was measured with HPLC using a vertical cultivation system with Bulbs of the Allium Cepa plant planted in these plastic bottles with monitored growth. Vertical cultivation was found to have a low level of BPA in the plant cells, making it a safe cultivation method under specific climate conditions. The mean concentration of BPA in vertical cultivation is 0.19 ug/ml (3.8 ng for a 20 uL injection), and the Limit of Quantification (LOQ) is 0.63 ug/ml (12.7 ng for 20 uL injection). While Scanning Electron Microscope (SEM) shows that the concentrations are relatively low in water samples stored at room temperature compared to those exposed to direct sunlight (40°C) and water bottle samples stored at (-4°C), The correlation coefficients were found to be good (0.9992). SEM is used for plastic bottle samples stored at different temperatures. The images identify compound decay and explore the morphology of BPA in manufactured plastic materials.

Bisphenol A (BPA) Contamination in Whole Milk Marketed in Different Packages

Bisphenol A (BPA), an important endocrine disruptor, is used in the manufacturing of various materials, including food packaging. Ingestion of contaminated foodstuffs is, in fact, the most relevant form of exposure to this substance. However, scarce data on the presence of this contaminant in milk, or whether different types of food packaging influence food contamination are available in Brazil. This study, therefore, aimed to evaluate the BPA contamination of whole milk (fluid and powder) samples packaged in different types of packaging (Tetra Pak?;PET: Poly (ethylene terephthalate;Metallic can (epoxy resin);Polyethylene (PE) and poly (vinylidene chloride) (PVDC);Laminated Film - Metallized Polyester-Polyethylene and glass) and marketed metropolitan region of Rio de Janeiro, Brazil. An analytical method for the BPA determination in milk was optimized for both fluid (pasteurized and ultra-high temperature) and powdered milk samples. A modified QuEChERS method was applied, and BPA determinations were conducted by ultra-performance liquid chromatography coupled with sequential mass spectrometry (HPLC-MS/MS). The validated method was then applied to 51 milk samples, where BPA was detected in five samples (9.8%) and quantified in two (3.8%).

Bisphenol A in Fluid and Powdered Milk Samples and Associated Child Dietary Exposures

Bisphenol A (BPA) is a synthetic chemical found in a wide range of consumer products and consumables that humans are exposed to. The aim of this study was to determine BPA contamination levels in 51 milk samples sold in the Rio de Janeiro Metropolitan Region, Brazil. Bisphenol A was detected (≥limit of detection, LOD) in five of the analyzed samples (9.8%) and quantified (≥limit of quantification, LOQ) in two (3.8%). The estimated daily intake (EDI) for children aged up to 12 months ranged from 24.95 to 97.72 ng/kg body weight/day, lower than the established European Union tolerable daily intake value. Recent evidence, however, suggests that even low doses of endocrine disruptors such as BPA may pose potential health risks, even more so when exposure occurs at such an early life stage.

Preparation and Property of Bisphenol A Bis (diphenyl phosphate) Oligomer

Bisphenol A bis（diphenyl phosphate） oligomer（BDP） is prepared successfully from the reactants consisting of phosphorus oxyehloride （POCl3）, bisphenol A and phenol with a Friedel-Crafts catalyst. The resultant products were examined with thermtygravimetrie analysis （TGA） and high performance liquid chro- matography（HPLC）. Thermogravimetry data shows that BDP decomposes at 375℃ when 5 % weight lost. Experiments results show that catalyst is preferably AICI3 and the amount of it is preferably 1% relative to bisphenol A by mole. POCl3/bisphenol A mole ratio is preferably about 5：1 to 6：1. Experiments unclosed that a seal apparatus is very important to the properties of product.

Simultaneous determination of 4-tert-octylphenol, 4-nonylphenol and bisphenol A in Guanting Reservoir using gas chromatography-mass spectrometry with selected ion monitoring

The wide occurrence of estrogenic compounds 4-tert-octylphenol, 4-nonylphenol, bisphenol A in surface water of Guanting Reservoir was successfully determined. The target compounds in water samples were preconcentrated by liquid-liquid extraction with dichloromethane, derivatized by trifluoroacetic anhydride, and quantified by gas chromatography-mass spectrometry(GC-MS) with selected ion monitoring(SIM). In the selected seven sampling sites(S1\_S7), the concentration of NP in sample S7 was significantly higher than the other in reservoir. The status of pollution in S3 and S7 were much more serious. The concentrations of OP, NP and BPA were in the range of 44.5—48.8, 221.6—349.6 and 30.2—82.7 ng/L, respectively. The pollutants were mainly inputted from the upper river and released from sediments in Guanting Reservoir.

A Study on Bisphenol A,Nonylphenol,and Octylphenol in Human Urine amples Detected by SPE-UPLC-MS

Objective To establish a comprehensive analytical method based on SPE‐UPLC‐MS for the simultaneous determination of bisphenol A （BPA）, nonylphenol （NP）, and octylphenol （OP） in urine samples. Methods Sixty urine samples collected from healthy subjects were analyzed for BPA, NP, and OP concentrations. The samples were de‐conjugated by adding β‐glucuronidase and sulfatase. After the enzymatic treatment, the samples were subjected to the OASIS HLB column solid phase extraction cartridges so as to be cleaned and concentrated. The UPLC separation was performed on a Acquity UPLCTM BEH C18 column （2.1×100 mm, 1.7 μm） with a gradient elution system of methanol‐water as the mobile phase. Triple‐quadrupole mass spectrometry analyzer was used for the qualitative and quantitative analysis of UPLC‐MS/MS system. Results The limit of detection of BPA, NP, and OP was 0.10, 0.10, and 0.15 ng/mL, respectively. The recoveries of BPA, NP and OP were 80.1%‐108%, 81.3%‐109%, and 81.5%‐98.7%, respectively. Among the 60 urine samples, BPA was detected in 8 samples at the level of 0.297‐32.7ng/mL, NP was detected in 29 samples at the level of 1.69‐27.8 ng/mL, and OP was detected in 17 samples at the level of 0.407‐11.1 ng/mL. Conclusion The method is simple with high sensitivity and selectivity, and is suitable for the determination of BPA, NP, and OP in urine. As shown by our analysis , BPA, NP, and OP appear to be prevalent in human urine. This is particularly true for NP. The results from our study is therefore valuable for future studies to assess the exposure to BPA, NP, and OP in the general population.

Spatial distribution and deposition history of nonylphenol and bisphenol A in sediments from the Changjiang River(Yangtze River) Estuary and its adjacent East China Sea

Nonylphenol（NP） and bisphenol A（BPA） are endocrine disruptors causing harmful effects including feminization and carcinogenesis to various organisms,and consequently,their contamination in natural environment has received wide concerns.This study reports the distribution characteristics of NP and BPA in surface sediments and their deposition history based on a dated sediment core in the Changjiang River（Yangtze River） Estuary and its adjacent East China Sea.The contents of NP and BPA in surface sediments ranged from 1.56-35.8 and 0.72-13.2 ng/g（dry mass）,respectively,with high values recorded in the two mud zones,the Changjiang River Estuarine Mud Zone and the Zhejiang Coastal Mud Zone.High values in the Zhejiang Coastal Mud Zone suggest the possibility of long distance transport of both contaminants through the Changjiang riverine plume.The contents were not correlated with the distance from the pollution source,indicating other factors including particle deposition rate and sediment grain size obviously affecting the distribution pattern.NP was also detected in a sediment core at layers deposited from the year of 1971 to 2001 with contents of up to 20.9 ng/g（dry mass）.The deposition fluxes of NP varied from 0.68 to 17.9 ng/（cm^2 · a） with peaks and valleys reflecting the traces of economic development history in China during the previous three decades.BPA was detected at sediment layers deposited from 1973 to 2001 with contents of up to 3.66 ng/g.The fluxes of BPA varied from 0.62 to 3.13 ng/（cm^2 · a） showing a similar pattern as NP.The contents of NP and BPA also indicated potential risks on benthic organisms in the study area.

Effects of estradiol-17β and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups＇ reproductive system

Aim： To assess the effect of estradiol-17β （E2） and bisphenol A （BPA） administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups＇ reproductive system in ICR mice. Methods： Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 μg, or 10 μg of E2, or 100 μg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E2 was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 μg/day. Results： Most of the mice given 1 μg and 10 lag of E2 did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights （testes, epididymides and accessory reproductive glands） in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E2 and 5 mg of BPA than that in the control. Conclusion： Chronic exposure to E2 and BPA might disrupt spermatogenesis in male pups. （Asian JAndrol 2008 Mar; 10： 271-276）

Immunotoxicity of bisphenol A to Carassius auratus lymphocytes and macrophages following in vitro exposure

Bisphenol A （BPA） is the monomer component of polycarbonate plastics and classified as an endocrine disrupting chemical （EDC）. The reproductive toxicity of BPA has been extensively studied in mammals; however, relatively little information is available on the immunotoxic responses of fish to BPA. In this study, we investigated the effects of BPA on the immune functions of lymphocytes and macrophages in Carassius auratus. The effects of BPA were compared with those of two natural steroid hormones, estradiol and hydrocortisone. Proliferation of the two types of cells in response to PHA was measured using colorimetric MTT assay. Macrophage respiratory burst stimulated by Con A was measured using chemiluminescence assay. Results showed that BPA （0.054-5.4 mg/L）, estradiol （0.0002-2.0 mg/L） and hydrocortisone （5-50 mg/L） significantly induced Carassius auratus lymphocyte proliferation while higher doses of hydrocortisone （500-5000 mg/L） appeared to be inhibitory. BPA （0.005-50 mg/L）, estradiol （0.005-800 mg/L） and hydrocortisone （0.005-500 mg/L） markedly enhanced macrophage proliferation, whereas higher doses of BPA （500-1000 mg/L） appeared to inhibit cell proliferation. Furthermore, higher dosage of BPA （50 mg/L） and hydrocortisone （50 and 500 mg/L） suppressed the macrophages respiratory burst while estradiol is stimulative all the doses tested （0.05-500 mg/L）. In conclusion, BPA could have immunotoxicity to Carassius auratus and functional changes of lymphocyte and macrophage in Carassius auratus may be different between low and high dosages.

Effects of nonionic surfactant Triton X-100 on the laccase-catalyzed conversion of bisphenol A

The laccase-catalyzed conversion of bisphenol A （BPA） in aqueous solutions was studied in the absence and presence of nonionic surfactant Triton X-100. It was found that the addition of Triton X-100 into the reaction system increased the conversion of BPA, especially near the critical micelle concentration of Triton X-100. Also it was found that the stability of laccase was greatly improved in the presence of TritonX-100. Studies on the endogenous fluorescence emission of laccase indicated that there existed an interaction between Triton X-100 and laccase, which was beneficial to folding and stabilizating of laccase. The binding of Triton X-100 to the laccase surface also mitigated the inactivation effect caused by the free radicals and polymerization products. Under otherwise identical conditions, a lower dosage of laccase was needed for the higher conversion of BPA in the presence of Triton X-100.

Estrogen Receptor α and β Expressions in Hypothalamus-pituitary-ovary Axis in Rats Exposed Lactationally to Soy Isoflavones and Bisphenol A

Objectives This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones （SIF） and bisphenol A （BPA） and to examine estrogen receptor α （ERα） and estrogen receptor β （ERβ） expressions in hypothalamus-pituitary-ovary axis and uterus.Methods Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group.Dams in different treatment groups received corn oil （control）,150 mg/kg BW of SIF,150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA,respectively,from postnatal day 5 to 11 （PND5-11） by gavage.On PND12 and PND70,10 female litters were killed and hypothalamus,pituitary,ovary and uterus were collected.ERα and ERβ expressions in these organs were detected with Western blotting assay.And vaginal opening time and estrus cycle were examined in animals fed for PND70.Results On PND12,the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats （P〈0.05）.But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA.On PND 70,however,the relative uterine weight in each treatment group was not statistically different from that in the control group （P〈0.05）.Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group （P〈0.05）.Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus,pituitary,ovary and uterus on PND12 and PND70.These regulation patterns for ERα and ERβ were different in different organs at different time points.Conclusion Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats,which disappeared in later life.But these data fail to suggest a possibility for synergic actions between SIF and BPA.It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might,at least,involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.

Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats

Bisphenol A （BPA）, an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA （2 μg/kg） for consecutive 14 days in adult rats （BPA rats） significantly reduced the sperm count and the number of germ cells compared to controls. The serum levels of testosterone and follicle-stimulating hormone （FSH）, as well as the level of GnRH mRNA in BPA rats were lower than those of control rats. Testosterone treatment could partially rescue the reduction of germ cells in BPA rats. Notably, the number of apoptotic germ cells was significantly increased in BPA rats, which was insensitive to testosterone. Furthermore, the levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased in comparison with controls. These results indicate that exposure to a low dose of BPA impairs spermatogenesis through decreasing reproductive hormones and activating the Fas/FasL signaling pathway.

Combined Subchronic Toxicity of Bisphenol A and Dibutyl Phthalate on Male Rats

Objective To evaluate the combined subchronic toxicity of bisphenol A（BPA） and dibutyl phthalate（DBP） in male Sprague Dawley（SD） rats.Methods Forty 4‐week‐old male rats weighing 115‐125 g were randomly divided into BPA‐treated,DBP‐treated group,BPA＋DBP‐treated and control groups and fed with a soy‐ and alfalfa‐free diet containing 285.4 ppm BPA,285.4 ppm DBP,285.4 ppm BPA plus 285.4 ppm DBP,and a control diet,respectively,for 90 consecutive days.At the end of the study,the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed.Organs,including liver,kidneys,spleen,thymus,heart,brain,and testis underwent pathological examination.The androgen receptor（AR）,gonadotropin‐releasing hormone receptor（GNRHR）,and progesterone hormone receptor（PR） genes from the hypothalamus were detected by real‐time PCR.The biomedical parameters were analyzed.Results No significant difference was found in food intake,body weight,tissue weight,organ/brain weight ratio,and biomedical parameters among the four groups（P〉0.05）.However,BPA and DBP up‐regulated AR,PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA＋DBP group.Conclusion The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.

Depolymerization of Poly(bisphenol A carbonate) in Subcritical and Supercritical Toluene

The depolymerization of poly（bisphenol A carbonate）（PC） in subcritical and supercritical toluene was studied. The experimental parameters, which influence the depolymerization reaction such as temperature （570-633 K）, pressure （4.0-7.0 MPa）, reaction time （5-60 min）, and toluene to PC weight ratio （3.0-11.0）, were investigated, and the reaction products were determined by CrC, GC/MS and FT-IR spectrometer. It was found that the main product of the depolymerization reaction was bisphenol A（BPA）. BPA accounted for over 55.7% of the depolymerization products at reaction temperature 613 K, pressure 5.0-6.0 MPa, reaction time 15 min and toluene/PC weight ratio of around 7.0.

Enhanced visible-light-assisted peroxymonosulfate activation over MnFe_(2)O_(4) modified g-C_(3)N_(4)/diatomite composite for bisphenol A degradation

The MnFe_(2) O_(4)/g-C_(3) N_(4)/diatomite composites(Mn/G/D) were prepared via a facile precipitation-calcination method in this study.The Mn/G/D possessed higher specific surface area,lower electron-hole pairs' recombination rate,as well as wider and stronger visible light absorption capacity.Since the synergistic effect between g-C_(3 )N_(4) and MnFe_(2) O_(4),the photogene rated electron could transfer from g-C3 N4 to MnFe_(2) O_(4),which could promote the migration of electrons as well as enhance the photocatalytic activity and peroxymonosulfate(PMS) activation efficiency.Mn/G/D-5% composite displayed the excellent degradation performance of bisphenol A(BPA) with the removal efficiency of 99.9% under PMS/Vis system,which was approximately 2.47 and 63.8 times as high as that of the Mn/G/D-5%/PMS and Mn/G/D-5%/Vis system,respectively.Moreover,negative electricity derived from diatomite surface also promoted the photogenerated carriers' migration,and the degradation rate constant was around 2.4 times higher than that of MnFe_(2) O_(4)/g-C_(3) N_(4)(Mn/G).In addition,quenching experiments showed that both radical pathway(h^(+),·OH,·O_(2)^(-)and SO_(4)·^(-)) and non-radical pathway(^(1) O_(2)) were responsible for the degradation of BPA.

QSAR of Estrogen of Bisphenol A with 3D Vector of Atomic Property Correlation

Considering atomic property vector and atomic correlative function, the 3-dimensional structural vector of atomic property correlation （3D-VAPC）, a novel descriptor,is defined to characterize a 3-dimensional molecular structure by introducing self-adaptability regulation mechanism and the idea of orientating to customers. Characterizing the structures of 25 bisphenol A compounds by this vector, the QSAR models of three kinds of estrogen activities （ER affinities, gene induction and cell proliferation） have high multiple correlation coefficient （Rcum^2=0.933, 0.813, 0.959） and cross verification coefficient （Qcum^2=0.847, 0.953, 0.798） by support vector machine （SVM）, which suits for nonlinear circumstances. The above results show that the models successfully express the correlation between structure and three kinds of estrogen activities. Therefore, 3D-VAPC exactly reflects the molecular structural information and SVM method correctly describes the correlation between information and property of the compounds.

Effect of Perinatal Bisphenol A Exposure on Serum Lipids and Lipid Enzymes in Offspring Rats of Different Sex

Rats were exposed to1 or 10 μg/mL bisphenol A （BPA） in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day （PND） 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin （ADP） levels in both female and male offspring rats. Liver adipose triglyceride lipase （Atgl） mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.