Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. This compound is a building block of polycarbonate plastics often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies have shown that BPA can leach from these and other products in contact with food and drink, and as a result, routine ingestion of BPA is presumed. This compound is also found in an enormous number of other products that we come into contact with daily, and therefore it is not surprising that it has been detected in the majority of individuals examined. BPA is a known endocrine disruptor. Although initially considered to be a weak environmental estrogen, more recent studies have demonstrated that BPA may be similar in potency to estradiol in stimulating some cellular responses. Moreover, emerging evidence suggests that BPA may influence multiple endocrine-related pathways. Studies in rodents have identified adverse effects of BPA at levels at or below the current acceptable daily intake level for this compound. The various reported adverse effects of BPA are reviewed, and potential mechanisms of BPA action are discussed. Much more investigation is needed to understand the potential adverse health effects of BPA exposure in humans and to understand the multiple pathways through which it may act. Although many questions remain to be answered, it is becoming increasingly apparent that exposure to BPA is ubiquitous and that the effects of this endocrine disruptor are complex and wide-ranging.     

Vertebrate evolution reflected in the evolution of nuclear ribosomal internal transcribed spacer 2

Plastics are widely used in modern life, and their unbound chemicals bisphenol A and phthalates can leach out into the surrounding environment. BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects. In The Comparative Toxicogenomics Database, BPA and five most frequently curated PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to have 1932 and 484 interactions with genes/proteins, respectively. Five of their top ten toxicity networks were found to be involved in inflammation, and their top ten diseases included genital, prostatic, endomentrial, ovarian and breast diseases. BPA and PAEs were found to exhibit similar toxicogenomics and adverse effects on human health owning to their 89 common interacting genes/proteins. These 89 genes/proteins may serve as biomarkers to assay the toxicities of different chemicals leached out from the widely used plastics.     

Bacteria-mediated bisphenol A degradation

Bisphenol A (BPA) is an important monomer in the manufacture of polycarbonate plastics, food cans, and other daily used chemicals. Daily and worldwide usage of BPA and BPA-contained products led to its ubiquitous distribution in water, sediment/soil, and atmosphere. Moreover, BPA has been identified as an environmental endocrine disruptor for its estrogenic and genotoxic activity. Thus, BPA contamination in the environment is an increasingly worldwide concern, and methods to efficiently remove BPA from the environment are urgently recommended. Although many factors affect the fate of BPA in the environment, BPA degradation is mainly depended on the metabolism of bacteria. Many BPA-degrading bacteria have been identified from water, sediment/soil, and wastewater treatment plants. Metabolic pathways of BPA degradation in specific bacterial strains were proposed, based on the metabolic intermediates detected during the degradation process. In this review, the BPA-degrading bacteria were summarized, and the (proposed) BPA degradation pathway mediated by bacteria were referred.     

Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice

Bisphenol A (BPA) is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5) because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females.     

Bisphenol a exposure causes meiotic aneuploidy in the female mouse

BACKGROUND: There is increasing concern that exposure to man-made substances that mimic endogenous hormones may adversely affect mammalian reproduction. Although a variety of reproductive complications have been ascribed to compounds with androgenic or estrogenic properties, little attention has been directed at the potential consequences of such exposures to the genetic quality of the gamete. RESULTS: A sudden, spontaneous increase in meiotic disturbances, including aneuploidy, in studies of oocytes from control female mice in our laboratory coincided with the accidental exposure of our animals to an environmental source of bisphenol A (BPA). BPA is an estrogenic compound widely used in the production of polycarbonate plastics and epoxy resins. We identified damaged caging material as the source of the exposure, as we were able to recapitulate the meiotic abnormalities by intentionally damaging cages and water bottles. In subsequent studies of female mice, we administered daily oral doses of BPA to directly test the hypothesis that low levels of BPA disrupt female meiosis. Our results demonstrated that the meiotic effects were dose dependent and could be induced by environmentally relevant doses of BPA. CONCLUSIONS: Both the initial inadvertent exposure and subsequent experimental studies suggest that BPA is a potent meiotic aneugen. Specifically, in the female mouse, short-term, low-dose exposure during the final stages of oocyte growth is sufficient to elicit detectable meiotic effects. These results provide the first unequivocal link between mammalian meiotic aneuploidy and an accidental environmental exposure and suggest that the oocyte and its meiotic spindle will provide a sensitive assay system for the study of reproductive toxins.     

Susceptibility of male reproductive system to bisphenol A,an endocrine disruptor: Updates from epidemiological and experimental evidence

Bisphenol A (BPA) is an omnipresent environmental pollutant. Despite being restrictions in-force for its utilization, it is widely being used in the production of polycarbonate plastics and epoxy resins. Direct, low-dose, and long-term exposure to BPA is expected when they are used in the packaging of food products and are used as containers for food consumption. Occupationally, workers are typically exposed to BPA at higher levels and for longer periods during the manufacturing process. BPA is a known endocrine disruptor chemical (EDC), that causes male infertility, which has a negative impact on human life from emotional, physical, and societal standpoints. To minimize the use of BPA in numerous consumer products, efforts and regulations are being made. Despite legislative limits in numerous nations, BPA is still found in consumer products. This paper examines BPA's overall male reproductive toxicity, including its impact on the hypothalamic-pituitary-testicular (HPT) axis, hormonal homeostasis, testicular steroidogenesis, sperm parameters, reproductive organs, and antioxidant defense system. Furthermore, this paper highlighted the role of non-monotonic dose–response (NMDR) in BPA exposure, which will help to improve the overall understanding of the harmful effects of BPA on the male reproductive system.     

Components of plastic: experimental studies in animals and relevance for human health

Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds.     

Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β

Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ-/- mice to study whether ERβ is involved in the rapid regulation of K(ATP) channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K(ATP) channel activity, increased glucose-induced [Ca(2+)](i) signals and insulin release in β-cells from WT mice but not in cells from ERβ-/- mice. The rapid reduction in the K(ATP) channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.     

Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor

Bisphenol A (BPA) is a well-known endocrine disruptor (ED) which represents a major toxicological and public health concern due to its widespread exposure to humans. BPA has been reported to induce DNA adduct and aneuploidy in rodents. Recent studies in humans depicted its association with recurrent miscarriages and male infertility due to sperm DNA damage indicating that BPA might have genotoxic activity. Hence, the present study was designed to determine genotoxic and mutagenic effects of BPA using in-vivo and in-vitro assays. The adult male and female rats were orally administered with various doses of BPA (2.4 μg, 10 μg, 5mg and 50mg/kgbw) once a day for six consecutive days. Animals were sacrificed, bone marrow and blood samples were collected and subjected to series of genotoxicity assay such as micronucleus, chromosome aberration and single cell gel electrophoresis (SCGE) assay respectively. Mutagenicity was determined using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolically active microsomal fractions (S9). Further, we estimated the levels of 8-hydroxydeoxyguanosine, lipid per-oxidation and glutathione activity to decipher the potential genotoxic mechanism of BPA. We observed that BPA exposure caused a significant increase in the frequency of micronucleus (MN) in polychromatic erythrocytes (PCEs), structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. These effects were observed at various doses tested except 2.4 μg compared to vehicle control. We did not observe the mutagenic response in any of the tester strains tested at different concentrations of BPA. We found an increase in the level of 8-hydroxydeoxyguanosine in the plasma and increase in lipid per-oxidation and decrease in glutathione activity in liver of rats respectively which were exposed to BPA. In conclusion, the data obtained clearly documents that BPA is not mutagenic but exhibit genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity.     

Acute toxicity of bisphenol A in rats

Bisphenol A (BPA), an estrogenic compound, is used in manufacturing plastics and is known to produce toxic effects on various systems in man and animals. Since the use of plastics in day-to-day life is increasing, exposure to BPA will also increase. Therefore, this study was undertaken to determine the median lethal dose (LD50) of BPA via intraperitoneal and intravenous route in adult rats (by Dixon's up and down method) and also to know the acute systemic changes (in blood pressure, respiration and ECG) produced by lethal dose of BPA. Adult female albino rats of Charles Foster strain were used in the study. LD50 of BPA was 841 and 35.26 mg/kg body weight for ip and iv route, respectively. Injection of lethal dose of BPA (40 mg/kg body weight) produced acute toxicity manifesting as immediate respiratory arrest and hypotension after the injection of BPA followed by bradycardia. The animals died within 7.3 +/- 0.7 min. Volume of ethanol (vehicle; 0.1 mL) present in the lethal dose of BPA was not lethal and had no effect on respiration, blood pressure and heart rate. The results provide evidence that the acute exposure to BPA produces lethality with a very narrow range of lethal and survival dose for iv route. Further, the lethality appears to be due to respiratory arrest and hypotension.     

Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway

Bisphenol A (BPA), a synthetic additive used to harden polycarbonate plastics and epoxy resin, is ubiquitous in our everyday environment. Many studies have indicated detrimental effects of BPA on the mammalian reproductive abilities. This study is aimed to test the potential effects of BPA on methylation of imprinted genes during oocyte growth and meiotic maturation in CD-1 mice. Our results demonstrated that BPA exposure resulted in hypomethylation of imprinted gene Igf2r and Peg3 during oocyte growth, and enhanced estrogen receptor (ER) expression at the levels of mRNA and protein. The relationship between ER expression and imprinted gene hypomethylation was substantiated using an ER inhibitor, ICI182780. In addition, BPA promoted the primordial to primary follicle transition, thereby speeding up the depletion of the primordial follicle pool, and suppressed the meiotic maturation of oocytes because of abnormal spindle assembling in meiosis I. In conclusion, neonatal exposure to BPA inhibits methylation of imprinted genes during oogenesis via the ER signaling pathway in CD-1 mice.     

双酚A对斑马鱼胚胎的毒性作用

Bisphenol A(BPA)is a chemical estrogen-like sub-stance with properties that are of environmental concern.It is widely used in the chemical industry to manufactureepoxy-and polyester-styrene resins.It has been reportedthat BPA ranges between0and33μg in each plasticcup[1].After atwo-weekexposureto0.5%bisphenol Aithas beenreportedthat disattachments betweensertoli cellsand spermatogonia were observed while spermatogoniawere arrangedin disorder and displacement of spermatogo-nia away fromthe basement membrance ...     

Transgenerational effects of prenatal bisphenol A on social recognition

Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders.     

Biological degradation of plastics: a comprehensive review

Lack of degradability and the closing of landfill sites as well as growing water and land pollution problems have led to concern about plastics. With the excessive use of plastics and increasing pressure being placed on capacities available for plastic waste disposal, the need for biodegradable plastics and biodegradation of plastic wastes has assumed increasing importance in the last few years. Awareness of the waste problem and its impact on the environment has awakened new interest in the area of degradable polymers. The interest in environmental issues is growing and there are increasing demands to develop material which do not burden the environment significantly. Biodegradation is necessary for water-soluble or water-immiscible polymers because they eventually enter streams which can neither be recycled nor incinerated. It is important to consider the microbial degradation of natural and synthetic polymers in order to understand what is necessary for biodegradation and the mechanisms involved. This requires understanding of the interactions between materials and microorganisms and the biochemical changes involved. Widespread studies on the biodegradation of plastics have been carried out in order to overcome the environmental problems associated with synthetic plastic waste. This paper reviews the current research on the biodegradation of biodegradable and also the conventional synthetic plastics and also use of various techniques for the analysis of degradation in vitro.     

基于氧化应激与细胞凋亡探究双酚A慢性暴露致小鼠肾毒性作用机制

双酚A (bisphenol A, BPA)被广泛应用于生产环氧树脂和聚碳酸酯塑料等制品,在强酸、强碱或高温条件下,BPA被释放出来,然后渗入环境中。在大多数生物液体中都检测到了不同浓度的BPA,BPA的存在已被证明与许多慢性疾病密切相关,包括慢性肾病(chronic kidney disease,CKD)。然而,关于BPA的有害作用及其对CKD的不良影响知之甚少。为了探讨BPA对动物肾毒性的作用机制,本研究通过向饮水中加入0.01、0.1和1 mg/L的BPA,暴露于雌性小鼠4周后,交配和怀孕的雌性小鼠持续接触BPA,直到断奶;F1代3周龄雄性仔鼠继续口服相同剂量的BPA,持续10周。结果表明,0.1mg/L和1mg/LBPA处理组小鼠的肾脏损伤严重,血清中肾脏功能指标尿素氮(urea nitrogen,UN)、肌酐(creatinine,CR)和尿酸(uric acid,UA)的含量均发生显著升高(P<0.05);肾脏组织形态结构被损害;肾脏抗氧化相关基因在mRNA和蛋白水平上的表达显著降低(P<0.05),包括谷胱甘肽硫转移酶(glutathione-S-transf...     

Bisphenol A Modulates Calcium Currents and Intracellular Calcium Concentration in Rat Dorsal Root Ganglion Neurons

The endocrine-disrupting chemical bisphenol A (BPA) is used to manufacture plastics including food containers, and it may leach into these containers. Consumption of BPA that has leached out of plastics may be harmful as recent research highlighted that BPA can induce alterations in the nervous system. In the present work, we studied the effects of BPA on Ca²⁺ channels in dorsal root ganglion (DRG) neurons. Using whole-cell patch-clamp recordings, we found that I _Ca could be reduced by BPA in a concentration-dependent manner. Additionally, BPA shifted the activation curve of calcium currents toward a depolarizing direction and increased the slope factor of the curve. The inactivation curve for the currents was also assessed, and the curve shifted toward the depolarizing direction, although it was not significant. Moreover, inhibitory effects of BPA on the increments of intracellular Ca²⁺ concentrations ([Ca²⁺]_i) induced by 50 mM KCl were observed in DRG neurons using a laser scanning confocal microscopy assay. Further work revealed that the PKA and PKC pathways may be involved in the inhibitory effects of BPA since the PKA antagonist GÖ-6983 and the PKC antagonist H-89 significantly alleviated the inhibitory effects of BPA on I _Ca. As such, the results of the present study provide direct evidence that BPA decreases I _Ca and impairs calcium homeostasis, which may be involved in any toxic effects of BPA on DRG neurons.     

Developmental exposure to bisphenol a modulates innate but not adaptive immune responses to influenza A virus infection

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.     

Clustered DNA damage induced by heavy ion particles.

Clustered DNA damage (locally multiply damaged site) is thought to be a critical lesion caused by ionizing radiation, and high LET radiation such as heavy ion particles is believed to produce high yields of such damage. Since heavy ion particles are major components of ionizing radiation in a space environment, it is important to clarify the chemical nature and biological consequences of clustered DNA damage and its relationship to the health effects of exposure to high LET particles in humans. The concept of clustered DNA damage emerged around 1980, but only recently has become the subject of experimental studies. In this article, we review methods used to detect clustered DNA damage, and the current status of our understanding of the chemical nature and repair of clustered DNA damage.     

Micronucleus assay in bovine lymphocytes after exposure to bisphenol A in vitro

Bisphenol A (BPA) [2,2-bis-(4-hydroxyphenyl) propane] is an important industrial agent, made by combining acetone and phenol, that is used extensively as a monomer in the production of polycarbonate plastics and as a precursor of epoxy resins. Micronucleus assays have served as an index of cytogenetic damage in in vivo and in vitro studies. We studied the genotoxic and cytotoxic effects of BPA on bovine peripheral lymphocytes in vitro. Lymphocyte cultures from two donors were exposed to four different concentrations of BPA (1?×?10^?4, 1?×?10^?5, 1?×?10^?6, and 1?×?10^?7 mol.L^?1) for 48 h. The highest concentration of BPA (1?×?10^?4 mol.L^?1) resulted in a significant increase in the number of micronuclei in comparison with the negative control (67.50?±?2.121/1,000 binucleated cells versus 36.0?±?5.657/1,000 binucleated cells in the DMSO control, P??=??0.018). BPA did not affect the nuclear division index at any treatment concentrations. The present results thus demonstrate a significant genotoxic effect by BPA on bovine peripheral lymphocytes in vitro, only at the highest concentration.