BPA
221132924
Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease
Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARg, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.
International journal of molecular sciences
Ilaria Cimmino Francesca Fiory Giuseppe Perruolo Claudia Miele Francesco Beguinot Pietro Formisano Francesco Oriente
61155737
BPA CRP: A balanced power aware clustering and routing protocol for wireless sensor networks
Abstract Advances in sensor technology has enabled the development of small, relatively inexpensive, and low power sensors, which are connected together through wireless medium, forming what is so called Wireless Sensor Networks (WSNs) WSNs have huge number of applications out of which military target tracking and surveillance. However, sensors operate on limited power resources; therefore, utilizing those resources has brought the attention of current researchers. In this paper, we propose a Balanced Power Aware Clustering and Routing protocol (BPA CRP) Specifically, we developed a batch based clustering and routing protocol in which the network topology divides the sensor field into equal sized layers and clusters. The clustering algorithm allows any cluster to operate multiple rounds (a batch) without any need for set up overhead. BPA CRP assigns four different broadcast ranges for each sensor. Not only to this extent, but rather, BPA CRP introduces a routing algorithm in which a new node role called "Forwarder" which is capable of relaying the collected data from the layer, it resides in, and far away forwarders toward the base station. As a complementary to prior described protocol, BPA CRP proposes that a batch ends when the energy of any of the forwarders dips below a certain threshold. Additionally, BPA CRP introduces the "Only Normal" operation mode, which primarily prevents exhausted nodes from serving as cluster heads or forwarders any longer. In fact, all of just mentioned enhancements not only are energy aware, but also contributes in accomplishing efficient load balancing. Finally, we put proper node death handling rules, which guarantee that each node dies smoothly without any loss of data, neither causing disruption for the network. Simulation results showed an exceptional performance of BPA CRP over different relevant works in terms of network lifetime and network energy utilization. The load balancing capability of BPA CRP is validated as well.
Ad Hoc Networks
Khalid A Darabkh Mohammad Z El-Yabroudi Ali H El-Mousa
71143927
Endocrine disruptors and the future of toxicology testing lessons from CLARITY BPA
Five years ago, an ambitious collaboration, the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY BPA; henceforth CLARITY) was launched by three US agencies. The goal was to provide a definitive evaluation of bisphenol A (BPA) and explain disparities between traditional regulatory studies and findings from independent investigators. BPA or vehicle treated rats from an FDA facility were used in a guideline study and animals and/or tissues were provided to academic researchers for analysis. An interim summary released in February 2018 by the FDA concluded that currently authorized uses of BPA continue to be safe. We disagree. In this Perspectives, we summarize the goals, design and problems of CLARITY. We conclude that, despite its flaws, CLARITY provides important insight and, taken together, the data provide compelling evidence that low dose BPA exposure induces marked adverse effects. Indeed, the greatest number of effects were observed at doses 20,000 times lower than the current 'safe' dose of BPA for humans.The aim of the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY BPA) was to provide a definitive evaluation of bisphenol A (BPA) In this Perspectives, the authors summarize the goals, design and problems of CLARITY BPA.
Nature Reviews Endocrinology
Laura N Vandenberg Patricia A Hunt Andrea C Gore
206554681
Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity A Review.
Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA) Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e. similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA) sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.
Environmental science technology
Da Chen Kurunthachalam Kannan Hongli Tan Zhengui Zheng Yong-lai Feng Yan Wu Margaret Widelka
198997956
Neuro toxic and Reproductive Effects of BPA
Background: Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. It has recognized activity as an endocrine disrupting chemical and has suspected roles as a neurological and reproductive toxicant. It interferes in steroid signaling, induces oxidative stress, and affects gene expression epigenetically. Gestational, perinatal and neonatal exposures to BPA affect developmental processes, including brain development and gametogenesis, with consequences on brain functions, behavior, and fertility. Methods: This review critically analyzes recent findings on the neuro toxic and reproductive effects of BPA (and its ana logues) with focus on neuronal differentiation, synaptic plasticity, glia and microglia activity, cognitive functions, and the central and local control of reproduction. Results: BPA has potential human health hazard associated with gestational, peri and neonatal exposure. Beginning with BPA's disposition, this review summarizes recent findings on the neurotoxicity of BPA and its analogues, on neuronal dif ferentiation, synaptic plasticity, neuro inflammation, neuro degeneration, and impairment of cognitive abilities. Furthermore, it reports the recent findings on the activity of BPA along the HPG axis, effects on the hypothalamic Gonadotropin Releas ing Hormone (GnRH) and the associated effects on reproduction in both sexes and successful pregnancy. Conclusion: BPA and its analogues impair neuronal activity, HPG axis function, reproduction, and fertility. Contrasting re sults have emerged in animal models and human. Thus, further studies are needed to better define their safety levels. This re view offers new insights on these issues with the aim to find the "fil rouge" if any, that characterize BPA's mechanism of action with outcomes on neuronal function and reproduction.
Current neuropharmacology
Antonietta Santoro Rosanna Chianese Jacopo Troisi Sean M Richards Stefania L Nori Silvia Fasano Maurizio Guida Elizabeth C Plunk Andrea Viggiano Riccardo Pierantoni Rosaria Meccariello
59604569
The Case for BPA as an Obesogen: Contributors to the Controversy
Since the inception of the term endocrine disruptor, the idea that the environment is an important determinant of phenotype has motivated researchers to explore the effect of low dose exposure to BPA during organogenesis. The syndrome observed was complex, affecting various endpoints such as reproduction and reproductive tissues, behavior, mammary gland development and carcinogenesis, glucose homeostasis, and obesity. This constellation of impacted endpoints suggests the possibility of complex interactions among the multiple effects of early BPA exposure. One key finding of our rodent studies was alterations of energy and amino acid metabolism that were detected soon after birth and continued to be present at all time points examined through 6 months of age. The classical manifestations of obesity and associated elements of metabolic disease took a longer time to become apparent. Here we examine the validity of the often mentioned lack of reproducibility of obesogenic effects of BPA, starting from the known environmental causes of variation, which are diverse and range from the theoretical like the individuation process and the non monotonicity of the dose response curve, to the very pragmatic like housing, feed, and time and route of exposure. We then explore environmental conditions that may hinder reproducibility and discuss the effect of confounding factors such as BPA induced hyperactivity. In spite of all the potential sources of variation, we find that some obesogenic or metabolic effects of BPA are reproducibly observed when study conditions are analogous. We recommend that study authors describe details of their study conditions including the environment, husbandry, and feed. Finally, we show that when experimental conditions are strictly maintained, reproducibility, and stability of the obese phenotype is consistently observed.
Front. Endocrinol.
Beverly S Rubin Cheryl M Schaeberle Ana M Soto
33052612
Human exposure to bisphenol A (BPA)
The plastic monomer and plasticizer bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in many consumer products. Here, we have outlined studies that address the levels of BPA in human tissues and fluids. We have reviewed the few epidemiological studies available that explore biological markers of BPA exposure and human health outcomes. We have examined several studies of levels of BPA released from consumer products as well as the levels measured in wastewater, drinking water, air and dust. Lastly, we have reviewed acute metabolic studies and the information available about BPA metabolism in animal models. The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.
Reproductive toxicology
Laura N Vandenberg Russ B Hauser Michele Marcus Nicolas Olea Wade V Welshons
44114524
Bisphenol A (BPA) the mighty and the mutagenic
Graphical abstract
Toxicology reports
Nasir Jalal Austin Richard Surendranath Janak Lal Pathak Shin Seung Songpa-ku Yu Chang Y Chung
23088708
A plurality of molecular targets: The receptor ecosystem for bisphenol A (BPA)
ABSTRACT Bisphenol A (BPA) is a well known endocrine disrupting compound (EDC) capable of affecting the normal function and development of the reproductive system, brain, adipose tissue, and more. In spite of these diverse and well characterized effects, there is often comparatively little known about the molecular mechanisms which bring them about. BPA has traditionally been regarded as a primarily estrogenic EDC, and this perspective is often what guides research into the effects of BPA. However, emerging data from in vitro and in silico models show that BPA binds with a significant number of hormone receptors, including a number of nuclear and membrane bound estrogen receptors, androgen receptors, as well as the thyroid hormone receptor, glucocorticoid receptor, and PPAR&ggr; With this increased diversity of receptor targets, it may be possible to explain some of the more puzzling aspects of BPA pharmacology, including its non monotonic dose response curve, as well as experimental results which disagree with estrogenic positive controls. This paper reviews the receptors for which BPA has a known interaction, and discusses the implications of taking these receptors into account when studying the disruptive effects of BPA on growth and development. HIGHLIGHTSBisphenol A exerts a range of non estrogenic effects.Care should be taken in selecting positive controls, given BPA's range of activity.Non estrogenic effects can account for many phenotypes produced by BPA exposure.
Hormones and Behavior
Harry Mackay Alfonso Abizaid
37866826
Differential in Vitro Biological Action, Coregulator Interactions, and Molecular Dynamic Analysis of Bisphenol A (BPA) BPAF, and BPS Ligand ERa Complexes
Background: Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that might be harmful to human health. Recently, there has been widespread usage of bisphenol chemicals (BPs) such as bisphenol AF (BPAF) and bisphenol S (BPS) as replacements for BPA. However, the potential biological actions, toxicity, and the molecular mechanism of these compounds are still poorly understood. Objectives: Our objective was to examine the estrogenic effects of BPA, BPAF, and BPS and the molecular mechanisms of action in the estrogen receptor alpha (ERa) complex. Methods: In vitro cell models were used to compare the estrogenic effects of BPA, BPAF, and BPS to estrogen. Microarray Assay for Real Time Coregulator Nuclear receptor Interaction (MARCoNI) analysis was used to identify coregulators of BPA, BPAF, and BPS, and molecular dynamic (MD) simulations were used to determine the compounds binding in the ERa complex. Results: We demonstrated that BPA and BPAF have agonistic activity for both ERa and ERb, but BPS has ERa selective specificity. We concluded that coregulators were differentially recruited in the presence of BPA, BPAF, or BPS. Interestingly, BPS recruited more corepressors when compared to BPA and BPAF. From a series of MD analysis, we concluded that BPA, BPAF, and BPS can bind to the ER ligand binding domain with differing energetics and conformations. In addition, the binding surface of coregulator interactions on ERa was characterized for the BPA, BPAF, and BPS complexes. Conclusion: These findings further our understanding of the molecular mechanisms of EDCs, such as BPs, in ER mediated transcriptional activation, biological activity, and their effects on physiological functions in human health. https:/doi.org/10.1289/EHP2505
Environmental health perspectives
Yin Li Lalith E Perera Laurel A Coons Katherine A Burns J Tyler Ramsey Katherine E Pelch Rene Houtman Rinie van Beuningen Christina T Teng Kenneth S Korach