WorldWideScience

Sample records for endocrine disruptor screening

  1. Endocrine Disruptor Screening Program Reports to Congress

    Science.gov (United States)

    This page includes EPA reports to congress on pesticide licensing and endocrine disruptor screening activities, Endocrine Disruptor Methods Validation Subcomittee (EDMVS) progress, and Endocrine Disruptor Screening Program (EDSP) implementation progress.

  2. Endocrine Disruptor Screening Program (EDSP) 1998 Federal Register Notices

    Science.gov (United States)

    EPA outlined the Endocrine Disruptor Screening Program (EDSP), which incorporated many of the Endocrine Disruptor Screening and Testing Advisory Committee's (EDSTAC) recommendations, in two Federal Register Notices published in 1998.

  3. 77 FR 15101 - Results From Inert Ingredient Test Orders Issued Under EPA's Endocrine Disruptor Screening...

    Science.gov (United States)

    2012-03-14

    ... . List of Subjects Environmental protection, Endocrine disruptors, Pesticides and pests. Dated: February... Test Orders Issued Under EPA's Endocrine Disruptor Screening Program: New Data Compensation Claims... required recipients to submit specific screening data on hormonal effects under EPA's Endocrine Disruptor...

  4. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report

    Science.gov (United States)

    The EDSTAC Report was developed through a deliberative process that encouraged the development of consensus solutions to complex problems and issues related to developing an Endocrine Disruptor Screening Program.

  5. 75 FR 77869 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension...

    Science.gov (United States)

    2010-12-14

    ... CONTACT. List of Subjects Environmental protection, Chemicals, Drinking water, Endocrine disruptors... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2009-0477; FRL-8856-5] Endocrine Disruptor Screening... Federal Register issue of November 17, 2010, concerning the Endocrine Disruptor Screening Program's (EDSP...

  6. Endocrine Disruptor Screening Program Tier 1 Assessments

    Science.gov (United States)

    EPA has completed weight-of-evidence (WoE) assessments under the Endocrine Distruptor Screening Program (EDSP) for 52 pesticides included in the final list of chemicals for Tier 1 screening. See weight of evidence reports and data evaluation records.

  7. 76 FR 60022 - Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability

    Science.gov (United States)

    2011-09-28

    ... identify the need for Tier 2 testing. List of Subjects Environmental protection, Endocrine disruptors... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8890-7] Endocrine Disruptor Screening... Agency (EPA). ACTION: Notice. SUMMARY: EPA's Endocrine Disruptor Screening Program (EDSP) is announcing...

  8. QSAR Methods to Screen Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Nicola Porta

    2016-08-01

    Full Text Available The identification of endocrine disrupting chemicals (EDCs is one of the important goals of environmental chemical hazard screening. We report on in silico methods addressing toxicological studies about EDCs with a special focus on the application of QSAR models for screening purpose. Since Estrogen-like (ER activity has been extensively studied, the majority of the available models are based on ER-related endpoints. Some of these models are here reviewed and described. As example for their application, we screen an assembled dataset of candidate substitutes for some known EDCs belonging to the chemical classes of phthalates, bisphenols and parabens, selected considering their toxicological relevance and broad application, with the general aim of preliminary assessing their ED potential. The goal of the substitution processes is to advance inherently safer chemicals and products, consistent with the principles of green chemistry. Results suggest that the integration of a family of different models accounting for different endpoints can be a convenient way to describe ED as properly as possible and allow also both to increase the confidence of the predictions and to maximize the probability that most active compounds are correctly found.

  9. 75 FR 67963 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Science.gov (United States)

    2010-11-04

    .... 321(q)(1)). List of Subjects Environmental protection, Endocrine disruptors, Screening assays, Weight... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8849-8] Endocrine Disruptor Screening...-tiered paradigm for screening and testing chemicals for endocrine activity (i.e., estrogen, androgen, and...

  10. 75 FR 81605 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Science.gov (United States)

    2010-12-28

    ..., Endocrine disruptors, Screening assays, Weight-of-evidence. Dated: December 20, 2010. Stephen A. Owens... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8858-9] Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight-of-Evidence Guidance Document...

  11. Steroidogenesis in vitro : towards relevant models for endocrine disruptor screening

    NARCIS (Netherlands)

    Roelofs, M.J.E.

    2016-01-01

    Starting our search for in vitro alternative methods to screen for steroidogenesis toxicity, we focused on the effects of (suggested) endocrine disrupting compounds (EDCs) on cytochrome P450 17 (CYP17) enzyme activity. CYP17 is responsible for conversion of progestagens to dehydroepiandrosterone

  12. Estrogenic compounds -endocrine disruptors

    OpenAIRE

    Munteanu Constantin; Hoteteu Mihai

    2011-01-01

    Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inf...

  13. Estrogenic compounds -endocrine disruptors

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-11-01

    Full Text Available Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions.

  14. Application of Adverse Outcome Pathways to U.S. EPA's Endocrine Disruptor Screening Program.

    Science.gov (United States)

    Browne, Patience; Noyes, Pamela D; Casey, Warren M; Dix, David J

    2017-09-01

    The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. This review describes the EDSP's use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304.

  15. Do endocrine disruptors cause hypospadias?

    Science.gov (United States)

    Botta, Sisir; Cunha, Gerald R; Baskin, Laurence S

    2014-12-01

    Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term "endocrine disruptor" is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias.

  16. Do endocrine disruptors cause hypospadias?

    Science.gov (United States)

    Botta, Sisir; Cunha, Gerald R.

    2014-01-01

    Introduction Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term “endocrine disruptor” is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. Methods A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. Results Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. Conclusions Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias. PMID:26816789

  17. Fetal and neonatal endocrine disruptors.

    Science.gov (United States)

    Unüvar, Tolga; Büyükgebiz, Atilla

    2012-06-01

    Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures.

  18. Report: EPA’s Endocrine Disruptor Screening Program Should Establish Management Controls to Ensure More Timely Results

    Science.gov (United States)

    Report #11-P-0215, May 3, 2011. Fourteen years after passage of the FQPA and Safe Drinking Water Act amendments, EPA’s EDSP has not determined whether any chemical is a potential endocrine disruptor.

  19. Research on Endocrine Disruptors

    Science.gov (United States)

    EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

  20. Effects of elevated glucocorticoids on reproduction and development: relevance to endocrine disruptor screening.

    Science.gov (United States)

    Witorsch, Raphael J

    2016-01-01

    This article reviews the influence of the hypothalamo-pituitary-adrenocortical (HPA) axis on mammalian male and female reproduction and development of offspring and its potential impact on the identification of endocrine disruptive chemicals by in vivo assays. In the adult male rat and baboon, stress suppresses testosterone secretion via a direct inhibitory effect of elevated glucocorticoids on Leydig cells. In adult female sheep, stress disrupts reproductive function via multi-stage mechanisms involving glucocorticoid-mediated suppression of LH secretion, LH action on the ovary and the action of estradiol on its target cells (e.g., uterus). While physiological concentrations of endogenous glucocorticoids are supportive of fetal development, excessive glucocorticoids in utero (i.e., maternal stress) adversely affect mammalian offspring by "programing" abnormalities that are primarily manifest postpartum. The influence of stress on reproduction and development can also be mediated by 11β-hydroxysteroid dehydrogenase (HSD), a bi-directional oxidative:reductive pathway, which governs the balance between biologically active (reduced) endogenous glucocorticoid and inactive (oxidized) metabolites. This pathway is mediated primarily by two isozymes, 11β - HSD1 (reductase) and 11β-HSD2 (oxidase) which act both in an intracrine (intracellular) and endocrine (systemic) fashion. The 11β-HSD pathway appears to play a variety of physiological roles in mammalian reproduction and development and is a target for selected xenobiotics. The effects of the HPA axis on mammalian reproduction and development are potential confounders for in vivo bioassays in rodents employed to identify endocrine disruptive chemicals. Accordingly, consideration of the impact of the HPA axis should be incorporated into the design of bioassays for evaluating endocrine disruptors.

  1. Endocrine Disruptors and Obesity.

    Science.gov (United States)

    Darbre, Philippa D

    2017-03-01

    The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.

  2. [Environmental contaminants and endocrine disruptors].

    Science.gov (United States)

    Fontenele, Eveline Gadelha Pereira; Martins, Manoel Ricardo Alves; Quidute, Ana Rosa Pinto; Montenegro, Renan Magalhães

    2010-02-01

    The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages.

  3. Developments in the EPA Computational Toxicology Program to Identify Environmental Endocrine Disruptors ( Environmental Endocrine Disruptors Gordon Conference)

    Science.gov (United States)

    Presentation at the Environmental Endocrine Disruptors Gordon Conference in Newry, ME June 22, 2016 to give an overview of the use of high throughput screening and high throughput toxicokinetics to build models for endocrine disruption by environmental chemicals for estrogen rece...

  4. [Endocrine disruptors and obesity: obesogens].

    Science.gov (United States)

    García-Mayor, Ricardo V; Larrañaga Vidal, Alejandra; Docet Caamaño, Maria F; Lafuente Giménez, Anunciación

    2012-04-01

    Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  5. Effect of Endocrine Disruptor Pesticides: A Review

    Science.gov (United States)

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-01-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

  6. Effect of Endocrine Disruptor Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Benoit Roig

    2011-06-01

    Full Text Available Endocrine disrupting chemicals (EDC are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air. For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  7. Neuroendocrine targets of endocrine disruptors.

    Science.gov (United States)

    Gore, Andrea C

    2010-01-01

    The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions.

  8. The effects of nanomaterials as endocrine disruptors.

    Science.gov (United States)

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-08-14

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.

  9. The impact of endocrine disruptors on endocrine targets.

    Science.gov (United States)

    Diamanti-Kandarakis, E; Palioura, E; Kandarakis, S A; Koutsilieris, M

    2010-07-01

    Endocrine disruption represents one of the most controversial environmental issues of our époque. So far, many substances, both natural and artificial, have been recognized to interfere with endocrine signaling pathways. In intact laboratory animals, this interaction has been documented to generate adverse health outcomes by impairing normal functions. With regard to humans, evidence is limited and inconsistent to clearly establish a causal inference, however, accumulating data incriminate endocrine disrupting chemicals to reproductive disorders and disturbed thyroid homeostasis. Recently, as a result of animal models and preliminary human studies, a new area of interest has arisen concerning the implication of endocrine disruptors in the etiology of obesity and diabetes, the two major, life-threatening, epidemics of modern world. This article reviews the evidence linking endocrine disrupting chemicals to a broad spectrum of clinical perturbations from reproduction and thyroid to metabolic regulation. (c) Georg Thieme Verlag KG Stuttgart . New York.

  10. [Endocrine disruptors are a novel direction of endocrinologic scientific investigation].

    Science.gov (United States)

    Iaglova, N V; Iaglov, V V

    2012-01-01

    Endocrine disruptors are exogenous anthropogenic chemicals (pesticides, herbicides, polychlorinated biphenyls, bisphenol A, polybrominated diphenyl ethers, phthalates and others), that are able to bind hormonal receptors of endocrine and other cells in vivo and act like hormones. These substances disrupt endocrine regulation of metabolism, reproduction and adaptive reactions of organisms and promote human and animal endocrine disorders.

  11. Endocrine disruptors and timing of human exposure.

    Science.gov (United States)

    Braw-Tal, Ruth

    2010-09-01

    A gradual decline in human fertility coincides with intensive industrial and agricultural development and the concomitant release of chemical waste into the environment. Among these chemicals are endocrine disruptors (EDs) which, in minute doses, have detrimental effects on reproductive health. Human exposure to EDs varies with age. Adults are exposed mainly through the ingestion of contaminated drinking water, meat, fat-dairy products and breathing polluted air. Infants are exposed to EDs through breast milk, baby products, and polluted air. Their abilities to detoxify xenobiotics are not mature yet and blood-brain barrier is not entirely developed, thus EDs may enter the central nervous system easily. Fetuses are exposed to EDs through the placenta. The most harmful effects on reproduction occur when embryos are exposed to them during "critical windows of development", leading to irreversible, pathological changes in adult life. To create a healthier environment, scientific research must be translated into preventive policy legislation.

  12. Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

    Science.gov (United States)

    Magnusson, Ulf; Persson, Sara

    2015-01-01

    Contents The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man-made endocrine disruptors. PMID:26382024

  13. Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

    Science.gov (United States)

    Magnusson, Ulf; Persson, Sara

    2015-09-01

    The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man-made endocrine disruptors. © 2015 The Authors. Reproduction in Domestic Animals Published by Blackwell Verlag GmbH.

  14. Human infertility: are endocrine disruptors to blame?

    Science.gov (United States)

    Marques-Pinto, André; Carvalho, Davide

    2013-01-01

    Over recent decades, epidemiological studies have been reporting worrisome trends in the incidence of human infertility rates. Extensive detection of industrial chemicals in human serum, seminal plasma and follicular fluid has led the scientific community to hypothesise that these compounds may disrupt hormonal homoeostasis, leading to a vast array of physiological impairments. Numerous synthetic and natural substances have endocrine-disruptive effects, acting through several mechanisms. The main route of exposure to these chemicals is the ingestion of contaminated food and water. They may disturb intrauterine development, resulting in irreversible effects and may also induce transgenerational effects. This review aims to summarise the major scientific developments on the topic of human infertility associated with exposure to endocrine disruptors (EDs), integrating epidemiological and experimental evidence. Current data suggest that environmental levels of EDs may affect the development and functioning of the reproductive system in both sexes, particularly in foetuses, causing developmental and reproductive disorders, including infertility. EDs may be blamed for the rising incidence of human reproductive disorders. This constitutes a serious public health issue that should not be overlooked. The exposure of pregnant women and infants to EDs is of great concern. Therefore, precautionary avoidance of exposure to EDs is a prudent attitude in order to protect humans and wildlife from permanent harmful effects on fertility. PMID:23985363

  15. Endocrine Disruptors: Improving Regulatory Science Policy.

    Science.gov (United States)

    Ricci, Paolo F

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose-response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices.

  16. Scientific and Regulatory Policy Committee (SRPC) Points to Consider: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors.

    Science.gov (United States)

    Keane, Kevin A; Parker, George A; Regan, Karen S; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R

    2015-12-01

    The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program. © 2015 by The Author(s).

  17. Scientific and Regulatory Policy Committee (SRPC) Points to Consider*: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors

    Science.gov (United States)

    Keane, Kevin A.; Parker, George A.; Regan, Karen S.; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R.

    2015-01-01

    The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program. PMID:25948506

  18. Endocrine Disruptor Degradation by Photocatalytic Pilot Plant Unit.

    Czech Academy of Sciences Publication Activity Database

    Spáčilová, Lucie; Morozová, Magdalena; Mašín, P.; Maléterová, Ywetta; Kaštánek, František; Dytrych, Pavel; Ezechiáš, Martin; Křesinová, Zdena; Šolcová, Olga

    2016-01-01

    Roč. 3, č. 4 (2016), s. 4613-4620 ISSN 2458-9403 R&D Projects: GA TA ČR TA04020700 Grant - others:NATO(US) SPS984398 Institutional support: RVO:67985858 ; RVO:61388971 Keywords : endocrine disruptor * titanium dioxide * photocatalysis Subject RIV: CI - Industrial Chemistry, Chemical Engineering; EE - Microbiology, Virology (MBU-M)

  19. Review: Environmental endocrine disruptors of testicular function ...

    African Journals Online (AJOL)

    Many of these chemicals found in our environment and households have oestrogenic properties (“xenoestrogens”) and are toxic because they affect the endocrine system (“endocrine disruptors”). Evidence of the health hazards of endocrine disrupting chemicals continues to mount. In terms of male fertility, it now seems that ...

  20. Putative Environmental-Endocrine Disruptors and Obesity: A Review

    Science.gov (United States)

    Elobeid, Mai A.; Allison, David B.

    2008-01-01

    Purpose of the review There has been a substantial increase in the prevalence of obesity in the last several decades. Recent evidence suggests that endocrine disrupting chemicals, e.g. halogenated aromatic hydrocarbons, may cause perturbations in endogenous hormonal regulation and alter other mechanisms involved in weight homeostasis, which may lead to weight gain by increased volume of adipose tissue. Synthetic chemicals derived from industrial processes are suspected to play a contributory role. Yet of the approximately 70,000 documented synthetic chemicals, few have been examined to determine their effects on the endocrine system. Recent findings The present study examines prior laboratory, epidemiological and experimental research findings. Data demonstrate migration of endocrine disruptors in the environment and are beginning to catalogue their effects on adiposity. We present postulated relationships between these chemicals, their mechanisms of action, and the obesity epidemic. Summary Endocrine disruptors may adversely impact human and environmental health by altering physiological control mechanism. Obesity, which is known to increase medical costs and reduce quality and length of life, may be increasing as a function of endocrine disruptor exposure. This merits concern among scientists and public health officials and warrants additional vigorous research in this area. PMID:18769210

  1. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... of endocrine disruption. Results: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis and it was correlated with a reduced testosterone production. The inhibition of PG synthesis occurs...

  2. Hormones and endocrine disruptors in human seminal plasma.

    Science.gov (United States)

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  3. The effects of metals as endocrine disruptors.

    Science.gov (United States)

    Iavicoli, Ivo; Fontana, Luca; Bergamaschi, Antonio

    2009-03-01

    This review reports current knowledge regarding the roles that cadmium (Cd), mercury (Hg), arsenic (As), lead (PB), manganese (Mn), and zinc (Zn) play as endocrine-disrupting chemicals (EDCs). The influence of these metals on the endocrine system, possible mechanisms of action, and consequent health effects were correlated between experimental animals and humans. Analysis of the studies prompted us to identify some critical issues related to this area and showed the need for more rigorous and innovative studies. Consequently, it was recommended that future studies need to: (1) identify the mechanisms of action, because at the present time only a few have been elucidated-in this context, the possible presence of hormesis need to be determined, as currently this was reported only for exposure Cd and As; (2) study the possible additive, synergistic, or antagonistic effects on the endocrine system following exposure to a mixture of metals since there is a lack of these studies available, and in general or occupational environments, humans are simultaneously exposed to different classes of xenobiotics, including metals, but also to organic compounds that might also be EDCs; (3) assess the potential adverse effects on the endocrine system of low-level exposures to metals, as most of the information currently available on EDCs originates from studies in which exposure levels were particularly high; and (4) assess the effects on the endocrine and reproductive systems of other metals that are present in the general and occupational environment that have not yet been evaluated.

  4. Spreeta-based biosensor for endocrine disruptors

    NARCIS (Netherlands)

    Marchesini, G.R.; Koopal, K.; Meulenberg, E.; Haasnoot, W.; Irth, H.

    2007-01-01

    The construction and performance of an automated low-cost Spreeta¿-based prototype biosensor system for the detection of endocrine disrupting chemicals (EDCs) is described. The system consists primarily of a Spreeta miniature liquid sensor incorporated into an aluminum flow cell holder, dedicated to

  5. System chemical biology studies of endocrine disruptors

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand...... effects resulting in the perturbation of different proteins associated to particular diseases (e.g., cryptorchidism) were evaluated....

  6. Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review).

    Science.gov (United States)

    Del Pup, Lino; Mantovani, Alberto; Cavaliere, Carla; Facchini, Gaetano; Luce, Amalia; Sperlongano, Pasquale; Caraglia, Michele; Berretta, Massimiliano

    2016-08-01

    Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age.

  7. Endocrine disruptors and Leydig cell function.

    Science.gov (United States)

    Svechnikov, K; Izzo, G; Landreh, L; Weisser, J; Söder, O

    2010-01-01

    During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  8. Endocrine Disruptors and Leydig Cell Function

    Directory of Open Access Journals (Sweden)

    K. Svechnikov

    2010-01-01

    Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  9. Endocrine disruptors and female cancer: Informing the patients (Review).

    Science.gov (United States)

    Del Pup, Lino; Mantovani, Alberto; Luce, Amalia; Cavaliere, Carla; Facchini, Gaetano; Di Francia, Raffaele; Caraglia, Michele; Berretta, Massimiliano

    2015-07-01

    Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty.

  10. Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

    Science.gov (United States)

    Schmitt, Emily E.; Vellers, Heather L.; Porter, Weston W.; Lightfoot, J. Timothy

    2016-01-01

    INTRODUCTION Voluntary physical activity levels are regulated by sex hormones. The purpose of this study was to determine the effect of the endocrine disruptor benzyl butyl phthalate (BBP) on the regulation of physical activity in mice. METHODS Mouse dams were treated with 500 mg·kg−1·day−1 of BBP or vehicle on gestation days 9–16. Pups were weaned and analyzed for voluntary physical activity levels, puberty development, sex hormone levels, and body composition over a 20 week period. RESULTS Seventy-three offspring from BBP treated dams were studied (n=43 males, n=30 females). Endocrine disruption was indicated by decreased anogenital distances in BBP-treated male offspring at 10 (p=0.001) and 20 weeks (p=0.038) and delayed vaginal openings in BBP-treated female offspring (p=0.001). Further, there was a significant decrease in serum testosterone concentration in male mice between control and BBP at 10 weeks (p=0.039) and at 20 weeks (p=0.022). In female mice there was a significant increase in serum testosterone concentration in BBP mice at 20 weeks (p=0.002), and a significant increase in estrogen (estradiol) concentrations at 20 weeks in the control female mice (p=0.015). Overall, BBP mice ran significantly less distance (males, p=0.008; females, p=0.042) than controls. Other than a significant increase in BBP-treated males in fat mass at 20 weeks (p=0.040), there was no significant decrease in weight, lean mass, or fat mass in either female or male mice, regardless of treatment. CONCLUSION Maternal endocrine disruption altered hormone response, but not body composition in either sex of offspring, with a corresponding decreased activity throughout early adulthood in all offspring. These results suggest that exposure to common environmental endocrine disruptors in utero, can reduce and alter physical activity levels in offspring. PMID:26895396

  11. Environmental endocrine disruptors: Effects on the human male reproductive system.

    Science.gov (United States)

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

  12. Cosmetics as endocrine disruptors: are they a health risk?

    Science.gov (United States)

    Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

  13. A review on endocrine disruptors and their possible impacts on human health.

    Science.gov (United States)

    Kabir, Eva Rahman; Rahman, Monica Sharfin; Rahman, Imon

    2015-07-01

    Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [Endocrine disruptors: echoes of congress of Endocrinology in 2012].

    Science.gov (United States)

    Nassouri, A S; Archambeaud, F; Desailloud, R

    2012-10-01

    The increased prevalence of certain diseases, along with the development of new technologies and industrialization raised the possibility of the involvement of environmental factors, industrial products, nutritional factors, infections, drugs... and endocrine disruptors. These factors may interfere via signaling pathways specific to the organism. Endocrine Disrupting Chemicals (EDCs) have been redefined by the Endocrine Society in 2012 as "exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action". They have therefore potentially deleterious effects on development, growth, metabolism, reproduction, the nervous, immune and cardiovascular systems. Therefore, they constitute a real public health issue. Their long half-life may explain delayed effects and their often lipophilic character may promote maternofetal transmission. Except diethylstilbestrol (DES), few formal proofs have been made on the direct role of EDCs ; arguments are based on cross-sectional studies, in vitro models and animal models. Basic research puts insight into mechanisms of action of EDCs but many questions remain unanswered. Epidemiological data are difficult to interpret because of interindividual differences in susceptibility to EDCs and of nonlinear/nonmonotonique action (as opposed to toxic dose effect), multiple interactions between environmental agents (additive effects and/or synergistic and/or antagonists), the role of the window of exposure, latency, and the possibility of transgenerational effects. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Androgen Receptor Genotype in Humans and Susceptibility to Endocrine Disruptors.

    Science.gov (United States)

    Lundberg Giwercman, Yvonne

    2016-01-01

    Although animal studies have raised concern that the influence of endocrine-disrupting compounds would obstruct the development of the male reproductive system, in general, exposure levels far above those found in humans have been needed to induce reproductive toxicity in animal models. Human data are inconclusive and have evoked the question whether endocrine-disrupting compounds can have any impact on hormonal function and thus health consequences when natural hormones are present. Indeed, many contaminants with hormone-like activity are much less potent than endogenous hormones themselves: 17β-oestradiol was, for instance, estimated to be 17,000 times more potent than o,p'-DDT. However, humans are exposed to a multitude of agents, and when present in sufficient number and concentration, they might in principle act collected on the actions of endogenous hormones. Whether such effects will be physiologically relevant is still not known. Nevertheless, in the worst-case scenario, there are no threshold levels below which there are no effects at all, and one target molecule is the androgen receptor. This mini review focuses on the androgen receptor gene, its link with classical endocrine disruptors and smoking, and how common genetic variants in the androgen receptor gene may influence physiological outcomes. © 2016 S. Karger AG, Basel.

  16. Neuroendocrine effects of endocrine disruptors in teleost fish.

    Science.gov (United States)

    Le Page, Yann; Vosges, Mélanie; Servili, Arianna; Brion, François; Kah, Olivier

    2011-01-01

    Because a large proportion of potential endocrine disruptors (EDC) end up in surface waters, aquatic species are particularly vulnerable to their potential adverse effects. Recent studies identified a number of brain targets for EDC commonly present in environmentally relevant concentrations in surface waters. Among those neuronal systems disrupted by EDC are the gonadotropin-releasing hormone (GnRH) neurons, the dopaminergic and serotoninergic circuits, and more recently the Kiss/GPR54 system, which regulates gonadotropin release. However, one of the most striking effects of EDC, notably estrogen mimics, is their impact on the cyp19a1b gene that encodes the brain aromatase isoform in fish. Moreover, this is the only example in which the molecular basis of endocrine disruption is fully understood. The aims of this review were to (1) synthesize the most recent discoveries concerning the EDC effects upon neuroendocrine systems of fish and (2) provide, when possible, the underlying molecular basis of disruption for each system concerned. The potential adverse effects of EDC on neurogenesis, puberty, and brain sexualization are also described. It is important to point out the future environmental, social, and economical issues arising from endocrine disruption studies in the context of risk assessment.

  17. Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Hatagima Ana

    2002-01-01

    Full Text Available Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.

  18. Endocrine Disruptors Leading to Obesity and Related Diseases

    Directory of Open Access Journals (Sweden)

    Demetrios Petrakis

    2017-10-01

    Full Text Available The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs. Specific population groups are vulnerable to ED exposure due to current dietary and environmental conditions. Obesity, morbidity and carcinogenicity induced by ED exposure are an evolving reality. Therefore, a new collective strategic approach is deemed essential, for the reappraisal of current global conditions pertaining to energy management.

  19. Endocrine Disruptors Leading to Obesity and Related Diseases

    Science.gov (United States)

    Petrakis, Demetrios; Vassilopoulou, Loukia; Psycharakis, Christos; Anifantaki, Aliki; Sifakis, Stavros; Docea, Anca Oana; Tsiaoussis, John; Makrigiannakis, Antonios; Tsatsakis, Aristides M.

    2017-01-01

    The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs) in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs. Specific population groups are vulnerable to ED exposure due to current dietary and environmental conditions. Obesity, morbidity and carcinogenicity induced by ED exposure are an evolving reality. Therefore, a new collective strategic approach is deemed essential, for the reappraisal of current global conditions pertaining to energy management. PMID:29064461

  20. Endocrine disruptors and asthma-associated chemicals in consumer products.

    Science.gov (United States)

    Dodson, Robin E; Nishioka, Marcia; Standley, Laurel J; Perovich, Laura J; Brody, Julia Green; Rudel, Ruthann A

    2012-07-01

    Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid

  1. New-tools to assess the toxicological hazard of endocrine disruptor organoclorine contaminants in Mediterranean cetaceans

    Energy Technology Data Exchange (ETDEWEB)

    M. Cristina Fossi; Marsili, L.; Casini, S. [Dept. of Environmental Sciences, Univ. of Siena (Italy)

    2004-09-15

    The Mediterranean top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants (OCs), incurring high toxicological risk. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Four types of organochlorine endocrine disruptors are commonly found in Mediterranean cetaceans: (1) environmental estrogens, (2) environmental androgens, (3) anti-estrogens and (4) anti-androgens. Endocrine disruptors act by mimicking sex steroid hormones, both estrogens and androgens, by binding to hormone receptors or influencing cell pathways (environmental estrogens and androgens), or by blocking and altering hormone receptor binding (anti-estrogens, antiandrogens). Environmental estrogens are the most common and most widely studied EDCs. The relative estrogenic power of these chemicals, identified by in vitro and in vivo screening methods is rather weak (10{sup -3} or less) compared with the reference power of 17-estradiol or DES. However, the high levels of organochlorine compounds detected in marine mammals, particularly in pinnipeds and odontocetes, and consequently, the high levels of organochlorines with ED capacity, cannot be ignored. Here the hypothesis that some Mediterranean cetaceans (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus) are ''potentially at risk'' due to organochlorines with endocrine disrupting capacity is investigated using new non-lethal tools. As ''diagnostic'' tool we use benzo(a)pyrene monooxygenase (CYP1A1) activity in skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. As ''prognostic'' tool we propose the immunofluorescence technique in fibroblast cell cultures, for a qualitative and quantitative evaluation of the target

  2. The menace of endocrine disruptors on thyroid hormone physiology and their impact on intrauterine development.

    Science.gov (United States)

    Mastorakos, George; Karoutsou, Eftychia I; Mizamtsidi, Maria; Creatsas, George

    2007-06-01

    The delivery of the appropriate thyroid hormones quantity to target tissues in euthyroidism is the result of unopposed synthesis, transport, metabolism, and excretion of these hormones. Thyroid hormones homeostasis depends on the maintenance of the circulating 'free' thyroid hormone reserves and on the development of a dynamic balance between the 'free' hormones reserves and those of the 'bound' hormones with the transport proteins. Disturbance of this hormone system, which is in constant interaction with other hormone systems, leads to an adaptational counter-response targeting to re-establish a new homeostatic equilibrium. An excessive disturbance is likely to result, however, in hypo- or hyper- thyroid clinical states. Endocrine disruptors are chemical substances forming part of 'natural' contaminating agents found in most ecosystems. There is abundant evidence that several key components of the thyroid hormones homeostasis are susceptible to the action of endocrine disruptors. These chemicals include some chlorinated organic compounds, polycyclic aromatic hydrocarbons, herbicides, and pharmaceutical agents. Intrauterine exposure to endocrine disruptors that either mimic or antagonize thyroid hormones can produce permanent developmental disorders in the structure and functioning of the brain, leading to behavioral changes. Steroid receptors are important determinants of the consequences of endocrine disruptors. Their interaction with thyroid hormones complicates the effect of endocrine disruptors. The aim of this review is to present the effect of endocrine disruptors on thyroid hormones physiology and their potential impact on intrauterine development.

  3. Endocrine disruptors and spontaneous premature labor: a case control study

    Directory of Open Access Journals (Sweden)

    Swaby Cheryl

    2007-11-01

    Full Text Available Abstract Background Premature labor is a poorly understood condition. Estrogen is thought to play a key role and therefore the labor process may be affected by endocrine disruptors. We sought to determine whether or not an environmental toxicant, DDE, or dietary derived endocrine disruptors, daidzein and genistein, are associated with spontaneous preterm labor. Methods Cases were defined as primiparous patients having a preterm delivery at or before 35 weeks following the spontaneous onset of labor. Controls were defined as primiparous women who delivered on the same day as the cases but at term gestation. Over approximately 1 year, 26 cases and 52 controls were recruited. Subjects agreed to have blood tests on day one postpartum for DDE and for the phytoestrogens genistein and daidzein. Results The mean concentration of DDE was similar in the case and control groups: 4.29 vs 4.32 ng/g lipid p = .85. In the case group, 13/26 had detectable levels of daidzein (range 0.20 – 1.56 ng/ml compared to 25/52 controls (range 0.21 – 3.26 ng/ml. The mean concentration of daidzein was similar in cases compared to controls: 0.30 vs .34 ng/ml p = 0.91. Of the case group,14/26 had detectable levels of genistein (range 0.20 – 2.19 ng/ml compared to 32/52 controls (range 0.21 – 2.55 ng/ml. The mean concentration of genistein was similar in cases compared to controls: 0.39 vs 0.31 ng/ml, p = 0.61. Conclusion The serum levels of DDE in this population were found to be low. There appears to be no relationship between serum concentrations of DDE, daidzein, and genistein and spontaneous preterm labor in our population. The inability to identify an effect may be related to the comparatively low concentrations of DDE in our population and the rapid and variable reduction of phytoestrogens from women in labor.

  4. The endocrine disruptors among the environmental risk factors for stillbirth

    Energy Technology Data Exchange (ETDEWEB)

    Roncati, Luca, E-mail: emailmedical@gmail.com [Provincial Health Care Services, Institute of Pathology, Santa Maria del Carmine Hospital, Rovereto, TN (Italy); Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena, MO (Italy); Piscioli, Francesco; Pusiol, Teresa [Provincial Health Care Services, Institute of Pathology, Santa Maria del Carmine Hospital, Rovereto, TN (Italy)

    2016-09-01

    Persistent organic pollutants have been lately taken into consideration for their adverse effects, as possible stillbirth contributors; stillbirth can be in fact considered the most dramatic pregnancy complication. Congenital abnormalities account for few stillbirths and many related disorders are potentially modifiable or often coexist, such as maternal infections, non-communicable diseases, lifestyle factors and maternal age. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour. For this reason, many current efforts are focusing on the study of endocrine disruptor (ED) placental transfer, to better understand the in utero exposure dynamics. In this regard, our research group has investigated, by gas chromatography–mass spectrometry, the EDs presence in brain samples of 24 stillbirths, collected over a 3-year period (2012–2014), coming from the Northeast Italy, a notorious area devoted to apple cultivation. Surprisingly, organochlorine pesticides (OCPs), well-known EDs, have been detected in 11 samples. Apart from the noteworthy evidence of pesticides' bio-persistence, this finding implies a redefinition of the placental barrier concept: not a real safety system, but a time-deferral mechanism of absorption. The term ‘placental barrier’ in fact refers to a 4-membrane structure, made up by two epithelial layers, which exactly lining the chorionic villi, and by two endothelial layers, belonging to the feeding vessels for the fetus. It is an effective barrier only for a low administration of water-soluble substances, which encounter obstacle to cross four instead of two membranes. High doses of water-soluble compounds can reach appreciable concentration in the fetal blood, and the lipid-soluble chemicals, such as EDs, are able to pass the placental barrier, through a simple mechanism of passive diffusion, even in minimal concentrations. After crossing the placental barrier

  5. Properties of irradiated PVC plasticized with non-endocrine disruptor

    Energy Technology Data Exchange (ETDEWEB)

    Hutzler, B.W.; Machado, L.D.B.; Lugao, A.B. E-mail: ablugao@net.ipen.br; Villavicencio, A.L.C.H

    2000-03-01

    Polyvinylchloride (PVC) is under heavy attack from environmentalist groups due to the use of plasticizers and its recycling difficulties. Chloro-organics and phtalates are considered now as ubiquitous global contaminants due to their potential as weak endocrine disruptor and huge consumption. In order to make PVC acceptable for the irradiation processing industry in the long term, non-toxic plasticizers should be used. PVC was added with dioctyl phtalate (DOP) and epoxy soybean oil (ESO) and irradiated up to 50 kGy. Mechanical properties, optical properties and viscosity were measured and compared. The elongation and mechanical strength were under the usual range and they didn't show any significant change in the studied range of irradiation dose. All the samples showed a weak yellowing effect after irradiation and the molecular weight measured by viscosimetry showed only negligible changes. In conclusion, DOP and ESO were shown to be effective in stabilizing the radiolytic abstraction of HCl from PVC. Both plasticizers imparted good color stability and overall properties to the products.

  6. Session 2 – Identification of endocrine disruptors and amendments of standard information requirements

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Holbech, Henrik

    2014-01-01

    Discussions regarding regulation of endocrine disruptors (EDs) and combination effects are ongoing in Europe. Among the central topics of discussion are establishment of criteria for identification of EDs, whether there is a threshold for endocrine disrupting effects and how EDs should be handled...

  7. In vitro steroid profiling system for the evaluation of endocrine disruptors.

    Science.gov (United States)

    Nakano, Yosuke; Yamashita, Toshiyuki; Okuno, Masashi; Fukusaki, Eiichiro; Bamba, Takeshi

    2016-09-01

    Endocrine disruptors (ED) are chemicals that affect various aspects of the endocrine system, often leading to the inhibition of steroidogenesis. Current chemical safety policies that restrict human exposure to such chemicals describe often time-consuming and costly methods for the evaluation of ED effects. We aimed to develop an effective tool for accurate phenotypic chemical toxicology studies. We developed an in vitro ED evaluation system using gas chromatography/mass spectrometry (GC/MS/MS) methods for metabolomic analysis of multi-marker profiles. Accounting for sample preparation and GC/MS/MS conditions, we established a screening method that allowed the simultaneous analysis of 17 steroids with good reproducibility and a linear calibration curve. Moreover, we applied the developed system to H295R human adrenocortical cells exposed to forskolin and prochloraz in accordance with the Organization for Economic Cooperation and Development (OECD) guidelines and observed dose-dependent variations in steroid profiles. While the OECD guidelines include only testosterone and 17β-estradiol, our system enabled a comprehensive and highly sensitive analysis of steroid profile alteration due to ED exposure. The application of our ED evaluation screen could be economical and provide novel insights into the hazards of ED exposure to the endocrine system. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Human endometrial cell coculture reduces the endocrine disruptor toxicity on mouse embryo development

    Directory of Open Access Journals (Sweden)

    Lee Myeong-Seop

    2012-04-01

    Full Text Available Abstract Backgrounds Previous studies suggested that endocrine disruptors (ED are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking. Methods Bisphenol A (BPA and Aroclor 1254 (polychlorinated biphenyls were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations. Results At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro. Conclusions In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors.

  9. Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Hyun Yang

    2012-02-01

    Full Text Available Endocrine disruptors (EDs are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k, that may be used to assess estrogenic activity of EDs.

  10. Effects of two endocrine disruptors Prochloraz and Ethinylestradiol on development of Rana Temporaria

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Christensen-Dalsgaard, Jakob; Korsgaard, Bodil

    2009-01-01

    on the effect of endocrine disruptors on the sexsteroid axis and reproductive function. However, another hormone system, the thyroid hormone axis may equally well be affected by xenobiotics. Thyroid hormones are essential in stimulating all aspects of amphibian metamorphosis and thyroid hormone disruptors may...... of phenotypic males. Moreover, ethinylestradiol caused estrogen-dependent induction of the egg yolk precursor protein vitellogenin. These results show that gonadal development and vitellogenin induction may be used as biomarkers for detection of endocrine disrupting chemicals. Most studies have focused...

  11. Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

    Science.gov (United States)

    Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

    2017-01-01

    This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease. PMID:28389628

  12. The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

    Energy Technology Data Exchange (ETDEWEB)

    Plotan, Monika; Elliott, Christopher T. [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom); Scippo, Marie Louise [Department of Food Sciences, University of Liege, 4000 Liege (Belgium); Muller, Marc [Molecular Biology and Genetic Engineering GIGA-R, University of Liege, 4000 Liege (Belgium); Antignac, Jean-Philippe [LABERCA, ENVN, USC INRA 2013, BP 50707, 44 307, Nantes (France); Malone, Edward [The State Laboratory, Young' s Cross, Celbridge, Co. Kildare (Ireland); Bovee, Toine F.H. [RIKILT Institute of Food Safety, P.O. Box 230, AE Wageningen 6700 (Netherlands); Mitchell, Samuel [Agri-Food and Biosciences Institute, Belfast BT9 5PX (United Kingdom); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom)

    2011-08-26

    The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC{sub 50} of 0.01 ng mL{sup -1} and 0.16 ng mL{sup -1} respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally

  13. The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

    International Nuclear Information System (INIS)

    Plotan, Monika; Elliott, Christopher T.; Scippo, Marie Louise; Muller, Marc; Antignac, Jean-Philippe; Malone, Edward; Bovee, Toine F.H.; Mitchell, Samuel; Connolly, Lisa

    2011-01-01

    The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC 50 of 0.01 ng mL -1 and 0.16 ng mL -1 respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the

  14. Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil

    OpenAIRE

    Furtado, CM; von Mühlen, C

    2015-01-01

    The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs thr...

  15. Steroids and endocrine disruptors--History, recent state of art and open questions.

    Science.gov (United States)

    Hampl, Richard; Kubátová, Jana; Stárka, Luboslav

    2016-01-01

    This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in

  16. A study on the degradation of endocrine disruptors and dioxins by ozonation and advanced oxidation processes

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, S.; Kenmochi, Y.; Tutumi, K.; Tanaka, T. [Ebara Corp., Fujisawa (Japan)

    2003-07-01

    Recently, enhancement and development of treatment technologies related to contaminated water environment by endocrine disruptors such as bisphenol-A(BPA), estradiol(E2) and dioxins have become a focus of attention. In this study, the influence of O{sub 3} dosage and the forms of endocrine disruptors on the degradability during O{sub 3} treatment and AOP treatment were investigated. A reaction kinetic evaluation of these processes was also carried out. In this study, the endocrine disruptors were classified into 2 groups: (1) DXNs: dioxins and (2) EDs: endocrine disruptors other than dioxins. For the case of DXNs decomposition, highly concentrated DXNs from incinerator washwater were degraded by UV/O{sub 3} combined treatment. Influence of O{sub 3} dosage and forms of DXNs on the reaction rate constant were evaluated. For the case of EDs decomposition, the effect of O{sub 3} dosage on the reaction rate constant were investigated during O{sub 3} treatment of secondary treated sewage. Also, a degradability comparison was made for the above 2 groups. (orig.)

  17. [The crisis of the hormonal system: the health-effects of endocrine disruptors].

    Science.gov (United States)

    Csaba, György

    2017-09-01

    The endocrine disruptors are natural or arteficial molecules wich are present in the animal (human) environment and entering into the organism. They are bound by hormone receptors, simulating or inhibiting the normal hormonal message. This way they are able to stimulate or hinder the function of the given cell, as well as the synthesis and transport of hormones or receptors. They can cause faulty hormonal imprinting in critical periods of development with lifelong consequences, as alteration of hormone-influenced cell functions, inclination to or manifestation of diseases, so they have medical importance. The number of endocrine disruptors as well as their amount are large and continously growing. Numerous, in adult age manifested disease (e.g. malignant tumors) can be deduced to perinatal harms. Their long-lasting effect can cause the alteration of basal human developmental characteristics (e.g. start of menarche). Vitamins A and D are hormones (exohormones) and could be endocrine disruptors. Perinatal imprinting caused by endocrine disruptors is transmitted to the progenies epigenetically, which also can influence the drug-sensitivity of offspring' receptors. If the epigenetic change is continuously transmitted to the progeny generations, this could have human-evolutionary importance. Orv Hetil. 2017; 158(37): 1443-1451.

  18. Effects of Endocrine Disruptors Ethinylestradiol and Procloraz on the vocal system of the frog Xenopus tropicalis

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Nørum, Ulrik; Korsgaard, Bodil

    2009-01-01

    for studying the effects of endocrine disruptors on sexual differentiation. We exposed tadpoles and metamorphs of the species Xenopus tropicalis to the synthetic estrogen ethinylestradiol and the fungicide prochloraz. Prochloraz masculinized the larynx of female frogs while ethinylestradiol had no effect...

  19. The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

    NARCIS (Netherlands)

    Plotan, M.; Elliot, C.T.; Scippo, M.L.; Müller, M.; Antignac, J.P.; Malone, E.; Bovee, T.F.H.; Mitchell, S.; Connolly, L.

    2011-01-01

    The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to

  20. The Substitution Principle within the REACH Regulation: Nuclear Receptor-Bound Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2017-09-01

    Full Text Available Within the REACH Regulation (EC/1907/2006, the substitution principle for chemicals classified as Substances of Very High Concern (SVHC for either human health or environmental risks has been implemented in order to support their replacement by suitable alternatives. Considering the thousands of chemicals to be tested within the frame of REACH, animal testing by internationally-accepted guidelines sounds unreasonable in terms of the required time, costs as well ethical issues. Hence, REACH recommended also the use of alternative methods to animal experimentation although no validated in silico or in vitro tools were available when regulation entried into force. To search for suitable alternatives to SVHC having an Endocrine Disruptor (ED-like Mode-of-Action (MoA by means of an integrated, tiered in silico-in vitro approach, the EU-granted project LIFE-EDESIA (contract no. LIFE12 ENV/IT/000633 is combining computational-based tools and cell-based bioassays, in order to develop a no-animal testing procedure to screen for chemicals having less or no toxicity in terms of endocrine disruption-like activities. A general view of the no-animal testing approach implementing REACH and the substitution principle will be given, emphasising ligand-nuclear receptor (NR assessment by molecular docking (one of the LIFE-EDESIA in silico approaches and the use of clinical biomarkers in in vitro toxicology to detect ED-like adverse effects in cell-based bioassays.

  1. Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

    Science.gov (United States)

    Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

  2. Endocrine disruptors in female reproductive tract development and carcinogenesis

    OpenAIRE

    Ma, Liang

    2009-01-01

    Growing concerns over endocrine disrupting chemicals (EDCs) and their effects on human fetal development and adult health have promoted research into the underlying molecular mechanisms of endocrine disruption. Gene targeting technology has allowed insight into the genetic pathways governing reproductive tract development and how exposure to EDCs during a critical developmental window can alter reproductive tract development, potentially forming the basis for adult diseases. This review prima...

  3. Bioindication in natural-like aquatic ecosystems: endocrine disruptors in outdoor microcosms. Status-report

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, K.W.; Severin, G.F.

    2002-07-01

    Over the past few decades scientists have shown that the hormone system of a wide range of organisms can be affected by numerous environmental chemicals. Society strongly demands studies about the fate and effects of such endocrine disruptors on the aquatic environment. It has been scientifically accepted that risk assessment studies done in aquatic microcosms can be used to extrapolate the potential impact of the tested compound on natural ecosystems. Realistic exposure situations were simulated and screening methods as well as analytical methods with high accuracy were applied on water and sediment. For the comprehensive risk assessment as many trophic levels as possible have to be investigated. Changes in the population dynamics and the community structure serve as ecotoxicological endpoints. Modelling the concentrations of the chemicals in the different aquatic compartments complements and confirms the analytical diagnostics. A directed design of the analytical procedures according to amount of sample and limits of determination becomes possible. Bridging acute and chronic time scales in effect diagnostics the 'area under the curve' - approach has been followed in combination with multivariate statistics. Haber's rule have been applied to the results about complex effect- and exposure-conditions. In some cases the interpretation of results becomes more easy and clear by this approach. (orig.)

  4. Effect of Sediment Humic Substances on Sorption of Selected Endocrine Disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W. L., E-mail: sunweiling@iee.pku.edu.cn; Ni, J. R.; Liu, T. T. [The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Department of Environmental Engineering, Peking University (China)

    2006-12-15

    Characterizing sorption processes is essential to understand the environmental distribution and toxicity potential of endocrine disruptors in terrestrial and aquatic systems. The sorption behaviors of three endocrine disruptors (bisphenol A (BPA), 17{beta}-estradiol (E2), and 17{alpha}-ethynylestradiol (EE2)) on sediments were investigated using batch techniques. Samples were taken from some representative reaches in several major Chinese rivers. More attention has been paid to the effect of sediment organic components on the sorption of BPA, E2, and EE2. The results show that the sediment organic carbon-normalized partition coefficients (K{sub oc}(sed)) for three endocrine disruptors are in the order of EE2 > E2 > BPA, which corresponds to the octanol-water partitioning coefficients (logK{sub ow}) of the compounds. Moreover, the K{sub oc} values for humic substances (K{sub oc}(hs)) are comparable with the K{sub oc}(sed) values and highly dependent on the physico-chemical properties of humic substances in sediments. The UV absorptivity at 272 nm (A{sub 272}), which suggests the abundance of aromatic rings in humic substance structure, correlates well with the K{sub oc}(hs) values. In addition, the infrared spectra of the humic substances extracted from sediments show four strong bands centered at 3,400 cm{sup -1}, 1,625 cm{sup -1}, 1,390 cm{sup -1}, and 1,025 cm{sup -1}. The K{sub oc}(hs) values have a positive linear relation with the peak area ratio for peak at 1,025 cm{sup -1} and a negative linear relation with the peak area ratio between peaks at 1,625 cm{sup -1} and 1,025 cm{sup -1}. Hence, the hydrogen bonds play a critical role to the sorption of selected endocrine disruptors.

  5. Global pollution by organochlorinated endocrine disruptors - possible challenge for mankind at the onset of millennium.

    Science.gov (United States)

    Langer, P

    2015-01-01

    Author of this review submits a comprehensive report of his long-lasting research regarding the global pollution by endocrine disruptors (EDs), EDs and diabetes and obesity, EDs and the thyroid in highly polluted Slovakia, Ah-receptor: the central pivot responsible for such global "EDs disaster", EDs and immune system, EDs and testosterone, EDs in mothers and newborns, EDs and human genome, and EDs at the beginning of the millennium.

  6. Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells

    Czech Academy of Sciences Publication Activity Database

    Brieno-Enriguez, M. A.; García-López, J.; Cárdenas, D.B.; Guibert, S.; Cleroux, E.; Děd, Lukáš; de Dios Hourcade, J.; Pěknicová, Jana; Weber, M.; del Mazo, J.

    2015-01-01

    Roč. 10, č. 4 (2015) E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : endocrine disruptor * epigenetics * primordial germ cells * vinclozolin * TUNEL analysis * methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  7. Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

    OpenAIRE

    Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe

    2015-01-01

    International audience; Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that repor...

  8. Drug residues and endocrine disruptors in drinking water: risk for humans?

    Science.gov (United States)

    Touraud, Evelyne; Roig, Benoit; Sumpter, John P; Coetsier, Clémence

    2011-11-01

    The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion. Copyright © 2011. Published by Elsevier GmbH.

  9. Endocrine disruptors, travel-associated illness, and media violence: important health considerations for children and adolescents.

    Science.gov (United States)

    Pattishall, Amy E; Spector, Nancy D

    2010-12-01

    This article addresses three important topics that are part of contemporary life for children: endocrine disruptors, hazards of international travel, and the impact of media violence on children and adolescents. Practitioners will learn about phthalates and Bisphenol-A as endocrine disruptors. In published studies, elevated phthalates were associated with an increase in pubertal gynecomastia and premature thelarche. Bisphenol-A was judged by the Food and Drug Administration as having some concern for potential effects on brain, behavior, and prostate gland in fetuses, infants, and young children: hence, the decision to take reasonable steps to reduce exposure of infants. In travel-related diseases, diarrheal disease (primarily Campylobacter and Salmonella), dermatologic conditions (animal bites), systemic febrile illness (malaria and dengue fever), and respiratory illnesses predominate. Children and adolescents spend more than 7 h using media per day. The degree to which media violence can be linked to behavior is not conclusive, but the prevention message for practitioners is important because parents can have an important mitigating effect. Endocrine disruptors, travel-related diseases, and media violence are part of modern day life for our children. Pediatricians need to stay abreast of recent findings and have access to up-to-date resources to assist them in providing contemporary advice and guidance to patients and families.

  10. Endocrine disruptors affect larval zebrafish behavior: Testing potential mechanisms and comparisons of behavioral sensitivity to alternative biomarkers.

    Science.gov (United States)

    Fraser, Thomas W K; Khezri, Abdolrahman; Lewandowska-Sabat, Anna M; Henry, Theodore; Ropstad, Erik

    2017-12-01

    Larval zebrafish (Danio rerio) are a tool for assessing endocrine disruption during early development. Here, we investigated the extent to which a simple light/dark behavioral test at five days post fertilization could compliment current methods within the field. We exposed fertilized embryos to hormones (17β-estradiol, testosterone, dihydrotestosterone, 11-ketotestosterone, thyroxine, triiodothyronine, progesterone, and hydrocortisone) and other relevant compounds (17α ethinylestradiol, bisphenol A, bisphenol S, nonylphenol, flutamide, nilutamide, linuron, drospirenone, potassium perchlorate, mifepristone, and fadrozole) to screen for behavioral effects between 96 and 118h post fertilization (hpf). With the exception of progesterone, all the hormones tested resulted in altered behaviors. However, some inconsistencies were observed regarding the age of the larvae at testing. For example, the xenoestrogens 17α- ethinylestradiol and nonylphenol had behavioral effects at 96hpf, but not at 118hpf. Furthermore, although thyroxine exposure had pronounced effects on behavior, the thyroid disruptor potassium perchlorate did not. Finally, we were unable to demonstrate a role of nuclear receptors following testosterone and 17α- ethinylestradiol exposure, as neither the androgen receptor antagonist flutamide nor the general estrogen receptor inhibitor fulvestrant (ICI) could rescue the observed behavioral effects, respectively. Similarly, molecular markers for androgen and estrogen disruption were upregulated at concentrations below which behavioral effects were observed. These results demonstrate hormones and endocrine disruptors can alter the behavior of larval zebrafish, but the mechanistic pathways remain unclear. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Elucidating the links between endocrine disruptors and neurodevelopment.

    Science.gov (United States)

    Schug, Thaddeus T; Blawas, Ashley M; Gray, Kimberly; Heindel, Jerrold J; Lawler, Cindy P

    2015-06-01

    Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes.

  12. Endocrine disruptors and female fertility: focus on (bovine) ovarian follicular physiology.

    Science.gov (United States)

    Petro, E M L; Leroy, J L M R; Van Cruchten, S J M; Covaci, A; Jorssen, E P A; Bols, P E J

    2012-12-01

    Throughout the previous century, the production, use and, as a result, presence of chemicals in the environment increased enormously. Consequently, humans and animals are exposed to a wide variety of chemical substances of which some possess the ability to disrupt the endocrine system in the body, thereby denominated as "endocrine disrupting chemicals" (EDCs) or "endocrine disruptors". Because the reproductive system is a target organ for endocrine disruption, EDCs are postulated as one of the possible causes of human subfertility. Within the reproductive system, the ovarian follicle can be considered as an extremely fragile microenvironment where interactions between the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In this review, we explore how EDCs can interfere with the well-balanced conditions in the ovarian follicle. In addition, we highlight the bovine ovarian follicle as an alternative in vitro model for EDC and broader toxicology research. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Spreeta-based biosensor assays for endocrine disruptors

    NARCIS (Netherlands)

    Marchesini, G.R.; Koopal, K.; meulenberg, E.P.; Haasnoot, W.; Irth, H.

    2007-01-01

    The construction and performance of an automated low-cost Spreeta™-based prototype biosensor system for the detection of endocrine disrupting chemicals (EDCs) is described. The system consists primarily of a Spreeta miniature liquid sensor incorporated into an aluminum flow cell holder, dedicated to

  14. Two Virus Based Endocrine Disruptor Assays Effective Across Vertebrate Classes.

    Science.gov (United States)

    The presence of hormone mimics, or endocrine disrupting compounds (EDC’s), in the environment are increasing. Sources range from agricultural run–off, pharmaceuticals in waste water, to industrial operations. Current levels of contamination are sufficient to alter sexual develo...

  15. Electrochemical nano biosensor alarm devices for the determination of endocrine disruptor agents

    International Nuclear Information System (INIS)

    Iwuoha, E.; Hendricks, N.; Baker, P.

    2009-01-01

    The role of cytochrome P450 (CYP) enzyme systems in the detoxification of bioactive and hydrophobic xenobiotics, such as drugs, environmental pollutants, food supplements, steroids and endocrine disruptors, cannot be over-emphasized. In this study we present the development and amperometric transduction of cytochromal biosensor alarm device for the determination of endocrine disruptors. As a class II microsomal b-type heme enzyme, CYP3A4 requires the obligatory presence of electron transfer donor redox protein, NAD(P)H, and cytochrome b5 for its physiological reactivity. Optimal reconstitution assays preferably involves vesicle forming phospholipids, detergents and specialized reducing agents. Biosensor offers the possibility of observing direct electron transfer reaction of cytochrome P450-3A4 (CYP3A4) without the requirement of the enzyme's physiological redox partners (1,2). In this study, a nanobiosensor alarm device for the determination of 2,4-dichlorophenol (an endocrine disruptor and hepatocarcinogen) was developed with genetically engineered CYP3A4 imprinted on carbon electrode chips that was modified with polypyrrole-gold nanoparticles. The sensor amperometric signals resulted from the two-electron monooxygenation reaction between the ferri-heme CYP3A4 enzyme and the endocrine disruptor compound. The biosensor was interrogated electrochemically for its ability to detect and report the presence of the endocrine disruptor compound in real time. Accordingly, the response time, sensitivity, storage stability, dynamic linear range and detection limits of the device were evaluated. The biosensor alarm device had a detection limit of 43 ng/L for 2,4-dichlorophenol which is lower than the European Union limit of 300 ng/L for pesticide compounds in ground water; as well as the USA Environmental Protection Agency's drinking water equivalent level (DWEL) of 2000 ng/L (3,4). Chromatographic studies despite their tedious sample preparation and time-consuming pre

  16. Familiar and novel reproductive endocrine disruptors: xenoestrogens, dioxins and nanoparticles.

    Science.gov (United States)

    Hutz, R J; Carvan, M J; Larson, J K; Liu, Q; Stelzer, R V; King-Heiden, T C; Baldridge, M G; Shahnoor, N; Julien, K

    Environmental contaminants are known to exert endocrine-disrupting effects on the reproductive axis of animals. Many of these molecules can affect steroid biosynthesis or estrogen-receptor signaling by behaving as estrogen-like molecules ("xenoestrogens"), or by exerting estrogenmodulatory effects. Exposure to some compounds has been correlated with the skewing of sex ratios in aquatic species, feminization and demasculinization of male animals, declines in human sperm counts, and overall diminution in fertility of birds, fish, and mammals. We herein devote space to several classes of endocrine-disrupting compounds (EDCs), including estrogenic substances such as bisphenol A (BPA), molecules that can behave at times anti-estrogenically while activating the aromatic hydrocarbon receptor (AHR), such as dioxins (a known human carcinogen), and novel, ubiquitous molecules such as nanoparticles, particularly gold nanoparticles (GNPs), that appear to alter the sexsteroid biosynthetic pathway.

  17. Minireview: Endocrine Disruptors: Past Lessons and Future Directions

    Science.gov (United States)

    Johnson, Anne F.; Birnbaum, Linda S.; Colborn, Theo; Guillette, Louis J.; Crews, David P.; Collins, Terry; Soto, Ana M.; vom Saal, Frederick S.; McLachlan, John A.; Sonnenschein, Carlos; Heindel, Jerrold J.

    2016-01-01

    Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health. PMID:27477640

  18. Biosensors for environmental monitoring of endocrine disruptors: a review article

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Mozaz, Sara; Lopez de Alda, Maria J.; Barcelo, Damia [Department of Environmental Chemistry, IIQAB-CSIC, C/ Jordi Girona 18-26, 08034, Barcelona (Spain); Marco, Maria-Pilar [Department of Biological Organic Chemistry, IIQAB-CSIC, C/ Jordi Girona 18-26, 08034, Barcelona (Spain)

    2004-02-01

    This article provides an overview of the applications of biosensors in analysis and monitoring of endocrine-disrupting compounds (EDCs) in the environment. Special attention is devoted to the various types of physical-chemical signal transduction elements, biological mechanisms employed as sensing elements and techniques used for immobilisation of the bioreceptor molecules on the transducer surface. Two different classes of biosensors for EDCs are considered: biosensors that measure endocrine-disrupting effects, and biosensors that respond to the presence of a specific substance (or group of substances) based on the specific recognition of a biomolecule. Several examples of them are presented to illustrate the power of the biosensor technology for environmental applications. Future trends in the development of new, more advanced devices are also outlined. (orig.)

  19. Our stolen figures: the interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance.

    Science.gov (United States)

    Schneider, Jill E; Brozek, Jeremy M; Keen-Rhinehart, Erin

    2014-06-01

    This article is part of a Special Issue "Energy Balance". The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother's experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits. Copyright © 2014. Published by Elsevier Inc.

  20. Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

    Science.gov (United States)

    Gore, Andrea C.

    2009-01-01

    The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

  1. Endocrine Disruptors: An Evolving Health Concern in International Organizations

    Directory of Open Access Journals (Sweden)

    Iris Borowy

    2016-12-01

    Full Text Available Endocrine disrupting chemicals (EDCs are compounds believed to mimic hormones in animal and human bodies and which are thought therefore to be a potential threat to health. Agencies including the European Commission, the International Labour Office (ILO, the Food and Agriculture Organization (FAO, the World Health Organization (WHO, the UN Environment Programme (UNEP each had some responsibility for chemicals in the wider environment over the last five decades. Despite this, the issue of how far the use of EDCs represents a threat to public health remains contested and policy remains uncertain. This article aims to examine the response of IHOs to the growing perception that EDCs can have negative health impacts by disentangling the various agendas and actors involved.

  2. Epigenetic impacts of endocrine disruptors in the brain☆

    Science.gov (United States)

    Walker, Deena M.; Gore, Andrea C.

    2017-01-01

    The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. PMID:27663243

  3. Early-onset androgenetic alopecia and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    M. Guarrera

    2011-01-01

    Full Text Available Androgenetic alopecia (AGA is the most common acquired non scarring alopecia in humans caused by androgen hormones in the setting of a genetic predisposition. Usually AGA starts after puberty, but recently it has been observed also in adolescents. Their mean age was 13 years with a slight prevalence in males. The premature AGA may be caused by environmental, alimentary (meat and milk or cosmetics overexposure to sexual hormones or to endocrine disrupters (EDs. EDs are "exogenous substances that interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body causing adverse effects to human health" and they are able bind to the steroid hormone receptors. Early onset AGA may be linked to the well known phenomenon of early puberty caused in some cases by hormones contained in food or by environmental chemicals. Therefore it is likely that the EDs may play a role also in the pathogenesis of early-onset AGA.

  4. Low-dose effects of hormones and endocrine disruptors.

    Science.gov (United States)

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately. © 2014 Elsevier Inc. All rights reserved.

  5. Verifying of endocrine disruptor chemical affect to the mouse testes: can raman spectroscopy support histology study?

    Science.gov (United States)

    Andriana, Bibin B.; Oshima, Yusuke; Takanezawa, Sota; Tay, Tat W.; Rosawati Soeratman, Catherine Linda; Alam, Mohammad S.; Mitsuoka, Hiroki; Zhu, Xiao B.; Suzuki, Toshiaki; Yamamoto, Yuko S.; Tsunekawa, Naoki; Kanai, Yoshiakira; Kurohmaru, Masamichi; Sato, Hidetoshi

    2009-02-01

    One of suspect environmental endocrine disruptors that affect mouse male reproduction by altering the morphology of Sertoli cells and spermatogenic cells is phthalate. The effects of mono(2-ethylhexyl)phthalate (MEHP), one of metabolites of di(2-ethylhexyl)phthalate , on immature mouse testes in vivo were examined. We have recently shown that MEHP induced Sertoli cells necrosis and spermatogenic cells apoptosis in mice by TUNEL method, F-actin staining, and ultrastructural study, but there is no data for biochemical changing of testes due to those methods could not explore. To verify in detail of it, we conducted Raman spectroscopy study with 785 nm wavelength laser line, 50mW of laser power and 3 minutes of exposure time to analysis the MEHP-treated testicular tissue, which has been fixatived by 4% paraformaldehyde (PFA). Five weeks old (5 w.o) male mice were used in this experiment. As the results, the alterations were observed by Raman spectroscopy that there are significantly differences of DNA, actin filament, type IV collagen and amide I between control group (0 μM MEHP) and treatment group (100 μM MEHP). These results significantly support histology staining observation (such as the apoptotic spermatogenic cells which is associated with DNA fragmentation and F-actin disruption) and ultrastructural observation (such as mitochondria rupture and disintegration of nucleus membrane). Raman spectroscopy can be used for 4% PFA-fixatived tissue observation. However, we recommend that Raman spectroscopy may be able to be expanded as an armamentarium not just for the clarification of histology staining and ultrastructural study, but furthermore, it may be as a non-invasion assessment for screening animal tissue toxicity of chemical in future.

  6. Ozone oxidation of pharmaceuticals, endocrine disruptors and pesticides during drinking water treatment.

    Science.gov (United States)

    Broséus, R; Vincent, S; Aboulfadl, K; Daneshvar, A; Sauvé, S; Barbeau, B; Prévost, M

    2009-10-01

    This study investigates the oxidation of pharmaceuticals, endocrine disrupting compounds and pesticides during ozonation applied in drinking water treatment. In the first step, second-order rate constants for the reactions of selected compounds with molecular ozone (k(O3)) were determined in bench-scale experiments at pH 8.10: caffeine (650+/-22M(-1)s(-1)), progesterone (601+/-9M(-1)s(-1)), medroxyprogesterone (558+/-9M(-1)s(-1)), norethindrone (2215+/-76M(-1)s(-1)) and levonorgestrel (1427+/-62M(-1)s(-1)). Compared to phenolic estrogens (estrone, 17beta-estradiol, estriol and 17alpha-ethinylestradiol), the selected progestogen endocrine disruptors reacted far slower with ozone. In the second part of the study, bench-scale experiments were conducted with surface waters spiked with 16 target compounds to assess their oxidative removal using ozone and determine if bench-scale results would accurately predict full-scale removal data. Overall, the data provided evidence that ozone is effective for removing trace organic contaminants from water with ozone doses typically applied in drinking water treatment. Ozonation removed over 80% of caffeine, pharmaceuticals and endocrine disruptors within the CT value of about 2 mg min L(-1). As expected, pesticides were found to be the most recalcitrant compounds to oxidize. Caffeine can be used as an indicator compound to gauge the efficacy of ozone treatment.

  7. Inhibitor of Differentiation-3 and Estrogenic Endocrine Disruptors: Implications for Susceptibility to Obesity and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Mayur Doke

    2018-01-01

    Full Text Available The rising global incidence of obesity cannot be fully explained within the context of traditional risk factors such as an unhealthy diet, physical inactivity, aging, or genetics. Adipose tissue is an endocrine as well as a metabolic organ that may be susceptible to disruption by environmental estrogenic chemicals. Since some of the endocrine disruptors are lipophilic chemicals with long half-lives, they tend to bioaccumulate in the adipose tissue of exposed populations. Elevated exposure to these chemicals may predispose susceptible individuals to weight gain by increasing the number and size of fat cells. Genetic studies have demonstrated that the transcriptional regulator inhibitor of differentiation-3 (ID3 promotes high fat diet-induced obesity in vivo. We have shown previously that PCB153 and natural estrogen 17β-estradiol increase ID3 expression. Based on our findings, we postulate that ID3 is a molecular target of estrogenic endocrine disruptors (EEDs in the adipose tissue and a better understanding of this relationship may help to explain how EEDs can lead to the transcriptional programming of deviant fat cells. This review will discuss the current understanding of ID3 in excess fat accumulation and the potential for EEDs to influence susceptibility to obesity or metabolic disorders via ID3 signaling.

  8. Endocrine disruptors and pharmaceuticals: implications for water sustainability.

    Science.gov (United States)

    Snyder, Shane A; Benotti, Mark J

    2010-01-01

    The presence of pharmaceuticals and endocrine disrupting compounds (EDCs) in the environment raises many questions about risk to the environment and risk to human health. Researchers have attributed adverse ecological effect effects to the presence of these compounds, particularly EDCs, though there is no consensus on what risk, if any, these compounds pose to human health. The scientific community is in the process of developing a better understanding of the occurrence, fate, and transport of pharmaceuticals and EDCs in the environment, including a better characterization of human exposure via drinking water. This paper provides a brief review of pharmaceuticals and EDCs in drinking water, as well as uses examples from Lake Mead, Nevada, USA, to highlight the issues associated with their fate and transport. Lastly, the effects of natural or anthropogenically driven processes, like natural seasonal flow or climate-change/prolonged drought are discussed as they are factors which can drastically alter environmental concentrations of these compounds. Without question, the propensity for the contamination of fresh water will rise as (1) human population continues to grow or (2) patterns of natural surface water slow and wastewater becomes a larger fraction of flow further highlighting the need for a more comprehensive understanding of their environmental behavior.

  9. Application of Thermosensitive Peptide Copolymer Gels to Removal of Endocrine Disruptor

    Directory of Open Access Journals (Sweden)

    Satoshi Tanimoto

    2009-01-01

    Full Text Available Poly(L-leucine-block-poly(ethylene glycol-block-poly(L-leucine triblock copolymers were synthesized by a ring-opening polymerization of α-amino acid N-carboxyanhydride with amino-terminated PEG as an initiator. The chloroform solution of these peptide copolymers showed a thermo-sensitive sol-gel transition. The transition temperature varied as a function of the length of peptide segments. Additionally, we used these peptide copolymers to remove an endocrine disruptor such as bisphenol A from its aqueous solution. As a result, it became clear that the peptide copolymer gel used in this study could capture bisphenol A efficiently.

  10. The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review.

    Science.gov (United States)

    Milla, Sylvain; Depiereux, Sophie; Kestemont, Patrick

    2011-03-01

    During the last decade, a number of studies have shown that, in addition to their classically described reproductive function, estrogens and androgens also regulate the immune system in teleosts. Today, several molecules are known to interfere with the sex-steroid signaling. These chemicals are often referred to as endocrine disrupting contaminants (EDCs). We review the growing evidence that these compounds interfere with the fish immune system. These studies encompass a broad range of approaches from field studies to those at the molecular level. This integrative overview improves our understanding of the various endocrine-disrupting processes triggered by these chemicals. Furthermore, the research also explains why fish that have been exposed to EDCs are more sensitive to pathogens during gametogenesis. In this review, we first discuss the primary actions of sex-steroid-like endocrine disruptors in fish and the specificity of the fish immune system in comparison to mammals. Then, we review the known interactions between the immune system and EDCs and interpret the primary effects of sex steroids (estrogens and androgens) and their related endocrine disruptors on immune modulation. The recent literature suggests that immune parameters may be used as biomarkers of contamination by EDCs. However, caution should be used in the assessment of such immunotoxicity. In particular, more attention should be paid to the specificity of these biomarkers, the external/internal factors influencing the response, and the transduction pathways induced by these molecules in fish. The use of the well-known mammalian models provides a useful guide for future research in fish.

  11. Characterization of the interactions between endocrine disruptors and aquatic humic substances from tropical rivers

    Energy Technology Data Exchange (ETDEWEB)

    Botero, Wander G. [Universidade Federal de Alagoas (UFAL), Arapiraca, AL (Brazil); Oliveira, Luciana C. de [Universidade Federal de Sao Carlos (UFSCar), Sorocaba, SP (Brazil); Cunha, Bruno B.; Oliveira, Lilian K. de; Goveia, Danielle; Fraceto, Leonardo F.; Rosa, Andre Henrique, E-mail: ahrosa@sorocaba.unesp.b [UNESP, Sorocaba, SP (Brazil). Dept. de Engenharia do Meio Ambiente; Rocha, Julio Cesar [UNESP, Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica Analitica

    2011-07-01

    Interactions between two endocrine disruptors (ED) and aquatic humic substances (AHS) from tropical rivers were studied using an ultrafiltration system equipped with a 1 kDa cut-off cellulose membrane to separate free ED from the fraction bound in the AHS. Quantification of 17{alpha}-ethynylestradiol and bisphenol A was performed using gas chromatography-mass spectrometry (GC-MS). The times required for establishment of equilibrium between the AHS and the ED were ca. 30 min, and complexation capacities for 17{alpha}-ethynylestradiol and bisphenol A were 18.53 and 2.07 mg g{sup -1} TOC, respectively. The greater interaction of AHS with 17{alpha}-ethynylestradiol, compared to bisphenol A, was due to the presence of hydrogen in the structure of 17{alpha}-ethynylestradiol, which could interact with ionized oxygenated groups of the AHS. The results indicate that AHS can strongly influence the transport and reactivity of endocrine disruptors in aquatic systems. (author)

  12. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  13. Inverse Effects on Growth and Development Rates by Means of Endocrine Disruptors in African Clawed Frog Tadpoles ("Xenopus Laevis")

    Science.gov (United States)

    Hackney, Zachary Carl

    2007-01-01

    Previous work on fish, frogs, and salamanders, showed the ability for estrogen (EE2) and anthropogenic endocrine disruptors to skew sex ratios and cause hermaphrodism. This study addressed the effects of estrogens on growth and development rates of African clawed frog tadpoles ("Xenopus laevis") during their gender determination stages. The…

  14. The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis

    NARCIS (Netherlands)

    López-Casas, Pedro P.; Mizrak, Sefika C.; López-Fernández, Luis A.; Paz, María; de Rooij, Dirk G.; del Mazo, Jesús

    2012-01-01

    Environmental contaminants considered endocrine disruptors have been shown to affect testis development and function but the mechanisms of action are not clear. We now have analyzed the effects on the transcriptome in testes of mice exposed to mono-(2-ethylhexyl)-phthalate (9.2; 46.3 or 92.7

  15. Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

    Directory of Open Access Journals (Sweden)

    Sofiane Boudalia

    2017-06-01

    Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

  16. Welcome to the revolution: integrative biology and assessing the impact of endocrine disruptors on environmental and public health.

    Science.gov (United States)

    Hayes, Tyrone B

    2005-04-01

    Concern continues to grow over the negative impact of endocrine disrupting chemicals on environmental and public health. The number of identified endocrine disrupting chemicals is increasing, but biological endpoints, experimental design, and approaches for examining and assessing the impact of these chemicals are still debated. Although some workers consider endocrine disruption an "emerging science," I argue here that it is equally, a "merging science" developing in the tradition of integrative biology. Understanding the impact of endocrine disruptors on humans and wildlife is an examination of "context dependent development" and one that Scott Gilbert predicted would require a "new synthesis" or a "revolution" in the biological sciences. Here, I use atrazine as an example to demonstrate the importance of an integrative approach in understanding endocrine disruptors.Atrazine is a potent endocrine disruptor that chemically castrates and feminizes amphibians and other wildlife. These effects are the result of the induction of aromatase, the enzyme that converts androgens to estrogens, and this mechanism has been confirmed in all vertebrate classes examined (fish, amphibians, reptiles, birds, and mammals, including humans). To truly assess the impact of atrazine on amphibians in the wild, diverse fields of study including endocrinology, developmental biology, molecular biology, cellular biology, ecology, and evolutionary biology need to be invoked. To understand fully the long-term impacts on the environment, meteorology, geology, hydrology, chemistry, statistics, mathematics and other disciplines well outside of the biological sciences are required.

  17. Endocrine Disruptors

    Science.gov (United States)

    ... About NIEHS Home Page Office of the Director Organizational Structure 2018-2023 Strategic Plan Advisory Boards & Councils Community ... Home Page About NIEHS Office of the Director Organizational Structure 2018-2023 Strategic Plan Advisory Boards & Councils Community ...

  18. Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

    Directory of Open Access Journals (Sweden)

    Mingyue Zhang

    2015-11-01

    Full Text Available Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256 collected from children in China were measured by liquid chromatography (LC-tandem mass spectrometry (MS/MS. Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

  19. Long-term effects of environmental endocrine disruptors on reproductive physiology and behavior

    Directory of Open Access Journals (Sweden)

    Heather B Patisaul

    2009-06-01

    Full Text Available It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs, either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates.

  20. Long-Term Effects of Environmental Endocrine Disruptors on Reproductive Physiology and Behavior

    Science.gov (United States)

    Patisaul, Heather B.; Adewale, Heather B.

    2009-01-01

    It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs), either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates. PMID:19587848

  1. Recent advances in sample preparation methods for analysis of endocrine disruptors from various matrices.

    Science.gov (United States)

    Singh, Baljinder; Kumar, Ashwini; Malik, Ashok Kumar

    2014-01-01

    Due to the high toxicity of endocrine disruptors (EDs), studies are being undertaken to design effective techniques for separation and detection of EDs in various matrices. Recently, research activities in this area have shown that a diverse range of chromatographic techniques are available for the quantification and analysis of EDs. Therefore, on the basis of significant, recent original publications, we aimed at providing an overview of different separation and detection methods for the determination of trace-level concentrations of selected EDs. The biological effects of EDs and current pretreatment techniques applied to EDs are also discussed. Various types of chromatographic techniques are presented for quantification, highlighting time- and cost-effective techniques that separate and quantify trace levels of multiple EDs from various environmental matrices. Reports related to methods for the quantification of EDs from various matrices primarily published since 2008 have been cited.

  2. Effects of prenatal exposure to endocrine disruptors and toxic metals on the fetal epigenome

    Science.gov (United States)

    Bommarito, Paige A; Martin, Elizabeth; Fry, Rebecca C

    2017-01-01

    Exposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study. PMID:28234024

  3. Endocrine Control of Mucosal Immunity in the Female Reproductive Tract: Impact of Environmental Disruptors

    Science.gov (United States)

    Dunbar, B.; Patel, M.; Fahey, J.; Wira, C.

    2015-01-01

    The complexity of the human female reproductive tract (FRT) with its multiple levels of hormonally controlled immune protection has only begun to be understood. Dissecting the functions and roles of the immune system in the FRT is complicated by the differential hormonal regulation of its distinct anatomical structures that vary throughout the menstrual cycle. Although many fundamental mechanisms of steroid regulation of reproductive tract immune function have been determined, the effects of exogenous synthetic steroids or endocrine disruptors on immune function and disease susceptibility in the FRT have yet to be evaluated in detail. There is increasing evidence that environmental or synthetic molecules can alter normal immune function. This review provides an overview of the innate and adaptive immune systems, the current status of immune function in the FRT and the potential risks of environmental or pharmacological molecules that may perturb this system. PMID:22289638

  4. The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

    International Nuclear Information System (INIS)

    Hao, Chan-Juan; Cheng, Xue-Jia; Xia, Hong-Fei; Ma, Xu

    2012-01-01

    Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders. -- Highlights: ► DES induced adipocyte differentiation in a dose-dependent manner in 3T3-L1 cells. ► DES activated adipogenic critical regulators and markers in vitro and in vivo. ► Perinatal exposure to DES led to the obese phenotype in female offspring. ► DES might be a potential chemical stressor for obesity and obesity-related disorders.

  5. The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Chan-Juan; Cheng, Xue-Jia; Xia, Hong-Fei, E-mail: hongfeixia@yahoo.com.cn; Ma, Xu

    2012-08-15

    Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders. -- Highlights: ► DES induced adipocyte differentiation in a dose-dependent manner in 3T3-L1 cells. ► DES activated adipogenic critical regulators and markers in vitro and in vivo. ► Perinatal exposure to DES led to the obese phenotype in female offspring. ► DES might be a potential chemical stressor for obesity and obesity-related disorders.

  6. Determination of endocrine disruptors in Kafue lechwe (Kobus leche kafuensis) samples from the Lochinvar National Park of Zambia.

    Science.gov (United States)

    Sichilongo, Kwenga; Torto, Nelson

    2006-08-01

    Analysis of serum, whole blood and liver tissue samples from Kafue lechwe in the Lochinvar National Park of Zambia for suspected endocrine disrupting compounds revealed high concentrations for some of the compounds. 45 samples of serum, whole blood and liver tissue were extracted by liquid-liquid extraction followed by an analysis using Gas Chromatography-Electron Capture Detection (GC-ECD). The following endocrine disruptors were analyzed: deltamethrin, aldrin, endosulfan, dieldrin, pp-DDD, heptachlor, d-t-allethrin, pp-DDE, endrin and pp-DDT. For all the samples, dieldrin showed the highest concentration ranging from 1.7 to 44.4 microg/ml in serum and whole blood sample extracts and 0.10-5.1 microg/g wet weight in liver sample extracts. The most frequently detected was deltamethrin in 62% of the samples. Percent recoveries in spiked laboratory blanks ranged between 60% and 100% while calculated detection limits ranged from 0.004 to 0.21 microg/ml for all the endocrine disruptors evaluated. Where endocrine disruptors were detected, the concentrations of most of them far exceeded the maximum residue limits (MRLs) and the extraneous maximum residue limits (EMRLs) set by the Codex Alimentarius of the United Nations (UN), Food and Agricultural Organization (FAO).

  7. Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil

    Directory of Open Access Journals (Sweden)

    CM Furtado

    Full Text Available The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and São Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources.

  8. Negative Role of the Environmental Endocrine Disruptors in the Human Neurodevelopment.

    Science.gov (United States)

    Roncati, Luca; Termopoli, Veronica; Pusiol, Teresa

    2016-01-01

    The endocrine disruptors (EDs) are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS) the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS) and 8 cases of sudden infant death syndrome (SIDS), collected by centralization in the last year (2015). More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs), chlorpyrifos and chlorfenvinfos, have been found in seven and three samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers but simply time-deferral mechanisms of absorption.

  9. Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil.

    Science.gov (United States)

    Furtado, C M; von Mühlen, C

    2015-05-01

    The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and São Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources.

  10. Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles.

    Science.gov (United States)

    Wagner, Martin; Oehlmann, Jörg

    2009-05-01

    Food consumption is an important route of human exposure to endocrine-disrupting chemicals. So far, this has been demonstrated by exposure modeling or analytical identification of single substances in foodstuff (e.g., phthalates) and human body fluids (e.g., urine and blood). Since the research in this field is focused on few chemicals (and thus missing mixture effects), the overall contamination of edibles with xenohormones is largely unknown. The aim of this study was to assess the integrated estrogenic burden of bottled mineral water as model foodstuff and to characterize the potential sources of the estrogenic contamination. In the present study, we analyzed commercially available mineral water in an in vitro system with the human estrogen receptor alpha and detected estrogenic contamination in 60% of all samples with a maximum activity equivalent to 75.2 ng/l of the natural sex hormone 17beta-estradiol. Furthermore, breeding of the molluskan model Potamopyrgus antipodarum in water bottles made of glass and plastic [polyethylene terephthalate (PET)] resulted in an increased reproductive output of snails cultured in PET bottles. This provides first evidence that substances leaching from plastic food packaging materials act as functional estrogens in vivo. Our results demonstrate a widespread contamination of mineral water with xenoestrogens that partly originates from compounds leaching from the plastic packaging material. These substances possess potent estrogenic activity in vivo in a molluskan sentinel. Overall, the results indicate that a broader range of foodstuff may be contaminated with endocrine disruptors when packed in plastics.

  11. Degradation of endocrine disruptor bisphenol A by ultrasound-assisted electrochemical oxidation in water.

    Science.gov (United States)

    Dietrich, Matz; Franke, Marcus; Stelter, Michael; Braeutigam, Patrick

    2017-11-01

    Micropollutants are becoming an increasing problem for the environment and wastewater treatment. One example is Bisphenol A (BPA), an endocrinic disruptor, which is widely used in plastic production. Due to its endocrine disrupting effects on aquatic (micro-)organisms and its ubiquity, in surface- and wastewater alike, adequate treatment techniques are necessary. In this study, the degradation of BPA by a sonoelectrochemical hybrid system was investigated, using a low frequency (24kHz) ultrasound horn and two boron doped diamond electrodes. It was found that by the combination of the individual processes, i.e. ultrasound and electrochemical oxidation, more than 90% of BPA could be removed within 30min at an initial concentration of 1mgL -1 . Moreover, synergistic effects were discovered and a considerable improvement compared to the individual processes could be achieved by using a potential of 5V, whereas synergistic effects were absent at a potential of 10V. This study provides investigation of ultrasound amplitude, potential and electrode positioning on BPA degradation. The reaction was found to follow pseudo first order kinetics with a rate constant of 0.089min -1 . Samples were analysed by high pressure liquid chromatography (HPLC) using a diode array detector. Moreover, the presence and distribution of hydroxyl radicals within the reactor was visualized by using sonochemiluminescence. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Endocrine Disruptors and Health Effects in Africa: A Call for Action.

    Science.gov (United States)

    Bornman, Maria S; Aneck-Hahn, Natalie H; de Jager, Christiaan; Wagenaar, Gesina M; Bouwman, Hindrik; Barnhoorn, Irene E J; Patrick, Sean M; Vandenberg, Laura N; Kortenkamp, Andreas; Blumberg, Bruce; Kimmins, Sarah; Jegou, Bernard; Auger, Jacques; DiGangi, Joseph; Heindel, Jerrold J

    2017-08-22

    Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.

  13. Endocrine disruptors induce cytochrome P450 by affecting transcriptional regulation via pregnane X receptor

    International Nuclear Information System (INIS)

    Mikamo, Eriko; Harada, Shingo; Nishikawa, Jun-ichi; Nishihara, Tsutomu

    2003-01-01

    Pregnane X receptor (PXR) is a nuclear receptor that regulates the expression of genes for cytochrome P450 3A (CYP3A), multidrug resistance 1 (MDR1), and organic anion-transporting peptide 2 (OATP2). These genes control the metabolism (CYP3A subfamily) and aspects of the pharmacokinetics (MDR1 and OATP2) of both endogenous and xenobiotic compounds. Since PXR is important in understanding the actions of endocrine disruptors (EDs), we determined the ability of suspected EDs to interact with PXR. In our study, 7 of 54 xenobiotics compounds interacted with PXR, including methoxychlor and benzophenone. All of the chemicals activated PXR in vitro and induced CYP3A mRNA in the male rat liver. In addition, CYP2C11 was also induced by some PXR agonists and converted methoxychlor into xenoestrogen. These findings suggest that some EDs affect sex hormone receptor indirectly by induction of metabolic enzyme via PXR, to produce rapidly higher concentrations of effective metabolites, leading to disturbance of the endocrine system

  14. Esterification of vertebrate like steroids in molluscs: a target of endocrine disruptors?

    Science.gov (United States)

    Giusti, Arnaud; Joaquim-Justo, Célia

    2013-11-01

    Alterations of the reproductive organs of gastropod molluscs exposed to pollutants have been reported in natural populations for more than 40 years. In some cases, these impacts have been linked to exposure to endocrine-disrupting chemicals (EDCs), which are known to induce adverse impacts on vertebrates, mainly by direct binding to steroid receptors or by altering hormone synthesis. Investigations on the mechanisms of action of endocrine disruptors in molluscs show that EDCs induce modifications of endogenous titres of androgens (e.g., testosterone, androstenedione) and oestrogens (e.g., 17ß-oestradiol). Alterations of the activity of enzymes related to steroid metabolism (i.e., cytochrome P-450 aromatase, acyltransferases) are also often observed. In bivalves and gastropods, fatty acid esterification of steroids might constitute the major regulation of androgen and oestrogen homeostasis. The present review indicates that metabolism of steroid hormones to fatty acid esters might be a target of synthetic EDCs. Alterations of this process would impact the concentrations of free, potentially bioactive, form of steroids. © 2013.

  15. Negative role of the environmental endocrine disruptors in the human neurodevelopment

    Directory of Open Access Journals (Sweden)

    Luca Roncati

    2016-08-01

    Full Text Available The endocrine disruptors (EDs are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS and 8 cases of sudden infant death syndrome (SIDS, collected by centralization in the last year (2015. More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides (OCPs, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs, chlorpyrifos and chlorfenvinfos, have been found in 7 and 3 samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers, but simply time-deferral mechanisms of absorption.

  16. Evaluation of organic endocrine disruptors in water at Brazilian Multipurpose Reactor - RMB installation area

    International Nuclear Information System (INIS)

    Silva, Larissa L.; Martins, Elâine A.J.; Cotrim, Marycel E.B.; Pires, Maria A.F.

    2017-01-01

    The study of pollutants with organic and inorganic characteristics in groundwater and surface waters of a given region is an important tool in the assessment of pollution. Endocrine interferers are synthetic or natural chemicals that have the ability to act on the endocrine system of humans and animals by mimetizing natural hormones and may produce adverse effects on organisms, even in low concentrations (μg or ng.L -1 ). Anthropic activities are the major source of input of endocrine disruptors into the environment. The Brazilian government has a project to construct a multipurpose reactor, Brazilian Multipurpose Reactor (RMB), at the Iperó city, to improve the nuclear research Brazilian capacity. The object of this research in to analyze 14 organic compounds that may be present in the groundwater and surface waters of the RMB installation area. This is an unprecedented and extremely important study for the evaluated region; since it will provide guidance on the degree of contamination of the local waters before the construction begins. The study will also make it possible to verify if the construction of the RMB will offer environmental issues to the place. For the determination of the compounds of interest, a developed and validated analytical method was used. This methodology consists of the concentration of the samples by solid phase extraction (SPE) followed by quantification by gas chromatography coupled to the mass spectrometry detector (GC/MS). The water column particulate was also evaluated by ultrasonic extraction, followed by quantification by GC/MS. The results reveal that some of the compounds were found and it was due to anthropic activities in the vicinity of the regions. By initial analysis it was possible verify river that cross the RMB area present values below 0.05 μg L -1 . (author)

  17. Evaluation of organic endocrine disruptors in water at Brazilian Multipurpose Reactor - RMB installation area

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Larissa L.; Martins, Elâine A.J.; Cotrim, Marycel E.B.; Pires, Maria A.F., E-mail: larissa.limeira07@gmail.com, E-mail: elaine@ipen.br, E-mail: mecotrim@ipen.br, E-mail: mapires@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    The study of pollutants with organic and inorganic characteristics in groundwater and surface waters of a given region is an important tool in the assessment of pollution. Endocrine interferers are synthetic or natural chemicals that have the ability to act on the endocrine system of humans and animals by mimetizing natural hormones and may produce adverse effects on organisms, even in low concentrations (μg or ng.L{sup -1}). Anthropic activities are the major source of input of endocrine disruptors into the environment. The Brazilian government has a project to construct a multipurpose reactor, Brazilian Multipurpose Reactor (RMB), at the Iperó city, to improve the nuclear research Brazilian capacity. The object of this research in to analyze 14 organic compounds that may be present in the groundwater and surface waters of the RMB installation area. This is an unprecedented and extremely important study for the evaluated region; since it will provide guidance on the degree of contamination of the local waters before the construction begins. The study will also make it possible to verify if the construction of the RMB will offer environmental issues to the place. For the determination of the compounds of interest, a developed and validated analytical method was used. This methodology consists of the concentration of the samples by solid phase extraction (SPE) followed by quantification by gas chromatography coupled to the mass spectrometry detector (GC/MS). The water column particulate was also evaluated by ultrasonic extraction, followed by quantification by GC/MS. The results reveal that some of the compounds were found and it was due to anthropic activities in the vicinity of the regions. By initial analysis it was possible verify river that cross the RMB area present values below 0.05 μg L{sup -1}. (author)

  18. Exposición a disruptores endocrinos y alteraciones del tracto urogenital masculino (criptorquidia e hipospadias Exposure to endocrine disruptors and male urogenital tract malformations [cryptorchidism and hypospadias

    Directory of Open Access Journals (Sweden)

    Mariana F. Fernández

    2007-12-01

    Full Text Available Antecedentes: Se ha sugerido que la exposición maternoinfantil a compuestos hormonalmente activos (disruptores endocrinos tiene en la etapa intrauterina una de sus fases más comprometidas. Objetivo: Revisar los estudios epidemiológicos, nacionales e internacionales, publicados entre 1990 y el primer trimestre de 2006, que tuvieran como hipótesis la asociación entre la exposición humana a disruptores endocrinos y el riesgo de criptorquidia e hipospadias. Métodos: Se han buscado artículos en MEDLINE/PubMed mediante las palabras clave: disruptores endocrinos, xenoestrógenos, pesticidas organoclorados y criptorquidia e hipospadias. La selección de los 16 trabajos incluidos se hizo atendiendo al diseño y la población de estudio, las medidas de exposición empleadas, los criterios de exclusión e inclusión establecidos y el análisis estadístico utilizado. Resultados y conclusiones: Aunque los estudios aquí revisados no son concluyentes para confirmar la asociación entre disruptores endocrinos y riesgo de malformación del tracto genitourinario, tampoco demuestran la falta de tal asociación. Por este motivo parece razonable sugerir que este aspecto de la patología hormonal debería investigarse más en profundidad, resolviendo, al menos, el diagnóstico adecuado de los individuos y la estimación de la exposición a múltiples compuestos químicos, contaminantes ambientales, que actúan conjuntamente a través de mecanismos similares a las hormonas endógenas.Background: It has been proposed that the intrauterine period of child-mother exposure to hormonally active compounds (endocrine disruptors is of critical importance. Objective: We reviewed all Spanish and English-language epidemiological studies published between 1990 and the first trimester of 2006 that studied the possible association between human exposure to chemical compounds and the risk of cryptorchidism and/or hypospadias. Methods: The MEDLINE (PubMed database was

  19. IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid.

    Science.gov (United States)

    Albrecht, C; Caniggia, I; Clifton, V; Göhner, C; Harris, L; Hemmings, D; Jawerbaum, A; Johnstone, E; Jones, H; Keelan, J; Lewis, R; Mitchell, M; Murthi, P; Powell, T; Saffery, R; Smith, R; Vaillancourt, C; Wadsack, C; Salomon, C

    2016-12-01

    Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology; 2) xenobiotics and endocrine disruptors and pregnancy; 3) lipid mediators and placental function. Copyright © 2016. Published by Elsevier Ltd.

  20. Effects of Neonatal Treatment With 6-Hydroxydopamine and Endocrine Disruptors on Motor Activity and Gene Expression in Rats

    Science.gov (United States)

    Masuo, Yoshinori; Ishido, Masami; Morita, Masatoshi; Oka, Syuichi

    2004-01-01

    To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 μg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6- hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive. PMID:15303306

  1. Disruptores endocrinos utilizados en la industria textil-confección en España Endocrine disruptors used in textile industry in Spain

    Directory of Open Access Journals (Sweden)

    Rafael Gadea

    2009-03-01

    Full Text Available Introducción: Los disruptores endocrinos son sustancias químicas que pueden alterar el sistema hormonal. Estas sustancias se utilizan en distintos procesos de la industria del textil-confección. Objetivos: Identificar las sustancias con efectos de disrupción endocrina utilizados en la industria del textil y la confección en España para prevenir la exposición de los trabajadores a estas sustancias. Material y métodos: En el estudio participaron 65 empresas de siete comunidades autónomas, seleccionadas mediante acuerdo entre las organizaciones empresariales y sindicales del sector. Técnicos de salud laboral de las federaciones sindicales visitaron las empresas participantes y recogieron información sobre los productos químicos utilizados mediante observación de etiquetas y fichas de datos de seguridad y mediante entrevistas con técnicos de prevención, trabajadores designados, delegados de prevención y trabajadores utilizando cuestionarios estandarizados. Resultados: Las empresas participantes cubren un amplio rango de actividades propias del sector, siendo la mayoría de ellas de tamaño medio (entre 51 y 250 trabajadores, n=39. Se identificaron diecisiete sustancias diferentes con efectos de disrupción endocrina utilizadas en distintos puestos de trabajo, incluyendo preparación de fibras y tejidos, lavado, tintado o acabado textil, entre otros. Conclusiones: Serían necesarios estudios que permitieran cuantificar el nivel de exposición en los puestos identificados para priorizar las medidas preventivas necesarias.Introduction: Endocrine disruptors are chemicals which can affect hormonal system in human beings. These substances are used in several processes in the textile industry. Objectives: Identifying chemicals with endocrine disruption potential used in Spanish textile industry to promoting risk prevention in exposed workers. Material and methods: The study includes 65 companies located in seven different Spanish regions

  2. Biological impact of environmental polycyclic aromatic hydrocarbons (ePAHs) as endocrine disruptors.

    Science.gov (United States)

    Zhang, Yanyan; Dong, Sijun; Wang, Hongou; Tao, Shu; Kiyama, Ryoiti

    2016-06-01

    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 benz[a]anthracene, benzo[a]pyrene, benz[l]aceanthrylene, cyclopenta[c,d]pyrene, 7,12-dimethylbenz[a]anthracene, 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

  3. Exposure to the endocrine disruptor nonylphenol alters structure and function of thyroid gland in rats.

    Science.gov (United States)

    Xi, Yue; Li, Dehua; San, Wei

    2013-08-10

    Nonylphenol (NP) is an estrogenic-like compound which can induce vitellogenin synthesis in males and immature teleostean species. Known as an endocrine disruptor, it has been reported to affect endocrine glands; however, little is known about its effects on thyroid function. The present study aimed to evaluate whether exposure to NP alters the structure and function of the thyroid gland of rats and/or the underlying mechanisms. Rats were gavaged with NP (40, 80 and 200 mg/kg/d) for 15 days. Serum levels of thyroid-stimulating hormone were determined by radioimmunoassay. Ultramicroscopic structure of follicular cells was examined by a transmission electron microscope. Histopathology was conducted with hematoxylin-eosin (HE) staining. We found that NP exposure induced a decrease in serum levels of free tetraiodothyronine (FT) 3 and FT4 while it induced an increase in serum levels of thyroid-stimulating hormone (TSH) in a dose-dependent manner. There was a negative correlation between different doses of NP with serum levels of FT3 and FT4 (FT4 r=-0.932; FT3 r=-0.926) and a positive correlation with serum levels of TSH (r=0.967). Histological and morphometric study in the NP-exposed group revealed dilation of endoplasmic reticulum into cystic in thyroid follicular cells. Mitochondrion was damaged in the 80 and 200 mg/kg/d groups. Exposure to NP may lead to thyroid dysfunction. It may be a potential contributor to thyroid disruption. © 2013 Elsevier B.V. All rights reserved.

  4. Characterizing the effect of endocrine disruptors on human health: The role of epidemiological cohorts.

    Science.gov (United States)

    Slama, Rémy; Vernet, Céline; Nassan, Feiby L; Hauser, Russ; Philippat, Claire

    Research on endocrine disruptors (EDs) developed from numerous disciplines. In this concert of disciplines, epidemiology is central to inform on the relevance for humans of mechanisms and dose-response functions identified in animals, to characterize the health impact (number of attributable disease cases), the cost associated with ED exposure, and the efficiency of the measures taken to limit exposure. Here, we present epidemiological tools to draw valid inference regarding effects of potential EDs. Epidemiology is generally observational, requiring care to control confounding bias. Many potential EDs have a short biological half-life; approaches relying on repeated biospecimens sampling allow limiting exposure misclassification and the resulting bias. For non-persistent compounds, couple-child cohorts are a central study design. Cohorts can now rely on molecular biology approaches to characterize exposures and intermediate pathways, which corresponds to the advent of molecular epidemiology and allows stronger interactions between epidemiology, toxicology, and molecular epidemiology to characterize the health effects of EDs. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  5. Removal of endocrine disruptors PAEs in drinking water by gamma-ray irradiation

    International Nuclear Information System (INIS)

    Zhao Yongfu; Zheng Zheng; Zheng Binguo; Wang Changbao; Li Lili

    2012-01-01

    Phthalic acid esters (PAEs) belong to environmental endocrine disruptor. The dimethyl phthalate (DMP), diethyl phthalate (DEP) and di-n-butyl phthalate (DBP) were selected for the radiation study. The removal efficiencies of DMP, DEP and DBP in drinking water by gamma-ray irradiation are discussed. The results show that these PAEs could be efficiently removed by gamma-ray irradiation. The removal efficiencies of DMP, DEP and DBP (12 mg/L) in aqueous solutions by 0.8 kGy gamma-ray treatment were 96.6%, 94.5% and 86.2%. The absorbed dose needed for the removal of total carbon in aqueous solutions was much larger than the doses for PAEs degradation. When 2 kGy was selected, the removal efficiencies of TC for DMP, DEP and DBP were only 23.6%, 14.3% and 12.9%. The study results also show that the radiation degradation reaction of PAEs should be divided into two stages: low dose addition reaction and high dose ring-opening reaction. This study is of significance in the disposal of micro-polluted drinking water. (authors)

  6. Estrogenic endocrine disruptors present in sports supplements. A risk assessment for human health.

    Science.gov (United States)

    Plotan, Monika; Elliott, Christopher T; Frizzell, Caroline; Connolly, Lisa

    2014-09-15

    Sports supplements are becoming a regular dietary addition for consumers who view such products as a means of improving their health and performance. Previously estrogenic endocrine disruptors (EDs) were detected in 80% of 116 sports supplements investigated by biological in vitro reporter gene assays (RGAs). The aim of this study was to quantify the hormonal activity in 50 of these sports supplement samples using a validated estrogen RGA and perform an exposure and risk assessment for human health. Results showed that 17β-estradiol equivalent levels were higher than those reported as being present in the typical human omnivore diet in 33 of the sports supplements and higher than the acceptable daily intake (ADI) in 13 of these products. The highest activity samples presented a potential to influence the human daily exposure to 17β-estradiol like activity in various risk groups with a predicted hormonal impact of greatest concern in young boys and postmenopausal women. In conclusion, consumers of sports supplements may be exposed to high levels of estrogenic EDs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Electrochemical performance of porous diamond-like carbon electrodes for sensing hormones, neurotransmitters, and endocrine disruptors.

    Science.gov (United States)

    Silva, Tiago A; Zanin, Hudson; May, Paul W; Corat, Evaldo J; Fatibello-Filho, Orlando

    2014-12-10

    Porous diamond-like carbon (DLC) electrodes have been prepared, and their electrochemical performance was explored. For electrode preparation, a thin DLC film was deposited onto a densely packed forest of highly porous, vertically aligned multiwalled carbon nanotubes (VACNT). DLC deposition caused the tips of the carbon nanotubes to clump together to form a microstructured surface with an enlarged surface area. DLC:VACNT electrodes show fast charge transfer, which is promising for several electrochemical applications, including electroanalysis. DLC:VACNT electrodes were applied to the determination of targeted molecules such as dopamine (DA) and epinephrine (EP), which are neurotransmitters/hormones, and acetaminophen (AC), an endocrine disruptor. Using simple and low-cost techniques, such as cyclic voltammetry, analytical curves in the concentration range from 10 to 100 μmol L(-1) were obtained and excellent analytical parameters achieved, including high analytical sensitivity, good response stability, and low limits of detection of 2.9, 4.5, and 2.3 μmol L(-1) for DA, EP, and AC, respectively.

  8. Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty.

    Science.gov (United States)

    Deng, Fang; Tao, Fang-biao; Liu, De-yun; Xu, Yuan-yuan; Hao, Jia-hu; Sun, Ying; Su, Pu-yu

    2012-05-01

    The incidence of idiopathic precocious puberty (IPP) might have an increasing trend. But the causes and risk factors of IPP are unknown. The objective of our study is to evaluate the effects of growth environments and two environmental endocrine disruptors (EDCs), zearalenone (ZEA), and 1,1-dichloro-2,2,bisethylene (p,p'-DDE), on patients with IPP. Case-control study. The study consisted of 78 IPP patients at diagnosis and 100 control children matched for age and sex. A questionnaire was designed to collect data on growth environments, and serum ZEA and p,p'-DDE were tested in all subjects. We analyzed data on growth environments, two EDCs, and biological interaction between growth environments and EDCs. In growth environments, small for gestational age, maternal physical disease during pregnancy, early maternal menarche, early puberty of same-degree relatives, and father's absence in 4- to 6-year olds were risk factors for children with IPP (P<0.05). Serum ZEA concentration, ZEA, and p,p'-DDE-positive rates in the IPP group were significantly higher than those in the control group (P<0.05). There was a biological interaction between growth environments and ZEA (relative excess risk due to interaction =34.562, attributable proportion due to interaction =0.745, synergy index =4.193). Results suggest possible effects of growth environments and two EDCs on the development of IPP. In addition, growth environments and ZEA have biological interaction that might increase the risk of developing IPP.

  9. Prenatal Exposure to Endocrine Disruptors and Reprogramming of Adipogenesis: An Early-Life Risk Factor for Childhood Obesity.

    Science.gov (United States)

    Shafei, Ayman El-Sayed; Nabih, Enas Samir; Shehata, Kirolos Atalla; Abd Elfatah, Emad Sherif Mohamed; Sanad, Abou Bakr Ahmed; Marey, Mohamed Yehia; Hammouda, Abd Alla Mohamed Ahmed; Mohammed, Mounir Mostafa Moussa; Mostafa, Randa; Ali, Mahmoud A

    2018-01-01

    Obesity is a global health problem. It is characterized by excess adipose tissue that results from either increase in the number of adipocytes or increase in adipocytes size. Adipocyte differentiation is a highly regulated process that involves the activation of several transcription factors culminating in the removal of adipocytes from the cell cycle and induction of highly specific proteins. Several other factors, including hormones, genes, and epigenetics, are among the most important triggers of the differentiation process. Although the main contributing factors to obesity are high caloric intake, a sedentary lifestyle, and genetic predisposition, strong evidence supports a role for life exposure to environmental pollutants. Endocrine-disrupting chemicals are exogenous, both natural and man-made, chemicals that disrupt the body signaling processes, thus interfering with the endocrine system. Several studies have shown that prenatal exposure to endocrine disruptors modulates the mechanisms, by which multipotent mesenchymal stem cells differentiate into adipocytes. This review discusses adipocytes differentiation and highlights the possible mechanisms of prenatal exposure to endocrine disruptors in reprogramming of adipogenesis and induction of obesity later in life. Therefore, this review provides knowledge that reduction of early life exposure to these chemicals could open the door for new strategies in the prevention of obesity, especially during childhood.

  10. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

    Directory of Open Access Journals (Sweden)

    Alison M Anderson

    Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

  11. Environmental endocrine disruptors and developmental abnormalities in wildlife; Kankyo horumon (gaiinsei naibunpi kakuran kagaku busshitsu) no kankyo seibutsu ni taisuru eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Iguchi, T. [Yokohama City Univ., Yokohama (Japan)

    1998-04-15

    The environmental endocrine disruptor, or the so-called environmental hormone, is outlined. Hormones are secreted from endocrine glands in trace amounts, transported by blood, and exert influence on the target organs and distal cells, this to sustain constancy in living organisms. There are two types: peptide hormones which are rows of amino acids and steroid hormones which are composed of cholesterol. Endocrine disruptors are chemical substances discharged into the environment which, once taken into human organisms, disrupt endocrine systems, some acting like female sex hormones and others resisting male sex hormones. Many a wild animal are found affected by them. They are accumulating in human organisms too. Synthesized chemical substances such as DDT, PCB, dioxins, and alkylphenols present in the water system affect a fish by disrupting its endocrine, immunity, nerve, growth, and regeneration. Embryos and larvae are quite susceptible, easy to turn abnormal. Voices are high across the world for the study of environmental endocrine disruptors. Introduced in this report are some animal experiments, typical cases of impact on the ecosystem, and systems for detecting environmental endocrine disruptors. 36 refs., 1 tab.

  12. Nuevos disruptores endocrinos: su importancia en la población pediátrica New endocrine disruptors: their importance in pediatric population

    Directory of Open Access Journals (Sweden)

    Juan Manuel Alfaro Velásquez

    2005-04-01

    Full Text Available Los cambios de nuestro hábitat en los últimos 40 años han generado contactos frecuentes con sustancias químicas tanto naturales como sintéticas que funcionan como disruptores endocrinos; son ejemplos los pesticidas ampliamente usados tras la introducción del DDT, los derivados petroquímicos en la industria del plástico, las medicinas sintéticas, y el volumen creciente de artículos de vestuario, aseo, cosmética y transporte. En cada uno de los grupos anotados hay señales de actividad de algún disruptor endocrino sea directamente o a través de sus derivados. La controversia inicial se centró principalmente en los compuestos químicamente similares a los estrógenos y en todos aquellos con actividad antiandrógenos o antitiroidea, debido a que se sospechaba que dañaban el ADN; recientemente se han estudiado otros compuestos y condiciones de vida que no lesionan el genoma pero sí interactúan con enzimas y sus metabolitos. Entre los efectos potenciales de estas sustancias cabe mencionar los siguientes: anomalías intrauterinas por daños del tejido fetal en formación; cambios del fenotipo genital al nacer y diversas manifestaciones clínicas durante la adolescencia; además, no pueden perderse de vista los efectos sobre las generaciones futuras. Los disruptores endocrinos son compuestos que pueden modular tanto la expresión endocrina e inmune del afectado como la homeostasis, la reproducción, el desarrollo y el comportamiento y tienen efectos sobre los tejidos reproductivos masculino y femenino, la fertilidad, la función tiroidea y el sistema nervioso central. Changes in the environment that have taken place during the last 40 years have generated frequent contacts with natural and synthetic chemical products with potential endocrine-disrupting roles; among them: the intensive use of pesticides after the introduction of DDT, the petrochemical derivatives of the plastic industry, the synthetic medicines and the growing market of

  13. The use of a unique co-culture model of fetoplacental steroidogenesis as a screening tool for endocrine disruptors: The effects of neonicotinoids on aromatase activity and hormone production.

    Science.gov (United States)

    Caron-Beaudoin, Elyse; Viau, Rachel; Hudon-Thibeault, Andrée-Anne; Vaillancourt, Cathy; Sanderson, J Thomas

    2017-10-01

    Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid. Aromatase catalytic activity was determined in both cell lines using the tritiated water-release assay. Hormone production was measured by ELISA. The three neonicotinoids induced aromatase activity in our fetoplacental co-culture and concordingly, estradiol and estrone production were increased. In contrast, estriol production was strongly inhibited by the neonicotinoids. All three pesticides induced the expression of CYP3A7 in H295R cells, and this induction was reversed by co-treatment of H295R cells with exogenous estriol. CYP3A7 is normally expressed in fetal liver and is a key enzyme involved in estriol synthesis. We suggest that neonicotinoids are metabolized by CYP3A7, thus impeding the 16α-hydroxylation of fetal DHEA(-sulfate), which is normally converted to estriol by placental aromatase. We successfully used the fetoplacental co-culture as a physiologically relevant tool to highlight the potential effects of neonicotinoids on estrogen production, aromatase activity and CYP3A7 expression during pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Biomonitoring of infant exposure to phenolic endocrine disruptors using urine expressed from disposable gel diapers.

    Science.gov (United States)

    Liu, Liangpo; Xia, Tongwei; Zhang, Xueqin; Barr, Dana Boyd; Alamdar, Ambreen; Zhang, Jie; Tian, Meiping; Huang, Qingyu; Shen, Heqing

    2014-08-01

    Infant exposure to endocrine disruptors (EDs) may cause adverse health effects because of their fast growth and development during this life stage. However, collecting urine from infants for exposure assessment using biological monitoring is not an easy task. For this purpose, we evaluated the feasibility of using urine expressed from disposable gel absorbent diapers (GADs) as a matrix for biomonitoring selected phenolic EDs. GADs urine was expressed with the assistance of CaCl(2) and was collected using a device fabricated in our laboratory. The analytes were extracted and concentrated using a liquid-liquid method and their hydroxyl groups were modified by dansyl chloride to enhance their chromatography and detection. Finally, the analytes were measured by high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS). The target chemicals were bisphenol A, triclosan, 17 α-ethynylestradiol, the natural hormone estrone, and 17 β-estradiol. The ratio of the CaCl(2) to the urine-wetted gel absorbent, variation of the inter-urination volume, and analyte deposition bias in the diaper were assessed. Analyte blank values in the diapers, the sample storage stabilities, and recoveries of the analytes were also evaluated. The results showed that 70-80 % of the urine could be expressed from the diaper with the assistance of CaCl(2) and 70.5-124 % of the spiked analytes can be recovered in the expressed urine. The limits of detections (LODs) were 0.02-0.27 ng/mL, well within the range for detection in human populations. Our pilot data suggest that infants are widely exposed to the selected EDs.

  15. Mass flows of endocrine disruptors in the Glatt River during varying weather conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jonkers, Niels; Kohler, Hans-Peter E.; Dammshaeuser, Anna [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Giger, Walter [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland)], E-mail: giger@eawag.ch

    2009-03-15

    . - Mass balance of endocrine disruptors in a wastewater-river system is strongly influenced by water flow conditions.

  16. The effect of endocrine disruptors on reproductive parameters and expression of selected testicular genes in male mice in vivo

    Czech Academy of Sciences Publication Activity Database

    Pěknicová, Jana; Elzeinová, Fatima; Žatecká, Eva; Děd, Lukáš; Dorosh, Andriy

    2012-01-01

    Roč. 67, Issue Supplement s1 (2012), s. 20 ISSN 1046-7408. [13th International Symposium for Immunology of reproduction "From the roots to the tops of Reproductive Immunology". 22.06.2012-24.06.2012, Varna] R&D Projects: GA ČR(CZ) GA523/09/1793; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : endocrine disruptors * testicular gene * reproductive parameters * reproduction Subject RIV: DN - Health Impact of the Environment Quality

  17. Proposal of how to update the standard information requirements in REACH, PPPR and BPR – a testing strategy for identification of endocrine disruptors

    DEFF Research Database (Denmark)

    Holbech, Henrik; Bjerregaard, Poul; Hass, Ulla

    This presentation is based on a project prepared by the Danish Centre on Endocrine Disrupters (CEHOS) for the Danish EPA. The project aim to provide a science based input to the on-going work in EU with regard to endocrine disruptors, i.e. the development of criteria for identification, REACH...... review on EDs and the revised strategy for the future work on endocrine disruptors, focusing on adequate detection of substances with endocrine disrupting properties under various legislative frameworks, including REACH (EC No 1907/2006), the Plant Protection Products Regulation (PPPR) (EC No 1107....../2009) and the Biocidal Products Regulation (BPR) (EC No 528/2012). There are currently no specific information requirements or testing strategies with regard to endocrine disruption in REACH and other relevant legislations. However, in relation to biocides and recently also to plant protection products, indications...

  18. Endocrine Disruptor Screening Program (EDSP) Comprehensive Management Plans

    Science.gov (United States)

    The EDSP Comprehensive Management Plan describes the technical review processes that will be used in implementing this program and how the agency intends to factor technology advancements into the program.

  19. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    Directory of Open Access Journals (Sweden)

    Brophy James T

    2012-11-01

    Full Text Available Abstract Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration. Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82; bars-gambling (OR = 2.28; 95% CI, 0.94-5.53; automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88, food canning (OR = 2.35; 95% CI, 1.00-5.53, and metalworking (OR = 1.73; 95% CI, 1.02-2.92. Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4 and food canning (OR = 5.70; 95% CI, 1.03-31.5. Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and

  20. Evaluation of endocrine disruptor levels in Kafue Lechwe (Kobus leche kafuensis) samples from the Blue Lagoon National Park of Zambia.

    Science.gov (United States)

    Sichilongo, Kwenga; Torto, Nelson

    2009-12-01

    The concentrations of endocrine disruptors were determined in 36 liver tissue, serum and whole blood sample extracts drawn from 15 Blue Lagoon National Park Kafue lechwe. Out of 10 analytes evaluated, 89% of the sample extracts showed very high dieldrin concentrations of between 0.08–100 μg/mL in serum, 0.08–24.8 μg/mL in whole blood and 0.08–4.6 μg/g wet weight in liver tissue extracts. pp-DDE was detected in 83% of the sample extracts at 0.006–5.1 μg/mL in serum, 0.006–8.5 μg/mL in whole blood and 0.006–0.12 μg/g wet weight in liver tissue extracts. There was strong correlation between pp-DDE and dieldrin in all the three matrices. Deltamethrin and endosulfan detected at 50% frequency each. Percent recoveries in spiked laboratory blanks ranged between 60–100% while calculated detection limits ranged from 0.004 to 0.21 μg/mL for all the endocrine disruptors evaluated.

  1. Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal.

    Science.gov (United States)

    Rovani, Suzimara; Censi, Monique T; Pedrotti, Sidnei L; Lima, Eder C; Cataluña, Renato; Fernandes, Andreia N

    2014-04-30

    A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800°C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N2 adsorption/desorption curves and point of zero charge (pHPZC). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0-11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298K). The maximum amounts of E2 and EE2 removed at 298K were 7.584 (E2) and 7.883mgg(-1) (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Decontamination of a municipal landfill leachate from endocrine disruptors using a combined sorption/bioremoval approach.

    Science.gov (United States)

    Loffredo, Elisabetta; Castellana, Giancarlo; Senesi, Nicola

    2014-02-01

    Sorption and biodegradation are the main mechanisms for the removal of endocrine disruptor compounds (EDs) from both solid and liquid matrices. There are recent evidences about the capacity of white-rot fungi to decontaminate water systems from phenolic EDs by means of their ligninolytic enzymes. Most of the available studies report the removal of EDs by biodegradation or adsorption separately. This study assessed the simultaneous removal of five EDs—the xenoestrogens bisphenol A (BPA), ethynilestradiol (EE2), and 4-n-nonylphenol (NP), and the herbicide linuron and the insecticide dimethoate—from a municipal landfill leachate (MLL) using a combined sorption/bioremoval approach. The adsorption matrices used were potato dextrose agar alone or added with each of the following adsorbent materials: ground almond shells, a coffee compost, a coconut fiber, and a river sediment. These matrices were either not inoculated or inoculated with the fungus Pleurotus ostreatus and superimposed on the MLL. The residual amount of each ED in the MLL was quantified after 4, 7, 12, and 20 days by HPLC analysis and UV detection. Preliminary experiments showed that (1) all EDs did not degrade significantly in the untreatedMLL for at least 28 days, (2) the mycelial growth of P. ostreatus was largely stimulated by components of the MLL, and (3) the enrichment of potato dextrose agar with any adsorbent material favored the fungal growth for 8 days after inoculation. A prompt relevant disappearance of EDs in the MLL occurred both without and, especially, with fungal activity, with the only exception of the very water soluble dimethoate that was poorly adsorbed and possibly degraded only during the first few days of experiments. An almost complete removal of phenolic EDs, especially EE2 and NP, occurred after 20 days or much earlier and was generally enhanced by the adsorbent materials used. Data obtained indicated that both adsorption and biodegradation mechanisms contribute

  3. TITLE: Twenty-five years after “Wingspread” – Environmental endocrine disruptors (EDCs) and human health: EDSP, HTS, AOPs, and TSCA

    Science.gov (United States)

    The aim of this paper is to provide the reader with a view of the Endocrine Disruptor Chemical (EDC) research field and its relevance to human health. My perspective is from working on the effects of EDCs that act via the androgen (A) or estrogen (E) signaling pathways in a regul...

  4. Estrogenic and androgenic activities in total plasma measured with reporter-gene bioassays: relevant exposure measures for endocrine disruptors in epidemiologic studies?

    NARCIS (Netherlands)

    Brouwers, M.M.; Besselink, H.; Bretveld, R.W.; Anzion, R.B.M.; Scheepers, P.T.J.; Brouwer, A.; Roeleveld, N.

    2011-01-01

    Measurements of estrogenic and androgenic activities in total plasma with Chemically Activated LUciferase gene eXpression (CALUX(R)) bioassays could provide biologically relevant measures for exposure to endocrine disruptors in epidemiologic studies. The objective of this study was to explore the

  5. Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives.

    Science.gov (United States)

    Rajamani, Uthra; Gross, Andrew R; Ocampo, Camille; Andres, Allen M; Gottlieb, Roberta A; Sareen, Dhruv

    2017-08-09

    Persistent exposure to man-made endocrine disrupting chemicals during fetal endocrine development may lead to disruption of metabolic homeostasis contributing to childhood obesity. Limited cellular platforms exist to test endocrine disrupting chemical-induced developmental abnormalities in human endocrine tissues. Here we use an human-induced pluripotent stem cell-based platform to demonstrate adverse impacts of obesogenic endocrine disrupting chemicals in the developing endocrine system. We delineate the effects upon physiological low-dose exposure to ubiquitous endocrine disrupting chemicals including, perfluoro-octanoic acid, tributyltin, and butylhydroxytoluene, in endocrine-active human-induced pluripotent stem cell-derived foregut epithelial cells and hypothalamic neurons. Endocrine disrupting chemicals induce endoplasmic reticulum stress, perturb NF-κB, and p53 signaling, and diminish mitochondrial respiratory gene expression, spare respiratory capacity, and ATP levels. As a result, normal production and secretion of appetite control hormones, PYY, α-MSH, and CART, are hampered. Blocking NF-κB rescues endocrine disrupting chemical-induced aberrant mitochondrial phenotypes and endocrine dysregulation, but not ER-stress and p53-phosphorylation changes.Harmful chemicals that disrupt the endocrine system and hormone regulation have been associated with obesity. Here the authors apply a human pluripotent stem cell-based platform to study the effects of such compounds on developing gut endocrine and neuroendocrine systems.

  6. Distrubution of the Endocrine Disruptor Nonylphenol and the Effects of Topographical Sheilding in an Eastern Sierra Nevada Mountain Drainage

    Science.gov (United States)

    Lyons, R. A.; Van de Bittner, K.; Morgan Jones, S.

    2013-12-01

    Nonylphenol is a biodegradation product of nonylphenol polyethoxylates, a pervasive compound used in many industrial processes and notably in pesticides as a surfactant. Nonylphenol has been shown to act as an endocrine disruptor at low concentrations. It causes hermaphrodism, birth defects, and high mortality in fish, frogs and other amphibians. The Sierra Nevada Mountains separate the Central Valley in the west from the high desert of Mono Country on the east side of the state of California. The Central Valley represents some of the most heavily cultivated agricultural land in the United States. San Joaquin County alone had an annual pesticide use of over 8 million pounds in 2009 according to the Pesticide Action Network, compared with 4800 pounds in Mono County the same year. Fragile alpine ecosystems in the Sierra Nevadas may be highly susceptible to the effects of endocrine disruptors like nonylphenol. The distribution of nonylphenol is affected by localized topography in a steep walled montane canyon in the Eastern Sierra Nevada Mountains, Convict Creek canyon. The concentration of nonylphenol in snow and surface water increases as the elevation in Convict Creek canyon decreases in an easterly direction from not detectable at the highest elevations to as much as .01mg/L in water and 1.8 mg/L in snow at the lowest elevations. The steep head wall of Convict Creek canyon, facing southeast, provides shielding to the higher elevation lakes from deposition of compounds and particulate matter. As a canyon becomes less steep and broader, more nonylphenol is deposited. Identifying these deposition patterns may assist in determining amphibian and fish populations that are at higher risk of negative impact from these compounds.

  7. Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal

    Energy Technology Data Exchange (ETDEWEB)

    Rovani, Suzimara; Censi, Monique T.; Pedrotti, Sidnei L.; Lima, Éder C.; Cataluña, Renato; Fernandes, Andreia N., E-mail: andreia.fernandes@ufrgs.br

    2014-04-01

    Highlights: • Development of a new adsorbent from agro-industrial waste. • Characterization by chemical and spectroscopic methods. • Alternative for the treatment of effluents that contain estrogens. • The AC adsorbent was successfully employed as solid phase adsorbent for the preconcentration of E2 and EE2 from aqueous solutions. - Abstract: A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800 °C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N{sub 2} adsorption/desorption curves and point of zero charge (pH{sub PZC}). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0–11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298 K). The maximum amounts of E2 and EE2 removed at 298 K were 7.584 (E2) and 7.883 mg g{sup −1} (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions.

  8. The OBELIX project: early life exposure to endocrine disruptors and obesity

    NARCIS (Netherlands)

    Legler, J.; Hamers, T.H.M.; van de Bor, M.; Schoeters, G.; van der Ven, L.; Eggesbo, M.; Koppe, J.; Trnovec, T.

    2011-01-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals:

  9. Biodegradation of pharmaceuticals and endocrine disruptors with oxygen, nitrate, manganese (IV), iron (III) and sulfate as electron acceptors

    Science.gov (United States)

    Schmidt, Natalie; Page, Declan; Tiehm, Andreas

    2017-08-01

    Biodegradation of pharmaceuticals and endocrine disrupting compounds was examined in long term batch experiments for a period of two and a half years to obtain more insight into the effects of redox conditions. A mix including lipid lowering agents (e.g. clofibric acid, gemfibrozil), analgesics (e.g. diclofenac, naproxen), beta blockers (e.g. atenolol, propranolol), X-ray contrast media (e.g. diatrizoic acid, iomeprol) as well as the antiepileptic carbamazepine and endocrine disruptors (e.g. bisphenol A, 17α-ethinylestradiol) was analyzed in batch tests in the presence of oxygen, nitrate, manganese (IV), iron (III), and sulfate. Out of the 23 selected substances, 14 showed a degradation of > 50% of their initial concentrations under aerobic conditions. The beta blockers propranolol and atenolol and the analgesics pentoxifylline and naproxen showed a removal of > 50% under anaerobic conditions. In particular naproxen proved to be degradable with oxygen and under most anaerobic conditions, i.e. with manganese (IV), iron (III), or sulfate. The natural estrogens estriol, estrone and 17β-estradiol showed complete biodegradation under aerobic and nitrate-reducing conditions, with a temporary increase of estrone during transformation of estriol and 17β-estradiol. Transformation of 17β-estradiol under Fe(III)-reducing conditions resulted in an increase of estriol as well. Concentrations of clofibric acid, carbamazepine, iopamidol and diatrizoic acid, known for their recalcitrance in the environment, remained unchanged.

  10. Effect of an endocrine disruptor on mammalian fertility. Application of monoclonal antibodies against sperm protein as marker for testing sperm damage

    Czech Academy of Sciences Publication Activity Database

    Pěknicová, Jana; Kyselová, Vendula; Buckiová, Daniela; Boubelík, Michael

    2002-01-01

    Roč. 2002, č. 47 (2002), s. 311-318 ISSN 1046-7408 R&D Projects: GA ČR GV524/96/K162; GA ČR GA303/00/1651; GA MZd NJ5851 Institutional research plan: CEZ:AV0Z5039906; CEZ:AV0Z5052915 Keywords : acrosome integrity * bisphenol -A * endocrine disruptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.413, year: 2002

  11. Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

    NARCIS (Netherlands)

    Costas, L.; Infante-Rivard, C.; Zock, J.P.; Tongeren, M. van; Boffetta, P.; Cusson, A.; Robles, C.; Casabonne, D.; Benavente, Y.; Becker, N.; Brennan, P.; Foretova, L.; Maynadié, M.; Staines, A.; Nieters, A.; Cocco, P.; Sanjose, S. de

    2015-01-01

    Background: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. Methods: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European

  12. The use of metabolising systems for in vitro testing of endocrine disruptors

    NARCIS (Netherlands)

    Jacobs, M.N.; Janssens, W.; Bernauer, U.; Brandon, E.; Coecke, S.; Combes, R.; Edwards, P.; Freidig, A.; Freyberger, A.; Kolanczyk, R.; Mc Ardie, C.; Mekenyan, O.; Schmieder, P.; Schrader, T.; Takeyoshi, M.; Burg, B. van der

    2008-01-01

    Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may

  13. Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

    NARCIS (Netherlands)

    van der Meer, Thomas P; Artacho-Cordón, Francisco; Swaab, Dick F; Struik, Dicky; Makris, Konstantinos C; Wolffenbuttel, Bruce H R; Frederiksen, Hanne; van Vliet-Ostaptchouk, Jana V

    2017-01-01

    Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain

  14. First year growth in relation to prenatal exposure to endocrine disruptors - a Dutch prospective cohort study

    NARCIS (Netherlands)

    de Cock, M.; de Boer, M.R.; Lamoree, M.H.; Legler, J.; van de Bor, M.

    2014-01-01

    Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE),

  15. Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health.

    Science.gov (United States)

    Bansal, Amita; Henao-Mejia, Jorge; Simmons, Rebecca A

    2018-01-01

    The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity. Copyright © 2018 Endocrine Society.

  16. Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: diethylstilbestrol and estradiol.

    Science.gov (United States)

    Hu, Lintong; Cheng, Qin; Chen, Danchao; Ma, Ming; Wu, Kangbing

    2015-01-01

    It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28V and 0.49V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87 nM and 4.9 nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Review on crosstalk and common mechanisms of endocrine disruptors: Scaffolding to improve PBPK/PD model of EDC mixture.

    Science.gov (United States)

    Sharma, Raju Prasad; Schuhmacher, Marta; Kumar, Vikas

    2017-02-01

    Endocrine disruptor compounds (EDCs) are environment chemicals that cause harmful effects through multiple mechanisms, interfering with hormone system resulting in alteration of homeostasis, reproduction and developmental effect. Many of these EDCs have concurrent exposure with crosstalk and common mechanisms which may lead to dynamic interactions. To carry out risk assessment of EDCs' mixture, it is important to know the detailed toxic pathway, crosstalk of receptor and other factors like critical window of exposure. In this review, we summarize the major mechanism of actions of EDCs with the different/same target organs interfering with the same/different class of hormone by altering their synthesis, metabolism, binding and cellular action. To show the impact of EDCs on life stage development, a case study on female fertility affecting germ cell is illustrated. Based on this summarized discussion, major groups of EDCs are classified based on their target organ, mode of action and potential risk. Finally, a conceptual model of pharmacodynamic interaction is proposed to integrate the crosstalk and common mechanisms that modulate estrogen into the predictive mixture dosimetry model with dynamic interaction of mixture. This review will provide new insight for EDCs' risk assessment and can be used to develop next generation PBPK/PD models for EDCs' mixture analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. On-Line Derivatization Gas Chromatography Ion Trap Mass Spectrometry for Determination of Endocrine Disruptors in Surface Water

    Energy Technology Data Exchange (ETDEWEB)

    Tzing, Shin-Hwa; Chang, Jia-Yaw; Ling, Yong-Chien

    2004-03-31

    A method has been developed for the determination of endocrine disruptors (EDs) (containing hydroxyl groups) in surface water from different sources. The surface water samples from different sites including school and local dormitory sewage effluents, lake water and river water were collected and analyzed. In this method, the pretreated sample is directly analyzed by GC-MS using on-line derivatization, where tetramethylammonium hydroxide (TMA-OH) was used as the derivatizing agent. Use of large-volume direct sample introduction (DSI) and co-injection of the sample and TMAOH avoids external contaminations as observed in conventional derivatization protocols. Additionally, the use of chemical ionization (CI) and CI-MS/MS could enable detection of EDs at lower concentrations and reduce the matrices' interference thereby enhancing detection sensitivity of EDs for quantification. In this work, the use of dichloromethane as CI reagent for EDs is reported for the first time and could detect EDs to concentrations as low as 0.5 pg/mL. The recovery ranged from 74 to 112 % and the relative standard derivations for replicate analyses ranged from 5 to 17 %. We hope that this method will be applicable for routine analysis of EDs with hydroxyl functional groups.

  19. Possible Roles of B1 Cells and Environmental Estrogens (Endocrine Disruptors in the Development of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Sho Ishikawa

    2005-01-01

    Full Text Available Autoimmune diseases as well as type-I allergic diseases have markedly increased in the past 30 years. Environmental estrogens or endocrine disruptors are possibly involved in the etiology of the increase in autoimmune diseases as one of environmental factors. In aged BWF1 mice, a murine model for SLE, B lymphocyte chemoattractant (BLC/CXCL13 is ectopically and highly expressed in target organs such as the thymus and kidney. B1 cells, a specialized cell population that are distinguished from conventional B cells (B2 cells by their origin, cell surface phenotype, unique tissue distribution, self-reactivity, etc., preferentially migrate towards BLC. Aberrant B1 cell trafficking to the target organs may result in activation of autoreactive CD4 T cells, autoantibody production, and impaired mucosal immunity in the gut during the development of SLE. Interestingly, B1 cells show a higher sensitivity to environmental estrogens than conventional B (B2 cells to produce autoantibodies. Thus, B1 cell can be a useful target for evaluating the pathological significance of environmental estrogens in the development of autoimmune diseases.

  20. Endocrine disruptors in freshwater streams of Hesse, Germany: Changes in concentration levels in the time span from 2003 to 2005

    Energy Technology Data Exchange (ETDEWEB)

    Quednow, Kristin [J. W. Goethe University Frankfurt am Main, Institute of Atmospheric and Environmental Sciences, Department of Environmental Analytical Chemistry, Georg-Voigt-Strasse 14, 60054 Frankfurt (Germany)], E-mail: quednow@kristall.uni-frankfurt.de; Puettmann, Wilhelm [J. W. Goethe University Frankfurt am Main, Institute of Atmospheric and Environmental Sciences, Department of Environmental Analytical Chemistry, Georg-Voigt-Strasse 14, 60054 Frankfurt (Germany)

    2008-03-15

    Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP). Measured concentrations of the target compounds in the river water samples ranged from <20 ng/l to 1927 ng/l, <10 ng/l to 770 ng/l, and <10 ng/l to 420 ng/l for BPA, 4-tert-OP and tech.-4-NP, respectively. BPA levels were, with the exception of two samples, below the predicted no-effect concentration (PNEC) for water organisms. Tech.-4-NP concentrations showed a significant tendency of decreasing concentrations during the sampling period. This is mainly attributed to the implementation of the European Directive 2003/53/EG, which restricts both the marketing and use of nonylphenols. Results from the analysis of additionally collected water samples from sewage treatment plant (STP) effluents indicate that the STPs cannot be the only sources for tech.-4-NP found in the river water. - Concentrations of 4-nonylphenols in rivers of Hessisches Ried in Germany decreased in the sampling period from September 2003 to September 2005.

  1. Phytotoxic, clastogenic and bioaccumulation effects of the environmental endocrine disruptor bisphenol A in various crops grown hydroponically.

    Science.gov (United States)

    Ferrara, Giuseppe; Loffredo, Elisabetta; Senesi, Nicola

    2006-04-01

    The effects of the endocrine disruptor bisphenol A (BPA) at concentrations of 10 and 50 mg l(-1) were evaluated on the germination and morphology, micronuclei (MN) content in root tip cells and BPA bioaccumulation of hydroponic seedlings of broad bean (Vicia faba L.), tomato (Lycopersicon esculentum Mill.), durum wheat (Triticum durum Desf.) and lettuce (Lactuca sativa L.) after 6 and 21 days of growth. In general, BPA at any dose used did not inhibit germination and early growth (6 days) of seedlings of the species examined, with the exception of primary root length of tomato which decreased at the higher BPA dose. In contrast, an evident phytotoxicity was induced by BPA in all species after 21 days of growth with evident morphological anomalies and significant reductions of the lengths and fresh and dry weights of shoots and roots of seedlings. With respect to the nutrient medium without seedlings, BPA concentration decreased markedly during the growth period in the presence of broad bean and tomato seedlings, and limitedly in the presence of durum wheat and, especially, lettuce. Further, the presence of BPA measured in roots and shoots of broad bean and tomato after 21-day growth indicated that bioaccumulation of BPA had occurred. The number of MN in broad bean and durum wheat root tip cells increased markedly by treatment with BPA at both concentrations, thus suggesting a potential clastogenic activity of BPA in these species.

  2. Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response.

    Directory of Open Access Journals (Sweden)

    N Couleau

    Full Text Available The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA, di-ethylhexyl-phthalate (DEHP, dibutyl phthalate (DBP and 4-tert-octylphenol (4-OP, either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 β and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 μM for each condition. Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations.

  3. Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: Diethylstilbestrol and estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Lintong; Cheng, Qin [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Chen, Danchao; Ma, Ming [Ningbo Entry-exit Inspection and Quarantine Bureau of China, Ningbo 315012 (China); Wu, Kangbing, E-mail: kbwu@hust.edu.cn [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2015-02-11

    Graphical abstract: - Highlights: • A novel electrochemical sensor was developed for diethylstilbestrol and estradiol. • Graphene prepared by solvent exfoliation greatly enhances the detection sensitivity. • The newly-developed method has promising application and the accuracy is good. - Abstract: It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28 V and 0.49 V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87 nM and 4.9 nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory.

  4. Monitoring and risk assessment for endocrine disruptors in the aquatic environment: a biomarker approach

    Energy Technology Data Exchange (ETDEWEB)

    Bjerregaard, P.; Korsgaard, B.; Christiansen, L.B.; Pedersen, K.L.; Christensen, L.J.; Pedersen, S.N.; Horn, P. [Odense Univ. (Denmark). Biologisk Inst.

    1998-12-31

    Evidence that a number of chemicals affect wildlife populations or individuals via interaction with endocrine systems has been increasing in recent years. Not all of the mechanisms of action are fully understood, but endocrine disrupting chemicals may work at various biochemical levels, e.g. affecting the synthesis of hormones, interfering with hormone transporting proteins in the blood, affecting the metabolisation of hormones or by direct effects on cellular hormone receptors. In dogwhelks Nucella lapillus tributyltin inhibits the aromatase that converts testosterone to oestrogen thereby masculinising the females (Oehlmann et al. 1996). Metabolites of polychlorinated biphenyls interfere with thyroxin transporting proteins in the blood of seals. Chemicals that induce MFO-activity may indirectly lead to altered hormone levels by increasing the metabolisation of hormones. Alkylphenols react directly with the oestrogen receptor which in turn may lead to feminisation of male organisms exposed. (orig.)

  5. Endocrine disruptors in food contact materials; is there a health threat?

    Science.gov (United States)

    Cwiek-Ludwicka, Kazimiera; Ludwicki, Jan K

    2014-01-01

    Food Contact Materials (FCMs) are a major source of endocrine disrupting chemical substances (EDCs), thus forming an important part of human exposure to these compounds, to which this article is addressed. The potential impact of such exposures on endocrine function, and thereby health outcomes, requires scientifically valid evidence so that appropriate risk management decisions can be taken to diminish human exposure, particularly in vulnerable population groups like infants and small children. Relevant aspects of exposure assessment are discussed based on testing migration of EDCs from FCMs, together with the different approaches so used. The specific migration testing determines whether limits for defined substances are met. However not all EDCs present in the leachate may be found by these means. In fact, the chances of detecting EDCs in the food simulant (leachate) are improved when it is subjected the relevant biological testing, thus helping to provide improved protection against these chemical substances. Nevertheless, official controls and risk management decisions do not necessarily take such testing into account, as the relevant legislation is based on specific migration limits that may be easily quantified and addressed in the risk management process. Elucidating the link between observed endocrine activity and any toxic effects so arising, is complicated by the complexity of endocrine interrelationships coupled with relatively limited sensitivity of toxicological tests. Any risk assessment implies a rather high uncertainty and should include also any cumulative effects. This review discusses the effects of the EDCs like bisphenol A, phthalates and benzophenone found in FCMs. In addition, the approaches from the USA and EU for systematically evaluating man-made EDCs in the environment are also considered, including appropriate prioritisation criteria.

  6. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors.

    Science.gov (United States)

    Derghal, Adel; Djelloul, Mehdi; Trouslard, Jérôme; Mounien, Lourdes

    2016-01-01

    Endocrine-disrupting chemicals (EDCs) are diverse natural and synthetic chemicals that may alter various mechanisms of the endocrine system and produce adverse developmental, reproductive, metabolic, and neurological effects in both humans and wildlife. Research on EDCs has revealed that they use a variety of both nuclear receptor-mediated and non-receptor-mediated mechanisms to modulate different components of the endocrine system. The molecular mechanisms underlying the effects of EDCs are still under investigation. Interestingly, some of the effects of EDCs have been observed to pass on to subsequent unexposed generations, which can be explained by the gametic transmission of deregulated epigenetic marks. Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. Epigenetic mechanisms, including histone modifications, DNA methylation, and specific micro-RNAs (miRNAs) expression, have been proposed to mediate transgenerational transmission and can be triggered by environmental factors. MiRNAs are short non-coding RNA molecules that post-transcriptionally repress the expression of genes by binding to 3'-untranslated regions of the target mRNAs. Given that there is mounting evidence that miRNAs are regulated by hormones, then clearly it is important to investigate the potential for environmental EDCs to deregulate miRNA expression and action.

  7. Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

    Science.gov (United States)

    Vandenberg, Laura N; Welshons, Wade V; Vom Saal, Frederick S; Toutain, Pierre-Louis; Myers, John Peterson

    2014-06-25

    For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of 'oral' exposures. It is now widely used--and in some cases required--by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, gavage exposures avoid these interactions, leading to dramatic differences in absorption, bioavailability and metabolism with implications for toxicokinetic assumptions and models. Additionally, there are well acknowledged complications associated with gavage, such as perforation of the esophagus that diminish its value in toxicological experiments. Finally, the gavage protocol itself can induce stress responses by the endocrine system and confound the assessment of EDCs. These serious flaws have not been taken into account in interpreting results of EDC research. We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic. We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful, and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs.

  8. [Endocrine disruptors : Evidence from epidemiological studies necessitates a critical review of model systems].

    Science.gov (United States)

    Hoffmann, M; Gebauer, S; Nüchter, M; Baber, R; Ried, J; von Bergen, M; Kiess, W

    2017-06-01

    Endocrine disruptive chemicals (EDCs) cause adverse health effects through interaction with endocrine systems. They are classified by chemical structure, effects on specific endocrine systems, bioaccumulation, persistence in the environment, or clinically observable effects. For research of the complex mechanisms of action in the human body, only in vitro model systems have so far been available, that have insufficient high-throughput capacity, which makes risk evaluation more difficult. In addition, in industrial nations, living people are often exposed to mixtures of substances, with various effects. The clinical importance of epigenetic changes caused by the action of EDCs during vulnerable phases of development is currently unclear. Epidemiological studies are criticized because reproducibility is not always guaranteed. Nevertheless, they remain the method of choice for the development and analysis of suitable model systems. Positive associations, in spite of sometimes conflicting results, are key in the selection of factors that can then be analysed in model systems in an unbiased way. This article depicts the mainly positive epidemiological findings for EDC-caused effects in the fields of growth and metabolism, neurocognitive development and sexual development and reproduction. As a result, there is a need for closer linkage between epidemiological studies and mechanistic research into model systems, especially focusing on the interaction of different EDCs and the consequences of prenatal and early life exposure.

  9. Analytical methods for the endocrine disruptor compounds determination in environmental water samples.

    Science.gov (United States)

    Locatelli, Marcello; Sciascia, Francesco; Cifelli, Roberta; Malatesta, Luciano; Bruni, Pantaleone; Croce, Fausto

    2016-02-19

    The potential risk of exposure to different xenobiotics, which can modulate the endocrine system and represent a treat for the wellness of an increasing number of people, has recently drawn the attention of international environmental and health agencies. Several agents, characterized by structural diversity, may interfer with the normal endocrine functions that regulate cell growth, homeostasis and development. Substances such as pesticides, herbicides, plasticizers, metals, etc. having endocrine activity (EDCs) are used in agriculture and industry and are also used as drugs for humans and animals. A difficulty in the analytical determination of these substances is the complexity of the matrix in which they are present. In fact, the samples most frequently analyzed consist of groundwater and surface water, including influent and effluent of wastewater treatment plants and drinking water. In this review, several sample pretreatment protocols, assays and different instrumental techniques recently used in the EDCs determination have been considered. This review concludes with a paragraph in which the most recent hyphenated-instrument techniques are treated, highlighting their sensitivity and selectivity for the analyses of environmental water samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, α-zearalanol, and genistein): Effects on interferon-γ

    International Nuclear Information System (INIS)

    Calemine, Jillian; Zalenka, Julie; Karpuzoglu-Sahin, Ebru; Ward, Daniel L.; Lengi, Andrea; Ahmed, S. Ansar

    2003-01-01

    The immune system is a potential target for estrogenic endocrine disrupters. To date, there is limited information on whether estrogenic endocrine disruptors modulate the immune system of aged individuals. To address this issue, groups of 74-week-old mice were given nine oral doses of selected estrogenic endocrine disrupters: diethylstilbestrol (DES, 3 μg/100 g bw), α-zearalanol (0.5 mg/100 g bw), or genistein (0.15 mg/100 g bw) in corn oil, or corn oil alone, over 2.5 weeks. Both developmental (thymus) and mature (spleen) lymphoid organs were affected, although specific effects varied with the chemical. DES significantly decreased thymocyte numbers. However, relative percentages of thymocyte subsets were not altered. While splenic cellularity and percentages of T and B cells were unchanged, splenocytes from DES-exposed mice had significantly decreased ability to proliferate in response to Concanavalin-A (Con-A). Con-A-activated splenocytes from mice treated with genistein or α-zearalanol had decreased levels of interferon-γ (IFNγ) protein in their culture supernatants compared to similar cultures from oil-treated mice. RT-PCR analysis of Con-A-activated splenocytes revealed that the expression of IFNγ gene is altered by DES or genistein treatment. Together, these results suggest that estrogenic endocrine disruptors modulate the immune system of aged mice

  11. Changes in male reproductive health and effects of endocrine disruptors in Scandinavian countries

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2002-01-01

    Full Text Available Male reproductive health has deteriorated in many ways during the last decades. The incidence of testicular cancer has rapidly increased in Europe and European-derived populations. Sperm concentrations have declined and sperm motility and morphology have worsened in many areas. Both adverse trends have been shown to be associated with year of birth. Older birth cohorts have better reproductive health than the younger generations. Incidences of cryptorchidism and hypospadias have also increased according to several studies. The reasons for secular trends are unknown, but the rapid pace of the change points to environmental causes. Endocrine disrupting chemicals have been hypothesized to influence male reproductive health.

  12. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    Science.gov (United States)

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  13. Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?

    Science.gov (United States)

    Bliatka, D; Lymperi, S; Mastorakos, G; Goulis, D G

    2017-05-01

    The so-called "endocrine disruption hypothesis" suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non-exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized-controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well-designed studies of case-control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures. © 2017 American Society of Andrology and European Academy of Andrology.

  14. Proteomic investigation of male Gammarus fossarum, a freshwater crustacean, in response to endocrine disruptors.

    Science.gov (United States)

    Trapp, Judith; Armengaud, Jean; Pible, Olivier; Gaillard, Jean-Charles; Abbaci, Khedidja; Habtoul, Yassine; Chaumot, Arnaud; Geffard, Olivier

    2015-01-02

    While the decrease in human sperm count in response to pollutants is a worldwide concern, little attention is being devoted to its causes and occurrence in the biodiversity of the animal kingdom. Arthropoda is the most species-rich phyla, inhabiting all aquatic and terrestrial ecosystems. During evolution, key molecular players of the arthropod endocrine system have diverged from the vertebrate counterparts. Consequently, arthropods may have different sensitivities toward endocrine disrupting chemicals (EDCs). Here alteration of sperm quality in a crustacean, Gammarus fossarum, a popular organism in freshwater risk assessment, was investigated after laboratory exposure to various concentrations of three different xenobiotics: cadmium, methoxyfenozide, and pyriproxyfen. The integrity of the reproductive process was assessed by means of sperm-quality markers. For each substance, semiquantitative/relative proteomics based on spectral counting procedure was carried out on male gonads to observe the biological impact. The changes in a total of 871 proteins were monitored in response to toxic pressure. A drastic effect was observed on spermatozoon production, with a dose-response relationship. While exposure to EDCs leads to strong modulations of male-specific proteins in testis, no induction of female-specific proteins was noted. Also, a significant portion of orphans proved to be sensitive to toxic stress.

  15. Isolation and characterisation of endocrine disruptor nonylphenol-using bacteria from South Africa

    Directory of Open Access Journals (Sweden)

    Lehlohonolo B. Qhanya

    2017-05-01

    Full Text Available Endocrine disrupting chemicals (EDCs are synthetic chemicals that alter the function of endocrine systems in animals including humans. EDCs are considered priority pollutants and worldwide research is ongoing to develop bioremediation strategies to remove EDCs from the environment. An understanding of indigenous microorganisms is important to design efficient bioremediation strategies. However, much of the information available on EDCs has been generated from developed regions. Recent studies have revealed the presence of different EDCs in South African natural resources, but, to date, studies analysing the capabilities of microorganisms to utilise/degrade EDCs have not been reported from South Africa. Here, we report for the first time on the isolation and enrichment of six bacterial strains from six different soil samples collected from the Mpumalanga Province, which are capable of utilising EDC nonylphenol as a carbon source. Furthermore, we performed a preliminary characterisation of isolates concerning their phylogenetic identification and capabilities to degrade nonylphenol. Phylogenetic analysis using 16S rRNA gene sequencing revealed that four isolates belonged to Pseudomonas and the remaining two belonged to Enterobacteria and Stenotrophomonas. All six bacterial species showed degradation of nonylphenol in broth cultures, as HPLC analysis revealed 41–46% degradation of nonylphenol 12 h after addition. The results of this study represent the beginning of identification of microorganisms capable of degrading nonylphenol, and pave the way for further exploration of EDC-degrading microorganisms from South Africa.

  16. Are endocrine disruptors among the causes of the deterioration of aquatic biodiversity?

    Science.gov (United States)

    Zhou, Jin; Cai, Zhong-Hua; Zhu, Xiao-Shan

    2010-07-01

    Exposure to environmental pollutants such as endocrine-disrupting compounds (EDCs) is now taken into account to explain partially the biodiversity decline of aquatic ecosystems. Much research has demonstrated that EDCs can adversely affect the endocrine system, reproductive health, and immune function in aquatic species. These toxicological effects include 1) interference with normal hormonal synthesis, release, and transport, 2) impairment of growth, development, and gonadal maturation, and 3) increased sensitivity to environmental stressors. Recent studies also have confirmed that EDCs have carcinogenic and mutagenic potential. In essence, these changes in physiological and biochemical parameters reflect, to some extent, some phenotypic characteristics of the deterioration of aquatic biodiversity. At present, evidence at the molecular level shows that exposure to EDCs can trigger genotoxicity, such as DNA damage, and can reduce genetic diversity. Field studies have also provided more direct evidence that EDCs contribute to the population decrease and biodiversity decline. Evolutionary toxicology and multigenerational toxicity tests have further demonstrated that EDCs can damage an organism's offspring and eventually likely lead to loss of evolutionary potential. Taken together, these results provide some basis for understanding the relationship between variety deterioration and EDC exposure. It is conceivable that there is a causal association between EDC exposure and variety deterioration of aquatic organisms. (c) 2010 SETAC.

  17. Biosensors for environmental monitoring of aquatic systems. Bioanalytical and chemical methods for endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Barcelo, Damia [IDAEA-CSIC, Barcelona (Spain). Dept. of Environmental Chemistry; Girona Univ. (ES). Catalan Inst. for Water Research (ICRA); Hansen, Peter-Diedrich (eds.) [Berlin Inst. of Technology, Berlin (Germany). Dept. of Ecotoxicology

    2009-07-01

    There is an increasing need for effective methods of estimating the risks caused by the large number of pollutants released into the environment by human activities. This volume provides an overview of biosensors as a key tool for the environmental monitoring of aquatic systems. Biosensor technology is based on a specific biological recognition element in combination with a transducer for signal processing. In particular, the detection and identification of endocrine-disrupting compounds and other toxins in wastewater are treated in detail. Biosensors are presented as a practical alternative or supplement to traditional chromatographic techniques. Emphasis is also placed on the validation of the applied technology and its application to real-world environmental samples. (orig.)

  18. Per- and polyfluoroalkyl substances (PFASs) – New endocrine disruptors in polar bears (Ursus maritimus)?

    DEFF Research Database (Denmark)

    Pedersen, Kathrine Eggers; Letcher, Robert J.; Sonne, Christian

    2016-01-01

    Per- and polyfluoroalkyl substances (PFASs) are emerging in the Arctic and accumulate in brain tissues of East Greenland (EG) polar bears. In vitro studies have shown that PFASs might possess endocrine disrupting abilities and therefore the present study was conducted to investigate potential PFAS...... induced alterations in brain steroid concentrations. The concentrations of eleven steroid hormones were determined in eight brain regions from ten EG polar bears. Pregnenolone (PRE), the dominant progestagen, was found in mean concentrations of 5-47ng/g (ww) depending on brain region. PRE showed...... significantly (pbears. Dehydroepiandrosterone (DHEA) found in mean concentrations 0.67-4.58ng/g (ww) was the androgen found in highest concentrations. Among the estrogens estrone (E1) showed mean concentrations of 0.90-2.21ng/g (ww) and was the most...

  19. Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

    DEFF Research Database (Denmark)

    van der Meer, Thomas P; Artacho-Cordón, Francisco; Swaab, Dick F

    2017-01-01

    Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain...... and BMI parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A......, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross...

  20. The influence of endocrine disruptors on growth and development of children.

    Science.gov (United States)

    DiVall, Sara A

    2013-02-01

    This review describes the most recent data about the effects of endocrine disrupting compounds (EDCs) on infant and early childhood growth and reproductive tract development as well as controversies in the field. EDCs are present in pregnant women, young children and adolescents. Whether the level of exposure contributes to disease is an ongoing debate. Epidemiological studies suggest associations between prenatal EDC exposure and disease outcome, but animal studies using controlled EDC exposure have varying results with underlying mechanisms largely unknown. Human exposure to EDCs is widespread; bisphenol A, phthalates and persistent organic pollutants are detectable in all age groups and geographical locations in the USA. Epidemiological and animal studies suggest that phthalates and bisphenol A have adverse effects on birth weight, promote development of childhood obesity and adversely affect male reproductive tract development. Differences in the interpretation of available studies underlie the disparate conclusions of scientific and regulatory body's panels on potential toxicological effects of EDCs at current levels of human exposure.

  1. Developmental toxicity of endocrine disruptors in early life stages of zebrafish, a genetic and embryogenesis study.

    Science.gov (United States)

    Santos, Dércia; Matos, Manuela; Coimbra, Ana M

    2014-01-01

    Endocrine disrupting compounds (EDCs) are capable of interfering with the endocrine system and are increasingly widespread in the aquatic environments. In the present study, zebrafish (Danio rerio) embryos and larvae were used to assess how EDCs may interfere with embryogenesis. Therefore, zebrafish embryos were exposed to 17α-ethinylestradiol (EE2: 0.4, 2, 4 and 20 ng/L), genistein (Gen: 2, 20, 200 and 2000 ng/L) and fadrozole (Fad: 2, 10, 50 and 250 μg/L), between 2 and 144 h post-fertilization (hpf). Somite development, heartbeat, malformations, mortality and hatching rates were evaluated. In parallel, the expression patterns of hormone receptors (esr1, esr2a, esr2b and ar) and apoptotic pathways related genes (p53 and c-jun) were determined using quantitative real-time PCR. Results showed that EE2, Gen and Fad caused a higher mortality and also malformations in larvae compared with control. A significant toxic effect was observed in the heartbeat rate, at 144 hpf, in larvae exposed to EE2 and Fad. QPCR revealed alterations in the expression levels of all the evaluated genes, at different time points. esr1 and c-jun genes were upregulated by EE2 and Gen exposure while the expression of esr2a, esr2b and ar genes was downregulated. Fad exposure decreased esr1, p53 and c-jun expression levels. This study shows a toxic effect of EE2, Gen and Fad to vertebrate embryogenesis and a relation between hormones action and apoptosis pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Per- and polyfluoroalkyl substances (PFASs) - New endocrine disruptors in polar bears (Ursus maritimus)?

    Science.gov (United States)

    Pedersen, Kathrine Eggers; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2016-11-01

    Per- and polyfluoroalkyl substances (PFASs) are emerging in the Arctic and accumulate in brain tissues of East Greenland (EG) polar bears. In vitro studies have shown that PFASs might possess endocrine disrupting abilities and therefore the present study was conducted to investigate potential PFAS induced alterations in brain steroid concentrations. The concentrations of eleven steroid hormones were determined in eight brain regions from ten EG polar bears. Pregnenolone (PRE), the dominant progestagen, was found in mean concentrations of 5-47ng/g (ww) depending on brain region. PRE showed significantly (pbears. Dehydroepiandrosterone (DHEA) found in mean concentrations 0.67-4.58ng/g (ww) was the androgen found in highest concentrations. Among the estrogens estrone (E1) showed mean concentrations of 0.90-2.21ng/g (ww) and was the most abundant. Remaining steroid hormones were generally present in concentrations below 2ng/g (ww). Steroid levels in brain tissue could not be explained by steroid levels in plasma. There was however a trend towards increasing estrogen levels in plasma resulting in increasing levels of androgens in brain tissue. Correlative analyses showed positive associations between PFASs and 17α-hydroxypregnenolone (OH-PRE) (e.g. perflouroalkyl sulfonates (∑PFSA): pbears. It is, however, not possible to determine whether alterations in brain steroid concentrations arise from interference with de novo steroid synthesis or via disruption of peripheral steroidogenic tissues mainly in gonads and feedback mechanisms. Steroids are important for brain plasticity and gender specific behavior as well as postnatal development and sexually dimorph brain function. The present work indicates an urgent need for a better mechanistic understanding of how PFASs may affect the endocrine system of polar bears and potentially other mammal species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Nuclear receptors and endocrine disruptors in fetal and neonatal testes: a gapped landscape.

    Directory of Open Access Journals (Sweden)

    Virginie eRouiller-Fabre

    2015-05-01

    Full Text Available During the last decades, many studies reported that male reproductive disorders are increasing among humans. It is currently acknowledged that these abnormalities can result from fetal exposure to environmental chemicals that are progressively becoming more concentrated and widespread in our environment. Among the chemicals present in the environment (air, water, food and many consumer products, several can act as endocrine disrupting compounds (EDCs, thus interfering with the endocrine system. Phthalates, bisphenol A (BPA and diethylstilbestrol (DES have been largely incriminated, particularly during the fetal and neonatal period, due to their estrogenic and/or anti-androgenic properties. Indeed, many epidemiological and experimental studies have highlighted their deleterious impact on fetal and neonatal testis development. As EDCs can affect many different genomic and non-genomic pathways, the mechanisms underlying the adverse effects of EDC exposure are difficult to elucidate. Using literature data and results from our laboratory, in the present review we discuss the role of classical nuclear receptors (genomic pathway in the fetal and neonatal testis response to EDC exposure, particularly to phthalates, BPA and DES. Among the nuclear receptors we focused on some of the most likely candidates, such as peroxisome-proliferator activated receptor (PPAR, androgen receptor (AR, estrogen receptors (ERα and β, liver X receptors (LXR and small heterodimer partner (SHP. First, we describe the expression and potential functions (based on data from studies using receptor agonists and mouse knockout models of these nuclear receptors in the developing testis. Then, for each EDC studied, we summarize the main evidences indicating that the reprotoxic effect of each EDC under study is mediated through a specific nuclear receptor(s. We also point-out the involvement of other receptors and nuclear receptor-independent pathways.

  4. New endocrine disruptors: their importance in pediatric population Nuevos disruptores endocrinos: su importancia en la población pediátrica

    OpenAIRE

    Juan Manuel Alfaro Velásquez; Alejandro Román González

    2005-01-01

    Changes in the environment that have taken place during the last 40 years have generated frequent contacts with natural and synthetic chemical products with potential endocrine-disrupting roles; among them: the intensive use of pesticides after the introduction of DDT, the petrochemical derivatives of the plastic industry, the synthetic medicines and the growing market of clothes, cleaning products, cosmetics and motor vehicles. In every one of these groups there are signals of an endocrine-d...

  5. A multi-residue method for characterization of endocrine disruptors in gaseous and particulate phases of ambient air

    Science.gov (United States)

    Alliot, Fabrice; Moreau-Guigon, Elodie; Bourges, Catherine; Desportes, Annie; Teil, Marie-Jeanne; Blanchard, Martine; Chevreuil, Marc

    2014-08-01

    A number of semi-volatile compounds occur in indoor air most of them being considered as potent endocrine disruptors and thus, exerting a possible impact upon health. To assess their concentration levels in indoor air, we developed and validated a method for sampling and multi-residue analysis of 58 compounds including phthalates, polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), parabens, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) in gaseous and particulate phases of air. We validated each step of procedures from extraction until analysis. Matrice spiking were performed at extraction, fractionation and purification stages. The more volatile compounds were analyzed with a gas chromatography system coupled with a mass spectrometer (GC/MS) or with a tandem mass spectrometer (GC/MS/MS). The less volatile compounds were analyzed with a liquid chromatography system coupled with a tandem mass spectrometer (LC/MS/MS). Labeled internal standard method was used ensuring high quantification accuracy. The instrumental detection limits were under 1 pg for all compounds and therefore, a limit of quantification averaging 1 pg m-3 for the gaseous and the particulate phases and a volume of 150 m3, except for phthalates, phenol compounds and BDE-209. Satisfactory recoveries were found except for phenol compounds. That method was successfully applied to several indoor air samples (office, apartment and day nursery) and most of the targeted compounds were quantified, mainly occurring in the gaseous phase. The most abundant were phthalates (up to 918 ng m-3 in total air), followed by PCBs > parabens > BPA > PAHs > PBDEs.

  6. Plastics derived endocrine disruptors (BPA, DEHP and DBP induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    Directory of Open Access Journals (Sweden)

    Mohan Manikkam

    Full Text Available Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3 following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA, bis(2-ethylhexylphthalate (DEHP and dibutyl phthalate (DBP at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  7. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    Science.gov (United States)

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2013-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  8. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  9. Multi-residue analysis of free and conjugated hormones and endocrine disruptors in rat testis by QuEChERS-based extraction and LC-MS/MS.

    Science.gov (United States)

    Pouech, Charlène; Tournier, Mikaël; Quignot, Nadia; Kiss, Agneta; Wiest, Laure; Lafay, Florent; Flament-Waton, Marie-Magdeleine; Lemazurier, Emmanuel; Cren-Olivé, Cécile

    2012-03-01

    Endocrine disrupting compounds (EDCs) are suspected to be responsible for many disorders of the human reproductive system. To establish a causality relationship between exposure to endocrine disruptors and disease, experiments on animals must be performed with improved or new analytical tools. Therefore, a simple, rapid, and effective multi-residue method was developed for the determination of four steroid hormones (i.e., testosterone, androstenedione, estrone, and estradiol), glucuronide and sulfate conjugates of estrone and estradiol and four endocrine disruptors in rat testis (i.e., bisphenol A, atrazine, and active metabolites of methoxychlor and vinclozolin). The sample preparation procedure was based on the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach. An analytical method was then developed to quantify these compounds at ultra-trace levels by liquid chromatography coupled to tandem mass spectrometry. The QuEChERS extraction was optimized with regard to the acetonitrile/water ratio used in the extraction step, the choice of the cleanup method and the acetonitrile/hexane ratio used in the cleanup step. The optimized extraction method exhibited recoveries between 89% and 108% for all tested compounds except the conjugates (31% to 58%). The detection limits of all compounds were below 20 ng g(-1) of wet weight of testis. The method was subsequently applied to determine the levels of hormones and EDCs in seven rat testis samples.

  10. Continuous removal of endocrine disruptors by versatile peroxidase using a two-stage system.

    Science.gov (United States)

    Taboada-Puig, Roberto; Lu-Chau, Thelmo A; Eibes, Gemma; Feijoo, Gumersindo; Moreira, Maria T; Lema, Juan M

    2015-01-01

    The oxidant Mn(3+) -malonate, generated by the ligninolytic enzyme versatile peroxidase in a two-stage system, was used for the continuous removal of endocrine disrupting compounds (EDCs) from synthetic and real wastewaters. One plasticizer (bisphenol-A), one bactericide (triclosan) and three estrogenic compounds (estrone, 17β-estradiol, and 17α-ethinylestradiol) were removed from wastewater at degradation rates in the range of 28-58 µg/L·min, with low enzyme inactivation. First, the optimization of three main parameters affecting the generation of Mn(3+) -malonate (hydraulic retention time as well as Na-malonate and H2 O2 feeding rates) was conducted following a response surface methodology (RSM). Under optimal conditions, the degradation of the EDCs was proven at high (1.3-8.8 mg/L) and environmental (1.2-6.1 µg/L) concentrations. Finally, when the two-stage system was compared with a conventional enzymatic membrane reactor (EMR) using the same enzyme, a 14-fold increase of the removal efficiency was observed. At the same time, operational problems found during EDCs removal in the EMR system (e.g., clogging of the membrane and enzyme inactivation) were avoided by physically separating the stages of complex formation and pollutant oxidation, allowing the system to be operated for a longer period (∼8 h). This study demonstrates the feasibility of the two-stage enzymatic system for removing EDCs both at high and environmental concentrations. © 2015 American Institute of Chemical Engineers.

  11. The Effects of Endocrine Disruptors on Adipogenesis and Osteogenesis in Mesenchymal Stem Cells: A Review

    Science.gov (United States)

    Bateman, Marjorie E.; Strong, Amy L.; McLachlan, John A.; Burow, Matthew E.; Bunnell, Bruce A.

    2017-01-01

    Endocrine-disrupting chemicals (EDCs) are prevalent in the environment, and epidemiologic studies have suggested that human exposure is linked to chronic diseases, such as obesity and diabetes. In vitro experiments have further demonstrated that EDCs promote changes in mesenchymal stem cells (MSCs), leading to increases in adipogenic differentiation, decreases in osteogenic differentiation, activation of pro-inflammatory cytokines, increases in oxidative stress, and epigenetic changes. Studies have also shown alteration in trophic factor production, differentiation ability, and immunomodulatory capacity of MSCs, which have significant implications to the current studies exploring MSCs for tissue engineering and regenerative medicine applications and the treatment of inflammatory conditions. Thus, the consideration of the effects of EDCs on MSCs is vital when determining potential therapeutic uses of MSCs, as increased exposure to EDCs may cause MSCs to be less effective therapeutically. This review focuses on the adipogenic and osteogenic differentiation effects of EDCs as these are most relevant to the therapeutic uses of MSCs in tissue engineering, regenerative medicine, and inflammatory conditions. This review will highlight the effects of EDCs, including organophosphates, plasticizers, industrial surfactants, coolants, and lubricants, on MSC biology. PMID:28119665

  12. Endocrine Disruptors and the Breast: Early Life Effects and Later Life Disease

    Science.gov (United States)

    Macon, Madisa B.

    2013-01-01

    Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5–27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future. PMID:23417729

  13. Diet-dependence of metabolic perturbations mediated by the endocrine disruptor tolylfluanid

    Directory of Open Access Journals (Sweden)

    Shane M Regnier

    2018-01-01

    Full Text Available Emerging evidence implicates environmental endocrine-disrupting chemicals (EDCs in the pathogenesis of metabolic diseases such as obesity and diabetes; however, the interactions between EDCs and traditional risk factors in disease pathogenesis remain incompletely characterized. The present study interrogates the interaction of the EDC tolylfluanid (TF and traditional dietary stressors in the promotion of metabolic dysfunction. Eight-week-old male C57BL/6 mice were fed a high-fat, high-sucrose diet (HFHSD or a high-sucrose diet (HSD, with or without TF supplementation at 100 μg/g, for 12 weeks. Food intake, body weight and visceral adiposity were quantified. Glucose homeostasis was interrogated by intraperitoneal glucose and insulin tolerance tests at 9 and 10 weeks of exposure, respectively. After 12 weeks of dietary exposure, metabolic cage analyses were performed to interrogate nutrient handling and energy expenditure. In the background of an HFHSD, TF promoted glucose intolerance; however, weight gain and insulin sensitivity were unchanged, and visceral adiposity was reduced. In the background of an HSD, TF increased visceral adiposity; however, glucose tolerance and insulin sensitivity were unchanged, while weight gain was reduced. Thus, these analyses reveal that the metabolic perturbations induced by dietary exposure to TF, including the directionality of alterations in body weight gain, visceral adiposity and glucose homeostasis, are influenced by dietary macronutrient composition, suggesting that populations may exhibit distinct metabolic risks based on their unique dietary characteristics.

  14. THE MERCURY AS ENDOCRINE DISRUPTOR ON THE ADRENOCARCINOMA CELL LINE H295R

    Directory of Open Access Journals (Sweden)

    Mária Rácz

    2012-02-01

    Full Text Available Mercury (Hg is one of the oldest heavy metals, which has various effects on the endocrine system. Target of this in vitro study was to determine the effects of mercuric chloride (HgCl2 on the steroidogenesis in adrenocarcinoma cells isolated from the cell line H295R. We examined the dose-dependent changes of HgCl2 on the production of testosterone (T. Release of steroid hormone by adrenocarcinoma cells was determined after 48 h HgCl2 exposure (1.0; 5.0; 25; 50; 100 µmol.dm-3 using an ELISA assay. Decreased hormone production was detected in all experimental groups with the addition of HgCl2. In regards to the release of T, significant differences (P<0.01 between the control group and all experimental groups was recorded. The lowest amount of T was found after administration at doses >50 μmol.dm-3 of HgCl2. Obtained data indicate, that Hg has toxic effect on the testosterone production and its toxicity can reflect also in the others pathways of the cells.

  15. Using adverse outcome pathway analysis to guide development of high-throughput screening assays for thyroid-disruptors

    Science.gov (United States)

    Using Adverse Outcome Pathway Analysis to Guide Development of High-Throughput Screening Assays for Thyroid-Disruptors Katie B. Paul1,2, Joan M. Hedge2, Daniel M. Rotroff4, Kevin M. Crofton4, Michael W. Hornung3, Steven O. Simmons2 1Oak Ridge Institute for Science Education Post...

  16. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines.

    Science.gov (United States)

    Gasnier, Céline; Dumont, Coralie; Benachour, Nora; Clair, Emilie; Chagnon, Marie-Christine; Séralini, Gilles-Eric

    2009-08-21

    Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.

  17. Endocrine disruptor regulation of microRNA expression in breast carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Syreeta L Tilghman

    Full Text Available Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER. The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs and more recently non-coding RNAs (ncRNAs. Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+ and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer.

  18. Nuevos disruptores endocrinos: su importancia en la población pediátrica New endocrine disruptors: their importance in pediatric population

    OpenAIRE

    Juan Manuel Alfaro Velásquez; Alejandro Román González

    2005-01-01

    Los cambios de nuestro hábitat en los últimos 40 años han generado contactos frecuentes con sustancias químicas tanto naturales como sintéticas que funcionan como disruptores endocrinos; son ejemplos los pesticidas ampliamente usados tras la introducción del DDT, los derivados petroquímicos en la industria del plástico, las medicinas sintéticas, y el volumen creciente de artículos de vestuario, aseo, cosmética y transporte. En cada uno de los grupos anotados hay señales de actividad de algún ...

  19. Environmental transport and fate of endocrine disruptors from non-potable reuse of municipal wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Hudson, B; Beller, H; Bartel, C M; Kane, S; Campbell, C; Grayson, A; Liu, N; Burastero, S

    2005-11-16

    This project was designed to investigate the important but virtually unstudied topic of the subsurface transport and fate of Endocrine Disrupting Compounds (EDCs) when treated wastewater is used for landscape irrigation (non-potable water reuse). Although potable water reuse was outside the scope of this project, the investigation clearly has relevance to such water recycling practices. The target compounds, which are discussed in the following section and include EDCs such as 4-nonylphenol (NP) and 17{beta}-estradiol, were studied not only because of their potential estrogenic effects on receptors but also because they can be useful as tracers of wastewater residue in groundwater. Since the compounds were expected to occur at very low (part per trillion) concentrations in groundwater, highly selective and sensitive analytical techniques had to be developed for their analysis. This project assessed the distributions of these compounds in wastewater effluents and groundwater, and examined their fate in laboratory soil columns simulating the infiltration of treated wastewater into an aquifer (e.g., as could occur during irrigation of a golf course or park with nonpotable treated water). Bioassays were used to determine the estrogenic activity present in effluents and groundwater, and the results were correlated with those from chemical analysis. In vitro assays for estrogenic activity were employed to provide an integrated measure of estrogenic potency of environmental samples without requiring knowledge or measurement of all bioactive compounds in the samples. For this project, the Las Positas Golf Course (LPGC) in the City of Livermore provided an ideal setting. Since 1978, irrigation of this area with treated wastewater has dominated the overall water budget. For a variety of reasons, a group of 10 monitoring wells were installed to evaluate wastewater impacts on the local groundwater. Additionally, these wells were regularly monitored for tritium ({sup 3}H

  20. The molecular mechanism of bisphenol A (BPA as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD simulations.

    Directory of Open Access Journals (Sweden)

    Lanlan Li

    Full Text Available Bisphenol A (BPA can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA.

  1. In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

    2004-09-15

    Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

  2. Effect of pharmaceutical potential endocrine disruptor compounds on protein disulfide isomerase reductase activity using di-eosin-oxidized-glutathione.

    Directory of Open Access Journals (Sweden)

    Danièle Klett

    Full Text Available BACKGROUND: Protein Disulfide Isomerase (PDI in the endoplasmic reticulum of all cells catalyzes the rearrangement of disulfide bridges during folding of membrane and secreted proteins. As PDI is also known to bind various molecules including hormones such as estradiol and thyroxin, we considered the hypothesis that adverse effects of endocrine-disrupter compounds (EDC could be mediated through their interaction with PDI leading to defects in membrane or secreted proteins. METHODOLOGY/PRINCIPAL FINDINGS: Taking advantage of the recent description of the fluorescence self quenched substrate di-eosin-oxidized-glutathione (DiE-GSSG, we determined kinetically the effects of various potential pharmaceutical EDCs on the in-vitro reductase activity of bovine liver PDI by measuring the fluorescence of the reaction product (E-GSH. Our data show that estrogens (ethynylestradiol and bisphenol-A as well as indomethacin exert an inhibition whereas medroxyprogesteroneacetate and nortestosterone exert a potentiation of bovine PDI reductase activity. CONCLUSIONS: The present data indicate that the tested EDCs could not only affect endocrine target cells through nuclear receptors as previously shown, but could also affect these and all other cells by positively or negatively affecting PDI activity. The substrate DiE-GSSG has been demonstrated to be a convenient substrate to measure PDI reductase activity in the presence of various potential EDCs. It will certainly be usefull for the screening of potential effect of all kinds of chemicals on PDI reductase activity.

  3. Exposure of rats to exogenous endocrine disruptors 17alpha-ethinylestradiol and benzo(a) pyrene and an estrogenic hormone estradiol induces expression of cytochromes P450 involved in their metabolism

    Czech Academy of Sciences Publication Activity Database

    Bořek-Dohalská, L.; Klusoňová, Z.; Holecová, J.; Martinková, M.; Bárta, F.; Dračínská, H.; Cajthaml, Tomáš; Stiborová, M.

    2016-01-01

    Roč. 37, Sup 1 (2016), s. 84-94 ISSN 0172-780X R&D Projects: GA ČR(CZ) GA15-02328S Institutional support: RVO:61388971 Keywords : endocrine disruptor * 17 alpha-ethinylestradiol * cytochrome P450 Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 0.918, year: 2016

  4. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J.D.; Chu, A.C.; Clark, G.C. [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M.D. [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M.S. [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  5. 75 FR 70248 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening

    Science.gov (United States)

    2010-11-17

    ... reasons, it is important to note that these exclusions do not imply that the Agency has no interest in the... 2007 Lindane 58-89-9 X Methanol 67-56-1 X Methoxychlor 72-43-5 X Methyl tert-butyl ether 1634-04-4 X...

  6. 75 FR 70557 - Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening Safe Drinking...

    Science.gov (United States)

    2010-11-17

    ... and for TSCA chemicals in 40 CFR part 792. Test order recipients would need to follow appropriate GLPs... data on the recipient's behalf. The designated lead for the consortium would need to complete the... recipient's ``Initial Response Form'' would need to include an explanation and documentation supporting its...

  7. 78 FR 35909 - Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening Safe Drinking...

    Science.gov (United States)

    2013-06-14

    ... in commerce. It is unclear what the commenter intends by requesting that EPA require self-disclosure... Agency's EDSP Web site. However, TSA and FOIA may apply and provide some protections against disclosure...

  8. Health surveillance and endocrine disruptors Vigilância sanitária e desreguladores endócrinos

    Directory of Open Access Journals (Sweden)

    William Waissmann

    2002-04-01

    Full Text Available The author discusses the extreme relevance of research on the presence of endocrine disruptors (EDs in products of interest to health surveillance (HS. Focusing on EDs, the author highlights the urgency of changes already under way in the direction of HS. The shift should be from product and product-registration approaches to the productive process and its realization in consumption, generation of contaminants, and alterations in the health of workers and the overall population. He briefly describes: regulatory gaps for dealing with EDs; difficulty in evaluating risk and suspension of the production and use of products with its characteristics and the need, as exemplified by such products, to enhance the inter-relationship among all stakeholders and to turn HS into a state-of-the-art technological setting, associated with the academic community and accountable to the public. The author reports on measures already taken in relation to EDs, including the establishment of a reference laboratory for analyzing persistent organic pollutants (POPs, interruption of the use of various POPs in Brazil and an initial review of requirements for registering pesticides under the Brazilian National Health Surveillance Agency (ANVISA.Descreve-se como da maior relevância, o estudo da presença de "desreguladores endócrinos" (DE em produtos sob interesse da vigilância sanitária (VS. Demonstra-se, tendo como foco os DE, como são urgentes as mudanças, já iniciadas, de direcionamento da VS. De abordagens centradas nos produtos e em ações cartoriais, há que se verter tanto para a análise do processo produtivo, de sua realização no consumo, na geração de contaminantes e nas alterações da saúde de trabalhadores e da população em geral. São descritas, de modo sucinto: deficiências normativas para o enfrentamento dos DE; a dificuldade de avaliação do risco que representam e a suspensão da produção e uso de produtos com suas características e; a

  9. Glifosato como desregulador endócrino químico / Glyphosate as an endocrine chemical disruptor

    Directory of Open Access Journals (Sweden)

    Renata Marino Romano

    2009-08-01

    Full Text Available ResumoDesreguladores endócrinos são moléculas exógenas ambientais que podem afetar a síntese, secreção, transporte, metabolismo, ligação, ação e catabolismo de hormônios naturais do organismo, podendo exercer seu efeito mesmo quando em mínimas quantidades. O glifosato é um herbicida utilizado no combate às plantas daninhas prejudiciais a diversas culturas, bastante efetivo, não seletivo e pós-emergente que inibe o crescimento da planta através da interferência com a produção de aminoácidos aromáticos essenciais pela inibição da fotossíntese. Em baixas concentrações não tóxicas ele causa efeito de desregulação sobre a enzima aromatase em células de placenta humana in vitro, reduzindo a atividade da enzima aromatase e reduzindo a expressão da proteína StAR (proteína de regulação rápida da esteroidogênese. Acontaminação do solo e da água tanto fluvial como subterrânea, pelo intenso uso do glifosato, pode levar a distúrbios reprodutivos, além da possibilidade da persistência de resíduos destas substâncias no sangue, na carne, no leite, na urina e nas fezes dos animais levando à recontaminação do solo e podendo chegar ao consumo humano. O objetivo desta revisão é apresentar informações atuais sobre a toxicologia do glifosato e a sua importância sobre a saúde humana, suscitando o debate nessa área, uma vez que a legislação brasileira ainda não contempla o controle desse tipo de efeito tóxico.AbstractEndocrine disruptors (EDs are exogenous molecular factors that may affect the synthesis, secretion, transport, metabolism, binding, action, and catabolism of the body’s natural hormones. They are able to produce their effect even when they are present in minimum quantities. Glyphosate is an herbicide used to combat weeds that are harmful to different plants. It is very effective, non-selective and post-emergent, inhibiting the plant growth by interfering with the production of essential

  10. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents.

    Science.gov (United States)

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Gérard, Arlette; Bourguignon, Jean-Pierre

    2015-07-01

    Puberty presents remarkable individual differences in timing reaching over 5 years in humans. We put emphasis on the two edges of the age distribution of pubertal signs in humans and point to an extended distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon. This suggests changing environmental influences including the possible role of nutrition, stress and endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms is very limited in humans. Using the rodent as a model, we examine the impact of environmental factors on the individual variations in pubertal timing and the possible underlying mechanisms. The capacity of environmental factors to shape functioning of the neuroendocrine system is thought to be maximal during fetal and early postnatal life and possibly less important when approaching the time of onset of puberty. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Photocatalytic degradation of endocrine disruptor Bisphenol-A in the presence of prepared CexZn1-xO nanocomposites under irradiation of sunlight.

    Science.gov (United States)

    Kamaraj, M; Ranjith, K S; Sivaraj, Rajeshwari; Kumar, R T Rajendra; Abdul Salam, Hasna

    2014-11-01

    Photocatalytic degradation of Bisphenol A (BPA), a representative endocrine disruptor chemical, was carried out under irradiation of sunlight in the presence of CexZn1-xO nanophotocatalyst. Cerium (Ce) ions were successfully incorporated into the bulk lattice of ZnO by simple co-precipitation process. The CexZn1-xO composite nanostructures exhibited higher photocatalytic efficiency than pure ZnO in the degradation of BPA under sunlight irradiation and nearly complete mineralization of BPA was achieved. The degradation rate was strongly dependent on factors such as the size and structure of catalyst, doping material concentration, BPA concentration, catalyst load, irradiation time and pH levels. This work suggested that the CexZn1-xO assisted photocatalytic degradation is a versatile, economic, environmentally benign and efficient method for BPA removal in the aqueous environment. Copyright © 2014. Published by Elsevier B.V.

  12. Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3-L1 Cell Line through Glucocorticoid Receptor Activation

    Science.gov (United States)

    Sargis, Robert M.; Johnson, Daniel N.; Choudhury, Rashikh A.; Brady, Matthew J.

    2014-01-01

    The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3-L1 cell line. Various EDCs were screened for glucocorticoid-like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator-activated receptor-γ. 3T3-L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte-specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes. PMID:19927138

  13. Endocrine disruptors and other inhibitors of 11β-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition.

    Science.gov (United States)

    Vitku, Jana; Starka, Luboslav; Bicikova, Marie; Hill, Martin; Heracek, Jiri; Sosvorova, Lucie; Hampl, Richard

    2016-01-01

    Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Endocrine disruptors in sludge wastewater treatment plants: environmental complications - doi: 10.4025/actascitechnol.v35i2.10619

    Directory of Open Access Journals (Sweden)

    Aldo Pacheco Ferreira

    2013-04-01

    Full Text Available Concern over exposure to endocrine disruptors (EDs and impacts on wildlife and human has gradually increased in importance in recent years. Wastewater systematically receives most if not all of these chemicals, so a deeper understanding of the fate of EDs in environment is sorely needed. We evaluated EDs concentration in the affluent and effluent from the Sludge Wastewater Treatment Plants (SWTPs Penha and Ilha do Governador. It was used as evaluation parameter the determination of some target compounds, such as: alkylphenols, 17β-estradiol, bisphenol A; complementing with measures of physical and chemical parameters: temperature, pH, dissolved oxygen, total suspended solids, volatile suspended solids, and total chemical oxygen demand. Samples were collected along the line of treatment of each SWTP, and after laboratory procedures, analyzed by LC-MS/MS and ELISA techniques. In some samples, we verified concentrations of chemical compounds with potential to disrupt the endocrine system of living organisms. Therefore, the release of this effluent, even within the effluent discharge standards (BRASIL, 2005 or in condition to be purified by the water course, may lead to physiological changes in the organisms of the receptor water body.  

  15. Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine

    Directory of Open Access Journals (Sweden)

    Gergely Jocsak

    2016-06-01

    Full Text Available Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs. While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous exposure to a combination of such chemicals; Methods: Here, we used an in vitro model to demonstrate how exposure to bisphenol A, zearalenone, arsenic, and 4-methylbenzylidene camphor, alone or in combination, affect estrogen receptor β (ERβ mRNA expression in primary cerebellar cell cultures. Additionally, we also show the modulatory role of intrinsic biological factors, such as estradiol (E2, triiodo-thyronine (T3, and glial cells, as potential effect modulators; Results: Results show a wide diversity in ED effects on ERβ mRNA expression, and that the magnitude of these ED effects highly depends on the presence or absence of E2, T3, and glial cells; Conclusion: The observed potency of the EDs to influence ERβ mRNA expression, and the modulatory role of E2, T3, and the glia suggests that environmental ED effects may be masked as long as the hormonal milieu is physiological, but may tend to turn additive or superadditive in case of hormone deficiency.

  16. Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study

    Science.gov (United States)

    Albouy-Llaty, Marion; Limousi, Frédérike; Carles, Camille; Dupuis, Antoine; Rabouan, Sylvie; Migeot, Virginie

    2016-01-01

    Background: The relationship between preterm birth (PTB) and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. Method: A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. Results: We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014–0.080) µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Conclusions: Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB. PMID:27517943

  17. Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study

    Directory of Open Access Journals (Sweden)

    Marion Albouy-Llaty

    2016-08-01

    Full Text Available Background: The relationship between preterm birth (PTB and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. Method: A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. Results: We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014–0.080 µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Conclusions: Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB.

  18. Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features

    Directory of Open Access Journals (Sweden)

    Cinzia La Rocca

    2015-10-01

    Full Text Available Internal levels of selected endocrine disruptors (EDs (i.e., perfluorooctane sulfonate (PFOS, perfluorooctanoic acid (PFOA, di-2-ethylhexyl-phthalate (DEHP, mono-(2-ethylhexyl-phthalate (MEHP, and bisphenol A (BPA were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs of same subjects, gene expression levels of a panel of nuclear receptors (NRs, namely estrogen receptor α (ERα estrogen receptor β (ERβ, androgen receptor (AR, aryl hydrocarbon receptor (AhR, peroxisome proliferator-activated receptor γ (PPARγ and pregnane X receptor (PXR were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.

  19. Estrogenic and androgenic activity of PCBs, their chlorinated metabolites and other endocrine disruptors estimated with two in vitro yeast assays

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Kateřina; Plačková, Martina; Novotná, V.; Cajthaml, Tomáš

    2009-01-01

    Roč. 407, č. 22 (2009), s. 5921-5925 ISSN 0048-9697 R&D Projects: GA MŠk LC06066; GA MŠk 2B06156; GA ČR GA525/09/1058 Institutional research plan: CEZ:AV0Z50200510 Keywords : endocrine distruptors * yeast bioassays * triclosan Subject RIV: EE - Microbiology, Virology Impact factor: 2.905, year: 2009

  20. Gonado-histopathological changes, intersex and endocrine disruptor responses in relation to contaminant burden in Tilapia species from Ogun River, Nigeria.

    Science.gov (United States)

    Ibor, Oju R; Adeogun, Aina O; Fagbohun, Olusegun A; Arukwe, Augustine

    2016-12-01

    In the present study, we investigated the occurrence of intersex condition, histopathological changes in the gonad and endocrine disruptor biomarker responses in Tilapia species (Tilaipia guineensis, Sarotherodon galileaus and Oreochromis niloticus) along the Ogun River, Nigeria. The study sites covered a length of 320 km and a total of 1074 tilapias were collected from three sampling sites (Abeokuta, Isheri and Ikorodu) with different degrees of anthropogenic contamination. Samples were also collected from an upstream putative control site (Igboho) along the Ogun River. Hepatic transcript levels for vitellogenin (Vtg), zona radiata (Zrp) and aromatase (cyp19a1) were analyzed using real-time PCR. Gross gonadal morphology revealed a 24% prevalence of intersex showing visible testis and ovary in phenotypic females (25.4%) or males (74.6%). The intersex condition paralleled histopathological changes (ovotestis or testis-ova) in the gonads of female and male fish, respectively. Plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), 11-ketotestosterone (11-KT) and estradiol-17β (E2) were measured using enzyme immunoassay, showing that male fish from downstream of the control site had significantly higher plasma E2, LH, and FSH concentrations compared to females. Similarly, Vtg, Zrp and cyp19a1 mRNA was significantly higher in males, compared to females. Analysis of contaminants showed the presence of 15 PCB congeners, lindane and dieldrin, and 4-iso-nonylphenol (4-iso-NP) and 4-tert-octylphenol (4-tert-OP) in fish muscle and sediment samples from Ogun River. Principal component analysis (PCA) revealed site and sex relationships between measured biological responses to groups of environmental contaminants, showing that the endocrine disruptive responses in fish were associated with biota and sediment contaminant burden. In addition, strong positive correlations were observed between male fish and Zrp, cyp19a1, E2, LH, FSH, PCBs, 4-iso

  1. Structural and functional evidences for the interactions between nuclear hormone receptors and endocrine disruptors at low doses.

    Science.gov (United States)

    Balaguer, Patrick; Delfosse, Vanessa; Grimaldi, Marina; Bourguet, William

    Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities. Here, we present a few representative examples to illustrate various means by which EDCs achieve high-affinity binding to NRs. These examples include the binding of the mycoestrogen α-zearalanol to estrogen receptors, the covalent interaction of organotins with the retinoid X- and peroxisome proliferator-activated receptors, and the cooperative binding of two chemicals to the pregnane X receptor. We also discuss some hypotheses that could further explain low-concentration effects of EDCs with weaker affinity towards NRs. Copyright © 2017. Published by Elsevier Masson SAS.

  2. 77 FR 12297 - Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening...

    Science.gov (United States)

    2012-02-29

    ... Halogenated Solvents Industry Alliance, Inc., and the People for the Ethical Treatment of Animals (PETA). The... Alliance, Inc., and the People for the Ethical Treatment of Animals (PETA). The petition requested that the...

  3. Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals and General Validation Principles

    Science.gov (United States)

    This document was developed by the EPA to provide guidance to staff and managers regarding the EDSP universe of chemicals and general validation principles for consideration of computational toxicology tools for chemical prioritization.

  4. In vitro screening for estrogenic endocrine disrupting compounds using Mozambique tilapia and sea bass scales.

    Science.gov (United States)

    Pinto, Patrícia I S; Estêvão, M Dulce; Santos, Soraia; Andrade, André; Power, Deborah M

    2017-09-01

    A wide range of estrogenic endocrine disruptors (EDCs) are accumulating in the environment and may disrupt the physiology of aquatic organisms. The effects of EDCs on fish have mainly been assessed using reproductive endpoints and in vivo animal experiments. We used a simple non-invasive assay to evaluate the impact of estrogens and EDCs on sea bass (Dicentrarchus labrax) and tilapia (Oreochromis mossambicus) scales. These were exposed to estradiol (E2), two phytoestrogens and six anthropogenic estrogenic/anti-estrogenic EDCs and activities of enzymes related to mineralized tissue turnover (TRAP, tartrate-resistant acid phosphatase and ALP, alkaline phosphatase) were measured. Semi-quantitative RT-PCR detected the expression of both membrane and nuclear estrogen receptors in the scales of both species, confirming scales as a target for E2 and EDCs through different mechanisms. Changes in TRAP or ALP activities after 30minute and 24h exposure were detected in sea bass and tilapia scales treated with E2 and three EDCs, although compound-, time- and dose-specific responses were observed for the two species. These results support again that the mineralized tissue turnover of fish is regulated by estrogens and reveals that the scales are a mineralized estrogen-responsive tissue that may be affected by some EDCs. The significance of these effects for whole animal physiology needs to be further explored. The in vitro fish scale bioassay is a promising non-invasive screening tool for E2 and EDCs effects, although the low sensitivity of TRAP/ALP quantification limits their utility and indicates that alternative endpoints are required. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Development of partial life-cycle experiments to assess the effects of endocrine disruptors on the freshwater gastropod Lymnaea stagnalis: a case-study with vinclozolin.

    Science.gov (United States)

    Ducrot, Virginie; Teixeira-Alves, Mickaël; Lopes, Christelle; Delignette-Muller, Marie-Laure; Charles, Sandrine; Lagadic, Laurent

    2010-10-01

    Long-term effects of endocrine disruptors (EDs) on aquatic invertebrates remain difficult to assess, mainly due to the lack of appropriate sensitive toxicity test methods and relevant data analysis procedures. This study aimed at identifying windows of sensitivity to EDs along the life-cycle of the freshwater snail Lymnaea stagnalis, a candidate species for the development of forthcoming test guidelines. Juveniles, sub-adults, young adults and adults were exposed for 21 days to the fungicide vinclozolin (VZ). Survival, growth, onset of reproduction, fertility and fecundity were monitored weekly. Data were analyzed using standard statistical analysis procedures and mixed-effect models. No deleterious effect on survival and growth occurred in snails exposed to VZ at environmentally relevant concentrations. A significant impairment of the male function occurred in young adults, leading to infertility at concentrations exceeding 0.025 μg/L. Furthermore, fecundity was impaired in adults exposed to concentrations exceeding 25 μg/L. Biological responses depended on VZ concentration, exposure duration and on their interaction, leading to complex response patterns. The use of a standard statistical approach to analyze those data led to underestimation of VZ effects on reproduction, whereas effects could reliably be analyzed by mixed-effect models. L. stagnalis may be among the most sensitive invertebrate species to VZ, a 21-day reproduction test allowing the detection of deleterious effects at environmentally relevant concentrations of the fungicide. These results thus reinforce the relevance of L. stagnalis as a good candidate species for the development of guidelines devoted to the risk assessment of EDs.

  6. Microsomal cytochrome P450-3A4 (CYP3A4) nanobiosensor for the determination of 2,4-dichlorophenol-An endocrine disruptor compound

    Energy Technology Data Exchange (ETDEWEB)

    Hendricks, Nicolette R.; Waryo, Tesfaye T.; Arotiba, Omotayo; Jahed, Nazeem; Baker, Priscilla G.L. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa); Iwuoha, Emmanuel I. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa)], E-mail: eiwuoha@uwc.ac.za

    2009-02-28

    Cytochrome P450-3A4 (CYP3A4) is a monooxygenase enzyme that plays a major role in the detoxification of bioactive compounds and hydrophobic xenobiotics (e.g. medicines, drugs, environmental pollutants, food supplements and steroids). Physiologically the monooxygenation reactions of this class II, microsomal, b-type heme enzyme, usually requires cytochrome P450 reductase, NADPH. A novel CYP3A4 biosensor system that essentially simplified the enzymatic redox processes by allowing electron transfer between the electrode and the enzyme redox centre to occur, without any need for the physiological redox partners, was developed for the detection of 2,4-dichlorophenol (2,4-DCP), a priority environmental pollutant and an endocrine disruptor. The biosensor, GC/Naf-Co(Sep){sup 3+}/CYP3A4/Naf, was constructed by encapsulating CYP3A4 in a Nafion-cobalt (III) sepulchrate (Naf-Co(Sep){sup 3+}) composite film on a glassy carbon (GC) electrode. The responses of the biosensor to 2,4-dichlorophenol, erythromycin (CYP3A4 native substrate) and ketoconazole (CYP 3A4 natural inhibitor) were studied by cyclic and square wave voltammetric techniques. The detection limit (DL) of the biosensor for 2,4-dichlorophenol was 0.043 {mu}g L{sup -1}, which is by an order of magnitude lower than the EU limit (0.3 {mu}g L{sup -1}) for any pesticide compound in ground water. The biosensor's DL is lower than the U.S. Environmental Protection Agency's drinking water equivalent level (DWEL) value for 2,4-DCP, which is 2 {mu}g L{sup -1}.

  7. Inhibition of the Functional Interplay between Endoplasmic Reticulum (ER) Oxidoreduclin-1α (Ero1α) and Protein-disulfide Isomerase (PDI) by the Endocrine Disruptor Bisphenol A*

    Science.gov (United States)

    Okumura, Masaki; Kadokura, Hiroshi; Hashimoto, Shoko; Yutani, Katsuhide; Kanemura, Shingo; Hikima, Takaaki; Hidaka, Yuji; Ito, Len; Shiba, Kohei; Masui, Shoji; Imai, Daiki; Imaoka, Susumu; Yamaguchi, Hiroshi; Inaba, Kenji

    2014-01-01

    Bisphenol A (BPA) is an endocrine disruptor that may have adverse effects on human health. We recently isolated protein-disulfide isomerase (PDI) as a BPA-binding protein from rat brain homogenates and found that BPA markedly inhibited PDI activity. To elucidate mechanisms of this inhibition, detailed structural, biophysical, and functional analyses of PDI were performed in the presence of BPA. BPA binding to PDI induced significant rearrangement of the N-terminal thioredoxin domain of PDI, resulting in more compact overall structure. This conformational change led to closure of the substrate-binding pocket in b′ domain, preventing PDI from binding to unfolded proteins. The b′ domain also plays an essential role in the interplay between PDI and ER oxidoreduclin 1α (Ero1α), a flavoenzyme responsible for reoxidation of PDI. We show that BPA inhibited Ero1α-catalyzed PDI oxidation presumably by inhibiting the interaction between the b′ domain of PDI and Ero1α; the phenol groups of BPA probably compete with a highly conserved tryptophan residue, located in the protruding β-hairpin of Ero1α, for binding to PDI. Consistently, BPA slowed down the reoxidation of PDI and caused the reduction of PDI in HeLa cells, indicating that BPA has a great impact on the redox homeostasis of PDI within cells. However, BPA had no effect on the interaction between PDI and peroxiredoxin-4 (Prx4), another PDI family oxidase, suggesting that the interaction between Prx4 and PDI is different from that of Ero1α and PDI. These results indicate that BPA, a widely distributed and potentially harmful chemical, inhibits Ero1-PDI-mediated disulfide bond formation. PMID:25122773

  8. An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors.

    Science.gov (United States)

    Gabb, Henry A; Blake, Catherine

    2016-08-01

    -associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155-1165; http://dx.doi.org/10.1289/ehp.1510529.

  9. First Year Growth in Relation to Prenatal Exposure to Endocrine Disruptors — A Dutch Prospective Cohort Study

    Science.gov (United States)

    de Cock, Marijke; de Boer, Michiel R.; Lamoree, Marja; Legler, Juliette; van de Bor, Margot

    2014-01-01

    Growth in the first year of life may already be predictive of obesity later in childhood. The objective was to assess the association between prenatal exposure to various endocrine disrupting chemicals (EDCs) and child growth during the first year. Dichloro-diphenyldichloroethylene (DDE), mono(2-ethyl-5-carboxypentyl)phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), polychlorinated biphenyl-153, perfluorooctanesulfonic acid, and perfluoro-octanoic acid were measured in cord plasma or breast milk. Data on weight, length, and head circumference (HC) until 11 months after birth was obtained from 89 mother-child pairs. Mixed models were composed for each health outcome and exposure in quartiles. For MEOHP, boys in quartile 1 had a higher BMI than higher exposed boys (p = 0.029). High DDE exposure was associated with low BMI over time in boys (0.8 kg/m2 difference at 11 m). Boys with high MECPP exposure had a greater HC (1.0 cm difference at 11 m) than other boys (p = 0.047), as did girls in the second quartile of MEHHP (p = 0.018) and DDE (p < 0.001) exposure. In conclusion, exposure to phthalates and DDE was associated with BMI as well as with HC during the first year after birth. These results should be interpreted with caution though, due to the limited sample size. PMID:25014249

  10. Impiego di materiali plastici nell'industria alimentare: rilascio di 'Endocrine Disruptors' valutato mediante test a breve termine in vitro

    Directory of Open Access Journals (Sweden)

    D. Reali

    2003-05-01

    Full Text Available

    Obiettivi: valutazione del rischio di esposizione della popolazione a composti chimici estrogenomimetici rilasciati da materiali plastici utilizzati nell’industria delle bevande e nel packaging di alimenti

    Metodi: messa a punto di un metodo di estrazione di composti organici da flussi acquosi tramite l’uso di resine di amberlite® XAD®-2 con passaggio di matrice acquosa (50ml/min attraverso tubi di adduzione. L’analisi chimica di eventuali composti chimici migranti da tubi e contenitori per bevande è stata effettuata con GC/MS e arricchimento con tecnica SPME. L’attività estrogeno mimetica degli estratti è stata saggiata con un test biologico a breve termine, il Yeast Estrogen Screen. Il costrutto di Saccharomyces cerevisiae è vettore di sequenze di DNA che codificano il recettore estrogenico alfaumano e i rispettivi response elements legati alla regione promotrice del gene reporter LacZ per la ßgalattosidasi. L’induzione di sintesi di ß-galattosidasi dipende dall’attivazione del gene reporter conseguente all’affinità di legame ligando-recettore e viene misurata spettrofotometricamente. La potenza estrogenica viene calcolata in riferimento all’attività elicitata dall’ormone naturale 17ß-estradiolo nelle stesse condizioni sperimentali preso come controllo positivo di riferimento (RIE.

    Risultati preliminari e Conclusioni: l’analisi tossicologica in vitro ha evidenziato che nell’acqua che è stata a contatto con silicone e PVC in condizioni dinamiche sono presenti composti chimici (1-10 μg/lt: con attività estrogeno-mimetica (RIE= 87.31;44.28. Sono emersi aspetti interessanti da studiare ulteriormente nell’ottica della promozione della sicurezza alimentare.

  11. Electrochemical enhancement of solar photocatalysis: degradation of endocrine disruptor bisphenol-A on Ti/TiO2 films.

    Science.gov (United States)

    Frontistis, Zacharias; Daskalaki, Vasileia M; Katsaounis, Alexandros; Poulios, Ioannis; Mantzavinos, Dionissios

    2011-04-01

    The photoelectrocatalytic oxidation over immobilized Ti/TiO(2) films in the presence of simulated solar light was investigated for the degradation of bisphenol-A (BPA) in water. The catalyst, consisting of 75:25 anatase:rutile, was prepared by a sol-gel method and characterized by cyclic voltammetry, X-ray diffraction and scanning electron microscopy. Experiments were conducted to assess the effect of applied current (0.02-0.32 mA/cm(2)), TiO(2) loading (1.3-9.2 mg), BPA concentration (120-820 μg/L), initial solution pH (1 and 7.5) and the aqueous matrix (pure water and treated effluent) on BPA photoelectrocatalytic degradation which was monitored by high performance liquid chromatography equipped with a fluorescence detector. The reaction was favored at anodic currents up to 0.04 mA/cm(2) and lower substrate concentrations, but it was hindered by the presence of residual organic matter and radical scavengers (e.g. bicarbonates) in treated effluents. Moreover, a pseudo-first order kinetic model could fit the experimental data well with the apparent reaction constant taking values between 2.9 and 32.4 10(-3)/min. The degradation of BPA by pure photocatalysis or electrochemical oxidation alone was also studied leading to partial substrate removal. In all cases, the contribution of applied potential to photocatalytic degradation was synergistic with the photocatalytic efficiency increasing between 24% and 97% possibly due to a more efficient separation and utilization of the photogenerated charge carriers. The effect of photoelectrocatalysis on the ecotoxic and estrogenic properties of BPA was also evaluated measuring the bioluminescence inhibition of Vibrio fischeri and performing the yeast estrogen screening assay, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. In vitro screening for endocrine disruptive activity in selected South ...

    African Journals Online (AJOL)

    Various waterborne anthropogenic contaminants disrupt the endocrine systems of wildlife and humans, targeting reproductive pathways, among others. Very little is known, however, regarding the occurrence of endocrine disruptive activity in South African freshwater ecosystems, and coastal ecosystems have not been ...

  13. Exposure of rats to exogenous endocrine disruptors 17alpha-ethinylestradiol and benzo(a)pyrene and an estrogenic hormone estradiol induces expression of cytochromes P450 involved in their metabolism.

    Science.gov (United States)

    Borek-Dohalska, Lucie; Klusonova, Zuzana; Holecova, Jana; Martinkova, Marketa; Barta, Frantisek; Dracinska, Helena; Cajthaml, Tomas; Stiborova, Marie

    2016-12-18

    The term "endocrine disruptor" (ED) is used for compounds that mimic or antagonize the effects of endogenous hormones. Synthetic estrogen 17α-ethinylestradiol (EE2) and a human carcinogen benzo[a]pyrene (BaP) are assigned as exogenous endocrine disruptors and an estrogenic hormone estradiol is a natural endogenous disruptor. Here, the potency of these three disruptors administered to rats individually and in combination to induce expression of cytochrome P450 (CYP) enzymes involved in their own metabolism (CYP1A1, 2C and 3A) in vivo was investigated. Changes in CYP protein expression after exposure of rats to BaP, EE2 or estradiol were analyzed by Western blotting. Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed. Whereas exposure to BaP induces expression of CYP1A1 protein and its marker activity (Sudan I oxidation) in liver, kidney and lung of rats, no significant induction of this CYP and its enzyme activity was produced by EE2 and estradiol. Treatment of BaP in combination with EE2 and/or estradiol decreased the BaP-mediated CYP1A1 induction in liver of exposed rats. BaP also induces CYP2C11 protein in rat liver and kidney, but does not increase its enzyme activity measured as testosterone 16α-hydroxylation. The enzyme activity of another enzyme of the 2C subfamily, CYP2C6, diclofenac 4'-hydroxylation, is even decreased by BaP. The CYP2C11 protein expression and/or its activity are also increased in liver of rats treated with EE2 and estradiol, but its expression is significantly decreased in lung. The CYP2C6 activity is also elevated by treatment of rats with EE2 and estradiol administered individually as well as in their combination. Whereas only a slight increase in CYP3A protein expression was found by BaP in rat liver, its enzyme activity, testosterone 6β-hydroxyalation, increased significantly in this organ. In contrast, no effect or even a decrease in CYP3A expression and its

  14. Microbial degradation of endocrine disruptors

    Czech Academy of Sciences Publication Activity Database

    Křesinová, Zdena; Svobodová, Kateřina; Cajthaml, Tomáš

    2009-01-01

    Roč. 103, č. 3 (2009), s. 200-207 ISSN 0009-2770 R&D Projects: GA MŠk LC06066; GA AV ČR KJB600200613 Institutional research plan: CEZ:AV0Z50200510 Keywords : WHITE-ROT FUNGI * ALKYLPHENOL POLYETHOXYLATE SURFACTANTS * POWDERED ACTIVATED CARBON Subject RIV: EE - Microbiology, Virology Impact factor: 0.717, year: 2009

  15. Disruptores endocrinos. El caso particular de los xenobióticos estrogénicos. II Estrógenos sintéticos Endocrine disrupters. The case of oestrogenic xenobiotics II: synthetic oestrogens

    Directory of Open Access Journals (Sweden)

    P. Martín Olmedo

    2001-11-01

    Full Text Available En los últimos años se ha puesto en evidencia que muchas sustancias químicas de origen antropogénico son capaces de alterar el sistema endocrino de los seres vivos y se ha acuñado el nombre de disruptores endocrinos para definirlas. El número de disruptores endocrinos es una preocupación creciente si se añade a la inclusión de nuevos compuestos químicos, hasta ahora insospechados, la información generada sobre sus precursores, metabolitos y productos de degradación que tan solo ahora empiezan a conocerse. No se ha podido definir una estructura química única que permita clasificar a un compuesto químico como mimetizador de las hormonas sexuales femeninas, de tal manera que estructuras químicas similares a los estrógenos naturales, basados en el ciclopentanoperhidrofenantreno, comparten con los estilbenos, bisfenoles, bifenilos, alquilfenoles, dioxinas, furanos y parabenes su efecto hormonal estrogénico. El reconocimiento de la actividad estrogénica en diferentes modelos biológicos se ha utilizado para actualizar el censo de xenoestrógenos y poner de manifiesto fuentes de exposición humana hasta el momento insospechadas.In recent years, it has been demonstrated that endocrine systems of living beings can be altered by many chemical substances of anthropogenic origin, designated as endocrine disrupters. There are growing concerns about the number of these endocrine disrupters. It has not been possible to define a single chemical structure that allows the classification of a chemical compound as a mimic of female sex hormones, so that chemical structures similar to natural estrogens, based on cyclopentanoperhydrophenanthrene, share their hormonal effect with stilbenes, bisphenols, alkylphenols, dioxins, furans and parabenes. The recognition of estrogenic activity in different biological models has been used to update the list of xenoestrogens and reveal sources of human exposure that were previously unknown. New previously

  16. Biological assessments of a mixture of endocrine disruptors at environmentally relevant concentrations in water following UV/H{sub 2}O{sub 2} oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, P.-J. [Department of Civil and Environmental Engineering, Duke University (United States); Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Rosenfeldt, Erik J. [Department of Civil and Environmental Engineering, Duke University (United States); Kullman, Seth W. [Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Hinton, David E. [Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Linden, Karl G. [Department of Civil and Environmental Engineering, Duke University (United States)]. E-mail: kglinden@duke.edu

    2007-04-15

    Numerous studies have investigated degradation of individual endocrine disrupting compounds (EDCs) in lab or natural waters. However, natural variations in water matrices and mixtures of EDCs in the environment may confound analysis of the treatment efficiency. Because chemical based analytical methods cannot represent the combined or synergistic activities between water quality parameters and/or the EDC mixtures at environmentally relevant concentrations ({mu}g L{sup -1}-ng L{sup -1}), bioanalytical assessments of residual estrogenic activity in treated water were used to evaluate the performance of the UV based advanced oxidation process for estrogenic contaminants in water. Four EDCs including estradiol (E{sub 2}), ethinyl estradiol (EE{sub 2}), bisphenol-A (BPA) and nonylphenol (NP) were spiked individually or as a mixture at {mu}g L{sup -1}-ng L{sup -1} in laboratory or natural river water. The removal rates of estrogenic activity were quantitatively evaluated by in vitro yeast estrogen screen (YES) and in vivo Vitellogenin (VTG) assays with Japanese medaka fish (Oryzias latipes). UV in combination with 10 ppm H{sub 2}O{sub 2} as an oxidation process was capable of decreasing in vitro and in vivo estrogenic activity, however, in vivo estrogenic activity of the EDC mixture in natural water was not completely removed at UV fluence up to 2000 mJ cm{sup -2}. The removal rates of in vitro estrogenic activity of the EDC mixtures were lower than those observed for single compounds, and slower in natural waters, likely due to lower steady-state concentrations of hydroxyl radicals ({center_dot}OH) in the presence of {center_dot}OH scavengers from the water matrix and EDC mixture.

  17. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of Experience to Improve Screening and Testing for Endocrine Active Chemicals##

    Science.gov (United States)

    This product is a brief description of the oral presentation given by Dr LE Gray Jr at the meeting for the T4 workshop report-Lessons learned, challenges, ansd opportunities: The U.S. Endocrine Disruptor Scrrening Program published in the journal ALTEX, edited by the Swiss Societ...

  18. Endocrine Disruptors Differentially Target ATP-Binding Cassette Transporters in the Blood-Testis Barrier and Affect Leydig Cell Testosterone Secretion In Vitro

    NARCIS (Netherlands)

    Dankers, A.C.A.; Roelofs, M.J.; Piersma, A.H.; Sweep, F.C.; Russel, F.G.M.; Berg, M. van den; Duursen, M.B. van; Masereeuw, R.

    2013-01-01

    Endocrine-disrupting chemicals (EDCs) are considered to cause testicular toxicity primarily via interference with steroid hormone function. Alternatively, EDCs could possibly exert their effects by interaction with ATP-binding cassette (ABC) transporters that are expressed in the blood-testis

  19. Using the Health Belief Model to Illustrate Factors That Influence Risk Assessment during Pregnancy and Implications for Prenatal Education about Endocrine Disruptors

    Science.gov (United States)

    Qiu, Xing; Chen, Shaw-Ree; Barrett, Emily S.; Velez, Marissa; Conn, Kelly; Heinert, Sara

    2014-01-01

    Endocrine disrupting chemicals (EDCs) such as Bisphenol A (BPA) and phthalates are ubiquitous in our environment and a growing body of research indicates that EDCs may adversely affect human development. Fetal development is particularly susceptible to EDC exposure, and prenatal care providers are being asked to educate women about the risks of…

  20. 78 FR 35922 - Endocrine Disruptor Screening Program; Final Second List of Chemicals and Substances for Tier 1...

    Science.gov (United States)

    2013-06-14

    ... regarding EDSP and requirements for Tier 1 and Tier 2 testing can be found on the Agency's EDSP Web site, at... second list based on the highly reactive physiochemical properties of the chemicals and test assay... reactive and incompatible with the testing assays. Other chemicals remain on the list as they are still in...

  1. Standard Evaluation Procedures (SEPs) and Data Entry Spreadsheet Templates (DESTs) for Endocrine Disruptor Screening Program (EDSP) Tier 1 Assays

    Science.gov (United States)

    This page provides information and access to Standard Evaluation Procedures (SEPs) and Data Entry Spreadsheet Templates (DESTs) developed by EPA's Office of Chemical Safety and Pollution Prevention (OCSPP).

  2. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria

    International Nuclear Information System (INIS)

    Adeogun, Aina O.; Onibonoje, Kolawole; Ibor, Oju R.; Omiwole, Roseline A.; Chukwuka, Azubuike V.; Ugwumba, Alex O.; Ugwumba, Adiaha A.A.; Arukwe, Augustine

    2016-01-01

    Highlights: • Occurrence and severity of intersex in Nigerian aquatic environment. • Estrogenic and reproductive developmental effects of effluents from a University community. • Biomarker of endocrine disruption in fish from a developing country. • Relationship between estrogenic responses and sediment contaminants burden in a dam used for University domestic water supply and for fisheries. • Possible health consequences of environmental contamination - Abstract: In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n = 57 and 32, males and females, respectively) and Tilapia guineensis (n = 23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam

  3. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria

    Energy Technology Data Exchange (ETDEWEB)

    Adeogun, Aina O.; Onibonoje, Kolawole; Ibor, Oju R.; Omiwole, Roseline A.; Chukwuka, Azubuike V.; Ugwumba, Alex O.; Ugwumba, Adiaha A.A. [Department of Zoology, University of Ibadan, Ibadan (Nigeria); Arukwe, Augustine, E-mail: arukwe@bio.ntnu.no [Department of Biology, Norwegian University of Science and Technology (NTNU), 7491 Trondheim (Norway)

    2016-05-15

    Highlights: • Occurrence and severity of intersex in Nigerian aquatic environment. • Estrogenic and reproductive developmental effects of effluents from a University community. • Biomarker of endocrine disruption in fish from a developing country. • Relationship between estrogenic responses and sediment contaminants burden in a dam used for University domestic water supply and for fisheries. • Possible health consequences of environmental contamination - Abstract: In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n = 57 and 32, males and females, respectively) and Tilapia guineensis (n = 23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam

  4. Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

    Science.gov (United States)

    Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

    2015-01-01

    Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

  5. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria.

    Science.gov (United States)

    Adeogun, Aina O; Onibonoje, Kolawole; Ibor, Oju R; Omiwole, Roseline A; Chukwuka, Azubuike V; Ugwumba, Alex O; Ugwumba, Adiaha A A; Arukwe, Augustine

    2016-05-01

    In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n=57 and 32, males and females, respectively) and Tilapia guineensis (n=23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam showed a high prevalence of intersex (34.8%), involving phenotypic males and females of both species. Analysis of sediment contaminant levels revealed that As, Cd, Pb, Hg and Ni (heavy metals), monobutyltin cation, 4-iso-nonyphenol and PCB congeners (138, 153 and 180) were significantly higher in Awba Dam, compared to the reference site. Principal component analysis (PCA) showed that fish variables were positively correlated with sediment contaminant burden at Awba Dam, indicating

  6. A comparative study of occurrence and fate of endocrine disruptors: diethyl phthalate and dibutyl phthalate in ASP- and SBR-based wastewater treatment plants.

    Science.gov (United States)

    Saini, Gita; Pant, Shalini; Singh, Shri Om; Kazmi, A A; Alam, Tanveer

    2016-11-01

    Phthalates are endocrine-disrupting chemicals which affect endocrine system by bio-accumulation in aquatic organisms and produce adverse health effects in aquatic organisms as well as human beings, when come in contact. Present study focuses on occurrence and removal of two phthalates: diethylphthalate (DEP) and dibutylphthalate (DBP) in two full-scale wastewater treatment plants (WWTPs) i.e. sewage treatment plants (STPs) based on well-adopted technologies, activated sludge process (ASP) and sequencing batch reactor (SBR).Gas chromatography-mass spectrometry (GC-MS) analysis was performed for both wastewater and sludge sample for determination and identification of the concentration of these compounds in both STPs by monitoring the STPs for 9 months. It was observed that the concentration of DEP was less than DBP in the influent of ASP and SBR. Average concentrations of DEP and DBP in sludge sample of ASP were found to be 2.15 and 2.08 ng/g, whereas in SBR plant, these values were observed as 1.71 and 2.01 ng/g, respectively. Concerning the removal efficiency of DEP, SBR and ASP plants were found effective with removal efficiency of 91.51 and 91.03 %, respectively. However, in the case of DBP, SBR showed lower removal efficiency (85.42 %) as compared to ASP (92.67 %). Comparative study of both plants proposed that in ASP plant, DBP reduction was higher than the SBR. Fourier transformation infrared (FTIR) analysis also confirmed the same result of sludge analysis for both STPs. Sludge disposal studied with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA) techniques confirmed that sludge of both STPs have high calorific value and can be used as fuel to make fuel-briquettes and bottom ash to make firebricks.

  7. Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem - Final Report - 09/15/1996 - 09/14/2000

    International Nuclear Information System (INIS)

    McLachlan, John A.

    2000-01-01

    The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites

  8. Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem - Final Report - 09/15/1996 - 09/14/2000

    Energy Technology Data Exchange (ETDEWEB)

    McLachlan, John A.

    2000-09-14

    The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites.

  9. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

    International Nuclear Information System (INIS)

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine

    2011-01-01

    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.

  10. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring.

    Science.gov (United States)

    Haraux, Elodie; Braun, Karine; Buisson, Philippe; Stéphan-Blanchard, Erwan; Devauchelle, Camille; Ricard, Jannick; Boudailliez, Bernard; Tourneux, Pierre; Gouron, Richard; Chardon, Karen

    2016-12-29

    Pregnant women are exposed to various chemical products at home and at work. Some of these products contain endocrine-disrupting chemicals (EDCs) such as cosmetics, pesticides, industrial chemicals, heavy metals, plastics or medications that could alter sexual differentiation and increase the risk of hypospadias. We evaluated maternal occupational and household exposures that could constitute risk factors for hypospadias. From 2011 to 2014, we enrolled 57 full-term newborns with hypospadias and three randomly selected controls per case (162 control newborns), matched for gestational age, from 11 maternity units in Picardy, France. Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history). Maternal occupational exposure was assessed by a job-exposure matrix for EDCs from a job history questionnaire completed by mothers. Odds ratios (OR) and 95% confidence intervals (CI) were calculated with univariate and multivariable logistic regression, and adjusted for relevant covariates. Multivariate analysis showed a strong association between hypospadias and potential maternal occupational exposure to EDCs and maternal household use of hair cosmetics (OR 6.1, 95% CI: 1.1-34.9; OR: 9.6, 95% CI: 1.4-66.1, respectively). Our results suggest that maternal occupational exposure to EDCs is a risk factor for hypospadias and suggests a possible influence of household use of hair cosmetics during early pregnancy on the incidence of hypospadias in the offspring. A larger study with more accurate exposure assessment should evaluate the impact of EDCs in hair cosmetics on the incidence of hypospadias.

  11. Quantification of endocrine disruptors and pesticides in water by gas chromatography-tandem mass spectrometry. Method validation using weighted linear regression schemes.

    Science.gov (United States)

    Mansilha, C; Melo, A; Rebelo, H; Ferreira, I M P L V O; Pinho, O; Domingues, V; Pinho, C; Gameiro, P

    2010-10-22

    A multi-residue methodology based on a solid phase extraction followed by gas chromatography-tandem mass spectrometry was developed for trace analysis of 32 compounds in water matrices, including estrogens and several pesticides from different chemical families, some of them with endocrine disrupting properties. Matrix standard calibration solutions were prepared by adding known amounts of the analytes to a residue-free sample to compensate matrix-induced chromatographic response enhancement observed for certain pesticides. Validation was done mainly according to the International Conference on Harmonisation recommendations, as well as some European and American validation guidelines with specifications for pesticides analysis and/or GC-MS methodology. As the assumption of homoscedasticity was not met for analytical data, weighted least squares linear regression procedure was applied as a simple and effective way to counteract the greater influence of the greater concentrations on the fitted regression line, improving accuracy at the lower end of the calibration curve. The method was considered validated for 31 compounds after consistent evaluation of the key analytical parameters: specificity, linearity, limit of detection and quantification, range, precision, accuracy, extraction efficiency, stability and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Binding modes of environmental endocrine disruptors to human serum albumin: insights from STD-NMR, ITC, spectroscopic and molecular docking studies.

    Science.gov (United States)

    Yang, Hongqin; Huang, Yanmei; Liu, Jiuyang; Tang, Peixiao; Sun, Qiaomei; Xiong, Xinnuo; Tang, Bin; He, Jiawei; Li, Hui

    2017-09-11

    Given that bisphenols have an endocrine-disrupting effect on human bodies, thoroughly exposing their potential effects at the molecular level is important. Saturation transfer difference (STD) NMR-based binding studies were performed to investigate the binding potential of two bisphenol representatives, namely, bisphenol B (BPB) and bisphenol E (BPE), toward human serum albumin (HSA). The relative STD (%) suggested that BPB and BPE show similar binding modes and orientations, in which the phenolic rings were spatially close to HSA binding site. ITC analysis results showed that BPB and BPE were bound to HSA with moderately strong binding affinity through electrostatic interactions and hydrogen bonds. The order of binding affinity of HSA for two test bisphenols is as follows: BPE > BPB. The results of fluorescence competitive experiments using 5-dimethylaminonaphthalene-1-sulfonamide and dansylsarcosine as competitors, combined with molecular docking indicated that both bisphenols are prone to attach to the binding site II in HSA. Spectroscopic results (FT-IR, CD, synchronous and 3D fluorescence spectra) showed that BPB/BPE induces different degrees of microenvironmental and conformational changes to HSA.

  13. Development of quantitative real-time PCR assays for fathead minnow (Pimephales promelas) gonadotropin ß subunit mRNAs to support endocrine disruptor research.

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, Daniel L.; Miracle, Ann L.; Jensen, Kathleen M.; Degitz, Sigmund J.; Kahl, Michael D.; Korte, Joseph J.; Greene, Katie J.; Blake, Lindsey S.; Linnum, Ann; Ankley, Gerald T.

    2007-03-01

    Fathead minnows (Pimephales promelas) are one of the most widely-used small fish models for regulatory ecotoxicology testing and research related to endocrine disrupting chemicals (EDCs). In this study, we isolated and sequenced cDNAs for fathead minnow follicle-stimulating hormone-like and luteinizing hormone-like β (FSHβ and LHβ) and glycoprotein α (GPα) subunits. Quantitative real-time PCR assays for measuring gonadotropin (GtH) β subunit transcripts were developed and used to examine “baseline” transcript levels over a range of age classes and reproductive states encompassed in EDC testing. In females, FSHβ and LHβ transcripts were greater in 4-5 month old than in younger fish and were significantly correlated with one another across all age classes examined. In males, FSHβ transcripts were greatest in 2-3 month old fish and were inversely correlated with various measures of testis development including, gonadal-somatic index (GSI), and histological stage. Overall, the pattern of GtHβ expression over age classes associated with gonad development was similar to that reported for other asynchronous-spawning fish. Despite significant changes in female GSI, gonad stage, and plasma vitellogenin within 24 h of spawning, GtHβ transcript levels in fish that had spawned within the preceding 24 h were not significantly different from those in fish that were 2-3 days post-spawn and expected to spawn within the next 24 h based on spawning history. Results of this study provide insights related to the role of GtHs in fathead minnow reproductive development and function. Additionally they provide useful “baseline” data needed to design and interpret effective experiments for studying direct and indirect effects of EDCs on GtH subunit mRNA expression, which will facilitate a greater understanding of integrated system-wide responses of the fathead minnow brain-pituitary-gonadal axis to stressors including EDCs.

  14. LC-MS/MS analytical procedure to quantify tris(nonylphenyl)phosphite, as a source of the endocrine disruptors 4-nonylphenols, in food packaging materials.

    Science.gov (United States)

    Mottier, Pascal; Frank, Nancy; Dubois, Mathieu; Tarres, Adrienne; Bessaire, Thomas; Romero, Roman; Delatour, Thierry

    2014-01-01

    Tris(nonylphenyl)phosphite, an antioxidant used in polyethylene resins for food applications, is problematic since it is a source of the endocrine-disrupting chemicals 4-nonylphenols (4NP) upon migration into packaged foods. As a response to concerns surrounding the presence of 4NP-based compounds in packaging materials, some resin producers and additive suppliers have decided to eliminate TNPP from formulations. This paper describes an analytical procedure to verify the "TNPP-free" statement in multilayer laminates used for bag-in-box packaging. The method involves extraction of TNPP from laminates with organic solvents followed by detection/quantification by LC-MS/MS using the atmospheric pressure chemical ionisation (APCI) mode. A further acidic treatment of the latter extract allows the release of 4NP from potentially extracted TNPP. 4NP is then analysed by LC-MS/MS using electrospray ionisation (ESI) mode. This two-step analytical procedure ensures not only TNPP quantification in laminates, but also allows the flagging of other possible sources of 4NP in such packaging materials, typically as non-intentionally added substances (NIAS). The limits of quantification were 0.50 and 0.48 µg dm⁻² for TNPP and 4NP in laminates, respectively, with recoveries ranging between 87% and 114%. Usage of such analytical methodologies in quality control operations has pointed to a lack of traceability at the packaging supplier level and cross-contamination of extrusion equipment at the converter level, when TNPP-containing laminates are processed on the same machine beforehand.

  15. Oxidative removal of selected endocrine-disruptors and pharmaceuticals in drinking water treatment systems, and identification of degradation products of triclosan.

    Science.gov (United States)

    Wu, Qihua; Shi, Honglan; Adams, Craig D; Timmons, Terry; Ma, Yinfa

    2012-11-15

    The potential occurrences of endocrine-disrupting compounds (EDCs), as well as pharmaceuticals, are considered to be emerging environmental problems due to their persistence and continuous input into the aquatic ecosystem, even at only trace concentrations. This study systematically investigated the oxidative removal of eight specially selected ECDs and pharmaceuticals by comparing their relative reactivity as a function of different oxidative treatment processes (i.e., free chlorine, ozone, monochloramine, and permanganate) under various pH conditions. For the oxidative removal study, EDC and pharmaceutical standards were spiked into both deionized water and natural water, followed by treatment using common oxidants at typical water treatment concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for identification and quantification. The removal efficiency of the EDCs and pharmaceuticals varied significantly between oxidation processes. Free chlorine, permanganate, and ozone treatments were all highly effective at the elimination of triclosan and estrone, while they were not effective for removing ibuprofen, iopromide, and clofibric acid. Monochloramine (at a dose of 3mg/L) was mostly ineffective in eliminating any of the selected EDCs and pharmaceuticals under the tested conditions. pH also played an important role in the removal efficiency of the EDCs and pharmaceuticals during free chlorine, permanganate, and ozone treatments. Additionally, the study identified the oxidation products of triclosan by permanganate, and 2,4-dichlorophenol was identified as the major oxidation product of triclosan by permanganate in drinking water system treatment. Furthermore, 2,4-dichlorophenol was further degradated to 4,5-dichloro-2-(2,4-dichlorophenoxy)phenol and/or 5,6-dichloro-2-(2,4-dichlorophenoxy)phenol. The kinetics for this reaction indicated that the reaction was first order in the drinking water system. Copyright © 2012 Elsevier B.V. All

  16. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring

    Directory of Open Access Journals (Sweden)

    Elodie Haraux

    2016-12-01

    Full Text Available Pregnant women are exposed to various chemical products at home and at work. Some of these products contain endocrine-disrupting chemicals (EDCs such as cosmetics, pesticides, industrial chemicals, heavy metals, plastics or medications that could alter sexual differentiation and increase the risk of hypospadias. We evaluated maternal occupational and household exposures that could constitute risk factors for hypospadias. From 2011 to 2014, we enrolled 57 full-term newborns with hypospadias and three randomly selected controls per case (162 control newborns, matched for gestational age, from 11 maternity units in Picardy, France. Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history. Maternal occupational exposure was assessed by a job-exposure matrix for EDCs from a job history questionnaire completed by mothers. Odds ratios (OR and 95% confidence intervals (CI were calculated with univariate and multivariable logistic regression, and adjusted for relevant covariates. Multivariate analysis showed a strong association between hypospadias and potential maternal occupational exposure to EDCs and maternal household use of hair cosmetics (OR 6.1, 95% CI: 1.1–34.9; OR: 9.6, 95% CI: 1.4–66.1, respectively. Our results suggest that maternal occupational exposure to EDCs is a risk factor for hypospadias and suggests a possible influence of household use of hair cosmetics during early pregnancy on the incidence of hypospadias in the offspring. A larger study with more accurate exposure assessment should evaluate the impact of EDCs in hair cosmetics on the incidence of hypospadias.

  17. Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect.

    Science.gov (United States)

    Kalfa, Nicolas; Paris, Françoise; Philibert, Pascal; Orsini, Mattea; Broussous, Sylvie; Fauconnet-Servant, Nadège; Audran, Françoise; Gaspari, Laura; Lehors, Hélène; Haddad, Myriam; Guys, Jean-Michel; Reynaud, Rachel; Alessandrini, Pierre; Merrot, Thierry; Wagner, Kathy; Kurzenne, Jean-Yves; Bastiani, Florence; Bréaud, Jean; Valla, Jean-Stéphane; Lacombe, Gérard Morisson; Dobremez, Eric; Zahhaf, Amel; Daures, Jean-Pierre; Sultan, Charles

    2015-12-01

    Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, phypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical

  18. Environmental analysis of endocrine disrupting effects from hydrocarbon contaminants in the ecosystem. 1997 annual progress report

    International Nuclear Information System (INIS)

    1997-01-01

    'The overall objective of the basic research grant is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. The three major lines of research include (1) a biotechnology based screening system to identify potential hormone mimics and antagonists; (2) an animal screening system to identify biomarkers of endocrine effects. and (3) a literature review to identify compounds at a variety of DOE sites that need to be examined for endocrine disrupting effects. By relating results obtained from this research project to contamination problems at various DOE sites. CBR will provide data and information on endocrine disrupting contaminants to DOE for consideration in risk analyses for determining clean-up levels and priorities needed at the sites.'

  19. Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility Polimorfismos genéticos e metabolismo dos desreguladores endócrinos na suscetibilidade ao câncer

    Directory of Open Access Journals (Sweden)

    Ana Hatagima

    2002-04-01

    Full Text Available Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.Estudos epidemiológicos estimam que cerca de 80% dos cânceres estão relacionados a fatores ambientais. A suscetibilidade individual ao câncer pode resultar de vários fatores relacionados ao metabolismo de xenobióticos, reparo do DNA, expressão de genes supressores de tumor e protoncogenes e estado nutricional. O metabolismo é o principal mecanismo para manter a homeostasia durante a exposição dos organismos aos xenobióticos. O equilíbrio das taxas de absorção e eliminação dos xenobióticos tem um papel importante na prevenção de danos no DNA, provocados por carcinógenos químicos. Sendo assim, a habilidade de metabolizar e eliminar os xenobióticos pode ser considerada uma das primeiras linhas de defesa dos organismos. Variações no metabolismo individual têm sido relacionadas aos polimorfismos enzimáticos, envolvidos na ativação e desintoxicação de carcinógenos químicos. Neste trabalho, é realizada

  20. In vitro bioassays to screen for endocrine active pharmaceuticals in surface and waste waters.

    Science.gov (United States)

    Kunz, Petra Y; Kienle, Cornelia; Carere, Mario; Homazava, Nadzeya; Kase, Robert

    2015-03-15

    In the context of the European Water Framework Directive (WFD) it is fully recognized that pharmaceuticals can represent a relevant issue for the achievement of the good chemical and ecological status of European surface water bodies. The recent European Directive on the review of priority substances in surface water bodies has included three pharmaceuticals of widespread use (diclofenac, 17α-ethinylestradiol (EE2), 17β-estradiol (E2)) in the European monitoring list, the so-called watch list. Endocrine active pharmaceuticals such as EE2 and E2 (also occurring as natural hormone) can cause adverse effects on aquatic ecosystems at very low levels. However, monitoring of these pharmaceuticals within the watch list mechanism of the WFD and national monitoring programs can be difficult because of detection problems of most routine analytical methods. With proposed annual average Environmental Quality Standards (AA-EQS) of 0.035 ng/L and 0.4 ng/L, respectively, the estrogenic pharmaceutical EE2 and the natural hormone E2 are among those substances. Sensitive in vitro bioassays could reduce the current detection problems by measuring the estrogenic activity of environmental samples. In a short review article the application of this approach to screen and assess the risks of endocrine active pharmaceuticals with a focus on estrogenic pharmaceuticals in environmental waters is discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. QSAR classification models for the screening of the endocrine-disrupting activity of perfluorinated compounds.

    Science.gov (United States)

    Kovarich, S; Papa, E; Li, J; Gramatica, P

    2012-01-01

    Perfluorinated compounds (PFCs) are a class of emerging pollutants still widely used in different materials as non-adhesives, waterproof fabrics, fire-fighting foams, etc. Their toxic effects include potential for endocrine-disrupting activity, but the amount of experimental data available for these pollutants is limited. The use of predictive strategies such as quantitative structure-activity relationships (QSARs) is recommended under the REACH regulation, to fill data gaps and to screen and prioritize chemicals for further experimentation, with a consequent reduction of costs and number of tested animals. In this study, local classification models for PFCs were developed to predict their T4-TTR (thyroxin-transthyretin) competing potency. The best models were selected by maximizing the sensitivity and external predictive ability. These models, characterized by robustness, good predictive power and a defined applicability domain, were applied to predict the activity of 33 other PFCs of environmental concern. Finally, classification models recently published by our research group for T4-TTR binding of brominated flame retardants and for estrogenic and anti-androgenic activity were applied to the studied perfluorinated chemicals to compare results and to further evaluate the potential for these PFCs to cause endocrine disruption.

  2. ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID FUNCTION IN THE MALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS. ENDOCRINE DISRUPTER SCREENING AND TESTING ADVISORY COMMITTEE

    Science.gov (United States)

    Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.Stoker TE, Parks LG, Gray LE, Cooper RL.

  3. Effect of endocrine disruptors on mammalian fertility

    Czech Academy of Sciences Publication Activity Database

    Pěknicová, Jana; Kyselová, V.; Buckiová, Daniela; Boubelík, Michael

    2001-01-01

    Roč. 46, č. 1 (2001), s. 88 ISSN 8755-8920. [International Congress of Reproductive Immunology /8./. 02.07.2001-06.07.2001, Opatija] R&D Projects: GA ČR GV524/96/K162; GA ČR GA303/00/1651; GA MZd NJ5851; GA MŠk EU1985 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology

  4. Efect of endocrine disruptors on in vivo

    Czech Academy of Sciences Publication Activity Database

    Pěknicová, Jana; Kyselová, Vendula; Buckiová, Daniela; Boubelík, Michael

    2002-01-01

    Roč. 48, č. 3 (2002), s. 154-155 ISSN 8755-8920. [Congress of the AASIR /8./. 07.09.2002-10.09.2002, Weimar] R&D Projects: GA ČR GA303/00/1651; GA MZd NJ5851 Keywords : xenoestrogen * phytoestrogen * fertility Subject RIV: EB - Genetics ; Molecular Biology

  5. Application of biotests for the characterization of exposure pathways for endocrine disrupters from plastics; Anwendung von Biotests zur Charakterisierung der Expositionspfade fuer Umwelthormone aus Kunststoffen

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Martin; Oehlmann, Joerg [Frankfurt Univ., Frankfurt am Main (Germany). Abteilung Aquatische Oekotoxikologie

    2011-12-15

    The present project aims to characterise the exposure pathways for endocrine disruptors from plastic materials. A bioassay-based approach was employed to investigate and characterise the endocrine activity. Migration studies with food packaging and plastic preforms document the leaching of estrogen-like compounds from several types of plastic in the Yeast Estrogen Screen and the E-Screen. Additionally, anti-estrogenic activity was predominant in many samples. The detection of complex migration profiles provides evidence for the leaching of several, diverse-acting endocrine disruptors. Moreover, extracts of plastic food packaging exhibited agonistic activity on the estrogen receptor, retinoid X receptor, and vitamin D receptor. A theoretical exposure assessment for marine molluscs implies that endocrine disruptors from plastic might induce relevant effect in the environment. Within the exemplary investigation of bottled mineral water, 60% of the products were characterised as significantly estrogenic using the YES and E-Screen. These in vitro data point to the plastic packaging being one source of estrogenic contamination. An in vivo study employing the estrogen-sensitive model organism Potamopyrgus antipodarum supports this hypothesis. By using several analytical techniques (GC-MS, LC-MS/MS) we identified several well-known endocrine disruptors in bottled water and the plastic material, e.g. numerous phthalates and phenols. Moreover, potent antagonists of the estrogen and androgen receptor were extracted from bottled water. In a non-target analysis (Orbitrap-MS) a compound with the exact mass of 363.1992 [M+H{sup +}] correlated highly significantly with the biological activity. On the basis of the methods optimised and applied within the project we elaborated a set of aspects that are crucial for the applicability of bioassays to characterise the endocrine activity of complex samples. Employing a bioassay-based approach we provide evidence for the presence and

  6. Consensus models to predict endocrine disruption for all ...

    Science.gov (United States)

    Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been tested for their ability to disrupt the endocrine system, in particular, their ability to interact with the estrogen receptor. EPA needs tools to prioritize thousands of chemicals, for instance in the Endocrine Disruptor Screening Program (EDSP). Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) was intended to be a demonstration of the use of predictive computational models on HTS data including ToxCast and Tox21 assays to prioritize a large chemical universe of 32464 unique structures for one specific molecular target – the estrogen receptor. CERAPP combined multiple computational models for prediction of estrogen receptor activity, and used the predicted results to build a unique consensus model. Models were developed in collaboration between 17 groups in the U.S. and Europe and applied to predict the common set of chemicals. Structure-based techniques such as docking and several QSAR modeling approaches were employed, mostly using a common training set of 1677 compounds provided by U.S. EPA, to build a total of 42 classification models and 8 regression models for binding, agonist and antagonist activity. All predictions were evaluated on ToxCast data and on an exte

  7. Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

    DEFF Research Database (Denmark)

    Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

    2015-01-01

    Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol......Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...

  8. 78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

    Science.gov (United States)

    2013-09-20

    ... the endocrine system. This draft guidance also discusses factors to consider in determining the need... interfere with some aspect of the endocrine system of an organism or its progeny. Any component of the endocrine system can be a target of endocrine disruptors, although the systems most commonly affected...

  9. Endocrine disrupting chemicals: harmful substances and how to test them

    Directory of Open Access Journals (Sweden)

    Olea-Serrano Nicolás

    2002-01-01

    Full Text Available This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.

  10. Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

    Science.gov (United States)

    Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P.

    2018-01-01

    , showing that they are as sensitive as molluscs, and for some species, even more sensitive. Concentrations in the range of 1 ng/L for water exposure (10 ng/g for whole-body burden) have been shown to elicit endocrine-type responses, whereas mortality occurs at water concentrations ten times higher. Current screening and assessment methodologies as compiled in the OECD CFEDTA are able to identify TBT as a potent endocrine disruptor with a high environmental risk for the original use pattern. If those approaches had been available when TBT was introduced to the market, it is likely that its use would have been regulated sooner, thus avoiding the detrimental effects on marine gastropod populations and communities as documented over several decades.

  11. Screening and management of adverse endocrine outcomes in adult survivors of childhood and adolescent cancer

    NARCIS (Netherlands)

    Tonorezos, Emily S.; Hudson, Melissa M.; Edgar, Angela B.; Kremer, Leontien C.; Sklar, Charles A.; Wallace, W. Hamish B.; Oeffinger, Kevin C.

    2015-01-01

    5 year survival for childhood and adolescent cancer in developed countries is now in excess of 80% and the number of survivors of cancer continues to increase worldwide. After completion of therapy, many of these survivors will face a lifelong risk of endocrine late effects. We summarise the

  12. Exposição ambiental a interferentes endócrinos com atividade estrogênica e sua associação com distúrbios puberais em crianças Environmental exposure to endocrine disruptors with estrogenic activity and the association with pubertal disorders in children

    Directory of Open Access Journals (Sweden)

    Crésio Alves

    2007-05-01

    Full Text Available A substância exógena que causa efeitos adversos na saúde de um organismo ou sua descendência, como resultado de distúrbios na função hormonal, é denominada interferente endócrino. Nos últimos anos, produtos ambientais com atividades hormonais têm sido documentados como causadores de anormalidades puberais ou reprodutivas em animais. Os poucos casos comprovados em humanos foram aqueles relacionados a exposições acidentais. Apesar disso, pediatras e pais recomendam a suspensão de todos os alimentos potencialmente contaminados, em especial carne (aves, gado e derivados da soja quando a criança apresenta alguma alteração puberal. Estas recomendações, se não embasadas cientificamente, podem ter conseqüências deletérias, não apenas pela eliminação de fontes protéicas da dieta, como também por retardar a investigação de causas tratáveis. Por outro lado, a não investigação dos efeitos adversos destes produtos é da mesma forma danosa. Esta revisão descreve os principais interferentes endócrinos responsáveis por alterações puberais em humanos e conclui que, excetuando exposições acidentais a altas quantidades destes produtos, mais estudos são necessários para responsabilizar a ação crônica e em baixas doses destas substâncias na alteração do tempo de desenvolvimento puberal em nossa espécie.Endocrine disruptors are exogenous substances with adverse health effects in intact organisms or their progeny, secondary to changes in endocrine function. Recent years have witnessed constant reports of environmental factors with hormone-like effects causing pubertal or reproductive abnormalities in animals. The few cases proven to be associated with pubertal disorders in humans have been related to accidental exposure. Nevertheless, pediatricians and parents recommend suspending all possible estrogen-contaminated food, especially meat (poultry, beef and soy products, when the child presents with a pubertal disorder

  13. Preliminary investigation into the possible endocrine disrupting ...

    African Journals Online (AJOL)

    ... reduction (p<0.05). The estrogen level in the female rats showed a general significant increase (p<0.05) in all the groups when compared with the female control group. This preliminary result suggest that Bonny-Light crude oil may have the potential to alter reproductive activity and hence a possible endocrine disruptor.

  14. Vliv endokrinních disruptorů na fertilitu savců

    Czech Academy of Sciences Publication Activity Database

    Pěknicová, Jana

    2007-01-01

    Roč. 5, č. 3 (2007), s. 6-10 ISSN 1801-7584 R&D Projects: GA MŠk 1M06011 Institutional research plan: CEZ:AV0Z50520514 Keywords : endocrine disruptors * acrosomal status * fertility Subject RIV: EB - Genetics ; Molecular Biology

  15. Endocrine disruption: fact or urban legend?

    Science.gov (United States)

    Nohynek, Gerhard J; Borgert, Christopher J; Dietrich, Daniel; Rozman, Karl K

    2013-12-16

    Endocrine disruptors (EDs) are substances that cause adverse health effects via endocrine-mediated mechanisms in an intact organism or its progeny or (sub) populations. Purported EDCs in personal care products include 4-MBC (UV filter) or parabens that showed oestrogenic activity in screening tests, although regulatory toxicity studies showed no adverse effects on reproductive endpoints. Hormonal potency is the key issue of the safety of EDCs. Oestrogen-based drugs, e.g. the contraceptive pill or the synthetic oestrogen DES, possess potencies up to 7 orders of magnitude higher than those of PCP ingredients; yet, in utero exposure to these drugs did not adversely affect fertility or sexual organ development of offspring unless exposed to extreme doses. Additive effects of EDs are unlikely due to the multitude of mechanisms how substances may produce a hormone-like activity; even after uptake of different substances with a similar mode of action, the possibility of additive effects is reduced by different absorption, metabolism and kinetics. This is supported by a number of studies on mixtures of chemical EDCs. Overall, despite of 20 years of research a human health risk from exposure to low concentrations of exogenous chemical substances with weak hormone-like activities remains an unproven and unlikely hypothesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    OpenAIRE

    Nashev Lyubomir G; Schuster Daniela; Laggner Christian; Sodha Seloni; Langer Thierry; Wolber Gerhard; Odermatt Alex

    2010-01-01

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here a 3D structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta hydr...

  17. Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches

    International Nuclear Information System (INIS)

    Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh; Zhu, Hao; Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia; Rusyn, Ivan; Tropsha, Alexander

    2013-01-01

    Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R 2 = 0.71, STL R 2 = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R 2 = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function. • The results

  18. Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States); Zhu, Hao [The Rutgers Center for Computational and Integrative Biology, Rutgers University, Camden, NJ (United States); Department of Chemistry, Rutgers University, Camden, NJ (United States); Afantitis, Antreas; Mouchlis, Varnavas D.; Melagraki, Georgia [NovaMechanics Ltd., Nicosia (Cyprus); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC (United States)

    2013-10-01

    Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα binding affinity (MTL R{sup 2} = 0.71, STL R{sup 2} = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R{sup 2} = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and function.

  19. Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System

    DEFF Research Database (Denmark)

    Autrup, Herman; Barile, Frank A; Blaauboer, Bas J

    2015-01-01

    The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can...

  20. Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

    DEFF Research Database (Denmark)

    Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

    2015-01-01

    Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...... the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream...... with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert...

  1. Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect.

    Directory of Open Access Journals (Sweden)

    Anna Pereira-Fernandes

    Full Text Available Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds, were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA. PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound.

  2. Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect

    Science.gov (United States)

    Pereira-Fernandes, Anna; Demaegdt, Heidi; Vandermeiren, Karine; Hectors, Tine L. M.; Jorens, Philippe G.; Blust, Ronny; Vanparys, Caroline

    2013-01-01

    Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. PMID:24155963

  3. Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem

    Energy Technology Data Exchange (ETDEWEB)

    McLachlan, John A.

    2000-06-01

    This annual report summarizes the progress of three years of a three-year grant awarded to the Center for Bioenvironmental Research (CBR) at Tulane and Xavier Universities. The objective of this project is to determine how environmental contaminants, namely hydrocarbons, can act as hormones or anti-hormones in different species present in aquatic ecosystems. The three major areas of research include (1) a biotechnology based screening system to identify potential hormone mimics and antagonists; (2) an animal screening system to identify biomarkers of endocrine effects; and (3) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular focus in this study are those which can serve as sentinel species (e.g., amphibians) and, thus, provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The focus of the literature research was to provide an analysis of the contaminants located on or around various Department of Energy (DOE) sites that are or have the potential to function as endocrine disruptors and to correlate the need for studying endocrine disruptors to DOE's programmatic needs. Previous research within the Center for Bioenvironmental Research at Tulane and Xavier Universities has focused on understanding the effects of environmental agents on the human and wildlife health and disease. In particular this research has focused on how exogenous agents can function to mimic or disrupt normal endocrine signaling, i.e. estrogen, thyroid within various systems from whole animal studies with fish, amphibians and insects to human cancer cell lines. Significant work has focused on the estrogenic and anti-estrogenic action of both synthetic organochlorine chemicals and naturally produced phytochemicals. Recent projects have extended these research objectives to examination of these environmental agents on the symbiotic relationship between

  4. Estarão alguns grupos populacionais brasileiros sujeitos à ação de disruptores endócrinos? Are some Brazilian population groups subject to endocrine disrupters?

    Directory of Open Access Journals (Sweden)

    Armando Meyer

    1999-10-01

    Full Text Available Várias substâncias químicas com atividade sobre o sistema endócrino têm sido amplamente utilizadas no Brasil tanto em atividades industriais quanto em outros ramos, como por exemplo, na agricultura. Alguns dados mostrando a contaminação de grupos populacionais brasileiros por substâncias supostamente possuidoras destas propriedades são apresentados neste trabalho. Entretanto, muito pouco, ou mesmo nada, se sabe sobre os efeitos que as mesmas têm sobre a saúde destas populações expostas, mostrando claramente a necessidade urgente de implementação de um programa destinado a esta finalidade.Several chemical substances suspected of endocrine disruption are currently being used in industrial and agricultural activities in Brazil. This paper presents analytical data showing contamination of some population groups by these substances. Virtually nothing is known about the related health effects, highlighting the need to implement a national program to evaluate such impacts.

  5. In Vitro Endocrine Disruption Screening of 3-nitro-1,2,4-triazol-5-one (NTO)

    Science.gov (United States)

    2012-09-25

    report; Appendix B. 6.3 Aromatase Assay The CYP19/Methoxy-4-trifluoromethyl- coumarin (MFC) High throughput Inhibition Screening Kit (Cat... coumarin (fluorescent substrate), glucose 6-phosphate dehydrogenase, cofactors, CYP19 enzyme, phosphate buffer- pH 7.4, positive control inhibitor...ketoconazole), and metabolite standard (7- hydroxy-4-trifluormethyl coumarin ). Briefly, on the day of the assay, reagents were removed from storage (-80 O

  6. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of experience to improve screening and testing for endocrine active chemicals

    Science.gov (United States)

    Outline of the presentationEDCs – from 1991 to 1996 – Wingspread and Our Stolen Future 1996 – FQPA and SDWA mandates endocrine screening 1996-1998 – EDSTAC (the assays, debates over modes of action included) The final battery – EAT in vivo and in vit...

  7. Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays.

    Science.gov (United States)

    Coady, Katherine K; Kan, H Lynn; Schisler, Melissa R; Gollapudi, B Bhaskar; Neal, Barbara; Williams, Amy; LeBaron, Matthew J

    2014-08-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was evaluated in five in vitro screening assays to assess the potential for interaction with the androgen, estrogen and steroidogenesis pathways in the endocrine system. The assays were conducted to meet the requirements of the in vitro component of Tier 1 of the United States Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP), and included assays for estrogen receptor (ER) binding (rat uterine cytosol ER binding assay), ER-mediated transcriptional activation (HeLa-9903-ERα transactivation assay), androgen receptor (AR) binding (rat prostate cytosol AR binding assay), aromatase enzymatic activity inhibition (recombinant human CYP19 aromatase inhibition assay), and interference with steroidogenesis (H295R steroidogenesis assay). Results from these five assays demonstrated that 2,4-D does not have the potential to interact in vitro with the estrogen, androgen, or steroidogenesis pathways. These in vitro data are consistent with a corresponding lack of endocrine effects observed in apical in vivo animal studies, and thus provide important supporting data valuable in a comprehensive weight of evidence evaluation indicating a low potential of 2,4-D to interact with the endocrine system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Reproductive toxicity of the endocrine disrupters vinclozolin and bisphenol A in the terrestrial isopod Porcellio scaber (Latreille, 1804).

    NARCIS (Netherlands)

    Lemos, M.F.L.; van Gestel, C.A.M.; Soares, A.M.V.M.

    2010-01-01

    Endocrine Disruptor Compounds (EDCs) have been largely studied concerning their effects on vertebrates. Nevertheless, invertebrates as targets for these chemicals have been neglected and few studies are available. Specifically for edaphic invertebrates, data concerning the effects of EDCs is

  9. Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility Efeitos da terapia medicamentosa, àlcool, cigarros e substância deletérias para o sistema endócrino na infertilidade masculina

    Directory of Open Access Journals (Sweden)

    Fábio Firmbach Pasqualotto

    2004-01-01

    Full Text Available Infertility affects up to 15% of the sexually active population, and in 50% of cases, a male factor is involved, either as a primary problem or in combination with a problem in the female partner. Because many commonly encountered drugs and medications can have a detrimental effect on male fertility, the medical evaluation should include a discussion regarding the use of recreational and illicit drugs, medications, and other substances that may impair fertility. With the knowledge of which drugs and medications may be detrimental to fertility, it may be possible to modify medication regimens or convince a patient to modify habits to decrease adverse effects on fertility and improve the chances of achieving a successful pregnancy. Concern is growing that male sexual development and reproduction have changed for the worse over the past 30 to 50 years. Although some reports find no changes, others suggest that sperm counts appear to be decreasing and that the incidence of developmental abnormalities such as hypospadias and cryptorchidism appears to be increasing, as is the incidence of testicular cancer. These concerns center around the possibility that our environment is contaminated with chemicals - both natural and synthetic - that can interact with the endocrine system.A infertilidade afeta até 15% da população sexualmente ativa e em 50% dos casos, o fator masculino está envolvido, como problema primário ou em combinação com causas de origem feminina. Como muitas drogas comumente encontradas e medicações podem ter efeitos deletérios na infertilidade masculina, a avaliação médica deve incluir uma discussão sobre o uso de drogas recreacionais e ilícitas, medicamentos e outras substâncias podem prejudicar a fertilidade. Com o conhecimento de quais drogas e medicamentos podem ser prejudiciais à fertilidade talvez seja possível mudar os hábitos ou a posologia das medicações para diminuir os efeitos adversos na fertilidade e

  10. A multi-assay screening approach for assessment of endocrine-active contaminants in wastewater effluent samples

    Energy Technology Data Exchange (ETDEWEB)

    Metcalfe, Chris D., E-mail: cmetcalfe@trentu.ca [Environmental and Resource Studies, Trent University, Peterborough, ON, K9J 7B8 (Canada); Kleywegt, Sonya [Standards Development Branch, Ontario Ministry of the Environment, 40 St. Clair Ave. West, Toronto, ON, M4V 1M2 (Canada); Letcher, Robert J. [Ecotoxicology and Wildlife Health Division, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, K1A 0H3 (Canada); Topp, Edward [Agriculture and Agri-Food Canada, Southern Crop Protection and Food Research Centre, London, ON, N5V 7T3 (Canada); Wagh, Purva; Trudeau, Vance L.; Moon, Thomas W. [Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON, K1N 6N5 (Canada)

    2013-06-01

    Environmental agencies must monitor an ever increasing range of contaminants of emerging concern, including endocrine disrupting compounds (EDCs). An alternative to using ultra-trace chemical analysis of samples for EDCs is to test for biological activity using in vitro screening assays, then use these assay results to direct analytical chemistry approaches. In this study, we used both analytical approaches and in vitro bioassays to characterize the EDCs present in treated wastewater from four wastewater treatment plants (WWTPs) in Ontario, Canada. Estrogen-mediated activity was assessed using a yeast estrogenicity screening (YES) assay. An in vitro competitive binding assay was used to assess capacity to interfere with binding of the thyroid hormone, thyroxine (T4) to the recombinant human thyroid hormone transport protein, transthyretin (i.e. hTTR). An in vitro binding assay with a rat peroxisome proliferator responsive element transfected into a rainbow trout gill cell line was used to evaluate binding and subsequent gene expression via the peroxisome proliferator activated receptor (PPAR). Analyses of a suite of contaminants known to be EDCs in extracts from treated wastewater were conducted using either gas chromatography with mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS/MS). Estrogenic activity was detected in the YES assay only in those extracts that contained detectable amounts of estradiol (E2). There was a positive relationship between the degree of response in the T4-hTTR assay and the amounts of polybrominated diphenyl ether (PBDE) congeners 47 and 99, triclosan and the PBDE metabolite, 4-OH-BDE17. Several wastewater extracts gave a positive response in the PPAR assay, but these responses were not correlated with the amounts of any of the EDCs analyzed by LC-MS/MS. Overall, these data indicate that a step-wise approach is feasible using a combination of in vitro testing and instrumental analysis to monitor for

  11. A multi-assay screening approach for assessment of endocrine-active contaminants in wastewater effluent samples

    International Nuclear Information System (INIS)

    Metcalfe, Chris D.; Kleywegt, Sonya; Letcher, Robert J.; Topp, Edward; Wagh, Purva; Trudeau, Vance L.; Moon, Thomas W.

    2013-01-01

    Environmental agencies must monitor an ever increasing range of contaminants of emerging concern, including endocrine disrupting compounds (EDCs). An alternative to using ultra-trace chemical analysis of samples for EDCs is to test for biological activity using in vitro screening assays, then use these assay results to direct analytical chemistry approaches. In this study, we used both analytical approaches and in vitro bioassays to characterize the EDCs present in treated wastewater from four wastewater treatment plants (WWTPs) in Ontario, Canada. Estrogen-mediated activity was assessed using a yeast estrogenicity screening (YES) assay. An in vitro competitive binding assay was used to assess capacity to interfere with binding of the thyroid hormone, thyroxine (T4) to the recombinant human thyroid hormone transport protein, transthyretin (i.e. hTTR). An in vitro binding assay with a rat peroxisome proliferator responsive element transfected into a rainbow trout gill cell line was used to evaluate binding and subsequent gene expression via the peroxisome proliferator activated receptor (PPAR). Analyses of a suite of contaminants known to be EDCs in extracts from treated wastewater were conducted using either gas chromatography with mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS/MS). Estrogenic activity was detected in the YES assay only in those extracts that contained detectable amounts of estradiol (E2). There was a positive relationship between the degree of response in the T4-hTTR assay and the amounts of polybrominated diphenyl ether (PBDE) congeners 47 and 99, triclosan and the PBDE metabolite, 4-OH-BDE17. Several wastewater extracts gave a positive response in the PPAR assay, but these responses were not correlated with the amounts of any of the EDCs analyzed by LC-MS/MS. Overall, these data indicate that a step-wise approach is feasible using a combination of in vitro testing and instrumental analysis to monitor for

  12. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

    Directory of Open Access Journals (Sweden)

    Huixiao Hong

    2016-03-01

    Full Text Available Endocrine disruptors such as polychlorinated biphenyls (PCBs, diethylstilbestrol (DES and dichlorodiphenyltrichloroethane (DDT are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69% and external validations using 22 chemicals (balanced accuracy of 71%. Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

  13. Integration of in silico methods and computational systems biology to explore endocrine-disrupting chemical binding with nuclear hormone receptors.

    Science.gov (United States)

    Ruiz, P; Sack, A; Wampole, M; Bobst, S; Vracko, M

    2017-07-01

    Thousands of potential endocrine-disrupting chemicals present difficult regulatory challenges. Endocrine-disrupting chemicals can interfere with several nuclear hormone receptors associated with a variety of adverse health effects. The U.S. Environmental Protection Agency (U.S. EPA) has released its reviews of Tier 1 screening assay results for a set of pesticides in the Endocrine Disruptor Screening Program (EDSP), and recently, the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) data. In this study, the predictive ability of QSAR and docking approaches is evaluated using these data sets. This study also presents a computational systems biology approach using carbaryl (1-naphthyl methylcarbamate) as a case study. For estrogen receptor and androgen receptor binding predictions, two commercial and two open source QSAR tools were used, as was the publicly available docking tool Endocrine Disruptome. For estrogen receptor binding predictions, the ADMET Predictor, VEGA, and OCHEM models (specificity: 0.88, 0.88, and 0.86, and accuracy: 0.81, 0.84, and 0.88, respectively) were each more reliable than the MetaDrug™ model (specificity 0.81 and accuracy 0.77). For androgen receptor binding predictions, the Endocrine Disruptome and ADMET Predictor models (specificity: 0.94 and 0.8, and accuracy: 0.78 and 0.71, respectively) were more reliable than the MetaDrug™ model (specificity 0.33 and accuracy 0.4). A consensus approach is proposed that reaches general agreement among the models (specificity 0.94 and accuracy 0.89). This study integrates QSAR, docking, and systems biology approaches as a virtual screening tool for use in risk assessment. As such, this systems biology pathways and network analysis approach provides a means to more critically assess the potential effects of endocrine-disrupting chemicals. Published by Elsevier Ltd.

  14. Effects of endocrine disrupting heavy metals on pituitary and ...

    African Journals Online (AJOL)

    Association of hypogonadism and visceral obesity (VO) was recently demonstrated in male auto-mechanics occupationally exposed to endocrine disruptors (ED)-lead, cadmium, mercury and arsenic, known to alter the hypothalamic-pituitary-testicular axis. The effects of exposure to these EDs on pituitary and gonadal ...

  15. Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?

    Science.gov (United States)

    Bolden, Ashley L; Rochester, Johanna R; Kwiatkowski, Carol F

    2017-10-05

    Melamine is commonly used in a variety of consumer products such as furniture, dining ware, and food utensils. The chemical infamously gained worldwide attention by its illegal addition to a variety of foodstuffs in order to falsify protein content, which led to serious, sometimes fatal, health impacts in children and pets. This resulted in a large amount of published primary studies and reviews of the impacts of melamine exposure on kidney function. However, a growing body of literature suggests that melamine may have impacts beyond renal dysfunction. We conducted a scoping review of this literature which yielded more than 40 studies with human, animal, and in vitro findings. Neurological impacts, reproductive function, and anthropometric outcomes were identified as possible candidates for systematic review based on evidence stream and replication of endpoints. The results of this analysis provide a basis for prioritizing future research on health impacts associated with melamine exposure. Copyright © 2017. Published by Elsevier B.V.

  16. Detection and Quantification of Oestrogenic Endocrine Disruptors in ...

    African Journals Online (AJOL)

    The aim of this study was to detect the presence and quantify the total oestrogens (estriol (E1), estradiol (E2), and estrone (E3)) in Lake Victoria water with a view of assessing their contribution to the health status of fish. A total of 27 water samples; three from each of the nine sampling sites were collected in Mwanza gulf in ...

  17. Impact of Endocrine Disruptors on the Thyroid Hormone System.

    Science.gov (United States)

    Gutleb, Arno C; Cambier, Sébastien; Serchi, Tommaso

    2016-01-01

    The thyroid hormone (TH) system plays a central role in central physiological processes of many species, including mammals and humans, ranging from growth and cell differentiation, energy metabolism, thermoregulation and phasing of hibernation or annual movements of migratory species, metamorphosis from larvae to adult forms, brain development, reproduction, or the cardiovascular system. Several chemicals are known to be TH-disrupting compounds (THDCs) and have been shown to interact with virtually all elements of TH homeostasis such as feedback mechanisms with the hypothalamus-pituitary axis, TH synthesis, TH storage and release from the thyroid gland, transport protein binding and TH distribution in tissues and organs, cellular TH uptake, intracellular TH metabolism, and TH receptor binding. Therefore, chemicals interfering with the TH homeostasis have the potential to interact with many of these important processes, and especially early-life stage exposure results in permanent alterations of tissue organization and homeostatic regulation of adaptive processes. This is not only of theoretical importance as the reported plasma concentrations of THDCs in human plasma fall well within the range of reported in vitro effect concentrations, and this is of even higher importance as the developing fetus and young children are in a sensitive developmental stage. © 2016 S. Karger AG, Basel.

  18. Disruptores endócrinos

    OpenAIRE

    Soeiro, Paula Isabel de São Pedro

    2014-01-01

    Trabalho final de mestrado integrado em Medicina (Endocrinologia), apresentado á Faculdade de Medicina da Universidade de Coimbra As doenças endócrino-mediadas no ser humano estão a aumentar em todo mundo e pensa-se que os disruptores endócrinos (EDs) sejam a causa. Este artigo visa identificar os principais EDs, as suas fontes, mecanismos de exposição e atuação geral, assim como patologias com correlação cientificamente demonstrada, com destaque para o cancro da mama, obesidade e doenças ...

  19. Information/testing strategy for identification of substances with endocrine disrupting properties

    DEFF Research Database (Denmark)

    Hass, Ulla; Christiansen, Sofie; Bjerregaard, Poul

    . The overall scope of this project is to provide a science based input to the ongoing work in EU with regard to endocrine disruptors, i.e. the development of criteria for identification, REACH review on EDs and the revised strategy for the future work on endocrine disruptors, focusing on adequate detection......This report has been prepared by the Danish Centre on Endocrine Disrupters (CeHoS) as a project contracted by the Danish Environmental Protection Agency. The Danish Centre on Endocrine Disrupters is an interdisciplinary scientific network without walls. The main purpose of the Centre is to build...... and gather new knowledge on endocrine disrupters (EDs) with the focus on providing information requested for the preventive work of the regulatory authorities. The Centre is financed by the Ministry of the Environment and the scientific work programme is followed by an international scientific advisory board...

  20. In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis.

    Directory of Open Access Journals (Sweden)

    Ling Li

    Full Text Available The effects of endocrine disrupting chemicals (EDCs on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio transgenic lines expressing the green fluorescent protein (GFP in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA, as well as the three drugs diclofenac, trichostatin A (TSA and valproic acid (VPA induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo.

  1. Uncertainty Quantification in High Throughput Screening: Applications to Models of Endocrine Disruption, Cytotoxicity, and Zebrafish Development (GRC Drug Safety)

    Science.gov (United States)

    Using uncertainty quantification, we aim to improve the quality of modeling data from high throughput screening assays for use in risk assessment. ToxCast is a large-scale screening program that analyzes thousands of chemicals using over 800 assays representing hundreds of bioche...

  2. Evaluation of OASIS QSAR Models Using ToxCast™ in Vitro Estrogen and Androgen Receptor Binding Data and Application in an Integrated Endocrine Screening Approach

    Science.gov (United States)

    Bhhatarai, Barun; Wilson, Daniel M.; Price, Paul S.; Marty, Sue; Parks, Amanda K.; Carney, Edward

    2016-01-01

    Background: Integrative testing strategies (ITSs) for potential endocrine activity can use tiered in silico and in vitro models. Each component of an ITS should be thoroughly assessed. Objectives: We used the data from three in vitro ToxCast™ binding assays to assess OASIS, a quantitative structure-activity relationship (QSAR) platform covering both estrogen receptor (ER) and androgen receptor (AR) binding. For stronger binders (described here as AC50 QSAR predictions of ER or AR binding to the results from 18 ER and 10 AR transactivation assays, 72 ER-binding reference compounds, and the in vivo uterotrophic assay. Methods: NovaScreen binding assay data for ER (human, bovine, and mouse) and AR (human, chimpanzee, and rat) were used to assess the sensitivity, specificity, concordance, and applicability domain of two OASIS QSAR models. The binding strength relative to the QSAR-predicted binding strength was examined for the ER data. The relationship of QSAR predictions of binding to transactivation- and pathway-based assays, as well as to in vivo uterotrophic responses, was examined. Results: The QSAR models had both high sensitivity (> 75%) and specificity (> 86%) for ER as well as both high sensitivity (92–100%) and specificity (70–81%) for AR. For compounds within the domains of the ER and AR QSAR models that bound with AC50 QSAR models accurately predicted the binding for the parent compounds. The parent compounds were active in all transactivation assays where metabolism was incorporated and, except for those compounds known to require metabolism to manifest activity, all assay platforms where metabolism was not incorporated. Compounds in-domain and predicted to bind by the ER QSAR model that were positive in ToxCast™ ER binding at AC50 QSAR models had high sensitivity and specificity when compounds were in-domain of the models. Based on this research, we recommend a tiered screening approach wherein a) QSAR is used to identify compounds in-domain of

  3. Endocrine Disrupting Chemicals (EDCs)

    Science.gov (United States)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

  4. Endocrine-disrupting chemicals: associated disorders and mechanisms of action.

    Science.gov (United States)

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  5. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Sam De Coster

    2012-01-01

    Full Text Available The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  6. A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, D.J.; Andrew, S.; Richardson, A.L. [Royal North Shore Hospital, St. Leonards (Australia)]|[Univ. of Sydney, New South Wales (Australia)] [and others

    1994-09-15

    Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. The authors have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and RMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. The authors have identified a mutation in codon 620, 2053 T {r_arrow}C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T {r_arrow} C (Cys634Arg) and 2096 G {r_arrow} A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families. 7 refs., 1 fig., 1 tab.

  7. Endocrine Diseases

    Science.gov (United States)

    ... Endocrine diseases and disorders also occur if your body does not respond to hormones the way it is supposed ... for Cystic Fibrosis An Important Proof of Principle for the "Combination Therapy" Approach to ...

  8. Endocrine Diseases

    Science.gov (United States)

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  9. Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer

    International Nuclear Information System (INIS)

    Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli

    2016-01-01

    The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. The online version of this article (doi:10.1186/s12885-016-2452-5) contains supplementary material, which is available to authorized users

  10. Novel in vitro, ex vivo and in vivo assays elucidating the effects of endocrine disrupting compounds (EDCs) on thyroid hormone action

    NARCIS (Netherlands)

    Schriks, M.

    2006-01-01

    The last years, both scientific and public concern about the possible threat of compounds in the environment that may affect endocrine functions has increased. Thus far, the majority of endocrine disruptor research has focused on the interference of compounds with the sex hormone homeostasis. Less

  11. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    Science.gov (United States)

    Nashev, Lyubomir G; Schuster, Daniela; Laggner, Christian; Sodha, Seloni; Langer, Thierry; Wolber, Gerhard; Odermatt, Alex

    2010-04-15

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), which catalyzes the last step of testosterone synthesis in testicular Leydig cells and plays an essential role during male sexual development. Among other chemicals, benzophenone (BP) UV-filters were predicted as potential 17beta-HSD3 inhibitors. Biological analyses revealed (2,4-dihydroxyphenyl)-phenylmethanone (also known as benzophenone-1, BP-1) as an inhibitor of human 17beta-HSD3 (IC(50) 1.05microM). BP-1 also efficiently blocked conversion of androstenedione to testosterone by mouse and rat 17beta-HSD3 in whole-organ enzyme assays. Moreover, BP-1 antagonized the testosterone-dependent activation of androgen receptors (IC(50) 5.7microM), suggesting synergistic anti-androgenic effects of BP-1 by preventing testosterone formation and blocking receptor activation. In addition, analyses of several commonly used UV-filters on estrogen- and androgen-metabolizing 17beta-HSD enzymes revealed 3-benzylidene camphor (3-BC) and 4-methylbenzylidene camphor (4-MBC) as low micromolar 17beta-HSD2 inhibitors. In conclusion, screening of virtual chemical structure libraries can facilitate the identification of compounds interfering with hormone action. The potential disruption of 17beta-HSD enzyme function by the UV-filters BP-1, 3-BC and 4-MBC requires further investigation and should be considered for safety assessment of these chemicals. 2009 Elsevier Inc. All rights reserved.

  12. Endocrine modulation and toxic effects of two commonly used UV screens on the aquatic invertebrates Potamopyrgus antipodarum and Lumbriculus variegatus

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, Claudia [Johann Wolfgang Goethe-University, Department Aquatic Ecotoxicology, Siesmayerstrasse 70, 60323 Frankfurt (Germany)], E-mail: claudia.schmitt@ua.ac.be; Oetken, Matthias; Dittberner, Olaf; Wagner, Martin; Oehlmann, Joerg [Johann Wolfgang Goethe-University, Department Aquatic Ecotoxicology, Siesmayerstrasse 70, 60323 Frankfurt (Germany)

    2008-03-15

    The two UV screens 3-benzylidene-camphor (3-BC) and 3-(4'-methylbenzylidene)-camphor (4-MBC) were tested regarding their toxicity and estrogenic activity. The Yeast Estrogen Screen (YES) and two sediment assays with the freshwater invertebrates Lumbriculus variegatus and Potamopyrgus antipodarum were performed. In the YES, both substances activated the human estrogen receptor {alpha} with EC{sub 50} values of 44.2 {mu}M for 3-BC and 44.3 {mu}M for 4-MBC, whereby 4-MBC attained only 8% of the maximal response of 17{beta}-estradiol. For P. antipodarum embryo production increased after exposure to both substances (EC{sub 50} of 4.60 {mu}M 4-MBC = 1.17 mg kg{sup -1} dw) while mortality increased at high concentrations. The reproduction of L. variegatus was decreased by 3-BC with an EC{sub 50} of 5.95 {mu}M (=1.43 mg kg{sup -1} dw) and also by 4-MBC, where no EC{sub 50} could be calculated. While reproduction decreased, the worms' weight increased after exposure to 3-BC with an EC{sub 50} of 26.9 {mu}M (= 6.46 mg kg{sup -1} dw), hence the total biomass remained unaffected. - UV screens can have a significant impact on reproduction and development of aquatic invertebrates.

  13. Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System

    NARCIS (Netherlands)

    Autrup, Herman; Barile, Frank A.; Blaauboer, Bas J.; Degen, Gisela H.; Dekant, Wolfgang; Dietrich, Daniel; Domingo, Jose L.; Gori, Gio Batta; Greim, Helmuth; Hengstler, Jan G.; Kacew, Sam; Marquardt, Hans; Pelkonen, Olavi; Savolainen, Kai; Vermeulen, Nico P.

    The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be

  14. QSAR modeling and prediction of the endocrine-disrupting potencies of brominated flame retardants.

    Science.gov (United States)

    Papa, Ester; Kovarich, Simona; Gramatica, Paola

    2010-05-17

    In the European Union REACH regulation, the chemicals with particularly harmful behaviors, such as endocrine disruptors (EDs), are subject to authorization, and the identification of safer alternatives to these chemicals is required. In this context, the use of quantitative structure-activity relationships (QSAR) becomes particularly useful to fill the data gap due to the very small number of experimental data available to characterize the environmental and toxicological profiles of new and emerging pollutants with ED behavior such as brominated flame retardants (BFRs). In this study, different QSAR models were developed on different responses of endocrine disruption measured for several BFRs. The multiple linear regression approach was applied to a variety of theoretical molecular descriptors, and the best models, which were identified from all of the possible combinations of the structural variables, were internally validated for their performance using the leave-one-out (Q(LOO)(2) = 73-91%) procedure and scrambling of the responses. External validation was provided, when possible, by splitting the data sets in training and test sets (range of Q(EXT)(2) = 76-90%), which confirmed the predictive ability of the proposed equations. These models, which were developed according to the principles defined by the Organization for Economic Co-operation and Development to improve the regulatory acceptance of QSARs, represent a simple tool for the screening and characterization of BFRs.

  15. New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

  16. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.

    Directory of Open Access Journals (Sweden)

    Malene Hansen

    2005-07-01

    Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

  17. Skin Manifestations of Endocrine Diseases.

    Science.gov (United States)

    Demirkesen, Cuyan

    2015-01-01

    Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

  18. Persistence of endocrine disruption in zebrafish (Danio rerio) after discontinued exposure to the androgen 17β-trenbolone

    DEFF Research Database (Denmark)

    Baumann, Lisa; Knörr, Susanne; Keiter, Susanne

    2014-01-01

    The aim of the present study was to investigate the effects of the androgenic endocrine disruptor 17β-trenbolone on the sexual development of zebrafish (Danio rerio) with special emphasis on the question whether adverse outcomes of developmental exposure are reversible or persistent. An exposure...

  19. Celiac disease and endocrine autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  20. Recent Advances on Endocrine Disrupting Effects of UV Filters.

    Science.gov (United States)

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-08-03

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

  1. Recent Advances on Endocrine Disrupting Effects of UV Filters

    Directory of Open Access Journals (Sweden)

    Jiaying Wang

    2016-08-01

    Full Text Available Ultraviolet (UV filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

  2. Evaluation of Endocrine Disrupting Effects of Nitrate after In Utero Exposure in Rats and of Nitrate and Nitrite in the H295R and T-Screen Assay

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Taxvig, Camilla; Christiansen, Sofie

    2009-01-01

    /l. At GD21, fetuses were examined for anogenital distance, plasma thyroxine levels, testicular and plasma levels of testosterone and progesterone, and testicular testosterone production and histopathology. In addition, endocrine disrupting activity of nitrate and nitrite were studied in two in vitro assays......Animal studies have shown that nitrate acts as an endocrine disrupter affecting the androgen production in adult males. This raises a concern for more severe endocrine disrupting effects after exposure during the sensitive period of prenatal male sexual development. As there are no existing studies...... of effects of nitrate on male sexual development, the aim of the study was to examine how in utero exposure to nitrate would affect male rat fetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD21 at the following dose levels 17.5, 50, 150, 450, and 900 mg...

  3. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  4. Genetic testing by cancer site: endocrine system.

    Science.gov (United States)

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  5. Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

    Science.gov (United States)

    Mallozzi, Maddalena; Leone, Chiara; Manurita, Francesca; Bellati, Filippo; Caserta, Donatella

    2017-01-01

    Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women’s health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies has increased. Methods: A systematic MEDLINE (PubMed) search was performed and relevant articles published in the last 23 years (from 1992 to 2016) were selected. Results: Human studies and animal experiments are confirming a carcinogenic effect due to the EDC exposure and its carcinogenesis process result to be complex, multifactorial and long standing, thus, it is extremely difficult to obtain the epidemiological proof of a carcinogenic effect of EDCs for the high number of confusing factors. Conclusions: The carcinogenic effects of endocrine disruptors are plausible, although additional studies are needed to clarify their mechanisms and responsible entities. Neverthless, to reduce endocrine disruptors (ED) exposure is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as embryonic period and puberty. PMID:28327540

  6. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  7. Multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Luzi Ettore

    2006-10-01

    Full Text Available Abstract Multiple Endocrine Neoplasia type 1 (MEN1 is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions is recommended.

  8. Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide

    Science.gov (United States)

    2017-07-01

    generated the disruptor peptides conjugated with green fluorescent protein (GFP) and/or Pen. Primary chondrocytes were treated with 10 M of disruptor...were stained with Safranin-O and Fast green . Arrow indicates cartilage loss. 7 PTHrP-induced PTHR coupling to G protein subunits will be...vitro and protect cartilage damage in a mouse OA model. 15. SUBJECT TERMS Osteoarthritis; Parathyroid hormone-related protein ; PTH receptor; Beta

  9. Multiple Endocrine Neoplasia Syndromes

    Science.gov (United States)

    ... switch to the Professional version Home Hormonal and Metabolic Disorders Multiple Endocrine Neoplasia Syndromes Multiple Endocrine Neoplasia Syndromes Types Type 1 disease Type 2A disease Type 2B disease Diagnosis Treatment Resources In This Article Drugs Mentioned In This ...

  10. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of experience to improve screening and testing for endocrine active chemicals.@@

    Science.gov (United States)

    In 1996 the Food Quality Protection and Safe Drinking Water Acts instructed the USEPA to determine “…whether the pesticide chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects;"*...

  11. Exposures, mechanisms, and impacts of endocrine-active flame retardants.

    Science.gov (United States)

    Dishaw, Laura V; Macaulay, Laura J; Roberts, Simon C; Stapleton, Heather M

    2014-12-01

    This review summarizes the endocrine and neurodevelopmental effects of two current-use additive flame retardants (FRs), tris (1,3-dichloro-isopropyl) phosphate (TDCPP) and Firemaster(®) 550 (FM 550), and the recently phased-out polybrominated diphenyl ethers (PBDEs), all of which were historically or are currently used in polyurethane foam applications. Use of these chemicals in consumer products has led to widespread exposure in indoor environments. PBDEs and their hydroxylated metabolites appear to primarily target the thyroid system, likely due to their structural similarity to endogenous thyroid hormones. In contrast, much less is known about the toxicity of TDCPP and FM 550. However, recent in vitro and in vivo studies suggest that both should be considered endocrine disruptors as studies have linked TDCPP exposure with changes in circulating hormone levels, and FM 550 exposure with changes in adipogenic and osteogenic pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. European Union's strategy on endocrine disrupting chemicals and the current position of Slovenia.

    Science.gov (United States)

    Perharič, Lucija; Fatur, Tanja; Drofenik, Jernej

    2016-06-01

    In view of the European Union regulations 1107/2009 and 528/2012, which say that basic substances in plant protection and biocidal products marketed in the European Union (EU) should not have an inherent capacity to cause endocrine disruption, an initiative was started to define scientific criteria for the identification of endocrine disruptors (EDs). The objectives of the EU strategy on EDs are to protect human health and the environment, to assure the functioning of the market, and to provide clear and coherent criteria for the identification of EDs that could have broad application in the EU legislation. Policy issues were to be addressed by the Ad-hoc group of Commission Services, EU Agencies and Member States established in 2010, whereas the scientific issues were to be addressed by the Endocrine Disruptors Expert Advisory Group (ED EAG), established in 2011. The ED EAG adopted the 2002 World Health Organization (WHO) definition of endocrine disruptor and agreed that for its identification it is necessary to produce convincing evidence of a biologically plausible causal link between an adverse effect and endocrine disrupting mode of action. In 2014, the European Commission proposed four ED identification criteria options and three regulatory options, which are now being assessed for socio-economic, environmental, and health impact. Slovenia supports the establishing of identification criteria and favours option 4, according to which ED identification should be based on the WHO definition with the addition of potency as an element of hazard characterisation. As for regulatory options, Slovenia favours the risk-based rather than hazard-based regulation.

  13. A Demonstration Study on Decomposition of Anntibiotics and Endocrine Disrupters Contained in Sewage Effluent by Mobile Electron Beam Accelerator

    International Nuclear Information System (INIS)

    Lee, Myun Joo; Kim, Tae Hoon; Jung, In Ha

    2012-01-01

    This report described a work plan on advanced sewage treatments focusing on reduction of antibiotics and endocrine disruptors and sterilization by radiation in Korea. It included a demonstration study on decomposition of antibiotics and endocrine disruptor contained in sewage effluent by MEB(Mobile Electron Beam accelerator). According to the KAERI’s national research plan, basic radiation application working on sterilization, decomposition of antibiotics and endocrine disruptor contained in effluent by using radiation were conducted in KAERI’s laboratory for three years. In 2011, a field study on advanced sewage treatment with a MEB was conducted and the results obtained from study played an important role in the acquiring a certification on advanced treatment of sewage effluent by radiation, NET(New Environmental Technology), which is issued by Korea ministry of environment. The field study was carried out over four seasons in order to observe the effect of seasonal temperature changes on decomposition of chemicals contained in effluent of sewage. The major antibiotics and endocrine disruptors with initial concentration of 0.5 mg/l were decomposed completely by the irradiation dose less than 1.5 kGy, and coli form and microorganisms were also sterilized under the same irradiation dose. Toxicity arising by antibiotics on algae was reduced according to irradiation dose. In a future, achievements from the field demonstration study will be transferred to industry. Research on by-products from irradiated antibiotics and toxicity before and after irradiation of antibiotics will be continued in the field with MEB. This information will be useful for the project by radiation treatment of wastewater for reuse, particularly focused on the wastewater containing organic pollutants. (author)

  14. Endocrine system: part 1.

    Science.gov (United States)

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  15. Endocrine manifestations in celiac disease.

    Science.gov (United States)

    Freeman, Hugh James

    2016-10-14

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.

  16. Twenty-five years after "Wingspread"- Environmental endocrine disruptors (EDCs) and human health

    Science.gov (United States)

    The development of life-stage and tissue-specific AOPs for EDCs can reduce the uncertainty in extrapolating of the effects of EDCs from in vitro and in vivo studies in laboratory animals to humans. When the key events (KEs) and molecular initiating event (MIEs) in a pathway are...

  17. Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

    Science.gov (United States)

    Albini, A.; Rosano, C.; Angelini, G.; Amaro, A.; Esposito, A.I.; Maramotti, S.; Noonan, D.M.; Pfeffer, U.

    2014-01-01

    Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ERα and ERβ and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs). PMID:24304271

  18. Modeling the dispersion of endocrine disruptors in the Santos Estuarine System (Sao Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Giovana Teixeira Gimiliani

    2016-03-01

    Full Text Available Abstract Estrogens are hormones responsible for growth and reproduction. They are naturally synthesized by animals and humans alike. Xenoestrogens are identical to natural hormones, but they are man-made and used as oral contraceptives. Xenoestrogens are a specific group of drugs found in domestic wastewater and some environmental matrices. These compounds remain after conventional sewage treatment and, consequently, affect both the environment and non-target aquatic organisms. In this study, we used the Delft3D hydrodynamic model to estimate the amount of both natural and synthetic estrogens that have been released in the Estuarine System of Santos and São Vicente and the Santos Bay. The data on flow from the sewage treatment plants and on average concentrations of natural and synthetic estrogens released in aquatic environments were obtained from the literature. The results of the modeling showed higher concentrations of estrogens in the estuarine waters of the Largo Pompeba region, the São Vicente Canal, and the Santos Bay, which are regions that receive greater inflows of domestic sewage. The results also suggest that higher concentrations of estrogenic compounds are expected to be found in areas with higher levels of salinity.

  19. Food intolerance at adulthood after perinatal exposure to the endocrine disruptor bisphenol A.

    Science.gov (United States)

    Menard, Sandrine; Guzylack-Piriou, Laurence; Leveque, Mathilde; Braniste, Viorica; Lencina, Corinne; Naturel, Manon; Moussa, Lara; Sekkal, Soraya; Harkat, Cherryl; Gaultier, Eric; Theodorou, Vassilia; Houdeau, Eric

    2014-11-01

    The food contaminant bisphenol A (BPA) is pointed out as a risk factor in development of food allergy and food intolerance, two adverse food reactions increasing worldwide. We evaluated the consequences of perinatal exposure to low doses of BPA on immune-specific response to the food antigen ovalbumin (OVA) at adulthood. Perinatal exposure to BPA (0.5, 5, or 50 μg/kg/d) from 15th day of gravidity to pups weaning resulted in an increase of anti-OVA IgG titers at all BPA dosages in OVA-tolerized rats, and at 5 μg/kg/d in OVA-immunized rats compared to control rats treated with vehicle. In BPA-treated and OVA-tolerized rats, increased anti-OVA IgG titers were associated with higher IFNγ secretion by the spleen. This result is in accordance with the increase of activated CD4(+)CD44(high)CD62L(low) T lymphocytes observed in spleen of BPA-exposed rats compared to controls. Finally, when BPA-treated OVA-tolerized rats were orally challenged with OVA, colonic inflammation occurred, with neutrophil infiltration, increased IFNγ, and decreased TGFβ. We show that perinatal exposure to BPA altered oral tolerance and immunization to dietary antigens (OVA). In summary, the naive immune system of neonate is vulnerable to low doses of BPA that trigger food intolerance later in life. © FASEB.

  20. Diuron metabolites act as endocrine disruptors and alter aggressive behavior in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Boscolo, Camila Nomura Pereira; Pereira, Thiago Scremin Boscolo; Batalhão, Isabela Gertrudes; Dourado, Priscila Leocadia Rosa; Schlenk, Daniel; de Almeida, Eduardo Alves

    2018-01-01

    Diuron and its biodegradation metabolites were recently reported to cause alterations in plasma steroid hormone concentrations with subsequent impacts on reproductive development in fish. Since steroid hormone biosynthesis is regulated through neurotransmission of the central nervous system (CNS), studies were conducted to determine whether neurotransmitters that control hormone biosynthesis could be affected after diuron and diuron metabolites treatment. As the same neurotransmitters and steroid hormones regulate behavioral outcomes, aggression was also evaluated in male Nile tilapia (Oreochromis niloticus). Male tilapias were exposed for 10 days to waterborne diuron and the metabolites 3,4-dichloroaniline (DCA), 3,4-dichlorophenyl-N-methylurea (DCPMU), at nominal concentrations of 100 ng L -1 . In contrast to Diuron, DCA and DCPMU significantly diminished plasma testosterone concentrations (39.4% and 36.8%, respectively) and reduced dopamine levels in the brain (47.1% and 44.2%, respectively). In addition, concentrations of the stress steroid, cortisol were increased after DCA (71.0%) and DCPMU (57.8-%) exposure. A significant decrease in aggressive behavior was also observed in animals treated with the metabolites DCA (50.9%) and DCPMU (68.8%). These results indicate that biotransformation of diuron to active metabolites alter signaling pathways of the CNS which may impact androgen and the stress response as well as behavior necessary for social dominance, growth, and reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver

    2013-01-01

    Sexual brain differentiation is a potential EDC target. It depends on a combination of estrogen receptor- and androgen receptor-mediated effects in males and on estrogens in females. It is not known how these processes are affected by real-world mixtures of EDCs. We investigated the effect of thr...

  2. UV-C photolysis of endocrine disruptors. The influence of inorganic peroxides

    Energy Technology Data Exchange (ETDEWEB)

    Rivas, Javier, E-mail: fjrivas@unex.es [Departamento de Ingenieria Quimica y Quimica Fisica, Facultad de Ciencias, Avenida de Elvas S/N, 06071 Badajoz (Spain); Gimeno, Olga; Borralho, Teresa; Carbajo, Maria [Departamento de Ingenieria Quimica y Quimica Fisica, Facultad de Ciencias, Avenida de Elvas S/N, 06071 Badajoz (Spain)

    2010-02-15

    Norfloxacin, doxycycline and mefenamic acid have been photolysed with UV-C radiation (254 nm) in the presence and absence of inorganic peroxides (hydrogen peroxide or sodium monopersulfate). Quantum yields in the range (1.1-4.5) x 10{sup -3} mol Einstein{sup -1} indicate the low photo-reactivity of these pharmaceuticals. Inorganic peroxides considerably enhanced the contaminants conversion, although no appreciable mineralization could be obtained. A simplistic reaction mechanism for the hydrogen peroxide promoted experiments allowed for a rough estimation of the rate constant between hydroxyl radicals and norfloxacin (k > 1 x 10{sup 9} M{sup -1} s{sup -1}), doxycycline (k > 1.5 x 10{sup 9} M{sup -1} s{sup -1}) and mefenamic acid (k > 11.0 x 10{sup 9} M{sup -1} s{sup -1}).

  3. Endocrine disruptors and dental materials: health implications associated with their use in Brazil

    Directory of Open Access Journals (Sweden)

    Coelho Antonio Jorge Molinário

    2002-01-01

    Full Text Available This study analyzes international historical trends in the use of different types of materials in dental practice. The author describes the chemical properties of their ingredients and the potential and observed adverse effects in patients and dental technicians resulting from clinical or occupational exposure to various metals like beryllium, used to produce metal alloys. The growing use of various products (resin cements, ionomer cements, aesthetic restorative materials, resins, endodontal cements, and others based on the compound bisphenol-A, whose chemical structure is similar to that of estrogen. Considering the demographic and contemporary work force characteristics of those involved in dental practice in the Brazil, the study highlights the possible effect of the use of these materials in both male and female patients and all age strata, as well as in health professionals with occupational exposure to products containing bisphenol-A.

  4. Intergenerational response to the endocrine disruptor vinclozolin is influenced by maternal genotype and crossing scheme.

    Science.gov (United States)

    Pietryk, Edward W; Clement, Kiristin; Elnagheeb, Marwa; Kuster, Ryan; Kilpatrick, Kayla; Love, Michael I; Ideraabdullah, Folami Y

    2018-03-10

    In utero exposure to vinclozolin (VIN), an antiandrogenic fungicide, is linked to multigenerational phenotypic and epigenetic effects. Mechanisms remain unclear. We assessed the role of antiandrogenic activity and DNA sequence context by comparing effects of VIN vs. M2 (metabolite with greater antiandrogenic activity) and wild-type C57BL/6 (B6) mice vs. mice carrying mutations at the previously reported VIN-responsive H19/Igf2 locus. First generation offspring from VIN-treated 8nrCG mutant dams exhibited increased body weight and decreased sperm ICR methylation. Second generation pups sired by affected males exhibited decreased neonatal body weight but only when dam was unexposed. Offspring from M2 treatments, B6 dams, 8nrCG sires or additional mutant lines were not similarly affected. Therefore, pup response to VIN over two generations detected here was an 8nrCG-specific maternal effect, independent of antiandrogenic activity. These findings demonstrate that maternal effects and crossing scheme play a major role in multigenerational response to in utero exposures. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Influence of temperature on thyroid hormone signaling and endocrine disruptor action in Rana (Lithobates) catesbeiana tadpoles.

    Science.gov (United States)

    Hammond, S Austin; Veldhoen, Nik; Helbing, Caren C

    2015-08-01

    Thyroid hormones (THs) are essential for normal growth, development, and metabolic control in vertebrates. Their absolute requirement during amphibian metamorphosis provides a powerful means to detect and assess the impact of environmental contaminants on TH signaling in the field and laboratory. As poikilotherms, frogs can experience considerable temperature fluctuations. Previous work demonstrated that low temperature prevents precocious TH-dependent induction of metamorphosis. However, a shift to a permissive higher temperature allows resumption of the induced metamorphic program regardless of whether or not TH remains. We investigated the impact of temperature on the TH-induced gene expression programs of premetamorphic Rana (Lithobates) catesbeiana tadpoles following a single injection of 10pmol/g body wet weight 3,3',5-triiodothyronine (T3). Abundance profiles of several T3-responsive mRNAs in liver, brain, lung, back skin, and tail fin were characterized under permissive (24°C), nonpermissive (5°C), or temperature shift (5-24°C) conditions. While responsiveness to T3 was retained to varying degrees at nonpermissive temperature, T3 modulation of thibz occurred in all tissues at 5°C suggesting an important role for this transcription factor in initiation of T3-dependent gene expression programs. Low temperature immersion of tadpoles in water containing 10nM T3 and the nonsteroidal anti-inflammatory drug, ibuprofen, or the antimicrobial agent, triclosan, perturbed some aspects of the gene expression programs of tail fin and back skin that was only evident upon temperature shift. Such temporal uncoupling of chemical exposure and resultant biological effects in developing frogs necessitates a careful evaluation of environmental temperature influence in environmental monitoring programs. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Photolytic destruction of endocrine disruptor atrazine in aqueous solution under UV irradiation: Products and pathways

    Energy Technology Data Exchange (ETDEWEB)

    Chen Cheng [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Yang Shaogui, E-mail: yangdlut@126.com [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Guo Yaping [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Sun Cheng, E-mail: envidean@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Gu Chenggang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Xu Bin [School of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resources Reuse, Tongji University, Shanghai (China)

    2009-12-30

    The ultraviolet (UV) photolysis of atrazine in aqueous solution was investigated at wavelength of 254 nm in this study. This paper was mainly focused on the identification of atrazine degradation intermediates by HPLC-MS/MS and its degradation mechanisms. The photodegradation products included the following seven classes: dechloro-hydroxylated products, chloro-dealkylated products, dechloro-dealkylated products, alkylic-oxidated products, delamination-hydroxylated products, olefinic products, and dechloro-hydrogenated products which were never reported in direct photolytic process, 4-isopropylamino-6-ethylamino-s-triazine (IEST), 4,6-dihydroxy-s-triazine (OOST). The main degradation products were 2-hydroxy-4-acetamido-6-ethylamino-s-triazine (OIET), 2-chloro-4-isopropyl-amino-6-methylamino-s-triazine (CIMT), 2-chloro-4,6-divinylamino-s-triazine (CVVT), 2-chloro-4-ethylamino-6-amino-s-triazine(CEAT), 2-methoxy-4-isopropyl-amino-6-methylamino-s-triazine (OIMT), 2-hydroxy-4-acetamindo-6-ethylamino-s-triazine (ODET), etc. Finally, the possible degradation mechanism was also proposed here.

  7. Speciation, Phenotypic Variation and Plasticity: What Can Endocrine Disruptors Tell Us?

    Directory of Open Access Journals (Sweden)

    Braulio Ayala-García

    2013-01-01

    Full Text Available Phenotype variability, phenotypic plasticity, and the inheritance of phenotypic traits constitute the fundamental ground of processes such as individuation, individual and species adaptation and ultimately speciation. Even though traditional evolutionary thinking relies on genetic mutations as the main source of intra- and interspecies phenotypic variability, recent studies suggest that the epigenetic modulation of gene transcription and translation, epigenetic memory, and epigenetic inheritance are by far the most frequent reliable sources of transgenerational variability among viable individuals within and across organismal species. Therefore, individuation and speciation should be considered as nonmutational epigenetic phenomena.

  8. impact of endocrine disruptors on man: the likely causes and effects 93

    African Journals Online (AJOL)

    DR. AMINU

    2014-06-01

    Jun 1, 2014 ... body of humans and wildlife, thereby mimicking the action of endogenous hormones that regulate maintenance of normal growth, ..... Sugano., M. (2009): Effect of dioxins on regulation of tyrosine hydroxylase gene .... Guo, Y. L., Hsu, P. C., Hsu, C. C. and Lambert, G. H.. (2000): Semen quality after prenatal.

  9. Endocrine disruptors and dental materials: health implications associated with their use in Brazil

    Directory of Open Access Journals (Sweden)

    Antonio Jorge Molinário Coelho

    2002-04-01

    Full Text Available This study analyzes international historical trends in the use of different types of materials in dental practice. The author describes the chemical properties of their ingredients and the potential and observed adverse effects in patients and dental technicians resulting from clinical or occupational exposure to various metals like beryllium, used to produce metal alloys. The growing use of various products (resin cements, ionomer cements, aesthetic restorative materials, resins, endodontal cements, and others based on the compound bisphenol-A, whose chemical structure is similar to that of estrogen. Considering the demographic and contemporary work force characteristics of those involved in dental practice in the Brazil, the study highlights the possible effect of the use of these materials in both male and female patients and all age strata, as well as in health professionals with occupational exposure to products containing bisphenol-A.

  10. A Novel Amphibian Tier 2 Testing Protocol: A 30-Week Exposure of Xenopus Tropicalis to the Antiandrogen Flutamide

    National Research Council Canada - National Science Library

    Knechtges, Paul L; Sprando, Robert L; Porter, Karen L; Brennan, Linda M; Miller, Mark F; Kumsher, David M; Dennis, William E; Brown, Charles C; Clegg Paul L. Knechtges. Robert L. Sprando. Karen L. Potter., Eric D

    2007-01-01

    ...) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs...

  11. Data for Summary of the Development the US Environmental Protection Agency’s Medaka Extended One Generation Reproduction Test (MEOGRT) Using Data from Nine Multigenerational Medaka Tests

    Data.gov (United States)

    U.S. Environmental Protection Agency — In response to various legislative mandates the United States Environmental Protection Agency (USEPA) formed its Endocrine Disruptor Screening Program (EDSP), which...

  12. Endocrine system and obesity.

    Science.gov (United States)

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients. Copyright © 2010. Published by Elsevier Inc.

  13. Point-of-Care Endocrine Diagnostics.

    Science.gov (United States)

    Ehrenkranz, Joel

    2017-09-01

    Endocrinology relies on hormone and metabolite measurement for public health screening, diagnostics, and disease management. Advances in microfluidics, immunoassay technology, electronics, and software are moving in vitro endocrine diagnostics from the laboratory to the point of care. Point-of-care endocrine diagnostics provide results clinically equivalent to those produced by expensive laboratory instrumentation for a fraction of the cost and with a substantially more rapid turnaround time. Similar to the transformation of mainframe computers into laptops, tablets, and smartphones, clinical laboratories are evolving into point-of-care technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. New in vitro reporter gene bioassays for screening of hormonal active compounds in the environment

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Kateřina; Cajthaml, Tomáš

    2010-01-01

    Roč. 88, č. 4 (2010), s. 839-847 ISSN 0175-7598 R&D Projects: GA ČR GAP503/10/0408 Institutional research plan: CEZ:AV0Z50200510 Keywords : endocrine disruptors * in vitro bioassays * reporter gene assays Subject RIV: EE - Microbiology, Virology Impact factor: 3.280, year: 2010

  15. Obesity as disruptor of the female fertility.

    Science.gov (United States)

    Silvestris, Erica; de Pergola, Giovanni; Rosania, Raffaele; Loverro, Giuseppe

    2018-03-09

    Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation. Moreover, endometrial implantation and other reproductive functions are affected in obese women with complications including delayed conceptions, increased miscarriage rate, reduced outcomes in assisted conception treatments.On the contrary, weight loss programs through lifestyle modification in obese women, have been proven to restore menstrual cyclicity and ovulation and improve the likelihood of conception.

  16. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    hormones and their precursors across the foeto-maternal interface. The endocrine system is the earliest system developing in foetal life, and it is functional from early intrauterine existence through old age. Regulation of the foetal endocrine system relies, to some extent, on precursors secreted......The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...

  17. Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

    Science.gov (United States)

    Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

    2018-01-01

    Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

  18. Overview of the Pathophysiological Implications of Organotins on the Endocrine System

    Directory of Open Access Journals (Sweden)

    Vinicius Bermond Marques

    2018-03-01

    Full Text Available Organotins (OTs are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis, altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus or peripheral (e.g., adipose tissue mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

  19. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Deborah Molehin

    2016-01-01

    Full Text Available Background. Thyroid hormones (THs are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers.

  20. Population Survey of Iodine Deficiency and Environmental Disruptors of Thyroid Function in Young Children in Haiti.

    Science.gov (United States)

    von Oettingen, Julia E; Brathwaite, Tesha D; Carpenter, Christopher; Bonnell, Ric; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N; Larco, Philippe; Larco, Nancy Charles; Jean-Baptiste, Eddy; Brown, Rosalind S

    2017-02-01

    Iodine deficiency is the leading cause of preventable neurodevelopmental delay in children worldwide and a possible public health concern in Haiti. To determine the prevalence of iodine deficiency in Haitian young children and its influence by environmental factors. Cross-sectional study, March through June 2015. Community churches in 3 geographical regions in Haiti. 299 healthy Haitian children aged 9 months to 6 years; one-third each enrolled in a coastal, mountainous, and urban region. Urinary iodide, serum thyrotropin (TSH), goiter assessment, and urinary perchlorate and thiocyanate. Mean age was 3.3±1.6 years, with 51% female, median family income USD 30/week, and 16% malnutrition. Median urinary iodide levels were normal in coastal (145 μg/L, interquartile range [IQR] 97 to 241) and urban regions (187 μg/L, IQR 92 to 316), but revealed mild iodine deficiency in a mountainous region (89 μg/L, IQR 56 to 129), P < 0.0001. Grade 1 goiters were palpated in 2 children, but TSH values were normal. Urinary thiocyanate and perchlorate concentrations were not elevated. Predictors of higher urinary iodide included higher urinary thiocyanate and perchlorate, breastfeeding, and not living in a mountainous region. Areas of mild iodine deficiency persist in Haiti's mountainous regions. Exposure to two well-understood environmental thyroid function disruptors is limited. Copyright © 2017 by the Endocrine Society

  1. QSAR model for human pregnane X receptor (PXR) binding: Screening of environmental chemicals and correlations with genotoxicity, endocrine disruption and teratogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Dybdahl, Marianne, E-mail: mdyb@food.dtu.dk; Nikolov, Nikolai G.; Wedebye, Eva Bay; Jónsdóttir, Svava Ósk; Niemelä, Jay R.

    2012-08-01

    The pregnane X receptor (PXR) has a key role in regulating the metabolism and transport of structurally diverse endogenous and exogenous compounds. Activation of PXR has the potential to initiate adverse effects, causing drug–drug interactions, and perturbing normal physiological functions. Therefore, identification of PXR ligands would be valuable information for pharmaceutical and toxicological research. In the present study, we developed a quantitative structure–activity relationship (QSAR) model for the identification of PXR ligands using data based on a human PXR binding assay. A total of 631 molecules, representing a variety of chemical structures, constituted the training set of the model. Cross-validation of the model showed a sensitivity of 82%, a specificity of 85%, and a concordance of 84%. The developed model provided knowledge about molecular descriptors that may influence the binding of molecules to PXR. The model was used to screen a large inventory of environmental chemicals, of which 47% was found to be within domain of the model. Approximately 35% of the chemicals within domain were predicted to be PXR ligands. The predicted PXR ligands were found to be overrepresented among chemicals predicted to cause adverse effects, such as genotoxicity, teratogenicity, estrogen receptor activation and androgen receptor antagonism compared to chemicals not causing these effects. The developed model may be useful as a tool for predicting potential PXR ligands and for providing mechanistic information of toxic effects of chemicals. -- Highlights: ► Global QSAR model for the identification of PXR ligands was developed. ► Molecular descriptors that may influence PXR binding were identified. ► 35% of a large set of environmental chemicals were predicted to be PXR ligands. ► Predicted PXR binding was associated with various adverse effects.

  2. Endocrine System (For Teens)

    Science.gov (United States)

    ... in the middle of the brain. It secretes melatonin (pronounced: meh-luh-TOE-nin), a hormone that ... cycle. These hormones also play a role in pregnancy. Although the endocrine glands are the body's main ...

  3. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V

    2001-01-01

    processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...... or embryo models for the evaluation of possible consequences of human exposure to endocrine disrupting compounds is discussed. Furthermore, possible consequences of exposure to endocrine disrupting compounds for the embryo transfer industry are addressed....

  4. Endocrine system: part 2.

    Science.gov (United States)

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-03

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  5. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  6. Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones

    Science.gov (United States)

    Endocrine disruption is considered a highly relevant endpoint for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening for endocrine disruption – with focus on vertebrates (fish and amphibians) and estrogen, and...

  7. Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology.

    Science.gov (United States)

    Weltje, Lennart; Wheeler, James R; Weyers, Arnd; Galay-Burgos, Malyka

    2013-12-16

    To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed. Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments. Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment. These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical. Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified. Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is 'negligible exposure'. This paper discusses and provides proposals on how to apply these concepts for assessment of substances. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Endocrine-disrupting chemicals and obesity development in humans: A review

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett; Andersen, Helle Raun; Jensen, Tina Kold

    2011-01-01

    This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The resu......This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans...... dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes...... predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors....

  9. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase...... hormones and their precursors across the foeto-maternal interface. The endocrine system is the earliest system developing in foetal life, and it is functional from early intrauterine existence through old age. Regulation of the foetal endocrine system relies, to some extent, on precursors secreted...

  10. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  11. Management of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Kahaly, G.J.

    2001-01-01

    Endocrine orbitopathy is the most common extrathyroidal manifestation of Basedow's disease and is characterized by a lymphocyte infiltration of the peribulbar space. Infiltrating and activated T cells react with orbital target cells and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema, and enlargement of the extra ocular muscels. Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with endocrine orbitopathy. Immunosuppressive treatment is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of thyroid eye disease. (orig.) [de

  12. Multiple Endocrine Neoplasia Type I

    Science.gov (United States)

    ... hormone (GnRH). GnRH is normally secreted by the hypothalamus and stimulates the pituitary gland to release follicle ... do not require treatment. Treatment of Pancreatic Endocrine Cancer in MEN1 Because the type of pancreatic endocrine ...

  13. Multiple endocrine neoplasia (MEN) II

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000399.htm Multiple endocrine neoplasia (MEN) II To use the sharing features on this page, please enable JavaScript. Multiple endocrine neoplasia, type II (MEN II) is a disorder passed ...

  14. Analytical Methodologies for the Determination of Endocrine Disrupting Compounds in Biological and Environmental Samples

    Directory of Open Access Journals (Sweden)

    Zoraida Sosa-Ferrera

    2013-01-01

    Full Text Available Endocrine-disruptor compounds (EDCs can mimic natural hormones and produce adverse effects in the endocrine functions by interacting with estrogen receptors. EDCs include both natural and synthetic chemicals, such as hormones, personal care products, surfactants, and flame retardants, among others. EDCs are characterised by their ubiquitous presence at trace-level concentrations and their wide diversity. Since the discovery of the adverse effects of these pollutants on wildlife and human health, analytical methods have been developed for their qualitative and quantitative determination. In particular, mass-based analytical methods show excellent sensitivity and precision for their quantification. This paper reviews recently published analytical methodologies for the sample preparation and for the determination of these compounds in different environmental and biological matrices by liquid chromatography coupled with mass spectrometry. The various sample preparation techniques are compared and discussed. In addition, recent developments and advances in this field are presented.

  15. Sleep and the endocrine system.

    Science.gov (United States)

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The influence of control group reproduction on the statistical power of the Environmental Protection Agency’s medaka Extended One-Generation Reproduction Test (MEOGRT)

    Science.gov (United States)

    Because of various Congressional mandates to protect the environment from endocrine disrupting chemicals (EDCs), the United States Environmental Protection Agency (USEPA) initiated the Endocrine Disruptor Screening Program. In the context of this framework, the Office of Research...

  17. Imaging of endocrine system

    International Nuclear Information System (INIS)

    Das, B.K.; Noreen Norfaraheen Lee Abdullah

    2012-01-01

    In recent years, the role of nuclear medicine in the study of morphology and pathophysiology of various endocrine organs has greatly expanded. Newly developed radiopharmaceuticals, new instrumentation, innovative study designs and dual isotope techniques have contributed significantly to the evaluation of parathyroid and adrenal diseases. In selected cases, patients with metabolic bone disorders and infertility have greatly been benefited. (author)

  18. Nigerian Endocrine Practice: Submissions

    African Journals Online (AJOL)

    Original Articles should be restricted to clinical or basic studies, particularly translational research, which add new information to the etiology, treatment, and outcomes of endocrine disorders that have not been published previously. These manuscripts should be restricted to 3,500 words, no more than 40 references, and no ...

  19. Nigerian Endocrine Practice

    African Journals Online (AJOL)

    The journal accepts original contributions related to the practice and science of clinical endocrinology, articles updating the clinical endocrinologist on current areas of interest in the diagnosis and treatment of endocrine disorders, articles discussing dilemma facing endocrinologists in the clinical, social, and ethical arena of ...

  20. FIFRA Scientific Advisory Panel Minutes No. 21015-04. A set of scientific issues being considered by the Environmental Protection Agency regarding integrated endocrine bioactivity and exposure-based prioritization & screening

    Science.gov (United States)

    On December 2-4, 2014, the US Environmental Protection Agency convened a public meeting of the FIFRA Scientific Advisory Panel (SAP) to address scientific issues associated with the agency’s “Integrated Endocrine Bioactivity and Exposure-Based Prioritization and Screening” methods. EPA is proposing ...

  1. [Xenoestrogens: endocrine disrupting compounds].

    Science.gov (United States)

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  2. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...... during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase...

  3. Endocrine Pancreas Regeneration

    Science.gov (United States)

    2010-06-01

    endocrine hormone-producing cells. PNAS 2002;99(12):8078- 83. 30. Horb ME, Shen CN, Tosh D, Slack JM. Experimental conversion of liver to pancreas...Transplantation, Rock - ville, MD; United Network for Organ Sharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MI. 10. R. W. G...and incubated for 1 h at room temperature on a rocking plate. Non-adherent U-937 cells were removed and adherent cells fixed in 1% glutaraldehyde. The

  4. Radiotherapy of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Weischedel, U.; Wieland, C.

    1985-01-01

    After a review of the history and a discussion of recent theories about pathogenesis of endocrine ophthalmopathy the authros give a report on their radiotherapeutical treatment results with cobalt-60-γ-rays in 50 patients. Amelioration was achieved in 50% of the cases, in the other 50% no progression was seen. Radiotherapy is of antiphlogistic and functional effectivity and should be integrated in the treatment regime in early stages. (orig.) [de

  5. [Endocrine function in obesity].

    Science.gov (United States)

    Álvarez-Castro, Paula; Sangiao-Alvarellos, Susana; Brandón-Sandá, Iria; Cordido, Fernando

    2011-10-01

    Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Corticosteroid production in H295R cells during exposure to 3 endocrine disrupters analyzed with LC-MS/MS

    DEFF Research Database (Denmark)

    Winther, Christina S; Nielsen, Frederik K; Hansen, Martin

    2013-01-01

    295R cell line. The method was applied by studying the effects of 2 model endocrine disrupters, ketoconazole and prochloraz, the pharmaceutical budesonide, and the inducer forskolin on the steroid production in this cell line. Dose-response curves were obtained for the correlation between hormone...... concentrations and the concentration of the individual disruptors. Exposing cells to ketoconazole resulted in a decrease in cortisol and corticosterone concentrations in a dose-dependent manner with EC₅₀ values of 0.24 and 0.40 μmol/L, respectively. The same applied for cells exposed to prochloraz with EC₅₀...

  7. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Skilton, Rebeca [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Lavado, Ramon [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Thibaut, Remi [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Minier, Christophe [Laboratoire d' Ecotoxicologie, Universite du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre (France); Porte, Cinta [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)]. E-mail: cpvqam@cid.csic.es

    2006-05-15

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17{beta}-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period.

  8. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    International Nuclear Information System (INIS)

    Martin-Skilton, Rebeca; Lavado, Ramon; Thibaut, Remi; Minier, Christophe; Porte, Cinta

    2006-01-01

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17β-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period

  9. Proteomic response of Macrobrachium rosenbergii hepatopancreas exposed to chlordecone: Identification of endocrine disruption biomarkers?

    Science.gov (United States)

    Lafontaine, Anne; Baiwir, Dominique; Joaquim-Justo, Célia; De Pauw, Edwin; Lemoine, Soazig; Boulangé-Lecomte, Céline; Forget-Leray, Joëlle; Thomé, Jean-Pierre; Gismondi, Eric

    2017-07-01

    The present work is the first study investigating the impacts of chlordecone, an organochlorine insecticide, on the proteome of the decapod crustacean Macrobrachium rosenbergii, by gel-free proteomic analysis. The hepatopancreas protein expression variations were analysed in organisms exposed to three environmental relevant concentrations of chlordecone (i.e. 0.2, 2 and 20µg/L). Results revealed that 62 proteins were significantly up- or down-regulated in exposed prawns compared to controls. Most of these proteins are involved in important physiological processes such as ion transport, defense mechanisms and immune system, cytoskeleton dynamics, or protein synthesis and degradation. Moreover, it appears that 6% of the deregulated protein are involved in the endocrine system and in the hormonal control of reproduction or development processes of M. rosenbergii (e.g. vitellogenin, farnesoic acid o-methyltransferase). These results indicate that chlordecone is potentially an endocrine disruptor compound for decapods, as already observed in vertebrates. These protein modifications could lead to disruptions of M. rosenbergii growth and reproduction, and therefore of the fitness population on the long-term. Besides, these disrupted proteins could be suggested as biomarkers of exposure for endocrine disruptions in invertebrates. However, further investigations are needed to complete understanding of action mechanisms of chlordecone on proteome and endocrine system of crustaceans. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Radiological imaging in endocrine hypertension

    Directory of Open Access Journals (Sweden)

    Chandan J Das

    2011-01-01

    Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

  11. Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kent Reifschneider

    2015-07-01

    Full Text Available Traumatic brain injuries (TBI are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

  12. Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts

    Directory of Open Access Journals (Sweden)

    Weihe Pal

    2003-10-01

    Full Text Available Abstract Background Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations. Methods We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard. Results and conclusions To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an

  13. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  14. [Dementia due to Endocrine Diseases].

    Science.gov (United States)

    Matsunaga, Akiko; Yoneda, Makoto

    2016-04-01

    Endocrine diseases affecting various organs, such as the pituitary gland, the thyroid, the parathyroid, the adrenal glands and the pancreas, occasionally cause dementia. While Alzheimer's disease (AD) is the main cause of dementia in the elderly and is untreatable, dementia caused by endocrine diseases is treatable in most cases. However, patients with dementia associated with endocrine diseases show memory impairments similar to those found in AD, often leading to misdiagnoses. Patients with endocrine diseases often present with other characteristic systemic and neuropsychiatric symptoms caused by altered hormone levels. Such neuropsychiatric symptoms include involuntary movements, depression, seizures, and muscle weakness. In these cases, abnormalities in imaging and blood or urine tests are helpful in making a differential diagnosis. As delays in the diagnosis and treatment of these patients may cause irreversible brain damage, it is imperative for clinicians to carefully exclude the possibility of latent endocrine diseases when treating patients with dementia.

  15. Endocrine disorders in mitochondrial disease.

    Science.gov (United States)

    Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

    2013-10-15

    Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. Cloning of the relative genes of endocrine exophthalmos

    International Nuclear Information System (INIS)

    Zheng, JG

    2004-01-01

    respectively, and was labeled with digoxigenin (DIG.). The colony PCR products of the relative genes of endocrine exophthalmos were degenerated, dotted on the nylon membrane, and hybridized with the labeled probes to test the positive clone. The inserted fragments of positive clone was sequenced by a professional biotechnical group. Results: The intact and high-pure mRNA was obtained. The double chains of cDNA were synthesized by using the mRNA as a model. The Hae III products was less than 3 kb. The efficacies of subtraction suggested that the subtraction happened really and the experience was successful. The PCR products could be used to construct the suppressive subtractive library. Fourty eight white bacteria clonies selected randomly had the amplification products of 2 transformants with double bands, the others with single one. Through dot blots, the transformation which had hybridization signal with thyroid tissues of endocrine exophthalmos, and had no that with thyroid tissues without endocrine exophthalmos, was positive clones. The positive ratio was about 40%. The insert fragments in the positive clones were endocrine exophthalmos-related genes/ cDNA fragments. Conclusions: The endocrine exophthalmos-specific subtractive products obtained by suppression subtractive hybridization were cloned. After a high throughput screening, the endocrine exophthalmos -related genes or cDNA fragments were obtained. (authors)

  17. Endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Mandrup, Karen

    BACKGROUND: Endocrine disrupting chemicals (EDCs) may contribute to reproductive changes in boys in the Western world, however, less is known about influence of EDCs in women. The incidence of precocious breast development is increasing in USA and Europe and mammary gland development has been...... gland development before puberty in whole mounted mammary glands and in adults in histological sections of the mammary glands. Moreover, female offspring were evaluated for external genital malformations. The EDCs studied for mammary gland effects were the estrogenic compounds ethinyl estradiol...... were sensitive to EDCs. EDCs with estrogenic mode of action appeared to increase mammary outgrowth in prepubertal female rats and a potent model compound, ethinyl estradiol, increased the density in females and males and the number of terminal end buds in male rats. Histological examination showed...

  18. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V

    2001-01-01

    of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3......With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

  19. Endocrine disrupting chemicals: harmful substances and how to test them Produtos químicos como desreguladores endócrinos: substâncias danosas e como devem ser testadas

    Directory of Open Access Journals (Sweden)

    Nicolás Olea-Serrano

    2002-04-01

    Full Text Available This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.Este artigo apresenta uma análise das opiniões de diferentes grupos, inclusive de cientistas, agências regulatórias internacionais, organizações não-governamentais e indústrias, interessados na questão da identificação de substâncias químicas com atividade desreguladora endócrina. Os autores discutem também o impacto da exposição aos desreguladores endócrinos sobre a saúde humana, considerando as seguintes questões: estimativa de risco; testes utilizados para detectar distúrbios endócrinos; dificuldades na identificação de uma associação entre dose, tempo de exposição, suscetibilidade individual e efeito e tentativas no sentido de mapear os desreguladores endócrinos. Finalmente, os autores argumentam que nem todos os agonistas hormonais devem ser incluídos sob a denominação genérica de desreguladores endócrinos.

  20. The effect of perinatal exposure to ethinyl oestradiol or a mixture of endocrine disrupting pesticides on kisspeptin neurons in the rat hypothalamus

    DEFF Research Database (Denmark)

    Overgaard, Agnete; Holst, Klaus; Mandrup, Karen

    2013-01-01

    Early life exposure to endocrine disruptors is considered to disturb normal development of hormone sensitive parameters and contribute to advanced puberty and reduced fecundity in humans. Kisspeptin is a positive regulator of the hypothalamic–pituitary–gonadal axis, and plays a key role in the in......Early life exposure to endocrine disruptors is considered to disturb normal development of hormone sensitive parameters and contribute to advanced puberty and reduced fecundity in humans. Kisspeptin is a positive regulator of the hypothalamic–pituitary–gonadal axis, and plays a key role.......We find that perinatal EE2 exposure did not affect Kiss1 mRNA expression in this study designed to model human exposure to estrogenic compounds, and we find only minor effects on puberty onset. Further, the Kiss1 system does not exhibit persistent changes and puberty onset is not affected after perinatal...... exposure to a pesticide mixture in this experimental setting. However, we find that the pesticide mancozeb tends to increase Kiss1 expression in the ARC, presumably through neurotoxic mechanisms rather than via classical endocrine disruption, calling for increased awareness that Kiss1 expression can...

  1. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    International Nuclear Information System (INIS)

    Martinez–Arguelles, D.B.; McIntosh, M.; Rohlicek, C.V.; Culty, M.; Zirkin, B.R.; Papadopoulos, V.

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

  2. Considerations for estimating daily intake values of non-persistent environmental endocrine disruptors based on urinary biomonitoring data

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Andersson, Anna-Maria

    2014-01-01

    -calculation of parabens in humans. The recovery of both oral and dermal triclosan in humans has been studied, but due to background levels of triclosan, the back-calculation is difficult to perform.ConclusionDue to limited data, reasonable estimates of daily intake values based on urinary data are often not possible...... into daily intake values for bisphenol A, phthalates, parabens and triclosan, and to identify knowledge gaps.MethodsHuman data was evaluated and supplied with relevant animal data. Focus was on recovery of the administered dose, the route of administration and on differences between humans and animals.......ResultsTwo human toxicokinetic studies are currently used to conclude that an oral dose of bisphenol A is recoverable in urine and that no free bisphenol A is present in plasma in spite of several contradicting biominotoring studies.Urinary recovery of an oral dose of phthalates in humans is complicated to assess...

  3. IFPA meeting 2015 workshop report III : nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid

    NARCIS (Netherlands)

    Albrecht, C.; Caniggia, I.; Clifton, V.; Göhner, C; Harris, L.; Hemmings, D.; Jawerbaum, A.; Johnstone, E.; Jones, H.; Keelan, J.; Lewis, R.; Mitchell, M.; Murthi, P.; Powell, T.; Saffery, R.; Smith, R.; Vaillancourt, C.; Wadsack, C.; Salomon, C.

    2016-01-01

    Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but

  4. Effects of Endocrine Disruptors Ethinylestradiol and Procloraz on the vocal system of the frog Xenopus tropicalis

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Nørum, Ulrik; Korsgaard, Bodil

    2009-01-01

      Prochloraz masculinizes the larynx of female Xenopus tropicalis   Endogenous sex steroids are not only important for sexual differentiation in amphibians, but also for the development of secondary sex characteristics. The advertisement call of male frogs is used to attract females and in male...... and shape of the larynx and other structures in the vocal pathway but also properties of the laryngeal muscles such as twitch type, enzymatic activity, dynamic properties, efficacy of the laryngeal synapses of the laryngeal neuromuscular junction, and the number of laryngeal motor neurons and axons...

  5. Phthalates and heavy metals as endocrine disruptors in food: A study on pre-packed coffee products

    Directory of Open Access Journals (Sweden)

    Luca De Toni

    Full Text Available Phthalate plasticizers and heavy metals are widely recognized to be pollutants that interfere with key developmental processes such as masculinization. We investigated the release of phthalates and heavy metals in coffee brewed from coffee packed in single-serve coffee containers made from different types of materials: metal, biodegradable and plastics. We detected with GC–MS small amounts phthalates, below the tolerated daily risks levels, in all the coffees prepared from the different types of capsules. Specifically, Di (2-ethyl-hexyl-phthalate and DiBP: Diisobuthyl-pthalate were ubiquitously present despite the high variability among the samples (respective range 0.16–1.87 μg/mL and 0.01–0.36 μg/mL. Whereas, diethyl-phthalate (range 0.20–0.26 μg/mL and di-n-buthyl-phthalate (range 0.02–0.14 μg/mL were detected respectively in one and three out of the four types of capsule tested. In contrast, we detected by atomic mass spectrometry on mineralized samples heavy metals lead (Pb and nickel (Ni, in all coffee tested. PB levels (respective range 0.32–211.57 μg/dose accounted for 42–79%, whereas Ni levels (respective range 166.25–1950.26 μg/dose accounted for >100% of the tolerable daily intake. These results add to the already present concerns related to the multiple pathways of human exposure and the ubiquitous presence of these pollutants in consumer products and their long-term effect on human health. Keywords: Masculinization, Coffee pods, Phthalates, Heavy metals, Hazard index, Tolerable daily intake

  6. Groundwater from infiltration galleries used for small public water supply systems: contamination with pesticides and endocrine disruptors.

    Science.gov (United States)

    Mansilha, C; Melo, A; Ferreira, I M P L V O; Pinho, O; Domingues, V; Pinho, C; Gameiro, P

    2011-09-01

    Infiltration galleries are among the oldest known means used for small public water fountains. Owing to its ancestral origin they are usually associated with high quality water. Thirty-one compounds, including pesticides and estrogens from different chemical families, were analysed in waters from infiltration galleries collected in Alto Douro Demarcated Wine region (North of Portugal). A total of twelve compounds were detected in the water samples. Nine of these compounds are described as presenting evidence or potential evidence of interfering with the hormone system of humans and wildlife. Although concentrations of the target analytes were relatively low, many of them below their limit of quantification, four compounds were above quantification limit and two of them even above the legal limit of 0.1 μg/L: dimethoate (30.38 ng/L), folpet (64.35 ng/L), terbuthylazine-desethyl (22.28 to 292.36 ng/L) and terbuthylazine (22.49 to 369.33 ng/L).

  7. Cofactor-embedded nanoporous activated carbon matrices for the immobilization of intracellular enzymes and degradation of endocrine disruptor.

    Science.gov (United States)

    Paranji, Saranya; Ganesan, Sekaran

    2017-05-01

    The mixed intracellular enzyme (MICE) from Citrobacter freundii, capable of degrading o-phenylene diamine (OPD), was extracted and characterized. Cofactors such as zinc and copper ions enhanced the MICE activity. The functionalized nanoporous-activated carbon (FNAC) matrix, zinc-impregnated FNAC matrix (Zn 2+ -FNAC), copper-impregnated FNAC matrix (Cu 2+ -FNAC), and zinc- and copper-impregnated FNAC matrix (Zn 2+ -Cu 2+ -FNAC) were prepared and characterized to immobilize MICE. The parameters such as time (0-240 Min), pH (1-10), temperature (20-50 ºC), amount of MICE (1-5 mg), particle size of carbon (100-600 μm), and mass of carbon (0.5-2.5 g) were optimized for immobilization of MICE on different FNAC matrices. The carrier matrices in the free and MICE immobilized form were characterized using SEM, FT-IR, XPS, XRD, thermogravimetric analysis (TGA), and DSC analyses. The kinetic and adsorption models for the immobilization of MICE on FNAC matrices were studied. The parameters such as time, pH, temperature, concentration of OPD, and agitation speed were optimized for the degradation of OPD using FNAC-MICE and MICE-immobilized metal-impregnated FNAC matrices. The maximum amount of pyruvic acid formed was found to be 133 μg/mg of OPD using Zn 2+ -Cu 2+ -FNAC-MICE matrix. The kinetic models were studied for the formation of pyruvic acid on OPD degradation and confirmed using FT-IR spectroscopy. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  8. Effects of two endocrine disruptors Prochloraz and Ethinylestradiol on development of Rana Temporaria

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Christensen-Dalsgaard, Jakob; Korsgaard, Bodil

    2009-01-01

      Effects of Prochloraz and Ethinylestradiol on development in Rana temporaria   The ontogeny of most amphibians is characterized by a large degree of sexual plasticity and sex steroids play an important role in the final differentiation of the gonads. One consequence of this plasticity is that e......  Effects of Prochloraz and Ethinylestradiol on development in Rana temporaria   The ontogeny of most amphibians is characterized by a large degree of sexual plasticity and sex steroids play an important role in the final differentiation of the gonads. One consequence of this plasticity...

  9. What Is Women's Endocrine Health?

    Science.gov (United States)

    ... aimed directly at them such as commercials on TV, radio and print magazines. Young girls receive so ... endocrine disorders during this age is pivotal. Young Women At this time of life, young women are ...

  10. Endocrine causes of dangerous fever.

    Science.gov (United States)

    Tenner, Andrea G; Halvorson, Karin M

    2013-11-01

    This article provides an overview of the pathogenesis and signs and symptoms of dangerous endocrine causes of hyperthermia. Treatment strategies based on specific causes are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2008-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  12. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert S

    2005-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40...

  13. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2007-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  14. Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System.

    Science.gov (United States)

    Autrup, Herman; Barile, Frank A; Blaauboer, Bas J; Degen, Gisela H; Dekant, Wolfgang; Dietrich, Daniel; Domingo, Jose L; Gori, Gio Batta; Greim, Helmuth; Hengstler, Jan G; Kacew, Sam; Marquardt, Hans; Pelkonen, Olavi; Savolainen, Kai; Vermeulen, Nico P

    2015-07-01

    The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be subjected to the well-evaluated health risk characterization approach used for many years including adverse outcome pathways. Many of the points arguing for a specific approach for risk characterization of chemicals with hormonal activity are based on highly speculative conclusions. These conclusions are not well supported when evaluating the available information. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Trauma and the endocrine system.

    Science.gov (United States)

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  16. Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

    Science.gov (United States)

    Siwamogsatham, Oranan; Alvarez, Jessica

    2015-01-01

    Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

  17. Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis.

    Science.gov (United States)

    Siwamogsatham, Oranan; Alvarez, Jessica A; Tangpricha, Vin

    2014-10-01

    The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

  18. Using short-term bioassays to evaluate the endocrine disrupting capacity of the pesticides linuron and fenoxycarb.

    Science.gov (United States)

    Spirhanzlova, Petra; De Groef, Bert; Nicholson, Freda E; Grommen, Sylvia V H; Marras, Giulia; Sébillot, Anthony; Demeneix, Barbara A; Pallud-Mothré, Sophie; Lemkine, Gregory F; Tindall, Andrew J; Du Pasquier, David

    2017-10-01

    Several short-term whole-organism bioassays based on transgenic aquatic models are now under validation by the OECD (Organization for Economic Co-operation and Development) to become standardized test guidelines for the evaluation of the endocrine activity of substances. Evaluation of the endocrine disrupting capacity of pesticides will be a domain of applicability of these future reference tests. The herbicide linuron and the insecticide fenoxycarb are two chemicals commonly used in agricultural practices. While numerous studies indicate that linuron is likely to be an endocrine disruptor, there is little information available on the effect of fenoxycarb on vertebrate endocrine systems. Using whole-organism bioassays based on transgenic Xenopus laevis tadpoles and medaka fry we assessed the potential of fenoxycarb and linuron to disrupt thyroid, androgen and estrogen signaling. In addition we used in silico approach to simulate the affinity of these two pesticides to human hormone receptors. Linuron elicited thyroid hormone-like activity in tadpoles at all concentrations tested and, showed an anti-estrogenic activity in medaka at concentrations 2.5mg/L and higher. Our experiments suggest that, in addition to its previously established anti-androgenic action, linuron exhibits thyroid hormone-like responses, as well as acting at the estrogen receptor level to inhibit estrogen signaling. Fenoxycarb on the other hand, did not cause any changes in thyroid, androgen or estrogen signaling at the concentrations tested. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Characteristics of the Danish families with multiple endocrine neoplasia type 1

    DEFF Research Database (Denmark)

    Jäger, Anne Charlotte; Friis-Hansen, Lennart; Hansen, Thomas V O

    2006-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier...... mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were...... found in 68 patients with other fore-/midgut endocrine tumours. Moreover, screening of 60 consecutive patients with primary prolactinoma did not identify any mutation carriers. Our data indicate that MEN1 mutation screening is efficient in patients with familial MEN1. Screening should also be offered...

  20. Endocrine disorders and the neurologic manifestations

    Directory of Open Access Journals (Sweden)

    Jeesuk Yu

    2014-12-01

    Full Text Available The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders.

  1. Multiple endocrine neoplasia type 2A in a black South African family

    African Journals Online (AJOL)

    1. $obol H. Narod SA, Nakamura Y. et al. Screening for multiple endocrine neoplasia type 2a with DNA-polymorphism analysis. N Engl J Med 1989: 321: 996-1001. 2. Mulligan LM, Eng C. He-aly CS, e-r al. Germ-line mutations of the RET proto- oncogene in multiple endocrine neoplasia type 2A Nature 1993; 363: 458-460_.

  2. Endocrine Health Problems Detected in 764 Patients Evaluated in a Late Effects Clinic

    Directory of Open Access Journals (Sweden)

    Maria Conceição Pereira

    2017-10-01

    Full Text Available Background: Many pediatric cancer survivors have endocrine conditions. After treatment with alkylating agents, steroids, methotrexate, and radiation, several endocrine dysfunctions may appear. Surveillance for late effects is recommended by guidelines worldwide. Objective: The objective of this study was to describe the endocrine outcomes of 764 patients followed during a 20 years’ period in our out-patient clinic. Design: We retrospectively reviewed the medical records. Patients: The study included 764 patients whose oncological or hematological dangerous diseases appeared before they were 18 years old. Larger groups were constituted by leukemias, central nervous tumors, and lymphomas. Outcome Measures: The frequency and types of endocrine conditions were analyzed. Results: 1,091 endocrine conditions were observed in all groups. The most common types of endocrine conditions were problems with growth and the thyroid. We found puberty abnormalities and bone problems in third and fourth places of frequency. ACTH insufficiency was found in seventh place. Conclusion: Endocrine dysfunctions are very common in survivor populations. Endocrinologists should be aware of international guidelines and make an effort to optimize screening and treatment of endocrine effects of cancer therapy. The crucial period is the puberty with growth spurt failure and accelerated maturity both of which can bring future social and professional difficulties.

  3. Genetic predisposition to endocrine tumors: Diagnosis, surveillance and challenges in care.

    Science.gov (United States)

    Petr, Elisabeth Joye; Else, Tobias

    2016-10-01

    Endocrine tumor syndromes, eg, multiple endocrine neoplasia types 1 and 2, were among the first recognized hereditary predisposition syndromes to tumor development. Over time, the number of endocrine tumor syndromes has significantly expanded, eg, with the recent inclusion of hereditary paraganglioma syndromes. Associations of non-endocrine tumors with hereditary endocrine tumor syndromes and endocrine tumors with non-classical endocrine tumor syndromes have emerged. These findings have certainly expanded the scope of care, necessitating a multidisciplinary approach by a team of medical professionals and researchers, integrating shared patient decision-making at every step of surveillance, diagnosis, and treatment. In the absence of evidence-based guidelines, multiple aspects of patient care remain individualized, based on a patient's clinical presentation and family pedigree. This is particularly important when determining a surveillance plan for unaffected or disease-free mutation carriers. In this review, we describe the main endocrine tumor manifestations found in familial cancer syndromes in an organ-based approach, focusing on adrenocortical carcinoma, pheochromocytoma and paraganglioma, neuroendocrine tumors, differentiated thyroid cancer, and medullary thyroid cancer. We highlight the challenges in diagnosis, surveillance, and therapy unique to the patient population with hereditary syndromes. Furthermore, we underscore the importance of evaluating for genetic predisposition to tumor development, provide features that can identify index patients, and discuss the approach to screening surveillance for mutation carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties.

    Science.gov (United States)

    Marx-Stoelting, P; Niemann, L; Ritz, V; Ulbrich, B; Gall, A; Hirsch-Ernst, K I; Pfeil, R; Solecki, R

    2014-12-01

    allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    Science.gov (United States)

    Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

    2013-12-01

    Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

  6. Endocrine system on chip for a diabetes treatment model.

    Science.gov (United States)

    Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu

    2017-02-21

    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  7. An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol.

    Science.gov (United States)

    Frizzell, Caroline; Ndossi, Doreen; Kalayou, Shewit; Eriksen, Gunnar S; Verhaegen, Steven; Sørlie, Morten; Elliott, Christopher T; Ropstad, Erik; Connolly, Lisa

    2013-08-15

    Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1-1000ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000ng/ml (3.87μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000ng/ml (3.87μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Scintigraphic imaging of endocrine organs

    International Nuclear Information System (INIS)

    Gross, M.D.; Shapiro, B.; Thrall, J.H.; Freitas, J.E.; Beierwaltes, W.H.

    1984-01-01

    The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach

  9. Endocrine ophthalmopathy and radioiodine therapy

    International Nuclear Information System (INIS)

    Karlsson, F. Anders

    2006-01-01

    Endocrine ophthalmopathy is to some degree present in most patients with Graves' disease. In few cases, a severe form of the condition develops and in the majority of these cases, the course of the eye problems has been influenced by the treatment for thyrotoxicosis. In this regard, radioiodine therapy has been increasingly recognized as carrying a special risk. Here, the current understanding of endocrine ophthalmopathy and the risks associated with the development of severe eye disease are discussed. The results of a retrospective investigation of patients with severe eye disease in our hospital, and the experience with corticosteroid administration following radioiodine in order to reduce the risk of ophthalmopathy, are also presented

  10. Neonatal endocrine emergencies: a primer for the emergency physician.

    Science.gov (United States)

    Park, Elizabeth; Pearson, Nadia M; Pillow, M Tyson; Toledo, Alexander

    2014-05-01

    The resuscitation principles of securing the airway and stabilizing hemodynamics remain the same in any neonatal emergency. However, stabilizing endocrine disorders may prove especially challenging. Several organ systems are affected simultaneously and the clinical presentation can be subtle. Although not all-inclusive, the implementation of newborn screening tests has significantly reduced morbidity and mortality in neonates. Implementing routine screening tests worldwide and improving the accuracy of present tests remains the challenge for healthcare providers. With further study of these disorders and best treatment practices we can provide neonates presenting to the emergency department with the best possible outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Arterial and venous thrombosis in endocrine diseases

    NARCIS (Netherlands)

    van Zaane, Bregje; Stuijver, Danka J. F.; Squizzato, Alessandro; Gerdes, Victor E. A.

    2013-01-01

    Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency,

  12. The impact of opioids on the endocrine system.

    Science.gov (United States)

    Katz, Nathaniel; Mazer, Norman A

    2009-02-01

    Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

  13. Endocrine emergencies in dogs and cats.

    Science.gov (United States)

    Koenig, Amie

    2013-07-01

    Success in treatment of endocrine emergencies is contingent on early recognition and treatment. Many endocrine diseases presenting emergently have nonspecific signs and symptoms. In addition, these endocrine crises are often precipitated by concurrent disease, further making early identification difficult. This article concentrates on recognition and emergency management of the most common endocrine crises in dogs and cats. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Selenium hyperaccumulation offers protection from cell disruptor herbivores.

    Science.gov (United States)

    Quinn, Colin F; Freeman, John L; Reynolds, Ray J B; Cappa, Jennifer J; Fakra, Sirine C; Marcus, Matthew A; Lindblom, Stormy D; Quinn, Erin K; Bennett, Lindsay E; Pilon-Smits, Elizabeth A H

    2010-08-27

    -disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.

  15. Selenium hyperaccumulation offers protection from cell disruptor herbivores

    Directory of Open Access Journals (Sweden)

    Quinn Colin F

    2010-08-01

    protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.

  16. Selenium hyperaccumulation offers protection from cell disruptor herbivores

    Science.gov (United States)

    2010-01-01

    hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops. PMID:20799959

  17. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Alexandra; Chervona, Yana [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Hall, Megan [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York (United States); Kluz, Thomas [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Gamble, Mary V., E-mail: mvg7@columbia.edu [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States)

    2015-05-01

    Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p < 0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females. - Highlights: • Males and females exhibit unique gene expression changes in response to arsenic. • Only 23 genes are common among the differentially expressed genes for the sexes. • Male and female gene lists exhibit common

  18. ENDOCRINE DISORDERS IN THE ELDERLY

    African Journals Online (AJOL)

    Enrique

    falls, cognitive dysfunction, depression, pain, erectile dysfunction and polypharmacy. ... in the elderly, so this article covers three common problems: type 2 diabetes mellitus, thyroid disorders and metabolic bone disease. ENDOCRINE DISORDERS IN THE. ELDERLY .... than 90% of women and 60% of men have nodules.

  19. Endocrine Function after Bariatric Surgery.

    Science.gov (United States)

    Kim, Ki-Suk; Sandoval, Darleen A

    2017-06-18

    Obesity increases the risks of metabolic disorders including type 2 diabetes mellitus (T2DM). Bariatric surgery is the most successful therapeutic option that causes sustained weight loss and improvements in obesity comorbidities. Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are two of the most frequently performed bariatric surgeries. Despite their different anatomical rearrangement, they have remarkably similar success in both weight loss and T2DM remission. Interestingly, they also both cause a wide range of endocrine changes. Many of these endocrine changes are reflected specifically within the intestine and are implicated as mechanisms for the metabolic success of surgery. However, while most of the work shows that these hormonal changes are associated with the metabolic changes after surgery, causation has been difficult to ascertain. Here, we review the endocrine changes after RYGB and VSG and explore their mechanistic role in the success of bariatric surgery. Further, we explore important changes in gastrointestinal function and the role of these changes in the increase in postprandial endocrine responses after bariatric surgery. © 2017 American Physiological Society. Compr Physiol 7:783-798, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  20. The Vitamin D Endocrine System.

    Science.gov (United States)

    Norman, Anthony W.

    1985-01-01

    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  1. Multiple endocrine neoplasia type I

    International Nuclear Information System (INIS)

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  2. Optimized quinoline amino alcohols as disruptors and dispersal agents of Vibrio cholerae biofilms

    Science.gov (United States)

    León, Brian; Jake Haeckl, F. P.; Linington, Roger G.

    2015-01-01

    The biofilm state is an integral part of the lifecycle of many bacterial pathogens. Identifying inhibitors as molecular probes against bacterial biofilms has numerous potential biomedical applications. Here we report quinoline amino alcohol 20 as a highly potent disruptor of V. cholerae biofilms. Additionally, 20 was able to disperse preformed biofilms, an activity exhibited by few compounds with biofilm inhibiting activity. PMID:26156292

  3. Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells

    International Nuclear Information System (INIS)

    Klann, Anja; Levy, Gregor; Lutz, Ilka; Mueller, Christian; Kloas, Werner; Hildebrandt, Jan-Peter

    2005-01-01

    We tested the ultraviolet screen 3-(4-methylbenzylidene)-camphor (4-MBC; Eusolex 6300), which has been implicated as a potential endocrine disruptor, for its potential to bind to and activate endogenous estrogen receptors (ER) and to mediate ER-dependent changes in gene transcription, in hepatocytes of the water-dwelling South African clawed frog Xenopus laevis. We were able to confirm previous findings that 4-MBC accelerates cell proliferation in estrogen-dependent human breast cancer cells (MCF-7). Results of competitive binding assays of [ 3 H]17β-estradiol and 4-MBC using cytosolic protein preparations from Xenopus hepatocytes indicated that 4-MBC weakly binds to the ER. 4-MBC at a concentration of 100 μmol/L is not able to completely replace estradiol from the receptor. However, when 4-MBC was tested in a gene induction assay using the relative amount of ER transcript as a marker for ER-dependent transcriptional activation, we found that micromolar concentrations of this substance produced an increase in the amount of ER mRNA that was not different from the amount of mRNA that was observed upon activation of cells with 17β-estradiol in concentrations above 1 nmol/L. The results indicate that 4-MBC has the potential to change physiological and developmental processes mediated by ER signaling mechanisms. It may therefore be a potentially harmful substance for water-dwelling animals when present in the environment at micromolar concentrations

  4. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  5. Towards an integrated biosensor array for simultaneous and rapid multi-analysis of endocrine disrupting chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Scognamiglio, Viviana, E-mail: viviana.scognamiglio@mlib.ic.cnr.it [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy); Pezzotti, Italo; Pezzotti, Gianni; Cano, Juan; Manfredonia, Ivano [Biosensor S.r.l. - Via degli Olmetti 44 00060 Formello, Rome (Italy); Buonasera, Katia [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy); Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe [Universita di Roma Tor Vergata, Dipartimento di Scienze e Tecnologie Chimiche - Via della Ricerca Scientifica 00133, Rome (Italy); Giardi, Maria Teresa [IC-CNR Istituto di Cristallografia, AdR1 Dipartimento Agroalimentare - Via Salaria Km 29.3 00015, Rome (Italy)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer A multitask biosensor for the detection of endocrine disrupting chemicals is proposed. Black-Right-Pointing-Pointer The sensing system employ an array of biological recognition elements. Black-Right-Pointing-Pointer Amperometric and optical transduction methods are provided in an integrated biosensor together with flow control systems. Black-Right-Pointing-Pointer The biosensing device results in an integrated, automatic and portable system for environmental and agrifood application. - Abstract: In this paper we propose the construction and application of a portable multi-purpose biosensor array for the simultaneous detection of a wide range of endocrine disruptor chemicals (EDCs), based on the recognition operated by various enzymes and microorganisms. The developed biosensor combines both electrochemical and optical transduction systems, in order to increase the number of chemical species which can be monitored. Considering to the maximum residue level (MRL) of contaminants established by the European Commission, the biosensor system was able to detect most of the chemicals analysed with very high sensitivity. In particular, atrazine and diuron were detected with a limit of detection of 0.5 nM, with an RSD% less than 5%; paraoxon and chlorpyrifos were revealed with a detection of 5 {mu}M and 4.5 {mu}M, respectively, with an RSD% less than 6%; catechol and bisphenol A were identified with a limit of detection of 1 {mu}M and 35 {mu}M respectively, with an RSD% less than 5%.

  6. Towards an integrated biosensor array for simultaneous and rapid multi-analysis of endocrine disrupting chemicals

    International Nuclear Information System (INIS)

    Scognamiglio, Viviana; Pezzotti, Italo; Pezzotti, Gianni; Cano, Juan; Manfredonia, Ivano; Buonasera, Katia; Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe; Giardi, Maria Teresa

    2012-01-01

    Highlights: ► A multitask biosensor for the detection of endocrine disrupting chemicals is proposed. ► The sensing system employ an array of biological recognition elements. ► Amperometric and optical transduction methods are provided in an integrated biosensor together with flow control systems. ► The biosensing device results in an integrated, automatic and portable system for environmental and agrifood application. - Abstract: In this paper we propose the construction and application of a portable multi-purpose biosensor array for the simultaneous detection of a wide range of endocrine disruptor chemicals (EDCs), based on the recognition operated by various enzymes and microorganisms. The developed biosensor combines both electrochemical and optical transduction systems, in order to increase the number of chemical species which can be monitored. Considering to the maximum residue level (MRL) of contaminants established by the European Commission, the biosensor system was able to detect most of the chemicals analysed with very high sensitivity. In particular, atrazine and diuron were detected with a limit of detection of 0.5 nM, with an RSD% less than 5%; paraoxon and chlorpyrifos were revealed with a detection of 5 μM and 4.5 μM, respectively, with an RSD% less than 6%; catechol and bisphenol A were identified with a limit of detection of 1 μM and 35 μM respectively, with an RSD% less than 5%.

  7. High levels of endocrine pollutants in US streams during low flow due to insufficient wastewater dilution

    Science.gov (United States)

    Rice, Jacelyn; Westerhoff, Paul

    2017-08-01

    Wastewater discharges from publicly owned treatment works are a significant source of endocrine disruptors and other contaminants to the aquatic environment in the US. Although remaining pollutants in wastewater pose environmental risks, treated wastewater is also a primary source of stream flow, which in turn is critical in maintaining many aquatic and riparian wildlife habitats. Here we calculate the dilution factor--the ratio of flow in the stream receiving discharge to the flow of wastewater discharge--for over 14,000 receiving streams in the continental US using streamflow observations and a spatially explicit watershed-scale hydraulic model. We found that wastewater discharges make up more than 50% of in-stream flow for over 900 streams. However, in 1,049 streams that experienced exceptional low-flow conditions, the dilution factors in 635 of those streams fell so low during those conditions that the safety threshold for concentrations of one endocrine disrupting compound was exceeded, and in roughly a third of those streams, the threshold was exceeded for two compounds. We suggest that streams are vulnerable to public wastewater discharge of contaminants under low-flow conditions, at a time when wastewater discharges are likely to be most important for maintaining stream flow for smaller sized river systems.

  8. Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

    Science.gov (United States)

    Oropesa, A L; Floro, A M; Palma, P

    2016-09-01

    In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1.7 %), in a non-concentration-dependent manner, acting as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ has shown to be toxic to daphnid embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages but not producing direct embryo toxicity. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination, and causes development abnormality in offspring. Therefore, CBZ could directly affect the population sustainability.

  9. Strain specific induction of pyometra and differences in immune responsiveness in mice exposed to 17α-ethinyl estradiol or the endocrine disrupting chemical bisphenol A.

    Science.gov (United States)

    Kendziorski, Jessica A; Kendig, Eric L; Gear, Robin B; Belcher, Scott M

    2012-08-01

    Pyometra is an inflammatory disease of the uterus that can be caused by chronic exposure to estrogens. It is unknown whether weakly estrogenic endocrine disruptors can cause pyometra. We investigated whether dietary exposures to the estrogenic endocrine disruptor bisphenol A (BPA) induced pyometra. Pyometra did not occur in CD1 mice exposed to different dietary doses of BPA ranging from 4.1 to >4000μg/kg-d or 17α-ethinyl estradiol (EE; 1.2 to >150μg/kg-d). In the C57BL/6 strain, pyometra occurred in the 15μg/kg-d EE and 33μg/kg-d BPA treatment groups. At the effective concentration of BPA, histological analysis revealed pathological alterations of uterine morphology associated with a >5.3-fold increase in macrophage numbers in non-pyometra uteri of C57BL/6 mice exposed to BPA. These results suggest that BPA enhances immune responsiveness of the uterus and that heightened responsiveness in C57BL/6 females is related to increased susceptibility to pyometra. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Assessment of Protocol Designed to Detect Endocine Disrupting Effects of Flutamide in Xenopus Tropicalis

    National Research Council Canada - National Science Library

    Kenchtges, Paul L; Sprando, Robert L; Bremman, Linda M; Miller, Mark F; Kumsher, David M; Dennis, William E; Brown, Charles C; Clegg, Eric D

    2006-01-01

    .... Environmental Protection Agency (USEPA) Endocrine Disruptor Screening and Testing Program. The frogs were exposed to the model anti-androgenic compound flutamine under flow-through conditions for a period of 30 weeks, beginning at 48 hours post-hatch...

  11. Evolution of the Medaka Extended One Generation Reproduction Test (MEOGRT)

    Science.gov (United States)

    In response to various legislative mandates, the United States Environmental Protection Agency (USEPA) formed its Endocrine Disruptor Screening Program (EDSP), which in turn, implemented a tiered testing strategy to determine the potential of pesticides, commercial chemicals, and...

  12. Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.

    Science.gov (United States)

    Morales, Mónica; Martínez-Paz, Pedro; Sánchez-Argüello, Paloma; Morcillo, Gloria; Martínez-Guitarte, José Luis

    2018-05-15

    Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  14. Multiple endocrine neoplasia type 2: achievements and current challenges

    Directory of Open Access Journals (Sweden)

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  15. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul

    2016-01-01

    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  16. Radiological imaging of endocrine diseases

    International Nuclear Information System (INIS)

    Bruneton, J.N.

    1999-01-01

    Imaging studies are playing an increasingly role in the evaluation of endocrine diseases; accordingly, familiarity with the specific indications for the various modalities, and with the characteristic findings, is essential. This multi-author work, which is intended for both radiologists and endocrinologists, considers the role of all the recent imaging techniques, including ultrasound (particular color Doppler), computed tomography, MRI, and scintigraphy. Following an extensive introduction on the pituitary, subsequent chapters discuss in detail the normal anatomy and pathology of the female and male reproductive systems. Remaining chapters provide state-of-the-art data on the thyroid, parathyroids, pancreatic endocrine tumors, adrenal glands, hormonal tumors (carcinoids and MEN), and imaging of the complications of hormone therapy. (orig.)

  17. Endocrine manifestations in celiac disease

    OpenAIRE

    Freeman, Hugh James

    2016-01-01

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid diseas...

  18. Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union.

    Science.gov (United States)

    Trasande, Leonardo; Zoeller, R Thomas; Hass, Ulla; Kortenkamp, Andreas; Grandjean, Philippe; Myers, John Peterson; DiGangi, Joseph; Bellanger, Martine; Hauser, Russ; Legler, Juliette; Skakkebaek, Niels E; Heindel, Jerrold J

    2015-04-01

    Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU). A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data. Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or $209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs. EDC exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in

  19. Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats.

    Directory of Open Access Journals (Sweden)

    Yixing Feng

    Full Text Available Triclosan (TCS is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P, estradiol (E2, testosterone (T, human chorionic gonadotropin (hCG and prolactin (PRL were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1, estrogen sulfotransferase 1E1 (SULT1E1, steroid 5α-reductase 1 (SRD5A1 and steroid 5α-reductase 2 (SRD5A2. Furthermore, the transcriptional expression levels of progesterone receptor (PR, estrogen receptor (ERα and androgen receptor (AR were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth.

  20. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    Science.gov (United States)

    Sheikh, Ishfaq A; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

  1. Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats

    Science.gov (United States)

    Zhang, Zhaobin; Shi, Jiachen; Jiao, Zhihao; Shao, Bing

    2016-01-01

    Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth. PMID:27149376

  2. Spectrum of Endocrine Disorders in Central Ghana

    Directory of Open Access Journals (Sweden)

    Osei Sarfo-Kantanka

    2017-01-01

    Full Text Available Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0 with an overall median age of 54 (IQR, 41–64 years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population.

  3. Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity.

    Science.gov (United States)

    Jiménez-Díaz, I; Molina-Molina, J M; Zafra-Gómez, A; Ballesteros, O; Navalón, A; Real, M; Sáenz, J M; Fernández, M F; Olea, N

    2013-10-01

    UV-filters are widely used in many personal care products and cosmetics. Recent studies indicate that some organic UV-filters can accumulate in biota and act as endocrine disruptors, but there are few studies on the occurrence and fate of these compounds in humans. In the present work, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to assess the presence of six UV-filters in current use (benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor, and 3-benzylidene camphor) in human placental tissue is proposed. The method involves the extraction of the analytes from the samples using ethyl acetate, followed by a clean-up step using centrifugation prior to their quantification by LC-MS/MS using an atmospheric pressure chemical ionization (APCI) interface. Bisphenol A-d16 was used as surrogate for the determination of benzyl salicylate, phenyl salicylate, octyl salicylate and homosalate in negative mode and benzophenone-d10, was used as surrogate for the determination of 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in positive mode. The found limits of detection ranged from 0.4 to 0.6ngg(-1) and the limits of quantification ranged from 1.3 to 2.0ngg(-1), while variability was under 13.7%. Recovery rates for spiked samples ranged from 97% to 104%. Moreover, the interactions of these compounds with the human estrogen receptor alpha (hERα) and androgen receptor (hAR), using two in vitro bioassays based on reporter gene expression and cell proliferation assessment, were also investigated. All tested compounds, except benzyl salicylate and octyl salicylate, showed estrogenic activity in the E-Screen bioassay whereas only homosalate and 3-(4-methylbenzylidene) camphor were potent hAR antagonists. Although free salicylate derivatives and free camphor derivatives were not detected in the human placenta samples analyzed, the observed estrogenic and anti-androgenic activities of some of these

  4. An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

    International Nuclear Information System (INIS)

    Frizzell, Caroline; Ndossi, Doreen; Kalayou, Shewit; Eriksen, Gunnar S.; Verhaegen, Steven; Sørlie, Morten; Elliott, Christopher T.; Ropstad, Erik; Connolly, Lisa

    2013-01-01

    Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene expression

  5. An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

    Energy Technology Data Exchange (ETDEWEB)

    Frizzell, Caroline [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Ndossi, Doreen [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Sokoine University of Agriculture, Morogoro (Tanzania, United Republic of); Kalayou, Shewit [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Mekelle University College of Veterinary Medicine, Mekelle (Ethiopia); Eriksen, Gunnar S. [Norwegian Veterinary Institute, Oslo (Norway); Verhaegen, Steven [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Sørlie, Morten [Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Elliott, Christopher T. [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Ropstad, Erik [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom)

    2013-08-15

    Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene expression.

  6. November 6, 2017, Virtual Meeting on the Charge Questions for the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) Meeting on Endocrine Disruption

    Science.gov (United States)

    This virtual FIFRA SAP meeting will be discus questions on Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways

  7. [Disperse endocrine system and APUD concept].

    Science.gov (United States)

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

    2011-01-01

    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  8. Update on endocrine disturbances in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Hangaard, J; Hagen, C

    2001-01-01

    The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes...... of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories....

  9. Radiotherapy for unresectable endocrine pancreatic carcinomas

    International Nuclear Information System (INIS)

    Tennvall, J.; Ljungberg, O.; Ahren, B.; Gustavsson, A.; Nillson, L.O.

    1992-01-01

    Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or α-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas. (author)

  10. Impacto de los disruptores endocrinos en la salud y el medio ambiente.

    OpenAIRE

    Alina Falero Morejón; Celso Pérez; Bárbara Luna; Magdalena Fonseca

    2005-01-01

    Los disruptores endocrinos comprenden diferentes sustancias químicas con efectos adversos sobre la salud de los organismos vivos o su progenie, como consecuencia de alteraciones en la función endocrina. Abarca un conjunto diverso y heterogéneo de compuestos químicos, capaces de alterar el equilibrio hormonal. Entre ellas se encuentran sustancias persistentes, bioacumulativas y organohalógenas que incluyen algunos plaguicidas (fungicidas, herbicidas e insecticidas), sustancias químicas industr...

  11. Primary Hyperparathyroidism in Young People. When Should We Perform Genetic Testing for Multiple Endocrine Neoplasia 1 (MEN-1)?

    DEFF Research Database (Denmark)

    Lassen, Tina Harmer; Friis-Hansen, Lennart Jan; Rasmussen, Åse Krogh

    2014-01-01

    CONTEXT: Multiple endocrine neoplasia (MEN-1) is a rare, autosomal dominant inherited disorder. Primary hyperparathyroidism (pHPT) is the most frequent and usually the earliest expression of MEN-1, with typical age of onset at 20-25 years. Early detection of the disease and correct treatment...... endocrine neoplasia 1 OR multiple endocrine neoplasia type 1 AND Mutational analysis OR genetic testing OR testing OR Hyperparathyroidism, primary [majr]. A total of 625 abstracts were reviewed. RESULTS AND DISCUSSION: Whether to perform screening of patients with pHPT under the age of 30, 35, or 40 years...

  12. The need for patients' endocrine function vigilance following treatment of head and neck cancer

    NARCIS (Netherlands)

    de Bree, R.; Lips, P.T.A.M.; Leemans, C.R.

    2008-01-01

    PURPOSE OF REVIEW: The aim of this article is to examine the need for screening of endocrine dysfunction following treatment of head and neck cancer. RECENT FINDINGS: The incidence of occult hypothyroidism following treatment of head and neck cancer is high. Patients who develop hypothyroidism after

  13. Toxicological profiling of sediments with in vitro mechanisms-based bioassays for endocrine disruption

    NARCIS (Netherlands)

    Houtman, C.J.; Cenijn, P.H.; Hamers, T.; Lamoree, M.H.; Legler, J.; Murk, A.J.; Brouwer, A.

    2004-01-01

    In vitro bioassays are valuable tools for screening environmental samples for the presence of bioactive (e.g., endocrine-disrupting) compounds. They can be used to direct chemical analysis of active compounds in toxicity identification and evaluation (TIE) approaches. In the present study, five in

  14. Toxicological profiling of sediments using in vitro bioassays, with emphasis on endocrine disruption

    NARCIS (Netherlands)

    Houtman, C.J.; Cenijn, P.H.; Hamers, T.; Lamoree, M.H.; Legler, J.; Murk, A.J.; Brouwer, A.

    2004-01-01

    In vitro bioassays are valuable tools for screening environmental samples for the presence of bioactive (e.g., endocrine-disrupting) compounds. They can be used to direct chemical analysis of active compounds in toxicity identification and evaluation (TIE) approaches. In the present study, five in

  15. ENDOCRINE OPHTHALMOPATHY: ETIOLOGY, PATHOGENESIS, CLINICAL PICTURE, DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Nikonova L. V.

    2018-03-01

    Full Text Available The relevance of the study of endocrine ophthalmopathy is due to the high prevalence of this disease and a high risk of developing impaired vision that leads to disability of patients. This lecture presents the main genetic, immunological, clinical manifestations of endocrine ophthalmopathy in order to improve the diagnosis and treatment of this pathology. The clinical picture of endocrine ophthalmopathy is various, unique for every patient and depends on the activity and severity of the process, which requires combined etiopathogenetic therapy. The importance of timely diagnosis for endocrine ophthalmopathy with an assessment of the activity of the process for choosing the right tactics for managing patients is very high.

  16. Endocrine aspects of cancer gene therapy.

    Science.gov (United States)

    Barzon, Luisa; Boscaro, Marco; Palù, Giorgio

    2004-02-01

    The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.

  17. In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia.

    Science.gov (United States)

    Shannon, Maeve; Rehfeld, Anders; Frizzell, Caroline; Livingstone, Christina; McGonagle, Caoimhe; Skakkebaek, Niels E; Wielogórska, Ewa; Connolly, Lisa

    2016-05-15

    The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Endocrine and metabolic aspects of the Wolfram syndrome.

    Science.gov (United States)

    Boutzios, Georgios; Livadas, Sarantis; Marinakis, Evangelos; Opie, Nicole; Economou, Frangiskos; Diamanti-Kandarakis, Evanthia

    2011-08-01

    Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a neurodegenerative disease with autosomal recessive inheritance with incomplete penetrance. DIDMOAD is a very rare disease with an estimated prevalence of 1 in 770,000 and it is believed to occur in 1 of 150 patients with juvenile-onset insulin-dependent diabetes mellitus. Additionally, WS may also present with different endocrine and metabolic abnormalities such as anterior and posterior pituitary gland dysfunction. This mini-review summarizes the variable presentation of WS and the need of screening for other metabolic and hormonal abnormalities, coexisting in this rare syndrome.

  19. The European strategy on endocrine disrupters: progress to date and EU/US cooperation.

    Science.gov (United States)

    Bontoux, L

    2001-01-01

    The European Commission has been active in the field of endocrine disrupters since 1995. Its first actions were to fund research projects through the Fourth Framework Programme for Research and Development covering various aspects of the issue (identification of endocrine disrupters, environmental and human health impacts). This involvement in research has continued through the Fifth Framework Programme and increased to this day. The publication of a specific call for proposals on endocrine disrupters on May 31, 2001 bears witness to these efforts. In parallel, the policy profile of the issue quickly rose and led to the adoption of the Community Strategy on Endocrine Disrupters (COM (1999)706 final) in 1999. This strategy identifies actions short, medium and long term and is supported by the European Parliament and the European Council. Its short-term actions focus on the establishment of a list of substances for further evaluation of their role in endocrine disruption and on the use of existing legislation to control the risk; the medium-term actions focus on the identification and assessment of endocrine disrupters as well as on further research to better understand the ED phenomenon, and the long-term actions focus on legislative actions to protect human health and the environment. These European developments have gone hand in hand with international cooperation with the USA on research (in the frame of the EC/US S&T cooperation agreement), with the WHO on health issues and with the OECD on screening and testing issues.

  20. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemelä, Jay Russell; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....