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Sample records for endocrine disruptor compound

  1. Endocrine Disruptors

    MedlinePlus

    ... and wildlife. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and plasticizers such as bisphenol A. Endocrine disruptors ...

  2. Endocrine Disruptors

    PubMed Central

    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. PMID:26740809

  3. A characterization of selected endocrine disruptor compounds in a Portuguese wastewater treatment plant.

    PubMed

    Maurício, R; Diniz, M; Petrovic, M; Amaral, L; Peres, I; Barceló, D; Santana, F

    2006-07-01

    Anthropogenic compounds that are able to disrupt the endocrine system of wildlife species are a major cause for concern and have led to a demand for new screening methods. The identification and quantification of endocrine disruptor compounds at wastewater treatment plant is of major interest to assess the endocrine activity of wastewater treatment plant discharges into the environment. This study consists of a preliminary survey of concentrations of previously selected endocrine disruptor compounds, undertaken to establish environmental concentrations and to support a biological program assay exposing freshwater fish to them. Selected endocrine disrupting chemicals (APEs, bisphenol A and 17 beta-estradiol) were measured in samples from a wastewater treatment plant located in Lisbon (Portugal), using recent commercial enzyme-linked immunosorbent assay kits and also LC-MS/MS. The results show that the wastewater treatment plant treatment process is efficient on the removal of target endocrine disruptor compounds. However, environmentally significant concentrations are still present in the treated effluent. The results also show that enzyme-linked immunosorbent assay kit is suitable for routine analysis of the selected compounds. The results are also useful since the wastewater treatment plant is located in a Mediterranean region, which results in an effluent with its own characteristics.

  4. ENDOCRINE DISRUPTORS IN THE ENVIRONMENT

    EPA Science Inventory

    The endocrine system produces hormones which are powerful natural chemicals that regulate important life processes. Endocrine disruptors are human-made chemicals distributed globally which have the potential to interfere with the endocrine system and produce serious biological e...

  5. Endocrine Disruptor Screening Program Reports to Congress

    EPA Pesticide Factsheets

    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.

  6. Characterization of paint samples used in drinking water reservoirs: identification of endocrine disruptor compounds.

    PubMed

    Romero, J; Ventura, F; Gomez, M

    2002-04-01

    Several migration tests are performed from various epoxy paint samples that, according to the regulation, can be used in food reservoirs such as drinking water reservoirs. The level of the organic compounds capable of producing migrations to water with special attention to endocrine disruptor compounds (EDCs) are identified and estimated by closed loop-stripping analysis (CLSA) and liquid-liquid extraction (LLE) methods coupled with gas chromatography (GC)-mass spectrometry (MS). Bisphenol A, a strong endocrine disruptor, is found in all migration experiments. Its concentration level reaches between 0.02 and 0.03 mg/cm2. The higher concentration corresponds with benzylic alcohol, which is used as a solvent and curing agent in epoxy paint. Other EDCs identified in the migration tests are phthalates, 4-nonylphenol, and t-butylphenol. The main non-EDCs identified are solvents, antioxidants, and rubber-like compounds. No great differences are found in the use of metallic plates or concrete slabs for migration experiments; only additional compounds related with the pretreatment of the concrete wall have been identified, too. In the study of a drinking water sample the same organic compounds identified in the migration test is not seen. This is probably because of the dynamic situation in a drinking water reservoir. Finally, a GC profile of a direct epoxy paint analysis is shown. The main peak identified is bisphenol A diglycidyl ether, monomer, and an active principle of the polymerization of epoxy resins based on bisphenol A. In addition, we report the recoveries of a selected group of EDCs using CLSA and LLE methods coupled with GC-MS.

  7. Effect of endocrine disruptor pesticides: a review.

    PubMed

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

    2011-06-01

    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.

  8. Research on Endocrine Disruptors

    EPA Pesticide Factsheets

    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.

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

    PubMed

    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.

  10. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  11. ANALYTICAL CHALLENGES OF ENVIRONMENTAL ENDOCRINE DISRUPTOR MONITORING

    EPA Science Inventory

    Reported increases in the incidence of endocrine-related conditions have led to speculation about environmental causes. Environmental scientists are focusing increased research effort into understanding the mechanisms by which endocrine disruptors affect human and ecological h...

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

    PubMed Central

    Couleau, N.; Falla, J.; Beillerot, A.; Battaglia, E.; D’Innocenzo, M.; Plançon, S.; Laval-Gilly, P.; Bennasroune, A.

    2015-01-01

    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. PMID:26133781

  13. Are brominated flame retardants endocrine disruptors?

    PubMed

    Legler, Juliette; Brouwer, Abraham

    2003-09-01

    Brominated flame retardants (BFRs) are a group of compounds that have received much attention recently due to their similarity with "old" classes of organohalogenated compounds such as polychlorinated biphenyls (PCBs), in terms of their fate, stability in the environment and accumulation in humans and wildlife. Toxic effects, including teratogenicity, carcinogenicity and neurotoxicity, have been observed for some BFR congeners, in particular the brominated diphenyl ethers (BDEs). This concise review focuses on the potency of BFRs and to disrupt endocrine systems, and attempts to answer the question whether or not BFRs are endocrine disruptors. Evidence is provided on the disruption of the thyroid hormone system by BFRs, with particular emphasis on the BDEs, as most recent data is available on this class of flame retardants. Similar to the hydroxylated PCBs, in vitro mechanistic studies as well as animal experiments have demonstrated the effects of BDEs on thyroid hormone transport and metabolism. An overview of possible effects of BFRs on the estrogen system is also provided. Research gaps are outlined, as well as ongoing and future studies in the European community aimed at contributing to comprehensive risk assessments based on the endocrine-disrupting effects of BFRs.

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

    EPA Pesticide Factsheets

    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.

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

    PubMed

    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.

  16. [Contamination, endocrine disruptors and cancer].

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

  17. Ecological risk assessment of endocrine disruptors.

    PubMed Central

    Hutchinson, T H; Brown, R; Brugger, K E; Campbell, P M; Holt, M; Länge, R; McCahon, P; Tattersfield, L J; van Egmond, R

    2000-01-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna. PMID:11102288

  18. Endocrine disruptors and thyroid hormone physiology.

    PubMed

    Jugan, Mary-Line; Levi, Yves; Blondeau, Jean-Paul

    2010-04-01

    Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame-retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

  19. Human infertility: are endocrine disruptors to blame?

    PubMed

    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.

  20. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

    PubMed

    Skinner, Michael K

    2014-12-01

    Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease.

  1. Unmasking the truth behind endocrine disruptors.

    PubMed

    DiDiego, Michele Lamse; Eggert, Julia A; Pruitt, Rosanne H; Larcom, Lyndon L

    2005-10-01

    The increase in reproductive cancers and developmental problems over the past 70 years has led researchers to suspect environmental influences as a root cause. Evidence from wildlife and laboratory studies suggests that exposure to endocrine disruptors (EnDs) may be the cause. An EnD is a foreign substance or mixture that alters the function of the endocrine system. They can be found in food, water, soil, or air. Research into their possible role provides an opportunity to decrease modifiable risk factors.

  2. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  3. The Effects of Nanomaterials as Endocrine Disruptors

    PubMed Central

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

    2013-01-01

    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. PMID:23949635

  4. Hormones and endocrine disruptors in human seminal plasma.

    PubMed

    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.

  5. Environmental endocrine disruptors: A proposed classification scheme

    SciTech Connect

    Fur, P.L. de; Roberts, J.

    1995-12-31

    A number of chemicals known to act on animal systems through the endocrine system have been termed environmental endocrine disruptors. This group includes some of the PCBs and TCDDs, as well as lead, mercury and a large number of pesticides. The common feature is that the chemicals interact with endogenous endocrine systems at the cellular and/or molecular level to alter normal processes that are controlled or regulated by hormones. Although the existence of artificial or environmental estrogens (e.g. chlordecone and DES) has been known for some time, recent data indicate that this phenomenon is widespread. Indeed, anti-androgens have been held responsible for reproductive dysfunction in alligator populations in Florida. But the significance of endocrine disruption was recognized by pesticide manufacturers when insect growth regulators were developed to interfere with hormonal control of growth. Controlling, regulating or managing these chemicals depends in no small part on the ability to identify, screen or otherwise know that a chemical is an endocrine disrupter. Two possible classifications schemes are: using the effects caused in an animal, or animals as an exposure indicator; and using a known screen for the point of contact with the animal. The former would require extensive knowledge of cause and effect relationships in dozens of animal groups; the latter would require a screening tool comparable to an estrogen binding assay. The authors present a possible classification based on chemicals known to disrupt estrogenic, androgenic and ecdysone regulated hormonal systems.

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

    PubMed

    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.

  7. New aspects of cadmium as endocrine disruptor.

    PubMed

    Takiguchi, Masufumi; Yoshihara, Shin'ichi

    2006-01-01

    Cadmium (Cd) is an industrial and environmental pollutant that exerts adverse effects on a number of organs in humans and animals. Reproductive organs, such as the testis and placenta, are sensitive to the toxic effects of Cd. In animal experiments, high-dose exposure to Cd induced severe testicular interstitial hemorrhage with edema, and increased incidence of fetal death and placental necrosis. Low-dose exposure to Cd affects steroid synthesis in male and female reproductive organs. In 1998, the Ministry of Environment in Japan listed Cd in the strategy plan SPEED98 as one of the chemicals suspected of having possible endocrine disrupting activity. Recently, it has been shown that Cd has potent estrogen- and androgen-like activities in vivo and in vitro, by directly binding to estrogen and androgen receptors. However, the precise mechanisms underlying the effects of Cd as an endocrine disruptor remain to be elucidated. In this review, we will discuss evidence thus far presented concerning the effects of Cd on the endocrine system.

  8. Determination of seventeen endocrine disruptor compounds and their spatial and seasonal distribution in Ria Formosa Lagoon (Portugal).

    PubMed

    Rocha, Maria João; Cruzeiro, Catarina; Reis, Mário; Rocha, Eduardo; Pardal, Miguel

    2013-10-01

    In spite of its outstanding ecological and touristic importance the Ria Formosa Lagoon shows signs of anthropogenic pollution. Nonetheless, until the present survey no studies had ever documented the measurement of natural and pharmaceutical estrogens (17β-estradiol, estrone, and 17α-ethynylestradiol), xenoestrogenic industrial pollutants (4-octylphenol, 4-nonylphenol, and their mono and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein), and sitosterol in this area. The 17 compounds measured herein are known as endocrine disrupters (EDCs) and act over the endocrine system even in few amounts (ng L(-1)-μg L(-1)). Thus to conclude about the influx of EDCs in the lagoon, water samples were taken every 2 months, during 1 year (2010), in low tide at nine sites distributed along the coastline. Water samples (1 L) were preconcentrated in the Oasis HLB cartridges and cleaned in silica cartridges before their analysis by GC-MS. Data showed the ubiquitous presence of potentially hazardous amounts of estrogens (particularly of ethynylestradiol, up to 24.3 ng L(-1)), nonylphenol (up to 547 ng L(-1)), and sitosterol (up to 12,300 ng L(-1)), mainly in summer, suggesting that the increase of the local number of inhabitants (tourists), the rise of the water temperature (up to 26 °C), and the blooming of local flora may interfere with the water quality parameters. This makes the lagoon a potential model to study. Taking into account the data, it was concluded that there are conditions for the occurrence of endocrine disruption in aquatic animals, even in areas included in the natural park of the Formosa. Besides, both the high amounts of un-ionized ammonia (up to 0.3 mg L(-1)) and phosphates (up to 1.6 mg L(-1)) my pose risks for local fauna and humans.

  9. REMOVAL OF ENDOCRINE DISRUPTOR CHEMICALS DURING DRINKING WATER TREATMENT

    EPA Science Inventory

    A group of chemicals, known as endocrine disruptor chemicals (EDCs) have been identified as having the potential to cause adverse health effects in humans and wildlife. Among this group DDT, PCBs, endosulfan, methoxychlor, diethylphthalate, diethylhexylphthalate, and bisphenol A ...

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

    EPA Pesticide Factsheets

    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.

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

    PubMed

    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.

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

    PubMed Central

    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. Switched impulsive control of the endocrine disruptor diethylstilbestrol singular model

    NASA Astrophysics Data System (ADS)

    Zamani, Iman; Shafiee, Masoud; Ibeas, Asier; de la Sen, M.

    2014-12-01

    In this work, a switched and impulsive controller is designed to control the Endocrine Disruptor Diethylstilbestrol mechanism which is usually modeled as a singular system. Then the exponential stabilization property of the proposed switched and impulsive singular model is discussed under matrix inequalities. A design algorithm is given and applied for the physiological process of endocrine disruptor diethylstilbestrol model to illustrate the effectiveness of the results.

  14. Endocrine disruptors compounds, pharmaceuticals and personal care products in urban wastewater: implications for agricultural reuse and their removal by adsorption process.

    PubMed

    Grassi, Mariangela; Rizzo, Luigi; Farina, Anna

    2013-06-01

    In the last years, a lot of emerging contaminants, such as, endocrine disruptors compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been detected in wastewater. Because of their toxicity and possible adverse effects on the environment and humans, their release from urban wastewater treatment plants (UWWTPs) effluents should be minimized, particularly when a wastewater reuse for crops irrigation is expected. Many processes have been investigated for advanced treatment of UWWTP effluents as well as for emerging contaminant degradation; among these, adsorption process was successfully used to remove EDCs and PPCPs from wastewater. This article shortly reviews EDCs and PPCPs removal from UWWTP effluents by adsorption process using conventional and non-conventional adsorbents. The fate of EDCs and PPCPs in UWWTPs and the implications for agricultural wastewater reuse has been addressed too. In spite of the adsorption process looking to be a valuable alternative to other advanced technologies for the removal of emerging contaminants from wastewater, some gaps still remain to evaluate the actual feasibility at full scale. However, according to a few studies available in scientific literature on the use of both powdered activated carbon and granular activated carbon at full scale, adsorption process by activated carbon is a promising, potentially effective, and economically feasible solution for producing safe wastewater for agricultural reuse.

  15. Enamel hypomineralization due to endocrine disruptors.

    PubMed

    Jedeon, Katia; Marciano, Clémence; Loiodice, Sophia; Boudalia, Sofiane; Canivenc Lavier, Marie-Chantal; Berdal, Ariane; Babajko, Sylvie

    2014-08-01

    There has been increasing concerns over last 20 years about the potential adverse effects of endocrine disruptors (EDs). Bisphenol A (BPA), genistein (G) and vinclozolin (V) are three widely used EDs having similar effects. Tooth enamel has recently been found to be an additional target of BPA that may be a causal agent of molar incisor hypomineralization (MIH). However, populations are exposed to many diverse EDs simultaneously. The purpose of this study was therefore to assess the effects of the combination of G, V and BPA on tooth enamel. Rats were exposed daily in utero and after birth to low doses of EDs mimicking human exposure during the critical fetal and suckling periods when amelogenesis takes place. The proportion of rats presenting opaque areas of enamel hypomineralization was higher when rats were treated with BPA alone than with a combination of EDs. The levels of mRNAs encoding the main enamel proteins varied with BPA treatment alone and did not differ significantly between controls and combined treatment groups. In vitro, rat ameloblastic HAT-7 cells were treated with the three EDs. BPA induced enamelin and reduced klk4 expression, G had no such effects and V reduced enamelin expression. These findings suggest that combinations of EDs may affect enamel less severely than BPA alone, and indicate that enamel hypomineralization may differ according to the characteristics of the ED exposure.

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

    EPA Science Inventory

    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...

  17. Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products

    PubMed Central

    Nishioka, Marcia; Standley, Laurel J.; Perovich, Laura J.; Brody, Julia Green; Rudel, Ruthann A.

    2012-01-01

    Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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

  18. Cancer and developmental exposure to endocrine disruptors.

    PubMed Central

    Birnbaum, Linda S; Fenton, Suzanne E

    2003-01-01

    Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection. PMID:12676588

  19. Cancer and developmental exposure to endocrine disruptors.

    PubMed

    Birnbaum, Linda S; Fenton, Suzanne E

    2003-04-01

    Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection.

  20. Endocrine disruptors and Leydig cell function.

    PubMed

    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.

  1. Determination of the uptake and release rates of multifamilies of endocrine disruptor compounds on the polar C18 Chemcatcher. Three potential performance reference compounds to monitor polar pollutants in surface water by integrative sampling.

    PubMed

    Camilleri, J; Morin, N; Miège, C; Coquery, M; Cren-Olivé, C

    2012-05-11

    The uptake kinetics of 27 emerging pollutants on the polar C18 Chemcatcher have been investigated. This investigation determined the sampling rates of 20 compounds, including 16 endocrine disruptors and 4 pharmaceuticals, which were used as overall pollution indicators. Calibrations were completed in a 50-L flow-through microcosm with continuous renewal of tap water spiked with approximately 3 μg/L of each pollutant and with sampling times at 1, 3, 6 and 12h and 1, 3, 7, 14, 21 and 28 days. Exponential regressions for the accumulation kinetics were plotted to confirm the maximum linear uptake times for each molecule using the half time of equilibrium (t(1/2)) criteria. Of the compounds tested, 17 were accumulated linearly for up to 14 or 21 days with an R(2) above 0.98 for linear correlations. The evaluation of the release kinetics of a C18 Chemcatcher spiked with 20 deuterated compounds identified 3 potential performance reference compounds (PRCs) with exponential desorption rates showing relatively good isotropic exchange.

  2. Amphibians as a model for the study of endocrine disruptors.

    PubMed

    Kloas, Werner

    2002-01-01

    Evidence shows that environmental compounds can interfere with the endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disruptors (EDs), which are mainly of anthropogenic origin, is surface water; thus, aquatic vertebrates such as fishes and amphibians are most endangered. Despite numerous reports on EDs in fishes, information about EDs in amphibians is scarce, and this paucity of information is of particular concern in view of the worldwide decline of amphibians. EDs could contribute to changes of amphibian populations via adverse effects on reproduction and the thyroid system. In amphibians, EDs can affect reproduction by (anti)estrogenic and (anti)androgenic modes of action that produce severe effects including abnormal sexual differentiation. ED actions on the thyroid system cause acceleration or retardation of metamorphosis, which may also affect population levels. Our broad knowledge of amphibian biology and endocrinology indicates that amphibians are very suitable models for the study of EDs. In particular, effects of EDs on the thyroid system triggering metamorphosis can be determined easily and most sensitively in amphibians compared to other vertebrates. A new classification of EDs according to their biological modes of action is proposed because EDs have quite heterogeneous chemical structures, which do not allow prediction of their biological effects. Methods and strategies are proposed for identification and risk assessment of EDs, whether as pure test substances or as mixtures from environmental samples. Effects of EDs on the thyroid system of amphibians can be assessed by a single animal model (Xenopus laevis), whereas the various types of reproduction need comparative studies to investigate whether general endocrine principles do exist among several species of anurans and urodeles. Thus, at least one anuran and one urodelean model are needed to determine ED interference with reproduction.

  3. 76 FR 60022 - Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... the endocrine system. The combined results and information will also be used to identify which tests... AGENCY Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA's Endocrine...

  4. Endocrine Disruptor Screening Program Tier 1 Assessments

    EPA Pesticide Factsheets

    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.

  5. Sun lotion chemicals as endocrine disruptors.

    PubMed

    Maipas, Sotirios; Nicolopoulou-Stamati, Polyxeni

    2015-01-01

    Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.

  6. Clinical correlates of environmental endocrine disruptors.

    PubMed

    Safe, Stephen

    2005-01-01

    Endocrine disrupting chemicals (EDCs), such as environmental estrogens, are hypothesized to be associated with a global decrease in sperm counts, other male reproductive tract problems and increasing rates of female breast cancer. Results of human population studies do not support the association between certain organochlorine EDCs and female breast cancer. Moreover, there is minimal evidence linking EDCs or exposure to other environmental chemicals with male reproductive tract problems. With the exception of the increasing incidence of testicular cancer, it is also questionable whether male reproductive tract problems are increasing, decreasing or unchanged. However, several studies report large differences in sperm count and quality and other endocrine-related problems within countries and regions, but the environmental, dietary and/or lifestyle factors responsible remain unknown.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27349723

  8. A treatise on hazards of endocrine disruptors and tool to evaluate them.

    PubMed

    Roy, Partha; Pereira, Ben M J

    2005-11-01

    Hormones mediate a major part of our essential physiological functions. Both endogenous and exogenous compounds and their metabolites are known to act through hormone receptors leading to regulation of endocrine function. The endogenous ligands that control reproductive functions are generally steroids such as 17beta-estradiol, androgens, progesterone, pregnenolone and glucocorticoids. However, exogenous compounds that are structurally and functionally similar gain entry into animals including humans through the diet or by occupational exposures, causing endocrine disruption. In the recent decade, there is a lot of apprehension about the so-called "endocrine disruptors" which are wide spread in the environment, mainly due to unrestricted human activity. These compounds of anthropogenic or natural origin mimic the action of sex hormones and can interfere with the endocrine system. It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine active compounds may be responsible for malformations in the male reproductive tract, crytorchidism, hypospadias, decrease in sperm counts, decreased male reproductive capacity and even testicular cancers. The increasing concern in both public and scientific communities about these abnormalities have prompted the initiation of epidemiological studies to not only identify, but to also analyze the short and long term effects of endocrine disruptors. As a result, a number of assays have been developed and are undergoing validation aimed at high throughput screening of chemical agents that disrupt endocrine activity. This review consolidates the findings of epidemiological studies, particularly in relation to male reproductive disorders and brings to light the various types of in vitro and in vivo models that are available for tiered testing of suspected compounds.

  9. Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen.

    PubMed

    Wagner, Martin; Oehlmann, Jörg

    2011-10-01

    Human exposure to endocrine disruptors is well documented by biomonitoring data. However, this information is limited to few chemicals like bisphenol A or phthalate plasticizers. To account for so-far unidentified endocrine disruptors and potential mixture effects we employ bioassays to detect endocrine activity in foodstuff and consequently characterize the integrated exposure to endocrine active compounds. Recently, we reported a broad contamination of commercially available bottled water with estrogenic activity and presented evidence for the plastic packaging being a source of this contamination. In continuation of that work, we here compare different sample preparation methods to extract estrogen-like compounds from bottled water. These data demonstrate that inappropriate extraction methods and sample treatment may lead to false-negative results when testing water extracts in bioassays. Using an optimized sample preparation strategy, we furthermore present data on the estrogenic activity of bottled water from France, Germany, and Italy: eleven of the 18 analyzed water samples (61.1%) induced a significant estrogenic response in a bioassay employing a human carcinoma cell line (MCF7, E-Screen). The relative proliferative effects ranged from 19.8 to 50.2% corresponding to an estrogenic activity of 1.9-12.2 pg estradiol equivalents per liter bottled water. When comparing water of the same spring that is packed in glass or plastic bottles made of polyethylene terephthalate (PET), estrogenic activity is three times higher in water from plastic bottles. These data support the hypothesis that PET packaging materials are a source of estrogen-like compounds. Furthermore, the findings presented here conform to previous studies and indicate that the contamination of bottled water with endocrine disruptors is a transnational phenomenon.

  10. Epigenetic transgenerational effects of endocrine disruptors on male reproduction.

    PubMed

    Guerrero-Bosagna, Carlos M; Skinner, Michael K

    2009-09-01

    Endocrine-disrupting chemicals generally function as steroid receptor signaling antagonists or agonists that influence development to promote adult-onset disease. Exposure to the endocrine disruptors during the initiation of male reproductive tract development interferes with the normal hormonal signaling and formation of male reproductive organs. In particular, exposure to the endocrine disruptor vinclozolin promotes transgenerational transmission of adult-onset disease states such as male infertility, increased frequencies of tumors, prostate disease, kidney diseases, and immune abnormalities that develop as males age. An epigenetic change in the germ line would be involved in the transgenerational transmission of these induced phenotypes. Nevertheless, other studies have also reported transgenerational transmission of induced epigenetic changes, without altering the germ line. Here we propose a nomenclature to help clarify both cases of transgenerational epigenetic transmission. An intrinsic epigenetic transgenerational process would require a germ-line involvement, a permanent alteration in the germ cell epigenome, and only one exposure to the environmental factor. An extrinsic epigenetic transgenerational process would involve an epigenetic alteration in a somatic tissue and require exposure at each generation to maintain the transgenerational phenotype.

  11. Risk assessment of 'endocrine substances': guidance on identifying endocrine disruptors.

    PubMed

    Lewis, Richard W

    2013-12-16

    The European regulation on plant protection products (1107/2009) and other related legislation only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. This legislation would appear to make the assumption that endocrine active chemicals should be managed differently from other chemicals presumably due to an assumed lack of a threshold for adverse effects. In the absence of agreed scientific criteria and guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation, a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The first ECETOC technical report and associated workshop, held in 2009, presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. Both sets of data (evidence of the adverse effect in apical studies and conclusive mode of action knowledge) are essential in order to correctly identify endocrine disruption according to accepted definitions. As the legislation seeks to regulate chemicals on a mode of action rather than the more traditional approach of adverse endpoints, then conclusive evidence of the mode of action of concern

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

    PubMed

    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.

  13. Evaluating the effects of endocrine disruptors on endocrine function during development.

    PubMed Central

    Bigsby, R; Chapin, R E; Daston, G P; Davis, B J; Gorski, J; Gray, L E; Howdeshell, K L; Zoeller, R T; vom Saal, F S

    1999-01-01

    The major concerns with endocrine disruptors in the environment are based mostly on effects that have been observed on the developing embryo and fetus. The focus of the present manuscript is on disruption of three hormonal systems: estrogens, androgens, and thyroid hormones. These three hormonal systems have been well characterized with regard to their roles in normal development, and their actions during development are known to be perturbed by endocrine-disrupting chemicals. During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult. Although it is known that there are differences in embryonic/fetal/neonatal versus adult endocrine responses, minimal experimental information is available to aid in characterizing the risk of endocrine disruptors with regard to a number of issues. Issues discussed here include the hypothesis of greater sensitivity of embryos/fetuses to endocrine disruptors, irreversible consequences of exposure before maturation of homeostatic systems and during periods of genetic imprinting, and quantitative information related to the shape of the dose-response curve for specific developmental phenomena. PMID:10421771

  14. ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

    PubMed Central

    Weiss, Bernard

    2011-01-01

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

  15. Endocrine disruptors as a threat to neurological function.

    PubMed

    Weiss, Bernard

    2011-06-15

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer.

  16. Environmental Endocrine Disruptors: Effects on the human male reproductive system

    PubMed Central

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

    2016-01-01

    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. PMID:26847433

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

    PubMed

    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.

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

    PubMed

    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".

  19. Multi-residue analytical method for the determination of endocrine disruptors and related compounds in river and waste water using dual column liquid chromatography switching system coupled to mass spectrometry.

    PubMed

    Gorga, Marina; Petrovic, Mira; Barceló, Damià

    2013-06-21

    The present study describes a novel, fully automated method, based on column switching using EQuan™ columns for an integrated sample preconcentration and liquid chromatography coupled to tandem mass spectrometry (LC-LC-MS/MS). The method allows the unequivocal identification and quantification of the most relevant environmental endocrine disruptors compounds (EDCs) and compounds suspected to be EDCs, such as natural and synthetic estrogens and their conjugates, antimicrobials, parabens, bisphenol A, alkylphenolic compounds, benzotriazoles, and organophosphorus flame retardants, in surface river water and wastewater samples. Applying this technique, water samples were directly injected into the chromatographic system and the target compounds were concentrated into the loading column. Thereafter, the analytes were transferred into the analytical column for subsequent detection by MS-MS (QqQ). A comparative study employing three types of columns, with different chemical modifications, was performed in order to determine the optimal column that allowed maximum retention and subsequent elution of the analytes. Using this new optimized methodology a fast and easy online methodology for the analysis of EDCs in surface river water and wastewater with low limits of quantification (LOQ) was obtained. LOQs ranged from 0.008 to 1.54 ng/L for surface river water and from 0.178/0.364 to 12.5/25.0 ng/L (except for alkylphenol monoethoxylates) for effluent/influent waste water. Moreover, employing approximately 1h, a complete analysis was performed which was significant improvement in comparison to other methods reported previously. This method was used to track the presence and fate of target compounds in the Ebro River which is the most important river in Spain whose intensive agricultural and industrial activities concentrate mainly close to the main cities in the basin, deteriorating soil and water quality.

  20. Competitive binding comparison of endocrine-disrupting compounds to recombinant androgen receptor from fathead minnow, rainbow trout, and human

    EPA Science Inventory

    Typically, in vitro hazard assessments for the identification of endocrine-disrupting compounds (EDCs), including those outlined in the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Tier 1 Screening protocols, utilize mammalian receptors. Evidence, however...

  1. The current preference for the immuno-analytical ELISA method for quantitation of steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.

    PubMed

    Manickum, Thavrin; John, Wilson

    2015-07-01

    requirements for steroid hormone quantitation. Further optimization of the sensitivity of the chemical-analytical LC-tandem mass spectrometry methods, especially for wastewater screening, in South Africa is required. Risk assessment studies showed that it was not practical to propose standards or allowable limits for the steroid estrogens E1, E2, EE2, and E3; the use of predicted-no-effect concentration values of the steroid estrogens appears to be appropriate for use in their risk assessment in relation to aquatic organisms. For raw water sources, drinking water, raw and treated wastewater, the use of bioassays, with trigger values, is a useful screening tool option to decide whether further examination of specific endocrine activity may be warranted, or whether concentrations of such activity are of low priority, with respect to health concerns in the human population. The achievement of improved quantitation limits for immuno-analytical methods, like ELISA, used for compound quantitation, and standardization of the method for measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g., estrogenic) are some areas for future EDC research.

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

    EPA Science Inventory

    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...

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

    PubMed

    Brieño-Enríquez, Miguel A; García-López, Jesús; Cárdenas, David B; Guibert, Sylvain; Cleroux, Elouan; Děd, Lukas; Hourcade, Juan de Dios; Pěknicová, Jana; Weber, Michael; Del Mazo, Jesús

    2015-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Hutzler, Beatriz W.; Machado, Luci D. B.; Lugão, Ademar B.; Villavicencio, Anna.-Lucia 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.

  5. PROGRESS IN THE OECD WORK ON ENDOCRINE DISRUPTORS TESTING AND ASSESSMENT FOR ENVIRONMENTAL SPECIES

    EPA Science Inventory

    The OECD Special Activity on endocrine disruptors testing and assessment (EDTA) started in 1996 at the request of member countries and industry with the objective to develop test methods for the detection and characterization of endocrine disrupting chemicals. The purpose of the ...

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:25798032

  7. Efficiencies of freshwater and estuarine constructed wetlands for phenolic endocrine disruptor removal in Taiwan.

    PubMed

    Hsieh, Chi-Ying; Yang, Lei; Kuo, Wen-Chien; Zen, Yi-Peng

    2013-10-01

    We examined the distribution and removal efficiencies of phenolic endocrine disruptors (EDs), namely nonylphenol diethoxylates (NP2EO), nonylphenol monoethoxylates (NP1EO), nonylphenol (NP), and octylphenol (OP), in wastewater treated by estuarine and freshwater constructed wetland systems in Dapeng Bay National Scenic Area (DBNSA) and along the Dahan River in Taiwan. Water samples were taken bimonthly at 30 sites in three estuarine constructed wetlands (Datan, Pengcun and Linbian right bank (A and B)) in DBNSA, for eight sampling campaigns. The average removal efficiencies were in the range of 3.13-97.3% for wetlands in DBNSA. The highest average removal occurred in the east inlet to the outlet of the Tatan wetland. The most frequently detected compound was OP (57.7%), whose concentration was up to 1458.7 ng/L in DBNSA. NP was seen in only 20.5% of the samples. The temporal variation of EDs showed a decrease across seasons, where summer>spring>winter>autumn in these constructed wetlands. The removal efficiencies of EDs by estuarine wetlands, in decreasing order, were Datan>Pengcun>Linbian right bank in DBNSA. Water samples collected at 18 sites in three freshwater constructed wetlands (Daniaopi, Hsin-Hai I, and Hsin-Hai II) along the riparian area of Dahan River. NP2EO was the most abundant compound, with a concentration of up to 11,200 ng/L. Removal efficiencies ranged from 55% to 91% for NP1EO, NP2EO, and NP in Hsin-Hai I. The average removal potential of EDs in freshwater constructed wetlands, in decreasing order, was Hsin-Hai II>Daniaopi>Hsin-Hai I constructed wetlands. The lowest concentrations of the selected compounds were observed in the winter. The highest removal efficiency of the selected phenolic endocrine disruptors was achieved by Hsin-Hai I wetland. The calculated risk quotients used to evaluate the ecological risk were up to 30 times higher in the freshwater wetlands along Dahan River than in the estuarine (DBNSA) constructed wetlands, indicating

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

    PubMed Central

    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

  9. Evaluation of Hydroxyatrazine in the Endocrine Disruptor Screening and Testing Program’s Male and Female Pubertal Protocols.

    EPA Science Inventory

    Evaluation of Hydroxyatrazine in the Endocrine Disruptor Screening and Testing Program’s Male and Female Pubertal Protocols. ABSTRACT Two critical components of the validation of any in vivo screening assay are to demonstrate sensitivity (ability to detect weak endocrine ...

  10. Endocrine disruptors and human health--is there a problem? An update.

    PubMed Central

    Safe, S H

    2000-01-01

    It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of recent studies show that there are large demographic variations in sperm counts within countries or regions, and analyses of North American data show that sperm counts have not decreased over the last 60 years. Analyses of records for hypospadias and cryptorchidism also show demographic differences in these disorders before 1985; however, since 1985 rates of hypospadias have not changed and cryptorchidism has actually declined. Temporal changes in sex ratios and fertility are minimal, whereas testicular cancer is increasing in most countries; however, in Scandinavia, the difference between high (Denmark) and low (Finland) incidence areas are not well understood and are unlikely to be correlated with differences in exposure to synthetic industrial chemicals. Results from studies on organochlorine contaminants (DDE/PCB) show that levels were not significantly different in breast cancer patients versus controls. Thus, many of the male and female reproductive tract problems linked to the endocrine-disruptor hypothesis have not increased and are not correlated with synthetic industrial contaminants. This does not exclude an endocrine-etiology for some adverse environmental effects or human problems associated with high exposures to some chemicals. Images Figure 1 PMID:10856020

  11. Optimisation of stir bar sorptive extraction and in-tube derivatisation-thermal desorption-gas chromatography-mass spectrometry for the determination of several endocrine disruptor compounds in environmental water samples.

    PubMed

    Iparraguirre, Arantza; Prieto, Ailette; Navarro, Patricia; Olivares, Maitane; Fernández, Luis-Ángel; Zuloaga, Olatz

    2011-07-01

    The analysis of organic pollutants in environmental water samples requires a pre-concentration step. Pre-concentration techniques such as stir bar sorptive extraction (SBSE) have gained popularity since they minimise the use of toxic organic solvents and can be considered as green analytical techniques. Similar to other pre-concentration techniques, one of the problems when SBSE is used is the matrix effect, which often occurs during the analysis of environmental water samples such as estuarine or wastewater samples. The present work studied the matrix effect during SBSE coupled to in-tube derivatisation-thermal desorption (TD)-gas chromatography-mass spectrometry for the determination of several endocrine disruptor compounds, such as alkylphenols, bisphenol A, estrogens and sterols, in environmental water samples, after optimisation of the major variables affecting the determination. Variables such as the addition of methanol or an inert salt to the donor phase, the extraction temperature, the volume of the donor phase, the stirring rate and the extraction time were studied during the SBSE optimisation. In the case of the in-tube derivatisation and TD step, the volume of the derivatisation reagent (N,O-bis(trimethylsilyl)triufloroacetamide with 1% of trimethylchlorosilane (BSTFA + 1% TMCS)) and the cryo-focusing temperature were fixed (2 μL and -50 °C, respectively) according to a consensus between maximum signal and optimal operation conditions. Good apparent recovery values (78-124%) were obtained for most of the analytes in Milli-Q water, except for 4-tert-octylphenol (4-tOP), which showed apparent recovery values exceeding 100%. Precision (n = 4) was in the 2-27%, and method detection limits were in the low nanogrammes per litre level for most of the analytes studied. The matrix effect was studied using two different approaches. On the one hand, Milli-Q water samples were spiked with humic acids, and apparent recovery values were studied with and

  12. Removal capacity and pathways of phenolic endocrine disruptors in an estuarine wetland of natural reed bed.

    PubMed

    Yang, Lina; Li, Zhengyan; Zou, Li; Gao, Huiwang

    2011-04-01

    Phenolic compounds are partly known as endocrine disruptors with various harmful effects including feminization and carcinogenesis at very low concentrations. Consequently, the pathways and removal of these compounds in natural and artificial sewage treatment systems such as wetlands have received wide concern. In this paper, a natural reed bed wetland with an area of 695ha located in the Liaohe River estuary in Northeast China was employed as a demonstration site to study the retention and removal efficiency of phenolic compounds including 4-nonylphenol (4-NP), bisphenol A (BPA), 4-t-octylphenol (4-t-OP), and 2,4-dichlorophenol (DCP), and to evaluate their purification capacity via water and mass balance analyses during an irrigation period from May 9 to September 8, 2009. The results showed that the phenolic compounds could be retained in the wetland system and removed through various processes. On average, 27.5% of phenolic compounds could be retained by the wetland substrate during the initial three-day irrigation period with a retention capacity order of 4-t-OP>4-NP>BPA>DCP. During the following 120d irrigation period, the phenolic compounds could be efficiently removed with an average percentage of 91.6%. It is estimated that 1.76kgd(-1) of phenolic compounds could be removed by the Liaohe River estuarine wetland (∼8×10(4)ha). The reed bed wetland system therefore provides a feasible mitigation option for phenolic pollutants in sewage and wastewater.

  13. Endocrine disruptors: a new scientific role for clinical pharmacologists? Impact on human health, wildlife, and the environment.

    PubMed

    Lathers, Claire M

    2002-01-01

    It is important for the clinical pharmacologist to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of planet Earth and to understand how they may negatively contribute to human disease. Clinical pharmacologists must understand the various definitions of endocrine disruptors and be able to "decipher" these terms for their patients. Understanding the need for the EPA endocrine disruptor screening program and possessing knowledge of the screening assays used to assess endocrine activity potential are two essential components relevant to the topic of endocrine disruptors. Clinical pharmacologists have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease since some scientists argue that the present evidence is not compelling. Clinical pharmacologists can also play an important role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to actions of endocrine disruptors. It is important that clinical pharmacologists work with veterinary clinical pharmacologists, toxicologists, industrial chemists, regulators, the scientific community, the general public, and environmental groups to understand the impact of endocrine disruptors on human health, wildlife, and the environment with an ultimate goal to minimize and/or alleviate the unwanted, detrimental effects of the endocrine disruptors.

  14. EVALUATION OF DRINKING WATER TREATMENT TECHNOLOGIES FOR REMOVAL OF ENDOCRINE DISRUPTORS

    EPA Science Inventory

    Evaluation of Drinking Water Treatment Technologies for Removal of Endocrine Disruptors. Schenck, K*, Speth, T, U.S. EPA, Cincinnati, OH, USA, Rosenblum, L, Wendelken, S, Pepich, B, and Krishnan, R, Shaw Environmental, Inc., Cincinnati, OH, USA. Many of the chemicals identified...

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

    EPA Science Inventory

    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...

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

    PubMed

    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.

  17. Biodegradation of Endocrine Disruptors in Solid-Liquid Two-Phase Partitioning Systems by Enrichment Cultures

    PubMed Central

    dos Santos, Silvia Cristina Cunha; Ouellette, Julianne; Juteau, Pierre; Lépine, François; Déziel, Eric

    2013-01-01

    Naturally occurring and synthetic estrogens and other molecules from industrial sources strongly contribute to the endocrine disruption of urban wastewater. Because of the presence of these molecules in low but effective concentrations in wastewaters, these endocrine disruptors (EDs) are only partially removed after most wastewater treatments, reflecting the presence of these molecules in rivers in urban areas. The development of a two-phase partitioning bioreactor (TPPB) might be an effective strategy for the removal of EDs from wastewater plant effluents. Here, we describe the establishment of three ED-degrading microbial enrichment cultures adapted to a solid-liquid two-phase partitioning system using Hytrel as the immiscible water phase and loaded with estrone, estradiol, estriol, ethynylestradiol, nonylphenol, and bisphenol A. All molecules except ethynylestradiol were degraded in the enrichment cultures. The bacterial composition of the three enrichment cultures was determined using 16S rRNA gene sequencing and showed sequences affiliated with bacteria associated with the degradation of these compounds, such as Sphingomonadales. One Rhodococcus isolate capable of degrading estrone, estradiol, and estriol was isolated from one enrichment culture. These results highlight the great potential for the development of TPPB for the degradation of highly diluted EDs in water effluents. PMID:23728808

  18. Determination of a broad spectrum of pharmaceuticals and endocrine disruptors in biofilm from a waste water treatment plant-impacted river.

    PubMed

    Huerta, B; Rodriguez-Mozaz, S; Nannou, C; Nakis, L; Ruhí, A; Acuña, V; Sabater, S; Barcelo, D

    2016-01-01

    Wastewater treatment plants (WWTPs) are one of the main sources of pharmaceuticals and endocrine disrupting compounds in freshwater ecosystems, and several studies have reported bioaccumulation of these compounds in different organisms in those ecosystems. River biofilms are exceptional indicators of pollution, but very few studies have focused on the accumulation of these emerging contaminants. The objectives of this study were first to develop an efficient analytical methodology for the simultaneous analysis of 44 pharmaceuticals and 13 endocrine disrupting compounds in biofilm, and second, to assess persistence, distribution, and bioaccumulation of these contaminants in natural biofilms inhabiting a WWTP-impacted river. The method is based on pressurized liquid extraction, purification by solid-phase extraction, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 31-137%, and for endocrine disruptors 32-93%. Method detection limits for endocrine disruptors were in the range of 0.2-2.4 ng g(-1), and for pharmaceuticals, 0.07-6.7 ng g(-1). A total of five endocrine disruptors and seven pharmaceuticals were detected in field samples at concentrations up to 100 ng g(-1).

  19. QSAR PRIORITIZATION OF CHEMICAL INVENTORIES FOR ENDOCRINE DISRUPTOR TESTING

    EPA Science Inventory

    Binding affinity between chemicals and the estrogen receptor (ER) serves as an indicator of the potential to cause endocrine disruption through this receptor-mediated endocrine pathway. Estimating ER binding affinity is, therefore, one strategic approach to reducing the costs of ...

  20. Update on the Mammalian Tier 1 Endocrine Disruptor Screening Protocols

    EPA Science Inventory

    The endocrine system provides a number of target sites that may be susceptible to disruption by environmental agents. In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system (http://w...

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

    EPA Pesticide Factsheets

    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.

  2. Neurotoxicity of endocrine disruptors: possible involvement in brain development and neurodegeneration.

    PubMed

    Masuo, Yoshinori; Ishido, Masami

    2011-01-01

    Environmental chemicals that act as endocrine disruptors do not appear to pose a risk to human reproduction; however, their effects on the central nervous systems are less well understood. Animal studies suggested that maternal exposure to endocrine-disrupting chemicals (EDC) produced changes in rearing behavior, locomotion, anxiety, and learning/memory in offspring, as well as neuronal abnormalities. Some investigations suggested that EDC exert effects on central monoaminergic neurons, especially dopaminergic neurons. Our data demonstrated that EDC attenuate the development of dopaminergic neurons, which might be involved in developmental disorders. Perinatal exposure to EDC might affect neuronal plasticity in the hippocampus, thereby potentially modulating neuronal development, leading to impaired cognitive and memory functions. Endocrine disruptors also attenuate gender differences in brain development. For example, the locus ceruleus is larger in female rats than in males, but treatments with bisphenol-A (BPA) enlarge this region in males. Some reports indicated that EDC induce hypothyroidism, which might be evidenced as abnormal brain development. Endocrine disruptors might also affect mature neurons, resulting in neurodegenerative disorders such as Parkinson's disease. The current review focused on alterations in the brain induced by EDC, specifically on the possible involvement of EDC in brain development and neurodegeneration.

  3. Environmental endocrine disruptors in farm animal reproduction: research and reality.

    PubMed

    Magnusson, U

    2012-08-01

    In this review, possible comparative advantages of studying endocrine disruption in farm animals vs laboratory rodents are discussed. First, using farm animals, the generality of findings in laboratory rodents are challenged. Farm animals may in certain aspects be better models for humans than laboratory rodents, and sometimes there might be methodological advantages in using farm animals. Second, there are several in vitro studies based on cell-culture systems from sows and cows where the effects of chemicals on sex steroid secretion can be measured and maturation and fertilization of oocytes may be assessed. These in vitro systems are powerful tools for dissecting the mechanisms of action for endocrine-disrupting chemicals. Third, in a set of recent in vivo studies using sheep, goats and pigs, in which very different exposure regimens to endocrine-disrupting chemicals have been used, a full panel of reproductive parameters pertinent to farm animals were assessed. Clinically, it is suggested that endocrine disruption in farm animals should be considered when impaired reproduction could be linked to change in source of feed or pasture. Finally, epigenetic and toxicogenomic approaches can be particularly rewarding in elucidating endocrine disruption in future farm animal studies.

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

    PubMed

    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.

  5. [Xenoestrogens: endocrine disrupting compounds].

    PubMed

    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).

  6. Elucidating the links between endocrine disruptors and neurodevelopment.

    PubMed

    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.

  7. A QSAR model for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors) by nanofiltration membranes.

    PubMed

    Yangali-Quintanilla, Victor; Sadmani, Anwar; McConville, Megan; Kennedy, Maria; Amy, Gary

    2010-01-01

    A quantitative structure activity relationship (QSAR) model has been produced for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors, pesticides and other organic compounds) by polyamide nanofiltration (NF) membranes. Principal component analysis, partial least square regression and multiple linear regressions were used to find a general QSAR equation that combines interactions between membrane characteristics, filtration operating conditions and compound properties for predicting rejection. Membrane characteristics related to hydrophobicity (contact angle), salt rejection, and surface charge (zeta potential); compound properties describing hydrophobicity (log K(ow), log D), polarity (dipole moment), and size (molar volume, molecular length, molecular depth, equivalent width, molecular weight); and operating conditions namely flux, pressure, cross flow velocity, back diffusion mass transfer coefficient, hydrodynamic ratio (J(o)/k), and recovery were identified as candidate variables for rejection prediction. An experimental database produced by the authors that accounts for 106 rejection cases of emerging contaminants by NF membranes as result of eight experiments with clean and fouled membranes (NF-90, NF-200) was used to produce the QSAR model. Subsequently, using the QSAR model, rejection predictions were made for external experimental databases. Actual rejections were compared against predicted rejections and acceptable R(2) correlation coefficients were found (0.75 and 0.84) for the best models. Additionally, leave-one-out cross-validation of the models achieved a Q(2) of 0.72 for internal validation. In conclusion, a unified general QSAR equation was able to predict rejections of emerging contaminants during nanofiltration; moreover the present approach is a basis to continue investigation using multivariate analysis techniques for understanding membrane rejection of organic compounds.

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

    PubMed

    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.

  9. Exposure to Environmental Endocrine Disruptors and Child Development

    PubMed Central

    Meeker, John D.

    2013-01-01

    Exposure to exogenous chemicals can impact endocrine function at multiple sites and through numerous specific modes of action, which may have far-reaching impacts on human health and development. Widespread human exposure to numerous known or suspected endocrine disrupting chemicals (EDCs) has been documented in the US and worldwide, as have trends for increased rates of endocrine-related diseases and disorders among children. While human epidemiology studies of exposure to EDCs and children’s health remain extremely limited, there is a growing body of evidence showing that exposure to a number of chemicals commonly found in consumer goods, personal care products, food, drinking water, and other sources may adversely impact child development through altered endocrine function. This narrative review provides a brief introduction to several common EDCs (with a specific focus on persistent organic pollutants, phthalates, bisphenol A, and contemporary use pesticides, which only represents a small number of all known or suspected EDCs), an overview of the state of the human evidence for adverse impacts of EDCs on child development (fetal growth, early reproductive tract development, pubertal development, neurodevelopment, and obesity), guidance for health care providers based on current knowledge, and recommendations for future research. PMID:22664748

  10. Endocrine Disruptor Screening Program: Tier I Screening Battery

    EPA Science Inventory

    In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system,' the Food Quality Protection Act and subsequent amendments to the Safe Drinking Water Act and Federal Food, Drug and Cosmetic A...

  11. Is nitrate an ecologically relevant endocrine disruptor in vertebrates?

    PubMed

    Guillette, Louis J; Edwards, Thea M

    2005-01-01

    The last three decades have brought clear recognition that many populations of animals are experiencing severe declines or local and global extinctions. Many examples have become common knowledge to the general public, such as worldwide declines in amphibian populations and extensive loss of coral reefs. The mechanisms underlying these and other changes are poorly understood. However, a growing literature indicates that a wide array of chemical contaminants have the potential to disrupt normal cell-to-cell signaling mechanisms. A global pollutant of most aquatic systems, nitrate has the potential to be an endocrine disrupting contaminant. This paper reviews studies performed on vertebrates demonstrating that nitrate and/or nitrite have the potential to alter endocrine function. Further, a retrospective study of our work on alligators from various lakes in Florida suggests that nitrate could contribute to some of the altered endocrine parameters previously reported in juvenile animals. We propose hypotheses suggesting that nitrate could alter steroidogenesis by 1) conversion to nitrite and nitric oxide in the mitochondria, the site of initial steroid synthesis, 2) altering Cl(-) ion concentrations in the cell by substituting for Cl(-) in the membrane transport pump or 3) binding to the heme region of various P450 enzymes associated with steroidogenesis and altering enzymatic action. Future studies are needed to examine the endocrine disruptive action of this ubiquitous pollutant. A growing literature indicates that all biologists studying natural systems, whether they choose to or not, must now consider contaminant exposure as a direct influence on their studies. That is, ubiquitous global contamination has the potential to alter the endocrine, nervous and immune systems of all organisms with resulting changes in gene expression and phenotypes.

  12. Viewpoint: Policy Requirements for Protecting Wildlife from Endocrine Disruptors

    PubMed Central

    Lyons, Gwynne

    2006-01-01

    Man-made endocrine-disrupting chemicals (EDCs) present a threat to biodiversity, even in remote areas. To date, numerous wildlife species have been affected by EDCs in the environment, but it is likely that many more species are suffering effects that have not yet been reported. Impaired reproduction, damaged brain function, and deficits of the immune system are of particular concern. In order to bring all endocrine-disrupting chemicals under control, the development of screens and tests to identify EDCs must be expedited. However, the World Wildlife Fund (WWF) considers that sufficient information is already available to merit action on several such substances. In addition, it must be recognized that proving the mechanism of action for some chemicals may take decades. Therefore, it is important to enable certain chemicals to be brought under stricter control on the basis of strong suspicion of endocrine disruption or biochemical signaling disruption. Furthermore, the risk assessment process itself also must be modified, and some suggestions are discussed in this article. WWF maintains that any effect that could reasonably be expected to affect the population level should be taken forward in environmental risk characterization, in particular, behavioral effects should be given more consideration. Current chemical management policies are not protective, and we argue for modifications in them to be made. PMID:16818260

  13. The US EPA's Endocrine Disruptor Screening Program: In VItro and In Vivo Mammalian Tier 1 Screening Assays

    EPA Science Inventory

    In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system, the Food Quality Protection Act mandated that the U.S. EPA develop and implement an endocrine disruptor screening program (EDSP...

  14. Can Endocrine Disruptors Influence Neuroplasticity In The Aging Brain?

    PubMed Central

    Weiss, Bernard

    2007-01-01

    Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer’s disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, anti-androgens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle. PMID:17350099

  15. Assessment of environmental endocrine disruptors in bald eagles of the Great Lakes.

    PubMed

    Bowerman, W W; Best, D A; Grubb, T G; Sikarskie, J G; Giesy, J P

    2000-11-01

    Environmental endocrine disruption in wildlife has primarily focused on estrogenic/androgenic end points and their antagonists. We describe here the work that has occurred within the Great Lakes of North America that has used the bald eagle (Haliaeetus leucocephalus) as a sentinel species of the effects of environmental toxicants, including endocrine disruption. Our data suggests that population level effects of hormone disrupting chemicals, not necessarily estrogen/androgen mimics and their antagonists, have been associated with reproductive and teratogenic effects observed in the bald eagle population within the Great Lakes Basin. Additional laboratory and field studies are necessary to further clarify the role of environmental endocrine disruptors on reproduction in avian populations. The use of sea eagles (Haliaeetus spp.) as biosentinels of pollution in other regions of the world is also discussed.

  16. Development of an extraction and purification method for the determination of multi-class pharmaceuticals and endocrine disruptors in freshwater invertebrates.

    PubMed

    Huerta, B; Jakimska, A; Llorca, M; Ruhí, A; Margoutidis, G; Acuña, V; Sabater, S; Rodriguez-Mozaz, S; Barcelò, D

    2015-01-01

    Aquatic organisms from freshwater ecosystems impacted by waste water treatment plant (WWTP) effluents are constantly exposed to constant concentrations of pharmaceuticals, endocrine disruptors and related compounds, among other anthropogenic contaminants. Macroinvertebrates inhabiting freshwater ecosystems might be useful bioindicators of exposure to contaminants, since their lives are long enough to bioaccumulate, but at the same time may integrate short-term changes in the environment. However, studies about potential bioaccumulation of emerging contaminants in these organisms are very scarce. The objectives of this study were to develop an analytical methodology for the analysis of 41 pharmaceuticals and 21 endocrine disruptors in freshwater invertebrates. In addition, bioaccumulation of these contaminants in three macroinvertebrate taxa inhabiting a waste water treatment plant -impacted river was evaluated. The method for the simultaneous extraction of both families of compounds is based on sonication, purification via removal of phospholipids, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 34-125%, and for endocrine disruptors were 48-117%. Method detection limits (MDLs) for EDCs were in the range of 0.080-2.4 ng g(-1), and for pharmaceuticals, 0.060-4.3 ng g(-1). These pollutants were detected in water samples taken downstream the waste water treatment plant effluent at concentrations up to 572 ng L(-1). Two non-esteroidal anti-inflammatory drugs, diclofenac and ibuprofen, and four endocrine disruptors - estrone, bisphenol A, TBEP, and nonylphenol - were detected in at least one macroinvertebrate taxa in concentrations up to 183 ng g(-1) (dry weight). An isobaric interference was identified during the analysis of diclofenac in Hydropsyche samples, which was successfully discriminated via accurate mass determination by TFC-LTQ Orbitrap.

  17. Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates.

    PubMed Central

    Wynne-Edwards, K E

    2001-01-01

    Hormone disruption is a major, underappreciated component of the plant chemical arsenal, and the historical coevolution between hormone-disrupting plants and herbivores will have both increased the susceptibility of carnivores and diversified the sensitivities of herbivores to man-made endocrine disruptors. Here I review diverse evidence of the influence of plant secondary compounds on vertebrate reproduction, including human reproduction. Three of the testable hypotheses about the evolutionary responses of vertebrate herbivores to hormone-disrupting challenges from their diet are developed. Specifically, the hypotheses are that a) vertebrate herbivores will express steroid hormone receptors in the buccal cavity and/or the vomeronasal organ; b) absolute sex steroid concentrations will be lower in carnivores than in herbivores; and c) herbivore steroid receptors should be more diverse in their binding affinities than carnivore lineages. The argument developed in this review, if empirically validated by support for the specific hypotheses, suggests that a) carnivores will be more susceptible than herbivores to endocrine-disrupting compounds of anthropogenic origin entering their bodies, and b) diverse herbivore lineages will be variably susceptible to any given natural or synthetic contaminant. As screening methods for hormone-disrupting potential are compared and adopted, comparative endocrine physiology research is urgently needed to develop models that predict the broad applicability of those screening results in diverse vertebrate species. PMID:11401754

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

    PubMed

    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.

  19. Endocrine disruptors and human health: is there a problem.

    PubMed

    Safe, Stephen

    2004-12-01

    It has been hypothesized that endocrine-active chemicals (EACs) may be responsible for the increased incidence of breast cancer and disorders of the male reproductive tract. Synthetic chemicals with estrogenic activity (xenoestrogen) and the organochlorine environmental contaminants polychlorinated biphenyls (PCBs) and DDE have been the prime etiologic suspects. However, results of extensive research on PCBs and DDE does not show a correlation between PCB/DDE exposure and development of breast cancer. Studies also show that sperm count levels vary with demography, and the hypothesized coordinate global decrease in sperm counts and other disorders of the male reproductive tract is not supported by published data. In contrast, testicular cancer is increasing in most countries, and causal environmental/lifestyle factors for this disease are unknown.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.

    PubMed

    Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

    2014-01-01

    Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.

  2. Modifications to the Current EPA Endocrine Disruptor Screening Program's Tier 1 Female Pubertal Protocol: A Study on the Effects of the Chlorotriazine Simazine

    EPA Science Inventory

    Currently the US EPA is implementing a screening program for environmental endocrine disruptors. One of the in vivo assays in the Tier 1 Screen of the Endocrine Disruptors Screening Program (EDSP) is a female pubertal assay. In this study we examined the chlorotriazine simazine, ...

  3. Endocrine disruptors and human corpus luteum: in vitro effects of phenols on luteal cells function.

    PubMed

    Romani, Federica; Tropea, Anna; Scarinci, Elisa; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

    2013-01-01

    Endocrine disruptors are well known to impair fertility. The aim of the present study was to investigate the effects of bisphenol A (BPA) and nonylphenol (p-NP) on human luteal function in vitro. In particular, in luteal cells isolated from 21 human corpora lutea progesterone, prostaglandin (PG) F2α, PGE2 and vascular endothelial growth factor (VEGF) release, as well as VEGF expression were evaluated. BPA and p-NP negatively affected both luteal steroidogenesis and luteotrophic/ luteolytic factors balance, without influencing VEGF mRNA expression. Actually, BPA and p-NP impaired human luteal cells function in vitro, underlining the already suggested correlation between phenols and reproductive failure.

  4. Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.

    PubMed Central

    Zacharewski, T

    1998-01-01

    It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy. PMID:9599705

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

    ERIC Educational Resources Information Center

    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…

  6. A NEW HIGH RESOLUTION MASS SPECTROMETRY TECHNIQUE FOR IDENTIFYING PHARMACEUTICALS AND POTENTIAL ENDOCRINE DISRUPTORS IN DRINKING WATER SOURCES

    EPA Science Inventory

    A New High Resolution Mass Spectrometry Technique for Identifying Pharmaceuticals and Potential Endocrine Disruptors in Drinking Water Sources

    Andrew H. Grange and G. Wayne Sovocool U.S.EPA, ORD, NERL, ESD, ECB, P.O. Box 93478, Las Vegas, NV 891933478

    Mass spectra...

  7. In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

    PubMed Central

    Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

    2016-01-01

    Background: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p′-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p′-DDT exposure and reproductive abnormalities. Objectives: To investigate the putative effects of p,p′-DDT on the human follitropin receptor (FSHR) function. Methods and Results: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p′-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p′-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p′-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p′-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p′-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p′-DDT was dependent on the FSHR. In addition, p,p′-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p′-DDT and potentiation of the FSHR response to FSH by p,p′-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p′-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p′-DDT and 16a into the FSHR transmembrane bundle. Conclusion: p,p′-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein–coupled receptors are additional targets of endocrine disruptors. Citation: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016

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

    PubMed

    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

  9. Assessing the effects of endocrine disruptors in the National Children's Study.

    PubMed Central

    Landrigan, Philip; Garg, Anjali; Droller, Daniel B J

    2003-01-01

    Children are uniquely vulnerable to toxic chemicals in the environment. Among the environmental toxicants to which children are at risk of exposure are endocrine disruptors (EDs)--chemicals that have the capacity to interfere with hormonal signaling systems. EDs may alter feedback loops in the brain, pituitary, gonads, thyroid, and other components of the endocrine system. They can affect development. Effects of EDs have been described in wildlife populations, in animals exposed experimentally, and to a more limited extent in humans. Mechanisms of action of EDs are increasingly being elucidated, and genetic polymorphisms that convey differential susceptibility to EDs are beginning to be explored. It is hypothesized that in utero and early childhood exposures to EDs may be responsible, at least in part, for decreases in semen quality; increasing incidence of congenital malformations of the reproductive organs, such as hypospadias; increasing incidence of testicular cancer; and acceleration of onset of puberty in females. The National Children's Study (NCS) will provide a unique opportunity to test the validity of these hypotheses in the context of a large prospective multi-year epidemiologic investigation. It will be essential in the NCS to assess exposures to a range of putative natural and synthetic EDs, to assess outcomes possibly due to ED exposure, to examine the potential interplay between EDs and genetic polymorphisms, and to seek links between ED exposures in early life and endocrine, reproductive, neurobehavioral, and other outcomes throughout the life span. PMID:14527850

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

    PubMed

    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.

  11. Advanced treatment process for pharmaceuticals, endocrine disruptors, and flame retardants removal.

    PubMed

    Sundaram, Vijay; Emerick, Robert W; Shumaker, Stanley E

    2014-02-01

    The objective of this project was to demonstrate the effectiveness of an advanced treatment process that did not utilize reverse osmosis for the removal of pharmaceuticals, endocrine disruptors and flame retardants (collectively referred as contaminants of emerging concern [CECs]) from municipal effluent. The advanced treatment process consisted of (in the order of use): membrane filtration, ozonation (O3), and biologically active carbon (BAC) filtration. Ozone dosage of 5 mg/L or more was needed for desired CEC removal. Biologically active carbon removed flame retardants, and ozonation byproducts including NDMA and aldehydes. The project successfully demonstrated 1) the removal of a wide range of CECs, 2) reduction of estrogen activity to background levels, and 3) removal of ozonation byproducts. Treatment was achieved at lower costs and power utilization than reverse osmosis and without generating a concentrate stream. Results from this project could make CEC removal feasible, especially in situations where reverse osmosis treatment is infeasible.

  12. Key learnings from performance of the U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 in vitro assays.

    PubMed

    LeBaron, Matthew J; Coady, Katie K; O'Connor, John C; Nabb, Diane L; Markell, Lauren K; Snajdr, Suzanne; Sue Marty, M

    2014-02-01

    Tier 1 of the U.S. EPA Endocrine Disruptor Screening Program comprises 11 studies: five in vitro assays, four in vivo mammalian assays, and two in vivo nonmammalian assays. The battery is designed to detect compounds with the potential to interact with the estrogen, androgen, or thyroid signaling pathways. This article examines the procedures, results, and data interpretation for the five Tier 1 in vitro assays: estrogen receptor (ER) and androgen receptor binding assays, an ER transactivation assay, an aromatase assay, and a steroidogenesis assay. Data are presented from two laboratories that have evaluated approximately 11 compounds in the Tier 1 in vitro assays. Generally, the ER and androgen receptor binding assays and the aromatase assay showed good specificity and reproducibility. As described in the guideline for the ER transactivation assay, a result is considered positive when the test compound induces a reporter gene signal that reaches 10% of the response seen with 1 nM 17β-estradiol (positive control). In the experience of these laboratories, this cutoff criterion may result in false-positive responses. For the steroidogenesis assay, there is variability in the basal and stimulated production of testosterone and estradiol by the H295R cells. This variability in responsiveness, coupled with potential cell stress at high concentrations of test compound, may make it difficult to discern whether hormone alterations are specific steroidogenesis alterations (i.e., endocrine active). Lastly, both laboratories had difficulty meeting some recommended performance criteria for each Tier 1 in vitro assay. Data with only minor deviations were deemed valid.

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

    SciTech Connect

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:27625632

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

    PubMed

    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.

  18. The effects of the endocrine disruptors dithiocarbamates on the mammalian ovary with particular regard to mancozeb.

    PubMed

    Cecconi, Sandra; Paro, Rita; Rossi, Gianna; Macchiarelli, Guido

    2007-01-01

    Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroidogenic effects have been extensively studied and the mechanisms of toxicity clarified also at molecular level. For many others, information is restricted to few epidemiological data and in vivo/in vitro experiments with animal models. This is the case of the dithiocarbamates, and in particular of the fungicide mancozeb, an ethylenedithiocarbamate widely used to protect fruit and vegetables, ginseng included, because of its low acute toxicity in humans. Although the mechanism(s) by which mancozeb may specifically act on female reproductive organs are largely unknown, data on experimental animals in vivo have demonstrated that the fungicide can induce several disturbances on estrus cycle. When used in vitro at concentrations considered too low to cause human health injuries, the fungicide impairs mouse embryo development and meiotic spindle assembly. The possibility that the female germ cell (the oocyte) could be a specific target of mancozeb suggests a role for this fungicide as probable inductor of infertility also in exposed human populations.

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

    PubMed

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

    2008-10-01

    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 be putative endocrine disruptors (EDs). To date, there is still little or no experience with incorporating metabolic and toxicokinetic aspects into in vitro tests for EAS. This is a situation in sharp contrast to genotoxicity testing, where in vitro tests are routinely conducted with and without metabolic capacity. Originally prepared for the Organisation of Economic Cooperation and Development (OECD), this detailed review paper reviews why in vitro assays for EAS should incorporate mammalian systems of metabolism and metabolic enzyme systems, and indicates how this could be done. The background to ED testing, the available test methods, and the role of mammalian metabolism in the activation and the inactivation of both endogenous and exogenous steroids are described. The available types of systems are compared, and the potential problems in incorporating systems in in vitro tests for EAS, and how these might be overcome, are discussed. Lastly, some recommendations for future activities are made.

  20. Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

    EPA Science Inventory

    Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

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

    PubMed

    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.

  2. Effects of environmental endocrine disruptors and phytoestrogens on the kisspeptin system.

    PubMed

    Patisaul, Heather B

    2013-01-01

    Sex steroid hormones, most notably estradiol, play a pivotal role in the sex-specific organization and function of the kisspeptin system. Endocrine--disrupting compounds are anthropogenic or naturally occurring compounds that interact with steroid hormone signaling. Thus, these compounds have the potential to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling pathways, resulting in adverse effects on neuroendocrine physiology. This chapter reviews the small but growing body of evidence for endocrine disruption of the kisspeptin system by the exogenous estrogenic compounds bisphenol A, polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is region, sex, and compound specific, and associated with shifts in the timing of pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These effects highlight that disruption of kisspeptin signaling pathways could have wide ranging effects across multiple organ systems, and potentially underlies a suite of adverse human health trends including precocious female puberty, idiopathic infertility, and metabolic syndrome.

  3. Assessment of endocrine disruptors - DDTs and DEHP (plasticizer) in source water: a case study from Selangor, Malaysia.

    PubMed

    Veerasingam, Santhi Armugam; Ali Mohd, Mustafa

    2013-06-01

    The presence of endocrine disruptors in source water is of great concern because of their suspected adverse effects on humans, even when present at very low levels. As the main source of potable water supply, rivers in Malaysia are highly susceptible to contamination by various endocrine disruptors originating from anthropogenic activities. In this study, the contamination levels of 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT) and its metabolites and di-(2-ethylhexyl) phthalate (DEHP) in rivers of Selangor were examined using gas chromatography-mass spectrometry. Samples were collected from sites representing source water for 18 drinking water treatment plants in Selangor between July 2008 and July 2009. DDT and its metabolites were detected in only 14% of the 192 samples analysed at levels ranging from 0.6 to 14.6 ng/L. Meanwhile DEHP was detected in 96.8% of the samples at levels ranging from below quantitation level (18 ng/L) to 970 ng/L. The detected levels of DDTs and DEHP were lower than the WHO and Malaysian Guidelines for Drinking Water Quality. Data obtained from this study should also serve as a reference point for future surveillance on these endocrine disruptors.

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

    PubMed Central

    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

  5. Altered Amphibian Secondary Sex Characteristics following Exposure to Model Endocrine Disruptors

    EPA Science Inventory

    The formation of the secondary sex characteristics, oviducts and nuptial pads, are under the control of steroid hormones in frogs and as such are potential targets for endocrine-disrupting compounds. Oviducts are large, convoluted tubules derived from the Mullerian ducts in whic...

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

    PubMed

    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

  7. Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region.

    PubMed

    Esteban, S; Moreno-Merino, L; Matellanes, R; Catalá, M; Gorga, M; Petrovic, M; López de Alda, M; Barceló, D; Silva, A; Durán, J J; López-Martínez, J; Valcárcel, Y

    2016-05-01

    The increasing human presence in Antarctica and the waste it generates is causing an impact on the environment at local and border scale. The main sources of anthropic pollution have a mainly local effect, and include the burning of fossil fuels, waste incineration, accidental spillage and wastewater effluents, even when treated. The aim of this work is to determine the presence and origin of 30 substances of anthropogenic origin considered to be, or suspected of being, endocrine disruptors in the continental waters of the Antarctic Peninsula region. We also studied a group of toxic metals, metalloids and other elements with possible endocrine activity. Ten water samples were analyzed from a wide range of sources, including streams, ponds, glacier drain, and an urban wastewater discharge into the sea. Surprisingly, the concentrations detected are generally similar to those found in other studies on continental waters in other parts of the world. The highest concentrations of micropollutants found correspond to the group of organophosphate flame retardants (19.60-9209ngL(-1)) and alkylphenols (1.14-7225ngL(-1)); and among toxic elements the presence of aluminum (a possible hormonal modifier) (1.7-127µgL(-1)) is significant. The concentrations detected are very low and insufficient to cause acute or subacute toxicity in aquatic organisms. However, little is known as yet of the potential sublethal and chronic effects of this type of pollutants and their capacity for bioaccumulation. These results point to the need for an ongoing system of environmental monitoring of these substances in Antarctic continental waters, and the advisability of regulating at least the most environmentally hazardous of these in the Antarctic legislation.

  8. Exposure assessment of endocrine disruptors in bottled drinking water of Lebanon.

    PubMed

    Dhaini, Hassan R; Nassif, Rana M

    2014-09-01

    Bisphenol A (BPA) is a commonly used monomer in various products including bottled water. Numerous studies have reported endocrine adverse effects and neoplasia associated with BPA exposure in animals. However, considerable discrepancies exist among these studies with respect to both the nature of the toxic effects and the threshold dose. In Lebanon, 19-L polycarbonate (PC) bottles of drinking water are widely used in urban areas. The present study aims at assessing BPA human exposure and associated health risks from drinking water in Lebanese. A total of 22 bottled water sources, packaged in PC, were identified from licensed and non-licensed sources. Water samples were analyzed following exposure to sunlight for 72 h. BPA in water was quantified by HPLC, and other potential organic pollutants were screened by GC/MS. Fifty-nine percent of samples showed BPA levels above detection limits (>0.05 ng/mL). The median BPA level was 0.1 ng/mL (range 0.05 to 1.37 ng/mL). The mean BPA level for the total number of samples was 0.169 ng/mL (±0.280). A higher mean BPA level was found in water from licensed companies compared to non-licensed sources, however, not statistically significant. Screening showed the presence of dibutyl-phthalate and dioctyl-phthalate in only two samples. Endocrine disruptors (EDR) are ubiquitous contaminants in bottled water in Lebanon with potential health risk implications. Although estimated exposure levels are below the reference dose (RfD), further studies are needed to quantitate exposure from various sources and to investigate EDR contribution to existing epidemics in the country.

  9. [Degradation of endocrine disruptor bisphenol A in drinking water by ozone oxidation].

    PubMed

    Xu, Bin; Gao, Nai-yun; Rui, Min; Wang, Hong; Wu, Hai-hui

    2006-02-01

    The ozone oxidation of endocrine disruptor (bisphenol A) in drinking water was investigated. With the initial concentration of 1.0 mg/L, the removal efficiency of BPA (bisphenol A) could be measure up to 70%, 82%, 90% when the dosage of ozone was 1 mg/L, 1.5 mg/L, 2 mg/L respectively within 30 minutes. The impacts of BPA degradation under the conditions of different ozone dosages, different water background value, different BPA initial concentration and different ozone adding time were analyzed. The results show that ozone dosage play a dominant role during the process of BPA degradation, while the impact of the contact time could be ignored. The UV wavelength scanning is used to conform that the by-products were produced, which can be absorbed at UV254, and the UV254 keeps changing with the ozonation process. From the change of UV254, it can be drawn that BPA can not be completely degraded with low ozone dosage, while less adding time of total ozone dosage, high ozone dosage, improvement of dissolved ozone concentration will do great contribution to the extent of BPA degradation.

  10. Bioremediation of endocrine disruptor di-n-butyl phthalate ester by Deinococcus radiodurans and Pseudomonas stutzeri.

    PubMed

    Liao, Chien-Sen; Chen, Lung-Chieh; Chen, Bing-Sheng; Lin, Sin-Hsien

    2010-01-01

    Di-n-butyl phthalate (DBP) is a group of phthalate esters (PAEs) that are widely used in cosmetics, perfumes, and plasticizers. Due to its high production and application figures, DBP is commonly found in wastewater, sewage sludge, and aquatic environments. It has been classified as suspected endocrine disruptors by most countries. In this study, we isolated two DBP degradable strains from activated sludge. The strains were identified with their 16S rRNA as Deinococcus radiodurans and Pseudomonas stutzeri. We constructed the optimal condition of DBP degradation by using different kinds of incubation factors such as temperature, initial pH, yeast extract and surfactants. The optimal conditions of DBP degradation for these two strains are: 30 degrees C, pH 7.5 and static culture. Besides, addition of 0.23 mM of Triton X-100 could enhance the DBP degradation for D. radiodurans. In the end, we amended these two strains into the origin activated sludge and analyzed the whole microbial community structure of mixed cultures by PCR-DGGE technique. The result showed that only D. radiodurans could survive in the activated sludge after 7d of incubation. Based on this work, we hope that these findings could provide some useful information for applying the bioremediation of DBP in our environment.

  11. Effect of nanoporous carbon surface chemistry on the removal of endocrine disruptors from water phase.

    PubMed

    Vidal, Carla B; Seredych, Mykola; Rodríguez-Castellón, Enrique; Nascimento, Ronaldo F; Bandosz, Teresa J

    2015-07-01

    Wood-based activated carbon and its sulfur-doped counterpart were used as adsorbents of endocrine disruptor chemicals (EDC) from aqueous solution. Adsorption process was carried out in dynamic conditions and Thomas model was used to predict the performance of the column. The results showed a good fitting of the theoretical curve to the experimental data. S-doped carbon exhibited a higher adsorption capacity of trimethoprim (TMP) and smaller of sulfamethoxazole (SMX) and diclofenac (DCF) in comparison with the carbon with no sulfur incorporated into the matrix. The surface features of the initial carbons and those exposed to EDC were evaluated in order to derive the adsorption mechanism and elucidate the role of surface features. An increase in the amount of TMP from a low concentration solution (10 mg/L) on sulfur-doped carbon was linked to acid-base interactions and the reactive adsorption/oxidation of TMP. A decrease in SMX and DCF after sulfur doping was explained by a considerable increase in surface hydrophobicity, which does not favor the retention of polar DCF and SMX molecules. When the adsorption was measured from a high concentration solution at equilibrium conditions at the dark or under solar light irradiation different trends in the adsorption capacities were found. This was linked to the photoactivity of carbons and the degradation of EDC in the pore system promoted by visible light followed by the adsorption of the products of surface reactions.

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

    PubMed

    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.

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

    PubMed

    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.

  14. Key lessons from performance of the U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male and female pubertal assays.

    PubMed

    Stump, Donald G; O'Connor, John C; Lewis, Joseph M; Marty, M Sue

    2014-02-01

    The male and female pubertal assays, which are included in the U.S. Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) Tier 1 battery, can detect endocrine-active compounds operating by various modes of action. This article uses the collective experience of three laboratories to provide information on pubertal assay conduct, interlaboratory reproducibility, endpoint redundancy, and data interpretation. The various criteria used to select the maximum tolerated dose are described. A comparison of historical control data across laboratories confirmed reasonably good interlaboratory reproducibility. With a reliance on apical endpoints, interpretation of pubertal assay effects as specifically endocrine-mediated or secondary to other systemic effects can be problematic and mode of action may be difficult to discern. Across 21-23 data sets, relative liver weight, a nonspecific endocrine endpoint, was the most commonly affected endpoint in male and female assays. For endocrine endpoints, patterns of effects were generally seen; rarely was an endocrine-sensitive endpoint affected in isolation. In males, most frequently missed EPA-established performance criteria included mean weights for kidney and thyroid, and the coefficient of variation for age and body weight at preputial separation, seminal vesicle weight, and final body weight. In females, the frequently missed EPA-established performance criteria included mean adrenal weight and mean age at vaginal opening. To ensure specificity for endocrine effects, the pubertal assays should be interpreted using a weight-of-evidence approach as part of the entire EDSP battery. Based on the frequency with which certain performance criteria were missed, an EPA review of these criteria is warranted.

  15. t4 workshop report--lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

    PubMed

    Juberg, Daland R; Borghoff, Susan J; Becker, Richard A; Casey, Warren; Hartung, Thomas; Holsapple, Michael P; Marty, M Sue; Mihaich, Ellen M; Van Der Kraak, Glen; Wade, Michael G; Willett, Catherine E; Andersen, Melvin E; Borgert, Christopher J; Coady, Katherine K; Dourson, Michael L; Fowle, John R; Gray, L Earl; Lamb, James C; Ortego, Lisa S; Schug, Thaddeus T; Toole, Colleen M; Zorrilla, Leah M; Kroner, Oliver L; Patterson, Jacqueline; Rinckel, Lori A; Jones, Brett R

    2014-01-01

    In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays). To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key learnings and recommendations related to future EDSP evaluations emanated from the collective sessions.

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

    DTIC Science & Technology

    2012-09-25

    bioassays that measure endocrine mediated endpoints were performed. Determining if NTO acts as an endocrine disruptor is important because...restrictions on the use of these compounds by the U.S. Army. 1.3 Conclusions NTO was tested in nine endocrine disruptor bioassays. Five of... endocrine disruptors : development of a stably transfected human ovarian cell line for the detection of estrogenic and anti- estrogenic chemicals. In

  17. [Alteration of thyroid hormone secretion after long-term exposure to low doses of endocrine disruptor DDT].

    PubMed

    Iaglova, N V; Iaglov, V V

    2014-01-01

    Endocrine disruptors are exogenous substances that exhibit hormone-like action and consequently disrupt homeostatic action of endogenous hormones. DDT is the most common disruptor. The objective was to evaluate changes in thyroid hormone secretion after long-term exposure to low doses of DDT. The experiment was performed on male Wistar rats. The rats were given DDT at doses of 1.89±0.86 мg/kg/day and 7.77±0.17 мg/kg/day for 6 and 10 weeks. Dose dependent increase of serum total thyroxine, total triiodthyronine, and thyroid peroxidase was revealed after 6 weeks exposure. After 10 weeks free thyroxine secretion was reduced. Such alterations of the thyroid status are typical for iodine deficient goiter. The data obtained indicate that the main mechanism of DDT action includes disruption of thyroxine secretion by thyrocytes, but not inhibition of deiodinase activity and decrease of blood thyroid binding proteins.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  20. Effects of endocrine disruptors on imprinted gene expression in the mouse embryo.

    PubMed

    Kang, Eun-Rim; Iqbal, Khursheed; Tran, Diana A; Rivas, Guillermo E; Singh, Purnima; Pfeifer, Gerd P; Szabó, Piroska E

    2011-07-01

    Environmental endocrine disruptors (EDs) are synthetic chemicals that resemble natural hormones and are known to cause epigenetic perturbations. EDs have profound effects on development and fertility. Imprinted genes had been identified as susceptible loci to environmental insults by EDs because they are functionally haploid, and because the imprints undergo epigenetic resetting between generations. To screen for possible epigenetic perturbations caused by EDs at imprinted loci, we treated pregnant mice daily between 8.5 and 12.5 days post coitum (dpc) with di-(2-ethylhexyl)-phthalate (DEHP), bisphenol A (BPA), vinclozolin (VZ), or control oil vehicle. After isolating RNA from the placenta, yolk sac, amnion, head, body, heart, liver, lung, stomach, and intestines of 13.5 dpc embryos we measured the allele-specific expression of 38 imprinted transcripts using multiplex single nucleotide primer extension (SNuPE) assays. In this representative data set we identified only a small number of transcripts that exhibited a substantial relaxation of imprinted expression with statistical significance: Slc22a18 with 10% relaxation in the embryo after BPA treatment; Rtl1as with 11 and 16% relaxation in the lung and placenta, respectively after BPA treatment; and Rtl1 with 12% relaxation in the yolk sac after DEHP treatment. Additionally, the standard deviation of allele-specificity increased in various organs after ED treatment for several transcripts including Igf2r, Rasgrf1, Usp29, Slc38a4, and Xist. Our data suggest that the maintenance of strongly biased monoallelic expression of imprinted genes is generally insensitive to EDs in the 13.5 dpc embryo and extra-embryonic organs, but is not immune to those effects.

  1. [Endocrine disruptors in food contact articles and baby toys with their transition].

    PubMed

    Kawamura, Yoko

    2010-01-01

    A number of endocrine disruptors have been reported in food contact articles and baby toys mainly during the second half of the 1990s. Bisphenol A, nonylphenol, phthalates, styrene dimers and trimers, and their transision are described in this article. Bisphenol A was found in polycarbonate tableware, nursing bottles and the epoxy resin coating of cans, therefore, it was also found in the canned foods and drinks. Polycarbonate is now only slightly used for tableware or nursing bottles in Japan because consumers refused them. The can manufacturers changed their coating material to the low bisphenol A resin or PET films and voluntarily regulate its migration limit to under 5 or 10 ng/ml. Nonylphenol was found in most PVC wrapping films and gloves. It was generated from an oxidant, tris (nonylphenyl) phosphite. PVC wrapping film was extensively used in markets, thus many kinds of foods were contaminated. Among them, fillet or minced fish and meat contained it at high levels. In 2000, manufacturers voluntarily changed their composition and all wrapping films in Japan no longer contain nonylphenol. Di(2-ethylhexyl) phthalate (DEHP) was found in PVC gloves, which contaminated packed lunches and hospital meals at high levels. The government prohibited these gloves for all food contact use in 2000, moreover, other PVC food contact articles containing DEHP were prohibited for contact use with fatty foods in 2002. DEHP was also found in PVC toys which was prohibited in 2002. Styrene dimers and trimers were found in PS products, which migrated into cupped noodles after cooking. No changes have been made in them. In Japan, the exposure to bisphenol A, nonylphenol and DEHP have been significantly reduced and people also have more concerns with the safety of food contact articles.

  2. Effect-directed identification of endocrine disruptors in plastic baby teethers.

    PubMed

    Berger, Elisabeth; Potouridis, Theodoros; Haeger, Astrid; Püttmann, Wilhelm; Wagner, Martin

    2015-11-01

    Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved.

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

    SciTech Connect

    Bedia, Carmen Dalmau, Núria Jaumot, Joaquim Tauler, Romà

    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

  4. Neural network integration of field observations for soil endocrine disruptor characterisation.

    PubMed

    Aitkenhead, M J; Rhind, S M; Zhang, Z L; Kyle, C E; Coull, M C

    2014-01-15

    A neural network approach was used to predict the presence and concentration of a range of endocrine disrupting compounds (EDCs), based on field observations. Soil sample concentrations of endocrine disrupting compounds (EDCs) and site environmental characteristics, drawn from the National Soil Inventory of Scotland (NSIS) database, were used. Neural network models were trained to predict soil EDC concentrations using field observations for 184 sites. The results showed that presence/absence and concentration of several of the EDCs, mostly no longer in production, could be predicted with some accuracy. We were able to predict concentrations of seven of 31 compounds with r(2) values greater than 0.25 for log-normalised values and of eight with log-normalised predictions converted to a linear scale. Additional statistical analyses were carried out, including Root Mean Square Error (RMSE), Mean Error (ME), Willmott's index of agreement, Percent Bias (PBIAS) and ratio of root mean square to standard deviation (RSR). These analyses allowed us to demonstrate that the neural network models were making meaningful predictions of EDC concentration. We identified the main predictive input parameters in each case, based on a sensitivity analysis of the trained neural network model. We also demonstrated the capacity of the method for predicting the presence and level of EDC concentration in the field, identified further developments required to make this process as rapid and operator-friendly as possible and discussed the potential value of a system for field surveys of soil composition.

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

    PubMed

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

    PubMed Central

    2012-01-01

    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 endocrine disruptors, and

  7. Evaluating bioaccumulation of suspected endocrine disruptors into periphytons and benthos in the Tama River.

    PubMed

    Takahashi, A; Higashitani, T; Yakou, Y; Saitou, M; Tamamoto, H; Tanaka, H

    2003-01-01

    There are two major routes through which fish are exposed to endocrine disruptors (EDs); one route is through water that is a habitat; the other is through aquatic food such as algae and benthos. Few studies on the bioaccumulation of EDs in food have been conducted. Therefore, we evaluated the concentration in food of nonylphenol (NP), bisphenol A (BPA) and 17beta-estradiol (E2), which were frequently detected in river water and in final discharge of Wastewater Treatment Plants (WWTPs) in Japan. We also evaluated the estrogenicity of samples using recombinant yeast. NP concentrations ranged 0.1-0.4 microg/L in the river water, while they ranged 8-130 microg/kg-wet in the periphytons and 8-140 microg/kg-wet in the benthos. BPA concentrations ranged 0.02-0.15 microg/L in the river water, while they ranged 2-8.8 microg/kg-wet in the periphytons and 0.3-12 microg/kg-wet in the benthos. E2 concentrations ranged 0.0001-0.0076 microg/L in the water, while they ranged 0.09-2.26 microg/kg-wet in the periphytons and <0.01-0.22 microg/kg-wet in the benthos. The estrogenicity ranged 0.0001-0.0464 microg-E2equivalent/L in the water, while it ranged 3.4-66.8 microg-E2equivalent/kg-wet in the periphytons and 7.4-5458 microg-E2equivalent/kg-wet in the benthos. Bioaccumulation factors of NP are estimated as 160-650 for the periphytons, and 63-990 for the benthos, respectively. Bioaccumulation factors of BPA are estimated as 18-650 for the periphytons, and 8-170 for the benthos, respectively. Bioaccumulation factors of E2 are estimated as 64-1,200 for the periphytons, and 100-160 for the benthos, respectively. The ratios of the periphytons and the benthos to the water in terms of the estrogenicity were larger than those in terms of the chemicals. In particularly, the ratio of the benthos to the water is about 10(6) in the maximum. The results suggest that food may be a more important route for fish exposed to EDs in water environment.

  8. The case for taking account of metabolism when testing for potential endocrine disruptors in vitro.

    PubMed

    Combes, Robert D

    2004-06-01

    Legislation in the USA, Europe and Japan will require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Such chemicals are known as endocrine disruptors (EDs), and will require extensive testing as part of the new European Union Registration, Evaluation and Authorisation of Chemicals (REACH) system for the risk assessment of chemicals. Both in vivo and in vitro tests are proposed for this purpose, and there has been much discussion and action concerning the development and validation of such tests. However, to date, little interest has been shown in incorporating metabolism into in vitro tests for EDs, in sharp contrast to other areas of toxicity testing, such as genotoxicity, and, ironically, such in vitro tests are criticised for not modelling in vivo metabolism. This is despite the existence of much information showing that endogenous and exogenous steroids are extensively metabolised by Phase I and Phase II enzymes both in the liver and in hormonally active tissues. Such metabolism can lead to the activation or detoxification of steroids and EDs. The absence of metabolism from these tests could give rise to false-positive data (due to lack of detoxification) or false-negative data (lack of activation). This paper aims to explain why in vitro assays for EDs should incorporate mammalian metabolising systems. The background to ED testing, the test methods available, and the role of mammalian metabolism in the activation and detoxification of both endogenous and exogenous steroids, are described. The available types of metabolising systems are compared, and the potential problems in incorporating metabolising systems into in vitro tests for EDs, and how these might be overcome, are discussed. It is recommended that there should be: a) an assessment of the intrinsic metabolising capacity of cell systems used in tests for EDs; b) an investigation into the relevance of using the prostaglandin H synthase system for metabolising EDs

  9. Defeminization in Daphnia magna: A screening test for endocrine-disruptors in the environment?

    SciTech Connect

    Gerritsen, A.A.M.; Hoeven, N. van der

    1995-12-31

    Long term consequences associated with exposure to endocrine disrupting chemicals in the environment have been found in mammals, birds, fish, turtles and gastropods. Despite their important role, however, hardly any attention has been paid to the long term effects of such chemicals on crustaceans. Experiments originally carried out to quantify the ability of Daphnia magna to recover from short term exposure to para-tert-pentylphenol, revealed the endocrine disrupting properties of the test compound. During one of the experiments animals were divided into six (8 hour) age groups between 0 and 48 hours and exposed to 6 mg of para-tert-pentylphenol 1{sup {minus}1} for a period of 8 hours. Within the age groups of 16 to 24 and of 24 to 32 hours old 51 and 70% of the females respectively lag-fed behind in growth and showed reduced fertility. In addition to this, about 37 and 16% of these females showed malformations suggesting defeminization. The males showed no delay in growth and had no malformations. Furthermore, in terms of survival the males were shown to be less sensitive towards the test compound than the females. The type of effects in females and the sharp distinction between the effects on males and females are indicative for the estrogenicity of para-tert-pentylphenol. The estrogenic effects of a number alkylphenols, including para-tert-pentylphenol, were demonstrated in rats and confirmed in tests with the human breast cell MCF7. To the best of knowledge estrogenicity has not been recorded before for any chemical for any crustacean. The observation of estrogenic effects in D. magna opens up the way to a standardized test for screening chemicals with potentially endocrine disrupting properties. Such a test may be a valuable tool in environmental risk assessment and conservation of environmental and human health.

  10. Reporter Cell Lines for the Characterization of the Interactions between Human Nuclear Receptors and Endocrine Disruptors

    PubMed Central

    Grimaldi, Marina; Boulahtouf, Abdelhay; Delfosse, Vanessa; Thouennon, Erwan; Bourguet, William; Balaguer, Patrick

    2015-01-01

    Endocrine-disrupting chemicals (EDCs) are exogenous substances interfering with hormone biosynthesis, metabolism, or action, and consequently causing disturbances in the endocrine system. Various pathways are activated by EDCs, including interactions with nuclear receptors (NRs), which are primary targets of numerous environmental contaminants. The main NRs targeted by environmental contaminants are the estrogen (ER α, β) and the androgen (AR) receptors. ERs and AR have pleiotropic regulatory roles in a diverse range of tissues, notably in the mammary gland, the uterus, and the prostate. Thus, dysfunctional ERs and AR signaling due to inappropriate exposure to environmental pollutants may lead to hormonal cancers and infertility. The pregnane X receptor (PXR) is also recognized by many environmental molecules. PXR has a protective role of the body through its ability to regulate proteins involved in the metabolism, the conjugation, and the transport of many exogenous and endogenous compounds. However, the permanent activation of this receptor by xenobiotics may lead to premature drug metabolism, the formation, and accumulation of toxic metabolites and defects in hormones homeostasis. The activity of other NRs can also be affected by environmental molecules. Compounds capable of inhibiting or activating the estrogen related (ERRγ), the thyroid hormone (TRα, β), the retinoid X receptors (RXRα, β, γ), and peroxisome proliferator-activated (PPAR α, γ) receptors have been identified and are highly suspected to promote developmental, reproductive, neurological, or metabolic diseases in humans and wildlife. In this review, we provide an overview of reporter cell lines established to characterize the human NR activities of a large panel of EDCs including natural as well as industrial compounds such as pesticides, plasticizers, surfactants, flame retardants, and cosmetics. PMID:26029163

  11. The Role of Oxysterols in a Computational Steroidogenesis Model of Human H295R Cells to Improve Predictability of Biochemical Responses to Endocrine Disruptors

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine disruptors (...

  12. Evolving the EPA Endocrine Disruptor Screening Program: The case for and against using high-throughput screening assays in EDSP Tier 1

    EPA Science Inventory

    Testing has begun as part of the EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 battery of 11 in vitro and in vivo tests. A recognized issue with the EDSP is that the current Tier 1 screening battery is highly resource intensive in terms of cost, time and animal usage fo...

  13. AN APPROACH TO THE DEVELOPMENT OF MODELS TO QUANTITATIVELY ASSESS THE EFFECTS OF EXPOSURE TO ENVIRONMENTALLY RELEVANT LEVELS OF ENDOCRINE DISRUPTORS

    EPA Science Inventory

    An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.

    Ben-Jonathan N, Cooper RL, Foster P, Hughes CL, Hoyer PB, Klotz D, Kohn M, Lamb DJ, Stancel GM.
    <...

  14. EVALUATION OF AMMONIUM PERCHLORATE IN THE ENDOCRINE DISRUPTOR SCREENING AND TESTING PROGRAM'S MALE PUBERTAL PROTOCOL: ABILITY TO DETECT EFFECTS OF THYROID ENDPOINTS.

    EPA Science Inventory

    The U.S EPA Endocrine Disruptor Screening Program Tier 1 male pubertal protocol was designed to detect reproductive development and thyroid function. One purpose of this in vivo protocol is to detect thyrotoxicants via a number of different mechanisms of action. Here we evaluate ...

  15. EFFECT OF THE ANTI-ANDROGENIC ENDOCRINE DISRUPTOR VINCLOZOLIN ON EMBRYONIC TESTIS CORD FORMATION AND POSTNATAL TESTIS DEVELOPMENT AND FUNCTION. (R827405)

    EPA Science Inventory

    Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is...

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

    PubMed

    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.

  17. 78 FR 35909 - Endocrine Disruptor Screening Program; Final Policies and Procedures for Screening Safe Drinking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... to human health or the environment due to disruption of the endocrine system. The determination of whether a chemical has the potential to interact with the endocrine system will be made on a weight of... endocrine system necessarily meets the standard for information that must be reported in accordance...

  18. Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

    SciTech Connect

    Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

    2010-08-15

    Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

  19. Effects of (Anti) Androgenic Endocrine Disruptors (DEHP and Butachlor) on Immunoglobulin M (IgM) and Leukocytes Counts of Male Rainbow Trout (Oncorhynchus mykiss).

    PubMed

    Ahmadivand, Sohrab; Farahmand, Hamid; Mirvaghefi, Alireza; Eagderi, Soheil; Zargar, Ashkan

    2015-06-01

    The effect of two anti-androgenic endocrine disrupting compounds, i.e. the plasticizer di (2-ethylhexyl) phthalate (DEHP) and herbicide butachlor, were evaluated for their effects on immunoglobulin M (IgM) and leukocytes in male rainbow trout. Also, plasma testosterone (T) concentration was measured to confirm their anti-androgenic effects. In the first experiment, trout were treated with 50 mg/kg (body weight) DEHP intraperitoneally, and in the second one, fish were exposed to 0.39 mg/L butachlor for 10 days. The results showed that T concentrations and white blood cells were significantly lower in fish exposed to either DEHP or butachlor compared to control fish (p < 0.05). Fish showed significantly elevated neutrophil levels and decreased lymphocyte levels in the butachlor (p < 0.05); however, no significant difference was observed in lymphocyte and neutrophils values in the DEHP treatment (p > 0.05). In addition, no significant differences were found in IgM, eosinophil and monocyte parameters in either DEHP or butachlor treatments (p > 0.05). These results confirmed that leukocytes counts can be considered as a novel marker of immunotoxicity triggered by (anti) androgenic endocrine disruptors.

  20. Bioaccumulation and trophic magnification of pharmaceuticals and endocrine disruptors in a Mediterranean river food web.

    PubMed

    Ruhí, Albert; Acuña, Vicenç; Barceló, Damià; Huerta, Belinda; Mor, Jordi-Rene; Rodríguez-Mozaz, Sara; Sabater, Sergi

    2016-01-01

    Increasing evidence exists that emerging pollutants such as pharmaceuticals (PhACs) and endocrine-disrupting compounds (EDCs) can be bioaccumulated by aquatic organisms. However, the relative role of trophic transfers in the acquisition of emerging pollutants by aquatic organisms remains largely unexplored. In freshwater ecosystems, wastewater treatment plants are a major source of PhACs and EDCs. Here we studied the entrance of emerging pollutants and their flow through riverine food webs in an effluent-influenced river. To this end we assembled a data set on the composition and concentrations of a broad spectrum of PhACs (25 compounds) and EDCs (12 compounds) in water, biofilm, and three aquatic macroinvertebrate taxa with different trophic positions and feeding strategies (Ancylus fluviatilis, Hydropsyche sp., Phagocata vitta). We tested for similarities in pollutant levels among these compartments, and we compared observed bioaccumulation factors (BAFs) to those predicted by a previously-developed empirical model based on octanol-water distribution coefficients (Dow). Despite a high variation in composition and levels of emerging pollutants across food web compartments, observed BAFs in Hydropsyche and Phagocata matched, on average, those already predicted. Three compounds (the anti-inflammatory drug diclofenac, the lipid regulator gemfibrozil, and the flame retardant TBEP) were detected in water, biofilm and (at least) one macroinvertebrate taxa. TBEP was the only compound present in all taxa and showed magnification across trophic levels. This suggests that prey consumption may be, in some cases, a significant exposure route. This study advances the notion that both waterborne exposure and trophic interactions need to be taken into account when assessing the potential ecological risks of emerging pollutants in aquatic ecosystems.

  1. Analytical Methodologies for the Determination of Endocrine Disrupting Compounds in Biological and Environmental Samples

    PubMed Central

    Sosa-Ferrera, Zoraida; Mahugo-Santana, Cristina; Santana-Rodríguez, José Juan

    2013-01-01

    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. PMID:23738329

  2. Nuclear Receptors and Endocrine Disruptors in Fetal and Neonatal Testes: A Gapped Landscape

    PubMed Central

    Rouiller-Fabre, Virginie; Guerquin, Marie Justine; N’Tumba-Byn, Thierry; Muczynski, Vincent; Moison, Delphine; Tourpin, Sophie; Messiaen, Sébastien; Habert, René; Livera, Gabriel

    2015-01-01

    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. PMID:25999913

  3. [Impact on human health of endocrine disruptors present in environmental water bodies: is there an association with obesity?].

    PubMed

    Pontelli, Regina Célia Nucci; Nunes, Altacilio Aparecido; Oliveira, de Sonia Valle Walter Borges

    2016-03-01

    There is growing evidence that endocrine disruptors (ED) may adversely affect humans. Surface and underground water are the main sources for obtaining potable water, however they can be contaminated with ED, which are not completely removed by conventional water and sewage treatment processes. Some health problems are related to the exposure of humans to ED, obesity being one of them. There is currently an increase in the prevalence of obesity worldwide, a fact that is considered a concern in view of its potential impact on the health care system, since obesity is the major risk factor of the leading chronic diseases including diabetes and cardiovascular disease. By means of a review of the literature, this paper sought to gather scientific publications linking exposure to ED with obesity, in order to verify the importance of removal of ED from water bodies, thereby preserving the population's health and aquatic biota. Most of the selected studies suggest an association between ED and obesity in humans.

  4. The endocrine disruptor nonylphenol induces sublethal toxicity in vascular plant development at environmental concentrations: A risk for riparian plants and irrigated crops?

    PubMed

    Esteban, S; Llamas, P M; García-Cortés, H; Catalá, M

    2016-09-01

    In recent years, there is a growing concern among the scientific community about the presence of the so-called emergent pollutants in waters of different countries, especially endocrine-disrupting compounds (EDCs) that have the ability to alter the hormonal system. One of the substances found almost ubiquitously and in higher concentrations is the alkylphenol nonylphenol. Albeit this compound is included in priority lists as a probable risk for human health and the environment, little is known about its effects on developing plants. The aim of this work is to assess the acute and sub-chronic toxicity of environmental concentrations of nonylphenol in riparian vascular plant development using spores of the fern Polystichum setiferum and a biomarker-based approach: mitochondrial activity (cell viability), chlorophyll (plant physiology) and DNA content (growth). Mitochondrial activity and DNA content show that nonylphenol induces acute and sub-chronic toxicity at 48 h and after 1 week, respectively. Significant effects are observed in both parameters in fern spores at ng L(-1) but chlorophyll autofluorescence shows little changes. The inhibition of germination by natural allelochemicals has been reported to be related with the active hydroxyl group of phenolic compounds and largely independent of the structural nucleus to which it is attached. Results presented in this study suggest that environmental concentrations of nonylphenol could interfere with higher plant germination development by mimicking natural allelochemicals and/or phytohormones acting as a "phytoendocrine disruptor" likely posing ecophysiological risks.

  5. Human biological monitoring of suspected endocrine-disrupting compounds

    PubMed Central

    Faniband, Moosa; Lindh, Christian H; Jönsson, Bo AG

    2014-01-01

    Endocrine-disrupting compounds are exogenous agents that interfere with the natural hormones of the body. Human biological monitoring is a powerful method for monitoring exposure to endocrine disrupting compounds. In this review, we describe human biological monitoring systems for different groups of endocrine disrupting compounds, polychlorinated biphenyls, brominated flame retardants, phthalates, alkylphenols, pesticides, metals, perfluronated compounds, parabens, ultraviolet filters, and organic solvents. The aspects discussed are origin to exposure, metabolism, matrices to analyse, analytical determination methods, determinants, and time trends. PMID:24369128

  6. ENDOCRINE DISRUPTORS FROM COMBUSTION AND VEHICULAR EMISSIONS: IDENTIFICATION AND SOURCE NOMINATION

    EPA Science Inventory

    During the last decade, concerns have been raised regarding the possible harmful effects of exposure to certain chemicals that are capable of modulating or disrupting the function of the endocrine system. These chemicals, which are referred to as endocrine disrupting chemicals (E...

  7. Toxicological relevance of endocrine disruptors in the Tagus River estuary (Lisbon, Portugal).

    PubMed

    Rocha, Maria João; Cruzeiro, Catarina; Reis, Mário; Pardal, Miguel Ângelo; Rocha, Eduardo

    2015-08-01

    The Tagus is the longest Iberian river, notwithstanding, the levels of natural and xenoestrogenic endocrine-disrupting compounds (EDCs) were never measured in its estuary. Suspecting for their presence, we made a major survey of 17 EDCs that include: (i) natural (17β-oestradiol and estrone) and pharmaceutical oestrogens (17α-ethynylestradiol); (ii) industrial and household pollutants (octylphenols, nonylphenols and their mono and diethoxylates, and bisphenol A); (iii) phytoestrogens (biochanin A, daidzein, formononetin, genistein); and (iv) the phytosterol (sitosterol). Water samples from the Tagus estuary were taken from nine locations every 2 months over a 1-year period and analysed by gas chromatography. Oestrogens, industrial/household pollutants were consistently higher at two sites-at Tagus River mouth and close to the Trancão tributary, both at Lisbon region. The overall oestrogenic load, in ethynylestradiol equivalents, was 13 ng/L for oestrogens, 2.3 ng/L for industrial/household pollutants and 43 ng/L for phytoestrogens; well in the range of toxicological significance. Water physicochemical parameters also indicated anthropogenic pollution, mainly at the two above-referred sampling sites.

  8. Comparison of different wastewater treatments for removal of selected endocrine-disruptors from paper mill wastewaters.

    PubMed

    Balabanič, Damjan; Hermosilla, Daphne; Merayo, Noemí; Klemenčič, Aleksandra Krivograd; Blanco, Angeles

    2012-01-01

    There is increasing concern about chemical pollutants that have the ability to mimic hormones, the so-called endocrine-disrupting compounds (EDCs). One of the main reasons for concern is the possible effect of EDCs on human health. EDCs may be released into the environment in different ways, and one of the most significant sources is industrial wastewater. The main objective of this research was to evaluate the treatment performance of different wastewater treatment procedures (biological treatment, filtration, advanced oxidation processes) for the reduction of chemical oxygen demand and seven selected EDCs (dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzyl butyl phthalate, bis(2-ethylhexyl) phthalate, bisphenol A and nonylphenol) from wastewaters from a mill producing 100 % recycled paper. Two pilot plants were running in parallel and the following treatments were compared: (i) anaerobic biological treatment followed by aerobic biological treatment, ultrafiltration and reverse osmosis (RO), and (ii) anaerobic biological treatment followed by membrane bioreactor and RO. Moreover, at lab-scale, four different advanced oxidation processes (Fenton reaction, photo-Fenton reaction, photocatalysis with TiO(2), and ozonation) were applied. The results indicated that the concentrations of selected EDCs from paper mill wastewaters were effectively reduced (100 %) by both combinations of pilot plants and photo-Fenton oxidation (98 %), while Fenton process, photocatalysis with TiO(2) and ozonation were less effective (70 % to 90 %, respectively).

  9. Optical immunosensor for endocrine disruptor nanolayer detection by surface plasmon resonance imaging

    NASA Astrophysics Data System (ADS)

    Karabchevsky, Alina; Tsapovsky, Lev; Marks, Robert S.; Abdulhalim, Ibrahim

    2011-10-01

    Endocrine disrupting compounds (EDCs) such as bisphenol A (BPA) and female hormone Estrone are especially prevalent in surface and waste-waters in nano-molar concentrations and therefore, there is a need for sensitive analytical device for their monitoring. We have designed a miniature, low cost and fast surface plasmon resonance (SPR) imaging liquid sensor based on the angular interrogation using Kretschmann configuration with diverged incident monochromatic light. During this paper we present a surface plasmon resonance imaging (SPRI) biosensor to detect EDCs such as BPA and estrone. A pattern of SPR line which is dark intensity line on bright area was reflected at angles range depending on the dielectric constant of the analye: Rabbit Anti-Estrone polyclonal IgG + Estrone 11-MUA attached to the silver or non-specific sensing of BPA in water with nanoprecision. For analyzing the SPR signals we used an efficient detection algorithm based on Radon Transform with less sensitivity to laser speckle noise and nonuniformity of the illumination.

  10. Direct UV photolysis of selected pharmaceuticals, personal care products and endocrine disruptors in aqueous solution.

    PubMed

    Carlson, Jules C; Stefan, Mihaela I; Parnis, J Mark; Metcalfe, Chris D

    2015-11-01

    Pharmaceuticals and personal care products (PPCPs), and endocrine disrupting compounds (EDCs) are micropollutants of emerging concern that have been detected in the aquatic environment and in some cases, in drinking water at nanogram per liter levels. The goal of this study was to evaluate the removal of 15 model PPCPs and EDCs from water by direct UV photolysis, using either low (LP)-or medium (MP) -pressure mercury vapor arc lamps. Some of the model compounds are either weak bases or weak acids, and therefore, the pKa values were determined or confirmed for those compounds using spectrophotometric titrations. The molar absorption coefficients of ionized and non-ionized forms were also determined. The quantum yields at 253.7 nm in phosphate buffer solutions of pH 7.2 were determined to be 0.033 ± 0.004 for sulfamethoxazole, 0.0035 ± 0.0008 for sulfachloropyridazine, 0.006 ± 0.002 for acetaminophen, 0.34 ± 0.07 for triclosan, 0.35 ± 0.14 for estrone, 0.08 ± 0.05 for 17α-ethinylestradiol, 0.086 ± 0.012 for ibuprofen. The quantum yield for 4-n-nonylphenol photolysis at 253.7 nm varied with the initial concentration from 0.32 ± 0.08 at 23 μg/L to 0.092 ± 0.006 at 230 μg/L. The pseudo-first order rate constants determined for direct photolysis at 253.7 nm of the studied micropollutants followed the order: triclosan ≈ sulfamethoxazole > 4-n-nonylphenol ≈ sulfachloropyridazine ≈ estrone > acetaminophen ≈ 17α-ethinylestradiol ≈ ibuprofen. In contrast to the results observed for the monochromatic radiation (LP lamp), all 15 model compounds photolyzed under exposure to the broadband radiation emitted by the MP lamp.

  11. Application of a fast and cost-effective in situ derivatization method prior to gas chromatography with mass spectrometry to monitor endocrine disruptors in water matrices.

    PubMed

    Melo, Armindo; Ferreira, Isabel M P L V O; Mansilha, Catarina

    2015-06-01

    This work deals with the optimization of a rapid, cost-effective, and eco-friendly gas chromatography with mass spectrometry method for the simultaneous determination of four endocrine disruptor compounds in water matrices: estrone, 17β-estradiol, 17α-ethinylestradiol, and bisphenol A, that are currently considered to be of main concern in the field of water policy and that could became candidates for future regulations. The method involves simultaneous derivatization and extraction of compounds by dispersive liquid-liquid microextraction followed by gas chromatography with mass spectrometry analysis. Derivatization and extraction parameters were optimized with the aid of experimental design approach. An excellent linear response was achieved for all analytes (r(2) ≥ 0.999). Limits of detection and quantification are 0.003-0.005 and 0.0094-0.0164 μg/L, respectively. Intraday precision ranged between 1.1 and 12.6%, whereas interday precision ranged between 0.5 and 14.7%. For accuracy, bias values varied between -15.0 and 13.7%. Recoveries at three concentration levels ranged from 86.4 to 118.2%. The proposed method can be applied to the routine analysis of groundwater, river, sea, tap, and mineral water samples with excellent sensitivity, precision, and accuracy.

  12. Endocrine Disruptors: Data-based survey of in vivo tests, predictive models and the Adverse Outcome Pathway.

    PubMed

    Benigni, Romualdo; Battistelli, Chiara Laura; Bossa, Cecilia; Giuliani, Alessandro; Tcheremenskaia, Olga

    2017-02-20

    The protection from endocrine disruptors is a high regulatory priority. Key issues are the characterization of in vivo assays, and the identification of reference chemicals to validate alternative methods. In this exploration, publicly available databases for in vivo assays for endocrine disruption were collected and compared: Rodent Uterotrophic, Rodent Repeated Dose 28-day Oral Toxicity, 21-Day Fish, and Daphnia magna reproduction assays. Only the Uterotrophic and 21-Day Fish assays results correlated with each other. The in vivo assays data were viewed in relation to the Adverse Outcome Pathway, using as a probe 18 ToxCast in vitro assays for the ER pathway. These are the same data at the basis of the EPA agonist ToxERscore model, whose good predictivity was confirmed. The multivariate comparison of the in vitro/in vivo assays suggests that the interaction with receptors is a major determinant of in vivo results, and is the critical basis for building predictive computational models. In agreement with the above, this work also shows that it is possible to build predictive models for the Uterotrophic and 21-Day Fish assays using a limited selection of Toxcast assays.

  13. Cadmium as an endocrine disruptor: correlation with anterior pituitary redox and circadian clock mechanisms and prevention by melatonin.

    PubMed

    Jiménez-Ortega, Vanesa; Cano Barquilla, Pilar; Fernández-Mateos, Pilar; Cardinali, Daniel P; Esquifino, Ana I

    2012-12-15

    To examine the effect of a low dose of cadmium (Cd) as an endocrine disruptor, male Wistar rats received CdCl2 (5ppm Cd) in drinking water or drinking water alone. After 1 month, the rats were euthanized at one of six time intervals around the clock and the 24-h pattern of adenohypophysial prolactin (PRL) synthesis and release, lipid peroxidation, and redox enzyme and metallothionein (MT) gene expression was examined. Cd suppressed 24-h rhythmicity in expression of the PRL gene and in circulating PRL by increasing them at early photophase only, in correlation with an augmented pituitary lipid peroxidation and redox enzyme expression. CdCl2 treatment effectively disrupted the 24-h variation in expression of every pituitary parameter tested except for MT-3. In a second experiment the effect of melatonin (3μg/ml in drinking water) was assessed at early photophase, the time of maximal endocrine-disrupting effect of Cd. Melatonin treatment blunted the effect of Cd on PRL synthesis and release, decreased Cd-induced lipid peroxidation, and counteracted the effect of Cd on expression of most redox enzymes. A third experiment was performed to examine whether melatonin could counteract Cd-induced changes in the 24-h pattern of pituitary circadian clock gene expression and plasma PRL, luteinizing hormone (LH), thyrotropin (TSH), and corticosterone levels. Rats receiving CdCl2 exhibited a suppressed daily rhythm of Clock expression and a significant disruption in daily rhythms of pituitary Bmal1, Per1, Per2, Cry1, and Cry2. The coadministration of melatonin restored rhythmicity in Clock and Bmal1 expression but shifted the maxima in pituitary Per1, Cry1, and Cry2 expression to the scotophase. Melatonin also counteracted the effect of Cd on 24-h rhythmicity of circulating PRL, LH, TSH, and corticosterone. The results highlight the occurrence of a significant endocrine disruptor effect of a low dose of Cd. Generally melatonin counteracted the effects of Cd and ameliorated

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

    SciTech Connect

    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

  15. USE OF THE LABORATORY RAT AS A MODEL IN ENDOCRINE DISRUPTOR SCREENING AND TESTING

    EPA Science Inventory

    The screening and testing program the US Environmental Protection Agency is currently developing to detect endocrine-disrupting chemicals (EDCs) is described. EDCs have been shown to alter the following activities: hypothalamic-pituitary-gonadal [HPG] function; estrogen, androge...

  16. SCIENTIFIC AND TECHNOLOGICAL SUPPORT ON IN VITRO ASSAYS FOR THE AGENCY'S ENDOCRINE DISRUPTOR SCREENING PROGRAM

    EPA Science Inventory

    In response to the 1996 legislative mandate for an endocrine screening and testing program, we are helping develop, standardize and validate relatively sensitive, robust and relatively simple methods for in vitro screening of chemicals that affect estrogen, and androgen function ...

  17. The Effects of Endocrine Disruptors on Steroidogenesis Gene Expression Dynamics in Fathead Minnow

    EPA Science Inventory

    Steroid hormones play key roles in regulating reproduction and development and fish and other vertebrates. This presentation reports results from two in vitro experiments aimed characterizing the dynamics of transcriptional and metabolomic responses to endocrine disrupting chemi...

  18. EVALUATION OF METHOXYCHLOR AS AN ENDOCRINE DISRUPTOR IN FATHEAD MINNOWS (PIMEPHALES PROMELAS)

    EPA Science Inventory

    Recent concerns over the possible effects of endocrine-disrupting chemicals (EDCs) on humans and wildlife has resulted in considerable interest in environmental contaminants that adversely affect aspects of sexual reproduction and early development. The U.S. Environmental Protect...

  19. REPRODUCTIVE AND DEVELOPMENTAL SCREENING PROTOCOLS FOR ENDOCRINE DISRUPTORS USING ESTUARINE CRUSTACEANS

    EPA Science Inventory

    The objective of this research is to develop in vivo screening protocols for endocrine disruption in marine crustaceans, invertebrates of ecological and economic importance. A series of comparative developmental and reproductive studies were performed on several species of estuar...

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

    PubMed

    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.

  1. Electrochemical detection of a powerful estrogenic endocrine disruptor: ethinylestradiol in water samples through bioseparation procedure.

    PubMed

    Martínez, Noelia A; Pereira, Sirley V; Bertolino, Franco A; Schneider, Rudolf J; Messina, Germán A; Raba, Julio

    2012-04-20

    The synthetic estrogen ethinylestradiol (EE2) is an active component of oral contraceptives (OCs), considered as an endocrine disrupting compound (EDC). It is excreted from humans and released via sewage treatment plant effluents into aquatic environments. EDCs are any environmental pollutant chemical that, once incorporated into an organism, affects the hormonal balance of various species including humans. Its presence in the environment is becoming of great importance in water quality. This paper describes the development of an accurate, sensitive and selective method for capture, preconcentration and determination of EE2 present in water samples using: magnetic particles (MPs) as bioaffinity support for the capture and preconcentration of EE2 and a glassy carbon electrode modified with multi-walled carbon nanotubes (MWCNTs/GCE) as detection system. The capture procedure was based on the principle of immunoaffinity, the EE2 being extracted from the sample using the anti-EE2 antibodies (anti-EE2 Ab) which were previously immobilized on MPs. Subsequently the analyte desorption was done employing a sulfuric acid solution and the determination of the EE2 in the pre-concentrated solution was carried out by square wave voltammetry (SWV). This method can be used to determine EE2 in the range of 0.035-70 ng L(-1) with a detection limit (LOD) of 0.01 ng L(-1) and R.S.D.<4.20%. The proposed method has been successfully applied to the determination of EE2 in water samples and it has promising analytical applications for the direct determination of EE2 at trace levels.

  2. Identification, assessment and management of "endocrine disruptors" in wildlife in the EU substance legislation--discussion paper from the German Federal Environment Agency (UBA).

    PubMed

    Frische, Tobias; Bachmann, Jean; Frein, Daniel; Juffernholz, Tanja; Kehrer, Anja; Klein, Anita; Maack, Gerd; Stock, Frauke; Stolzenberg, Hans-Christian; Thierbach, Claudia; Walter-Rohde, Susanne

    2013-12-16

    A discussion paper was developed by a panel of experts of the German Federal Environment Agency (UBA) contributing to the on-going debate on the identification, assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation (plant protection products, biocides, industrial chemicals). Based on a critical synthesis of the state-of-the-art regarding regulatory requirements, testing methods, assessment schemes, decision-making criteria and risk management options, we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe. Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations. With respect to the latter, a more explicit consideration of the principle of proportionality of regulatory decision making and socio-economic benefits in the on-going debate is further encouraged.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-14

    ... accepted during the Docket Facility's normal hours of operation (8:30 a.m. to 4 p.m., Monday through Friday... from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket Facility... systems. Extensive background on the Agency's endocrine program is available at...

  4. MYSID CRUSTACEANS AS POTENTIAL TEST ORGANISMS FOR THE EVALUATION OF ENVIRONMENTAL ENDOCRINE DISRUPTORS: A REVIEW

    EPA Science Inventory

    Verslycke, Tim A., Nancy Fockedey, Charles L. McKenney, Jr., Stephen D. Roast, Malcolm B. Jones, Jan Mees and Colin R. Janssen. 2004. Mysid Crustaceans as Potential Test Organisms for the Evaluation of Environmental Endocrine Disruption: A Review. Environ. Toxicol. Chem. 23(5):12...

  5. EMERGING APPROACHES FOR ASSESSING THE EXPOSURE OF CHILDREN TO ENDOCRINE DISRUPTORS

    EPA Science Inventory

    Humans can be exposed to endocrine disrupting chemicals (EDC's) from environmental sources such as water, food, air, dust and soil. A major concern is that children may be exposed to higher amounts of pollutants than adults because of their different activity patterns, higher b...

  6. Computational Model of Adrenal Steroidogenesis to Predict Biochemical Response to Endocrine Disruptors

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme mediated reactions. The activity of steroidogenic enzymes can be altered by various endocrine disrupters (ED), ...

  7. The Use of Metabolising Systems for In Vitro Testing of Endocrine Disruptors

    EPA Science Inventory

    Legislation and prospective 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...

  8. STATUS OF ENDOCRINE DISRUPTOR SCREENING AND TESTING ACTIVITIES IN THE US: IMPLEMENTATION OF THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. In 1996, the US Congress passed the Food Quality Protection Act (FQPA) that mandated the US Environmental Protection Ag...

  9. Testosterone levels and fecundity in the hermaphroditic aquatic snail Lymnaea stagnalis exposed to testosterone and endocrine disruptors.

    PubMed

    Giusti, Arnaud; Ducrot, Virginie; Joaquim-Justo, Célia; Lagadic, Laurent

    2013-08-01

    Endocrine disruptors are known to alter endogenous free and esterified levels of androgenic and estrogenic steroid hormones in aquatic mollusks. The origin of steroids in these animals, however, remains controversial. In the present study, free and esterified testosterone concentrations were measured in the hermaphroditic aquatic gastropod Lymnaea stagnalis exposed to molecules known for their androgenic (testosterone and tributyltin), anti-androgenic (cyproterone-acetate), and estrogenic (chlordecone) properties, by reference to their mode of action in vertebrates. In parallel, snail oviposition and fecundity were followed over a 21-d exposure period. Testosterone exposure resulted in increased esterified testosterone levels, whereas free testosterone concentrations remained stable. In contrast, cyproterone-acetate significantly increased the free form of testosterone with no changes in the esterified form, whereas chlordecone showed a tendency to reduce (though not significantly) esterified testosterone concentrations without changing free testosterone levels. Finally, tributyltin did not alter testosterone homeostasis. The production of egg clutches and eggs was significantly reduced only in the snails exposed to the highest concentrations of chlordecone (19.6 µg/L) and tributyltin (94.2 ng Sn/L). Overall, the present study demonstrates that uptake of testosterone from the exposure medium occurs in L. stagnalis. Moreover, it shows that cyproterone-acetate and, to a lesser extent, chlordecone can alter endogenous testosterone levels in this freshwater snail. However, the relationship between hormonal changes and snail reproduction has not been established. Environ Toxicol Chem 2013;32:1740-1745. © 2013 SETAC.

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

    SciTech Connect

    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.

  11. Polycyclodextrin and Carbon Nanotubes as Composite for Tyrosinase Immobilization and Its Superior Electrocatalytic Activity Towards Butylparaben an Endocrine Disruptor.

    PubMed

    Rather, Jahangir Ahmad; Pilehvar, Sanaz; De Wael, Karolien

    2015-05-01

    We developed a protocol for the immobilization of tyrosinase (Tyr) on the composite of polycyclodextrin polymer (CDP) and carbon nanotubes for the detection of an endocrine disruptor, i.e., butylparaben (BP). The formation of the CDP polymer was characterized by UV-Vis spectrophotometry. The conducting film of cross-linked CDP and carbon nanotubes, displays excellent matrix capabilities for Tyr immobilization. The host-guest chemical reaction ability of CD and the π-π stacking interaction assure the bioactivity of Tyr towards butylparaben. The developed biosensor was characterized electrochemically by electrochemical impedance spectroscopy. The enzyme-substrate kinetic parameters such as the apparent Michaelis-Menten constant (K(M)(app)) was measured under saturated substrate concentration. The determination of butylparaben was carried out by using square wave voltammetry over the concentration range of 2.1 to 35.4 μM with a detection limit of 0.1 μM. The fabricated biosensor was successfully applied in real-life cosmetic samples with good recovery ranging from 98.5 to 102.8%.

  12. Reduced graphene oxide-silver nanoparticle composite as visible light photocatalyst for degradation of colorless endocrine disruptors.

    PubMed

    Bhunia, Susanta Kumar; Jana, Nikhil R

    2014-11-26

    Sunlight-induced degradation of organic pollutants is an ideal approach for environmental pollution control and wastewater treatment. Although a variety of photocatalysts have been designed toward this goal, efficient degradation of colorless organic pollutants by visible light is a challenging issue. Here, we show that a reduced graphene oxide (rGO)-based composite with silver nanoparticle (rGO-Ag) can act as an efficient visible-light photocatalyst for the degradation of colorless organic pollutants. We have developed a simple, large-scale synthesis method for rGO-Ag and used it for the degradation of three well-known endocrine disruptors (phenol, bisphenol A, and atrazine) under UV and visible light. It is found that photocatalytic efficiency by rGO-Ag under visible light is significantly higher compared to that of rGO or silver nanoparticles. It is proposed that Ag nanoparticles offer visible-light-induced excitation of silver plasmons, and conductive rGO offers efficient charge separation and thus induces oxidative degradation of the organic pollutant. This approach can be extended for sunlight-induced degradation of different organic pollutants.

  13. Metabolic and immune impairments induced by the endocrine disruptors benzo[a]pyrene and triclosan in Xenopus tropicalis.

    PubMed

    Regnault, Christophe; Willison, John; Veyrenc, Sylvie; Airieau, Antinéa; Méresse, Patrick; Fortier, Marlène; Fournier, Michel; Brousseau, Pauline; Raveton, Muriel; Reynaud, Stéphane

    2016-07-01

    Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role played by endocrine disruptors (EDs) in the decline of amphibian populations remains unclear. EDs have been extensively studied in adult amphibians for their capacity to disturb reproduction by interfering with the sexual hormone axis. Here, we studied the in vivo responses of Xenopus tropicalis males exposed to environmentally relevant concentrations of each ED, benzo[a]pyrene (BaP) and triclosan (TCS) alone (10 μg L(-1)) or a mixture of the two (10 μg L(-1) each) over a 24 h exposure period by following the modulation of the transcription of key genes involved in metabolic, sexual and immunity processes and the cellular changes in liver, spleen and testis. BaP, TCS and the mixture of the two all induced a marked metabolic disorder in the liver highlighted by insulin resistance-like and non-alcoholic fatty liver disease (NAFLD)-like phenotypes together with hepatotoxicity due to the impairment of lipid metabolism. For TCS and the mixture, these metabolic disorders were concomitant with modulation of innate immunity. These results confirmed that in addition to the reproductive effects induced by EDs in amphibians, metabolic disorders and immune system disruption should also be considered.

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

    PubMed

    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.

  15. Early developmental actions of endocrine disruptors on the hypothalamus, hippocampus and cerebral cortex

    PubMed Central

    PARENT, Anne-Simone; NAVEAU, Elise; GERARD, Arlette; BOURGUIGNON, Jean-Pierre; WESTBROOK, Gary L.

    2011-01-01

    Sex steroids and thyroid hormones play a key role in the development of the central nervous system. The critical role of these hormonal systems may explain the sensitivity of the hypothalamus, the cerebral cortex and the hippocampus to endocrine disrupting chemicals (EDCs). This review examines the evidence for endocrine disruption of glial-neuronal functions in the hypothalamus, the hippocampus and the cerebral cortex. We focus on two well-studied EDCs, the insecticide dichlorodiphenyltrichloroethane (DDT) and the polychlorinated biphenyls (PCBs). DDT is involved in neuroendocrine disruption of the reproductive axis whereas PCBs interact with both the thyroid hormone- and sex steroid-dependent systems and disturb the neuroendocrine control of reproduction and the development of the hippocampus and cortex. These results highlight the impact of EDCs on the developing nervous system and the need for more research in this area. PMID:21790315

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

    PubMed Central

    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. PMID:27445682

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

    PubMed Central

    2014-01-01

    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. PMID:24961440

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

    PubMed

    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.

  19. The use and acceptance of Other Scientifically Relevant Information (OSRI) in the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program.

    PubMed

    Bishop, Patricia L; Willett, Catherine E

    2014-02-01

    The U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP) currently relies on an initial screening battery (Tier 1) consisting of five in vitro and six in vivo assays to evaluate a chemical's potential to interact with the endocrine system. Chemical companies may request test waivers based on Other Scientifically Relevant Information (OSRI) that is functionally equivalent to data gathered in the screening battery or that provides information on a potential endocrine effect. Respondents for 47 of the first 67 chemicals evaluated in the EDSP submitted OSRI in lieu of some or all Tier 1 tests, seeking 412 waivers, of which EPA granted only 93. For 20 of the 47 chemicals, EPA denied all OSRI and required the entire Tier 1 battery. Often, the OSRI accepted was either identical to data generated by the Tier 1 assay or indicated a positive result. Although identified as potential sources of OSRI in EPA guidance, Part 158 guideline studies for pesticide registration were seldom accepted by EPA. The 93 waivers reduced animal use by at least 3325 animals. We estimate 27,731 animals were used in the actual Tier 1 tests, with additional animals being used in preparation for testing. Even with EPA's shift toward applying 21st-century toxicology tools to screening of endocrine disruptors in the future, acceptance of OSRI will remain a primary means for avoiding duplicative testing and reducing use of animals in the EDSP. Therefore, it is essential that EPA develop a consistent and transparent basis for accepting OSRI.

  20. 78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... determine the potential for a drug to disrupt the endocrine system. This draft guidance also discusses... compounds that have the potential to 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,...

  1. Fungal Laccases Degradation of Endocrine Disrupting Compounds

    PubMed Central

    Macellaro, Gemma; Cicatiello, Paola; Sannia, Giovanni

    2014-01-01

    Over the past decades, water pollution by trace organic compounds (ng/L) has become one of the key environmental issues in developed countries. This is the case of the emerging contaminants called endocrine disrupting compounds (EDCs). EDCs are a new class of environmental pollutants able to mimic or antagonize the effects of endogenous hormones, and are recently drawing scientific and public attention. Their widespread presence in the environment solicits the need of their removal from the contaminated sites. One promising approach to face this challenge consists in the use of enzymatic systems able to react with these molecules. Among the possible enzymes, oxidative enzymes are attracting increasing attention because of their versatility, the possibility to produce them on large scale, and to modify their properties. In this study five different EDCs were treated with four different fungal laccases, also in the presence of both synthetic and natural mediators. Mediators significantly increased the efficiency of the enzymatic treatment, promoting the degradation of substrates recalcitrant to laccase oxidation. The laccase showing the best performances was chosen to further investigate its oxidative capabilities against micropollutant mixtures. Improvement of enzyme performances in nonylphenol degradation rate was achieved through immobilization on glass beads. PMID:24829908

  2. Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.

    PubMed Central

    Melnick, Ronald; Lucier, George; Wolfe, Mary; Hall, Roxanne; Stancel, George; Prins, Gail; Gallo, Michael; Reuhl, Kenneth; Ho, Shuk-Mei; Brown, Terry; Moore, John; Leakey, Julian; Haseman, Joseph; Kohn, Michael

    2002-01-01

    At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when

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

    PubMed

    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.

  4. The endocrine disruptor effect of the herbicides atrazine and glyphosate on Biomphalaria alexandrina snails.

    PubMed

    Omran, Nahla Elsayed; Salama, Wesam Mohamed

    2016-04-01

    Atrazine (AZ) and glyphosate (GL) are herbicides that are widely applied to cereal crops in Egypt. The present study was designed to investigate the response of the snailBiomphalaria alexandrina(Mollusca: Gastropoda) as a bioindicator for endocrine disrupters in terms of steroid levels (testosterone (T) and 17β-estradiol (E)), alteration of microsomal CYP4501B1-like immunoreactivity, total protein (TP) level, and gonadal structure after exposure to sublethal concentrations of AZ or GL for 3 weeks. In order to study the ability of the snails' recuperation, the exposed snails were subjected to a recovery period for 2 weeks. The results showed that the level of T, E, and TP contents were significantly decreased (p ≤ 0.05) in both AZ- and GL-exposed groups compared with control (unexposed) group. The level of microsomal CYP4501B1-like immunoreactivity increased significantly (p ≤ 0.05) in GL- and AZ-exposed snails and reach nearly a 50% increase in AZ-exposed group. Histological investigation of the ovotestis showed that AZ and GL caused degenerative changes including azoospermia and oocytes deformation. Interestingly, all the recovered groups did not return back to their normal state. It can be concluded that both herbicides are endocrine disrupters and cause cellular toxicity indicated by the decrease of protein content and the increase in CYP4501B1-like immunoreactivity. This toxicity is irreversible and the snail is not able to recover its normal state. The fluctuation of CYP4501B1 suggests that this vertebrate-like enzyme may be functional also in the snail and may be used as a biomarker for insecticide toxicity.

  5. REMOVAL OF ENDOCRINE DISRUPTING COMPOUNDS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    A growing body of scientific information has shown that man-made industrial chemicals and pesticides may interfere with the normal functioning of human and wildlife endocrine systems. These agents are referred to collectively as endocrine disrupting compounds (EDCs) and they are ...

  6. Transcriptome analysis of the copepod Eurytemora affinis upon exposure to endocrine disruptor pesticides: Focus on reproduction and development.

    PubMed

    Legrand, Eléna; Forget-Leray, Joëlle; Duflot, Aurélie; Olivier, Stéphanie; Thomé, Jean-Pierre; Danger, Jean-Michel; Boulangé-Lecomte, Céline

    2016-07-01

    Copepods-which include freshwater and marine species-represent the most abundant group of aquatic invertebrates. Among them, the calanoid copepod Eurytemora affinis is widely represented in the northern hemisphere estuaries and has become a species of interest in ecotoxicology. Like other non-target organisms, E. affinis may be exposed to a wide range of chemicals such as endocrine disruptors (EDs). This study investigated the gene expression variation in E. affinis after exposure to ED pesticides-chosen as model EDs-in order to (i) improve the knowledge on their effects in crustaceans, and (ii) highlight relevant transcripts for further development of potential biomarkers of ED exposure/effect. The study focused on the reproduction function in response to ED. Copepods were exposed to sublethal concentrations of pyriproxyfen (PXF) and chlordecone (CLD) separately. After 48h, males and females (400 individuals each) were sorted for RNA extraction. Their transcriptome was pyrosequenced using the Illumina(®) technology. Contigs were blasted and functionally annotated using Blast2GO(®). The differential expression analysis between ED- and acetone-exposed organisms was performed according to sexes and contaminants. Half of the 19,721 contigs provided by pyrosequencing were annotated, mostly (80%) from arthropod sequences. Overall, 2,566 different genes were differentially expressed after ED exposures in comparison with controls. As many genes were differentially expressed after PXF exposure as after CLD exposure. In contrast, more genes were differentially expressed in males than in females after both exposures. Ninety-seven genes overlapped in all conditions. Finally, 31 transcripts involved in reproduction, growth and development, and changed in both chemical exposures were selected as potential candidates for future development of biomarkers.

  7. [Determination of four phenolic endocrine disruptors in environmental water samples by high performance liquid chromatography-fluorescence detection using dispersive liquid-liquid microextraction coupled with derivatization].

    PubMed

    Wang, Xiaoyan; Qi, Weimei; Zhao, Xian'en; Lü, Tao; Wang, Xiya; Zheng, Longfang; Yan, Yehao; You, Jinmao

    2014-06-01

    To achieve accurate, fast and sensitive detection of phenolic endocrine disruptors in small volume of environmental water samples, a method of dispersive liquid-liquid microextraction (DLLME) coupled with fluorescent derivatization was developed for the determination of bisphenol A, nonylphenol, octylphenol and 4-tert-octylphenol in environmental water samples by high performance liquid chromatography-fluorescence detection (HPLC-FLD). The DLLME and derivatization conditions were investigated, and the optimized DLLME conditions for small volume of environmental water samples (pH 4.0) at room temperature were as follows: 70 microL chloroform as extraction solvent, 400 microL acetonitrile as dispersing solvent, vortex mixing for 3 min, and then high-speed centrifugation for 2 min. Using 2-[2-(7H-dibenzo [a, g] carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEC-Cl) as precolumn derivatization reagent, the stable derivatives of the four phenolic endocrine disruptors were obtained in pH 10.5 Na2CO3-NaHCO3 buffer/acetonitrile at 50 degrees C for 3 min, and then separated within 10 min by HPLC-FLD. The limits of detection (LODs) were in the range of 0.9-1.6 ng/L, and the limits of quantification (LOQs) were in the range of 3.8-7.1 ng/L. This method had perfect linearity, precision and recovery results, and showed obvious advantages and practicality comparing to the previously reported methods. It is a convenient and validated method for the routine analysis of phenolic endocrine disruptors in waste water of paper mill, lake water, domestic wastewater, tap water, etc.

  8. Effects of bisphenol A, an environmental endocrine disruptor, on the endogenous hormones of plants.

    PubMed

    Wang, Shengman; Wang, Lihong; Hua, Weiqi; Zhou, Min; Wang, Qingqing; Zhou, Qing; Huang, Xiaohua

    2015-11-01

    Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical in the environment that exerts potential harm to plants. Phytohormones play important roles both in regulating multiple aspects of plant growth and in plants' responses to environmental stresses. But how BPA affects plant growth by regulating endogenous hormones remains poorly understood. Here, we found that treatment with 1.5 mg L(-1) BPA improved the growth of soybean seedlings, companied by increases in the contents of indole-3-acetic acid (IAA) and zeatin (ZT), and decreases in the ratios of abscisic acid (ABA)/IAA, ABA/gibberellic acid (GA), ABA/ZT, ethylene (ETH)/GA, ETH/IAA, and ETH/ZT. Treatment with higher concentrations of BPA (from 3 to 96 mg L(-1)) inhibited the growth of soybean seedlings, meanwhile, decreased the contents of IAA, GA, ZT, and ETH, and increased the content of ABA and the ratios of ABA/IAA, ABA/GA, ABA/ZT, ETH/GA, ETH/IAA, and ETH/ZT. The increases in the ratios of growth and stress hormones were correlated with the increase in the BPA content of the roots. Thus, BPA could affect plant growth through changing the levels of single endogenous hormone and the ratios of growth and stress hormones in the roots because of BPA absorption by the roots.

  9. Cell-Free Protein Synthesis Approach to Biosensing hTRβ-Specific Endocrine Disruptors.

    PubMed

    Salehi, Amin S M; Shakalli Tang, Miriam J; Smith, Mark T; Hunt, Jeremy M; Law, Robert A; Wood, David W; Bundy, Bradley C

    2017-03-21

    Here we introduce a Rapid Adaptable Portable In vitro Detection biosensor platform (RAPID) for detecting ligands that interact with nuclear hormone receptors (NHRs). The RAPID platform can be adapted for field use, allowing rapid evaluation of endocrine disrupting chemicals (EDCs) presence or absence in environmental samples, and can also be applied for drug screening. The biosensor is based on an engineered, allosterically activated fusion protein, which contains the ligand binding domain from a target NHR (human thyroid receptor β in this work). In vitro expression of this protein using cell-free protein synthesis (CFPS) technology in the presence of an EDC leads to activation of a reporter enzyme, reported through a straightforward colorimetric assay output. In this work, we demonstrate the potential of this biosensor platform to be used in a portable "just-add-sample" format for near real-time detection. We also demonstrate the robust nature of the cell-free protein synthesis component in the presence of a variety of environmental and human samples, including sewage, blood, and urine. The presented RAPID biosensor platform is significantly faster and less labor intensive than commonly available technologies, making it a promising tool for detecting environmental EDC contamination and screening potential NHR-targeted pharmaceuticals.

  10. Endocrine disruptors: new players in the pathophysiology of type 2 diabetes?

    PubMed

    Chevalier, N; Fénichel, P

    2015-04-01

    The prevalence of type 2 diabetes (T2D) has dramatically increased worldwide during the last few decades. While lifestyle factors, such as decreased physical activity and energy-dense diets, together with genetic predisposition, are well-known actors in the pathophysiology of T2D, there is accumulating evidence suggesting that the increased presence of endocrine-disrupting chemicals (EDCs) in the environment, such as bisphenol A, phthalates and persistent organic pollutants, may also explain an important part in the incidence of metabolic diseases (the metabolic syndrome, obesity and T2D). EDCs are found in everyday products (including plastic bottles, metal cans, toys, cosmetics and pesticides) and used in the manufacture of food. They interfere with the synthesis, secretion, transport, activity and elimination of natural hormones. Such interferences can block or mimic hormone actions and thus induce a wide range of adverse effects (developmental, reproductive, neurological, cardiovascular, metabolic and immune). In this review, both in vivo and in vitro experimental data and epidemiological evidence to support an association between EDC exposure and the induction of insulin resistance and/or disruption of pancreatic β-cell function are summarized, while the epidemiological links with disorders of glucose homoeostasis are also discussed.

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

    PubMed Central

    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. miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets

    PubMed Central

    Klinge, Carolyn M.

    2015-01-01

    MicroRNAs (miRNAs) are short (22 nucleotides), single-stranded, non-coding RNAs that form complimentary base-pairs with the 3’ untranslated region of target mRNAs within the RNA-induced silencing complex (RISC) and block translation and/or stimulate mRNA transcript degradation. The non-coding miRBase (release 21, June 2014) reports that human genome contains ~2,588 mature miRNAs which regulate ~ 60% of human protein-coding mRNAs. Dysregulation of miRNA expression has been implicated in estrogen-related diseases including breast and endometrial cancers. The mechanism for estrogen regulation of miRNA expression and the role of estrogen-regulated miRNAs in normal homeostasis, reproduction, lactation, and in cancer is an area of great research and clinical interest. Estrogens regulate miRNAs transcription through estrogen receptors α and β in a tissue-specific and cell-dependent manner. This review focuses primary on the regulation of miRNA expression by ligand-activated ERs and their bona fide gene targets and includes miRNAs regulation by tamoxifen and endocrine disrupting chemicals (EDCs) in breast cancer and cell lines. PMID:25659536

  13. Methods of analysis for chemicals that disrupt cellular signaling pathways: risk assessment for potential endocrine disruptors.

    PubMed

    Umezawa, Yoshio; Ozawa, Takeaki; Sato, Moritoshi; Inadera, Hidekuni; Kaneko, Shuichi; Kunimoto, Manabu; Hashimoto, Shin-ichi

    2005-01-01

    Here we present a basic concept and several examples of methods of analysis for chemicals that disrupt cellular signaling pathways, in view of risk assessment for potential endocrine disrupting chemicals (EDCs). The key cellular signaling pathways include 1) ER/coactivator interaction, 2) AR translocation into the nucleus, 3) ER/NO/sGC/cGMP, 4) ER/Akt, 5) ER/Src, 6)ER/Src/Grb2, and 7) ER/Ca2+/CaM/CaMK pathways. These were visualized in relevant live cells using newly developed fluorescent and bioluminescent probes. Changes in cellular signals were thereby observed in nongenomic pathways of steroid hormones upon treatment of the target cells with steroid hormones and related chemicals. This method of analysis appears to be a rational approach to high-throughput prescreening (HTPS) of biohazardous chemicals, EDCs, in particular. Also described was the screening of gene expression by serial analysis of gene expression and gene chips upon applying EDCs to breast cancer cells, mouse livers, and human neuroblastoma NB-1 cells.

  14. Endocrine-Disrupting Compounds in Aquatic Ecosystems.

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are a ubiquitous issue of concern in our aquatic systems. Commonly detected EDCs include natural and synthetic hormones, surfactants, plasticizers, disinfectants, herbicides and metals. The potency of these chemicals varies substantially, as ...

  15. Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes.

    PubMed

    Stouder, Christelle; Paoloni-Giacobino, Ariane

    2011-02-01

    Endocrine-disrupting chemicals (EDCs), among which methoxychlor (MXC), have been reported to affect the male reproductive system. This study evaluates the possible deleterious effects of MXC on imprinted genes. After administration of the chemical in adult male mice or in pregnant mice we analyzed by pyrosequencing possible methylation defects in two paternally imprinted (H19 and Meg3 (Gtl2)) and three maternally imprinted (Mest (Peg1), Snrpn, and Peg3) genes in the sperm and in the tail, liver, and skeletal muscle DNAs of the adult male mice and of the male offspring. MXC treatment of adult mice decreased the percentages of methylated CpGs of Meg3 and increased those of Mest, Snrpn, and Peg3 in the sperm DNA. MXC treatment of pregnant mice decreased the mean sperm concentrations by 30% and altered the methylation pattern of all the imprinted genes tested in the F1 offspring. In the latter case, MXC effects were transgenerational but disappeared gradually from F1 to F3. MXC did not affect imprinting in the somatic cells, suggesting that it exerts its damaging effects via the process of reprogramming that is unique to gamete development. A systematic analysis at the CpG level showed a heterogeneity in the CpG sensitivity to MXC. This observation suggests that not only DNA methylation but also other epigenetic modifications can explain the transgenerational effects of MXC. The reported effects of EDCs on human male spermatogenesis might be mediated by complex imprinting alterations analogous to those described in this study.

  16. [Endocrine disruptors: A missing link in the pandemy of type 2 diabetes and obesity?].

    PubMed

    Chevalier, Nicolas; Fénichel, Patrick

    2016-01-01

    The prevalence of metabolic syndrome, obesity and type 2 diabetes has dramatically increased worldwide during the last few decades and exceeds World Health Organisation's predictions. Lifestyle factors such as decreased physical activity and energy dense diet, together with a genetic predisposition, are well-known actors in the pathophysiology of these metabolic diseases. However, there is accumulating evidence suggesting that the increased presence of endocrine disrupting chemicals (EDCs) in the environment, may also explain an important part in the incidence of metabolic syndrome, obesity and type 2 diabetes. EDCs are found in everyday products (including food, plastic bottles, metal cans, toys, cosmetics, pesticides…) and used in the manufacture of food. They interfere with the synthesis, secretion, transport, activity and/or elimination of natural hormones. Those interferences can block or mimic hormone actions and thus induce a wide range of adverse effects (especially reproductive effects and hormone-dependent cancers). In rodents, acute exposure to bisphenol A is responsible for modifications of insulin synthesis and secretion in pancreatic beta cells but also for modifications of insulin signalling in liver, skeletal muscle and adipose tissue, which both lead to insulin-resistance, a major condition in pathophysiology of metabolic syndrome, obesity and type 2 diabetes. In humans, some epidemiologic reports suggested a strong link between exposure to some persistant EDCs (as organochlorine pesticides, dioxins and polychlorinated biphenyl ethers) and type 2 diabetes and obesity, especially after acute and accidental releases of EDCs (Seveso plant explosion, Vietnam war veterans). Other cross-sectional studies among the world reported suggestive to strong association between diabetes and obesity and EDCs exposure, especially for persistant organic pollutants, which should now be considered as insulin-resistance risk factors.

  17. Evaluation of the Daphnia magna reproduction test for detecting endocrine disruptors.

    PubMed

    Dang, ZhiChao; Cheng, Yan; Chen, Hui-ming; Cui, Yuan; Yin, Huan-huan; Traas, Theo; Montforts, Mark; Vermeire, Theo

    2012-07-01

    The Daphnia 21 d reproduction test is considered as a comprehensive and decisive test in the OECD Conceptual Framework for testing and assessment of endocrine disrupting chemicals (EDCs). However, how to interpret results of the Daphnia 21 d reproduction test for identification, risk assessment and testing strategy of EDCs remains an unsolved issue. This study analysed a total number of 135 published studies encompassing 86 known EDCs and non-EDCs with different modes of action. Our results show that the majority of effects on apical endpoints (survival, molting, growth, time to reproductive maturity, brood size, the number of broods, and the total number of offspring) do not seem to be EDC-specific. In contrast, the endpoint sex ratio is likely specific to juvenile hormones and their mimics. Variability is quantified for three most reported endpoints survival, the total number of offspring and sex ratio. Quantification of the endpoint sensitivity shows that the sensitivity of the sex ratio is lower than that of the total number of offspring. The Daphnia 21 d reproduction test gives insufficient information to conclude if a substance is an EDC or not. EDCs that are potent in assays in vitro may not be potent in the Daphnia 21 d reproduction test. We conclude that the Daphnia 21 d reproduction test is important for deriving No Observed Effect Concentrations for risk assessment but may produce false negatives in identification of EDCs when used on its own. A targeted testing strategy for selection of species, tests, and endpoints is suggested for identifying EDCs.

  18. CE with a boron-doped diamond electrode for trace detection of endocrine disruptors in water samples.

    PubMed

    Browne, Damien J; Zhou, Lin; Luong, John H T; Glennon, Jeremy D

    2013-07-01

    Off-line SPE and CE coupled with electrochemical detection have been used for the determination of bisphenol A (BPA), bisphenol F, 4-ethylphenol, and bisphenol A diglycidyl ether in bottled drinking water. The use of boron-doped diamond electrode as an electrochemical detector in amperometric mode that provides a favorable analytical performance for detecting these endocrine-disrupting compounds, such as lower noise levels, higher peak resolution with enhanced sensitivity, and improved resistance against electrode passivation. The oxidative electrochemical detection of the endocrine-disrupting compounds was accomplished by boron-doped diamond electrode poised at +1.4 V versus Ag/AgCl without electrode pretreatment. An off-line SPE procedure (Bond Elut® C18 SPE cartridge) was utilized to extract and preconcentrate the compounds prior to separation and detection. The minimum concentration detectable for all four compounds ranged from 0.01 to 0.06 μM, having S/N equal to three. After exposing the plastic bottle water container under sunlight for 7 days, the estimated concentration of BPA in the bottled drinking water was estimated to be 0.03 μM. This proposed approach has great potential for rapid and effective determination of BPA content present in water packaging of plastic bottles that have been exposed to sunlight for an extended period of time.

  19. Steroid levels in crinoid echinoderms are altered by exposure to model endocrine disruptors.

    PubMed

    Lavado, Ramón; Barbaglio, Alice; Carnevali, M Daniela Candia; Porte, Cinta

    2006-06-01

    Sexual steroids (testosterone and estradiol) were measured in the whole body of wild specimens of the crinoid Antedon mediterranea collected from the Tyrrhenian Sea (Italy). Testosterone levels (274-1,488 pg/g wet weight (w.w.)) were higher than those of estradiol (60-442 pg/g w.w.) and no significant differences between males and females were observed. No clear seasonal trend was either detected - individuals from February, June and October 2004 analyzed - apart from a peak of estradiol in males in autumn. Nonetheless, dramatic changes on tissue steroid levels were observed when individuals were exposed to model androgenic and anti-androgenic compounds for 2 and 4 weeks. The selected compounds were 17 alpha-methyltestosterone (17 alpha-MT), triphenyltin (TPT), fenarimol (FEN), cyproterone acetate (CPA), and p,p'-DDE. Endogenous testosterone levels were significantly increased after exposure to 17 alpha-MT, TPT and FEN, while different responses were observed for estradiol; 17 alpha-MT and FEN increased endogenous estradiol (up to seven-fold), and TPT lead to a significant decrease. Concerning the anti-androgenic compounds, CPA significantly reduced testosterone in a dose-dependent manner without altering estradiol levels, whereas specimens exposed to p,p'-DDE at a low dose (24 ng/L) for 4 weeks showed a four-fold increase in T levels. Overall, the data show the ability of the selected compounds to alter endogenous steroid concentrations in A. mediterranea, and suggest the existence in this echinoderm species of vertebrate-like mechanisms that can be affected by exposure to androgenic and anti-androgenic chemicals.

  20. Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis.

    PubMed

    Kardas, Fatih; Bayram, Ayse Kacar; Demirci, Esra; Akin, Leyla; Ozmen, Sevgi; Kendirci, Mustafa; Canpolat, Mehmet; Oztop, Didem Behice; Narin, Figen; Gumus, Hakan; Kumandas, Sefer; Per, Huseyin

    2016-04-01

    The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 ± 0.14 µg/ml, 2.70 ± 0.90 µg/ml, 1.25 ± 0.30 ng/ml) compared to healthy control subjects (0.29 ± 0.05 µg/ml, 1.62 ± 0.56 µg/ml, 0.88 ± 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders.

  1. The Molecular Mechanism of Bisphenol A (BPA) as an Endocrine Disruptor by Interacting with Nuclear Receptors: Insights from Molecular Dynamics (MD) Simulations

    PubMed Central

    Li, Lanlan; Wang, Qianqian; Zhang, Yan; Niu, Yuzhen; Yao, Xiaojun; Liu, Huanxiang

    2015-01-01

    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. PMID:25799048

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

    PubMed

    Li, Lanlan; Wang, Qianqian; Zhang, Yan; Niu, Yuzhen; Yao, Xiaojun; Liu, Huanxiang

    2015-01-01

    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.

  3. SUPRAMOLECULAR COMPOSITE MATERIALS FROM CELLULOSE, CHITOSAN AND CYCLODEXTRIN: FACILE PREPARATION AND THEIR SELECTIVE INCLUSION COMPLEX FORMATION WITH ENDOCRINE DISRUPTORS

    PubMed Central

    Duri, Simon; Tran, Chieu D.

    2013-01-01

    We have successfully developed a simple and one step method to prepare high performance supramolecular polysaccharide composites from cellulose (CEL), chitosan (CS) and (2,3,6-tri-O-acetyl)-α-, β- and γ-cyclodextrin (α-, β- and γ-TCD). In this method, [BMIm+Cl−], an ionic liquid (IL), was used as a solvent to dissolve and prepare the composites. Since majority (>88%) of the IL used was recovered for reuse, the method is recyclable. XRD, FT-IR, NIR and SEM were used to monitor the dissolution process and to confirm that the polysaccharides were regenerated without any chemical modifications. It was found that unique properties of each component including superior mechanical properties (from CEL), excellent adsorbent for pollutants and toxins (from CS) and size/structure selectivity through inclusion complex formation (from TCDs) remain intact in the composites. Specifically, results from kinetics and adsorption isotherms show that while CS-based composites can effectively adsorb the endocrine disruptors (polychlrophenols, bisphenol-A), its adsorption is independent on the size and structure of the analytes. Conversely, the adsorption by γ-TCD-based composites exhibits strong dependency on size and structure of the analytes. For example, while all three TCD-based composites (i.e., α-, β- and γ-TCD) can effectively adsorb 2-, 3- and 4-chlorophenol, only γ-TCD-based composite can adsorb analytes with bulky groups including 3,4-dichloro- and 2,4,5-trichlorophenol. Furthermore, equilibrium sorption capacities for the analytes with bulky groups by γ-TCD-based composite are much higher than those by CS-based composites. Together, these results indicate that γ-TCD-based composite with its relatively larger cavity size can readily form inclusion complexes with analytes with bulky groups, and through inclusion complex formation, it can strongly adsorb much more analytes and with size/structure selectivity compared to CS-based composites which can adsorb the

  4. Supramolecular composite materials from cellulose, chitosan, and cyclodextrin: facile preparation and their selective inclusion complex formation with endocrine disruptors.

    PubMed

    Duri, Simon; Tran, Chieu D

    2013-04-23

    We have successfully developed a simple one-step method of preparing high-performance supramolecular polysaccharide composites from cellulose (CEL), chitosan (CS), and (2,3,6-tri-O-acetyl)-α-, β-, and γ-cyclodextrin (α-, β-, and γ-TCD). In this method, [BMIm(+)Cl(-)], an ionic liquid (IL), was used as a solvent to dissolve and prepare the composites. Because a majority (>88%) of the IL used was recovered for reuse, the method is recyclable. XRD, FT-IR, NIR, and SEM were used to monitor the dissolution process and to confirm that the polysaccharides were regenerated without any chemical modifications. It was found that unique properties of each component including superior mechanical properties (from CEL), excellent adsorption for pollutants and toxins (from CS), and size/structure selectivity through inclusion complex formation (from TCDs) remain intact in the composites. Specifically, the results from kinetics and adsorption isotherms show that whereas CS-based composites can effectively adsorb the endocrine disruptors (polychlrophenols, bisphenol A), their adsorption is independent of the size and structure of the analytes. Conversely, the adsorption by γ-TCD-based composites exhibits a strong dependence on the size and structure of the analytes. For example, whereas all three TCD-based composites (i.e., α-, β-, and γ-TCD) can effectively adsorb 2-, 3-, and 4-chlorophenol, only the γ-TCD-based composite can adsorb analytes with bulky groups including 3,4-dichloro- and 2,4,5-trichlorophenol. Furthermore, the equilibrium sorption capacities for the analytes with bulky groups by the γ-TCD-based composite are much higher than those by CS-based composites. Together, these results indicate that the γ-TCD-based composite with its relatively larger cavity size can readily form inclusion complexes with analytes with bulky groups, and through inclusion complex formation, it can strongly adsorb many more analytes and has a size/structure selectivity compared to

  5. Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

    PubMed Central

    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

  6. Magnetic recovery of modified activated carbon powder used for removal of endocrine disruptors present in water.

    PubMed

    Borghi, Chiara Caterina; Fabbri, Massimo

    2014-01-01

    This paper was aimed at studying sustainable solutions for the treatment of water polluted by octylphenols and nonylphenols that are xenoextrogen compounds affecting human health and dangerous for the aquatic environment. We studied the removal of 4-octylphenol and 4-n-nonylphenol with concentrations of the order of 5-10 mg/l on a laboratory scale. A mixing time of 10 min with 0.1 g/l of magnetic-activated carbons (MACs) was enough to obtain 95 +/- 5% adsorption of both 4-octylphenol and 4-n-nonylphenol. The adsorption of the surfactants IGEPAL CO-630 and TRITON X-100, which are precursors of branched 4-nonylphenol and the carcinogenic 4-tert-octylphenol, respectively, was also studied using the same technique. For concentrations between 2 and 10mg/l of these alkylphenols ethoxylated, after 10min mixing with 0.5 g/l of MACs, a 95 +/- 5% adsorption was obtained. A 97 +/- 1% removal of MACs was achieved after 10min of continuous-flow magnetic filtration (14.5 l/min). The filter used was made of SUS440C magnetic steel spheres. Srm-Co permanent magnets provided a uniform flux density field of about 500 mT.

  7. Occurrence and removal of pharmaceuticals and endocrine disruptors in South Korean surface, drinking, and waste waters.

    PubMed

    Kim, Sang D; Cho, Jaeweon; Kim, In S; Vanderford, Brett J; Snyder, Shane A

    2007-03-01

    Liquid chromatography/tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) was used to measure the concentrations of 14 pharmaceuticals, 6 hormones, 2 antibiotics, 3 personal care products (PCPs), and 1 flame retardant in surface waters and wastewater treatment plant effluents in South Korea. Tris (2-chloroethyl) phosphate (TCEP), iopromide, naproxen, carbamazepine, and caffeine were quite frequently observed (>80%) in both surface waters and effluents. The analytes of greatest concentration were iopromide, TCEP, sulfamethoxazole, and carbamazepine. However, the primary estrogen hormones, 17alpha-ethynylestradiol and 17beta-estradiol, were rarely detected, while estrone was detected in both surface water and wastewater effluent. The elimination of these chemicals during drinking water and wastewater treatment processes at full- and pilot-scale also was investigated. Conventional drinking water treatment methods were relatively inefficient for contaminant removal, while efficient removal (approximately equal to 99%) was achieved by granular activated carbon (GAC). In wastewater treatment processes, membrane bioreactors (MBR) showed limited target compound removal, but were effective at eliminating hormones and some pharmaceuticals (e.g., acetaminophen, ibuprofen, and caffeine). Membrane filtration processes using reverse osmosis (RO) and nanofiltration (NF) showed excellent removal (>95%) for all target analytes.

  8. [Degradation of endocrine disruptor atrazine in drinking water by UV radiation].

    PubMed

    Wang, Li; Gao, Nai-yun; Wei, Hong-bin; Xia, Li-hua; Cui, Jing

    2006-06-01

    The degradation of atrazine with low concentration in drinking water by UV radiation was studied. The main influencing factors and degradation mechanism of this technology were discussed. Experimental results show that the photolytic degradation of atrazine by UV radiation alone is very efficient. Under 205 microW/cm2 irradiation intensity, atrazine removal ratio is 92.38% after 120 minutes. The rate of photodecomposition in aqueous solution follows first-order kinetics. The removal ratio of atrazine can be greatly enhanced by increasing the intensity of UV radiation. The initial concentration of atrazine has no effect on the oxidation reaction. The organic matter and various ion in tap water will decrease the degradation rate. The primary degradation pathway is dechlorination. The reaction rate is high. The hydroxylated compound is the major intermediate product. Hydroyatrazine can be further decomposed by UV radiation and form dealkylated derivatives. But the rate of dealkylated reaction is very low. There is intimate relationship between the change of pH in the solution and the formation of intermediate products.

  9. Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

    PubMed

    Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

    2006-11-10

    The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

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

    PubMed

    Svobodová, K; Placková, M; Novotná, V; Cajthaml, T

    2009-11-01

    Investigations of environmental pollution by endocrine-disrupting chemicals are now in progress. Up to now, several in vitro bioassays have been developed for evaluation of the endocrine disruptive activity; however, there is still a lack of comparative studies of their sensitivity. In this work comparison of the estrogen screening assay based on beta-galactosidase expression and a bioluminescent estrogen screen revealed differences in the sensitivity and specificity of the two tests. With the beta-galactosidase screen a slight estrogen-like activity of Delor 103, a commercial mixture of PCB congeners, and a fungicide triclosan was measured whereas no activity was detected using the bioluminescent assay. A bioluminescent androgen test negated previously suggested androgenic potential of triclosan. Further, this work demonstrates the androgenic activity of Delor 103, with an EC(50) value of 2.29 x 10(-2)mg/L. On the other hand, chlorobenzoic acids (CBAs), representing potential PCB degradation metabolites, exhibited no androgenic activity but were slightly estrogenic. Their estrogenicity varied with their chemical structure, with 2,3-CBA, 2,3,6-CBA, 2,4,6-CBA and monochlorinated compounds exhibiting the highest activity. Thus the results indicated possible transitions of the hormonal activity of PCBs during bacterial degradation.

  11. Determination of endocrine disruptors in honey by CZE-MS using restricted access materials for matrix cleanup.

    PubMed

    Rodríguez-Gonzalo, Encarnación; Domínguez-Alvarez, Javier; García-Gómez, Diego; García-Jiménez, María-Guadalupe; Carabias-Martínez, Rita

    2010-07-01

    An analytical method based on CZE coupled to ESI-MS is proposed for the identification and simultaneous quantification of several endocrine-disrupting chemicals in honey. The target compounds were the chlorophenols: 2,4-dichlorophenol, 2,4,5-trichlorophenol and pentachlorophenol, and bisphenol-A, 4-tert-butylphenol, and 4-tert-butylbenzoic acid. A two-step optimization of the ESI-MS detection was carried out. First, the organic solvent present in the sheath liquid was selected and its effect on the analytical signal was studied. The best results in terms of the intensity of the MS signals were obtained with methanol. Thus, an experimental design technique (Doehlert type) was used for the optimization of the other parameters: the NH(3) concentration in the sheath liquid, the flow of the sheath liquid, the nebulizer pressure in ESI, and the drying gas temperature and flow. Here, we developed a new sample treatment based on the combined use of a restricted access material and a polymeric sorbent for SPE. The LOD achieved were in the range of 5-31 ng/g. The intraday precision of the proposed method was determined from replicate analyses (n=4) at a concentration level of 50 ng/g, with RSD values in the range of 15-23%. The results revealed that the proposed method is suitable for the reliable quantification of endocrine-disrupting chemicals in honey at nanograms per gram levels.

  12. Broad range analysis of endocrine disruptors and pharmaceuticals using gas chromatography and liquid chromatography tandem mass spectrometry.

    PubMed

    Trenholm, Rebecca A; Vanderford, Brett J; Holady, Janie C; Rexing, David J; Snyder, Shane A

    2006-12-01

    Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) have been globally detected in impacted natural waters. The detection of trace quantities of EDCs and PPCPs in the environment is of great concern since some of these compounds have known physiological responses at low concentrations. EDCs can have a wide range of polarities, acidic and basic moieties, and exist in trace quantities, which often requires numerous complex extractions, large sample collection volumes, and multiple instrumental analyses. A comprehensive method has been developed allowing for the analysis of 58 potential EDCs in various water matrices using a single solid-phase extraction (SPE) of a 1L sample with subsequent analyses using both gas chromatography and liquid chromatography, each coupled with tandem mass spectrometry (GC-MS/MS and LC-MS/MS). Instrument detection limits ranged between 0.12-7.5 pg with corresponding method reporting limits of 1-10 ng l(-1) in water. Recoveries for most compounds were between 50% and 112% with good reproducibility (RSD 6-22%).

  13. Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

    PubMed

    Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-12-12

    Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic

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

    PubMed

    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.

  15. Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors.

    PubMed

    Soto, Ana M; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-06-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer.

  16. Targeted high-resolution ion mobility separation coupled to ultrahigh-resolution mass spectrometry of endocrine disruptors in complex mixtures.

    PubMed

    Benigni, Paolo; Thompson, Christopher J; Ridgeway, Mark E; Park, Melvin A; Fernandez-Lima, Francisco

    2015-04-21

    Traditional separation and detection of targeted compounds from complex mixtures from environmental matrices requires the use of lengthy prefractionation steps and high-resolution mass analyzers due to the large number of chemical components and their large structural diversity (highly isomeric). In the present work, selected accumulation trapped ion mobility spectrometry (SA-TIMS) is coupled to Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for direct separation and characterization of targeted endocrine-disrupting compounds (EDC) from a complex environmental matrix in a single analysis. In particular, targeted identification based on high-resolution mobility (R ∼ 70-120) and ultrahigh-resolution mass measurements (R > 400 000) of seven commonly targeted EDC and their isobars (e.g., bisphenol A, (Z)- and (E)-diethylstilbestrol, hexestrol, estrone, α-estradiol, and 17-ethynylestradiol) is shown from a complex mixture of water-soluble organic matter (e.g., Suwannee River Fulvic Acid Standard II) complemented with reference standard measurements and theoretical calculations (<3% error).

  17. Peer review of validation studies: an assessment of the role of the OECD by reference to the validation of the uterotrophic assay for endocrine disruptors.

    PubMed

    Combes, Robert D

    2004-06-01

    The involvement of the OECD in managing the validation of the rat uterotrophic assay for endocrine disruptors, and in organising the peer review of the results of this study, has been assessed and compared with the many conclusions and recommendations in several published reports of international workshops on validation, and information in guidance documents, produced by the European Centre for the Validation of Alternative Methods (ECVAM), the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the OECD itself. It is concluded that the OECD has not followed the recommendations for full transparency and independence of the peer-review process. This is based on the fact that it has published a draft guidance document that differs from the report of a recent OECD workshop on validation, in such a way as to give the OECD the flexibility to fully control the peer-review process and, in so doing, to avoid full transparency. Comparison of the timing of the organisation of workshops by the OECD and the progression of the validation study, together with the fact that a draft test guideline for the assay was written before completion of the peer review, suggest that the OECD has given a higher priority to the expedition of the validation and regulatory acceptance of the uterotrophic assay than it has to good scientific and logistical practice. This severely undermines its credibility in the validation process, so, in order for the OECD to be rightly perceived as an honest broker, it is recommended that the OECD should play no role in the validation of new or revised tests, until after they have been successfully validated, peer reviewed, and endorsed by the appropriate authorities, and are ready for test guideline development. With regard to the on-going OECD validation studies of other in vivo assays for endocrine disruptors, the OECD should take immediate steps to ensure full independence and transparency of their peer review.

  18. The endocrine disruptor bisphenol A increases the expression of HSP70 and ecdysone receptor genes in the aquatic larvae of Chironomus riparius.

    PubMed

    Planelló, R; Martínez-Guitarte, J L; Morcillo, G

    2008-05-01

    Bisphenol A (BPA) is an endocrine disruptor that can mimic the action of estrogens by interacting with hormone receptors and is, therefore, potentially able to influence reproductive functions in vertebrates. Although information about the interaction with the endocrine systems in invertebrates is limited, it has also been shown its effect on reproductive and developmental parameters in these organisms. As little is known about its mechanism of action in aquatic invertebrates, we have examined the effects of BPA on the expression of some selected genes, including housekeeping, stress-induced and hormone-related genes in Chironomus riparius larvae, a widely used organism in aquatic ecotoxicology. The levels of different gene transcripts were measured by Northern blot or by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Exposure to BPA (3 mgl(-1), 12-24h) did not affect the levels of rRNA or those of mRNAs for both L11 or L13 ribosomal proteins, selected as examples of housekeeping genes involved in ribosome biogenesis. Nevertheless, BPA treatment induced the expression of the HSP70 gene. Interestingly, it was found that BPA significantly increases the mRNA level of the ecdysone receptor (EcR). These results show for the first time that exposure to endocrine disrupting chemicals, such as BPA, can selectively affect the expression of the ecdysone receptor gene suggesting a direct interaction with the insect endocrine system. Furthermore, this finding suggests a common way of BPA action, shared by vertebrates and invertebrates, through interaction with steroid hormone receptors. Our study adds a new element, the EcR, which may be a useful tool for the screening of environmental xenoestrogens in insects.

  19. Exposure assessment of prepubertal children to steroid endocrine disruptors. 2. Determination of steroid hormones in milk, egg, and meat samples.

    PubMed

    Courant, Frédérique; Antignac, Jean-Philippe; Laille, Julie; Monteau, Fabrice; Andre, François; Le Bizec, Bruno

    2008-05-14

    In the present study, the occurrence of the main sex steroid hormones in milk, egg, and meat was evaluated on the basis of a highly specific gas chromatography-tandem mass spectrometry measurement method. Globally, the results indicated that targeted estrogens and androgens occurred at similar levels (concentration levels in the 10-100 ng kg (-1) range) in the analyzed muscle and milk samples. The same compounds occurred at about 10-fold higher concentrations (i.e., in the 100-1000 ng kg (-1) range) in eggs and kidney samples. More precisely, egg and milk appeared as a non-negligible sources of estradiol (i.e., 2.2 +/- 0.8 and 3.1 +/- 2.0 ng day (-1), respectively), whereas testosterone exposure is caused by ingestion of meat and/or egg (i.e., 12.2 +/- 48.2 and 5.2 +/- 2.3 ng day (-1), respectively). The provided exposure data will be further exploited in the scope of a risk assessment study regarding endocrine disruption associated with these molecules.

  20. Application of endocrine disruptor screening program fish short-term reproduction assay: Reproduction and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.

    PubMed

    Fort, Douglas J; Mathis, Michael; Fort, Chelsea E; Fort, Hayley M; Bacon, Jamie P

    2015-06-01

    A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short-term reproduction assay (FSTRA) was used to evaluate the effects of sediment exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus). Reproductively active male and female fish were exposed to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2 marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals via flow-through exposure for 21 d. Reproductive fecundity was monitored daily. At termination, the status of the reproductive endocrine system was assessed by the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2], testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes (aromatase and combined 3β/17β -hydroxysteroid dehydrogenase [3β/17β-HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower male body weight, and altered endocrinological measures of reproductive status were observed in both species. Higher plasma T levels in female minnows and 11-KT levels in both male and female minnows and female killifish exposed to freshwater and brackish sediments, respectively. Decreased female E2 and VTG levels and gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed females from both species. No effect on female 3β/17β-HSD activity was found in either species. The FSTRA provided a robust model capable of modification to evaluate reproductive effects of sediment exposure in fish.

  1. Measurement of Steroids in Rats after Exposure to an Endocrine Disruptor: Mass Spectrometry and Radioimmunoassay Demonstrate Similar Results

    EPA Science Inventory

    Commercially available radioimmunoassays (RIAs) are frequently used in toxicological studies to evaluate effects of endocrine disrupting chemicals (EDCs) on steroidogenesis in rats. Currently there are limited data comparing steroid concentrations in rats as measured by RIAs to t...

  2. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

    PubMed Central

    Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

    2015-01-01

    Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator–activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT. PMID:25687586

  3. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

    NASA Astrophysics Data System (ADS)

    Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-Ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

    2015-02-01

    Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

  4. Exposure to environmental endocrine disrupting compounds and men's health.

    PubMed

    Meeker, John D

    2010-07-01

    Human exposure to environmental endocrine disrupting compounds (EDCs) have received increased attention in recent years due to the documentation of widespread exposure to a number of EDCs among the general population, experimental data demonstrating endocrine-related effects on reproduction, development, metabolism, and cancer, and observations for increasing trends (as well as geographic trends) in endocrine-related disorders among populations. However, human studies of exposure to most environmental EDCs in relation to adverse health outcomes remain limited. This review focuses on the human data generated to date on the relationship between exposures to environmental EDCs and men's health. The agents discussed here, which include polychlorinated biphenyls (PCBs), pesticides, phthalates, bisphenol A (BPA), and polybrominated diphenyl ethers (PBDEs), were chosen based on their exposure prevalence and the presence of existing human data in studies of male reproductive health, altered reproductive and thyroid hormone levels, diabetes and/or metabolic syndrome, and endocrine-related cancers. Taken together, the epidemiologic data on the environmental EDCs suggest that there may be associations between exposure and adverse health outcomes in men. However, the limited human data, and in many instances inconsistent data across studies, highlight the need for further research on these chemicals. Future longitudinal molecular epidemiology studies with appropriately designed exposure assessments are needed to determine potential causal relationships, to identify the most important time windows/life stages of exposure, and to define individual susceptibility factors for adverse effects on men's health in response to exposure.

  5. Endocrine-disrupting compounds: a review of their challenge to sustainable and safe water supply and water reuse.

    PubMed

    Falconer, Ian R; Chapman, Heather F; Moore, Michael R; Ranmuthugala, Geetha

    2006-04-01

    The relevance of endocrine-disrupting compounds as potential contaminants of drinking water is reviewed, particularly in the reuse of wastewater. Growing populations and increasing intensification of land and water use for industry and agriculture have increased the need to reclaim wastewater for reuse, including to supplement the drinking water supply. The variety of anthropogenic chemicals that have been identified as potential endocrine disruptors in the environment and the problems arising from their use as human and livestock pharmaceuticals, as agricultural chemicals and in industry are discussed. The potentially adverse impact of these chemicals on human health and the ecology of the natural environment are reviewed. Data for the removal of estrogenic compounds from wastewater treatment are presented, together with the comparative potencies of estrogenic compounds. The relative exposure to estrogens of women on oral contraceptives, hormone replacement therapy, and through food consumption is estimated. A brief overview of some methods available or under development for the assessment of estrogenic activity in environmental samples is provided. The review concludes with a discussion of the directions for further investigation, which include human epidemiology, methodology development, and wastewater monitoring.

  6. Environmentally-friendly in situ plated bismuth-film electrode for the quantification of the endocrine disruptor parathion in skimmed milk.

    PubMed

    Gerent, Giles G; Spinelli, Almir

    2016-05-05

    An in situ bismuth-film electrode (BiFE) together with square-wave cathodic voltammetry (SWCV) was used to determine the concentration of the endocrine disruptor parathion in skimmed milk. The experimental conditions (deposition time, deposition potential and Bi (III) concentration) were optimized for the preparation of the BiFE. A glassy carbon electrode was used as the substrate. The selection of the chemical composition of the supporting electrolyte and the solution pH was aimed at improving the reduction of parathion at the BiFE surface. In addition, the parameters of the square-wave cathodic voltammetry were adjusted to improve the sensor performance. A cathodic current identified at -0.523 V increased linearly with the parathion concentration in the range of 0.2-2.0 μmol L(-1) (R=0.999). The sensitivity of the calibration curve obtained was 4.09 μA L μmol(-1), and the limits of detection (LOD) and quantification (LOQ) were 55.7 nmol L(-1) and 169.0 nmol L(-1), respectively. The performance of the sensor was tested using a sample of skimmed milk with parathion added. The same determination was carried out by UV-vis spectroscopy and the results obtained were used for the statistical evaluation of the data obtained.

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

    PubMed Central

    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

  8. Comparison of activation media and pyrolysis temperature for activated carbons development by pyrolysis of potato peels for effective adsorption of endocrine disruptor bisphenol-A.

    PubMed

    Arampatzidou, Anastasia C; Deliyanni, Eleni A

    2016-03-15

    Activated carbon prepared from potato peels, a solid waste by product has been studied for the adsorption of an endocrine disruptor, Bisphenol-A, from aqueous solutions. The potato peels biomass was activated with H3PO4, KOH and ZnCl2 in order the effect of the activation agent to be evaluated. The activated biomass was carbonized at 400, 600 and/or 800 °C in order the effect of carbonization temperature on the texture, surface chemistry and adsorption properties to be found. The activated carbons prepared were characterized by nitrogen adsorption, Scanning Electron Microscope, thermal analysis and Fourier Transform Infrared Spectroscopy. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second order rate kinetics. The adsorption capacity calculated from the Langmuir isotherm was found 454.62 mg g(-1) at an initial pH 3 at 25 °C for the phosphoric acid activated carbon carbonized at 400 °C that proved to be the best adsorbent.

  9. 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

    PubMed Central

    Jocsak, Gergely; Kiss, David Sandor; Toth, Istvan; Goszleth, Greta; Bartha, Tibor; Frenyo, Laszlo V.; Horvath, Tamas L.; Zsarnovszky, Attila

    2016-01-01

    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. PMID:27338438

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

    PubMed Central

    La Rocca, Cinzia; Tait, Sabrina; Guerranti, Cristiana; Busani, Luca; Ciardo, Francesca; Bergamasco, Bruno; Perra, Guido; Mancini, Francesca Romana; Marci, Roberto; Bordi, Giulia; Caserta, Donatella; Focardi, Silvano; Moscarini, Massimo; Mantovani, Alberto

    2015-01-01

    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. PMID:26445054

  11. A biosensor fabricated by incorporation of a redox mediator into a carbon nanotube/nafion composite for tyrosinase immobilization: detection of matairesinol, an endocrine disruptor.

    PubMed

    Rather, Jahangir Ahmad; Pilehvar, Sanaz; De Wael, Karolien

    2013-01-07

    An electrochemical matairesinol biosensor was fabricated by immobilizing tyrosinase on a poly(thionine)/nafion/multi-walled carbon nanotube composite film. A polymeric film of the redox dye thionine enables the stable immobilization of tyrosinase while acting as a mediator for the enzymatic process has been incorporated into the carbon nanotube/nafion composite film. The immobilization method is based on crosslinking of the tyrosinase layer with an electropolymerized film of poly(thionine). The good homogenization of the electron conductor CNTs in the integrated films provides the possibility of a three-dimensional electron conductive network. The biosensor was characterized by electrochemical impedance spectroscopy and electrochemical characterization. The composite electrode exhibits catalytic activity, high sensitivity, stability and is applicable over a wide range of concentrations from 180 nM to 4.33 μM with a detection limit (LOD) of 37 nM. The obtained results suggest that the developed sensor can be successfully used for the determination of phenolic endocrine disruptors over a concentration range covering their environmental levels.

  12. Levels of endocrine disrupting compounds in South China Sea.

    PubMed

    Zhang, Li-Peng; Wang, Xin-Hong; Ya, Miao-Lei; Wu, Yu-Ling; Li, Yong-Yu; Zhang, Zu-lin

    2014-08-30

    The occurrence of estrogens in the aquatic environment has become a major concern worldwide because of their strong endocrine disrupting potency. In this study, concentrations of four estrogenic compounds, estrone (E1), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), estriol (E3) were determined with liquid chromatography-tandem mass spectrometry analyses in surface water from South China Sea, and distributions and potential risks of their estrogenic activity were assessed. The estrogenic compounds E1, E2 and E3 were detected in most of the samples, with their concentrations up to 11.16, 3.71 and 21.63 ng L(-1). However, EE2 was only detected in 3 samples. Causality analysis, EEQ values from chemical analysis identified E2 as the main responsible compounds. Based on the EEQ values in the surface water, high estrogenic risks were in the coastal water, and low estrogenic risks in the open sea.

  13. Mixture effects of endocrine disrupting compounds in vitro.

    PubMed

    Kjaerstad, M B; Taxvig, C; Andersen, H R; Nellemann, C

    2010-04-01

    Four different equi-molar mixtures were investigated for additive endocrine disrupting effects in vitro using the concentration addition model. It was found that additive effects on the same molecular target (the androgen receptor; AR) can be predicted for both mixtures of compounds with effect on the AR (flutamide, procymidone and vinclozolin) and of compounds with and without effects on the AR [finasteride, mono-(2-ethylhexyl) phthalate, prochloraz and vinclozolin]. For a paraben mixture (methyl paraben, ethyl paraben, propyl paraben, butyl paraben and iso-butyl paraben) antagonistic effect on AR could not be predicted under assumption of additivity in our model system. For a mixture containing three azole fungicides (epoxiconazole, propiconazole and tebuconazole), the observed AR antagonistic effects were close to the predicted effect assuming additivity. Azole fungicides are known inhibitors of androgen biosynthesis and in the steroid synthesis assay using H295R cells, the inhibition of testosterone production was close to additive, whereas the inhibition of oestradiol production was over-estimated for the mixture of azole fungicides, when compared with the effect predicted when assuming additivity. Overall these and other studies show that weak endocrine disrupting compounds, like parabens and azole fungicides, give rise to combination effects when they occur in mixtures. These combination effects should be taken into account in regulatory risk assessment not to under-estimate the risks for adverse effects associated with exposure to disrupting chemicals.

  14. Ecological risk assessments of endocrine disrupting organotin compounds using marine neogastropods in Hong Kong.

    PubMed

    Leung, Kenneth M Y; Kwong, Rita P Y; Ng, W C; Horiguchi, Toshihiro; Qiu, J W; Yang, Ruiqiang; Song, Maoyong; Jiang, Guibin; Zheng, Gene J; Lam, Paul K S

    2006-11-01

    As active ingredients of anti-fouling paints that are widely used on ship hulls, organotin compounds, in particular tributyltin (TBT), are well-known endocrine disruptors causing sex changes in marine organisms and widespread in coastal waters and sediments worldwide. In this study, a comprehensive ecological risk assessment (ERA) of organotins was conducted in Hong Kong waters through determining the imposex status, sex ratio and tissue burdens of these compounds in the neogastropods, Thais clavigera and Thais luteostoma collected from 29 coastal sites. We also investigated the historical trend of organotin effects on these gastropods, and performed a probabilistic ERA based on tissue burden of TBT in the animals. Our results demonstrated that imposex indices were positively correlated with the body burden of organotins in the gastropods. Across all sites, the sex ratio (female:male) decreased significantly with increasing imposex levels or tissue burden of organotins, implying that such pollutants can result in a male-biased population, potentially leading to local extinction in extreme cases. Based on the ERA, 5.4% of all populations of T. clavigera are at risk due to exposure to TBT; the risks include growth inhibition, impairment of immune functions and reduced fitness. Seriously impacted areas included Aberdeen, Repulse Bay, Butterfly Beach, Mui Wo and Ha Mei Wan. A comparison with historical data revealed that there had been some improvement in the areas with low marine traffic, and distant from the major harbour/port. This could partly be due to the restriction on the use of TBT on small vessels (<25m in length) since 1992. Nevertheless, the organotin contamination still remains severe in areas with high marine traffic or adjacent to large harbours/ports. In particular, the situation in the northeastern waters of Hong Kong has been getting worst since 1996 that is probably associated with the rapid development of the cargo container port at Yantian in China.

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

    PubMed

    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

  16. Nitromusk compounds in women with gynecological and endocrine dysfunction.

    PubMed

    Eisenhardt, S; Runnebaum, B; Bauer, K; Gerhard, I

    2001-12-01

    Musk xylene (MX), musk ketone (MK), musk ambrette, musk moskene, and musk tibetene are synthetic fragrances. Between 1994 and 1996 these five nitromusk compounds (NMCs) were tested in the blood of 152 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. The testing was conducted by gas chromotography with mass-specific detector and mass spectrometry in a retrospective cross-sectional study. MX was detected in 95% and MK in 85% of the blood samples (>20 ng per liter whole blood). The median concentration of MX was 65.5 ng/L and the maximum level of MX was 1183 ng/L; the corresponding values for MK were respectively 55.5 and 518 ng/L. The other three NMCs were found in only a few patients or not at all. Significant associations between MX and MK concentrations were found in blood and different clinical parameters of the endocrine system. MX and MK may act centrally as a disrupter of the (supra-) hypothalamic-ovarian axis, which may result in a mild ovarian insufficiency. On the basis of our data, a reproductive toxicity and an endocrine effect of NMCs in women cannot be ruled out. Further experimental and clinical studies should be conducted.

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

    PubMed Central

    Gabb, Henry A.; Blake, Catherine

    2016-01-01

    exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155–1165; http://dx.doi.org/10.1289/ehp.1510529 PMID:26955064

  18. Are endocrine disrupting compounds a health risk in drinking water?

    PubMed

    Falconer, Ian R

    2006-06-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17Beta-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water

  19. Are Endocrine Disrupting Compounds a Health Risk in Drinking Water?

    PubMed Central

    Falconer, Ian R.

    2006-01-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17β-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water. In

  20. Histone methyltransferase EZH2 is transcriptionally induced by estradiol as well as estrogenic endocrine disruptors bisphenol-A and diethylstilbestrol.

    PubMed

    Bhan, Arunoday; Hussain, Imran; Ansari, Khairul I; Bobzean, Samara A M; Perrotti, Linda I; Mandal, Subhrangsu S

    2014-10-09

    Enhancer of Zeste homolog 2 (EZH2), a methyltransferase specific to histone 3 lysine 27, is a critical player in gene silencing and is overexpressed in breast cancer. Our studies demonstrate that EZH2 is transcriptionally induced by estradiol in cultured breast cancer cells and in the mammary glands of ovariectomized rats. EZH2 promoter contains multiple functional estrogen-response elements. Estrogen receptors (ERs) and ER coregulators such as mixed lineage leukemia (MLL) histone methylases (MLL2 and MLL3) and histone acetyltransferase CBP/P300 bind to the EZH2 promoter in the presence of estradiol and regulate estradiol-induced EZH2 expression. EZH2 expression is also increased upon exposure to estrogenic endocrine disrupting chemicals (EDCs) such as bisphenol-A (BPA) and diethylstilbestrol (DES). Similar to estradiol, BPA and DES-induced EZH2 expression is coordinated by ERs, MLLs and CBP/P300. In summary, we demonstrate that EZH2 is transcriptionally regulated by estradiol in vitro and in vivo, and its expression is potentially dysregulated upon exposure to estrogenic EDCs.

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

    PubMed Central

    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

  2. Effects of endocrine disruptor di-n-butyl phthalate on the growth of Bok choy (Brassica rapa subsp. chinensis).

    PubMed

    Liao, Chien-Sen; Yen, Jui-Hung; Wang, Yei-Shung

    2006-12-01

    The effects of the endocrine disrupter, di-n-butyl phthalate (DBP), on the growth of leaf vegetable Bok choy (Brassica rapa subsp. chinensis, white stem Bok choy) were investigated. The results showed that leaves of Bok choy became white in color with the occurrence of chlorosis and necrosis upon treating with 30 mg l(-1) DBP for 42 days. Transmission electron microscopic images revealed that changes in the chloroplast structures accompanied the chlorosis. In addition, a decrease in biomass and chlorophyll, and accumulation of DBP, were found in DBP-treated Bok choy. The growth and morphology of Bok choy showed a significant dose-response relationship upon treatment with DBP in a hydroponic culture medium. The proteome of the leaf tissue was analyzed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Six protein spots were identified in 2-DE that showed reproducible differences in expression between the normal control and the DBP-treated sample. Based on proteome level studies two protein spots increased and were identified as superoxide dismutase (SOD) and peroxidase 21 precursor. These proteins are believed to increase in expression in response to free radical exposure as a detoxification mechanism. The other four protein spots that disappeared on treatment with DBP were identified as heat shock cognate protein 80, protein disulfide isomerase precursor, apocytochrome f precursor, and RNA polymerase beta subunit. The first two play an important role in polypeptide folding, the third is associated with electron transport, and the last has a critical function in DNA transcription. This study indicated that DBP affects the proteome formation as well as the physiology and the morphology of Bok choy during growth. The decrease in those four proteins might be related to the growth and development of a plant.

  3. Simultaneous monitoring of seven phenolic metabolites of endocrine disrupting compounds (EDC) in human urine using gas chromatography with tandem mass spectrometry.

    PubMed

    Schmidt, Lukas; Müller, Johannes; Göen, Thomas

    2013-02-01

    A gas chromatographic-tandem mass spectrometric (GC-MS/MS) method for the simultaneous determination of the three well-known endocrine disruptors, bisphenol A, daidzein and genistein, as well as of four human pesticide metabolites which are supposed to have proper endocrine activity or which are metabolites of endocrine-disrupting compounds, viz., 1- and 2-naphthol, 2-isopropoxyphenol and 3,5,6-trichloropyridinol, has been developed and validated. The method involves enzymatic cleavage of the conjugates using β-glucuronidase/arylsulfatase followed by solid-phase extraction and derivatisation with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. Isotopically labelled internal standards were used for all analytes, to achieve best analytical error correction. The method proved to be both sensitive and reliable in human urine with detection limits ranging from 0.1 to 0.6 μg/L for all analytes. Precision and repeatability was determined to range from 1 to 15 %. Compared with other published analytical procedures, the present method enables the simultaneous determination of a couple of phenolic agents with competitive or improved analytical reliability. Thus, the present method is suitable for a combined monitoring of the exposure to prominent xenobiotics with effects on the human endocrine system (bisphenol A, carbaryl, chlorpyrifos, chlorpyrifos-methyl, naphthalene, propoxur, triclopyr) and phytoestrogens (daidzein, genistein) in population studies.

  4. 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

    PubMed Central

    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

  5. Effects of hypothyroidism and endocrine disruptor-dependent non-thyroidal illness syndrome on the GnRH-gonadotroph axis of the adult male rat.

    PubMed

    Toni, R; Della Casa, C; Castorina, S; Cocchi, D; Celotti, F

    2005-01-01

    Effects of primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of GnRH to HYPO rats and humans may increase or decrease gonadotropin secretion. Since inhibitory effects of HYPO on the GnRH-gonadotropin axis are reversed by replacement with L-T4, it has been suggested that thyroid hormone (TH) may regulate tuberoinfundibular GnRH and pituitary gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic GnRH neurons, LH, PRL and vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when GnRH biosynthesis is reduced by HYPO, gonadotropin secretion may be rescued by local activating effects of VIP. Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether central

  6. Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health.

    PubMed

    Tapia-Orozco, Natalia; Santiago-Toledo, Gerardo; Barrón, Valeria; Espinosa-García, Ana María; García-García, José Antonio; García-Arrazola, Roeb

    2017-02-10

    Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis.

  7. Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds.

    PubMed

    Rissman, Emilie F; Adli, Mazhar

    2014-08-01

    The idea that what we eat, feel, and experience influences our physical and mental state and can be transmitted to our offspring and even to subsequent generations has been in the popular realm for a long time. In addition to classic gene mutations, we now recognize that some mechanisms for inheritance do not require changes in DNA. The field of epigenetics has provided a new appreciation for the variety of ways biological traits can be transmitted to subsequent generations. Thus, transgenerational epigenetic inheritance has emerged as a new area of research. We have four goals for this minireview. First, we describe the topic and some of the nomenclature used in the literature. Second, we explain the major epigenetic mechanisms implicated in transgenerational inheritance. Next, we examine some of the best examples of transgenerational epigenetic inheritance, with an emphasis on those produced by exposing the parental generation to endocrine-disrupting compounds (EDCs). Finally, we discuss how whole-genome profiling approaches can be used to identify aberrant epigenomic features and gain insight into the mechanism of EDC-mediated transgenerational epigenetic inheritance. Our goal is to educate readers about the range of possible epigenetic mechanisms that exist and encourage researchers to think broadly and apply multiple genomic and epigenomic technologies to their work.

  8. Development of a molecular recognition based approach for multi-residue extraction of estrogenic endocrine disruptors from biological fluids coupled to liquid chromatography-tandem mass spectrometry measurement.

    PubMed

    Bousoumah, Radia; Antignac, Jean Philippe; Camel, Valérie; Grimaldi, Marina; Balaguer, Patrick; Courant, Frederique; Bichon, Emmanuelle; Morvan, Marie-Line; Le Bizec, Bruno

    2015-11-01

    Multi-residue methods permitting the high-throughput and affordable simultaneous determination of an extended range of endocrine disrupting chemicals (EDCs) with reduced time and cost of analysis is of prime interest in order to characterize a whole set of bioactive compounds. Such a method based on UHPLC-MS/MS measurement and dedicated to 13 estrogenic EDCs was developed and applied to biological matrices. Two molecular recognition-based strategies, either molecular imprinted polymer (MIP) with phenolic template or estrogen receptors (ERα) immobilized on a sorbent, were assessed in terms of recovery and purification efficiency. Both approaches demonstrated their suitability to measure ultra-trace levels of estrogenic EDCs in aqueous samples. Applicability of the MIP procedure to urine and serum samples has also been demonstrated.

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

    PubMed

    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.

  10. Androgenic endocrine disruptors in wastewater treatment plant effluents in India: Their influence on reproductive processes and systemic toxicity in male rats

    SciTech Connect

    Kumar, Vikas; Chakraborty, Ajanta; Viswanath, Gunda; Roy, Partha

    2008-01-01

    Endocrine-disrupting chemicals (EDC) are linked to human health and diseases as they mimic or block the normal functioning of endogenous hormones. The present work dealt with a comparative study of the androgenic potential of wastewater treatment plant (WWTP) influents and effluents in Northern region of India, well known for its polluted water. Water samples were screened for their androgenic potential using the Hershberger assay and when they were found positive for androgenicity, we studied their mode of action in intact rats. The data showed a significant change in the weight and structure of sex accessory tissues (SATs) of castrated and intact rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change in the expression patterns of the major steroidogenic enzymes in adrenal and testis: cytochrome P450{sub SCC}, cytochrome P450{sub C17}, 3{beta}-hydroxysteroid dehydrogenase, 17{beta}-hydroxysteroid dehydrogenase. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile showed a decreased level of gonadotrophic hormones and increased testosterone level. Further, increase in the serum level of alkaline phosphatase, SGPT and SGOT and histopathological changes in kidney and liver of treated animals, confirmed the toxic effects of contaminating chemicals. Analysis of water samples using HPLC and GC-MS showed the presence of various compounds and from them, four prominent aromatic compounds viz. nonylphenol, hexachlorobenzene and two testosterone equivalents, were identified. Our data suggest that despite rigorous treatment, the final treated effluent from WWTP still has enough androgenic and toxic compounds to affect general health.

  11. Occurrence of pharmaceuticals and endocrine disruptors in raw sewage and their behavior in UASB reactors operated at different hydraulic retention times.

    PubMed

    Queiroz, F B; Brandt, E M F; Aquino, S F; Chernicharo, C A L; Afonso, R J C F

    2012-01-01

    This work investigated the occurrence of pharmaceuticals and endocrine disrupting compounds (EDCs) in raw sewage (from Belo Horizonte city, Minas Gerais state, Brazil) and assessed their behavior in demo-scale upflow anaerobic sludge blanket reactors (UASB reactors) operated at different hydraulic retention times (HRT). The dissolved concentration of the studied micropollutants in the raw and treated sewage was obtained using solid phase extraction (SPE) followed by analysis in a liquid chromatography system coupled to a hybrid high resolution mass spectrometer consisting of an ion-trap and time of flight (LC-MS-IT-TOF). The natural (estradiol) and synthetic (ethinylestradiol) estrogens were hardly detected; when present, however, their concentrations were lower than the method quantification limits. The concentrations of bisphenol A and miconazole in raw sewage were similar to that reported in the literature (around 200 ng L⁻¹ and hardly detected, respectively). The antibiotics sulfamethoxazole (median 13.0 ng L⁻¹) and trimethoprim (median 61.5 ng L⁻¹), and the other pharmaceutical compounds (diclofenac and bezafibrate, with median 99.9 and 94.4 ng L⁻¹, respectively) were found in lower concentrations when compared with reports in the literature, which might indicate a lower consumption of such drugs in Brazil. The UASB reactors were inefficient in the removal of bisphenol A, and led to an increased concentration of nonylphenol in the effluent. The anaerobic reactors were also inefficient in the removal of diclofenac, and led to a partial removal of bezafibrate; whereas, for sulfamethoxazole there seemed to be a direct relationship between the HRT and removal efficiencies. For trimethoprim the sludge retention time (SRT) seemed to play an important role, although it was only partially removed in the UASB reactors.

  12. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

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

    PubMed

    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.

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

    PubMed

    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. Biotransformation of Endocrine-Disrupting Compounds in Groundwater: Bisphenol A, Nonylphenol, Ethynylestradiol and Triclosan by a Laccase Cocktail from Pycnoporus sanguineus CS43.

    PubMed

    Garcia-Morales, R; Rodríguez-Delgado, M; Gomez-Mariscal, K; Orona-Navar, C; Hernandez-Luna, C; Torres, E; Parra, R; Cárdenas-Chávez, D; Mahlknecht, J; Ornelas-Soto, N

    The biodegradation of organic compounds present in water at trace concentration has become a critical environmental problem. In particular, enzymatic oxidation by fungal laccases offers a promising alternative for efficient and sustainable removal of organic pollutants in water. In this work, the biocatalytic ability of laccases from the Pycnoporus sanguineus CS43 fungus was evaluated. A filtered culture supernatant (laccase cocktail) evidenced an enhanced biotransformation capability to remove common endocrine-disruptor compounds (EDCs), such as bisphenol A, 4-nonylphenol, 17-α-ethynylestradiol and triclosan. A biodegradation of around 89-100 % was achieved for all EDCs using synthetic samples (10 mg L(-1)) and after the enzymatic treatment with 100 U L(-1) (50.3 U mg (-1)). The biodegradation rates obtained were fitted to a first order reaction. Furthermore, enzymatic biocatalytic activity was also evaluated in groundwater samples coming from northwestern Mexico, reaching biotransformation percentages between 55 and 93 % for all tested compounds. As far as we know this is the first study on real groundwater samples in which the enzymatic degradation of target EDCs by a laccase cocktail from any strain of Pycnoporus sanguineus was evaluated. In comparison with purified laccases, the use of cocktail offers operational advantages since additional purification steps can be avoided.

  16. RISKS OF ENDOCRINE DISRUPTING COMPOUNDS TO WILDLIFE: EXTRAPOLATING FROM EFFECTS ON INDIVIDUALS TO POPULATION RESPONSE

    EPA Science Inventory

    Much of the research conducted on the effects of endocrine disrupting compounds (EDCs) has been focused on effects at the individual or subindividual level. The challenge from the point of view of ecological risk assessment is to determine effects on populations and higher levels...

  17. INFLUENCE OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ON MAMMARY GLAND DEVELOPMENT AND TUMOR SUSCEPTIBILITY

    EPA Science Inventory

    Influence of Endocrine Disrupting Compounds (EDCs) on Mammary Gland Development and Tumor Susceptibility.

    Suzanne E. Fenton1, and Jennifer Rayner1,2

    1 Reproductive Toxicology Division, NHEERL/ORD, U.S. EPA, Research Triangle Park, NC, and 2 Department of Environmen...

  18. EVALUATION OF DRINKING WATER TREATMENT TECHNOLOGIES FOR REMOVAL OF ENDOCRINE DISRUPTING COMPOUNDS

    EPA Science Inventory

    Many of the chemicals identified as potential endocrine disrupting compounds (EDCs) may be present in surface or ground waters used as drinking water sources due to their introduction from domestic and industrial sewage treatment systems and wet-weather runoff. In order to dec...

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

    ERIC Educational Resources Information Center

    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. Occurrence, fate, and ecosystem implications of endocrine active compounds in select rivers of Minnesota

    NASA Astrophysics Data System (ADS)

    Writer, J.; Keefe, S.; Barber, L. B.; Brown, G.; Schoenfuss, H.; Kiesling, R.; Gray, J. L.

    2009-12-01

    Select endocrine active compounds (EACs) were measured in four rivers in southern Minnesota. Additionally, caged and wild fish were assessed for indication of endocrine disruption using plasma vitellogenin and histopathology. Low concentrations of EACs were identified in all rivers, as was elevated plasma vitellogenin in caged and wild fish, indicating potential endocrine disruption. To evaluate the persistence of these compounds in small rivers, a tracer study was performed on one of the rivers (Redwood River) using Lagrangian sampling coupled with hydrologic modeling incorporating transient storage. Mass exchange (transient storage, sorption) and degradation were approximated as pseudo first order processes, and in-stream removal rates were then computed by comparing conservative tracer concentrations to organic compound concentrations. Production of estrone and 4-nonylphenol in the studied reach as a result of biochemical transformation from their parent compounds (17β-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17β-estradiol and nonylphenol to undergo a 50% reduction in concentration was >2 km and >10 km, respectively. These results indicate that EACs are transported several kilometers downstream from discharge sources and therefore have the potential of adversely impacting the lotic ecosystem over these distances.

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

    PubMed

    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

  2. The Novel Endocrine Disruptor Tolylfluanid Impairs Insulin Signaling in Primary Rodent and Human Adipocytes through a Reduction in Insulin Receptor Substrate-1 Levels

    PubMed Central

    Sargis, Robert M.; Neel, Brian A.; Brock, Clifton O.; Lin, Yuxi; Hickey, Allison T.; Carlton, Daniel A.; Brady, Matthew J.

    2012-01-01

    Emerging data suggest that environmental endocrine disrupting chemicals (EDCs) may contribute to the pathophysiology of obesity and diabetes. In prior work, the phenylsulfamide fungicide tolylfluanid (TF) was shown to augment adipocyte differentiation, yet its effects on mature adipocyte metabolism remain unknown. Because of the central role of adipose tissue in global energy regulation, the present study tested the hypothesis that TF modulates insulin action in primary rodent and human adipocytes. Alterations in insulin signaling in primary mammalian adipocytes were determined by the phosphorylation of Akt, a critical insulin signaling intermediate. Treatment of primary murine adipose tissue in vitro with 100 nM TF for 48 h markedly attenuated acute insulin-stimulated Akt phosphorylation in a strain- and species-independent fashion. Perigonadal, perirenal, and mesenteric fat were all sensitive to TF-induced insulin resistance. A similar TF-induced reduction in insulin-stimulated Akt phosphorylation was observed in primary human subcutaneous adipose tissue. TF-treatment led to a potent and specific reduction in insulin receptor substrate-1 (IRS-1) mRNA and protein levels, a key upstream mediator of insulin’s diverse metabolic effects. In contrast, insulin receptor-β, phosphatidylinositol 3-kinase, and Akt expression were unchanged, indicating a specific abrogation of insulin signaling. Additionally, TF-treated adipocytes exhibited altered endocrine function with a reduction in both basal and insulin-stimulated leptin secretion. These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes. PMID:22387882

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

    PubMed Central

    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

  4. Male pubertal development: are endocrine-disrupting compounds shifting the norms?

    PubMed

    Zawatski, William; Lee, Mary M

    2013-01-01

    Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health. In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females, this review will focus on the small number of studies performed in males that report an association of polychlorinated biphenyls with earlier sexual maturity rating and confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal onset and progression in boys. Recent studies have also demonstrated that EDC exposure may affect pubertal testosterone production without having a noticeable effect on sexual maturity rating. A limitation to understand the effects of EDCs in humans is the potential for confounding due to the long temporal lag from early-life exposures to adult outcomes. The complex interplay of multiple environmental exposures over time also complicates the interpretation of human studies. These studies have identified critical windows of vulnerability during development when exposures to EDCs alter critical pathways and affect postnatal reproductive health. Contemporaneous exposures can also disrupt the hypothalamic-pituitary-gonadal axis. This paper will review the normal process of puberty in males and summarize human data that suggest potential perturbations in pubertal onset and tempo with early-life exposures to EDCs.

  5. Development and recovery of histopathological alterations in the gonads of zebrafish (Danio rerio) after single and combined exposure to endocrine disruptors (17α-ethinylestradiol and fadrozole).

    PubMed

    Luzio, Ana; Monteiro, Sandra M; Rocha, Eduardo; Fontaínhas-Fernandes, António A; Coimbra, Ana M

    2016-06-01

    Exposure of wildlife to endocrine disrupting chemicals (EDCs) is not necessarily continuous. Due to seasonal changes and variable industrial and agricultural activities it often occurs intermittently. Thus, it is possible that aquatic organisms may be more affected by periodic peak exposure than by chronic exposure. Therefore, an experimental scenario including an exposure from 2h to 90 days post-fertilization (dpf) and a subsequent recovery period until 150 dpf was chosen to assess the potential reversibility of the effects of sex steroids on sexual and gonad development of zebrafish (Danio rerio). The aim of this study was to investigate the persistence of the endocrine effects of an estrogen (EE2-17α-ethinylestradiol, 4ng/L), an inhibitor of estrogen synthesis (Fad-fadrozole, 50μg/L) or their binary mixture (Mix-EE2+ Fad, 4ng/L+50μg/L). Afterwards, a semi-quantitative histological assessment was used to investigate histopathological changes on gonad differentiation and development. The data showed that fadrozole, alone or in combination with EE2, permanently disrupts the sexual development, inducing masculinization and causing severe pathological alterations in testis, such as intersex associated to the enlargement of sperm ducts, interstitial changes, asynchronous development and detachment of basal membrane. After exposures to both EDCs and their mixture, the gonad histopathology revealed interstitial proteinaceous fluid deposits and, in ovaries, there were atretic oocytes, and presumably degenerative mineralization. On the other hand, the gonadal changes induced by EE2 alone seem to be partially reversible when the exposure regime changed to a recovery period. In addition, EE2 enhanced zebrafish growth in both genders, with male fish presenting signs of early obesity such as the presence of adipocytes in testis. Moreover, sex ratio was slightly skewed toward females, at 90 and 105 dpf, in zebrafish exposed to EE2. The data further indicate that long

  6. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

    PubMed Central

    Kavlock, R J; Daston, G P; DeRosa, C; Fenner-Crisp, P; Gray, L E; Kaattari, S; Lucier, G; Luster, M; Mac, M J; Maczka, C; Miller, R; Moore, J; Rolland, R; Scott, G; Sheehan, D M; Sinks, T; Tilson, H A

    1996-01-01

    The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research. PMID:8880000

  7. A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain.

    PubMed

    Fernández, M; Paradisi, M; D'Intino, G; Del Vecchio, G; Sivilia, S; Giardino, L; Calzà, L

    2010-11-01

    Polychlorinated dibenzo-dioxins, furans and dioxin-like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a lipophilic endocrine-disrupting molecule that accumulates in adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known to interfere with thyroid hormone metabolism and signaling in the developing brain. As thyroid hormone is critical in the myelination process during development, we investigated the effect of a single dose of TCDD prenatal exposure (gestational day 18) on the myelination process. A semi-quantitative analysis of oligodendrocyte markers at different stages of maturation was performed in the offspring's medulla oblongata, cerebellum, diencephalon and telenchephalon at different postnatal days (2/3, 14, 30 and 135). The most significant alterations observed were: (i) cerebellum and medulla oblongata: altered expression of oligodendroglial lineage and platelet-derived growth factor alpha receptor, myelin basic protein (MBP) mRNAs (P2/3, P135) and MBP protein (P135); (ii) diencephalon: increase in platelet- derived growth factor alpha receptor mRNA level (P2/3); (iii) telenchephalon: decrease in MBP mRNA expression. The oligodendroglial generation capability of adult neural stem/precursor cells obtained ex vivo from TCDD and vehicle-treated dams was then explored. TCDD impairs neurosphere proliferation and retards CNPase-positive cell generation from adult neurospheres.

  8. Seasonal variation of endocrine disrupting compounds, pharmaceuticals and personal care products in wastewater treatment plants.

    PubMed

    Yu, Yong; Wu, Laosheng; Chang, Andrew C

    2013-01-01

    The occurrence of 14 endocrine disrupting compounds (EDCs), pharmaceuticals and personal care products (PPCPs) in influents, effluents and sludge from five wastewater treatment plants (WWTPs) in southern California was studied in winter and summer. All 14 compounds were detected in influent samples from the five WWTPs except for estrone. Paracetamol, naproxen and ibuprofen were the dominant compounds, with mean concentrations of 41.7, 35.7 and 22.3 μg/L, respectively. The treatment removal efficiency for most compounds was more than 90% and concentrations in the effluents were relatively low. Seasonal variation of the compounds' concentration in the wastewater was significant: the total concentration of each compound in the wastewater was higher in winter than in summer, which is attributed to more human consumption of pharmaceuticals during winter and faster degradation of the compounds in summer. The highest concentrations of triclosan and octylphenol were detected in sewage sludge, with mean concentrations of 1505 and 1179 ng/g, respectively. Risk quotients (RQs), expressed as the ratios of environmental concentrations and the predicted no-effect concentrations (PNEC), were less than unity for all the compounds except for estrone in the effluents, indicating no immediate ecological risk is expected. However, RQs were higher than unity for 2 EDCs (estrone and octylphenol) and carbamazepine in sludge samples, indicating a significant ecotoxicological risk to human health. Therefore, appropriate treatment of sewage sludge is required before its application.

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

    PubMed Central

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

    2016-01-01

    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. PMID:28036072

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

    SciTech Connect

    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.

  11. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    USGS Publications Warehouse

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  12. Workshop on perinatal exposure to dioxin-like compounds. III. Endocrine effects

    SciTech Connect

    Feeley, M.M.

    1995-03-01

    Studies involving endocrine effects in humans and experimental animals resulting from the exposure to dioxin-like (non-ortho-substituted PCBs, PCDDs/PCDFs) and nondioxin-like (PCBs, OC pesticides) compounds (DLCs and NDLCs) were presented. A variety of reproductive and hormonal parameters, including androgen status, sexual differentiation, and thyroid functionality, were discussed. As in utero and lactational exposure of the human fetus/neonate to these environmental contaminants is inevitable, continued research to identify sensitive biomarkers of effect and susceptibility as well as to define dose-response relationships is required. 15 refs., 1 fig.

  13. Review of Bioassays for Monitoring Fate and Transport ofEstrogenic Endocrine Disrupting Compounds in Water

    SciTech Connect

    CGCampbell@lbl.gov

    2004-01-30

    Endocrine disrupting compounds (EDCs) are recognizedcontaminants threatening water quality. Despite efforts in sourceidentification, few strategies exist for characterization or treatment ofthis environmental pollution. Given that there are numerous EDCs that cannegatively affect humans and wildlife, general screening techniques likebioassays and biosensors provide an essential rapid and intensiveanalysis capacity. Commonly applied bioassays include the ELISA and YESassays, but promising technologies include ER-CALUXa, ELRA, Endotecta,RIANA, and IR-bioamplification. Two biosensors, Endotecta and RIANA, arefield portable using non-cellular biological detection strategies.Environmental management of EDCs in water requires integration ofbiosensors and bioassays for monitoring and assessment.

  14. COMPUTATIONAL MODELING OF SERUM BINDING PROTEINSAND CLEARANCE IN EXTRAPOLATIONS ACROSS LIFE-STAGES AND SPECIES FOR ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    One measure of the potency of compounds that lead to adverse effects through ligand-dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g. gen...

  15. Negative impact of endocrine-disrupting compounds on human reproductive health.

    PubMed

    Balabanič, Damjan; Rupnik, Marjan; Klemenčič, Aleksandra Krivograd

    2011-01-01

    There is increasing concern about chemical pollutants that are able to mimic hormones, the so-called endocrine-disrupting compounds (EDCs), because of their structural similarity to endogenous hormones, their ability to interact with hormone transport proteins or because of their potential to disrupt hormone metabolic pathways. Thus, the effects of endogenous hormones can be mimicked or, in some cases, completely blocked. A substantial number of environmental pollutants, such as polychlorinated biphenyls, dioxins, polycyclic aromatic hydrocarbons, phthalates, bisphenol A, pesticides, alkylphenols and heavy metals (arsenic, cadmium, lead, mercury), have been shown to disrupt endocrine function. These compounds can cause reproductive problems by decreasing sperm count and quality, increasing the number of testicular germ cells and causing male breast cancer, cryptorchidism, hypospadias, miscarriages, endometriosis, impaired fertility, irregularities of the menstrual cycle, and infertility. Although EDCs may be released into the environment in different ways, the main sources is industrial waste water. The present paper critically reviews the current knowledge of the impact of EDCs on reproductive disorders in humans.

  16. The environmental endocrine disruptor p-nitrophenol interacts with FKBP51, a positive regulator of androgen receptor and inhibits androgen receptor signaling in human cells.

    PubMed

    Wu, Dan; Tao, Xuanyu; Chen, Zhi-Peng; Han, Jian-Ting; Jia, Wen-Juan; Zhu, Ning; Li, Xiangkai; Wang, Zhiping; He, Yong-Xing

    2016-04-15

    The compound p-nitrophenol, which shows the anti-androgenic activity, can easily become anthropogenic pollutants and pose a threat to the environment and human health. Previous work indicates that the anti-androgenic mechanism of p-nitrophenol is complex and may involve several components in the AR signaling pathway, but the molecular details of how p-nitrophenol inhibits AR signaling are still not quite clear. Here, we characterized p-nitrophenol binds to the FK1 domain of an AR positive regulator FKBP51 with micromolar affinity and structural analysis of FK1 domain in complex with p-nitrophenol revealed that p-nitrophenol occupies a hydrophobic FK1 pocket that is vital for AR activity enhancement. Molecular dynamics simulation indicated that p-nitrophenol is stably bound to the FK1 pocket and the hotspot residues that involved p-nitrophenol binding are mainly hydrophobic and overlap with the AR interaction site. Furthermore, we showed that p-nitrophenol inhibits the androgen-dependent growth of human prostate cancer cells, possibly through down-regulating the expression levels of AR activated downstream genes. Taken together, our data suggests that p-nitrophenol suppresses the AR signaling pathway at least in part by blocking the interaction between AR and its positive regulator FKBP51. We believe that our findings could provide new guidelines for assessing the potential health effects of p-nitrophenol.

  17. Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing

    PubMed Central

    Crain, D. Andrew; Janssen, Sarah J.; Edwards, Thea M.; Heindel, Jerrold; Ho, Shuk-mei; Hunt, Patricia; Iguchi, Taisen; Juul, Anders; McLachlan, John A.; Schwartz, Jackie; Skakkebaek, Niels; Soto, Ana M.; Swan, Shanna; Walker, Cheryl; Woodruff, Teresa K.; Woodruff, Tracey J.; Giudice, Linda C.; Guillette, Louis J.

    2014-01-01

    Objective To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. Design Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. Conclusion(s) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which women’s health can be improved. PMID:18929049

  18. Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments

    PubMed Central

    Ortiz-Zarragoitia, Maren; Bizarro, Cristina; Rojo-Bartolomé, Iratxe; Diaz de Cerio, Oihane; Cajaraville, Miren P.; Cancio, Ibon

    2014-01-01

    Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs) can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition). Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions. PMID:25222666

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

    PubMed

    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.

  20. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

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

    SciTech Connect

    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.

  2. COMPARISON OF FATHEAD MINNOW AND HUMAN ESTROGEN RECEPTOR BINDING TO ENDOCRINE DISRUPTING COMPOUNDS

    EPA Science Inventory

    Environmental estrogens have the potential to disrupt endocrine function in a myriad of species. However, in vitro assays designed to detect and characterize endocrine disrupting chemicals (EDCs) typically utilize mammalian estrogen receptors. Our overall objective is to charac...

  3. SPECIATION OF NON-PESTICIDAL ORGANOTIN COMPOUNDS USING GAS CHROMATOGRAPHY WITH INDUCTIVELY COUPLED PLASMA-MASS SPECTROMETRY

    EPA Science Inventory

    Organotins can be classified into a broad class of compounds referred to as endocrine disruptors and are presently being used in many applications such as UV stabilizers in polyvinyl chloride (PVC) pipes, antifoulants in marine paints, and as fungicides to name a few. The organo...

  4. CANCER AND DEVELOPMENTAL EXPOSURE TO ENDOCRINE DISRUPTORS

    EPA Science Inventory

    ABSTRACT
    Developing organisms have been shown to have increased susceptibility to cancer if exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer following prenatal exposure to ionizing radiatio...

  5. ENDOCRINE DISRUPTORS: MODELING THE INTRACELLULAR RESPONSE

    EPA Science Inventory

    WE ARE DEVELOPING A MECHANISTIC MATHEMATICAL MODEL OF THE INTRATESTICULAR AND INTRAOVARIAN METABOLIC NETWORK THAT MEDICATES STEROID SYNTHESIS TO IDENTIFY A LINK NEW ROBUST MOLECULAR BIOMARKERS OF EXPOSURE THAT ARE INDICATIVE OF THE ULTIMATE ADVERSE EFFECTS.

  6. Endocrine disrupting compounds and echinoderms: new ecotoxicological sentinels for the marine ecosystem.

    PubMed

    Sugni, Michela; Mozzi, Daniela; Barbaglio, Alice; Bonasoro, Francesco; Candia Carnevali, Maria Daniela

    2007-02-01

    Echinoderms are valuable test species in marine ecotoxicology and offer a wide range of biological processes appropriate for this approach. In spite of this potential, available data in literature are still rather limited, particularly with regard to the possible effects of endocrine disrupter compounds (EDCs). This review presents echinoderms as useful models for ecotoxicological tests and gives a brief overview of the most significant results obtained in recent years, particularly in the context of the COMPRENDO EU project. In this research project two different aspects of echinoderm physiology, plausibly regulated by humoral mechanisms, were investigated: reproductive biology and regenerative development. Selected EDCs suspected for their androgenic or antiandrogenic action were tested at low concentrations. The results obtained so far showed that different parameters such as regenerative growth, histological pattern, egg diameter and gonad maturation were affected by the exposure to the selected compounds. These results substantiate that reproductive and regenerative phenomena of echinoderms can be considered valuable alternative models for studies on EDCs and confirm that these compounds interfere with fundamental physiological processes, including growth, development and reproductive competence.

  7. THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS. JG Teeguarden1 and HA Barton2. 1ENVIRON International, Ruston LA; 2US EPA, ORD, NHEERL, ETD, Pharmacokinetics Branch, RTP, NC.

    One measure of th...

  8. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    EPA Science Inventory

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  9. Seasonal distribution, source investigation and vertical profile of phenolic endocrine disrupting compounds in Dianchi Lake, China.

    PubMed

    Wang, Bin; Huang, Bin; Jin, Wei; Wang, Yu; Zhao, Shimin; Li, Farong; Hu, Ping; Pan, Xuejun

    2012-04-01

    Phenolic endocrine disrupting compounds, including nonylphenol-di-ethoxylate (NP2EO), nonylphenol-mono-ethoxylate (NP1EO), 4-nonylphenol (4-NP), bisphenol A (BPA), 4-cumylphenol (4-CP) and 4-tert-octylphenol (4-t-OP), were investigated in water, surface sediment and sediment cores in Dianchi Lake to track their seasonal distributions, pollution sources and historical trends. The concentrations of NP2EO, NP1EO, 4-NP, BPA, 4-CP and 4-t-OP were up to 295.14, 448.48, 45.28, 530.33, 8.96 and 21.37 ng L(-1) in water, and up to 297.11, 809.63, 4.58, 166.87, 3.62 and 40.69 ng g(-1) dry weight in surface sediment, respectively. Except BPA in water, concentrations of all the other phenolic compounds in both of the matrices were higher in January than in July, 2011. The concentrations decreased significantly with an increase in distance from the sampling locations which were adjacent to the urban areas (Kunming City, Chenggong City and Jinning City). The pollution of phenolic EDCs came mainly from industry, agriculture and daily life. The relationships between the concentrations of target compounds and the six water quality parameters were evaluated. There were significant positive correlations between concentrations of phenolic compounds in water and in surface sediment. For sediment cores, three clearly separated maxima occurred in segments 0-5 cm (the late 2000s), 5-10 cm (the early and mid of 2000s) and 20-25 cm (the mid of 1980s), respectively. NP2EO, NP1EO and BPA were the three dominant compounds in the lake.

  10. Occurrence of Endocrine-Disrupting and Other Wastewater Compounds during Water Treatment with Case Studies from Lincoln, Nebraska and Berlin, Germany

    EPA Science Inventory

    Except for herbicides, research on the fate and transport of endocrine disrupting compounds and other organic wastewater compounds released into the environment and their potential presence in drinking water is in its infancy. Analytical methods still are being developed, evalua...

  11. Biodegradation of endocrine-disrupting compounds and suppression of estrogenic activity by ligninolytic fungi.

    PubMed

    Cajthaml, Tomás; Kresinová, Zdena; Svobodová, Katerina; Möder, Monika

    2009-05-01

    Endocrine-disrupting compounds (EDCs) represent a large group of substances of natural and anthropogenic origin. They are widely distributed in the environment and can pose serious risks to aquatic organisms and to public health. In this study, 4-n-nonylphenol, technical 4-nonylphenol, bisphenol A, 17alpha-ethinylestradiol, and triclosan were biodegraded by eight ligninolytic fungal strains (Irpex lacteus 617/93, Bjerkandera adusta 606/93, Phanerochaete chrysosporium ME 446, Phanerochaete magnoliae CCBAS 134/I, Pleurotus ostreatus 3004 CCBAS 278, Trametes versicolor 167/93, Pycnoporus cinnabarinus CCBAS 595, Dichomitus squalens CCBAS 750). The results show that under the used conditions the fungi were able to degrade the EDCs within 14d of cultivation with exception of B. adusta and P. chrysosporium in the case of triclosane and bisphenol A, respectively. I. lacteus and P. ostreatus were found to be most efficient EDC degraders with their degradation efficiency exceeding 90% or 80%, respectively, in 7d. Both fungi degraded technical 4-nonylphenol, bisphenol-A, and 17alpha-ethinylestradiol below the detection limit within first 3d of cultivation. In general, estrogenic activities assayed with a recombinant yeast test decreased with advanced degradation. However, in case of I. lacteus, P. ostreatus, and P. chrysosporium the yeast assay showed a residual estrogenic activity (28-85% of initial) in 17alpha-ethinylestradiol cultures. Estrogenic activity in B. adusta cultures temporally increased during degradation of technical 4-nonylphenol, suggesting a production of endocrine-active intermediates. Attention was paid also to the effects of EDCs on the ligninolytic enzyme activities of the different fungi strains to evaluate their possible stimulation or suppression of activities during the biodegradation processes.

  12. Reproductive endocrine patterns and volatile urinary compounds of Arctictis binturong: discovering why bearcats smell like popcorn

    NASA Astrophysics Data System (ADS)

    Greene, Lydia K.; Wallen, Timothy W.; Moresco, Anneke; Goodwin, Thomas E.; Drea, Christine M.

    2016-06-01

    Members of the order Carnivora rely on urinary scent signaling, particularly for communicating about reproductive parameters. Here, we describe reproductive endocrine patterns in relation to urinary olfactory cues in a vulnerable and relatively unknown viverrid—the binturong ( Arctictis binturong). Female binturongs are larger than and dominate males, and both sexes engage in glandular and urinary scent marking. Using a large ( n = 33), captive population, we collected serum samples to measure circulating sex steroids via enzyme immunoassay and urine samples to assay volatile chemicals via gas chromatography-mass spectrometry. Male binturongs had expectedly greater androgen concentrations than did females but, more unusually, had equal estrogen concentrations, which may be linked to male deference. Males also expressed a significantly richer array of volatile chemical compounds than did females. A subset of these volatile chemicals resisted decay at ambient temperatures, potentially indicating their importance as long-lasting semiochemicals. Among these compounds was 2-acetyl-1-pyrroline (2-AP), which is typically produced at high temperatures by the Maillard reaction and is likely to be responsible for the binturong's characteristic popcorn aroma. 2-AP, the only compound expressed by all of the subjects, was found in greater abundance in males than females and was significantly and positively related to circulating androstenedione concentrations in both sexes. This unusual compound may have a more significant role in mammalian semiochemistry than previously appreciated. Based on these novel data, we suggest that hormonal action and potentially complex chemical reactions mediate communication of the binturong's signature scent and convey information about sex and reproductive state.

  13. Analytical approach for monitoring endocrine-disrupting compounds in urban waste water treatment plants.

    PubMed

    Roda, Aldo; Mirasoli, Mara; Michelini, Elisa; Magliulo, Maria; Simoni, Patrizia; Guardigli, Massimo; Curini, Roberta; Sergi, Manuel; Marino, Alessandra

    2006-06-01

    The presence of endocrine-disrupting compounds in influent and effluent water samples from four waste water treatment plants located in Italy was studied. The estrogen-like activity of the water samples was measured using a chemiluminescent recombinant yeast assay which is based on genetically engineered yeast cells that express the human estrogen receptor. This receptor, once activated, elicits the expression of the reporter gene lac-Z and, consequently, the production of beta-galactosidase, which is then measured by chemiluminescence. To control and minimize sample matrix effects, an external control based on a modified yeast strain stably expressing beta-galactosidase was developed and also used in the assay. Rapid and sensitive chemiluminescent enzyme immunoassays were also developed and validated for the quantification of 17beta-estradiol, estrone, and estriol in waste water samples. Results from both methods were compared with a reference high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC ESI-MS-MS) method developed for the quantification of natural estrogens. The recombinant yeast assay revealed a significant estrogenic activity in the influent samples, ranging from 80 to 400 pmol/L 17beta-estradiol equivalents (EEQ), which was reduced by 70-95% in the effluent samples. The yeast assay also showed a systematic 20-30% overestimation of estrogenic activity relative to the HPLC ESI-MS-MS method, suggesting the presence of other compounds in the samples with estrogenic activity. The chemiluminescent enzyme immunoassays showed the presence of estrogens in the influent samples (mean concentrations: 350-450 pmol/L for estrone, 5-100 pmol/L for 17beta-estradiol, 25-300 pmol/L for estriol), with significantly lower concentrations detected in the respective effluent samples. The waste water treatment was able to reduce natural estrogen concentrations by 40-95%, although a high variability was observed. The enzyme

  14. Sources of endocrine-disrupting compounds in North Carolina waterways: a geographic information systems approach

    USGS Publications Warehouse

    Sackett, Dana K.; Pow, Crystal Lee; Rubino, Matthew J.; Aday, D.D.; Cope, W. Gregory; Kullman, Seth W.; Rice, J.A.; Kwak, Thomas J.; Law, L.M.

    2015-01-01

    The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17β-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17β-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17β-estradiol levels than reference sites. The results suggested that water 17β-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships.

  15. Comparison of the removal efficiency of endocrine disrupting compounds in pilot scale sewage treatment processes.

    PubMed

    Lee, Jiho; Lee, Byoung C; Ra, Jin S; Cho, Jaeweon; Kim, In S; Chang, Nam I; Kim, Hyun K; Kim, Sang D

    2008-04-01

    The removal efficiency of endocrine disrupting compounds from effluents using pilot scale sewage treatment processes, including various treatment technologies, such as membrane bioreactors (MBR), nanofiltration (NF) and reverse osmosis (RO) for the purpose of water reuse, were estimated and compared. The calculated estrogenic activity, expressed in ng-EEQ/l, based on the concentration detected by GC/MS, and relative potencies for each target compound were compared to those measured using the E-screen assay. The removal efficiencies for nonylphenol, was within the range of 55-83% in effluents. High removal efficiencies of approximately >70% based on the detection limits were obtained for bisphenol A, E1, EE2 and genistein with each treatment processes, with the exception of E1 ( approximately 64%) using the MBR process. The measured EEQ values for the effluents from the MBR, NF and RO processes also indicated low estrogenic activities of 0.65, 0.23 and 0.05 ng-EEQ/l, respectively. These were markedly reduced values compared with the value of 1.2 ng-EEQ/l in influent. Consequently, the removals of EDCs in terms of the EEQ value from the biological and chemical determinations were sufficiently achieved by the treatment process applied in this study, especially in the cases of the NF and RO treatments.

  16. Endocrine disrupting compounds in the atmosphere of the urban area of Thessaloniki, Greece

    NASA Astrophysics Data System (ADS)

    Salapasidou, M.; Samara, C.; Voutsa, D.

    2011-07-01

    The aim of this study was to investigate the occurrence of endocrine disrupting compounds (EDCs) in a complex urban atmosphere. Target compounds were alkylphenols (NP, tOP, nOP), nonylphenol monoethoxylate (NP1EO), bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and phthalates (DMP, DEP, DBP, BBP, DEHP, DNOP). EDCs were determined in ambient PM10 from two sampling sites, one urban-traffic and one urban-industrial, located in the city of Thessaloniki, northern Greece. At both sites, DEHP and NP were found to be the predominant EDCs in airborne PM10. Concentrations of NP did not exhibit any spatial difference, whereas concentrations of DEHP were significantly higher at the urban-traffic site. Wind direction was not found to have any significant effect on ambient EDCs concentrations suggesting impact from local sources rather than transport; however some peak concentrations might be attributed to short-distance sources. The gas/particle partition coefficient, Kp, and the gaseous phase of EDCs were calculated by employing two approaches based on literature data (a) for the subcooled liquid vapor pressure ( PL0) and (b) the octanol-air partition coefficient ( KOA). It appeared that the g/ p partition of phthalates estimated by the KOA approach is in better agreement with experimental partition data reported by other investigators. Absorption in organic matter was found to be significant partition mechanism at the urban-traffic site.

  17. Sources of endocrine-disrupting compounds in North Carolina waterways: a geographic information systems approach.

    PubMed

    Sackett, Dana K; Pow, Crystal Lee; Rubino, Matthew J; Aday, D Derek; Cope, W Gregory; Kullman, Seth; Rice, James A; Kwak, Thomas J; Law, Mac

    2015-02-01

    The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17β-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17β-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17β-estradiol levels than reference sites. The results suggested that water 17β-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships.

  18. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

    PubMed

    Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

    2016-11-01

    Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes.

  19. Optimization of an SPE and GC/MS Method for Analyzing Endocrine Disrupting Compounds in Water

    NASA Astrophysics Data System (ADS)

    Thomas, S. M.; Bodour, A.; Murray, K. E.

    2006-12-01

    Endocrine disrupting compounds (EDCs) are compounds that interrupt hormonal functions in the body. The literature reports the presence of EDCs in all environmental matrices (air, water and soil) at concentrations of at least 1 nanogram/liter (ng/l), which may be high enough to induce adverse health effects. Therefore, reliable analytical methods for detecting trace amounts of EDCs in water is very important for investigating and controlling their concentrations in the environment. This study investigated a method for analyzing four known or suspected EDCs (chlorpyrifos, musk HHCB, diethyl phthalate, and butylated hydroxyanisole) in water samples. The analytical method was based on the USGS wastewater method developed by Zaugg et al. (2001), but modified, using solid phase extraction (SPE) followed by gas chromatography and mass spectrometry (GC/MS) analysis. The EDCs were extracted using 60mg Water Oasis hydrophilic-lipophillic balance (HLB) extraction cartridges. The SPE efficiency was investigated by using different initial extraction volumes and different EDC concentrations. The lowest concentration was 1ng/l and the lowest extraction volume was 100mL. Results of the study indicate that the initial oven temperature conditions and rate of temperature increases affects the peak signal to noise ratio and the sample run-time in the GC/MS. An increase in gas flow rate did not show any significant changes and hence was maintained at 1ml/min. Preliminary data suggests that the percent recovery of the compounds obtained using this method either met or exceeded those presented by Zaugg et al. (2001) as the USGS wastewater method.

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

    SciTech Connect

    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.'

  1. Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies

    PubMed Central

    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

  2. Parental effects of endocrine disrupting compounds in aquatic wildlife: Is there evidence of transgenerational inheritance?

    PubMed

    Schwindt, Adam R

    2015-08-01

    The effects of endocrine disrupting compounds (EDCs) on aquatic wildlife are increasingly being recognized for their complexity. Investigators have detected alterations at multiple levels of biological organization in offspring exposed to EDCs through the blood or germ line of the parents, suggesting that generational consequences of EDCs are evident. Exposure to EDCs through the parents is concerning because if the resulting phenotype of the offspring is heritable and affects fitness, then evolutionary consequences may be evident. This review summarizes the evidence for transgenerational effects of EDCs in aquatic wildlife and illustrates cases where alterations appear to be transmitted maternally, paternally, or parentally. The literature indicates that EDC exposure to the parents induces developmental, physiological, endocrinological, and behavioral changes as well as increased mortality of offspring raised in clean environments. What is lacking, however, is a clear demonstration of heritable transgenerational effects in aquatic wildlife. Therefore, it is not known if the parental effects are the result of developmental or phenotypic plasticity or if the altered phenotypes are durably passed to subsequent generations. Epigenetic changes to gene regulation are discussed as a possible mechanism responsible for EDC induced parental effects. Additional research is needed to evaluate if heritable effects of EDCs are evident in aquatic wildlife, as has been demonstrated for terrestrial mammals.

  3. Protein differential expression induced by endocrine disrupting compounds in a terrestrial isopod.

    PubMed

    Lemos, Marco F L; Esteves, Ana Cristina; Samyn, Bart; Timperman, Isaak; van Beeumen, Jozef; Correia, António; van Gestel, Cornelis A M; Soares, Amadeu M V M

    2010-04-01

    Endocrine disrupting compounds (EDCs) have been studied due to their impact on human health and increasing awareness of their impact on wildlife species. Studies concerning the organ-specific molecular effects of EDC in invertebrates are important to understand the mechanisms of action of this class of toxicants but are scarce in the literature. We have used a dose/response approach to unravel the protein expression in different organs of isopods exposed to bisphenol A (BPA) and vinclozolin (Vz) and assess their potential use as surrogate species. Male isopods were exposed to a range of Vz or of BPA concentrations. After animal dissection, proteins were extracted from gut, hepatopancreas and testes. Protein profiles were analysed by electrophoresis and differentially expressed proteins were identified by MALDI mass spectrometry. EDCs affected proteins involved in the energy metabolism (arginine kinase), proteins of the heat shock protein family (Hsp70 and GRP78) and most likely microtubule dynamics (tubulin). Different proteins expressed at different concentrations in different organs are indicative of the organ-specific effects of BPA and Vz. Additionally, several proteins were up-regulated at lower but not higher BPA or Vz concentrations, bringing new data to the non-monotonic response curve controversy. Furthermore, our findings suggest that some common responses to EDCs in both vertebrates and invertebrates may exist.

  4. Removal of endocrine disrupting compounds from wastewater by microalgae co-immobilized in alginate beads.

    PubMed

    Solé, Alba; Matamoros, Víctor

    2016-12-01

    Microalgae systems have been found to be efficient for removing microcontaminants from wastewater effluents, but the effectiveness of immobilized microalgae for removing endocrine disrupting compounds (EDCs) has not yet been addressed. This paper assesses the effect of free and immobilized microalgae on removal efficiency for 6 EDCs by mixing them in 2.5 L reactors with treated wastewater. The experimental design also included control reactors without microalgae. After 10 days of incubation, 64 and 89% of the NH4-N and 90 and 96% of total phosphorous (TP) had been eliminated in the free microalgae and immobilized microalgae reactors, respectively, while the control reactors eliminated only 40% and 70% of the NH4-N and TP, respectively. Both the free and immobilized microalgae reactors were able to remove up to 80% of most of the studied EDCs within 10 days of incubation. Free microalgae were found to increase the kinetic removal rate for bisphenol A, 17-α-ethinylestradiol, and 4-octylphenol (25%, 159%, and 41%, respectively). Immobilizing the microalgae in alginate beads additionally enhanced the kinetic removal rate for bisphenol AF, bisphenol F, and 2,4-dichlorophenol. This study shows that the use of co-immobilized microalgae-based wastewater treatment systems increases the removal efficiency for nutrients and some EDCs from wastewater effluents.

  5. Cognitive effects of endocrine-disrupting chemicals in animals.

    PubMed Central

    Schantz, S L; Widholm, J J

    2001-01-01

    A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research. PMID:11748026

  6. Cognitive effects of endocrine-disrupting chemicals in animals.

    PubMed

    Schantz, S L; Widholm, J J

    2001-12-01

    A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research.

  7. Removal of endocrine disruptors and non-steroidal anti-inflammatory drugs through wastewater chlorination: the effect of pH, total suspended solids and humic acids and identification of degradation by-products.

    PubMed

    Noutsopoulos, Constantinos; Koumaki, Elena; Mamais, Daniel; Nika, Maria-Christina; Bletsou, Anna A; Thomaidis, Nikolaos S

    2015-01-01

    Endocrine disrupting chemicals (EDCs) and non-steroidal anti-inflammatory drugs (NSAIDs) are two groups of emerging pollutants the significance of which rests on their persistent detection in the aquatic environment and their possible adverse effects. Wastewater treatment plants are one of the major ways for transporting such chemicals in the aquatic environment. Chlorination is usually the last stage of treatment before wastewater being disposed to the aquatic environment. This work focuses on the evaluation of the effect of chlorine dose and specific wastewater characteristics (pH, total suspended solids and humic acids) on the removal of target EDCs and NSAIDs through chlorination. Another objective of this study is the identification of chlorination by-products of specific EDCs and NSAIDs and their dependence on contact time. Based on the results it is concluded that the effect of chlorine dose and humic acids concentration on the degradation of target compounds during chlorination is minimal. On the contrary, pH is a critical parameter which highly affects process performance. Moreover, it is concluded that not only the free available chlorine species, but also the properties of EDCs and NSAIDs under different pH conditions can affect chlorination process performance. The effect of TSS on the degradation of the target compounds during chlorination is more profound for chemicals with high Kow values and therefore higher affinity to partition to the particulate phase (i.e. nonylphenols, triclosan). Several degradation by-products were identified through chlorination of nonylphenol, bisphenol A and diclofenac. The dependence of these by-products on chlorination contact time is also demonstrated.

  8. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.

    PubMed

    Roepke, Troy A; Snyder, Mark J; Cherr, Gary N

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng

  9. Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain.

    PubMed

    Esteban, S; Gorga, M; Petrovic, M; González-Alonso, S; Barceló, D; Valcárcel, Y

    2014-01-01

    Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further

  10. Occurrence of Endocrine Active Compounds and Biological Responses in the Mississippi River - Study Design and Data, June through August 2006

    USGS Publications Warehouse

    Lee, Kathy E.; Yaeger, Christine S.; Jahns, Nathan D.; Schoenfuss, Heiko L.

    2008-01-01

    Concern that selected chemicals in the environment may act as endocrine active compounds in aquatic ecosystems is widespread; however, few studies have examined the occurrence of endocrine active compounds and identified biological markers of endocrine disruption such as intersex occurrence in fish longitudinally in a river system. This report presents environmental data collected and analyzed by the U.S. Geological Survey, Minnesota Pollution Control Agency and St. Cloud State University as part of an integrated biological and chemical study of endocrine disruption in fish in the Mississippi River. Data were collected from water, bed sediment, and fish at 43 sites along the river from the headwaters at Lake Itasca to 14 miles downstream from Brownsville, Minnesota during June through August 2006. Twenty-four individual compounds were detected in water samples, with cholesterol, atrazine, N,N-diethyl-meta-toluamide, metolachlor, and hexahydrohexamethylcyclopentabenzopyran detected most frequently (in at least 10 percent of the samples). The number of compounds detected in water per site ranged from 0 to 8. Forty individual compounds were detected in bed-sediment samples. The most commonly detected compounds (in at least 50 percent of the samples) were indole, beta-sitosterol, cholesterol, beta-stigmastanol, 3-methyl-1H-indole, p-cresol, pyrene, phenol, fluoranthene, 3-beta coprostanol, benzo[a]pyrene, acetophenone, and 2,6-dimethylnaphthalene. The total number of detections in bed sediment (at a site) ranged from 3 to 31. The compounds NP1EO, NP2EO, and 4-nonylphenol were detected in greater than 10 percent of the samples. Most (80 percent) female fish collected had measurable concentrations of vitellogenin. Vitellogenin also was detected in 62, 63, and 33 percent of male carp, smallmouth bass, and redhorse, respectively. The one male walleye sample plasma sample analyzed had a vitellogenin detection. Vitellogenin concentrations were lower in male fish (not

  11. Computational modeling of serum-binding proteins and clearance in extrapolations across life stages and species for endocrine active compounds.

    PubMed

    Teeguarden, Justin G; Barton, Hugh A

    2004-06-01

    One measure of the potency of compounds that lead to the effects through ligand-dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g., estradiol, genistein, bisphenol A, and octylphenol) comprise one class of such compounds. For making simple comparisons, receptor-binding affinity has been equated to in vivo potency, which consequently defines the dose-response characteristics for the compound. Direct extrapolation of in vitro estimated affinities to the corresponding in vivo system and to specific species or life stages (e.g., neonatal, pregnancy) can be misleading. Accurate comparison of the potency of endocrine active compounds requires characterization of biochemical and pharmacokinetic factors that affect their free concentration. Quantitative in vitro and in vivo models were developed for integrating pharmacokinetics factors (e.g., serum protein and receptor-binding affinities, clearance) that affect potency. Data for parameterizing these models for several estrogenic compounds were evaluated and the models exercised. While simulations of adult human or rat sera were generally successful, difficulties in describing early life stages were identified. Exogenous compounds were predicted to be largely ineffective at competing estradiol off serum-binding proteins, suggesting this was unlikely to be physiologically significant. Discrepancies were identified between relative potencies based upon modeling in vitro receptor-binding activity versus in vivo activity in the presence of clearance and serum-binding proteins. The examples illustrate the utility of this approach for integrating available experimental data from in vitro and in vivo studies to estimate the relative potency of these compounds.

  12. ENDOCRINE DISRUPTING COMPOUNDS: PROCESSES FOR REMOVAL FROM DRINKING WATER AND WASTEWATER

    EPA Science Inventory

    Although the list of potentially harmful substances is still being compiled and more sophisticated laboratory tests for detection of endocrine disrupting chemicals (EDCs) are being developed, an initial list of known EDCs has been made and an array of drinking water and wastewate...

  13. A Comparison of Pathology Found in Three Marine Fish Treated with Endocrine Disrupting Compounds

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs), such as the estrogen estradiol (E2) have been reported to affect fish reproduction. This study histopathologically compared and evaluated the effect of EDCs in three species of treated fish. Juvenile male summer flounder (Paralichthys dentat...

  14. Mysid crustaceans as potential test organisms for the evaluation of environmental endocrine disruption: a review.

    PubMed

    Verslycke, Tim A; Fockedey, Nancy; McKenney, Charles L; Roast, Stephen D; Jones, Malcolm B; Mees, Jan; Janssen, Colin R

    2004-05-01

    Anthropogenic chemicals that disrupt the hormonal systems (endocrine disruptors) of wildlife species recently have become a widely investigated and politically charged issue. Invertebrates account for roughly 95% of all animals, yet surprisingly little effort has been made to understand their value in signaling potential environmental endocrine disruption. This omission largely can be attributed to the high diversity of invertebrates and the shortage of fundamental knowledge of their endocrine systems. Insects and crustaceans are exceptions and, as such, appear to be excellent candidates for evaluating the environmental consequences of chemically induced endocrine disruption. Mysid shrimp (Crustacea: Mysidacea) may serve as a viable surrogate for many crustaceans and have been put forward as suitable test organisms for the evaluation of endocrine disruption by several researchers and regulatory bodies (e.g., the U.S. Environmental Protection Agency). Despite the long-standing use of mysids in toxicity testing, little information exists on their endocrinology, and few studies have focused on the potential of these animals for evaluating the effects of hormone-disrupting compounds. Therefore, the question remains as to whether the current standardized mysid endpoints can be used or adapted to detect endocrine disruption, or if new procedures must be developed, specifically directed at evaluating hormone-regulated endpoints in these animals. This review summarizes the ecological importance of mysids in estuarine and marine ecosystems, their use in toxicity testing and environmental monitoring, and their endocrinology and important hormone-regulated processes to highlight their potential use in assessing environmental endocrine disruption.

  15. Uncertainties for endocrine disrupters: our view on progress.

    PubMed

    Daston, George P; Cook, Jon C; Kavlock, Robert J

    2003-08-01

    The hypothesis that hormonally active compounds in the environment--endocrine disrupters--are having a significant impact on human and ecological health has captured the public's attention like no other toxicity concern since the publication of Rachel Carson's Silent Spring 1962. In the early 1990s, Theo Colborn and others began to synthesize information about the potential impacts of endocrine-mediated toxicity in the scientific literature (Colborn and Clement, 1992) and the popular press (Colborn et al., 1997). Recognizing the possibility of an emerging health threat, the U.S. Environmental Protection Agency (EPA) convened two international workshops in 1995 (Ankley et al., 1997; Kavlock et al., 1996) that identified research needs relative to future risk assessments for endocrine-disrupting chemicals (EDCs). These workshops identified effects on reproductive, neurological, and immunological function, as well as carcinogenesis as the major endpoints of concern and made a number of recommendations for research. Subsequently, the EPA developed a research strategy to begin addressing the recommendations (EPA, 1998a), and the federal government as a whole, working through the White House's Committee on the Environment and Natural Resources, increased funding levels and coordinated research programs to fill the major data gaps (Reiter et al., 1998). In parallel with these research efforts that were attempting to define the scope and nature of the endocrine disruptor hypothesis, the U.S. Congress added provisions to the Food Quality Protection Act (FQPA) and the Safe Drinking Water Act of 1996 to require the testing of food-use pesticides and drinking water contaminants, respectively, for estrogenicity and other hormonal activity. These bills were enacted into law, giving the EPA the mandate to implement them. The EPA, with the help of an external advisory committee, the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), determined that other

  16. Screening of endocrine disruption activity in sediments from the Uruguay River.

    PubMed

    Rivas-Rivera, Noelia; Eguren, Gabriela; Carrasco-Letelier, Leonidas; Munkittrick, Kelly R

    2014-08-01

    Sediment constitutes an important sink of endocrine disruptor compounds; however, the potential of sediments to act as a source of endocrine disruptors should be more extensively investigated. The main objective of this study was to determine whether exposure of immature common carp to Uruguay River sediments undergo physiological and endocrine alterations. The lower Uruguay River watershed supports intensive agricultural and forest production, receives municipal sewage discharge and industrial effluent, and a new large pulp mill was constructed in 2006. A 30-day semi-static assay was performed using sediments from four sites along the Uruguay River and compared with an unexposed group in dechlorinated water as a negative control. We focused on two upstream and two downstream sites of a new elemental chlorine free pulp mill. The results showed that plasma vitellogenin levels increased in fish along the river and significant differences were found between the exposed and unexposed groups. Condition factor and gonadosomatic index were not different; however, a significant difference in hepatosomatic index was observed in fish exposed to sediment from an industrial site. A significant reduction in primary spermatocyte accumulation was observed in the exposed group compared with that in the control group, and some individuals exposed to sediments from industrial sites presented with testis-ova. Our results suggest that Uruguay River sediments act as an important source of estrogenic compounds that could be responsible for the alterations observed. Future studies are needed to identify the causal agents and determine exposure routes.

  17. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds.

  18. Assessing an intermittently operated household scale slow sand filter paired with household bleach for the removal of endocrine disrupting compounds.

    PubMed

    Kennedy, Timothy J; Anderson, Todd A; Hernandez, E Annette; Morse, Audra N

    2013-01-01

    Endocrine disrupting compounds (EDCs) are a contaminant of emerging concern throughout the world, including developing countries where centralized water and wastewater treatment plants are not common. In developing countries, household scale water treatment technologies such as the biosand filter (BSF) are used to improve drinking water quality. No studies currently exist on the ability of the BSF to remove EDCs. In this experiment, the BSF was evaluated for the removal of three EDCs, estrone (E1), estriol (E3), and 17α-ethinyl estradiol (EE2). Removal results were compared to the slow sand filter (SSF) from the literature, which is similar to the BSF in principal but comparisons have revealed differences in removal of other water quality parameters between SSF and BSF. In general, the BSF minimally removed the compounds from spiked lake water as removal was less than 15% for all three compounds, though mass removal much higher than other studies in which the SSF was used. Household bleach was added to the rate was BSF effluent as suggested in order to achieve different Cl- concentrations (0.67, 2.0, 5.0, and 10.0 mg/L) and subsequent removal of EDCs by oxidation was examined. Concentrations were reduced > 98% for all compounds when the Cl- concentration was greater than 5 mg/L. Removal efficiency was > 50% at the 0.67 mg/L Cl- concentration, while almost 70% removal was observed for all compounds at the 2.0 mg/L Cl- concentration.

  19. Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2008-06-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in

  20. Endocrine Profiling and Prioritization Using ToxCast Assays

    EPA Science Inventory

    The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) is charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife (http://www.epa.gov/endo/). The prioritization of chemicals for test...

  1. Evaluation of a photocatalytic reactor membrane pilot system for the removal of pharmaceuticals and endocrine disrupting compounds from water.

    PubMed

    Benotti, Mark J; Stanford, Benjamin D; Wert, Eric C; Snyder, Shane A

    2009-04-01

    A photocatalytic reactor membrane pilot system, employing UV/TiO(2) photocatalysis, was evaluated for its ability to remove thirty-two pharmaceuticals, endocrine disrupting compounds, and estrogenic activity from water. Concentrations of all compounds decreased following treatment, and removal followed pseudo-first-order kinetics as a function of the amount of treatment. Twenty-nine of the targeted compounds in addition to total estrogenic activity were greater than 70% removed while only three compounds were less than 50% removed following the highest level of treatment (4.24 kW h/m(3)). No estrogenically active transformation products were formed during treatment. Additionally, the unit was operated in photolytic mode (UV only) and photolytic plus H(2)O(2) mode (UV/H(2)O(2)) to determine the relative amount of energy required. Based on the electrical energy per order (EEO), the unit achieved the greatest efficiency when operated in photolytic plus H(2)O(2) mode for the conditions tested.

  2. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

  3. STATUS OF THE U.S. ENVIRONMENTAL PROTECTION AGENCY'S ENCODRINE DISRUPTOR SCREENING PROGRAM

    EPA Science Inventory

    Status of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program. Susan Laws. Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, U.S. EPA, RTP, NC.

    In response to emergi...

  4. Clustering of sex hormone disruptors in Singapore's marine environment.

    PubMed Central

    Gong, Yinhan; Chin, Hong Soon; Lim, Lis Sa Elissa; Loy, Chong Jin; Obbard, Jeffrey P; Yong, E L

    2003-01-01

    Abnormal sexual differentiation and other reproductive abnormalities in marine animals indicate the presence in seawater of endocrine-disrupting compounds (EDCs) that perturb the function of the sex hormone signaling pathways. However, most studies to date have reported on EDC effects in freshwater and sewage samples, and there is a paucity of bioassay data on the effects of EDCs in marine waters. Our aims in this study were to devise robust methodologies suitable for extracting potential EDCs and to measure their summated effects on activities of androgen receptors (ARs) and estrogen receptors (ER-alpha and ER-beta) in marine samples from Singapore's coastal waters. In this study, we examined the ability of C18, hydrophilic and lipophilic balance, and diol cartridges to extract potential EDCs from seawater samples. Extracts from C18 cartridges exhibited the highest sex hormone bioactivities in reporter gene assays based on a human cell line expressing AR, ER-alpha, and ER-beta. Examination of extracts from 20 coastal locations showed high androgenic and estrogenic agonist activities in confined clusters closest to the main island of Singapore. Sex hormone activity declined rapidly in clusters farther from the main coastline and in more open waters. Unexpectedly, surface and mid-depth samples from the confined high-activity clusters, in the presence of hormone, exhibited AR and ER-alpha activities that were 200-900% higher than those observed for the cognate hormone alone. This enhanced sex hormone activity suggests that analyses of complex seawater mixtures may uncover unusual bioactivities that may not be obvious by studying individual compounds. Our data present a "snapshot" of the sex hormone disruptor activity in Singapore's marine environment and indicate that C18 extraction for EDCs used in conjunction with reporter gene bioassays represents a robust and sensitive methodology for measuring summated androgenic and estrogenic activities in seawater. PMID

  5. Novel heterogeneous fenton oxidation using magentic iron oxidedecorated carbon nanotube to remove endocrine disrupting compounds in wastewater and water

    NASA Astrophysics Data System (ADS)

    Cleveland, Vincent J.

    Endocrine disrupting compounds are becoming a growing concern in our modern world. Bisphenol A, a known estrogen mimic, is produced on a massive scale exposing it to humans and the environment on a daily basis. Recent studies since 1995 have shown that bisphenol A has negative effects even at ultra-low concentrations. Unfortunately, bisphenol A is biologically recalcitrant and passes through most traditional waste water treatment methods. In order to develop an effective and efficient treatment method, a combined approach is proposed. Iron amended carbon nanotubes can act as a heterogeneous Fenton catalyst and as an adsorbent of the contaminant. This project synthesized and characterized a magnetite decorated carbon nanotube catalyst. Additionally the adsorption kinetics and thermodynamics were investigated in both batch adsorption and column adsorption reactors.

  6. Endocrine disruptive compounds and cardio-metabolic risk factors in children.

    PubMed

    Khalil, Naila; Chen, Aimin; Lee, Miryoung

    2014-12-01

    The endocrine disrupting chemicals (EDC) are exogenous chemicals that can disrupt hormonal signaling system. EDCs are ubiquitous in our environment and many EDC are detectable in humans. With the increasing obesity prevalence in children it is imperative to explore the role of EDC as obesogens. This review summarizes recent epidemiological evidence regarding impact of these EDC on weight gain and metabolic outcomes in children. The EDCs include pharmaceuticals, pesticides, industrial by-products, and cigarette smoke. Current evidence suggests a link between early life exposure to some industrial by-products, synthetic hormones and cigarette smoke with weight gain. However, there is inconclusive evidence of an association between exposure to fungicides, dioxin, phytoestrogens, flame retardants, heavy metals and childhood obesity.

  7. Chemical fate and biological effects of several endocrine disrupters compounds in two echinoderm species.

    PubMed

    Sugni, Michela; Tremolada, Paolo; Porte, Cinta; Barbaglio, Alice; Bonasoro, Francesco; Carnevali, M Daniela Candia

    2010-03-01

    Two echinoderm species, the sea urchin Paracentrotus lividus and the feather star Antedon mediterranea, were exposed for 28 days to several EDCs: three putative androgenic compounds, triphenyltin (TPT), fenarimol (FEN), methyltestosterone (MET), and two putative antiandrogenic compounds, p,p'-DDE (DDE) and cyproterone acetate (CPA). The exposure nominal concentrations were from 10 to 3000 ng L(-1), depending on the compound. This paper is an attempt to join three different aspects coming from our ecotoxicological tests: (1) the chemical behaviour inside the experimental system; (2) the measured toxicological endpoints; (3) the biochemical responses, to which the measured endpoints may depend. The chemical fate of the different compounds was enquired by a modelling approach throughout the application of the 'Aquarium model'. An estimation of the day-to-day concentration levels in water and biota were obtained together with the amount assumed each day by each animal (uptake in microg animal(-1) d(-1) or ng g-wet weight(-1) d(-1)). The toxicological endpoints investigated deal with the reproductive potential (gonad maturation stage, gonad index and oocyte diameter) and with the regenerative potential (growth and histology). Almost all the compounds exerted some kind of effect at the tested concentrations, however TPT was the most effective in altering both reproductive and regenerative parameters (also at the concentration of few ng L(-1)). The biochemical analyses of testosterone (T) and 17beta-estradiol (E(2)) also showed the ability of the selected compounds to significantly alter endogenous steroid concentrations.

  8. Utilization of Mytilus digestive gland cells for the in vitro screening of potential metabolic disruptors in aquatic invertebrates.

    PubMed

    Balbi, Teresa; Ciacci, Caterina; Grasselli, Elena; Smerilli, Arianna; Voci, Adriana; Canesi, Laura

    2017-01-01

    In vertebrate systems, many endocrine disruptors (EDs) can also interfere with energy and lipid metabolism, thus acting as metabolic disruptors. At the cellular level, these effects are mainly mediated by interactions with nuclear receptors/transcription factors, leading to the modulation of genes involved in lipid homeostasis, as well as by rapid, receptor-independent pathways. Several potential metabolic disruptors are found in aquatic environments. In fish, different EDs have been shown to affect hepatic lipid homeostasis both in vivo and in vitro. However, little information is available in aquatic invertebrates due to our poor knowledge of the regulatory pathways of lipid metabolism. In this work, primary cell cultures from the digestive gland of the bivalve Mytilus galloprovincialis were utilized to investigate the effects of model EDs (bisphenol A (BPA) and perfluorooctane sulphonate (PFOS)) on lipid homeostasis. Both compounds (at 24 and 3h of exposure) increased intracellular lipid and tryglyceride-TAG content, with strongest effects of PFOS at 10(-7)M. Acyl-CoA oxidase activity was unaffected, whereas some changes in the activity of glycolytic, antioxidant/biotransformation enzymes were observed; however, no clear relationship was found with lipid accumulation. Evaluation of mitochondrial membrane potential Δψm and determination of extracellular TAG content indicate that PFOS interferes with mitochondrial function and lipid secretion, whereas BPA mainly affects lipid secretion. Experiments with specific inhibitors showed that activation of PI-3 kinase and extracellularly regulated mitogen-activated protein kinase (ERK MAPK) plays a key role in mediating lipid accumulation. Mussel digestive gland cells represent a simple in vitro model for screening the metabolic effects of EDs in marine invertebrates.

  9. Determination of endocrine-disrupting compounds in drinking waters by fast liquid chromatography-tandem mass spectrometry.

    PubMed

    Magi, Emanuele; Scapolla, Carlo; Di Carro, Marina; Liscio, Camilla

    2010-09-01

    Growing attention has been recently paid to safety of food and drinking water, making necessary the adoption of policies for water sources protection and the development of sensitive and rapid analytical methods to identify micropollutants. Endocrine-disrupting compounds (EDCs) have emerged as a major issue as they alter the functioning of the endocrine system. Since ingestion of EDCs via food is considered the major exposure route, there is a growing interest in understanding EDC fate during drinking water treatment and in monitoring potential contamination of surface waters and groundwaters. In this work, a fast liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the determination of 4-n-nonylphenol (NP), bisphenol A (BPA), estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) in drinking waters. In the literature analytical articles seldom provide details regarding fragmentation pathways. In this paper spectra of the five EDCs in negative ESI were interpreted with the support of accurate mass spectra acquired by a quadrupole time-of-flight instrument; fragmentation pathways were also proposed. The chromatographic separation of EDCs was optimized on a Pinnacle DB Biphenylic column with a water-acetonitrile gradient. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode using bisphenol A-d(16) (BPA-d(16)) as internal standard; calibration curves showed good correlation coefficients (0.9989-0.9997). All figures of merit of the method were satisfactory; limits of detection were in the range 0.2-0.4 ng/ml. The method was applied to the determination of the analytes in waters sampled by polar organic chemical integrative samplers in a drinking water treatment plant. Rather low concentration of BPA, NP and E1 were measured in the inlet, while none of the considered EDCs was detected in the outlet.

  10. Simultaneous determination of four trace level endocrine disrupting compounds in environmental samples by solid-phase microextraction coupled with HPLC.

    PubMed

    Wang, Lingling; Zhang, Zhenzhen; Xu, Xu; Zhang, Danfeng; Wang, Fang; Zhang, Lei

    2015-09-01

    A simple, rapid, sensitive and effective method for the simultaneous determination of four endocrine disrupting compounds (EDCs) (bisphenol A (BPA), bisphenol F (BPF), bisphenol AF (BPAF) and bisphenol AP (BPAP)) in environment water samples based on solid-phase microextraction (SPME) coupled with high performance liquid chromatography (HPLC) was developed. Multi-wall carbon nanotubes (MWCNTs) adsorbents showed a good affinity to the target analytes. These compounds were rapidly extracted within 10 min. Various experimental parameters that could affect the extraction efficiencies had been investigated in detail. Under the optimum conditions, the enrichment factors of the method for the target EDCs were found to be 500. Satisfactory precision and accuracy of the method were obtained in a low concentration range of 2.0-500.0 ng mL(-1). The method detection limits were in the range of 0.10-0.30 ng mL(-1). The high pre-concentration rate and efficiency of the method ensure its successful application in extraction of trace EDCs from large volumes of environmental water samples. The extraction recoveries in real samples ranged from 85.3% to 102.5% with the relative standard deviations (n=5) less than 3.74%.

  11. Occurrence of pharmaceuticals and endocrine disrupting compounds in macroalgaes, bivalves, and fish from coastal areas in Europe.

    PubMed

    Álvarez-Muñoz, D; Rodríguez-Mozaz, S; Maulvault, A L; Tediosi, A; Fernández-Tejedor, M; Van den Heuvel, F; Kotterman, M; Marques, A; Barceló, D

    2015-11-01

    The occurrence and levels of PhACs, Endocrine Disrupting and related Compounds (EDCs) in seafood from potential contaminated areas in Europe has been studied. Macroalgae (Saccharina latissima and Laminaria digitata), bivalves (Mytilus galloprovincialis, Mytilus spp., Chamalea gallina and Crassostrea gigas) and fish (Liza aurata and Platichthys flesus) from Portugal, Spain, Italy, Netherlands, and Norway were analysed following 4 different analytical protocols depending on the organism and target group of contaminants. The results revealed the presence of 4 pharmaceutical compounds in macroalgae samples, 16 in bivalves and 10 in fish. To the best of our knowledge, this is the first time that PhACs have been detected in marine fish and in macroalgae. Besides, this is also the first time that dimetridazole, hydrochlorothiazide and tamsulosin have been detected in biota samples. The highest levels of PhACs corresponded to the psychiatric drug velanfaxine (up to 36.1 ng/g dry weight (dw)) and the antibiotic azithromycin (up to 13.3 ng/g dw) in bivalves from the Po delta (Italy). EDCs were not detected in macroalgae samples, however, the analysis revealed the presence of 10 EDCs in bivalves and 8 in fish. The highest levels corresponded to the organophosphorus flame retardant tris(2-butoxyethyl)phosphate (TBEP) reaching up to 98.4 ng/g dw in mullet fish from the Tagus estuary. Bivalves, in particular mussels, have shown to be good bioindicator organisms for PhACs and fish for EDCs. Taking into consideration the concentrations and frequencies of detection of PhACs and EDCs in the seafood samples analysed, a list of candidates' compounds for priorization in future studies has been proposed.

  12. Occurrence of endocrine disrupting compounds, pharmaceuticals, and personal care products in the Han River (Seoul, South Korea).

    PubMed

    Yoon, Yeomin; Ryu, Jaena; Oh, Jeill; Choi, Byeong-Gyu; Snyder, Shane A

    2010-01-01

    The occurrence of 31 selected endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) in Korean surface waters was investigated. The area was selected since there is a lack of information in the Seoul area on the suspected contamination of rivers by micropollutants, although over 99% of drinking water is produced from surface waters in this area that has a population of approximately 15 million inhabitants. Samples were collected from upstream/downstream and effluent-dominated creeks along the Han River, Seoul (South Korea) and analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). Most target compounds were detected in both the Han River samples (63%) and the effluent-dominated creek samples (79%). Iopromide, atenolol, TCPP, TECP, musk ketone, naproxen, DEET, carbamazepine, caffeine, and benzophenone were frequently detected in both river and creek samples, although the mean concentrations in effluent-dominated creek samples (102 ng/L-3745 ng/L) were significantly higher than those in river samples (56 ng/L-1013 ng/L). However, the steroid hormones 17beta-estradiol, 17alpha-ethynylestradiol, progesterone, and testosterone, were not detected (<1 ng/L) in both the river and creek samples. Numerous target compounds (15) were found to be positively correlated (over 0.8) to the conventional water quality parameters (chemical oxygen demand, biochemical oxygen demand, dissolved organic carbon, and ultraviolet absorbance). Results of this study provide increasing evidence that certain EDCs and PPCPs commonly occur in the Han River as the result of wastewater outfalls.

  13. Occurrence and fate of endocrine disrupting compounds in wastewater treatment plants in Israel and the Palestinian West Bank.

    PubMed

    Dotan, Pniela; Godinger, Tal; Odeh, Wad; Groisman, Ludmila; Al-Khateeb, Nader; Rabbo, Alfred Abed; Tal, Alon; Arnon, Shai

    2016-07-01

    Israel and its Palestinian neighbors constitute a unique venue for evaluating the treatment efficiency and potential environmental risks of endocrine disrupting compounds (EDCs) in wastewater treatment plants (WWTPs), because of their physical proximity yet contrasting societal dynamics. Israel primarily relies on advanced tertiary sewage treatment and recycles over 85% of its treated wastewater, while in the Palestinian Authority (PA), there is only secondary treatment levels at WWTPs and reuse is minimal (<1%). To evaluate the extent of EDC occurrence and treatment efficiency, we conducted four sampling campaigns over two consecutive years, and measured the concentrations of selected EDCs in raw wastewater (WW), treated WW and sludge in six WWTPs in Israel, as well as in two Palestinian plants. Low concentrations of bisphenol A, octylphenol and triclosan measured in the raw WW in the Palestinian WWTPs reflected the relatively modest industrial activity and consumption habits as compared to the westernized consumer patterns in Israel. On the other hand, hormone concentrations in raw WW were higher in the Palestinian WWTPs than those in the Israeli WWTPs, presumably because of a dilution effect associated with a higher water per capita consumption among Israelis. Despite these differences in raw WW concentrations, the removal efficiency in all advanced WWTPs was relatively high when compared to averages reported internationally.

  14. Occurrence of endocrine disrupting compounds in five estuaries of the northwest coast of Spain: Ecological and human health impact.

    PubMed

    Salgueiro-González, N; Turnes-Carou, I; Viñas-Diéguez, L; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D

    2015-07-01

    The occurrence and spatial distribution of alkylphenols (4-tert-octylphenol, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol) and bisphenol A were examined in five estuaries along the Northwest coastal area of Spain. As far as we know, no previous works about this topic could be found in the literature. A total of 98 seawater samples were collected during May 2011-July 2012 and analyzed by a highly sensitive DLLME-LC-MS/MS methodology recently developed. Results indicated nonylphenol was the most ubiquitous compound with maximal concentration of 0.337 μg L(-1) (Ría de Vigo). The environmental quality standards (EQS) established in Directive 2013/39/EU for 4-tert-octylphenol were slightly exceeded in some sampling points. Fishing harbours, water treatment plant and industrial discharges were supposed as the main sources of contamination. Low and medium ecological risk was determined in all estuaries. Possible endocrine effects on biota and population were estimated in terms of estrogenic activity and daily intake respectively, and no risk was found in any case.

  15. Simultaneously photocatalytic treatment of hexavalent chromium (Cr(VI)) and endocrine disrupting compounds (EDCs) using rotating reactor under solar irradiation.

    PubMed

    Kim, Youngji; Joo, Hyunku; Her, Namguk; Yoon, Yeomin; Sohn, Jinsik; Kim, Sungpyo; Yoon, Jaekyung

    2015-05-15

    In this study, simultaneous treatments, reduction of hexavalent chromium (Cr(VI)) and oxidation of endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), 17α-ethinyl estradiol (EE2) and 17β-estradiol (E2), were investigated with a rotating photocatalytic reactor including TiO₂ nanotubes formed on titanium mesh substrates under solar UV irradiation. In the laboratory tests with a rotating type I reactor, synergy effects of the simultaneous photocatalytic reduction and oxidation of inorganic (Cr(VI)) and organic (BPA) pollutants were achieved. Particularly, the concurrent photocatalytic reduction of Cr(VI) and oxidation of BPA was higher under acidic conditions. The enhanced reaction efficiency of both pollutants was attributed to a stronger charge interaction between TiO₂ nanotubes (positive charge) and the anionic form of Cr(VI) (negative charge), which are prevented recombination (electron-hole pair) by the hole scavenging effect of BPA. In the extended outdoor tests with a rotating type II reactor under solar irradiation, the experiment was extended to examine the simultaneous reduction of Cr(VI) in the presence of additional EDCs, such as EE2 and E2 as well as BPA. The findings showed that synergic effect of both photocatalytic reduction and oxidation was confirmed with single-component (Cr(VI) only), two-components (Cr(VI)/BPA, Cr(VI)/EE2, and Cr(VI)/E2), and four-components (Cr(VI)/BPA/EE2/E2) under various solar irradiation conditions.

  16. Simultaneous determination of selected endocrine disrupter compounds in wastewater samples in ultra trace levels using HPLC-ES-MS/MS.

    PubMed

    Komesli, Okan Tarık; Bakırdere, Sezgin; Bayören, Ceren; Gökçay, Celal Ferdi

    2012-08-01

    An analytical procedure for the simultaneous determination of six selected endocrine disrupter compounds (EDCs: diltiazem, progesterone, benzyl butyl phthalate (BBP), estrone, carbamazepine (Cbz), acetaminophen) was developed by liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ES-MS/MS). All of the parameters for HPLC and ES-MS/MS systems including mobile phase composition, flow rate, and sample injection volume were optimized to obtain not only the best separation of species interested but also low detection limits. Reverse phase chromatography coupled to ES-MS/MS was used for the separation and detection of EDCs. Formic acid (0.10% ) and 5.0 mM ammonium formate were selected as mobile phase composition in gradient elution. Detection limits for diltiazem, progesterone, BBP, estrone, Cbz, and acetaminophen were found to be 0.13, 0.12, 0.04, 0.13, 0.12, and 0.05 ng/mL, respectively. Influent and effluents from three different wastewater treatment plants located in Ankara, i.e., rotating flat-sheet membrane unit, pilot type flat-sheet membrane unit located at METU Campus and samples from Ankara central wastewater treatment plant were analyzed for their EDCs contents under the optimum conditions.

  17. Polymer-immobilized ready-to-use recombinant yeast assays for the detection of endocrine disruptive compounds.

    PubMed

    Bittner, Michal; Jarque, Sergio; Hilscherová, Klára

    2015-08-01

    Recombinant yeast assays (RYAs) constitute a suitable tool for the environmental monitoring of compounds with endocrine disrupting activities, notably estrogenicity and androgenicity. Conventional procedures require yeast reconstitution from frozen stock, which usually takes several days and demands additional equipment. With the aim of applying such assays to field studies and making them more accessible to less well-equipped laboratories, we have optimized RYA by the immobilization of Saccharomyces cerevisiae cells in three different polymer matrices - gelatin, Bacto agar, and Yeast Extract Peptone Dextrose agar - to obtain a ready-to-use version for the fast assessment of estrogenic and androgenic potencies of compounds and environmental samples. Among the three matrices, gelatin showed the best results for both testosterone (androgen receptor yeast strain; AR-RYA) and 17β-estradiol (estrogen receptor yeast strain; ER-RYA). AR-RYA was characterized by a lowest observed effect concentration (LOEC), EC50 and induction factor (IF) of 1nM, 2.2nM and 51, respectively. The values characterizing ER-RYA were 0.4nM, 1.8nM, and 63, respectively. Gelatin immobilization retained yeast viability and sensitivity for more than 90d of storage at 4°C. The use of the immobilized yeast reduced the assay duration to only 3h without necessity of sterile conditions. Because immobilized RYA can be performed either in multiwell microplates or glass tubes, it allows multiple samples to be tested at once, and easy adaptation to existing portable devices for direct in-field applications.

  18. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound.

    PubMed

    Jorgenson, Z G; Buhl, K; Bartell, S E; Schoenfuss, H L

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio

  19. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound

    USGS Publications Warehouse

    Jorgenson, Zachary G.; Buhl, Kevin J.; Bartell, Stephen E.; Schoenfuss, Heiko L.

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption—as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration—than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered

  20. Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

    USGS Publications Warehouse

    Erickson, Melinda L.

    2012-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

  1. The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

    PubMed

    Goldstein, R S; Mayor, G H; Gingerich, R L; Hook, J B; Rosenbaum, R W; Bond, J T

    1983-07-01

    Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

  2. Endocrine-active chemicals in mammary cancer causation and prevention.

    PubMed

    Jenkins, Sarah; Betancourt, Angela M; Wang, Jun; Lamartiniere, Coral A

    2012-04-01

    Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'.

  3. CHANGES IN GENE AND PROTEIN EXPRESSION IN ZEBRAFISH (DANIO RERIO) FOLLOWING EXPOSURE TO ENVIRONMENTALLY-RELEVANT ENDOCRINE DISRUPTING COMPOUNDS (EDCS)

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs) are increasingly being reported in waterways worldwide and have been shown to affect fish species by disrupting numerous aspects of development, behavior, reproduction, and survival. Furthermore, new data have suggested that the reduced repr...

  4. Airborne particulate endocrine disrupting compounds in China: Compositions, size distributions and seasonal variations of phthalate esters and bisphenol A

    NASA Astrophysics Data System (ADS)

    Li, Jianjun; Wang, Gehui

    2015-03-01

    Phthalate esters and bisphenol A (BPA) are endocrine disrupting compounds (EDCs) and ubiquitously occur in the environment. In the past decade we have characterized atmospheric organic aerosols from various environments (e.g., urban, rural, mountain and marine) of East Asia on a molecular level, but not investigated EDCs in the samples. In the current study we re-analyzed our database for concentrations, compositions and size distributions of phthalates and BPA and compared with those in the literature to improve the understanding on air pollution status in China. Our results showed that airborne particulate phthalates and BPA are 63-1162 ng m- 3 and 1.0-20 ng m- 3 in the urban regions in China, respectively, being one to two orders of magnitude higher than those in the developed countries. Among the detected phthalates in Chinese urban areas, bis(2-ethylhexyl) phthalate (BEHP) is the predominant congener, contributing to 23-79% (ave. 53 ± 15%) of the total phthalates. Concentrations of phthalates and bisphenol A in Shanghai and Xi'an (two mega-cities in China) in 2009 were 3-84% lower than those in 2003, probably indicating a positive effect of the government's air pollution control in the recent years. Phthalates are higher in summer than in winter, because they are not chemically bonded to the polymeric matrix and more easily evaporate into the air under higher temperature conditions. Based on the size distribution observation, we found that diisobutyl and dibutyl phthalates mainly exist in coarse particles because of high volatilities, in contrast to BEHP and BPA, which are dominant in fine particles due to less volatility. Our results also indicate that BPA is mostly derived from the open burning of solid waste while phthalates are derived from both direct evaporation from the matrix and solid waste combustion.

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

    SciTech Connect

    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 nitrogen

  6. Biological Profiling of Endocrine Related Effects of Chemicals in ToxCast

    EPA Science Inventory

    The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

  7. Biological Profiling of Endocrine Related Effects of Chemicals Using ToxCast

    EPA Science Inventory

    The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

  8. DETERMINING INDICATORS OF EXPOSURE AND EFFECTS FOR ENDOCRINE DISRUPTING CHEMICALS (EDCS): AN OVERVIEW.

    EPA Science Inventory

    Endocrine disruptors are characterized by their influence on animal endocrine systems resulting in reproductive, developmental, neurological, and immune dysfunction. The purpose of this overview is to provide the reader with a sense of the activities within the U.S. Environmental...

  9. 76 FR 49473 - Petition to Maximize Practical Utility of List 1 Chemicals Screened Through EPA's Endocrine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-10

    ... AGENCY Petition to Maximize Practical Utility of List 1 Chemicals Screened Through EPA's Endocrine... decisions on data received in response to the test orders issued under the Endocrine Disruptor Screening...'' system, which means EPA will not know your identity or contact information unless you provide it in...

  10. Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals

    EPA Science Inventory

    Over the past 20 years, an increased focus on detecting environmental chemicals posing a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. EPA Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP, whic...

  11. The gonadotropin releasing hormone (GnRH)-like molecule in prosobranch Patella caerulea: potential biomarker of endocrine-disrupting compounds in marine environments.

    PubMed

    De Lisa, Emilia; Carella, Francesca; De Vico, Gionata; Di Cosmo, Anna

    2013-02-01

    It has been reported that endocrine disrupter compounds (EDCs) interfere with the endocrine system, mimicking the action of sex steroid hormones in different species of mollusks. Prosobranchs are frequently used as a reliable bioindicator to evaluate EDC exposure. In this article, we evaluate the effects of the xenoestrogen 4-n-nonylphenol (NP) in the prosobranch gastropod Patella caerulea, which exhibits protandrous hermaphroditism as its reproductive strategy. We isolated a partial sequence of a GnRH-like molecule from the gonads of Patella caerulea. The deduced amino acid sequence is highly homologous to that reported for the Lottia gigantea GnRH. Patella caerulea GnRH (pGnRH) mRNA expression is widespread in both male and female germ lines during gametogenesis. We suggest pGnRH as a novel biomarker for the early assessment of presence of EDCs and monitoring short and long-term impacts on Patella caerulea community structure.

  12. Toxicogenomics to Evaluate Endocrine Disrupting Effects of Environmental Chemicals Using the Zebrafish Model.

    PubMed

    Caballero-Gallardo, Karina; Olivero-Verbel, Jesus; Freeman, Jennifer L

    2016-12-01

    The extent of our knowledge on the number of chemical compounds related to anthropogenic activities that can cause damage to the environment and to organisms is increasing. Endocrine disrupting chemicals (EDCs) are one group of potentially hazardous substances that include natural and synthetic chemicals and have the ability to mimic endogenous hormones, interfering with their biosynthesis, metabolism, and normal functions. Adverse effects associated with EDC exposure have been documented in aquatic biota and there is widespread interest in the characterization and understanding of their modes of action. Fish are considered one of the primary risk organisms for EDCs. Zebrafish (Danio rerio) are increasingly used as an animal model to study the effects of endocrine disruptors, due to their advantages compared to other model organisms. One approach to assess the toxicity of a compound is to identify those patterns of gene expression found in a tissue or organ exposed to particular classes of chemicals, through new technologies in genomics (toxicogenomics), such as microarrays or whole-genome sequencing. Application of these technologies permit the quantitative analysis of thousands of gene expression changes simultaneously in a single experiment and offer the opportunity to use transcript profiling as a tool to predict toxic outcomes of exposure to particular compounds. The application of toxicogenomic tools for identification of chemicals with endocrine disrupting capacity using the zebrafish model system is reviewed.

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

    PubMed

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-03-25

    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.

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

    PubMed Central

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-01-01

    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. PMID:27023588

  15. Endocrine Disruption and Human Prostate Cancer

    DTIC Science & Technology

    2008-03-01

    described in Task 1, was to expose pregnant female rats to vinclozolin and test if the inductive and instructive properties of the prostate stroma is...ethane dimethane sulphonate ) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind Health...BPH Benign prostate hyperplasia cDNA Complementary deoxyribonucleic acid DP Dorsal prostate EDC Endocrine disruptor E Estrogen FgF10

  16. Occurrence, fate and environmental risk assessment of endocrine disrupting compounds at the wastewater treatment works in Pietermaritzburg (South Africa).

    PubMed

    Manickum, T; John, W

    2014-01-15

    Steroid hormone Endocrine Disrupting Compounds (EDCs) (natural estrogens (17-β-estradiol (E2), estrone (E1), estriol (E3), synthetic estrogen (17-α-ethinylestradiol (EE2)), natural androgen (testosterone) (tes) and natural progestogen (progesterone) (pro)) at an activated sludge wastewater works (WWW), were quantitated using Enzyme-linked immunosorbent assay (ELISA). The steroid hormone profile in the adjacent surface water was also determined. Pro was the most abundant (41%, 408 ng/L) in the influent, followed by tes (35%, 343 ng/L) and E2 (12%, 119 ng/L). E1 was the most abundant (35%, 23 ng/L) in effluent, followed by E2 (30%, 20 ng/L) and tes (17%, 11 ng/L). Chemical removal efficiencies of the steroid hormones by the WWW averaged 92%. High removal efficiency was observed for pro (98% ± 2) and tes (96% ± 1), compared to natural (72-100%) and synthetic estrogen (90% ± 3), with biodegradation being the major removal route for pro and tes. The lowest removal for E2 is in spring (65%), and maximum removal is in winter (95%). Natural (E2, E1) and synthetic estrogen (EE2) were major contributors to influent (E2 = 69%) and effluent (E2 = 73%) estrogenic potency. The estrogenic potency removal averaged 85% (range: 73-100). Risk assessment of the steroid hormones present in wastewater effluent, and surface water, indicated that EE2 and E2 pose the highest risk to human health and fish. EE2 was found to be much more resistant to biodegradation, compared to E2, in surface water. Estrone, as the breakdown product of E2 and EE2 in wastewater, appears to be suitable as an indicator of EDCs. The study suggests that a battery of tests: quantitative chemical assay, bioassay for estrogenic activity and risk assessment methods, collectively, are preferred in order to make meaningful, accurate conclusions regarding potential adverse effects of EDCs present in treated wastewater effluent or surface water, to the aquatic environment, human health, and wildlife systems.

  17. Performance of calcium peroxide for removal of endocrine-disrupting compounds in waste activated sludge and promotion of sludge solubilization.

    PubMed

    Zhang, Ai; Wang, Jie; Li, Yongmei

    2015-03-15

    Removal of six phenolic endocrine disrupting compounds (EDCs) (estrone, 17β-estradiol, 17α-ethinylestradiol, estriol, bisphenol A, and 4-nonylphenols) from waste activated sludge (WAS) was investigated using calcium peroxide (CaO2) oxidation. Effects of initial pH and CaO2 dosage were investigated. The impacts of CaO2 treatment on sludge solubilization and anaerobic digestion were also evaluated. Specifically, the role of reactive oxygen species (ROS) in EDC degradation during CaO2 oxidation was tested. Effects of 6 metal ions contained in the sludge matrix on EDC degradation were also evaluated. The results showed that CaO2 treatment can be a promising technology for EDC removal and facilitating sludge reuse. The EDC removal efficiencies increased with the increase in CaO2 dosage. At CaO2 doses of more than 0.34 g per gram of total solid (g g(-1) TS), more than 50% of EDCs were removed in a wide pH range of 2-12. Higher removal efficiencies were achieved at initial pH values of 12 and 2. The products of EDCs during CaO2 oxidation had less estrogenic activity than the originals. Under the conditions of neutral pH and CaO2 dosage = 0.34 g g(-1) TS, the sludge solubilization can be improved by increasing the soluble total organic carbon (STOC) and volatile suspended solids (VSS) reduction by 25% and 27% in 7 d, respectively; the volatile fatty acid (VFA) production was enhanced by 96% in the 15 d following anaerobic digestion. The ROS released by CaO2 are the main factors contributing to EDC removal, among which, hydroxyl radicals (OH) play the most important role. Metal ions contained in the sludge matrix also affected EDC removal. For most cases, Fe, Cu, and Zn had positive effects; Mn and Ag had negative effects; and Mg had an insignificant effect on EDC removal.

  18. Lifestyle behaviors associated with exposures to endocrine disruptors

    PubMed Central

    Martina, Camille A.; Weiss, Bernard; Swan, Shanna H.

    2013-01-01

    Identifying and characterizing sources of exposure to phthalates and bisphenol A (BPA) have proved challenging due to the presence of multiple co-exposures resulting from a wide variety of home environments and lifestyles. We hypothesized that the consistent lifestyle of an Old Order Mennonite (OOM) community would provide an ideal setting in which to characterize sources of exposure to BPA and phthalates. We obtained urine samples from ten mid-term pregnant OOM women (ages-21–39) to determine concentrations of 9 phthalate metabolites and BPA and collected a self-reported survey of participants' household environment, product use, and lifestyle within a 48-h period prior to urine collection. We compared their metabolite concentrations to pregnant women included in the National Health and Nutrition Examination Survey (NHANES 2007–2008). Although OOM participants reported some use of plastic and fragranced household products, concentrations of metabolites were lower and significantly less for BPA (p = 0.002) and phthalate metabolites MEHP (p = 0.0215), MiBP (p = 0.0020) and MEP (p = 0.021), when compared to NHANES pregnant women. Levels of other phthalate metabolites were also lower in this population. Our data suggest three practices that may contribute to these lower levels: (1) consuming mostly homegrown produce (ingestion), (2) no cosmetics and limited use of personal care products, and (3) transportation primarily by sources other than automobiles. PMID:22739065

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

    EPA Pesticide Factsheets

    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.

  20. Lifestyle behaviors associated with exposures to endocrine disruptors.

    PubMed

    Martina, Camille A; Weiss, Bernard; Swan, Shanna H

    2012-12-01

    Identifying and characterizing sources of exposure to phthalates and bisphenol A (BPA) have proved challenging due to the presence of multiple co-exposures resulting from a wide variety of home environments and lifestyles. We hypothesized that the consistent lifestyle of an Old Order Mennonite (OOM) community would provide an ideal setting in which to characterize sources of exposure to BPA and phthalates. We obtained urine samples from ten mid-term pregnant OOM women (ages-21-39) to determine concentrations of 9 phthalate metabolites and BPA and collected a self-reported survey of participants' household environment, product use, and lifestyle within a 48-h period prior to urine collection. We compared their metabolite concentrations to pregnant women included in the National Health and Nutrition Examination Survey (NHANES 2007-2008). Although OOM participants reported some use of plastic and fragranced household products, concentrations of metabolites were lower and significantly less for BPA (p=0.002) and phthalate metabolites MEHP (p=0.0215), MiBP (p=0.0020) and MEP (p=0.021), when compared to NHANES pregnant women. Levels of other phthalate metabolites were also lower in this population. Our data suggest three practices that may contribute to these lower levels: (1) consuming mostly homegrown produce (ingestion), (2) no cosmetics and limited use of personal care products, and (3) transportation primarily by sources other than automobiles.

  1. In vivo and in vitro mixture modeling of endocrine disruptors

    EPA Science Inventory

    Humans, fish and wildlife are exposed to more than one chemical at a time. There is concern over the potential effects of exposure to mixtures of EDs. We have conducted invitro and in vivo studies to determine how EDs in mixtures interact. Our in vivo studies have examined the ef...

  2. Sex Differentiation as a Target of Endocrine Disrupting Compounds in Early Life Stage Fathead Minnows (Pimephales promelas)

    EPA Science Inventory

    The occurrence of endocrine disrupting chemicals (EDCs) in concentrated animal feed operation (CAFO) waste, and the potential effects of these chemicals on aquatic ecosystems have been of recent concern. There is evidence that exposure to EDCs during enhanced windows of sensitiv...

  3. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells

    PubMed Central

    Saito, Ryuta; Terasaki, Natsuko; Yamazaki, Makoto; Masutomi, Naoya; Tsutsui, Naohisa; Okamoto, Masahiro

    2016-01-01

    Adrenal toxicity is one of the major concerns in drug development. To quantitatively understand the effect of endocrine-active compounds on adrenal steroidogenesis and to assess the human adrenal toxicity of novel pharmaceutical drugs, we developed a mathematical model of steroidogenesis in human adrenocortical carcinoma NCI-H295R cells. The model includes cellular proliferation, intracellular cholesterol translocation, diffusional transport of steroids, and metabolic pathways of adrenal steroidogenesis, which serially involve steroidogenic proteins and enzymes such as StAR, CYP11A1, CYP17A1, HSD3B2, CYP21A2, CYP11B1, CYP11B2, HSD17B3, and CYP19A1. It was reconstructed in an experimental dynamics of cholesterol and 14 steroids from an in vitro steroidogenesis assay using NCI-H295R cells. Results of dynamic sensitivity analysis suggested that HSD3B2 plays the most important role in the metabolic balance of adrenal steroidogenesis. Based on differential metabolic profiling of 12 steroid hormones and 11 adrenal toxic compounds, we could estimate which steroidogenic enzymes were affected in this mathematical model. In terms of adrenal steroidogenic inhibitors, the predicted action sites were approximately matched to reported target enzymes. Thus, our computer-aided system based on systems biological approach may be useful to understand the mechanism of action of endocrine-active compounds and to assess the human adrenal toxicity of novel pharmaceutical drugs. PMID:27057163

  4. Evaluation of the Presence of Endocrine-Disrupting Compounds in Dissolved and Solid Wastewater Treatment Plant Samples of Gran Canaria Island (Spain)

    PubMed Central

    Vega-Morales, T.; Sosa-Ferrera, Z.; Santana-Rodríguez, J. J.

    2013-01-01

    Liquid and solid samples from two wastewater treatment plants (WWTPs) on Gran Canaria Island (Spain) have been tested for the presence of compounds with endocrine-disrupting properties. The selected degradation stages were sampled bimonthly from each WWTP over the 12-month period from July 2010 to July 2011. The analytical methods used for the determination of the endocrine-disrupting compounds (EDCs) were based on on-line solid phase extraction, microwave-assisted extraction (MAE), and ultrasonic-assisted extraction (UAE) coupled to UHPLC-MS/MS. All of the hyphenated methodologies employed in this work showed good recoveries (72–104%) and sensitivities, with LODs lower than 7.0 ng L−1 and 6.3 ng g−1 for the dissolved and solid fractions, respectively. We have also evaluated the estrogenicity of the samples in terms of their estradiol equivalent concentrations (EEQs). The chemical analysis of the selected EDCs revealed fairly low concentrations for both natural and synthetic oestrogens, alkylphenolic compounds, and bisphenol-A in each of the dissolved, particulate, and sludge samples (ng L−1 or ng g−1). However, the estimated estrogenic activity indicated that the majority of samples could represent an important environmental risk, clearly surpassing the threshold to exert deleterious consequences on living beings. PMID:24163820

  5. Endocrine glands

    MedlinePlus Videos and Cool Tools

    ... and nervous systems work very closely together. The brain continuously sends instructions to the endocrine system, and ... master switchboard because it's the part of the brain that controls the endocrine system. The pituitary gland, ...

  6. Vitellogenin and zona radiata proteins as biomarkers of endocrine disruption in peregrine falcon (Falco peregrinus).

    PubMed

    Jiménez, Begoña; Mori, Gabriele; Concejero, Miguel A; Merino, Rubén; Casini, Silvia; Fossi, María Cristina

    2007-04-01

    The aim of this study was to test a specific method for the detection of Vitellogenin (Vtg) and Zona Radiata Proteins (Zrp) in plasma from peregrine falcon (Falco peregrinus) as specific biomarkers for the evaluation of the effects of endocrine disruptors. The method was assayed with different peregrine falcon individuals (including mature and immature birds of both sexes) from a Spanish population being studied in terms of their contamination with organochlorine compounds with endocrine disrupting properties. This study shows that mouse anti bird Vtg monoclonal antibody ND3C3 (Biosense) seems to be the most specific antibody in binding plasmatic lipoproteins in peregrine falcon when compared to other anti Vtg antibodies. Rabbit anti salmon Zrp polyclonal antibodies O146 (Biosense) show cross-reactivity with Zrp in the samples studied. These preliminary results confirm the applicability of both of these diagnostic tools assayed (induction of Vtg and Zrp) in detecting exposure to Endocrine Disrupting Chemicals (EDCs) in this species. The increase of Vtg and Zrp detected in male specimens suggest a potential hazard to EDCs in the peregrine falcon which represents a species still affected by organochlorine compounds, and in particular those with estrogenic activity.

  7. Impedance Measurements as a Tool for the Detection of Endocrine Disrupting Chemicals

    DTIC Science & Technology

    2007-11-02

    endocrine disruptors on human health has created a need for screening systems to detect xenoestrogens, a diverse group of chemicals that mimic...Impedance Measurements as a Tool for the Detection of Endocrine Disrupting Chemicals V. Sacks, J. Rishpon* Department of Molecular...sensitive and amenable to use on-site, providing an efficient and economic tool for measuring minuscule amounts of endocrine disrupting chemicals

  8. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours.

    PubMed

    Patisaul, Heather B

    2016-07-08

    A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.

  9. [The concept of endocrine disruption and human health].

    PubMed

    Cravedi, Jean-Pierre; Zalko, Daniel; Savouret, Jean-François; Menuet, Arnaud; Jégou, Bernard

    2007-02-01

    In Europe, endocrine disruptors (EDs) have been defined as substances foreign to the body that have deleterious effects on the individuals or their descendants, due to changes in endocrine function. In the United States, EDs have been described as exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of the natural ligands responsible for maintaining homeostasis and regulating body development. These two definitions are complementary, but both indicate that the effects induced by EDs probably involve mechanisms relating in some way to hormonal homeostasis and action. EDs are generally described as substances with anti-oestrogenic, oestrogenic, anti-androgenic or androgenic effects. More recently, other targets have been evidenced such as the thyroid and immune system. Many different EDs are present in the various compartments of the environment (air, water and land) and in foods (of plant and animal origin). They may originate from food packaging, combustion products, plant health treatments, detergents and the chemical industry in general. In addition to the potential effects of these compounds on adults, the sensitivity of embryos and fetuses to many of the xenobiotic compounds likely to cross the placenta has raised considerable concern and led to major research efforts. With the exception of the clearly established links between diethylstilbestrol, reproductive health abnormalities and cancers, very little is known for certain about the effects of EDs on human health. Given the lack of available data, current concerns about the possible involvement of EDs in the increase in the incidence of breast cancer, and possibly of endometriosis and early puberty in girls, remain hypothetical. Conversely, the deterioration in male reproductive health is at the heart of preoccupations and progress in analyses of the relationship between EDs and human health. This literature review aims to describe the current

  10. Determination of acidic pharmaceuticals and potential endocrine disrupting compounds in wastewaters and spring waters by selective elution and analysis by gas chromatography-mass spectrometry.

    PubMed

    Gibson, Richard; Becerril-Bravo, Elías; Silva-Castro, Vanessa; Jiménez, Blanca

    2007-10-26

    Although the trend in development of analytical methods for emerging contaminants is towards reduced sample preparation and increased detector selectivity, there are still benefits from removal of matrix material during sample preparation. This paper describes a simple method for acidic pharmaceuticals and a range of potential endocrine disrupting compounds in untreated wastewaters and spring waters. It is based on separation of the two classes during elution from the extraction cartridge with final analysis by gas chromatography-mass spectrometry. 3,4-D was used as the recovery standard for the acids while 4-n-nonylphenol and [2H4]estrone were used for the endocrine disrupters; mean recoveries varied between 89% and 111%. The method was also extensively validated by fortification with the target compounds. Recoveries of acids were from 68% to 97% with relative standard deviations generally less than 10% and recoveries of endocrine disrupters were 68-109% with relative standard deviations less than 20%. Detection limits varied from 0.005 to 1 ng/L in spring water, and from 0.5 to 100 ng/L in untreated wastewater. Concentrations of the analytes in the wastewater ranged from 0.018 to 22.4 microg/L. Values were comparable to reported data, although concentrations were generally relatively high, probably because of a lack of treatment. Triclosan, phthalates, estrone, 17beta-estradiol, ibuprofen, and naproxen were present in the spring water from aquifers recharged indirectly with this wastewater after its use for irrigation; concentrations ranged from 0.01 to 25.0 ng/L. The much lower concentrations compared to wastewater indicate effective removal processes on passage through the soil and subsoil.

  11. Classical Nuclear Hormone Receptor Activity as a Mediator of Complex Concentration Response Relationships for Endocrine Active Compounds

    PubMed Central

    Cookman, Clifford J.; Belcher, Scott M.

    2014-01-01

    Nonmonotonic concentration response relationships are frequently observed for endocrine active ligands that act via nuclear receptors. The curve of best fit for nonmonotonic concentration response relationships are often inverted U-shaped with effects at intermediate concentrations that are different from effects at higher or lower concentrations. Cytotoxicity is a major mode of action responsible for inverted U-shaped concentration response relationships. However, evidence suggests that ligand selectivity, activation of multiple molecular targets, concerted regulation of multiple opposing endpoints, and multiple ligand binding sites within nuclear receptors also contribute to nonmonotonic concentration response relationships of endocrine active ligands. This review reports the current understanding of mechanisms involved in classical nuclear receptor mediated nonmonotonic concentration response relationships with a focus on studies published between 2012 and 2014. PMID:25299165

  12. Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) in the aquatic environment: implications for the drinking water industry and global environmental health.

    PubMed

    Rahman, M F; Yanful, E K; Jasim, S Y

    2009-06-01

    Endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) are a group of chemical compounds with diverse physical and chemical properties. Recent studies have indicated undesired effects of EDCs and PPCPs at their reported trace concentrations (ng l(-1) to microg l(-1)). This paper reviews the current knowledge on the sources, properties, occurrence and health impacts of EDCs and PPCPs, and their removal from drinking water using ozonation and ozone/hydrogen peroxide-based advanced oxidation. The paper also examines the potential threats posed by these chemicals to drinking water and public health. While these compounds are known to have adverse effects on ecosystem health, notably in the fish population, a similar link is yet to be established between ingestion of these compounds through drinking water and human health. In addition, data on the effectiveness of existing methods for the removal of these compounds are not conclusive. Further studies are required to characterize risks, and also to evaluate and optimize existing removal processes. Also concerted international effort is urgent to cut down the risk of exposure and restrain the production and marketing of toxic chemicals.

  13. Endocrine Diseases

    MedlinePlus

    ... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  14. EDCs DataBank: 3D-Structure database of endocrine disrupting chemicals.

    PubMed

    Montes-Grajales, Diana; Olivero-Verbel, Jesus

    2015-01-02

    Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system, frequently found in everyday products and epidemiologically associated with several diseases. The purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of information from different databases and text mining tools, useful for almost any kind of research regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors, through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several formats. This database is freely available at http://edcs.unicartagena.edu.co.

  15. Multiresidue analysis of endocrine-disrupting compounds and perfluorinated sulfates and carboxylic acids in sediments by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Cavaliere, Chiara; Capriotti, Anna Laura; Ferraris, Francesca; Foglia, Patrizia; Samperi, Roberto; Ventura, Salvatore; Laganà, Aldo

    2016-03-18

    A multiresidue analytical method for the determination of 11 perfluorinated compounds and 22 endocrine-disrupting compounds (ECDs) including 13 natural and synthetic estrogens (free and conjugated forms), 2 alkylphenols, 1 plasticiser, 2 UV-filters, 1 antimicrobial, and 2 organophosphorus compounds in sediments has been developed. Ultrasound-assisted extraction followed by solid phase extraction (SPE) with graphitized carbon black (GCB) cartridge as clean-up step were used. The extraction process yield was optimized in terms of solvent composition. Then, a 3(2) experimental design was used to optimize solvent volume and sonication time by response surface methodology, which simplifies the optimization procedure. The final extract was analyzed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The optimized sample preparation method is simple and robust, and allows recovery of ECDs belonging to different classes in a complex matrix such as sediment. The use of GCB for SPE allowed to obtain with a single clean-up procedure excellent recoveries ranging between 75 and 110% (relative standard deviation <16%). The developed methodology has been successfully applied to the analysis of ECDs in sediments from different rivers and lakes of the Lazio Region (Italy). These analyses have shown the ubiquitous presence of chloro-substituted organophosphorus flame retardants and bisphenol A, while other analyzed compounds were occasionally found at concentration between the limit of detection and quantification.

  16. Optimized quinoline amino alcohols as disruptors and dispersal agents of Vibrio cholerae biofilms

    PubMed Central

    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

  17. Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

    PubMed Central

    Auger, Jacques; Le Denmat, Dominique; Berges, Raymond; Doridot, Ludivine; Salmon, Benjamin; Canivenc-Lavier, Marie Chantal; Eustache, Florence

    2013-01-01

    Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D–5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans. PMID:23926155

  18. Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

    PubMed

    Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

    2014-09-01

    Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive.

  19. Probing the binding of an endocrine disrupting compound-Bisphenol F to human serum albumin: Insights into the interactions of harmful chemicals with functional biomacromolecules

    NASA Astrophysics Data System (ADS)

    Pan, Fang; Xu, Tianci; Yang, Lijun; Jiang, Xiaoqing; Zhang, Lei

    2014-11-01

    Bisphenol F (BPF) as an endocrine disrupting compounds (EDCs) pollutant in the environment poses a great threat to human health. To evaluate the toxicity of BPF at the protein level, the effects of BPF on human serum albumin (HSA) were investigated at three temperatures 283, 298, and 308 K by multiple spectroscopic techniques. The experimental results showed that BPF effectively quenched the intrinsic fluorescence of HSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and the binding subdomain were measured, and indicated that BPF could spontaneously bind with HSA on subdomain IIA through H-bond and van der Waals interactions. Furthermore, the conformation of HSA was demonstrably changed in the presence of BPF. The work provides accurate and full basic data for clarifying the binding mechanisms of BPF with HSA in vivo and is helpful for understanding its effect on protein function during its transportation and distribution in blood.

  20. Endocrine disrupting compounds reduction and water quality improvement in reclaimed municipal wastewater: A field-scale study along Jialu River in North China.

    PubMed

    Sun, Jie; Ji, Xiaowen; Zhang, Rui; Huang, Yu; Liang, Ying; Du, Jinhui; Xie, Xianchuan; Li, Aimin

    2016-08-01

    Several ecological restoration projects have been constructed along urban rivers in North China to purify reclaimed municipal wastewater and improve the water quality of urban rivers. These projects attempt to address several environmental issues, including treating water contamination that is not fully remediated through standard wastewater treatment. This study investigated the efficiency of reducing endocrine disrupting compounds (EDCs) and estrogenic activity in reclaimed municipal wastewater along an 18.5 km field-scale ecological restoration project in Jialu River. The river only receives reclaimed municipal wastewater without natural effluent in North China. Data show that the chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) of reclaimed municipal effluent improved when compared to the Chinese surface water standard, and natural estrogens, such as estrone (E1) and estradiol (E2), were effectively removed during ecological restoration purification processes. The estradiol activity based on measured EDCs concentrations (ΣEEQEDC) was less than 0.01 ng/L after the ecological purification of restoration river; however, synthetic endocrine disrupting compounds in reclaimed municipal wastewater, such as octylphenol (OP), bisphenol A (BPA), and dibutyl phthalate (DBP), were difficult to eliminate. The bioassays of MDA-kb2 cells and recombinant yeast in vitro showed no direct androgen response and estrogen effect in reclaimed municipal effluent after the purification processes. However, a chorionic long-term (21d) exposure in vivo test showed that exposure to the reclaimed municipal effluents, even after river purification, still significantly induced yolk protein vitellogenin (Vtg) in male zebrafish, leading to abnormal expression of testosterone (T) and E2. This indicates continued potent estrogenic activity to aquatic organisms, even after treatment and purification.

  1. The role of phytoplankton composition, biomass and cell volume in accumulation and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The Gulf of Gdansk).

    PubMed

    Staniszewska, Marta; Nehring, Iga; Zgrundo, Aleksandra

    2015-12-01

    Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among others phytoplankton. This paper describes BPA, OP and NP concentrations in phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011-2012. The assays of BPA, OP and NP in samples were performed using HPLC with fluorescence detection. The concentrations of BPA, the most commonly used of the three compounds, were over ten times higher than OP and NP concentrations. The concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk depended on anthropogenic factors and on phytoplankton properties (species composition, biomass, volume). An increase in phytoplankton biomass did not always result in an increase of BPA, OP and NP concentrations. However, the load of the studied EDCs accumulated in phytoplankton biomass increase with a rise of biomass. An increase in BPA, OP and NP concentrations was effected by biomass growth and the proportions ofciliates, dinoflagellates, diatoms and green algae. A strong positive correlation between OP and NP concentrations and negative correlation between BPA concentrations and biomass of organisms with cells measuring <1000 μm(3) in volume results from the differing properties of these compounds.

  2. Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore's marine environment: influence of hydrodynamics and physical-chemical properties.

    PubMed

    Bayen, Stéphane; Zhang, Hui; Desai, Malan Manish; Ooi, Seng Keat; Kelly, Barry C

    2013-11-01

    The fate and exposure risks of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in marine environments are not well-understood. In this study we developed a multi-residue analytical method for quantifying concentrations of forty target compounds in seawater from Singapore. Analyses of samples (n = 24) from eight sites showed the occurrence of several compounds, including gemfibrozil (<0.09-19.8 ng/L), triclosan (<0.55-10.5 ng/L), carbamazepine (<0.28-10.9 ng/L) and ibuprofen (<2.2-9.1 ng/L). A 3D hydrodynamic model for Singapore was used to predict residence time (tR). Principal Components Analysis revealed a strong relationship between tR and contaminant concentrations. While source emissions are undoubtedly important, proximate distance to a wastewater treatment plant had little influence on concentrations. The site with the greatest tR, which exhibited the highest concentrations, is adjacent to Singapore's largest protected wetland reserve. The results highlight an important linkage between hydrodynamic behavior and contaminant exposure risks in complex coastal marine ecosystems.

  3. Endocrine System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Endocrine System KidsHealth > For Teens > Endocrine System A A A ... is called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  4. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  5. AB159. Endocrine disrupting chemicals: toxicological risk assessment in vivo and in vitro models

    PubMed Central

    Thuy, Vo Thi Bich; Nguyen Binh, Le Thi; Phuong Oanh, Kim Thi; Van Hai, Nong

    2015-01-01

    In several studies, scientists asserted that many of endocrine disruptors (EDs), which have been involved in developmental, reproductive, neural, immunological, and other problems in wildlife and laboratory animals. Some environmental EDs, such as di-(2-ethylhexyl) phthalate (DEHP), flutamide (Flu), parabens, are used in many products in life and environment. However, the adverse effects caused by EDs can be temporary or permanent and the mechanism(s) through which these chemicals elicit their effects on biological systems of human and animal health is not clearly understood. The specific aim of this study is to evaluate endocrine disrupting chemicals-induced impact on the male or female reproductive system. An attempt is also made to elucidate the impact of these EDs in an in vitro model, i.e., GH3 rat pituitary cell line. A great deal of work has been carried out on the toxicity of phthalate, Flu, parabens in vivo and in vitro models. In brief, studies have been indicated that long-term and short-term exposure to various endocrine disrupting compounds (i.e., DEHP, Flu, parabens) during development stage (i.e., gestation, neonatal, immature, peripubertal) were done to find alternative dysfunctions later in animal life. The development and function of male or female reproductive tract showed many abnormalities, e.g., menstrual cycle irregularities; impaired fertility, endometriosis, and polycystic ovarian syndrome in female or morphological and functional gonadal dysfunction, e.g., infertility and decreased libido, congenital malformations (altered embryonic and fetal intrauterine development) and testicular dysgenesis syndrome in male. In addition, the differential gene expression patterns by microarray analysis following EDs exposure were found, particularly in steroid hormone synthesis, androgen and/or estrogen synthesis, and sex determination-related gene. On the other hand, studies revealed that parabens, a weak estrogenic chemical, exerted their actions on

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

    PubMed Central

    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. PMID:22991565

  7. Sorptive removal of endocrine-disruptive compound (estriol, E3) from aqueous phase by batch and column studies: kinetic and mechanistic evaluation.

    PubMed

    Kumar, A Kiran; Mohan, S Venkata; Sarma, P N

    2009-05-30

    Endocrine disruptive compounds (EDC) are a wide variety of chemicals which typically exert effects, either directly or indirectly, through receptor-mediated processes. They mimic endogenous hormones by influencing the activities of hormone activities even at nanogram concentrations and reported to disrupt the vital systems (e.g., the endocrine system) in aquatic organisms. The EDC are present in aquatic water bodies and sediments mainly due to the release of human and animal excreted waste. Estriol (E3) removal by adsorption process was investigated in this study to evaluate the potential of activated charcoal as adsorbent. Agitated non-flow batch sorption studies showed good E3 removal efficiency. Sorption kinetic data illustrated good fit with pseudo-first-order rate equation. Experimental data confirmed to linear Langmuir's isotherm model. Neutral pH condition showed comparatively good sorption of E3. Adsorption capacity showed a consistent increasing trend with increase in the operating temperature [DeltaH degrees , -9.189 kJ/mol); DeltaS degrees , 0.492 J/mol K) suggesting exothermic nature of E3 sorption process. Free energy (DeltaG degrees ) increased from 2.51 to 2.97 kJ/mol with increase in temperature from 0 to 50 degrees C. Further, E3 spiked distilled water, untreated domestic sewage and treated domestic sewage were studied in fixed bed column to assesses the potential of sorption process as tertiary unit operation in the ETP system. Total E3 concentration was determined quantitatively by employing direct competitive enzymatic-immuno assay (EIA) procedure.

  8. Determination of endocrine-disrupting compounds in water samples by magnetic nanoparticle-assisted dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry.

    PubMed

    Pérez, Rosa Ana; Albero, Beatriz; Tadeo, José Luis; Sánchez-Brunete, Consuelo

    2016-11-01

    A rapid extraction procedure is presented for the determination of five endocrine-disrupting compounds, estrone, ethinylestradiol, bisphenol A, triclosan, and 2-ethylhexylsalicylate, in water samples. The analysis involves a two-step extraction procedure that combines dispersive liquid-liquid microextraction (DLLME) with dispersive micro-solid phase extraction (D-μ-SPE), using magnetic nanoparticles, followed by in situ derivatization in the injection port of a gas chromatograph coupled to triple quadrupole mass spectrometry. The use of uncoated or oleate-coated Fe3O4 nanoparticles as sorbent in the extraction process was evaluated and compared. The main parameters involved in the extraction process were optimized applying experimental designs. Uncoated Fe3O4 nanoparticles were selected in order to simplify and make more cost-effective the procedure. DLLME was carried out at pH 3, during 2 min, followed by the addition of the nanoparticles for D-μ-SPE employing 1 min in the extraction. Analysis of spiked water samples of different sources gave satisfactory recovery results for all the compounds with detection limits ranging from 7 to 180 ng l(-1). Finally, the procedure was applied in tap, well, and river water. Graphical abstract Diagram of the extraction method using magnetic nanoparticles (MNPs).

  9. Endocrine Diseases

    MedlinePlus

    ... 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 ...

  10. From ‘Omics to Otoliths: Responses of an Estuarine Fish to Endocrine Disrupting Compounds across Biological Scales

    PubMed Central

    Brander, Susanne M.; Connon, Richard E.; He, Guochun; Hobbs, James A.; Smalling, Kelly L.; Teh, Swee J.; White, J. Wilson; Werner, Inge; Denison, Michael S.; Cherr, Gary N.

    2013-01-01

    Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i

  11. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    in vivo ACTH challenge test to prove adrenocortical competency, and the H295R cell line to examine molecular mechanisms of steroidogenic pathway toxicity, are discussed. Finally, because of the central role of the adrenal in the physiologically adaptive stress response, the distinguishing features of stress, compared with adrenocortical toxicity, are discussed with reference to the evidence required to claim that adrenal hypertrophy results from stress rather than adrenocortical enzyme inhibition which is a serious adverse toxicological finding. This article is part of a special issue entitled 'Endocrine disruptors and steroids'.

  12. SIGNIFICANCE OF EXPERIMENTAL STUDIES FOR ASSESSING ADVERSE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS

    EPA Science Inventory

    The U.S. Environmental Protection Agency (US EPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce andr...

  13. Evidence of reproductive endocrine effects in women with occupational fuel and solvent exposures.

    PubMed Central

    Reutman, Susan R; LeMasters, Grace Kawas; Knecht, Edwin A; Shukla, Rakesh; Lockey, James E; Burroughs, G Edward; Kesner, James S

    2002-01-01

    Hydrocarbons (HCs) found in fuels and solvents are ubiquitous in the environment, yet we know little about their effects on the endocrine system. The objective of this study was to assess the potential reproductive endocrine effects of low-dose HCs encountered by female U.S. Air Force personnel with fuel (primarily JP-8 jet fuel) and solvent exposures (n = 63). We estimated the internal dose of HCs in fuels and solvents by measuring their levels in exhaled breath, including the sum of aliphatic HCs (C6H14-C16H34) and the sum of aromatic HCs (benzene, ethylbenzene, toluene, and m,p,o-xylenes). Adverse outcome measures included urinary endocrine markers that have been associated with nonconceptive (vs. conceptive) menstrual cycles in ovulatory women: lower preovulatory luteinizing hormone (LH) and mid-luteal phase pregnanediol 3-glucuronide (Pd3G) and estrone 3-glucuronide, and higher follicle phase Pd3G. We also obtained reproductive and exposure information from baseline questionnaires and daily diaries. Toluene was the most frequently found analyte in the breath, with values up to 52.0 ppb, and benzene breath levels were up to 97.5 ppb. Regression analysis revealed that preovulatory LH levels were significantly lower (p = 0.007) among women whose total aliphatic HC levels were above the median. The relationship between elevated aliphatic HC exposure and lowered preovulatory LH levels in the present study suggests that compounds in fuels and some solvents may act as reproductive endocrine disruptors. Confirmation of these findings is needed, not only to determine if fuel and solvent exposure may impact other LH-dependent physiologic functions but also to examine effects of fuels and solvents on conception. PMID:12153763

  14. Bioprofiling of Surface/Wastewater and Bioquantitation of Discovered Endocrine-Active Compounds by Streamlined Direct Bioautography.

    PubMed

    Klingelhöfer, Ines; Morlock, Gertrud E

    2015-11-03

    A direct bioautography has been used for the simultaneous determination of four estrogens [estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2)] and two xenoestrogens [bisphenol A (BPA) and 4-n-nonyl-phenol (NP)] in surface water and wastewater samples from a sewage treatment plant. After either direct application or a liquid-liquid extraction of the water samples, the qualitative and quantitative detection of estrogen-effective compounds was performed with a planar yeast estrogen screen. The limits of detection were different for each compound, due to the specific receptor binding of individual (xeno)estrogens (1 ng/L to 15 μg/L). The mean recovery rate for all six substances at this ultratrace level was 88% [mean percent relative standard deviation (%RSD) of 17%, n = 3]. Over the whole procedure, precisions of three estrogens discovered in a wastewater sample were below 17%, n = 3. The identification of the detected bioactive compounds was performed by high-performance thin-layer chromatography-electrospray ionization mass spectrometry (HPTLC-ESI-MS) via the elution-head-based TLC-MS Interface. Whereas the estrogens E1 and E2 could always be detected in the influent of the treatment plant, E3 was detected occasionally. The concentrations of E1 and E2 ranged from 3 to 50 ng/L, and for E3 from 98 to 210 ng/L. EE2, BPA, and NP could not be detected at the given LOD. In every second surface water sample, E1 and E2 were detected, but not E3, EE2, BPA, and NP.

  15. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 1. Adsorption capacity and kinetics

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative PhACs (naproxen and carbamazepine) and one EDC (nonylphenol) were evaluated on two granular activated carbons (GAC) namely coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. The primary objective was to investigate preloading effects by natural organic matter (NOM) on adsorption capacity and kinetics under conditions and concentrations (i.e., ng/L) relevant for drinking water treatment. Isotherms demonstrated that all compounds were significantly negatively impacted by NOM fouling. Adsorption capacity reduction was most severe for the acidic naproxen, followed by the neutral carbamazepine and then the more hydrophobic nonylphenol. The GAC with the wider pore size distribution had considerably greater NOM loading, resulting in lower adsorption capacity. Different patterns for the change in Freundlich KF and 1/n with time revealed different competitive mechanisms for the different compounds. Mass transport coefficients determined by short fixed-bed (SFB) tests with virgin and preloaded GAC demonstrated that film diffusion primarily controls mass transfer on virgin and preloaded carbon. Naproxen suffered the greatest deteriorative effect on kinetic parameters due to preloading, followed by carbamazepine, and then nonylphenol. A type of surface NOM/biofilm, which appeared to add an additional mass transfer resistance layer and thus reduce film diffusion, was observed. In addition, electrostatic interactions between NOM/biofilm and the investigated compounds are proposed to contribute to the reduction of film diffusion. A companion paper building on this work describes treatability studies in pilot-scale GAC adsorbers and the effectiveness of a selected fixed-bed model. 32 refs., 3 figs., 2 tabs.

  16. Exposure to endocrine disrupting chemicals and neurodevelopmental alterations.

    PubMed

    Pinson, A; Bourguignon, J P; Parent, A S

    2016-07-01

    The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling.

  17. Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2016-11-16

    In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g(-1) to 6.1 ng g(-1), except for hexabromocyclododecane (36 ng g(-1)). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g(-1)) and parabens (100% of samples; concentrations up to 624 ng g(-1)). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g(-1)). Hexabromocyclododecane was not detected.

  18. Environmental exposures that affect the endocrine system: public health implications.

    PubMed

    DeRosa, C; Richter, P; Pohl, H; Jones, D E

    1998-01-01

    In recent years much attention has been focused on the potential for a wide range of xenobiotic chemicals to interact with and disrupt the endocrine systems of animal and human populations. An overview of the chemicals that have been implicated as endocrine disruptors is presented. The ubiquity in the environment and associated body burdens of these chemicals in human populations are described. Potential mechanisms of action are reviewed, including the role of specific intracellular receptors and their interactions with endogenous and exogenous materials. The subsequent upregulation or downregulation of physiological processes at critical stages of development is discussed. The potential for joint toxic action and interaction of chemical mixtures is also discussed. The acknowledged role of wildlife populations as sentinels of potential human health effects is reviewed, and the weight of evidence for the role and impact of endocrine disruptors is presented. The implications of exposure to endocrine-disrupting chemicals for human health are reviewed, with special emphasis on the potential for transgenerational effects in at-risk populations. Recommendations for future research include the development of (1) structural activity and in vivo and in vitro functional toxicology methods to screen chemicals for their endocrine-disrupting ability, (2) biomarkers of exposure and effect, and (3) in situ sentinel systems.

  19. Construction of amphiphilic segments on polypropylene nonwoven surface and its application in removal of endocrine disrupting compounds (EDCs) from aqueous solution

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Wei, Junfu; Zhou, Xiangyu; Liu, Nana

    2015-05-01

    The amphiphilic segments on polypropylene nonwoven (PP nonwoven) surface were constructed using the ultraviolet (UV) irradiation graft polymerization for the removal of endocrine disrupting compounds (EDCs) with different polarity from aqueous solution. The stearyl acrylate (SA) as hydrophobic functional monomer was introduced onto the surface of PP nonwoven fabric at first stage and then the hydroxyethyl acrylate (HEA) as hydrophilic functional monomer was introduced subsequently. The effect of functional monomer concentration and UV irradiation time on grafting ratio was studied and discussed. The novel amphiphilic structure was designed and constructed based on adsorption capacity for the target micropollutants. The structure and composition of the amphiphilic adsorption materials were characterized by Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and contact angle (CA). The adsorption behaviors for EDCs of the amphiphilic adsorption materials were studied and the results indicated that the adsorption capacity and adsorption rate were superior to single SA grafted PP nonwoven (PP-g-SA) and single HEA grafted PP nonwoven (PP-g-HEA). The novel amphiphilic adsorption material was efficient for the removal of EDCs with different polarity and could be utilized as a potential adsorption material for removing EDCs from aqueous solution.

  20. Application of ionic liquid-based dispersive liquid phase microextraction for highly sensitive simultaneous determination of three endocrine disrupting compounds in food packaging.

    PubMed

    Wang, Lingling; Zhang, Danfeng; Xu, Xu; Zhang, Lei

    2016-04-15

    Ionic liquid (IL) dispersive liquid-liquid microextraction (DLLME) method was successfully developed for extracting three endocrine disrupting compounds (EDCs) (bisphenol A, bisphenol AF and bisphenol AP) from the food packaging. 1-Octyl-3-methylimidazoliumhexafluorophosphate ([C8MIM][PF6]) was selected as extraction solution. The extraction procedure did not require a dispersive solvent. Three EDCs extraction kinetics were found to be very fast and the equilibrium was attained within 3.0 min following the pseudo-first-order model. The H-bonding and hydrophobic interactions play an important role in the partitioning of EDCs into IL from aqueous solution. The recovered IL could be reused for three runs without significant loss of extraction efficiencies. The spiked recoveries of three targets in food packaging were in the range of 97.8-103.1%. The limits of detection ranged from 0.50 to 1.50 ng mL(-1) (S/N=3). As a result, this method has been successfully applied for the sensitive detection of three EDCs in real samples.

  1. One-pot synthesized functionalized mesoporous silica as a reversed-phase sorbent for solid-phase extraction of endocrine disrupting compounds in milks.

    PubMed

    Gañán, Judith; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Marina, María Luisa; Sierra, Isabel

    2016-01-08

    A new procedure for the determination of 12 naturally occurring hormones and some related synthetic chemicals in milk, commonly used as growth promoters in cattle, is reported. The method is based on liquid-liquid extraction followed by solid-phase extraction (SPE) using a new one-pot synthesized ordered mesoporous silica (of the SBA-15 type) functionalized with octadecyl groups (denoted as SBA-15-C18-CO) as reversed-phase sorbent. The analytes were eluted with methanol and then submitted to HPLC with diode array detection. Under optimal conditions, the method quantification limit for the analytes ranged from 0.023 to 1.36μg/mL. The sorbent affored the extraction of estrone, 17β-estradiol, estriol, progesterone, hexestrol, diethylstilbestrol, 4-androstene-3,17-dione, ethinylestradiol, 17α-methyltestosterone, nandrolone, prednisolone and testosterone with mean recoveries ranging from 72% to 105% (except for diethylstilbestrol) with RSD<11%. These results were comparable and, in some cases, even better than those obtained with other extraction methods, therefore SBA-15-C18-CO mesoporous silica possess a high potential as a reversed-phase sorbent for SPE of the 12 mentioned endocrine disrupting compounds in milk samples.

  2. Endocrine System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Endocrine System KidsHealth > For Parents > Endocrine System A A A ... to help the body function properly. About the Endocrine System The foundations of the endocrine system are the ...

  3. Raw and biologically treated paper mill wastewater effluents and the recipient surface waters: Cytotoxic and genotoxic activity and the presence of endocrine disrupting compounds.

    PubMed

    Balabanič, Damjan; Filipič, Metka; Krivograd Klemenčič, Aleksandra; Žegura, Bojana

    2017-01-01

    Paper mill effluents are complex mixtures containing different toxic compounds including endocrine-disrupting (EDCs) and genotoxic compounds. In the present study non-concentrated raw and biologically treated wastewaters from two paper mill plants with different paper production technologies i) Paper mill A uses virgin fibres, and ii) Paper mill B uses recycled fibres for paper production and the corresponding receiving surface waters, were assessed for their cytotoxic/genotoxic activity with SOS/umuC, Ames MPF 98/100 Aqua, and comet assay with human hepatoma HepG2 cells. In addition the levels of seven selected EDCs were quantified in wastewater samples and receiving surface waters. All investigated EDCs were confirmed in raw and biologically treated effluents from both paper mills with concentrations being markedly higher in Paper mill B effluents. In the receiving surface waters three of the studied EDCs were determined downstream of both paper mills effluent discharge. The wastewater samples and the recipient surface water samples from Paper mill A were not mutagenic for bacteria and did not induce DNA damage in HepG2 cells. On the contrary, half of the raw wastewater samples from Paper mill B were mutagenic whereas biologically treated wastewater and the recipient surface water samples were negative. In HepG2 cells most of the raw and biologically treated wastewater samples from Paper mill B as well as surface water samples collected downstream of Paper mill B effluent discharge induced DNA damage. The results confirmed that genotoxic contaminants were present only in wastewaters from Paper mill B that uses recycled fibres for paper production, and that the combined aerobic and anaerobic wastewater treatment procedure efficiently reduced contaminants that are bacterial mutagens, but not those that induce DNA damage in HepG2 cells. This study highlights that in addition to chemical analyses bioassays are needed for a comprehensive toxicological evaluation of

  4. Trace analysis of endocrine disrupting compounds in environmental water samples by use of solid-phase extraction and gas chromatography with mass spectrometry detection.

    PubMed

    Azzouz, Abdelmonaim; Ballesteros, Evaristo

    2014-09-19

    A novel analytical method using a continuous solid-phase extraction system in combination with gas chromatography-mass spectrometry for the simultaneous separation and determination of endocrine disrupting compounds (EDCs) is reported. The method was applied to major EDCs of various types including parabens, alkylphenols, phenylphenols, bisphenol A and triclosan in water. Samples were preconcentrated by using an automatic solid-phase extraction module containing a sorbent column, and retained analytes eluted with acetonitrile for derivatization with a mixture of N,O-bis(trimethylsilyl)trifluoroacetamide and trimethylchlorosilane. A number of variables potentially influencing recovery of the target compounds such as the type of SPE sorbent (Silica gel, Florisil, RP-C18, Amberlite XAD-2 and XAD-4, Oasis HLB and LiChrolut EN), eluent and properties of the water including pH and ionic strength, were examined. LiChrolut EN was found to be the most efficient sorbent for retaining the analytes, with ∼100% efficiency. The ensuing method was validated with good analytical results including low limits of detection (0.01-0.08ng/L for 100mL of sample) and good linearity (r(2)>0.997) throughout the studied concentration ranges. The method exhibited good accuracy (recoveries of 90-101%) and precision (relative standard deviations less than 7%) in the determination of EDCs in drinking, river, pond, well, swimming pool and waste water. Waste water samples were found to contain the largest number and highest concentrations of analytes (3.2-390ng/L).

  5. Calculation methods to perform mass balance of endocrine disrupting compounds in a submerged membrane bioreactor: fate and distribution of estrogens during the biological treatment.

    PubMed

    Estrada-Arriaga, E B; Mijaylova, P

    2011-01-01

    The purpose of this paper is to report the study of the fate and distribution of three endocrine disrupting compounds (estrogens); Estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) in a laboratory scale submerged membrane bioreactor (SMBR). For this matter, both aqueous and solids phases were analyzed for the presence of E1, E2 and EE2. The outcome of this study was that three SMBRs showed enhanced elimination of estrogens in different operational conditions; the estrogen removal was close to 100% in SMBR. Additionally, E1, E2 and EE2 were detected in SMBR sludge at concentrations of up to 41.2, 37.3 and 36.9 ng g(-1) dry weight, respectively. The estrogen removal in the SMBRs was directly influenced by a combination of simultaneous biodegradation-adsorption processes, indicating that the main removal mechanism of the estrogens in the SMBRs is the biodegradation process. The E1, E2 and EE2 were biologically degraded in the SMBR (87-100%). The sorption of estrogens onto activated sludge was from 2%. Therefore, a high potential for estrogen removal by biodegradation in the SMBR was observed, allowing less estrogen concentration in the dissolved phase available for the adsorption of these compounds onto biological flocs. Two different methods were carried out for mass balance calculations of estrogens in SMBR. For the first method, the measured data was used in both liquid and solid phases, whereas for the second one, it was in aqueous phase and solid-water distribution coefficients (K(d)) value of E1, E2 and EE2. The purpose of these methodologies is to make easier the identification of the main mechanisms involved in the removal of E1, E2 and EE2 in a SMBR. Both methods can be applied in order to determine the mechanism, fate and distribution of estrogens in a SMBR.

  6. Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

    PubMed

    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.

  7. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    PubMed

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species.

  8. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    PubMed

    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.

  9. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

    PubMed Central

    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. PMID:26963243

  10. Maternal exposure to estradiol and endocrine disrupting compounds alters the sensitivity of sea urchin embryos and the expression of an orphan steroid receptor.

    PubMed

    Roepke, Troy A; Chang, Ernest S; Cherr, Gary N

    2006-10-01

    Endocrine disrupting compounds (EDCs) are known to affect reproduction and development in marine invertebrates. In previous work, we have shown that developing sea urchin embryos were sensitive to estradiol and estrogenic EDCs at environmentally relevant concentrations in a tamoxifen-sensitive manner (Roepke et al. 2005. Aquat Toxicol 71:155-173). In this study, we report the effects of maternal exposure to EDCs on embryo sensitivity and regulation of an orphan steroid receptor in sea urchin eggs. Maternal exposures were conducted by injecting female Strongylocentrotus purpuratus sea urchins initiating oogenesis with two concentrations of estradiol, octylphenol, tributyltin and o, p-DDD for 8 weeks with an induced spawning before and after the injection cycle. Developing embryos were less sensitive to estradiol following maternal exposure to estradiol, octylphenol and DDD. The steroidogenesis inhibitor, spironolactone, and the aromatase inhibitor, formestane, affected normal sea urchin development with EC50 values of 18 and 2 microM, respectively. Binding of estradiol was demonstrated in homogenates supernatants of sea urchin embryos by filtration centrifugation and column chromatography, but saturation was not reached until 4-6 hr and was highly variable. Analysis of eggs from pre- and post-injection spawns using real-time Q-PCR for the mRNA of an orphan steroid receptor, SpSHR2, shows that receptor mRNA increased in eggs with estradiol, octylphenol and tributyltin but decreased with DDD. RIA showed that estradiol may be present during gastrulation. In summary, maternal exposure to estradiol and EDCs alters embryo sensitivity and regulates the expression of an orphan steroid receptor in the egg.

  11. Relationship between sex steroid and vitellogenin concentrations in flounder (Platichthys flesus) sampled from an estuary contaminated with estrogenic endocrine-disrupting compounds.

    PubMed

    Scott, Alexander P; Katsiadaki, Ioanna; Kirby, Mark F; Thain, John

    2006-04-01

    High concentrations of vitellogenin (VTG; egg yolk protein) have previously been found in male flounder (Platichthys flesus) from several UK estuaries; these levels have been ascribed to the presence of estrogenic endocrine-disrupting compounds (EDCs). Gonadal abnormalities, including intersex, have also been recorded in these estuaries. However, there is no firm evidence to date that these two findings are causally linked or that the presence of estrogenic EDCs has any adverse population effects. In the present study, we examined the relationship between concentrations of VTG and sex steroids (11-oxo-testosterone in males and 17beta-estradiol in females) in specimens of flounder captured from the estuary of the River Mersey. We first questioned whether the high concentrations of VTG in male and immature female flounder were indeed caused by a direct effect of exogenous EDCs and not indirectly via the endogenous secretion of 17beta-estradiol. The data favored the direct involvement of estrogenic EDCs. We then questioned whether the presence of estrogenic EDCs not only stimulated inappropriate VTG synthesis but whether it might also have had a negative effect on endogenous steroid secretion. It should be noted that the predicted consequences of a drop in steroid secretion include smaller gonads, smaller oocytes, fewer numbers of sperm, and depressed spawning behavior. This question was more difficult to answer because of the strong effect of the seasonal reproductive cycle and stage of maturation on steroid concentrations. However, matched by month of capture and stage of maturation, both 17beta-estradiol in females and 11-keto-testosterone in males were in most cases significantly lower in those years when VTG concentrations were higher.

  12. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity. PMID:19433244

  13. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society.

    PubMed

    Zoeller, R Thomas; Brown, T R; Doan, L L; Gore, A C; Skakkebaek, N E; Soto, A M; Woodruff, T J; Vom Saal, F S

    2012-09-01

    An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.

  14. Zearalenone, an estrogenic mycotoxin, is an immunotoxic compound.

    PubMed

    Hueza, Isis M; Raspantini, Paulo Cesar F; Raspantini, Leonila Ester R; Latorre, Andreia O; Górniak, Silvana L

    2014-03-13

    The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.

  15. Incorporation of endocrine disruption into chemical hazard scoring for pollution prevention and current list of endocrine disrupting chemicals.

    PubMed

    Whaley, D A; Keyes, D; Khorrami, B

    2001-11-01

    Research continues to support the theory of endocrine disruption. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. The University of Tennessee, Knoxville (UTN), developed a method for hazard scoring chemicals for the aquatic ecosystem. The Indiana Clean Manufacturing Technology and Safe Materials Institute at Purdue University (CMTI) later expanded the scoring system to include terms for worker hazard as well as terms for contamination of soil and air quality, and for stratospheric ozone depletion. We call the CMTI chemical hazard score the Purdue score. At West Virginia University, two improvements of the Purdue chemical hazard score are developed, a normalizing of the term for soil contamination, and addition of hazard score terms for ecosystem endocrine disruption. The results of incorporating endocrine disruption terms into the hazard scoring equations resulted in increased hazard rankings, often substantially increased, for 26 endocrine disrupting chemicals (EDCs) among 200 Superfund chemicals. Because data suggesting human endocrine disruption from such chemicals is still controversial, no endocrine disruptor term has been added to the human toxicity portions of the chemical hazard scoring system at this time. The third product of this work is assembly of a current consolidated list of (1) established or probable, mostly synthetic, industrial chemical and medication EDCs and (2) suspect (less certain) synthetic and natural (phytoestrogen) possible endocrine disrupting chemicals, with the goal of contributing to future development of quantitative structure activity

  16. Predictive Endocrine Testing in the 21st Century Using In Vitro Assays of Estrogen Receptor Signaling Responses

    EPA Science Inventory

    Thousands of environmental chemicals are subject to regulatory review for their potential to be endocrine disruptors (ED). In vitro high-throughput screening (HTS) assays have emerged as a potential tool for prioritizing chemicals for ED-related whole-animal tests. In this study,...

  17. Assessment of the Endocrine Toxicity of the Fungicide Prochloraz using the Larval Amphibian Growth and Development Assay

    EPA Science Inventory

    Prochloraz is a broad spectrum fungicide that acts by inhibiting ergosterol biosynthesis in target species. Toxicity results in non-target vertebrate species suggest this toxicant acts as an endocrine disruptor that inhibits aromatase, the enzyme responsible for the conversion of...

  18. Science Plan U.S. Geological Survey Florida District

    DTIC Science & Technology

    2001-01-01

    reconnaissance sampling for emergent contaminants (pharmaceuticals, pesticides , endocrine disruptor compounds) to develop additional projects. Figure 31...coastline of the United States during a particularly active period of hurricane activity in 1998. endocrine disruptors , are beginning to receive...pathogens, and endocrine disruptor compounds. (Issue 4) • Evaluation of new instrumentation for specific applications in Florida, such as

  19. Recent Advances on Endocrine Disrupting Effects of UV Filters

    PubMed Central

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-01-01

    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. PMID:27527194

  20. Longer-term and short-term variability in pollution of fluvial sediments by dioxin-like and endocrine disruptive compounds.

    PubMed

    Macikova, P; Kalabova, T; Klanova, J; Kukucka, P; Giesy, J P; Hilscherova, K

    2014-04-01

    Changes in pollutant loads in relatively dynamic river sediments, which contain very complex mixtures of compounds, can play a crucial role in the fate and effects of pollutants in fluvial ecosystems. The contamination of sediments by bioactive substances can be sensitively assessed by in vitro bioassays. This is the first study that characterizes detailed short- and long-term changes in concentrations of contaminants with several modes of action in river sediments. One-year long monthly study described seasonal and spatial variability of contamination of sediments in a representative industrialized area by dioxin-like and endocrine disruptive chemicals. There were significant seasonal changes in both antiandrogenic and androgenic as well as dioxin-like potential of river sediments, while there were no general seasonal trends in estrogenicity. Aryl hydrocarbon receptor-dependent potency (dioxin-like potency) expressed as biological TCDD-equivalents (BIOTEQ) was in the range of 0.5-17.7 ng/g, dry mass (dm). The greatest BIOTEQ levels in sediments were observed during winter, particularly at locations downstream of the industrial area. Estrogenicity expressed as estradiol equivalents (EEQ) was in the range of 0.02-3.8 ng/g, dm. Antiandrogenicity was detected in all samples, while androgenic potency in the range of 0.7-16.8 ng/g, dm dihydrotestosterone equivalents (DHT-EQ) was found in only 30 % of samples, most often during autumn, when antiandrogenicity was the least. PAHs were predominant contaminants among analyzed pollutants, responsible, on average, for 13-21 % of BIOTEQ. Longer-term changes in concentrations of BIOTEQ corresponded to seasonal fluctuations, whereas for EEQ, the inter-annual changes at some locations were greater than seasonal variability during 1 year. The inter- as well as intra-annual variability in concentrations of both BIOTEQ and EEQ at individual sites was greater in spring than in autumn which was related to hydrological conditions in the

  1. Development of biomarkers of stress related to endocrine disruption in gastropods: alkali-labile phosphates, protein-bound lipids and vitellogenin-like proteins.

    PubMed

    Gagnaire, Beatrice; Gagné, François; André, Chantale; Blaise, Christian; Abbaci, Khedidja; Budzinski, Hélène; Dévier, Marie-Hélène; Garric, Jeanne

    2009-05-05

    The occurrence in aquatic environments of compounds capable of acting as endocrine disruptors (ED) is of concern for wildlife. Elevated levels of the egg-yolk precursor protein vitellogenin (Vg) are widely accepted as a biomarker for xenoestrogen exposure in aquatic organisms. The purpose of this study was to develop a method for tracking changes in levels of Vg-like proteins in gastropods. Vg-like and egg-yolk proteins were analyzed in three freshwater gastropods having different modes of reproduction: Potamopyrgus antipodarum (asexual reproduction), Valvata piscinalis (hermaphroditism) and Lithoglyphus naticoides (sexual reproduction). Vitellogenin-like protein levels were examined by the alkali-labile phosphate (ALP) technique, a novel protein-bound lipid (PBL) assay, and by gradient gel electrophoresis with silver staining. The first phase of the study was dedicated to the development and optimization of an analytical method for detecting Vg-like proteins in these three gastropod species. In the second phase, the snails P. antipodarum and V. piscinalis were exposed to bisphenol A (BPA), octylphenol (OP) and tributyltin (TBT) for 14 and 28 days. Vg-like proteins were resolved in one major band at 250-300 kDa for L. naticoides and V. piscinalis and in two bands at 100 and 30 kDa for P. antipodarum. After 14 days of exposure, all techniques showed an increase in Vg-like protein levels at 100 microg/L BPA and at 1 microg/L OP in P. antipodarum. A decrease in these proteins was observed with high concentrations of OP (100 microg/L) and TBT (>or=5 ng/L). In V. piscinalis, a decrease in Vg-like proteins was shown after 14 days of exposure for OP >or=10 microg/L and TBT >or=5 ng/L; however, at 28 days, gel electrophoresis revealed an increase in these proteins. Histological observations showed significant necrosis in ovotestes of V. piscinalis with the three endocrine-disrupting compounds, while tissue modifications were not detected for P. antipodarum. A method for

  2. Calibration and field test of the Polar Organic Chemical Integrative Samplers for the determination of 15 endocrine disrupting compounds in wastewater and river water with special focus on performance reference compounds (PRC).

    PubMed

    Vallejo, A; Prieto, A; Moeder, M; Usobiaga, A; Zuloaga, O; Etxebarria, N; Paschke, A

    2013-05-15

    In this work, home-made Polar Organic Chemical Integrative Samplers (POCIS) were studied for passive sampling of 15 endocrine disrupting compounds (4 alkylphenols and steroid hormones) in influent and effluent samples of wastewater treatment plants (WWTPs) as well as up- and downstream of the receiving river water. POCIS calibration at laboratory conditions was carried out using a continuous-flow calibration system. The influence of the exposure position of the POCIS within the calibration device, horizontal or vertical, to the water flow direction was evaluated. While the sampling rates of most of the target substances were not affected by the sampler position, for cis-ADT, E1, E2 and E3, the vertical position provided the highest analyte accumulation. Hence, the POCIS samplers were preferably exposed vertical to the water flow in overall experiments. Using the continuous-flow calibration device, lab-based sampling rates were determined for all the target compounds (RSBPA = 0.0326 L/d; RScisADT = 0.0800 L/d, RSE1 = 0.0398 L/d, RSEQ = 0.0516 L/d, RSTT = 0.0745 L/d, RSE2 = 0.0585 L/d, RSEE2 = 0.0406 L/d, RSNT = 0.0846 L/d, RSPG = 0.0478 L/d and RSE3 = 0.1468 L/d), except for DES, MeEE2, 4tOP, 4OP, 4NPs, where the uptake after 14 days POCIS exposure was found to be insignificant or indicated a no linear behaviour. Recoveries from POCIS extractions were in the range between 71 and 152% for most of the target analytes except for DES and E3 with around 59%. Good precision of the sampling procedure up till 20% was observed and limits of detection were at ng/L level. Two deuterated compounds ([(2)H3]-E2 and [(2)H4]-EQ) were successfully tested as performance reference compounds (PRC, [Formula: see text] = 0.0507 L/d and [Formula: see text] = 0.0543 L/d)). Finally, the POCIS samplers were tested for monitoring EDCs at two wastewater treatment plants, in Halle and Leipzig (Germany). BPA, E1, EQ, E2, MeEE2, NT, EE2, PG and E3 were quantified and their time-weighted average

  3. Energy disruptors: rising stars in anticancer therapy?

    PubMed Central

    Bost, F; Decoux-Poullot, A-G; Tanti, J F; Clavel, S

    2016-01-01

    The metabolic features of tumor cells diverge from those of normal cells. Otto Warburg was the first to observe that cancer cells dramatically increase their glucose consumption to generate ATP. He also claimed that cancer cells do not have functional mitochondria or oxidative phosphorylation (OXPHOS) but simply rely on glycolysis to provide ATP to the cell, even in the presence of oxygen (aerobic glycolysis). Several studies have revisited this observation and demonstrated that most cancer cells contain metabolically efficient mitochondria. Indeed, to sustain high proliferation rates, cancer cells require functional mitochondria to provide ATP and intermediate metabolites, such as citrate and cofactors, for anabolic reactions. This difference in metabolism between normal and tumors cells causes the latter to be more sensitive to agents that can disrupt energy homeostasis. In this review, we focus on energy disruptors, such as biguanides, 2-deoxyglucose and 5-aminoimidazole-4-carboxamide ribonucleotide, that interfere with the main metabolic pathways of the cells, OXPHOS, glycolysis and glutamine metabolism. We discuss the preclinical data and the mechanisms of action of these disruptors at the cellular and molecular levels. Finally, we consider whether these drugs can reasonably contribute to the antitumoral therapeutic arsenal in the future. PMID:26779810

  4. Endocrine disrupters and menopausal health.

    PubMed

    Holmes, Philip; Rumsby, Paul; Harrison, Paul T C

    2004-06-01

    Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

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

    PubMed

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

    2010-02-01

    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 residual. Influences of EDCs on the reproduction systems of these organisms, with consequences at the population level, are expected but have not been confirmed. This work aimed to study the effects of bisphenol A (BPA) and vinclozolin (Vz) on the reproduction of the terrestrial isopod Porcellio scaber. Isopods were coupled and exposed to increasing concentrations of Vz and BPA and the females' reproductive cycle followed for 56d. Both compounds elicited reproductive toxicity. Vz and BPA decreased female reproductive allocation. Vz reduced pregnancy duration; increased the abortion percentage; decreased the number of pregnancies; and decreased the number of juveniles per female while BPA increased abortions at the lowest and highest test concentrations. The reproductive endpoints presented in here are indicative of the possible impact that this type of compounds might have on isopod population dynamics, which may eventually lead to population decline.

  6. Quantifying Hormone Disruptors with an Engineered Bacterial Biosensor

    PubMed Central

    2017-01-01

    Endocrine disrupting compounds are found in increasing amounts in our environment, originating from pesticides, plasticizers, and pharmaceuticals, among other sources. Although the full impact of these compounds is still under study, they have already been implicated in diseases such as obesity, diabetes, and cancer. The list of chemicals that disrupt normal hormone function is growing at an alarming rate, making it crucially important to find sources of contamination and identify new compounds that display this ability. However, there is currently no broad-spectrum, rapid test for these compounds, as they are difficult to monitor because of their high potency and chemical dissimilarity. To address this, we have developed a new detection strategy for endocrine disrupting compounds that is both fast and portable, and it requires no specialized skills to perform. This system is based on a native estrogen receptor construct expressed on the surface of Escherichia coli, which enables both the detection of many detrimental compounds and signal amplification from impedance measurements due to the binding of bacteria to a modified electrode. With this approach, sub-ppb levels of estradiol and ppm levels of bisphenol A are detected in complex solutions. Rather than responding to individual components, this system reports the total estrogenic activity of a sample using the most relevant biological receptor. As an applied example, estrogenic chemicals released from a plastic baby bottle following microwave heating were detectable with this technique. This approach should be broadly applicable to the detection of chemically diverse classes of compounds that bind to a single receptor. PMID:28280777

  7. Effects of Estrogens and Estrogenic Disrupting Compounds on Fish Mineralized Tissues

    PubMed Central

    Pinto, Patricia I. S.; Estêvão, Maria D.; Power, Deborah M.

    2014-01-01

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities. PMID:25196834

  8. Effects of estrogens and estrogenic disrupting compounds on fish mineralized tissues.

    PubMed

    Pinto, Patricia I S; Estêvão, Maria D; Power, Deborah M

    2014-08-15

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities.

  9. Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators.

    PubMed

    Mihaich, Ellen M; Schäfers, Christoph; Dreier, David A; Hecker, Markus; Ortego, Lisa; Kawashima, Yukio; Dang, Zhi-Chao; Solomon, Keith

    2017-03-01

    As regulatory programs evaluate substances for their endocrine-disrupting properties, careful study design and data interpretation are needed to distinguish between responses that are truly endocrine specific and those that are not. This is particularly important in regulatory environments where criteria are under development to identify endocrine-disrupting properties to enable hazard-based regulation. Irrespective of these processes, most jurisdictions use the World Health Organization/International Programme on Chemical Safety definition of an endocrine disruptor, requiring that a substance is demonstrated to cause a change in endocrine function that consequently leads to an adverse effect in an intact organism. Such a definition is broad, and at its most cautious might capture many general mechanisms that would not specifically denote an endocrine disruptor. In addition, endocrine responses may be adaptive in nature, designed to maintain homeostasis rather than induce an irreversible adverse effect. The likelihood of indirect effects is increased in (eco)toxicological studies that require the use of maximum tolerated concentrations or doses, which must produce some adverse effect. The misidentification of indirect effects as truly endocrine mediated has serious consequences for prompting animal- and resource-intensive testing and regulatory consequences. To minimize the risk for misidentification, an objective and transparent weight-of-evidence procedure based on biological plausibility, essentiality, and empirical evidence of key events in an adverse outcome pathway is recommended to describe the modes of action that may be involved in toxic responses in nontarget organisms. Confounding factors such as systemic toxicity, general stress, and infection can add complexity to such an evaluation and should be considered in the weight of evidence. A recommended set of questions is proffered to help guide researchers and regulators in discerning endocrine and

  10. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely t...

  11. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrined-disrupting chemicals

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely to...

  12. A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals (poster)

    EPA Science Inventory

    The fish short term reproduction assay (FSTRA) is a key component of the USEPA endocrine disruptor screening program (EDSP). The FSTRA considers several mechanistic and apical responses in fathead minnows (Pimephales promelas) to determine whether an unknown chemical is likely to...

  13. Occupation and occupational exposure to endocrine disrupting chemicals in male breast cancer: a case-control study in Europe

    PubMed Central

    Villeneuve, Sara; Cyr, Diane; Lynge, Elsebeth; Orsi, Laurent; Sabroe, Svend; Merletti, Franco; Gorini, Giuseppe; Morales-Suarez-Varela, Maria; Ahrens, Wolfgang; Baumgardt-Elms, Cornelia; Kaerlev, Linda; Eriksson, Mikael; Hardell, Lennart; Févotte, Joëlle; Guénel, Pascal

    2010-01-01

    Objectives Male breast cancer is a rare disease of largely unknown etiology. Besides genetic or hormone-related risk factors, a large number of environmental chemicals are suspected to play a role in breast cancer. The identification of occupations or occupational exposures associated with an increased incidence of breast cancer in men may help to identify mammary carcinogens in the environment. Methods Occupational risk factors of male breast cancer were investigated in a multi-centre case-control study conducted in 8 European countries, including 104 cases and 1901 controls. Lifetime work history was obtained during in-person interviews. Occupational exposures to endocrine disrupting chemicals (alkylphenolic compounds, phthalates, PCBs and dioxins) were assessed on a case-by-case basis from expert judgment. Results Male breast cancer incidence was more particularly increased in motor vehicle mechanics (OR=2.1, CI 1.0–4.4) with a dose-effect relationship with duration employment. It was also increased in paper makers and painters, and in workers in forestry and logging, health and social work, and manufacture of furniture. The odds ratio for exposure to alkylphenolic compounds above median was 3.8 (CI 1.5–9.5). This association persisted after adjustment for occupational exposures to other environmental estrogens. Conclusion These findings suggest that some environmental chemicals are possible mammary carcinogens. Gasoline, organic petroleum solvents or PAH can be suspected from the consistent elevated risk of male breast cancer observed in motor vehicle mechanics. Endocrine disruptors such as alkylphenolic compounds may play a role in breast cancer. PMID:20798010

  14. Reproductive effects of oestrogenic endocrine disrupting chemicals in Astyanax rivularis inhabiting headwaters of the Velhas River, Brazil.

    PubMed

    Weber, André Alberto; Moreira, Davidson Peruci; Melo, Rafael Magno Costa; Vieira, Augusto Bicalho Cruz; Prado, Paula Suzanna; da Silva, Mirra Angelina Neres; Bazzoli, Nilo; Rizzo, Elizete

    2017-03-21

    The Velhas River is the most polluted river in the state of Minas Gerais, south-eastern Brazil. Due to its historical and environmental relevance, the aim of this study was to evaluate the effects of oestrogenic endocrine disruptors on the reproduction of the lambari Astyanax rivularis, a small-sized species found in headwaters of the São Francisco River basin. Quarterly field samplings were carried out during a reproductive cycle in three streams of the upper Velhas River: S1 (reference site) and S2 and S3 (sites contaminated by untreated sewage). The main oestrogenic compounds were evaluated in water using HPLC/MS. Molecular, histological and reproductive biomarkers were assessed in liver and gonad. The results showed higher average concentrations of oestradiol (>200ng/l) in S2 and S3, oestrone (>250ng/l) in S2 as well as oestriol (>200ng/l), bisphenol A (>190ng/l), and nonylphenol (>600ng/l) in S3 compared to S1 (<70ng/l for all compounds). In S2 and S3, there was an increase in the proportion of females, higher ELISA levels of vitellogenin (Vtg) and proteins of the zona radiata (Zrp) in liver males. Insulin-like growth factor (IGF-I) levels were lower in S2 males, which also had a smaller body size, a smaller seminiferous tubule diameter, a higher proportion of spermatogonia, and lower proportion of spermatozoa in relation to S1. Histopathological analyses detected an increase in yolk deficient oocytes and over-ripening in the contaminated sites, and these alterations were associated to a reduction of hepatic Vtg levels and a delay in spawning, respectively. Intersex specimens with perinucleolar follicles in a multifocal distribution in the testis were detected in S2 and S3. These results indicate that chronic exposure to oestrogenic compounds induced endocrine disruption that may affect wild populations of A. rivularis in the Velhas River.

  15. Predicting chemical impacts on vertebrate endocrine systems.

    PubMed

    Nichols, John W; Breen, Miyuki; Denver, Robert J; Distefano, Joseph J; Edwards, Jeremy S; Hoke, Robert A; Volz, David C; Zhang, Xiaowei

    2011-01-01

    Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. From a governmental regulatory perspective, these protective responses complicate efforts to establish acceptable levels of chemical exposure. To explore this issue, we considered vertebrate endocrine systems as potential targets for environmental contaminants. Using the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes as case examples, we identified features of these systems that allow them to accommodate and recover from chemical insults. In doing so, a distinction was made between effects on adults and those on developing organisms. This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems, resulting in permanent changes in phenotypic expression later in life. Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures. A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals, resulting in adverse consequences for populations. Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery. In the short term, these models can be used to design experiments and interpret study findings. Over the long term, a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species, and exposure scenarios. With appropriate modification, Tier 2 assays developed in support of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models.

  16. Amphibians as model to study endocrine disrupters.

    PubMed

    Kloas, Werner; Lutz, Ilka

    2006-10-13

    Environmental compounds can interfere with endocrine systems of wildlife and humans. These so-called endocrine disrupters (ED) are known to affect reproductive biology and thyroid system. The classical model species for these endocrine systems are amphibians and therefore they can serve as sentinels for detection of the modes of action (MOAs) of ED. Recently, amphibians are being reviewed as suitable models to assess (anti)estrogenic and (anti)androgenic MOAs influencing reproductive biology as well as (anti)thyroidal MOAs interfering with the thyroid system. The development of targeted bioassays in combination with adequate chemical analyses is the prerequisite for a concise risk assessment of ED.

  17. Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs).

    PubMed

    Palioura, Eleni; Diamanti-Kandarakis, Evanthia

    2015-12-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.

  18. Exposures, Mechanisms, and Impacts of Endocrine-Active Flame Retardants

    PubMed Central

    Dishaw, Laura; Macaulay, Laura; Roberts, Simon C.; Stapleton, Heather M.

    2014-01-01

    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 FM550. 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. PMID:25306433

  19. Exposures, mechanisms, and impacts of endocrine-active flame retardants.

    PubMed

    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.

  20. Environmental Endocrine Disruption of Energy Metabolism and Cardiovascular Risk

    PubMed Central

    Kirkley, Andrew G.; Sargis, Robert M.

    2014-01-01

    Rates of metabolic and cardiovascular diseases have increased at an astounding rate in recent decades. While poor diet and physical inactivity are central drivers, these lifestyle changes alone fail to fully account for the magnitude and rapidity of the epidemic. Thus, attention has turned to identifying novel risk factors, including the contribution of environmental endocrine disrupting chemicals. Epidemiological and preclinical data support a role for various contaminants in the pathogenesis of diabetes. In addition to the vascular risk associated with dysglycemia, emerging evidence implicates multiple pollutants in the pathogenesis of atherosclerosis and cardiovascular disease. Reviewed herein are studies linking endocrine disruptors to these key diseases that drive significant individual and societal morbidity and mortality. Identifying chemicals associated with metabolic and cardiovascular disease as well as their mechanisms of action is critical for developing novel treatment strategies and public policy to mitigate the impact of these diseases on human health. PMID:24756343

  1. Endocrine system and obesity.

    PubMed

    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.

  2. Introduction to the Endocrine System

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... in Balance › Hormones and Health › Journey Through the Endocrine System Journey Through the Endocrine System Endocrine-related Organs ...

  3. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    NASA Astrophysics Data System (ADS)

    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.

  4. Parts per trillion level determination of endocrine-disrupting chlorinated compounds in river water and wastewater effluent by stir-bar-sorptive extraction followed by gas chromatography-triple quadrupole mass spectrometry.

    PubMed

    Chary, N Sridhara; Herrera, Sonia; Gómez, Maria Jose; Fernández-Alba, Amadeo R

    2012-10-01

    A new analytical method using stir-bar-sorptive extraction (SBSE) followed by liquid desorption (LD) and gas chromatography with triple-quadrupole mass spectrometric detection (GC-QqQ-MS-MS) has been used for quantitative determination of 25 chlorinated endocrine-disrupting compounds (EDCs) in river water and wastewater. The experimental conditions affecting the SBSE-LD performance were studied and are discussed in detail. Results from systematic assay revealed that a 100-mL water sample, stir bars coated with 47 μL PDMS, an extraction time of 14 h (at 900 rpm), 5 % MeOH as modifier and 10 % NaCl resulted in the best analytical recovery of all the target compounds studied. Use of 1:1 ACN-MeOH as back-extraction solvent and two successive sonication steps, each for 5 min, resulted in the best performance for monitoring EDCs in water matrices. The method detection limits for most of the target compounds were very good- ≤ 2 ng L(-1) and ≤10 ng L(-1) for river water and wastewater effluents respectively. Experimental recovery for all the compounds was >70 %, with the exception of simazine for which recovery from the matrix was 65 %. Signal enhancement observed for a few of the compounds in wastewater effluents was managed by use of matrix-matched standards and different injection liners. The method was successfully used for analysis of river water samples from Henares River (Spain) and wastewater effluent samples from wastewater-treatment plants (WWTP). Eleven of the 25 compounds studied were detected in both river water and wastewater effluents. Terbutylazine and methoxychlor were detected in almost all the river water and effluent samples; amounts varied between 37-58.5 ng L(-1) and 15.2-46.8 ng L(-1), respectively. This method was shown enable reliable, effective, and sensitive monitoring of chlorinated EDCs at nanogram levels in surface water and wastewater effluent.

  5. Endocrine disruption: fact or urban legend?

    PubMed

    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.

  6. European Union's strategy on endocrine disrupting chemicals and the current position of Slovenia.

    PubMed

    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.

  7. EADB: an estrogenic activity database for assessing potential endocrine activity.

    PubMed

    Shen, Jie; Xu, Lei; Fang, Hong; Richard, Ann M; Bray, Jeffrey D; Judson, Richard S; Zhou, Guangxu; Colatsky, Thomas J; Aungst, Jason L; Teng, Christina; Harris, Steve C; Ge, Weigong; Dai, Susie Y; Su, Zhenqiang; Jacobs, Abigail C; Harrouk, Wafa; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2013-10-01

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

  8. Endocrine control of epigenetic mechanisms in male reproduction.

    PubMed

    Ankolkar, Mandar; Balasinor, N H

    2016-01-01

    Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders. Investigations of the female in cases of poor reproductive outcome have been the main strategy towards diagnosis. However, despite the male partner contributing half of his genome to the progeny, thorough investigations in the male have been ignored. Environmental pollutants are all pervading and are encountered in our day-to-day life. Many of these pollutants have potential to disrupt the endocrine system. Here, we discuss how the male gametes (spermatozoa) are susceptible to a myriad of epigenetic insults inflicted by exposure to endocrine disruptors and how important is the contribution of the epigenetic marks of the spermatozoa in healthy reproduction. We advocate that sperm epigenetics should be considered as a significant contributor to reproductive health and should be researched further and be subsequently included in routine diagnostic workup in cases of poor reproductive outcome.

  9. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  10. Exposure to a Complex Cocktail of Environmental Endocrine-Disrupting Compounds Disturbs the Kisspeptin/GPR54 System in Ovine Hypothalamus and Pituitary Gland

    PubMed Central

    Bellingham, Michelle; Fowler, Paul A.; Amezaga, Maria R.; Rhind, Stewart M.; Cotinot, Corinne; Mandon-Pepin, Beatrice; Sharpe, Richard M.; Evans, Neil P.

    2009-01-01

    Background Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to “real-life,” environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal. Objectives We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein–coupled receptor 54) system. Methods KiSS-1, GPR54, and ERα (estrogen receptor α) mRNA expression was quantified in control (C) and treated (T) maternal and fetal (110-day) hypothalami and pituitary glands using semiquantitative reverse transcription polymerase chain reaction, and colocalization of kisspeptin with LHβ (luteinizing hormone β) and ERα in C and T fetal pituitary glands quantified using dual-labeling immunohistochemistry. Results Fetuses exposed in utero to the EDC mixture showed reduced KiSS-1 mRNA expression across three hypothalamic regions examined (rostral, mid, and caudal) and had fewer kisspetin immunopositive cells colocalized with both LHβ and ERα in the pituitary gland. In contrast, treatment had no effect on parameters measured in the adult ewe hypothalamus or pituitary. Conclusions This study demonstrates that the developing fetus is sensitive to real-world mixtures of environmental chemicals, which cause significant neuroendocrine alterations. The important role of kisspeptin/GPR54 in regulating puberty and adult reproduction means that in utero disruption of this system is likely to have long-term consequences in adulthood and represents a novel, additional pathway through which environmental chemicals perturb human reproduction. PMID:20019906

  11. 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##

    EPA Science Inventory

    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...

  12. Endocrine system: part 1.

    PubMed

    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.

  13. Endocrine glands (image)

    MedlinePlus

    Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which ...

  14. [Postpartum endocrine syndrome].

    PubMed

    Ducarme, G; Châtel, P; Luton, D

    2008-05-01

    Postpartum endocrine syndromes occur in the year after delivery. They are due to immunologic and vascular modifications during pregnancy. The Sheehan syndrome is the first described postpartum endocrine syndrome and consists on a hypophyse necrosis in relation with a hypovolemic shock during delivery. The immunologic consequences of the pregnancy are the most frequent, sometimes discrete and transitory. The physiological evolution of the endocrine glands during pregnancy and the most frequent post-partum endocrine syndromes are discussed: postpartum lymphocytic hypophysitis, thyroiditis and Sheehan' syndrome.

  15. 75 FR 67963 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Number EPA-HQ-OPPT-2010-0877. The DCO is open from 8 a.m. to 4 p.m., Monday through Friday, excluding...., Washington, DC. The EPA/DC Public Reading Room hours of operation are 8:30 a.m. to 4:30 p.m., Monday through... the EDSP Web site http://www.epa.gov/endo . This document was prepared to provide a...

  16. 75 FR 70557 - Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening Safe Drinking...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    .... Attention: Docket ID Number EPA-HQ-OPPT-2007-1080. The DCO is open from 8 a.m. to 4 p.m., Monday through... Public Reading Room hours of operation are 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal... site, at http://www.epa.gov/endo/ (Ref. 3). EPA is aware of no issue specific to the chemicals in...

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

    EPA Pesticide Factsheets

    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.

  18. Considerations for estimating daily intake values of nonpersistent environmental endocrine disruptors based on urinary biomonitoring data.

    PubMed

    Søeborg, Tue; Frederiksen, Hanne; Andersson, Anna-Maria

    2014-01-01

    Human exposure to chemicals may be estimated by back-calculating urinary concentrations resulting from biomonitoring studies if knowledge of the chemical's toxicokinetic properties is available. In this paper, available toxicokinetic data for back-calculating urinary concentrations into daily intake values for bisphenol A (BPA), phthalates, parabens, and triclosan (TCS) are reviewed and knowledge gaps are identified. Human data is evaluated and presented with relevant animal data. Focus is on the recovery of the administered dose, the route of administration, and differences between humans and animals. Two human toxicokinetic studies are currently used to conclude that an oral dose of BPA is recoverable in urine and that no free BPA 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 due to extensive metabolism. In animals using (14)C-marked phthalates, near-complete recovery is observed. An oral dose of (14)C-marked parabens is also almost completely recovered in animals. In both humans and animals, however, two unspecific metabolites are formed, which complicates the back-calculation of parabens in humans. The recovery of both oral and dermal TCS in humans has been studied, but due to background levels of TCS, the back-calculation is difficult to perform. In conclusion, due to limited data, reasonable estimates of daily intake values based on urinary data are often not possible to obtain. Several knowledge gaps are identified and new studies are suggested. The route of administration used in toxicokinetic studies often does not match realistic scenarios.

  19. 75 FR 77869 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ... general information contact: The TSCA-Hotline, ABVI-Goodwill, 422 South Clinton Ave., Rochester, NY 14620; telephone number: (202) 554-1404; e-mail address: TSCA-Hotline@epa.gov . SUPPLEMENTARY INFORMATION:...

  20. 75 FR 81605 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ...: The TSCA-Hotline, ABVI-Goodwill, 422 South Clinton Ave., Rochester, NY 14620; telephone number: (202) 554-1404; e-mail address: TSCA-Hotline@epa.gov . SUPPLEMENTARY INFORMATION: This document extends...

  1. Exposure assessment for endocrine disruptors: some considerations in the design of studies.

    PubMed Central

    Rice, Carol; Birnbaum, Linda S; Cogliano, James; Mahaffey, Kathryn; Needham, Larry; Rogan, Walter J; vom Saal, Frederick S

    2003-01-01

    In studies designed to evaluate exposure-response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data. A number of issues that must be considered in study design are summarized here. PMID:14527851

  2. 75 FR 70248 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... Ethylbenzene 100-41-4 X Ethylene dibromide 106-93-4 X Ethylene glycol 107-21-1 X Ethylene thiourea 96-45-7 X... be affected. The North American Industrial Classification System (NAICS) codes have been provided to... releases to the environment, pesticide application rates, and production volumes (73 FR 9628, February...

  3. MATHEMATICAL MODEL OF STERIODOGENESIS TO PREDICT DYNAMIC RESPONSE TO ENDOCRINE DISRUPTORS

    EPA Science Inventory

    WE ARE DEVELOPING A MECHANISTIC MATHEMATICAL MODEL OF THE INTRATESTICULAR AND INTRAOVARIAN METABOLIC NETWORK THAT MEDIATES STEROID SYNTHESIS, AND THE KINETICS FOR ENZYME INHIBITION BY EDCs TO PREDICT THE TIME AND DOSE-RESPONSE.

  4. 77 FR 12297 - Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ..., fertilizer, and other agricultural chemical manufacturing (NAICS code 3253), e.g., persons who manufacture, import or process pesticide, fertilizer and agricultural chemicals. Scientific research and...

  5. From endocrine disruptors to nanomaterials: advancing our understanding of environmental health to protect public health.

    PubMed

    Birnbaum, Linda S; Jung, Paul

    2011-05-01

    Environmental health science is the study of the impact of the environment on human health. This paper introduces basic topics in environmental health, including clean air, clean water, and healthful food, as well as a range of current issues and controversies in environmental health. Conceptual shifts in modern toxicology have changed the field. There is a new understanding of the effects of exposure to chemicals at low doses, and in combination, and the impact on human growth and development. Other emerging topics include the role of epigenetics, or changes in genes and gene expression that can be brought about by chemical exposure; environmental justice; and potential effects of engineered nanomaterials and climate change. We review the important implications for public health policy and recommend a broad environmental health research strategy aimed at protecting and improving human health.

  6. DISTURBED SEXUAL CHARACTERISITCS IN MALE MOSQUITOFISH (GAMBUSIA HOLBROOKI) FROM A LAKE CONTAMINATED WITH ENDOCRINE DISRUPTORS.

    EPA Science Inventory

    Previous laboratory studies have demonstrated that estrogenic and antiandrogenic chemicals can alter several sexual characteristics in male poeciliid fishes. Whether similar disturbances occur under field conditions remains to be confirmed. Lake Apopka, Florida, is contaminated w...

  7. Determination of endocrine disrupting chemicals and antiretroviral compounds in surface water: A disposable sorptive sampler with comprehensive gas chromatography - Time-of-flight mass spectrometry and large volume injection with ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wooding, Madelien; Rohwer, Egmont R; Naudé, Yvette

    2017-05-05

    Many rural dwellers and inhabitants of informal settlements in South Africa are without access to treated water and collect untreated water from rivers and dams for personal use. Endocrine disrupting chemicals (EDCs) have been detected in surface water and wildlife of South Africa. EDCs are often present in complex environmental matrices at ultra-trace levels complicating detection thereof. We report a simplified multi-residue approach for the detection and quantification of EDCs, emerging EDCs, and antiretroviral drugs in surface water. A low cost (less than one US dollar), disposable, sorptive extraction sampler was prepared in-house. The disposable samplers consisted of polydimethylsiloxane (PDMS) tubing fashioned into a loop which was then placed in water samples to concentrate EDCs and emerging pollutants. The PDMS samplers were thermally desorbed directly in the inlet of a GC, thereby eliminating the need for expensive consumable cryogenics. Comprehensive gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS) was used for compound separation and identification. Linear retention indices of EDCs and emerging pollutants were determined on a proprietary Crossbond(®) phase Rtx(®)-CLPesticides II GC capillary column. In addition, large volume injection of surface water into an ultra-performance liquid chromatograph tandem mass spectrometer (UPLC-MS/MS) was used as complementary methodology for the detection of less volatile compounds. Large volume injection reduced tedious and costly sample preparation steps. Limits of detection for the GC method ranged from 1 to 98pg/l and for the LC method from 2 to 135ng/l. Known and emerging EDCs such as pharmaceuticals, personal care products and pesticides, as well as the antiretroviral