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Sample records for endocrine disruptor compound

  1. 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

  2. Adsorption of pharmaceutical compounds and an endocrine disruptor from aqueous solutions by carbon materials.

    PubMed

    Sotelo, José L; Rodríguez, Araceli R; Mateos, María M; Hernández, Sergio D; Torrellas, Silvia A; Rodríguez, Juan G

    2012-01-01

    Adsorption has been used to study the removal of atenolol, caffeine, diclofenac and isoproturon, pharmaceutical compounds as emerging contaminants and an endocrine disruptor from ultrapure water and a municipal wastewater treatment plant effluent with three carbonaceous materials: activated carbon, multiwalled carbon nanotubes and carbon nanofibers. The adsorption capacities were studied in the temperature range of 25-65°C and pH range from 3 to 9. Several model isotherms were used to model the adsorption equilibrium data. Also, the competitive adsorption was evaluated.

  3. Effect of Endocrine Disruptor Pesticides: A Review

    PubMed Central

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

    2011-01-01

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

  4. 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.

  5. Do endocrine disruptors cause hypospadias?

    PubMed Central

    Botta, Sisir; Cunha, Gerald R.

    2014-01-01

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

  6. 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. PMID:24647264

  7. 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...

  8. Endocrine disruptors and obesity.

    PubMed

    Heindel, Jerrold J; Newbold, Retha; Schug, Thaddeus T

    2015-11-01

    The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes. PMID:26391979

  9. 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...

  10. [Environmental contaminants and endocrine disruptors].

    PubMed

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

    2010-02-01

    The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages. PMID:20414542

  11. Endocrine disruptors and prostate cancer risk.

    PubMed

    Prins, Gail S

    2008-09-01

    There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging.

  12. Endocrine disruptors and prostate cancer risk

    PubMed Central

    Prins, Gail S

    2010-01-01

    There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

  13. 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

  14. [Endocrine disruptors: are they carcinogens?].

    PubMed

    Rochefort, Henri; Balaguer, Patrick

    2010-06-01

    Concerned with the high incidence of breast and prostate cancers in industrialized countries, including France, we reviewed the literature and national reports on the potential carcinogenic effects of several endocrine disruptors (ED) present in the environment. We examine why it is extremely difficult to obtain clear proof of a carcinogenic effect of ED in humans. Yet the results of several independent studies strongly point to such a carcinogenic effect, particularly in the case of hormone-dependent cancers. Such malignancies have been induced experimentally in rodents and have also been observed in humans. For example, a moderately elevated incidence of prostate cancer has been noted in U.S. farmers and, more recently in the French West Indian population exposed for more than 30 years to the insecticide chlordecone. We discuss the molecular mechanisms involved in this effect in prostate cancer Lessons from the observed trans-generational carcinogenic effect of the synthetic estrogen diethylstilboestrol also strongly suggests that future generations must be protected from widespread distribution of synthetic estrogens in the environment. We argue that a reduction in the use of some EDs in agriculture and the plastics industry would be much more beneficial in France than the prohibition of transgenic plants. PMID:21513143

  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. 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. PMID:26805600

  17. [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. PMID:27382804

  18. 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

  19. Human infertility: are endocrine disruptors to blame?

    PubMed Central

    Marques-Pinto, André; Carvalho, Davide

    2013-01-01

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

  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. Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

    PubMed Central

    Skinner, Michael K.

    2014-01-01

    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. PMID:25088466

  2. 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. PMID:25088466

  3. EPIGENETIC TRANSGENERATIONAL ACTIONS OF ENDOCRINE DISRUPTORS

    PubMed Central

    Skinner, Michael K.; Manikkam, Mohan; Guerrero-Bosagna, Carlos

    2010-01-01

    Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes. PMID:21055462

  4. Epigenetic transgenerational actions of endocrine disruptors and male fertility.

    PubMed

    Anway, Matthew D; Cupp, Andrea S; Uzumcu, Mehmet; Skinner, Michael K

    2005-06-01

    Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compound) induced an adult phenotype in the F1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of male infertility. These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4). The effects on reproduction correlate with altered DNA methylation patterns in the germ line. The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.

  5. 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. ...

  6. The effects of nanomaterials as endocrine disruptors.

    PubMed

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

    2013-08-14

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

  7. 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

  8. The effects of nanomaterials as endocrine disruptors.

    PubMed

    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

  9. Possible effects of endocrine disruptors on male reproductive function.

    PubMed

    Mori, C

    2001-08-01

    Endocrine disruptors act to alter blood hormone levels or the subsequent action of hormones, including effects on hormone production, release, transport, metabolism and/or elimination together with effects on cognate receptor binding and/or subsequent intracellular receptor actions. Confirmed alterations in reproductive development in wildlife species together with reports touting an increase in the incidence of human male reproductive tract abnormalities and decreased adult sperm counts in some parts of the world have increased public concern with endocrine disruptors. A biological plausible hypothesis has suggested that man-made chemicals act as endocrine disruptors resulting in altered development of the reproductive tract causing the observed effects. Based on current knowledge, the impact of endocrine disruptors on the male reproductive function remains to be appreciated. Epidemiological human studies are necessary to fill in the gap in our knowledge. Disturbances of hormonal regulation during fetal or postnatal development in humans may induce adverse effects on the male reproductive system, but these adverse effects of endocrine disruptors on humans are subtle, and difficult to research and detect. We have investigated fetal exposure to endocrine disruptors in Japan by analyzing umbilical cords, and changes of testis-weight in Japanese men by using analytical data of necropsy. This mini-review summarizes current endocrine disruptor issues on possible effects of endocrine disruptors on male reproductive function and the results of our recent research.

  10. Possible effects of endocrine disruptors on male reproductive function.

    PubMed

    Mori, C

    2001-08-01

    Endocrine disruptors act to alter blood hormone levels or the subsequent action of hormones, including effects on hormone production, release, transport, metabolism and/or elimination together with effects on cognate receptor binding and/or subsequent intracellular receptor actions. Confirmed alterations in reproductive development in wildlife species together with reports touting an increase in the incidence of human male reproductive tract abnormalities and decreased adult sperm counts in some parts of the world have increased public concern with endocrine disruptors. A biological plausible hypothesis has suggested that man-made chemicals act as endocrine disruptors resulting in altered development of the reproductive tract causing the observed effects. Based on current knowledge, the impact of endocrine disruptors on the male reproductive function remains to be appreciated. Epidemiological human studies are necessary to fill in the gap in our knowledge. Disturbances of hormonal regulation during fetal or postnatal development in humans may induce adverse effects on the male reproductive system, but these adverse effects of endocrine disruptors on humans are subtle, and difficult to research and detect. We have investigated fetal exposure to endocrine disruptors in Japan by analyzing umbilical cords, and changes of testis-weight in Japanese men by using analytical data of necropsy. This mini-review summarizes current endocrine disruptor issues on possible effects of endocrine disruptors on male reproductive function and the results of our recent research. PMID:11577437

  11. 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.

  12. 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.

  13. Contribution of primary and secondary treatment on the removal of benzothiazoles, benzotriazoles, endocrine disruptors, pharmaceuticals and perfluorinated compounds in a sewage treatment plant.

    PubMed

    Stasinakis, Athanasios S; Thomaidis, Nikolaos S; Arvaniti, Olga S; Asimakopoulos, Alexandros G; Samaras, Vasilios G; Ajibola, Akinranti; Mamais, Daniel; Lekkas, Themistokles D

    2013-10-01

    The occurrence and fate of 36 emerging contaminants, belonging to five different classes, (benzotriazoles, BTRs; benzothiazoles, BTHs; perfluorinated compounds, PFCs; non-steroidal anti-inflammatory drugs, NSAIDs and endocrine disruptors, EDCs) were investigated in raw, treated wastewater (both particulate and dissolved phases), and in sludge from a sewage treatment plant (STP) in Athens, Greece. The average concentrations of BTRs, BTHs, NSAIDs and EDCs in raw wastewater ranged between 11 ng L(-1) and 7.27 μg L(-1), while PFCs did not exceed 100 ng L(-1). In dewatered sludge, the average concentrations ranged between 0.8 ng g(-1) dw (perfluorohexanoic acid, PFHxA) and 3895 ng g(-1) dw (nonylphenol, NP). The distribution of emerging contaminants between particulate and dissolved phase was different among the compounds. BTRs and BTHs showed lower solid-liquid distribution coefficients (Kd) than all other compounds. For 9 over the 27 compounds detected in influents, the removal efficiency was higher than 70%, while the others either were removed to a lesser extent or detected at higher concentrations in effluents. Based on this, advanced treatment processes should be applied in the future for achieving adequate emerging contaminants removal in STPs. Regarding removal mechanisms, almost 60% of BTRs and 30 to 75% of BTHs were removed in bioreactors, while the contribution of primary and secondary clarifiers was of minor importance. Sorption to primary sludge was a significant mechanism affecting EDCs fate in STP. PMID:23891999

  14. Endocrine Disruptors and Childhood Social Impairment

    PubMed Central

    Miodovnik, Amir; Engel, Stephanie M.; Zhu, Chenbo; Ye, Xiaoyun; Soorya, Latha V.; Silva, Manori J.; Calafat, Antonia M.; Wolff, Mary S.

    2011-01-01

    Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n = 404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 to 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n = 137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight phthalate (LMW) metabolite concentrations were associated with greater social deficits (β = 1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β = 1.40, 95% CI 0.1-2.7); Social Communication (β = 1.86, 95% CI 0.5-3.2) and Social Awareness (β = 1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β = 1.18, 95% CI: -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure. PMID:21182865

  15. Causal Inference Considerations for Endocrine Disruptor Research in Children's Health

    PubMed Central

    Engel, Stephanie M.; Wolff, Mary S.

    2014-01-01

    Substantial population exposure to endocrine disrupting chemicals, combined with available biomarkers and public concern, has resulted in an explosion of human health effects research. At the same time, remarkable shifts in the regulations governing the composition of some consumer products that contain endocrine disruptors (EDs) has occurred. However, important questions remain as to the weight of evidence linking EDs to human health end points. In this review, we critically examine the literature linking ED exposures to child neurodevelopment, focusing in particular on two model exposures to demonstrate issues related to bioaccumulative [e.g., polychlorinated biphenyls (PCBs)] and rapidly metabolized (e.g., phthalates) compounds, respectively. Issues of study design, confounding, and exposure measurement are considered. Given widespread exposure to these compounds, the potential public health consequences of even small effects on human health are substantial. Therefore, advancing our understanding of any impact calls for careful attention to the principles of causal inference. PMID:23514318

  16. 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 ...

  17. Endocrine disruptors and male reproductive function--a short review.

    PubMed

    Chia, S E

    2000-01-01

    Semen quality has decline in many countries over the last few decades. There has been an increase in the incidence of testicular cancer world-wide. The incidences of cryptorchidism and hypospadias have also increased in many countries. A biological plausible hypothesis has suggested that man-made chemicals act as endocrine disruptors resulting in altered development of the reproductive tract causing the observed effects. Endocrine disruptors include natural products, pharmaceuticals, industrial products and environmental pollutants. There are limitations in the current in vivo and in vitro assays for the assessment of endocrine disruptors. Epidemiological human studies are necessary to fill in the gap of knowledge. Based on the current knowledge, the impact of endocrine disruptors on the male reproductive function remain to be appreciated. PMID:10849494

  18. 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. PMID:26382024

  19. 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

  20. 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.

  1. 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.

  2. 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. PMID:23532534

  3. Endocrine disruptor activity of multiple environmental food chain contaminants.

    PubMed

    Wielogórska, E; Elliott, C T; Danaher, M; Connolly, L

    2015-02-01

    Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation. Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens( n = 3), UV filters (n = 6), phthalates (n = 4) and a metabolite, pyrethroids (n = 9) and their metabolites (n = 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17b-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

  4. [Endocrine disruptors, reproduction and hormone-dependent cancers].

    PubMed

    Fenichel, Patrick; Brucker-Davis, Françoise; Chevalier, Nicolas

    2016-01-01

    Endocrine disruptors are natural or synthetic chemical compounds which are present in the environment and which are able to interfere with hormonal regulation pathways and to induce human health deleterious effects. While their precise implication in human health and diseases is still matter of debates, it becomes likely that they have to be considered as risk factors in numerous chronic diseases: developmental and reproductive defects and hormone dependent cancers (present review), metabolic diseases (obesity and type 2 diabetes), neurodevelopmental or neurodegenerative diseases. Low doses exposure during critical windows of exposure such as foetal, perinatal and peri-pubertal periods, or chronic exposure with bioaccumulation in the adipose tissue, and possible synergic effects of several compounds ("cocktail effect") may participate to the genetic/environment interface suspected to participate to the pathophysiology of many diseases. PMID:26655259

  5. 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...

  6. 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

  7. 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.

  8. Perils of paradigm: Complexity, policy design, and the Endocrine Disruptor Screening Program

    PubMed Central

    Vogel, Jason M

    2005-01-01

    The Endocrine Disruptor Screening Program (EDSP), mandated by the United States Congress in the Food Quality Protection Act of 1996, attempts to protect public health from adverse endocrine effects of synthetic chemical compounds by establishing a new testing regime. But the complexities and uncertainties of endocrine disruption and its broader regulatory and social context all but ensure the failure of this policy. This article addresses the issues facing EDSP comprehensively and in detail, in order to move beyond the current regulatory paradigm and foster discourse on a positive role for scientists in support of EDSP's end goal: to protect public health. PMID:15701170

  9. 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.

  10. Urban Endocrine Disruptors Targeting Breast Cancer Proteins.

    PubMed

    Montes-Grajales, Diana; Bernardes, Gonçalo J L; Olivero-Verbel, Jesus

    2016-02-15

    Humans are exposed to a huge amount of environmental pollutants called endocrine disrupting chemicals (EDCs). These molecules interfere with the homeostasis of the body, usually through mimicking natural hormones leading to activation or blocking of their receptors. Many of these compounds have been associated with a broad range of diseases including the development or increased susceptibility to breast cancer, the most prevalent cancer in women worldwide, according to the World Health Organization. Thus, this article presents a virtual high-throughput screening (vHTS) to evaluate the affinity of proteins related to breast cancer, such as ESR1, ERBB2, PGR, BCRA1, and SHBG, among others, with EDCs from urban sources. A blind docking strategy was employed to screen each protein-ligand pair in triplicate in AutoDock Vina 2.0, using the computed binding affinities as ranking criteria. The three-dimensional structures were previously obtained from EDCs DataBank and Protein Data Bank, prepared and optimized by SYBYL X-2.0. Some of the chemicals that exhibited the best affinity scores for breast cancer proteins in each category were 1,3,7,8-tetrachlorodibenzo-p-dioxin, bisphenol A derivatives, perfluorooctanesulfonic acid, and benzo(a)pyrene, for catalase, several proteins, sex hormone-binding globulin, and cytochrome P450 1A2, respectively. An experimental validation of this approach was performed with a complex that gave a moderate binding affinity in silico, the sex hormone binding globulin (SHBG), and bisphenol A (BPA) complex. The protein was obtained using DNA recombinant technology and the physical interaction with BPA assessed through spectroscopic techniques. BPA binds on the recombinant SHBG, and this results in an increase of its α helix content. In short, this work shows the potential of several EDCs to bind breast cancer associated proteins as a tool to prioritize compounds to perform in vitro analysis to benefit the regulation or exposure prevention by the

  11. 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...

  12. Environmental fate of phenolic endocrine disruptors: field and laboratory studies.

    PubMed

    Giger, Walter; Gabriel, Frédéric L P; Jonkers, Niels; Wettstein, Felix E; Kohler, Hans-Peter E

    2009-10-13

    Alkylphenolic compounds derived from microbial degradation of non-ionic surfactants became a major focus of environmental research in the early 1980s. More toxic than the parent compounds and weakly oestrogenic, certain metabolites of nonylphenol polyethoxylate (NPnEO) surfactants, especially nonylphenol (NP), raised sustained concern over the risk they pose to the environment and triggered legal measures as well as partly voluntary actions by the manufacturing industry. Continuous progress in the development of analytical techniques is crucial to understand how these alkylphenolic compounds behave in wastewater treatment, the aquatic environment and in laboratory experiments. Measured concentrations and mass flows of phenolic endocrine disruptors, particularly nonylphenolic compounds, bisphenol A and parabens in municipal wastewater effluents and in the Glatt River, Switzerland, show that rain events leading to discharges of untreated wastewater into rivers have a great impact on the riverine mass flows of contaminants. Biotransformation experiments in our laboratory with nonylphenoxyacetic acid and individual NP isomers enabled the elucidation of degradation pathways of these compounds. The finding that nonylphenoxyacetic acid is metabolized via NP further underscores the role of NP as the most relevant metabolite in the degradation of NPnEO. Several Sphingomonadaceae bacterial strains were found to degrade alpha-quaternary 4-NP isomers by an ipso-substitution mechanism, and to use only the aromatic part of the molecule. These reactions turned out to be isomer specific, meaning that rate and extent of transformation depend on constitution, and possibly also on the absolute configuration of the alkyl side chain of a specific isomer. The observation that NP isomers with distinct oestrogenic activities are differentially degraded has significant implications for risk assessment.

  13. Environmental fate of phenolic endocrine disruptors: field and laboratory studies.

    PubMed

    Giger, Walter; Gabriel, Frédéric L P; Jonkers, Niels; Wettstein, Felix E; Kohler, Hans-Peter E

    2009-10-13

    Alkylphenolic compounds derived from microbial degradation of non-ionic surfactants became a major focus of environmental research in the early 1980s. More toxic than the parent compounds and weakly oestrogenic, certain metabolites of nonylphenol polyethoxylate (NPnEO) surfactants, especially nonylphenol (NP), raised sustained concern over the risk they pose to the environment and triggered legal measures as well as partly voluntary actions by the manufacturing industry. Continuous progress in the development of analytical techniques is crucial to understand how these alkylphenolic compounds behave in wastewater treatment, the aquatic environment and in laboratory experiments. Measured concentrations and mass flows of phenolic endocrine disruptors, particularly nonylphenolic compounds, bisphenol A and parabens in municipal wastewater effluents and in the Glatt River, Switzerland, show that rain events leading to discharges of untreated wastewater into rivers have a great impact on the riverine mass flows of contaminants. Biotransformation experiments in our laboratory with nonylphenoxyacetic acid and individual NP isomers enabled the elucidation of degradation pathways of these compounds. The finding that nonylphenoxyacetic acid is metabolized via NP further underscores the role of NP as the most relevant metabolite in the degradation of NPnEO. Several Sphingomonadaceae bacterial strains were found to degrade alpha-quaternary 4-NP isomers by an ipso-substitution mechanism, and to use only the aromatic part of the molecule. These reactions turned out to be isomer specific, meaning that rate and extent of transformation depend on constitution, and possibly also on the absolute configuration of the alkyl side chain of a specific isomer. The observation that NP isomers with distinct oestrogenic activities are differentially degraded has significant implications for risk assessment. PMID:19736229

  14. 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

    ... systems. Extensive background on the Agency's endocrine program is available at http://www.epa.gov/endo..., ``Endocrine Disruptor Screening Program; Policies and Procedures for Initial Screening,'' (74 FR 17560), http... AGENCY Results From Inert Ingredient Test Orders Issued Under EPA's Endocrine Disruptor Screening...

  15. 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

    ... endocrine system or not; (2) has practical utility before proceeding with more Tier 1 screening orders for... AGENCY Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening... Request (ICR) of the first list of 67 chemicals to receive orders under the Endocrine Disruptor...

  16. 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. PMID:25885102

  17. 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.

  18. Impact of endocrine disruptors on ovarian steroidogenesis.

    PubMed

    Mlynarcikova, A; Fickova, M; Scsukova, S

    2014-10-01

    Production of steroid hormones by the ovary plays a key role in the female phenotype maintenance, as well as is critical for regular ovarian processes, including follicle growth, oocyte maturation and ovulation. Thus, optimal ovarian steroid synthesis is an indispensable requisite for the female reproductive health. In the past decades, along with an increased incidence of female reproductive disorders, an increasing concern for the potential reproductive impact of exogenous factors, particularly of environmental pollutants with endocrine disrupting properties, has risen. The scientific studies report that ovarian steroid hormone production is being recognized as an important target for the action of endocrine disrupting chemicals (EDCs). The fact that these chemicals have been detected in the biological samples of general population, and even directly in the follicular fluid of women, emphasizes the demands for testing the influence of EDCs on ovarian steroidogenesis. For these purposes, different methodological approaches have been employed, from in vivo studies on female rodents to in vitro experimental procedures using steroidogenically active follicular cells. In the present review, the effects of selected EDCs (pesticides, phthalate and phenol derivatives, and halogenated arylhydrocarbons) on the processes of ovarian steroidogenesis are summarized, and possible mechanisms of action of these agents are outlined.

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

    PubMed

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

    2016-08-01

    Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age. PMID:27349723

  20. 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

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

    PubMed

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

    2015-07-01

    Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty. PMID:25998096

  2. 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.

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

    PubMed

    Roncati, Luca; Piscioli, Francesco; Pusiol, Teresa

    2016-09-01

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

  4. 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

    ... (75 FR 70248) (FRL-8848-7). In that notice, EPA announced the second list of chemicals and substances... AGENCY Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension of... Endocrine Disruptor Screening Program's (EDSP) second list of chemicals for Tier 1 screening. This...

  5. 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.

  6. 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". PMID:26825071

  7. 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. PMID:26847433

  8. A critical review finds styrene lacks direct endocrine disruptor activity.

    PubMed

    Gelbke, Heinz-Peter; Banton, Marcy; Leibold, Edgar; Pemberton, Mark; Samson, Susan Leanne

    2015-01-01

    The European Commission lists styrene (S) as an endocrine disruptor based primarily on reports of increased prolactin (PRL) levels in S-exposed workers. The US Environmental Protection Agency included S in its list of chemicals to be tested for endocrine activity. Therefore, the database of S for potential endocrine activity is assessed. In vitro and in vivo screening studies, as well as non-guideline and guideline investigations in experimental animals indicate that S is not associated with (anti)estrogenic, (anti)androgenic, or thyroid-modulating activity or with an endocrine activity that may be relevant for the environment. Studies in exposed workers have suggested elevated PRL levels that have been further examined in a series of human and animal investigations. While there is only one definitively known physiological function of PRL, namely stimulation of milk production, many normal stress situations may lead to elevations without any chemical exposure. Animal studies on various aspects of dopamine (DA), the PRL-regulating neurotransmitter, in the central nervous system did not give mechanistic explanations on how S may affect PRL levels. Overall, a neuroendocrine disruption of PRL regulation cannot be deduced from a large experimental database. The effects in workers could not consistently be reproduced in experimental animals and the findings in humans represented acute reversible effects clearly below clinical and pathological levels. Therefore, unspecific acute workplace-related stress is proposed as an alternative mode of action for elevated PRL levels in workers. PMID:26406562

  9. OECD test strategies and methods for endocrine disruptors.

    PubMed

    Gelbke, H P; Kayser, M; Poole, A

    2004-12-01

    The question whether (man-made or natural) chemical substances may have an adverse effect on the endocrine system has gained high visibility in the public as well as in the scientific community. This relates to possible effects on the environment as well as on human health for chemicals with (anti)estrogenic, (anti)androgenic or (anti)thyroid activity. Taking into account the broad universe of chemicals to which humans or the environment may be exposed, a sound testing strategy and robust test methods are urgently needed. Both subjects have been addressed by a specific OECD working group (EDTA-Endocrine Disruptor Testing and Assessment Task Force) involving regulatory agencies, the scientific community, chemical industry and NGOs. Like other organizations the OECD has adopted a tiered-testing strategy with the first tier using screening assays as quick and inexpensive tools, providing a way of generating alerts to potential endocrine activity that can be used to prioritize substances for definitive tests that then can determine the toxicological consequences of endocrine toxicity. The efforts of the OECD have therefore concentrated on the validation of specific screening and testing guidelines, like the uterotrophic, the Hershberger, and the "enhanced TG 407" test. The experimental testing necessary for this validation procedure is completed for the uterotrophic and the "enhanced TG 407" tests and near completion for the Hershberger assay. The data obtained so far have been published (for the uterotrophic assay) or will be submitted to the EDTA working group for final evaluation. Overall, the validation program has been very successful and should be sufficient for setting up OECD test guidelines for these experimental procedures. This will add substantially to the "tool-box" of OECD test methods that is available internationally to regulatory agencies and chemical industry for the identification and assessment of possible endocrine disruptors. Despite this success

  10. 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.

  11. 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. PMID:23683400

  12. Effects of Environmental Endocrine Disruptors on Pubertal Development

    PubMed Central

    Darcan, Şükran

    2011-01-01

    The onset and course of puberty are under the control of the neuroendocrine system. Factors affecting the timing and regulation of the functions of this system may alter the onset and course of puberty. Several environmental endocrine disruptors (EDs) with significant influences on the normal course of puberty have been identified. Numerous animal and human studies concerning EDs have been conducted showing that these substances may extensively affect human health; nevertheless, there are still several issues that remain to be clarified. In this paper, the available evidence from animal and human studies on the effects of environmental EDs with the potential to cause precocious or delayed puberty was reviewed. Conflict of interest:None declared. PMID:21448326

  13. 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

    ... more specific chemical effects on the endocrine system, and are currently in the process of being... substance interferes with the endocrine systems of humans or other species simply because it has been listed... AGENCY Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening...

  14. 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

    ... screening and testing chemicals with the potential to interact with the endocrine system. Tier 1 screening... AGENCY Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight-of... submitted as part of EPA's two-tiered paradigm for screening and testing chemicals for endocrine activity...

  15. 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...

  16. Update of OECD DART guidelines with endocrine disruptor relevant endpoints: Practical considerations.

    PubMed

    Beekhuijzen, Manon; van Otterdijk, Francois; Wieland, Willemien; van Tuyl, Miranda; Rijcken, Robert Pels; Peter, Birgit; Emmen, Harry

    2016-09-01

    In 1998, the OECD initiated a high-priority project aimed at revising existing test guidelines and developing new test guidelines for screening of potential endocrine disruptors. In 2011, OECD 443 was adopted, and in 2015 OECD 421 and OECD 422 were updated with endocrine disruptor relevant endpoints. A feasibility study for the enhancement of OECD 414 with endocrine disruptor relevant endpoints is currently ongoing. The addition of these endpoints is considered crucial for gaining more information on endocrine disruptor potency of tested chemicals, however it should be noted that these additions have a major impact on the study designs and give rise to several practical challenges. The aim of this review is to discuss important aspects of these challenging study designs and to share our knowledge on their implementation in our laboratory. Together, this review can be used as guidance for other laboratories, study monitors and registration officers. PMID:27063183

  17. 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. PMID:25845526

  18. 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.

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

    PubMed

    Sichilongo, Kwenga; Torto, Nelson

    2006-08-01

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

  20. 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.

  1. 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 ...

  2. 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

  3. 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

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

    PubMed Central

    2012-01-01

    Backgrounds Previous studies suggested that endocrine disruptors (ED) are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking. Methods Bisphenol A (BPA) and Aroclor 1254 (polychlorinated biphenyls) were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations. Results At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro. Conclusions In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors. PMID:22546201

  5. 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

  6. 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 ...

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

    PubMed Central

    Zhang, Mingyue; Duan, Zhenghua; Wu, Yinghong; Liu, Zhen; Li, Ke; Wang, Lei

    2015-01-01

    Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S. PMID:26633438

  8. Selecting appropriate animal models and experimental designs for endocrine disruptor research and testing studies.

    PubMed

    Stokes, William S

    2004-01-01

    Evidence that chemicals in the environment may cause developmental and reproductive abnormalities in fish and wildlife by disrupting normal endocrine functions has increased concern about potential adverse human health effects from such chemicals. US laws have now been enacted that require the US Environmental Protection Agency (EPA) to develop and validate a screening program to identify chemicals in food and water with potential endocrine-disrupting activity. EPA subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro and in vivo test systems to identify chemicals that may adversely affect humans and ecologically important animal species. However, the endocrine system can be readily modulated by many experimental factors, including diet and the genetic background of the selected animal strain or stock. It is therefore desirable to minimize or avoid factors that cause or contribute to experimental variation in endocrine disruptor research and testing studies. Standard laboratory animal diets contain high and variable levels of phytoestrogens, which can modulate physiologic and behavioral responses similar to both endogenous estrogen as well as exogenous estrogenic chemicals. Other studies have determined that some commonly used outbred mice and rats are less responsive to estrogenic substances than certain inbred mouse and rat strains for various estrogen-sensitive endpoints. It is therefore critical to select appropriate biological models and diets for endocrine disruptor studies that provide optimal sensitivity and specificity to accomplish the research or testing objectives. An introduction is provided to 11 other papers in this issue that review these and other important laboratory animal experimental design considerations in greater detail, and that review laboratory animal and in vitro models currently being used or evaluated for endocrine disruptor research and testing. Selection of appropriate animal models and experimental design

  9. 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

  10. Key Learnings from the Endocrine Disruptor Screening Program (EDSP) Tier 1 Rodent Uterotrophic and Hershberger Assays

    PubMed Central

    Marty, M Sue; O'Connor, John C

    2014-01-01

    In 2009, companies began screening compounds using the US Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP). EDSP has two tiers: Tier 1 includes 11 assays to identify compounds with potential endocrine activity. This article describes two laboratories' experiences conducting Tier 1 uterotrophic and Hershberger assays. The uterotrophic assay detects estrogen receptor agonists through increases in uterine weight. The advantages of the uterotrophic rat models (immature vs. adult ovariectomized) and exposure routes are discussed. Across 29 studies, relative differences in uterine weights in the vehicle control group and 17α-ethynylestradiol–positive control group were reasonably reproducible. The Hershberger assay detects androgen receptor (AR) agonists, antagonists, and 5α-reductase inhibitors through changes in accessory sex tissue (AST) weights. Across 23 studies, AST weights were relatively reproducible for the vehicle groups (baseline), testosterone propionate (TP) groups (androgenic response), and flutamide + TP groups (antiandrogenic response). In one laboratory, one and four compounds were positive in the androgenic and antiandrogenic portions of the assay, respectively. Each compound was also positive for AR binding. In the other laboratory, three compounds showed potential antiandrogenic activity, but each compound was negative for AR binding and did not fit the profile for 5α-reductase inhibition. These compounds induced hepatic enzymes that enhanced testosterone metabolism/clearance, resulting in lower testosterone and decreased capacity to maintain AST weights. The Hershberger androgenic and antiandrogenic performance criteria were generally attainable. Overall, the uterotrophic and Hershberger assays were easily adopted and function as described for EDSP screening, although the mode of action for positive results may not be easily determined. PMID:24515841

  11. Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action

    PubMed Central

    Anderson, Alison M.; Carter, Kim W.; Anderson, Denise; Wise, Michael J.

    2012-01-01

    Background Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. Methodology/Principal Findings The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. Conclusions/Significance This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods. PMID:22496781

  12. Effect of wastewater chlorination on endocrine disruptor removal.

    PubMed

    Noutsopoulos, C; Mamais, D; Samaras, V; Bouras, T; Marneri, M; Antoniou, K

    2013-01-01

    Endocrine disrupting chemicals (EDCs) are compounds of mainly anthropogenic origin that interfere with the endocrine system of animals and humans thus causing a series of disorders. Wastewater treatment plants are one of the major routes for transporting such chemicals to the water courses. In the context of this study, several chlorination batch tests were performed in order to assess the effectiveness of chlorination to remove bisphenol A (BPA), triclosan (TCS), nonylphenol (NP) and its ethoxylates (NP1EO and NP2EO) from secondary effluent. According to the results, an appreciable removal of NP, BPA and TCS to the order of 60-84% was observed as an effect of moderate chlorination doses. This was not the case for NP1EO and NP2EO as even at high chlorine doses, removal efficiencies were lower (37% for NP1EO and 52% for NP2EO). Removal efficiencies of NP, BPA and TCS are practically independent of contact time, although this was not the case for NP1EO and NP2EO. Based on toxicity experiments, it is anticipated that following chlorination of the target chemicals, production of more toxic metabolites is taking place. Therefore the effectiveness of chlorination to remove EDCs is questionable and more research is needed to guarantee safe wastewater reuse. PMID:23552244

  13. 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...

  14. 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...

  15. 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. PMID:26270219

  16. 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

  17. 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.

  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. 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). PMID:26087856

  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. Dietary exposure to the endocrine disruptor tolylfluanid promotes global metabolic dysfunction in male mice.

    PubMed

    Regnier, Shane M; Kirkley, Andrew G; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A; Kamau, Wakanene; Thomas, Celeste C; Williams, Ayanna K; Hayes, Emily T; Massad, Nicole L; Johnson, Daniel N; Huang, Lei; Zhang, Chunling; Sargis, Robert M

    2015-03-01

    Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome. PMID:25535829

  2. Annelid Endocrine Disruptors and a Survey of Invertebrate FMRFamide-Related Peptides.

    PubMed

    Krajniak, Kevin G

    2005-01-01

    There is a growing body of literature describing the actions of endocrine disruptors on annelids. These pollutants cause decreases in growth and reproductive output, delay sexual maturation, and inhibit the immune system in annelids. More studies are needed to determine the mechanisms that underlie these responses. Most invertebrate endocrine disruptor research focuses on steroids. In recent years many new invertebrate peptide hormones including those related to the molluscan peptide FMRFamide have been identified. Since the storage of these peptides can be inhibited by steroids during insect metamorphosis, they may be affected by endocrine disruptors. Therefore, it is worthwhile to give a brief overview of this peptide family to those studying endocrine disruption in invertebrates with the hope that they may begin to consider these peptides in their future research. In 1977 Price and Greenberg isolated FMRFamide from the cerebral ganglia of the clam, Macrocallista nimbosa. Since then researchers have used bioassays and immunoassays to identify a large number of FMRFamide-related peptides (FaRPs) from many invertebrate phyla. Even more peptides are predicted by the FaRP genes that have been sequenced. FaRPs have a variety of functions and act as neurotransmitters, neuromodulators, or neurohormones. Each function is species and tissue specific. Most FaRP receptors are linked to a second messenger system. However, at least one is a ligand gated sodium channel. On going studies are examining FaRPs from the molecular to organismal level.

  3. Dietary Exposure to the Endocrine Disruptor Tolylfluanid Promotes Global Metabolic Dysfunction in Male Mice

    PubMed Central

    Regnier, Shane M.; Kirkley, Andrew G.; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A.; Kamau, Wakanene; Thomas, Celeste C.; Williams, Ayanna K.; Hayes, Emily T.; Massad, Nicole L.; Johnson, Daniel N.; Huang, Lei; Zhang, Chunling

    2015-01-01

    Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome. PMID:25535829

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

    PubMed

    Langer, P

    2015-01-01

    Author of this review submits a comprehensive report of his long-lasting research regarding the global pollution by endocrine disruptors (EDs), EDs and diabetes and obesity, EDs and the thyroid in highly polluted Slovakia, Ah-receptor: the central pivot responsible for such global "EDs disaster", EDs and immune system, EDs and testosterone, EDs in mothers and newborns, EDs and human genome, and EDs at the beginning of the millennium. PMID:25687678

  5. 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.

  6. Potential of various herbaceous species to remove the endocrine disruptor bisphenol A from aqueous media.

    PubMed

    Loffredo, Elisabetta; Eliana Gattullo, C; Traversa, Andreina; Senesi, Nicola

    2010-09-01

    Several different plants are capable of removing and detoxifying the endocrine disruptor bisphenol A from water starting with initial concentrations of 4.6 mg L(-1) and 46 mg L(-1). Bisphenol A seems to be glycosylated, transformed to polar compounds, and bound as residue by five forage grasses, fescue, couch grass, perennial ryegrass, Siberian wheatgrass, and white clover, and three horticultural species, cucumber, marrow plant, and radish. Septic and axenic testing established that microbial degradation is possible for fescue and radish, and perennial ryegrass exudates seemed to contain enzymatic activity that transforms bisphenol A, but this activity is evidently deactivated by microorganisms. Although the grasses tested were more effective than the horticultural species, the optimal species of plants best suited for phytoremediation of bisphenol A was not determined. The limited plant testing during 16d does not define how nor which phytoremediation practices can be applied, but the removal efficiency and evident transformation of bisphenol A justify further feasibility, pilot, and treatability testing of different wastewaters.

  7. Pollution by endocrine disruptors in a southwest European temperate coastal lagoon (Ria de Aveiro, Portugal).

    PubMed

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

    2016-02-01

    Ria de Aveiro is a Portuguese lagoon renowned for its ecological and economic importance. Nonetheless, in literature, few data exist about its organic pollution. Accordingly, this study chemically monitored for the first time a series of 17 endocrine disruptor compounds (EDCs). The target EDCs include natural (17β-oestradiol, oestrone) and pharmaceutical (17α-ethynylestradiol) oestrogens, industrial/household xenoestrogenic pollutants (octylphenols, nonylphenols and their mono and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For the investigation of these EDCs, water samples were taken from eight sampling sites widely spread along the lagoon, at three different occasions in 2011, and analysed by gas chromatography-mass spectrometry. Results not only proved the ubiquitous distribution of all analysed EDCs but revealed that their amounts were extremely high at all sampling sites. The annual average concentrations were ≈ 46 ng/L for oestrogens, ≈ 3962 ng/L for industrial/household chemicals, ≈ 1740 ng/L for phytoestrogens and ≈ 908 ng/L for SITO. Normalising these values in ethynylestradiol equivalents (EE2eq), the oestrogenic load in this lagoon attained ≈ 50 ng/L EE2eq, which is a value well above that known to produce oestrogenic-induced disorders in aquatic fauna. Additionally, phosphate concentrations were also above the legal limits (>1 mg/L). Overall, data show EDCs at toxic relevant levels in the Ria de Aveiro and stress the need to enforce depollution measures in this habitat.

  8. The quantification and characterization of endocrine disruptor bisphenol-A leaching from epoxy resin.

    PubMed

    Bae, B; Jeong, J H; Lee, S J

    2002-01-01

    Bisphenol-A (BPA), a known endocrine disruptor, is a main building block of epoxy resin which has been widely used as a surface coating agent on residential water storage tanks. Therefore, BPA leaching from the epoxy resin can adversely affect human health. In this study, BPA leaching from three epoxy resins were quantified at 20, 50, 75 and 100 degrees C both in deionized water and the specified test water, respectively. BPA leached to the test water was identified using GC-MS and quantified with GC-FID after a sequential extraction and concentration. The results showed that BPA leaching has occurred in all three samples tested. The quantity of BPA from unit area of epoxy resin coating was in the range of 01.68-273. 12 microg/m2 for sample A, 29.74-1734.05 microg/m2 for sample B and 52.86-548.78 microg/m2 for sample C depending on the test temperature, respectively. In general, the amount of BPA leashing increased as the water temperature increases. This result implies a higher risk of BPA leaching to drinking water during a summer season. In addition, microbial growth, measured by colony forming units, in epoxy coated water tanks was higher than that in a stainless steel tank. The results suggest that compounds leaching from epoxy resin may support the growth of microorganisms in a residential water holding tank.

  9. 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...

  10. 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

  11. 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. PMID:25714811

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

    PubMed

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

    2016-08-01

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

  13. Perinatal exposure to endocrine disruptors: sex, timing and behavioral endpoints

    PubMed Central

    Palanza, Paola; Nagel, Susan C; Parmigiani, Stefano; vom Saal, Frederick S

    2016-01-01

    Of the approximately 85,000 chemicals in use, 1000 have been identified as having the ability to disrupt normal endocrine function. Exposure to endocrine disrupting chemicals (EDCs) during critical period in brain differentiation (prenatal and neonatal life) via the mother can alter the course of the development of sexually dimorphic behaviors. Bisphenol A (BPA) is a very high volume chemical used in plastic, resins and other products, and virtually everyone examined has detectable BPA. BPA has estrogenic activity and is one of the most studied EDCs. We review evidence from studies in rodents using dose levels relevant to human exposure. BPA alters behavior and eliminates or in some cases reverses sexually dimorphic behaviors observed in unexposed animals. PMID:27019862

  14. 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...

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

    PubMed

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

    2014-06-01

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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Meeting report: international workshop on endocrine disruptors: exposure and potential impact on consumers health.

    PubMed

    Rousselle, C; Ormsby, J N; Schaefer, B; Lampen, A; Platzek, T; Hirsch-Ernst, K; Warholm, M; Oskarsson, A; Nielsen, P J; Holmer, M L; Emond, C

    2013-02-01

    The French Agency for Food, Environmental and Occupational Health and Safety (Anses) hosted a two-day workshop on Endocrine Disruptors: Exposure and Potential Impact on Consumers Health, bringing together participants from international organizations, academia, research institutes and from German, Swedish, Danish and French governmental agencies. The main objective of the workshop was to share knowledge and experiences on endocrine disruptors (ED) exposure and potential impact on consumers' health, to identify current risk assessment practices and knowledge gaps and issue recommendations on research needs and future collaboration. The following topics were reviewed: (1) Definition of ED, (2) endpoints to be considered for Risk assessment (RA) of ED, (3) non-monotonic dose response curves, (4) studies to be considered for RA (regulatory versus academic studies), (5) point of departure and uncertainty factors, (6) exposure assessment, (7) regulatory issues related to ED. The opinions expressed during this workshop reflect day-to-day experiences from scientists, regulators, researchers, and others from many different countries in the fields of risk assessment, and were regarded by the attendees as an important basis for further discussions. Accordingly, the participants underlined the need for more exchange in the future to share experiences and improve the methodology related to risk assessment for endocrine disrupters. PMID:23211416

  3. Environmental causes of cancer: endocrine disruptors as carcinogens

    PubMed Central

    Soto, Ana M.; Sonnenschein, Carlos

    2014-01-01

    Environmental endocrine disrupting chemicals (EDCs), including pesticides and industrial chemicals, have been and are released into the environment producing deleterious effects on wildlife and humans. The effects observed in animal models after exposure during organogenesis correlate positively with an increased incidence of malformations of the male genital tract and of neoplasms and with the decreased sperm quality observed in European and US populations. Exposure to EDCs generates additional effects, such as alterations in male and female reproduction and changes in neuroendocrinology, behavior, metabolism and obesity, prostate cancer and thyroid and cardiovascular endocrinology. This Review highlights the carcinogenic properties of EDCs, with a special focus on bisphenol A. However, humans and wildlife are exposed to a mixture of EDCs that act contextually. To explain this mindboggling complexity will require the design of novel experimental approaches that integrate the effects of different doses of structurally different chemicals that act at different ages on different target tissues. The key to this complex problem lies in the adoption of mathematical modeling and computer simulations afforded by system biology approaches. Regardless, the data already amassed highlight the need for a public policy to reduce exposure to EDCs. PMID:20498677

  4. Steroids in semen, their role in spermatogenesis, and the possible impact of endocrine disruptors.

    PubMed

    Hampl, Richard; Kubátová, Jana; Sobotka, Vladimír; Heráček, Jiří

    2013-06-01

    The data on hormonal steroids in the human seminal plasma and their role in spermatogenesis are summarized. The seminal steroid levels need not correlate with the blood plasma levels. The recent reports showed that androgen, especially dihydrotestosterone, and the estrogen levels in the seminal fluid may be used as the markers of spermatogenesis impairment. The estradiol concentration in the seminal plasma was higher than in the blood plasma, and its levels were significantly increased in men with impaired spermatogenesis. A good indicator for predicting the normal spermatogenesis, therefore, seems to be the testosterone/estradiol ratio. The seminal plasma also contains significant amounts of cortisol, which influences the androgen biosynthesis through its receptors in the Leydig cells. The local balance between cortisol and inactive cortisone is regulated by 11β-hydroxysteroid dehydrogenase, the activity of which may be affected by the environmental chemicals acting as the endocrine disruptors (EDCs). These compounds are believed to participate in worsening the semen quality - the sperm count, motility, and morphology, as witnessed in the recent last decades. As to the steroids' role in the testis, the EDCs may act as antiandrogens by inhibiting the enzymes of testosterone biosynthesis, as the agonists or antagonists through their interaction with the steroid hormone receptors, or at the hypothalamic-pituitary-gonadal axis. Surprisingly, though the EDCs affect the steroid action in the testis, there is no report of a direct association between the concentrations of steroids and the EDCs in the seminal fluid. Therefore, measuring the steroids in the semen, along with the various EDCs, could help us better understand the role of the EDCs in the male reproduction.

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

    PubMed Central

    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. PMID:24497529

  6. Pollution by endocrine disruptors in a southwest European temperate coastal lagoon (Ria de Aveiro, Portugal).

    PubMed

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

    2016-02-01

    Ria de Aveiro is a Portuguese lagoon renowned for its ecological and economic importance. Nonetheless, in literature, few data exist about its organic pollution. Accordingly, this study chemically monitored for the first time a series of 17 endocrine disruptor compounds (EDCs). The target EDCs include natural (17β-oestradiol, oestrone) and pharmaceutical (17α-ethynylestradiol) oestrogens, industrial/household xenoestrogenic pollutants (octylphenols, nonylphenols and their mono and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For the investigation of these EDCs, water samples were taken from eight sampling sites widely spread along the lagoon, at three different occasions in 2011, and analysed by gas chromatography-mass spectrometry. Results not only proved the ubiquitous distribution of all analysed EDCs but revealed that their amounts were extremely high at all sampling sites. The annual average concentrations were ≈ 46 ng/L for oestrogens, ≈ 3962 ng/L for industrial/household chemicals, ≈ 1740 ng/L for phytoestrogens and ≈ 908 ng/L for SITO. Normalising these values in ethynylestradiol equivalents (EE2eq), the oestrogenic load in this lagoon attained ≈ 50 ng/L EE2eq, which is a value well above that known to produce oestrogenic-induced disorders in aquatic fauna. Additionally, phosphate concentrations were also above the legal limits (>1 mg/L). Overall, data show EDCs at toxic relevant levels in the Ria de Aveiro and stress the need to enforce depollution measures in this habitat. PMID:26787270

  7. 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.

  8. 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, ...

  9. Development and validation of a GC-MS method for the evaluation of 17 endocrine disruptor compounds, including phytoestrogens and sitosterol, in coastal waters - their spatial and seasonal levels in Porto costal region (Portugal).

    PubMed

    Rocha, Maria João; Cruzeiro, Catarina; Rocha, Eduardo

    2013-06-01

    A gas chromatography with mass spectrometric detection (GC-MS) method was developed and optimized for the determination of 17 endocrine disrupting compounds (EDCs) in coastal water samples. The evaluated EDCs were from different origins and included estrogens, bisphenol A, alkylphenolethoxylates, alkylphenols, phytoestrogens and sitosterol (SITO). The EDCs were extracted from samples using Oasis HLB (Hydrophilic-Lipophilic Balance) cartridges and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) added with 1% trimethylchlorosilane (TMCS). The validation parameters revealed that this method was highly specific for all assayed compounds (>99%) and the linearity of the calibration curves showed a correlation higher than 0.99. The detection limits were at low ng/L level and the recovery rates were higher than 70%. The performance of the method was checked using coastal water samples taken every 2 months during 2009-2010 from the Douro River estuary and the Porto coastline (Portugal). These data revealed that approximately 98.0% of the analyzed compounds showed levels above their limits of detection (LODs). The measured estrogens (2-20 ng/L) and industrial pollutants (up to 1.1 μg/L) were in biologic hazardous concentrations. Besides, a clear seasonal pattern of fluctuation was established for phytoestrogens and SITO. The physicochemical data, namely the amounts of nitrates, nitrites and phosphorous, confirmed the low water quality of this area.

  10. 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

  11. Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination.

    PubMed

    Chang, Hung-Shu; Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K

    2006-12-01

    Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal sex determination was previously found to promote transgenerational disease states. The actions of vinclozolin appear to be due to epigenetic alterations in the male germline that are transmitted to subsequent generations. Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm. These sequences were identified and mapped to specific genes and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered methylation pattern of 15 of the candidate DNA sequences. Alterations in the epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in the F2 and F3 generation germline. Therefore, the reprogramming of the male germline involves the induction of new imprinted-like genes/DNA sequences that acquire an apparent permanent DNA methylation pattern that is passed at least through the paternal allele. The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F1 and F2 generation testis. A number of the imprinted-like genes/DNA sequences identified are associated with epigenetic linked diseases. In summary, an endocrine disruptor exposure during embryonic gonadal sex determination was found to promote an alteration in the epigenetic (i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline, and this is associated with the development of transgenerational disease states.

  12. Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance.

    PubMed

    Ventura, Clara; Nieto, María Rosa Ramos; Bourguignon, Nadia; Lux-Lantos, Victoria; Rodriguez, Horacio; Cao, Gabriel; Randi, Andrea; Cocca, Claudia; Núñez, Mariel

    2016-02-01

    Endocrine disruptors (EDs) are compounds that interfere with hormone regulation and influence mammary carcinogenesis. We have previously demonstrated that the pesticide chlorpyrifos (CPF) acts as an ED in vitro, since it induces human breast cancer cells proliferation through estrogen receptor alpha (ERα) pathway. In this work, we studied the effects of CPF at environmental doses (0.01 and 1mg/kg/day) on mammary gland, steroid hormone receptors expression and serum steroid hormone levels. It was carried out using female Sprague-Dawley 40-days-old rats exposed to the pesticide during 100 days. We observed a proliferating ductal network with a higher number of ducts and alveolar structures. We also found an increased number of benign breast diseases, such as hyperplasia and adenosis. CPF enhanced progesterone receptor (PgR) along with the proliferating cell nuclear antigen (PCNA) in epithelial ductal cells. On the other hand, the pesticide reduced the expression of co-repressors of estrogen receptor activity REA and SMRT and it decreased serum estradiol (E2), progesterone (Pg) and luteinizing hormone (LH) levels. Finally, we found a persistent decrease in LH levels among ovariectomized rats exposed to CPF. Therefore, CPF alters the endocrine balance acting as an ED in vivo. These findings warn about the harmful effects that CPF exerts on mammary gland, suggesting that this compound may act as a risk factor for breast cancer. PMID:26518068

  13. Simple and rapid analysis of endocrine disruptors in liquid medicines and intravenous injection solutions by automated in-tube solid-phase microextraction/high performance liquid chromatography.

    PubMed

    Mitani, Kurie; Narimatsu, Shizuo; Izushi, Fumio; Kataoka, Hiroyuki

    2003-07-14

    A simple and rapid method was developed for analyzing contamination of endocrine disruptors in liquid medicines and intravenous injection solutions. Endocrine disrupting compounds such as bisphenol A (BPA), alkylphenols and phthalates were quantitated by on-line in-tube solid-phase microextraction coupled with high performance liquid chromatography (in-tube SPME/HPLC) with UV detection. The liquid medicines and intravenous injection solutions could be used directly without any pretreatment, and the BPA, alkylphenols and phthalates in these solutions were automatically analyzed. The limits of quantification for these compounds were 1-10 ng/ml. Recoveries of these compounds spiked to the intravenous injection solutions was over 80%, except for some phthalates. Di-n-butyl phthalate (DBP) was detected at a concentration of 7-60 ng/ml in most intravenous injection solutions in plastic containers, but it was not detected in solutions in glass bottles. Diethyl phthalate, di-n-propyl phthalate, DBP and di-2-ethylhexyl phthalate (DEHP) were also detected in syrup, lotion and eye drops in plastic containers. On the other hand, BPA and alkylphenols were not detected at all in these solutions. DEHP contamination from an administration set increased when total vitamin formulation was added to the infusion solution. DEHP was easily leached from polyvinyl chloride tubing by polysorbate 80. The in-tube SPME/HPLC method is simple, rapid and automatic, and it provides a useful tool for the screening and determination of endocrine disruptor contamination in liquid medicines and intravenous injection solutions.

  14. 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...

  15. 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…

  16. Will we be taught ethics by our clones? The mutations of the living, from endocrine disruptors to genetics.

    PubMed

    Vandelac, L; Bacon, M H

    1999-12-01

    Considering the worldwide threat to health and reproduction related to endocrine disruptors (by-products of the chemical industry); considering the untrammelled development of the industrialization and engineering of the living, ethics and gynaecology/obstetrics itself is at a crossroads. Endocrine disruptors (derived from organochlorines and persistent organic pollutants such as PCBs, dioxins and furans, and pesticides such as aldrin, chlordane and DDT), are prime suspects in the deterioration of fertility and intellectual faculties and possibly a key factor in endometriosis, breast cancer and prostate cancer. The long-term and pernicious impacts of endocrine disruptors show our poor understanding of the complexities of life's mechanisms. Paradoxically, with our short-term perspectives and predilection for a technological fix, the problem posed by endocrine disruptors may accelerate the use of reproductive technologies such as ICSI and even cloning, as well as the dissemination of genetically modified organisms. The cure could be worse than the disease. Given the gravity of the challenge to humanity related to the chemical erosion of human health, the mutation of human conception introduced by reproductive technologies and by the drive to genetically modify nature and even human nature, we must urgently re-evaluate the direction in which our societies are headed and the reliance on profit-oriented technology to save us from ourselves. In these circumstances, the collective exercise of wisdom, prudence and responsibility towards the essence and integrity of humanity has become, more than ever, an ethical, and perhaps even a survival, imperative. PMID:10718712

  17. Occurrence and sources of selected phenolic endocrine disruptors in Ria de Aveiro, Portugal

    PubMed Central

    Sousa, Ana; Galante-Oliveira, Susana; Barroso, Carlos M.; Kohler, Hans-Peter E.; Giger, Walter

    2009-01-01

    Background, aim and scope Ria de Aveiro (Portugal) is a shallow coastal lagoon of high economic and ecological importance. Hardly any data on its chemical pollution by polar organic pollutants are available in literature. This study focused on the presence and sources of a series of phenolic endocrine-disrupting compounds (EDCs) in this area, including parabens, alkylphenolic compounds and bisphenol-A (BPA). A number of possible sources of pollution are present in the area, including the large harbours present in the lagoon, the city of Aveiro and the rivers discharging into the area. A recently constructed submarine wastewater outfall, located a few kilometres from the lagoon inlet has also been suggested as a possible source of pollution to Ria de Aveiro in several publications. The aim of the current field study was to investigate the occurrence and main sources of phenolic endocrine disruptors in Ria de Aveiro. Materials and methods An extensive sampling campaign was performed, with surface water and wastewater grab samples taken at over 50 locations, in duplicate on different days. Samples were treated using solid phase extraction and analysed by liquid chromatography tandem mass spectrometry. Results and discussion Concentrations in lagoon water were generally low: not exceeding 20 ng/L for most analytes. Levels in river water exceeded those in the lagoon by a factor 3 to 500 (o-phenylphenol (PhP) and nonylphenoxy ethoxy acetic acids (A9PEC), respectively), with concentrations up to 700 ng/L for BPA and 7,300 ng/L for A9PEC. Samples from the harbours showed EDC levels similar to those in the rest of the lagoon, but in the city of Aveiro, elevated concentrations were observed for alkylphenol ethoxylates (A9PEO), A9PEC, PhP and BPA. Wastewater effluents showed low levels for parabens, whilst alkylphenolic compounds reached several micrograms per litre. The effluents are discharged into the ocean via a submarine outfall, but as marine water near the outfall

  18. 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

  19. 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.

  20. 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. PMID:26979344

  1. 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.

  2. 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.

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

    PubMed

    Hampl, Richard; Kubátová, Jana; Stárka, Luboslav

    2016-01-01

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

  4. 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.

  5. 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. PMID:26912073

  6. 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.

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

    PubMed

    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

  8. 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.

  9. 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. PMID:24004916

  10. 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

  11. Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia

    PubMed Central

    Brown, James S.

    2009-01-01

    In recent years, numerous substances have been identified as so-called “endocrine disruptors” because exposure to them results in disruption of normal endocrine function with possible adverse health outcomes. The pathologic and behavioral abnormalities attributed to exposure to endocrine disruptors like bisphenol-A (BPA) have been studied in animals. Mental conditions ranging from cognitive impairment to autism have been linked to BPA exposure by more than one investigation. Concurrent with these developments in BPA research, schizophrenia research has continued to find evidence of possible endocrine or neuroendocrine involvement in the disease. Sufficient information now exists for a comparison of the neurotoxicological and behavioral pathology associated with exposure to BPA and other endocrine disruptors to the abnormalities observed in schizophrenia. This review summarizes these findings and proposes a theory of endocrine disruption, like that observed from BPA exposure, as a pathway of schizophrenia pathogenesis. The review shows similarities exist between the effects of exposure to BPA and other related chemicals with schizophrenia. These similarities can be observed in 11 broad categories of abnormality: physical development, brain anatomy, cellular anatomy, hormone function, neurotransmitters and receptors, proteins and factors, processes and substances, immunology, sexual development, social behaviors or physiological responses, and other behaviors. Some of these similarities are sexually dimorphic and support theories that sexual dimorphisms may be important to schizophrenia pathogenesis. Research recommendations for further elaboration of the theory are proposed. PMID:18245062

  12. Evaluation of hydroxyatrazine in the endocrine disruptor screening and testing program's male and female pubertal protocols.

    PubMed

    Stoker, Tammy E; Hallinger, Daniel R; Seely, John C; Zorrilla, Leah M

    2013-10-01

    Two critical components of the validation of any in vivo screening assay are to demonstrate sensitivity and specificity. Although the Endocrine Disruptor Screening Program's Tier 1 Male and Female Pubertal Protocols have been shown to be sensitive assays for the detection of weak endocrine disrupting chemicals (EDCs), there are concerns that the assays lack specificity for EDC effects when a chemical induces systemic toxicity. A lack of specificity, or the ability to correctly identify an inactive or "negative" chemical, would increase the probability of identifying false positives. Here, we orally exposed rats to hydroxyatrazine (OH-ATR), a biotransformation by-product of the chlorotriazine herbicides that produced nephrotoxicity following a 13-week dietary exposure. Based on a previous study in our laboratory, males were dosed with 11.4 to 183.4 mg/kg OH-ATR and females were dosed with 45.75 to 183.4 mg/kg OH-ATR. Following exposure in both sexes, there was a dose-response increase in mean kidney weights and the incidence and severity of kidney lesions. These lesions included the deposition of mineralized renal tubule concretions, hydronephrosis, renal tubule dilatation, and pyelonephritis. However, no differences in body weight, liver weight, or reproductive tissue weights, reproductive or thyroid histology, hormone concentrations or the age of pubertal onset were observed. Therefore, the results demonstrate that the endpoints included in the pubertal assay are useful for nonendocrine (systemic) effects that define an no observable effect level (NOEL) or lowest observable effect level (LOEL) and provide one example where an impact on kidney function does not alter any of the endocrine-specific endpoints of the assay.

  13. 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...

  14. Pyrethroid Pesticides as Endocrine Disruptors: Molecular Mechanisms in Vertebrates with a Focus on Fishes.

    PubMed

    Brander, Susanne M; Gabler, Molly K; Fowler, Nicholas L; Connon, Richard E; Schlenk, Daniel

    2016-09-01

    Pyrethroids are now the fourth most used group of insecticides worldwide. Employed in agriculture and in urban areas, they are detected in waterways at concentrations that are lethally and sublethally toxic to aquatic organisms. Highly lipophilic, pyrethroids accumulate in sediments and bioaccumulate in fishes. Additionally, these compounds are demonstrated to act as endocrine disrupting compounds (or EDCs) in mammals and fishes, and therefore interfere with endocrine signaling by blocking, mimicking, or synergizing endogenous hormones through direct receptor interactions, and indirectly via upstream signaling pathways. Pyrethroid metabolites have greater endocrine activity than their parent structures, and this activity is dependent on the enantiomer present, as some pyrethroids are chiral. Many EDCs studied thus far in fish have known estrogenic or antiestrogenic effects, and as such cause the inappropriate or altered expression of genes or proteins (i.e., Vtg-vitellogenin, Chg-choriogenin), often leading to physiological or reproductive effects. Additionally, these compounds can also interfere with other endocrine pathways and immune response. This review highlights studies that focus on the mechanisms of pyrethroid biotransformation and endocrine toxicity to fishes across a broad range of different pyrethroid types, and integrates literature on the in vitro and mammalian responses that inform these mechanisms. PMID:27464030

  15. Validation and application of reporter gene assays for the determination of estrogenic and androgenic endocrine disruptor activity in sport supplements.

    PubMed

    Plotan, Monika; Elliott, Christopher T; Oplatowska, Michalina; Connolly, Lisa

    2012-07-01

    Previously developed estrogen and androgen mammalian reporter gene assays (RGAs) were assessed for their potential use as a quantitative screening method in the detection of estrogenic and androgenic endocrine disruptors (EDs) in sport supplements. The validation of both RGAs coupled with dispersive solid phase extraction (dSPE) was performed in accordance with European Commission Decision EC/2002/6579 for biological screening methods. Decision limits (CCα) and detection capabilities (CCβ) were established for both the estrogen and androgen RGAs. All samples were compliant with CCα and CCβ in both bioassays. Recovery rates were 96 % for 17β-estradiol and 115 % for dihydrotestosterone as obtained in their corresponding RGA. Both estrogens and androgens were stable in samples for more than 3 weeks, when stored at -20 °C. Specificity, good repeatability (coefficients of variation (CV), 12-25 %), reproducibility and robustness of both bioassays were also observed. Four different ED modes of action were determined for estrogens and androgens in 53 sport supplements, using the validated RGAs. This study revealed that 89 % of the investigated sport supplements contained estrogenic EDs and 51 % contained androgenic compounds. In conclusion, both bioassays are suitable for sport supplement screening of estrogenic and androgenic EDs.

  16. 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...

  17. 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

  18. 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.

  19. 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. PMID:26882535

  20. 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.

  1. Removal of a combination of endocrine disruptors from aqueous systems by seedlings of radish and ryegrass.

    PubMed

    Gattullo, C Eliana; Cunha, Bruno Barboza; Rosa, André H; Loffredo, Elisabetta

    2013-01-01

    Endocrine disruptors (EDs) are widespread in the environment, especially aquatic systems, and cause dangerous effects on wildlife and humans. This work was aimed to assess the capacity of radish (Raphanus sativus L.) and ryegrass (Lolium perenne L.) seedlings to tolerate and remove two combinations of EDs containing bisphenol A (BPA), 17alpha-ethynilestradiol (EE2), and linuron from four aqueous media: distilled water, a solution of natural organic matter (NOM), a lake water and a river water. Seeds of the two species were germinated in each contaminated medium and, at the end of germination, the seedling growth was evaluated by biometric measurements and residual EDs were quantified by chromatographic analysis. Biometric measurements revealed that the phytotoxicity of the two combinations of EDs depended on the medium used. Radish showed a discrete tolerance in distilled water and lake water but was inhibited in the solution of NOM and river water. Ryegrass was negatively affected mainly in river water. The concentration of each ED appeared significantly reduced in all media in the presence of seedlings of both species, but not in the blanks without plants. In 5 days, radish removed up to 88% of BPA, 100% of EE2 and 42% of linuron, and in 6 days ryegrass removed up to 92% of BPA, 74% of EE2 and 16% of linuron. The considerable removal capacity of radish and ryegrass in all media tested encourages the use of phytoremediation to remove EDs from waters. PMID:24617071

  2. Removal of a combination of endocrine disruptors from aqueous systems by seedlings of radish and ryegrass.

    PubMed

    Gattullo, C Eliana; Cunha, Bruno Barboza; Rosa, André H; Loffredo, Elisabetta

    2013-01-01

    Endocrine disruptors (EDs) are widespread in the environment, especially aquatic systems, and cause dangerous effects on wildlife and humans. This work was aimed to assess the capacity of radish (Raphanus sativus L.) and ryegrass (Lolium perenne L.) seedlings to tolerate and remove two combinations of EDs containing bisphenol A (BPA), 17alpha-ethynilestradiol (EE2), and linuron from four aqueous media: distilled water, a solution of natural organic matter (NOM), a lake water and a river water. Seeds of the two species were germinated in each contaminated medium and, at the end of germination, the seedling growth was evaluated by biometric measurements and residual EDs were quantified by chromatographic analysis. Biometric measurements revealed that the phytotoxicity of the two combinations of EDs depended on the medium used. Radish showed a discrete tolerance in distilled water and lake water but was inhibited in the solution of NOM and river water. Ryegrass was negatively affected mainly in river water. The concentration of each ED appeared significantly reduced in all media in the presence of seedlings of both species, but not in the blanks without plants. In 5 days, radish removed up to 88% of BPA, 100% of EE2 and 42% of linuron, and in 6 days ryegrass removed up to 92% of BPA, 74% of EE2 and 16% of linuron. The considerable removal capacity of radish and ryegrass in all media tested encourages the use of phytoremediation to remove EDs from waters.

  3. 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.

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

    PubMed

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

    2014-09-15

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

  5. 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.

  6. Application of an integrated testing strategy to the U.S. EPA endocrine disruptor screening program.

    PubMed

    Willett, Catherine E; Bishop, Patricia L; Sullivan, Kristie M

    2011-09-01

    New approaches to generating and evaluating toxicity data for chemicals are needed to cope with the ever-increasing demands of new programs. One such approach involves the use of an integrated testing and evaluation strategy based on the specific properties and activities of a chemical. Such an integrated strategy, whether applied to existing or future programs, can promote efficient use of resources and save animals. We demonstrate the utility of such a strategy by applying it to the current U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP). Launched in October 2009, the EDSP utilizes a two-tiered approach, whereby each tier requires a battery of animal-intensive and expensive tests. Tier 1 consists of five in vitro and six in vivo assays that are intended to determine a chemical's potential to interact with the estrogen (E), androgen (A), or thyroid (T) hormone pathways. Tier 2 is proposed to consist of multigenerational reproductive and developmental toxicity tests in several species and is intended to determine whether a chemical can cause adverse effects resulting from E, A, or T modulation. In contrast to the existing EDSP structure, we show, using the pesticide atrazine as an example, that a multilevel testing framework combined with an integrated evaluation process would significantly increase efficiency by minimizing testing.

  7. 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.

  8. 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. PMID:24114257

  9. [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. PMID:25552505

  10. [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.

  11. 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.

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

    PubMed Central

    Tran, Diana A; Rivas, Guillermo E; Singh, Purnima; Pfeifer, Gerd P

    2011-01-01

    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 candidate susceptibility loci to environmental insults 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 39 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. PMID:21636974

  13. Endocrine Disruptors Fludioxonil and Fenhexamid Stimulate miR-21 Expression in Breast Cancer Cells

    PubMed Central

    Teng, Yun; Manavalan, Tissa T.; Klinge, Carolyn M.

    2013-01-01

    Fenhexamid and fludioxonil are antifungal agents used in agricultural applications, which are present at measurable amounts in fruits and vegetables. Fenhexamid and fludioxonil showed endocrine disruptor activity as antiandrogens in an androgen receptor reporter assay in engineered human breast cancer cells. Little is known about how environmental chemicals regulate microRNA (miRNA) expression. This study examined the effect of fenhexamid and fludioxonil on the expression of the oncomiR miR-21 in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and downstream targets of miR-21 in MCF-7 cells. Fenhexamid and fludioxonil stimulated miR-21 expression in a concentration-dependent manner and reduced the expression of miR-21 target Pdcd4 protein. Antisense to miR-21 blocked the increase in Pdcd4 protein by fenhexamid and fludioxonil. Fenhexamid and fludioxonil reduced miR-125b and miR-181a, demonstrating specificity of miRNA regulation. Induction of miR-21 was inhibited by the estrogen receptor antagonist fulvestrant, by androgen receptor antagonist bicalutamide, by actinomycin D and cycloheximide, and by inhibitors of the mitogen-activated protein kinases and phosphoinositide 3-kinase pathways. Fenhexamid activation was inhibited by the arylhydrocarbon receptor antagonist α-napthoflavone. Fenhexamid and fludioxonil did not affect dihydrotestosterone-induced miR-21 expression. Fludioxonil, but not fenhexamid, inhibited MCF-7 cell viability, and both inhibited estradiol-induced cell proliferation and reduced cell motility. Together these data indicate that fenhexamid and fludioxonil use similar and distinct mechanisms to increase miR-21 expression with downstream antiestrogenic activity. PMID:23052036

  14. Endocrine disruptors differently influence estrogen receptor β and androgen receptor in male and female rat VSMC.

    PubMed

    Pellegrini, Marco; Bulzomi, Pamela; Lecis, Marco; Leone, Stefano; Campesi, Ilaria; Franconi, Flavia; Marino, Maria

    2014-08-01

    Sex steroid hormones differently control the major physiological processes in male and female organisms. In particular, their effects on vascular smooth muscle cells (VSMCs) migration are at the root of sex/gender-related differences reported in the cardiovascular system. Several exogenous substances, defined endocrine disruptor chemicals (EDCs), could interfere with these androgen and estrogen effects; however, the sex/gender-related susceptibility of VSMC motility to EDCs is completely unknown. Here, the effect of naturally occurring (naringenin, Nar) and synthetic (bisphenol A, BPA) EDCs on male and female VSMC motility has been evaluated. 17β-estradiol (E2, 0.1 nM-1 µM) induced a dose-dependent inhibition of motility in female-derived VSMC. In contrast, neither dihydrotestosterone (DHT, 0.01-100 nM) nor the common precursor of sex steroid hormones, testosterone (Tes, 0.01-100 nM) modified male-derived VSMC motility. Estrogen receptor (ER) β subtype-dependent activation of p38 was necessary for the E2 effect on cell motility. High BPA concentration prevented E2 effects in female-derived cells being without any effect in male-derived cells. Nar mimicked E2 effects on female-derived cells even in the presence of E2 or BPA. Intriguingly, Nar also inhibited the male-derived VSMC mobility. This latter effect was prevented by ERβ inhibitor, but not by the androgen receptor (AR) inhibitor. As a whole, ERβ-dependent signals in VSMC results more susceptible to the impact of EDCs than AR signals suggesting a possible high and overall susceptibility of female to EDCs. However, several male-derived cells, including VSMC, express ERβ, which could also serve as target of EDC disruption in male organisms. PMID:24347325

  15. [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.

  16. 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.

  17. 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. PMID:25988240

  18. 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

  19. 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.

  20. 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

  1. 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.

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

    PubMed

    Sichilongo, Kwenga; Torto, Nelson

    2009-12-01

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

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

    PubMed

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

    2011-12-01

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

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

    PubMed

    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

  5. 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

  6. 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 ...

  7. 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.
    <...

  8. 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 (...

  9. 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...

  10. 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...

  11. 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...

  12. 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

    ... to human health or the environment due to disruption of the endocrine system. The determination that a chemical does or is not likely to have the potential to interact with the endocrine system will be... determine ] that a particular chemical has the potential to interact with the endocrine system and...

  13. 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.

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

    PubMed

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

    2016-01-01

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

  15. 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.

  16. 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. PMID:25708297

  17. 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. PMID:26170111

  18. 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

  19. Monitoring endocrine disrupting compounds and estrogenic activity in tap water from Central Spain.

    PubMed

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

    2014-01-01

    The aims of this study are to investigate the presence of 30 substances known or thought to act as endocrine disrupting compounds in tap water from the main water supply areas for region of Madrid, to determine the total estrogenic activity of the samples analysed and to estimate the health risk for the population resulting from those compounds found at detectable concentrations. To this end, a one-off composite sampling was performed in August 2012 in which six tap water samples were collected from private residences in the drinking water supply network of the region of Madrid. A total of 14 of the 30 endocrine disruptors analysed were found at concentrations ranging from 0.3 to 165 ng/L. The organophosphorus flame retardants were detected at the highest concentrations followed by the plasticizer bisphenol A, alkylphenols, anticorrosion agents and preservatives. Tap water in the region of Madrid is contaminated with traces (ng/L) of compounds with endocrine disrupting properties. Although the concentrations of endocrine disrupting compounds obtained are too low to be able to confirm a public health risk, and no risk has been detected upon evaluation, it should be remembered that these compounds act at very low doses and that their effects may only appear in the long term. PMID:24728544

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

    PubMed

    Jonkers, Niels; Kohler, Hans-Peter E; Dammshäuser, Anna; Giger, Walter

    2009-03-01

    This study focused on the occurrence and behaviour in wastewater and surface waters of several phenolic endocrine disrupting compounds (EDCs) including parabens, alkylphenolic compounds, phenylphenol (PhP) and bisphenol A (BPA). Analytical procedures using solid-phase-extraction and LC-MS/MS techniques were applied to samples of influents and effluents of wastewater treatment plants (WWTPs) discharging into the Glatt River (Switzerland) as well as to river water samples. A mass flow analysis provided insight into the main sources and the fate of these contaminants during different weather conditions. Concentrations in influents were in the low microg/L range for most analytes. Removal of parabens in the WWTPs was mostly above 99%. Nonylphenol polyethoxylates (A(9)PEO) removal amounted to 98%, but in some cases nonylphenoxy acetic acid (A(9)PEC) or nonylphenols (NP) were formed. In effluents, concentrations were highest for the A(9)PEC, A(9)PEO and NP. Concentrations in river water were in the high ng/L range for alkylphenolic compounds and in the low ng/L range for BPA, PhP and the parabens. During the sampling period, in which several rain events occurred, both water flows and mass flows varied strongly. Mass flows in WWTP effluents and in the river increased with increasing water flows for most compounds indicating that higher water flows do not lead necessarily to a proportional dilution of the pollutants. Throughout the low water flow period, mass flows predicted from the known inputs were similar to the actual mass flows at the end of the river for most analytes. For none of the EDCs, significant in-stream removal could be observed. In the periods with high water flows, mass flows in the river were much higher than can be explained by the initially defined sources. Discharge of untreated wastewater influent into the river was assessed as an additional source. Adding this source improved the mass balance for some, but not all of the analytes.

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

    PubMed

    Jonkers, Niels; Kohler, Hans-Peter E; Dammshäuser, Anna; Giger, Walter

    2009-03-01

    This study focused on the occurrence and behaviour in wastewater and surface waters of several phenolic endocrine disrupting compounds (EDCs) including parabens, alkylphenolic compounds, phenylphenol (PhP) and bisphenol A (BPA). Analytical procedures using solid-phase-extraction and LC-MS/MS techniques were applied to samples of influents and effluents of wastewater treatment plants (WWTPs) discharging into the Glatt River (Switzerland) as well as to river water samples. A mass flow analysis provided insight into the main sources and the fate of these contaminants during different weather conditions. Concentrations in influents were in the low microg/L range for most analytes. Removal of parabens in the WWTPs was mostly above 99%. Nonylphenol polyethoxylates (A(9)PEO) removal amounted to 98%, but in some cases nonylphenoxy acetic acid (A(9)PEC) or nonylphenols (NP) were formed. In effluents, concentrations were highest for the A(9)PEC, A(9)PEO and NP. Concentrations in river water were in the high ng/L range for alkylphenolic compounds and in the low ng/L range for BPA, PhP and the parabens. During the sampling period, in which several rain events occurred, both water flows and mass flows varied strongly. Mass flows in WWTP effluents and in the river increased with increasing water flows for most compounds indicating that higher water flows do not lead necessarily to a proportional dilution of the pollutants. Throughout the low water flow period, mass flows predicted from the known inputs were similar to the actual mass flows at the end of the river for most analytes. For none of the EDCs, significant in-stream removal could be observed. In the periods with high water flows, mass flows in the river were much higher than can be explained by the initially defined sources. Discharge of untreated wastewater influent into the river was assessed as an additional source. Adding this source improved the mass balance for some, but not all of the analytes. PMID:19117654

  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. Pharmacodynamic model of the rat estrus cycle in relation to endocrine disruptors.

    PubMed

    Andersen, M E; Clewell, H J; Gearhart, J; Allen, B C; Barton, H A

    1997-10-24

    Several strains of laboratory rats have a high background incidence of mammary tumors and develop a persistent, anovulatory estrus condition at about 12 mo of age. The increased tumor incidence is believed to be associated with elevated estradiol (E2) and prolactin during the period of persistent estrus. A pharmacodynamic estrus cycle (PD-EC) model for the Sprague-Dawley rats has been developed in an attempt to analyze the physiological basis of early-onset persistent estrus and to examine the potential sites of interactions in the hypothalamic-pituitary-ovarian axis for endocrine-modulating xenobiotics that accelerate the onset of persistent estrus. This initial estrus cycle model focused solely on cyclical changes in E2 and luteinizing hormone (LH). An LH surge was scheduled when a hypothetical estrus cycle-related protein (EC-RP) under transcriptional control by the E2 receptor reached a critical concentration. In the model, aging-related cumulative hypothalamic E2 exposure impaired the LH surge by reducing the rate of production of the EC-RP. The progressively decreasing intercycle resynthesis rate leads first to longer, variable-length cycles and finally to persistent estrus at about 12 mo of age. This model construct is consistent with early-onset persistent estrus related to neonatal E2 exposures, with acyclicity associated with high-dose E2 exposure in the adult, and with persistent estrus conditions associated with exposures to xenobiotic endocrine modulators that are either weak E2 antagonists or weak E2 agonists. With further development these pharmacodynamic estrus cycle models should be useful in aiding risk assessments for compounds causing mammary-tissue tumors associated with persistent estrus states.

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

    PubMed

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

    2014-01-01

    Endocrine disrupting compounds (EDCs) are capable of interfering with the endocrine system and are increasingly widespread in the aquatic environments. In the present study, zebrafish (Danio rerio) embryos and larvae were used to assess how EDCs may interfere with embryogenesis. Therefore, zebrafish embryos were exposed to 17α-ethinylestradiol (EE2: 0.4, 2, 4 and 20 ng/L), genistein (Gen: 2, 20, 200 and 2000 ng/L) and fadrozole (Fad: 2, 10, 50 and 250 μg/L), between 2 and 144 h post-fertilization (hpf). Somite development, heartbeat, malformations, mortality and hatching rates were evaluated. In parallel, the expression patterns of hormone receptors (esr1, esr2a, esr2b and ar) and apoptotic pathways related genes (p53 and c-jun) were determined using quantitative real-time PCR. Results showed that EE2, Gen and Fad caused a higher mortality and also malformations in larvae compared with control. A significant toxic effect was observed in the heartbeat rate, at 144 hpf, in larvae exposed to EE2 and Fad. QPCR revealed alterations in the expression levels of all the evaluated genes, at different time points. esr1 and c-jun genes were upregulated by EE2 and Gen exposure while the expression of esr2a, esr2b and ar genes was downregulated. Fad exposure decreased esr1, p53 and c-jun expression levels. This study shows a toxic effect of EE2, Gen and Fad to vertebrate embryogenesis and a relation between hormones action and apoptosis pathways. PMID:25172296

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Macon, Madisa B.

    2013-01-01

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

  8. Reduction of endocrine disruptor emissions in the environment: the benefit of wastewater treatment.

    PubMed

    Janex-Habibi, Marie-Laure; Huyard, Alain; Esperanza, Mar; Bruchet, Auguste

    2009-04-01

    The occurrence and fate of four estrogens and five alkylphenolic compounds were studied in thirteen plants with various treatment processes, sizes and countries. Complete load mass balance, including water and sludge phases, has shown a high reduction of the total load of hormones, around 90%. The removal of alkylphenols was more variable, due to the degradation of nonylphenol (NP) precursors - alkylphenol polyethoxylates (APnEO) - during the treatment, resulting in significant production of shorter and toxic alkylphenols (NP and short polyethoxylates) that concentrate in the sludges. Under anaerobic conditions, such as anaerobic digestion process, the load of NP was in most cases observed to increase. When considering the environmental impact, the high reduction of endocrine disrupting compounds (EDC) concentrations between raw wastewater and effluent enables to satisfy the requirements of the Water Framework Directive for NP except in very critical situations where the dilution factor of the effluent in the river would be lower than 7. For sludges, the pending European Directive on spreading of sludge on land would be complied with in all cases. PMID:19203777

  9. Deposition patterns and transport mechanisms for the endocrine disruptor 4-nonylphenol across the Sierra Nevada Mountains, California.

    PubMed

    Lyons, Rebecca; Van de Bittner, Kyle; Morgan-Jones, Sean

    2014-12-01

    Dust and particulate distribution patterns are shifting as global climate change brings about longer drought periods. Particulates act as vehicles for long range transport of organic pollutants, depositing at locations far from their source. Nonylphenol, a biodegradation product of nonylphenol polyethoxylate, is a known endocrine disruptor. Nonylphenol polyethoxylate enters the environment as an inert ingredient in pesticide sprays, potentially traveling great distances from its application site. This is of concern when a highly agricultural region, California's Central Valley, lies adjacent to sensitive areas like the Eastern Sierra Nevada Mountains. The distribution and transport mechanisms for 4-nonylphenol were investigated in Eastern Sierra Nevada canyons. Regions close to canyon headwalls showed trace amounts of 4-nonylphenol in surface water, snow, and atmospheric deposition. Exposed areas had yearly average concentrations as high as 9 μg/L. Distribution patterns are consistent with particulate-bound transport. This suggests with increasing drought periods, higher levels of persistent organic pollutants are likely.

  10. Exposure Levels of Environmental Endocrine Disruptors in Mother-Newborn Pairs in China and Their Placental Transfer Characteristics

    PubMed Central

    Li, Lu-Xi; Chen, Li; Meng, Xiang-Zhou; Chen, Bing-Heng; Chen, Shang-Qin; Zhao, Yan; Zhao, Li-Fang; Liang, Yuan; Zhang, Yun-Hui

    2013-01-01

    There is a growing concern about the potential health effects of exposure to various environmental chemicals during pregnancy and infancy. The placenta is expected to be an effective barrier protecting the developing embryo against some endocrine disruptors (EDs) circulating in maternal blood. The current study was designed to assess in utero exposure levels of non-persistent organic pollutants (non-POPs) and persistent organic pollutants (POPs) in Chinese newborns and potential role of placenta barrier against fetal exposure to these commonly-used environmental endocrine disruptors. A total of 230 newborn-mother pairs were enrolled during 2010–2011, 201 pairs of which were recruited from Shanghai, and the other 29 pairs came from Wenzhou. Maternal blood, cord blood, and meconium specimens were collected in the subject population from Shanghai and analyzed for non-POPs, including mono-2-ethylhexyl phthalate (MEHP), octylphenol (OP) and 4-nonylphenol (4-NP). A total of 19 polybrominated diphenyl ethers (PBDEs) congeners, which belong to POPs, were detected in maternal and cord blood specimens from the other 29 pairs. Fetal-maternal ratios (F-M ratios) and regression coefficients were presented to assess potential function of placenta on barricading the mother/fetal transfer of these EDs. Concentrations of the detected non-POPs in cord blood samples were approximately 20% lower than those in maternal blood, and regression coefficients of which were all over 0.80. In contrast, PBDEs levels in cord blood samples were significantly higher than those in maternal blood. MEHP levels in meconium were much higher than those in cord blood samples, and highly correlated. Therefore, observations demonstrated that the placental barrier slightly decreased the fetal exposure to most non-POPs, while PBDEs seemed to be totally transferred across the placenta and finally reached the fetus. For in utero exposure assessment of Di-2-ethylhexyl phthalate (DEHP), MEHP level in meconium

  11. 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.

  12. 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. PMID:27312331

  13. 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

  14. 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.

  15. 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). PMID:22571523

  16. 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.

  17. 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. PMID:26135642

  18. 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...

  19. 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. PMID:26282501

  20. 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.

  1. A green method for the quantification of plastics-derived endocrine disruptors in beverages by chemometrics-assisted liquid chromatography with simultaneous diode array and fluorescent detection.

    PubMed

    Vidal, Rocío B Pellegrino; Ibañez, Gabriela A; Escandar, Graciela M

    2016-10-01

    The aim of this study was to develop a novel analytical method for the determination of bisphenol A, nonylphenol, octylphenol, diethyl phthalate, dibutyl phthalate and diethylhexyl phthalate, compounds known for their endocrine-disruptor properties, based on liquid chromatography with simultaneous diode array and fluorescent detection. Following the principles of green analytical chemistry, solvent consumption and chromatographic run time were minimized. To deal with the resulting incomplete resolution in the chromatograms, a second-order calibration was proposed. Second-order data (elution time-absorbance wavelength and elution time-fluorescence emission wavelength matrices) were obtained and processed by multivariate curve resolution-alternating least-squares (MCR-ALS). Applying MCR-ALS allowed quantification of the analytes even in the presence of partially overlapped chromatographic and spectral bands among these compounds and the potential interferents. The obtained results from the analysis of beer, wine, soda, juice, water and distilled beverage samples were compared with gas chromatography-mass spectrometry (GC-MS). Limits of detection (LODs) in the range 0.04-0.38ngmL(-1) were estimated in real samples after a very simple solid-phase extraction. All the samples were found to contain at least three EDs, in concentrations as high as 334ngmL(-1). PMID:27474316

  2. 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.

  3. A green method for the quantification of plastics-derived endocrine disruptors in beverages by chemometrics-assisted liquid chromatography with simultaneous diode array and fluorescent detection.

    PubMed

    Vidal, Rocío B Pellegrino; Ibañez, Gabriela A; Escandar, Graciela M

    2016-10-01

    The aim of this study was to develop a novel analytical method for the determination of bisphenol A, nonylphenol, octylphenol, diethyl phthalate, dibutyl phthalate and diethylhexyl phthalate, compounds known for their endocrine-disruptor properties, based on liquid chromatography with simultaneous diode array and fluorescent detection. Following the principles of green analytical chemistry, solvent consumption and chromatographic run time were minimized. To deal with the resulting incomplete resolution in the chromatograms, a second-order calibration was proposed. Second-order data (elution time-absorbance wavelength and elution time-fluorescence emission wavelength matrices) were obtained and processed by multivariate curve resolution-alternating least-squares (MCR-ALS). Applying MCR-ALS allowed quantification of the analytes even in the presence of partially overlapped chromatographic and spectral bands among these compounds and the potential interferents. The obtained results from the analysis of beer, wine, soda, juice, water and distilled beverage samples were compared with gas chromatography-mass spectrometry (GC-MS). Limits of detection (LODs) in the range 0.04-0.38ngmL(-1) were estimated in real samples after a very simple solid-phase extraction. All the samples were found to contain at least three EDs, in concentrations as high as 334ngmL(-1).

  4. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs.

    PubMed

    Markey, Caroline M; Coombs, Macall A; Sonnenschein, Carlos; Soto, Ana M

    2003-01-01

    Recent findings in the field of environmental endocrine disruption have revealed that developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. The aim of the present study was to determine the effects of in utero exposure to low doses of the estrogenic chemical bisphenol A (BPA) on the development of the female reproductive tissues and mammary glands in CD-1 mice. Humans are exposed to BPA, which leaches from dental materials and plastic food and beverage containers. Here we report that prenatal exposure to BPA induces alterations in tissue organization within the ovaries and mammary glands and disrupts estrous cyclicity in adulthood. Because estrogen receptors are expressed developmentally in these estrogen-target organs, we propose that BPA may directly affect the expression of genes involved in their morphogenesis. In addition, alterations in the sexual differentiation of the brain, and thus the hypothalamic-pituitary-gonadal axis, may further contribute to the observed phenotype. The emerging field of endocrine disruptors promises to provide new insights into the mechanisms underlying the development of hormone-target organs and demonstrates that the environment plays important roles in the making of phenotypes.

  5. 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

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

    EPA Science Inventory

    Recent concern 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 ...

  7. 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...

  8. 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 ...

  9. 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...

  10. 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...

  11. 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.

  12. An integrated study of endocrine disruptors in sediments and reproduction-related parameters in bivalve molluscs from the Biosphere's Reserve of Urdaibai (Bay of Biscay).

    PubMed

    Puy-Azurmendi, Eunate; Ortiz-Zarragoitia, Maren; Kuster, Marina; Martínez, Elena; Guillamón, Míriam; Domínguez, Carmen; Serrano, Teresa; Barbero, Mari Carmen; Alda, Miren López de; Bayona, Josep M; Barceló, Damiá; Cajaraville, Miren P

    2010-01-01

    Urdaibai was declared a Biosphere's Reserve by UNESCO in 1984. Because we observed a high prevalence of hermaphroditism in mussels sampled in Urdaibai in March 2004, we started the present research work in order to determine the presence of endocrine disruptors (EDs) in sediments and to study possible EDs effects on mussels and oysters using gonad index and vitellogenin (VTG)-like protein levels as biomarkers. Samples were collected at five localities in April 2007 and 2008, and in October 2007. Estrogenic hormones were not detected in sediments and levels of bisphenol A and organotin compounds were very low. Alkylphenols were found at moderate levels and showed a time-dependent decrease. Phthalates were found at levels up to 8000 ng/g. High prevalence of oocyte atresia and necrosis occurred in mussels sampled in April. Retarded gametogenesis was observed in an oyster population from a shipyard. Hermaphrodites or alterations in VTG-like protein levels were not found but the high prevalence of histopathological alterations in oocytes is of concern.

  13. IDENTIFICATION OF ENDOCRINE DISRUPTORS USING A SHORT-TERM REPRODUCTION ASSAY WITH THE FATHEAD MINNOW

    EPA Science Inventory

    Tests with small fish have been a recommended of virtually every proposed regulatory program for endocrine-disrupting chemicals (EDCs). An ideal test would provide information suitable for determination of whether a chemical has the potential to exert adverse effects via specific...

  14. 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...

  15. 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...

  16. 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...

  17. EVALUATION OF FADROZOLE AS AN ENDOCRINE DISRUPTOR IN FATHEAD MINNOW (PIMEPHALES PROMELAS)

    EPA Science Inventory

    The EPA has received a legislative mandate to develop and implement standardized screening and testing methods to identify and assess potential endocrine disrupting chemicals (EDCs). The objective of this research was to evaluate a short-term EDC screening/testing assay which ass...

  18. 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...

  19. 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), ...

  20. The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.

    PubMed Central

    Reiter, L W; DeRosa, C; Kavlock, R J; Lucier, G; Mac, M J; Melillo, J; Melnick, R L; Sinks, T; Walton, B T

    1998-01-01

    The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and

  1. 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. PMID:27153234

  2. [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. PMID:26960088

  3. 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.

  4. 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.

  5. 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.

  6. 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. PMID:27445682

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

    PubMed

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

    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

  8. 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

  9. Fungal laccases degradation of endocrine disrupting compounds.

    PubMed

    Macellaro, Gemma; Pezzella, Cinzia; Cicatiello, Paola; Sannia, Giovanni; Piscitelli, Alessandra

    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

  10. 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

  11. 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.

  12. 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,...

  13. A Computational Model to Predict Rat Ovarian Steroid Secretion from In Vitro Experiments with Endocrine Disruptors

    PubMed Central

    Quignot, Nadia; Bois, Frédéric Y.

    2013-01-01

    A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs). The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole. PMID:23326527

  14. 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 ...

  15. 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.

  16. 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. PMID:27111276

  17. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.

    PubMed

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2008-07-01

    The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the

  18. 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 ...

  19. 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.

  20. Relationships of putative endocrine disruptors to human sexual maturation and thyroid activity in youth

    PubMed Central

    Schell, Lawrence M.; Gallo, Mia V.

    2009-01-01

    Endocrine disruption has become a significant human health concern, but is difficult to study outside of the laboratory for several reasons including the multiplicity of exposures, the difficulty in assessing each exposure, and the variety of possible outcomes among human populations. This review summarizes our studies of the relationships of measured persistent organic pollutants (PCBs, p,p′-DDE, HCB and mirex), and heavy metals (lead and mercury), to outcomes directly related to thyroid function and sexual maturation. These studies were conducted in a sample of Native American youth from the Akwesasne Mohawk community. The participants were first studied during puberty (10–16.9 years of age) and then at approximately 18 years of age. Results from these studies show that PCB levels are positively related to TSH and negatively to free T4. Further, these effects are conditioned by breastfeeding history. Anti-thyroid peroxidase antibody levels also are related to PCB levels suggesting elevated risk of autoimmune disease among the exposed. Earlier age at menarche is associated with higher PCB levels while risk of delay is associated with higher lead levels. Some evidence that the timing of exposure produces different effects is presented, and the level of exposure in the participants suggests that effects observed may be relevant to a considerable proportion of the US population. Further investigations are warranted to determine effect thresholds and mechanisms. PMID:19800354

  1. Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors.

    PubMed

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Pinson, Anneline; Bourguignon, Jean-Pierre

    2016-01-01

    The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle.

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

    PubMed

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

    2014-07-01

    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

  3. Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors.

    PubMed

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Pinson, Anneline; Bourguignon, Jean-Pierre

    2016-01-01

    The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle. PMID:26680578

  4. 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. PMID:26150296

  5. 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.

  6. Disturbed sexual characteristics in male mosquitofish (Gambusia holbrooki) from a lake contaminated with endocrine disruptors.

    PubMed Central

    Toft, Gunnar; Edwards, Thea M; Baatrup, Erik; Guillette, Louis J

    2003-01-01

    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 with numerous chemicals, some of which possess endocrine-disrupting activity. Male mosquitofish (Gambusia holbrooki) were collected monthly from December 2000 through May 2001 from Lake Apopka and two nearby reference lakes, Orange Lake and Lake Woodruff National Wildlife Refuge. Selected sexual characteristics were compared temporally and among lakes during the collection period. Male fish from Lake Apopka had slightly shorter gonopodia and on average 32 and 47% fewer sperm cells per milligram testis, when compared with the fish collected from Orange Lake and Lake Woodruff, respectively. The testes weights increased markedly during spring, with significantly smaller testes in fish from Lake Apopka than from Orange Lake, but surprisingly, the smallest testes occurred in males obtained from the Lake Woodruff population. The highest liver weights were found in the Lake Apopka population. Whole-body concentrations of testosterone and estradiol varied among months; the peak testosterone concentration occurred in January and was significantly lower in male fish from Lake Apopka compared with Orange Lake. The intensity of male courtship behavior was highly correlated to body testosterone concentration, but no statistically significant differences in sexual behavior among the lakes were found. We conclude that sexual characteristics of relevance to male reproductive capacity are altered in the Lake Apopka mosquitofish population, and we discuss the presence of chemicals with antiandrogenic effects in Lake Apopka as a possible cause of the observed alterations. PMID:12727596

  7. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes.

    PubMed

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2009-10-01

    Exposure to endocrine-disrupting chemicals during development could alter the epigenetic programming of the genome and result in adult-onset disease. Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and antiandrogenic activities. Previous studies showed that fetal/neonatal exposure to MXC caused adult ovarian dysfunction due to altered expression of key ovarian genes including estrogen receptor (ER)-beta, which was down-regulated, whereas ERalpha was unaffected. The objective of the current study was to evaluate changes in global and gene-specific methylation patterns in adult ovaries associated with the observed defects. Rats were exposed to MXC (20 microg/kgxd or 100 mg/kg.d) between embryonic d 19 and postnatal d 7. We performed DNA methylation analysis of the known promoters of ERalpha and ERbeta genes in postnatal d 50-60 ovaries using bisulfite sequencing and methylation-specific PCRs. Developmental exposure to MXC led to significant hypermethylation in the ERbeta promoter regions (P < 0.05), whereas the ERalpha promoter was unaffected. We assessed global DNA methylation changes using methylation-sensitive arbitrarily primed PCR and identified 10 genes that were hypermethylated in ovaries from exposed rats. To determine whether the MXC-induced methylation changes were associated with increased DNA methyltransferase (DNMT) levels, we measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05), suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary. Overall, these data suggest that transient exposure to MXC during fetal and neonatal development affects adult ovarian function via altered methylation patterns.

  8. 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.

  9. [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. PMID:26655260

  10. Passive sampling methods for monitoring endocrine disruptors in the Svratka and Svitava rivers in the Czech Republic.

    PubMed

    Grabic, Roman; Jurcikova, Jana; Tomsejova, Sarka; Ocelka, Tomas; Halirova, Jarmila; Hypr, Dusan; Kodes, Vit

    2010-03-01

    Endocrine-disrupting chemicals (EDC) are manmade or natural chemicals that have the ability to interfere with the endocrine system of animals. They have not been monitored systematically in the Czech Republic. The goal of the present study was the characterization of aquatic environmental pollution from the Brno (Czech Republic) city agglomeration focusing on EDC. Passive sampling devices, as well as semipermeable membrane devices (SPMD) and polar organic chemical integrative samplers (POCIS), were used for the pilot assessment of EDC. They were deployed for 21- to 28-d periods at nine locations in the Svratka and Svitava Rivers, Brno, Czech Republic, including at the inlet and outlet of Brno's wastewater treatment plant. The SPMDs were used to monitor nonpolar compounds such as polychlorinated biphenyls (PCBs), polynuclear aromatic hydrocarbons (PAHs), and organochlorinated pesticides (OCP). The POCIS were used to monitor polar compounds such as pesticides and their metabolites, perfluoro-organic compounds (PFOC), and pharmaceuticals. The passive samplers allowed very low detection limits for soluble (bioavailable) fractions of pollutants. The contribution of PAH, PCB, and HCB in sewage water to pollution of the Svratka River was low. The Brno wastewater treatment plant was identified as the main source of pharmaceuticals, triclosan, methyl triclosan, and some polar pesticides.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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. PMID:26450281

  16. 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.

  17. 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. PMID:24645486

  18. Endocrine disruptors and other food-contaminating environmental pollutants as risk factors in animal reproduction.

    PubMed

    Rhind, S M

    2008-07-01

    Pollutants of many chemical classes, derived primarily from anthropogenic activities, are ubiquitous in the environment, persistent, biologically available and can exert adverse effects on the reproductive and other, indirectly related, physiological systems. Food is generally considered to be the major route of animal exposure in vertebrate species but the relative contributions of other routes of exposure such as through lungs, gills or skin are not well studied and may be of importance for certain animal groups, depending on their immediate environment. Animals are particularly sensitive to exposure during developmental stages but the pattern of exposure to chemicals is likely to be different to that of adults. Quantification of the risk posed by the ingestion of pollutants in food is complex and depends on many factors including species, diet composition, duration of exposure to the food, efficiency of pollutant absorption, subsequent metabolism, sensitivity of target organs and stage of development. While the effects of high doses of single chemicals are proven, dietary exposure to pollutants generally involves prolonged, low-level exposure to a large number of compounds, each of which has different chemical characteristics, exerts different biological effects and is present at varying concentrations. Thus, while exposure to pollutants through feed is undoubtedly a significant risk factor for many species and may be the most important one for many terrestrial vertebrates, other routes of exposure may be more important in other groups.

  19. 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.

  20. Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.

    PubMed

    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).

  1. 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

  2. Rational Selection of the 3D Structure of Biomacromolecules for Molecular Docking Studies on the Mechanism of Endocrine Disruptor Action.

    PubMed

    Yang, Xianhai; Liu, Huihui; Liu, Jining; Li, Fei; Li, Xuehua; Shi, Lili; Chen, Jingwen

    2016-09-19

    Molecular modeling has become an essential tool in predicting and simulating endocrine disrupting effects of chemicals. A key prerequisite for successful application of molecular modeling lies in the correctness of 3D structure for biomacromolecules to be simulated. To date, there are several databases that can provide the experimentally-determined 3D structures. However, commonly, there are many challenges or disadvantageous factors, e.g., (a) lots of 3D structures for a given biomacromolecular target in the protein database; (b) the quality variability for those structures; (c) belonging to different species; (d) mutant amino acid residue in key positions, and so on. Once an inappropriate 3D structure of a target biomacromolecule was selected in molecular modeling, the accuracy and scientific nature of the modeling results could be inevitably affected. In this article, based on literature survey and an analysis of the 3D structure characterization of biomacromolecular targets belonging to the endocrine system in protein databases, six principles were proposed to guide the selection of the appropriate 3D structure of biomacromolecules. The principles include considering the species diversity, the mechanism of action, whether there are mutant amino acid residues, whether the number of protein chains is correct, the degree of structural similarity between the ligand in 3D structure and the target compounds, and other factors, e.g., the experimental pH conditions of the structure determined process and resolution. PMID:27556396

  3. Metabolism of the endocrine disruptor pesticide-methoxychlor by human P450s: pathways involving a novel catechol metabolite.

    PubMed

    Hu, Yiding; Kupfer, David

    2002-09-01

    The metabolism of methoxychlor, a proestrogenic pesticide (endocrine disruptor), was investigated with cDNA expressed human cytochrome P450s and liver microsomes (HLM). In addition to 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-M), 1,1,1-trichloro-2, 2-bis(4-hydroxyphenyl)ethane (bis-OH-M), and 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (tris-OH-M), a new metabolite was identified as 1,1,1-trichloro-2-(4-methoxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (catechol-M; previously assumed to be ring-OH-M) and as a key metabolic intermediate. A novel metabolic route was proposed involving methoxychlor O-demethylation to mono-OH-M, followed by bifurcation of the pathway, both leading to the same final product tris-OH-M: pathway a, mono-OH-M is demethylated to bis-OH-M, followed by ortho-hydroxylation forming tris-OH-M and pathway b, mono-OH-M is ortho-hydroxylated forming catechol-M that is O-demethylated forming tris-OH-M. Among the human cDNA-expressed P450s examined, CYP1A2, 2A6, 2C8, 2C9, 2C19, and 2D6 exhibited mainly O-demethylation, with CYP2C19 being the most catalytically competent. CYP3A4, 3A5, and rat 2B1 catalyzed primarily ortho-hydroxylation of mono-OH-M (CYP3A4 being catalytically the most active) but were weak in O-demethylation. CYP1A1, 1B1, 2E1, and 4A11 demonstrated little or no catalytic activity. CYP2B6 appeared unique, catalyzing effectively both O-demethylation and ortho-hydroxylation. Thus, CYP2B6 demethylated methoxychlor to mono-OH-M and ortho-hydroxylated the mono-OH-M forming catechol-M; however, 2B6 did not appreciably demethylate mono-OH-M or ortho-hydroxylate bis-OH-M, suggesting a narrow substrate specificity. CYP2C19-catalyzed demethylation of methoxychlor, mono-OH-M and catechol-M, demonstrating relatively good substrate affinity (K(m) = 0.23 - 0.41 microM). However, the 3A4 ortho-hydroxylation of mono-OH-M and bis-OH-M exhibited lower affinity, K(m) = 12 and 25 microM, respectively. Thus, a

  4. 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

  5. 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.

  6. Effects of selected endocrine disruptors on meiotic maturation, cumulus expansion, synthesis of hyaluronan and progesterone by porcine oocyte-cumulus complexes.

    PubMed

    Mlynarcíková, Alzbeta; Nagyová, Eva; Ficková, Mária; Scsuková, Sona

    2009-04-01

    In most mammals, before ovulation, cumulus cells synthesize a large amount of hyaluronan (HA) that is organized into an extracellular matrix (ECM), which provides an essential microenvironment for in vivo oocyte fertilization. This process is called cumulus expansion. The present study assessed effects of selected endocrine disruptors (bisphenol A, BPA; 4-chloro-3-methyl phenol, CMP; di(2-ethylhexyl) phthalate, DEHP; and benzyl butyl phthalate, BBP) in a range of 100pM-100microM, on follicle-stimulating hormone (FSH)-induced meiotic maturation and cumulus expansion of porcine oocyte-cumulus complexes (OCC) cultured in vitro. Moreover, FSH-stimulated production of hyaluronic acid (HA) and progesterone by cumulus cells was measured. Both phenols, BPA and CMP (100microM), significantly affected meiotic maturation of oocytes. The number of oocytes that underwent germinal vesicle breakdown (GVBD) (78.7% and 72.4%, respectively) as well as the rate of oocytes that reached metaphase II stage (MII) (50% and 53.6%, respectively) after 44h culture were decreased compared to control (89.6% for GVBD and 81.5% for MII). FSH-stimulated expansion of cumulus was altered by the highest concentration of BPA and CMP (70% and 64%, respectively vs. 80.3% in control). Although BPA did not alter FSH-stimulated HA synthesis by cumulus cells, its incorporation within the complex was reduced to a half of control value. Progesterone production by OCC was significantly changed in the presence of BPA or DEHP. Finally, our results provide valuable information that oocyte meiotic progression was adversely affected during in vitro culture with endocrine disruptors. PMID:19162163

  7. Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration.

    PubMed

    Kariyazono, Yudai; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Narimatsu, Shizuo; Fujimura, Masatake; Takeda, Tomoki; Yamada, Hideyuki

    2015-12-01

    The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a ß-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2-ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2',4,4'-tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHß mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHß. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis.

  8. 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.

  9. 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.

  10. 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...

  11. Pollution by oestrogenic endocrine disruptors and β-sitosterol in a south-western European river (Mira, Portugal).

    PubMed

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

    2016-04-01

    The Mira River is a Portuguese water body widely known for its wilderness and is advertised as one of the less polluted European rivers. On this presumption, the levels of endocrine-disrupting compounds (EDCs) in Mira waters were never measured. However, because environmentalists have claimed that the Mira could be moderately polluted, a range of 17 EDCs were measured not only at the estuary but also along the river. The targeted EDCs included natural and pharmaceutical oestrogens (17β-oestradiol, oestrone and 17α-ethynylestradiol), industrial/household pollutants (octylphenols, nonylphenols and their monoethoxylates and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For this propose, waters from six sampling sites were taken every 2 months, over a 1-year period (2011), and analysed by gas chromatography-mass spectrometry. Unexpectedly high levels of oestrogens and of industrial/household pollutants were measured at all sampling sites, including those located inside natural protected areas. Indeed, the annual average sum of EDCs was ≈57 ng/L for oestrogens and ≈1.3 μg/L for industrial/household chemicals. In contrast, the global average levels of phytoestrogens (≈140 ng/L) and of SITO (≈295 ng/L) were lower than those reported worldwide. The EDC concentrations were normalised for ethynylestradiol equivalents (EE2eq). In view of these, the oestrogenic load of the Mira River attained ≈47 ng/L EE2eq. In addition, phosphates were above legal limits at both spring and summer (>1 mg/L). Overall, data show EDCs at toxicant relevant levels in the Mira and stress the need to monitor rivers that are allegedly less polluted.

  12. Pollution by oestrogenic endocrine disruptors and β-sitosterol in a south-western European river (Mira, Portugal).

    PubMed

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

    2016-04-01

    The Mira River is a Portuguese water body widely known for its wilderness and is advertised as one of the less polluted European rivers. On this presumption, the levels of endocrine-disrupting compounds (EDCs) in Mira waters were never measured. However, because environmentalists have claimed that the Mira could be moderately polluted, a range of 17 EDCs were measured not only at the estuary but also along the river. The targeted EDCs included natural and pharmaceutical oestrogens (17β-oestradiol, oestrone and 17α-ethynylestradiol), industrial/household pollutants (octylphenols, nonylphenols and their monoethoxylates and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For this propose, waters from six sampling sites were taken every 2 months, over a 1-year period (2011), and analysed by gas chromatography-mass spectrometry. Unexpectedly high levels of oestrogens and of industrial/household pollutants were measured at all sampling sites, including those located inside natural protected areas. Indeed, the annual average sum of EDCs was ≈57 ng/L for oestrogens and ≈1.3 μg/L for industrial/household chemicals. In contrast, the global average levels of phytoestrogens (≈140 ng/L) and of SITO (≈295 ng/L) were lower than those reported worldwide. The EDC concentrations were normalised for ethynylestradiol equivalents (EE2eq). In view of these, the oestrogenic load of the Mira River attained ≈47 ng/L EE2eq. In addition, phosphates were above legal limits at both spring and summer (>1 mg/L). Overall, data show EDCs at toxicant relevant levels in the Mira and stress the need to monitor rivers that are allegedly less polluted. PMID:27004433

  13. 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.

  14. How do environmental estrogen disruptors induce precocious puberty?

    PubMed

    Massart, F; Parrino, R; Seppia, P; Federico, G; Saggese, G

    2006-06-01

    Puberty is regulated by the endocrine system. Disruption of that system by exposure to environmental hormone-mimicking substances (i.e. endocrine disruptors) may, therefore, affect this development profoundly. There has been a great secular trend in the earlier timing of puberty such as both puberty onset and menarche age. This is apparently caused by environmental factors such as improved socioeconomic status, better healthcare and improved nutrition. However, part of the phenomenon could be associated with exposure to endocrine disruptors that have intrinsic estrogen activity or increase endogenous sex hormone levels. These estrogen pollutants tend to degrade slowly in the environment, to bioaccumulate in the food chain and to have long half-lives in humans. Because most of environmental chemicals, called estrogen disruptors or xenoestrogens, are toxic and estrogen/antiandrogen active, they can disregulate hypothalamic-pituitary-gonadal axis potentially inducing reproductive disorders. There are several case reports of accidental exposure to estrogenic compounds in cosmetic products, food and pharmaceuticals. The outbreak of epidemics of premature thelarche in some geographical areas has also been suggested to be linked to exposure to estrogen disrupters such as dioxins, furans and organohalogens. We review data on adverse health and reproductive outcomes have been attributed to estrogen disruptors in laboratory animals and in wildlife as well as in humans, specially focusing on the puberty timing.

  15. Evaluation of Water Treatment Methods for Endocrine Disrupting Compounds

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

    Endocrine disrupting compounds (EDCs) have caught recent attention as one of the major concerns in the environment. They are known to interfere with the activity of growth-related hormones and usually, as a result, cause disruption in normal functioning of the body. The compounds currently classified as EDCs range from a variety of both natural and synthetic organic compounds and also some heavy metals. Most of these compounds are used in household, pharmaceutical, industrial, agricultural activities, the consumption or usage of which increases with population. There is a lack of detailed chemical and biological analysis as to what concentrations each of these EDCs pose harmless to the environment because of the large number of the suspected compounds. However, several published reports have established that endocrine disruption is observed in aquatic species due to chronic exposure to concentrations of some EDCs as low as a few ng/l. Conventional water treatment facilities do not usually suffice to remove EDCs in concentrations below 1 ng/l. Available technologies for removal of EDCs include adsorption, degradation and membrane treatment. The removal rates, however, are dependant on the properties of the compound, such as molecular weight, water- octanol partition coefficient and vapor pressure; physiochemical conditions of the matrix such as, redox and temperature conditions; type and dose of degrading agent and the concentration of the EDCs. Since, EDCs comprise a vast variety of compounds, their response to each of these treatment methods will be different and hence it is plausible that a single treatment technique will not be sufficient to remove the EDCs to very low concentrations. Based on our review of existing water treatment methods, we believe that a sequential treatment technique that consists of an adsorption, a degradation and finally a fine membrane treatment, each optimized for favorable, efficient and inexpensive removal may be required to remove

  16. Removal of endocrine disrupting compounds from wastewater using polymer particles.

    PubMed

    Murray, Audrey; Örmeci, Banu; Lai, Edward P C

    2016-01-01

    This study evaluated the use of particles of molecularly imprinted and non-imprinted polymers (MIP and NIP) as a wastewater treatment method for endocrine disrupting compounds (EDCs). MIP and NIP remove EDCs through adsorption and therefore do not result in the formation of partially degraded products. The results show that both MIP and NIP particles are effective for removal of EDCs, and NIP have the advantage of not being as compound-specific as the MIP and hence can remove a diverse range of compounds including 17-β-estradiol (E2), atrazine, bisphenol A, and diethylstilbestrol. Removal of E2 from wastewater was also tested to determine the effectiveness of NIP in the presence of interfering substances and natural organic matter. Removal of E2 from wastewater samples was high and increased with increasing NIP. NIP represent an effective way of removing a wide variety of EDCs from wastewater. PMID:26744949

  17. 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.

  18. Endocrine-disrupting effects of compounds in Danish streams.

    PubMed

    Long, Manhai; Strand, Jakob; Lassen, Pia; Krüger, Tanja; Dahllöf, Ingela; Bossi, Rossana; Larsen, Martin M; Wiberg-Larsen, Peter; Bonefeld-Jørgensen, Eva Cecilie

    2014-01-01

    Effluents from municipal wastewater-treatment plants and scattered dwellings, as well as runoff from agricultural fields, are sources of endocrine-disrupting compounds (EDCs) in the aquatic environment. The present study investigated the correlation between the occurrence of EDCs in nine Danish streams using passive samplers (polar organic integrative samplers and silicone membranes) and determined their possible biological effects as assessed by mammal cell cultures and the mussel (Unio tumidus). The passive samplers and mussels were exposed simultaneously at the study sites. The extracts from the passive samplers were used to measure the concentrations of EDCs and the biological effects on the estrogen (ER), androgen (AR), and aryl hydrocarbon (AhR)-receptor transactivation. Male mussels were investigated for biomarkers of endocrine effects, such as the levels of vitellogenin-like proteins measured as alkali-labile phosphate (ALP). EDC concentrations, hormone-receptor transactivation (ER, AR, AhR), and level of ALP were greater downstream of wastewater-treatment plants compared with upstream sites and sites supposed to be relatively nonimpacted by wastewater. Furthermore, there was a significant positive correlation between in vitro AhR transactivation and frequency of ALP of male mussels. We conclude that wastewater effluent is an important source of endocrine-disrupting effects in the aquatic environment and that the combination of biological effect measurements and chemical analyses based on passive sampling is useful in the assessment of the ecological state of the aquatic environment. PMID:24145922

  19. 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

  20. 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

  1. 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

  2. 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.

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

    PubMed

    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

    2015-10-01

    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

  4. An experimental design approach employing artificial neural networks for the determination of potential endocrine disruptors in food using matrix solid-phase dispersion.

    PubMed

    Boti, Vasiliki I; Sakkas, Vasilios A; Albanis, Triantafyllos A

    2009-02-27

    Matrix solid-phase dispersion (MSPD) as a sample preparation method for the determination of two potential endocrine disruptors, linuron and diuron and their common metabolites, 1-(3,4-dichlorophenyl)-3-methylurea (DCPMU), 1-(3,4-dichlorophenyl) urea (DCPU) and 3,4-dichloroaniline (3,4-DCA) in food commodities has been developed. The influence of the main factors on the extraction process yield was thoroughly evaluated. For that purpose, a 3 fractional factorial design in further combination with artificial neural networks (ANNs) was employed. The optimal networks found were afterwards used to identify the optimum region corresponding to the highest average recovery displaying at the same time the lowest standard deviation for all analytes. Under final optimal conditions, potato samples (0.5 g) were mixed and dispersed on the same amount of Florisil. The blend was transferred on a polypropylene cartridge and analytes were eluted using 10 ml of methanol. The extract was concentrated to 50 microl of acetonitrile/water (50:50) and injected in a high performance liquid chromatography coupled to UV-diode array detector system (HPLC/UV-DAD). Recoveries ranging from 55 to 96% and quantification limits between 5.3 and 15.2 ng/g were achieved. The method was also applied to other selected food commodities such as apple, carrot, cereals/wheat flour and orange juice demonstrating very good overall performance.

  5. 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. PMID:26707777

  6. Identifying potential endocrine disruptors among industrial chemicals and their metabolites--development and evaluation of in silico tools.

    PubMed

    Rybacka, Aleksandra; Rudén, Christina; Tetko, Igor V; Andersson, Patrik L

    2015-11-01

    The aim of this study was to improve the identification of endocrine disrupting chemicals (EDCs) by developing and evaluating in silico tools that predict interactions at the estrogen (E) and androgen (A) receptors, and binding to transthyretin (T). In particular, the study focuses on evaluating the use of the EAT models in combination with a metabolism simulator to study the significance of bioactivation for endocrine disruption. Balanced accuracies of the EAT models ranged from 77-87%, 62-77%, and 65-89% for E-, A-, and T-binding respectively. The developed models were applied on a set of more than 6000 commonly used industrial chemicals of which 9% were predicted E- and/or A-binders and 1% were predicted T-binders. The numbers of E- and T-binders increased 2- and 3-fold, respectively, after metabolic transformation, while the number of A-binders marginally changed. In-depth validation confirmed that several of the predicted bioactivated E- or T-binders demonstrated in vivo estrogenic activity or influenced blood levels of thyroxine in vivo. The metabolite simulator was evaluated using in vivo data from the literature which showed a 50% accuracy for studied chemicals. The study stresses, in summary, the importance of including metabolic activation in prioritization activities of potentially emerging contaminants. PMID:26210185

  7. 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.

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

    PubMed Central

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

    2014-01-01

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

  9. Activin A and equine chorionic gonadotropin recover reproductive dysfunction induced by neonatal exposure to an estrogenic endocrine disruptor in adult male mice.

    PubMed

    Warita, Katsuhiko; Okamoto, Kazutaka; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa; Yue, Zhan-Peng; Yokoyama, Toshifumi; Matsumoto, Yoshiki; Miki, Takanori; Takeuchi, Yoshiki; Kitagawa, Hiroshi; Sugawara, Teruo; Hoshi, Nobuhiko

    2008-01-01

    We aimed to elucidate the mechanism of action of estrogenic endocrine disruptors and the rescue of reproductive function, particularly the responsiveness of testes to eCG and/or activin A (ACT) after establishing reproductive disorders. Newborn male mice (n = 29) were randomly divided into an untreated group and three treatment groups that received diethylstilbestrol (DES; 100 mug per animal) subcutaneously on Postnatal Day 3 to establish reproductive disorders and daily treatment with PBS (controls: DES + PBS), eCG (eCG group: DES + eCG), or eCG + ACT (eCG + ACT group: DES + eCG + ACT) at 6-8 wk of age prior to mating. After treatment, the controls showed diminished Leydig cells in the testes and thin germ cell layers containing pyknotic germ cells and multinucleated cells. In the eCG and eCG + ACT groups, spermatids and Leydig cells increased markedly. The immunoexpression of androgen receptors in the eCG group and steroidogenic acute regulatory (STAR) protein in the eCG and eCG + ACT groups recovered to approximately the levels in the untreated group; plasma LH and testosterone levels also increased relative to those in the controls. In addition, the cell proliferation index, which is estimated from 5-bromo-2'-deoxyuridine immunoexpression in spermatogonia, increased significantly under eCG treatment, and even more with eCG + ACT. However, the numbers of germ and Leydig cells decreased at 12 wk of age. Thus, ACT and eCG help the testes to recover from the dysfunction induced by neonatal DES administration. Furthermore, the permanent male reproductive disorder induced by neonatal exposure to estrogenic agents may be more likely to result from dysfunction of the hypothalamic-pituitary axis than from dysfunction of the lower reproductive organs.

  10. Evaluation of magnetic nanoparticles to serve as solid-phase extraction sorbents for the determination of endocrine disruptors in milk samples by gas chromatography mass spectrometry.

    PubMed

    Synaridou, Maria-Evangelia S; Sakkas, Vasilios A; Stalikas, Constantine D; Albanis, Triantafyllos A

    2014-06-27

    A rapid magnetic solid-phase extraction (MSPE) is proposed based on C18-functionalized magnetic silica nanoparticles as sorbents, for the determination of endocrine disruptors - 20 organochlorine pesticides and 6 polychlorinated biphenyls - in milk samples. Magnetic nanoparticles are characterized by several techniques, such as Scanning Electron Microscopy, X-Ray diffraction, Brunauer-Emmett-Teller and Fourier transform-infrared. The MSPE is performed by dispersion of the Fe3O4@SiO2@C18 nanoparticles in milk samples with sonication, after protein precipitation. Then, the sorbent is collected by applying an external magnetic field and the analytes are desorbed by n-hexane. Several parameters affecting the extraction efficiency of target analytes by the magnetic nanoparticles are investigated, including washing and elution solvents, amount of sorbents, time of extraction and elution, sample and elution solvent volume. The proposed method is optimized by means of experimental design and response surface methodology. When coupled with gas chromatography-mass spectrometry detection and under optimum extraction conditions, average recoveries of target analytes are found to be in the range of 79% to 116%. The proposed MSPE-GC-MS analytical method has a linear calibration curve for all target analytes with coefficients of determination to range from 0.9950 to 0.9999. The limits of quantification are found to be between 0.2 and 1μg/L ensuring compliance with the maximum residue limits established by European Commission and Codex Alimentarius, for OCPs and PCBs residues in milk. The proposed method is applied to the determination of target analytes in milk samples from local markets.

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

    PubMed

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

    2010-10-01

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

  12. 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

  13. Arsenic as an Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–and Thyroid Hormone Receptor–Mediated Gene Regulation and Thyroid Hormone–Mediated Amphibian Tail Metamorphosis

    PubMed Central

    Davey, Jennifer C.; Nomikos, Athena P.; Wungjiranirun, Manida; Sherman, Jenna R.; Ingram, Liam; Batki, Cavus; Lariviere, Jean P.; Hamilton, Joshua W.

    2008-01-01

    Background Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors. Objectives The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid regulation. Methods and results Human embryonic NT2 or rat pituitary GH3 cells were treated with 0.01–5 μM sodium arsenite for 24 hr, with or without RA or TH, respectively, to examine effects of As on receptor-mediated gene transcription. At low, noncytotoxic doses, As significantly altered RAR-dependent gene transcription of a transfected RAR response element–luciferase construct and the native RA-inducible cytochrome P450 CYP26A gene in NT2 cells. Likewise, low-dose As significantly altered expression of a transfected TR response element–luciferase construct and the endogenous TR-regulated type I deiodinase (DIO1) gene in a similar manner in GH3 cells. An amphibian ex vivo tail metamorphosis assay was used to examine whether endocrine disruption by low-dose As could have specific pathophysiologic consequences, because tail metamorphosis is tightly controlled by TH through TR. TH-dependent tail shrinkage was inhibited in a dose-dependent manner by 0.1– 4.0 μM As. Conclusions As had similar effects on RAR- and TR-mediated gene regulation as those previously observed for the steroid receptors, suggesting a common mechanism or action. Arsenic also profoundly affected a TR-dependent developmental process in a model animal system at very low concentrations. Because RAR and TH are

  14. 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

  15. 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

  16. An invertebrate embryo test with the apple snail Marisa cornuarietis to assess effects of potential developmental and endocrine disruptors.

    PubMed

    Schirling, M; Bohlen, A; Triebskorn, R; Köhler, H-R

    2006-09-01

    A novel invertebrate embryo test with the apple snail, Marisa cornuarietis, comprising a test protocol for the following developmental endpoints is described: formation of eyes and tentacles, heart rate, hatching, weight after hatching. To evaluate effects on embryonic development, the snails were treated in a first step with 250 or 500 microg/l cadmium. Sublethal effects in terms of a significant delay in hatching could be found in the 250 microg/l treated animals, whereas 500 microg/l Cd were lethal for the snail embryos. To test endocrine disrupting chemicals with this protocol, experiments with bisphenol A (50 microg/l, 100 microg/l) and 17alpha-ethinylestradiol (10 microg/l) were performed. In both treatments an increase of weight after hatching was observed as well as a significant decline in the heart rate of the embryos. As shown here, the sensitivity of M. cornuarietis embryos test is equal or even higher than other test species like zebrafish embryos and, therefore, this test can be regarded as an alternative or supplement for ecotoxicological studies.

  17. 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.

  18. 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. PMID:16824579

  19. Groundwater from infiltration galleries used for small public water supply systems: contamination with pesticides and endocrine disruptors.

    PubMed

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

    2011-09-01

    Infiltration galleries are among the oldest known means used for small public water fountains. Owing to its ancestral origin they are usually associated with high quality water. Thirty-one compounds, including pesticides and estrogens from different chemical families, were analysed in waters from infiltration galleries collected in Alto Douro Demarcated Wine region (North of Portugal). A total of twelve compounds were detected in the water samples. Nine of these compounds are described as presenting evidence or potential evidence of interfering with the hormone system of humans and wildlife. Although concentrations of the target analytes were relatively low, many of them below their limit of quantification, four compounds were above quantification limit and two of them even above the legal limit of 0.1 μg/L: dimethoate (30.38 ng/L), folpet (64.35 ng/L), terbuthylazine-desethyl (22.28 to 292.36 ng/L) and terbuthylazine (22.49 to 369.33 ng/L).

  20. 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. PMID:23241820

  1. 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

  2. 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

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

    2015-12-01

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

  3. Fate of endocrine disrupting compounds in membrane bioreactor systems.

    PubMed

    Hu, J Y; Chen, X; Tao, G; Kekred, K

    2007-06-01

    Yeast estrogen screen (YES) bioassay and liquid chromatography-mass spectrum-mass spectrum (LC-MS-MS) analysis were performed to investigate the fate of active and potential endocrine disrupting compounds in 3 pilot-scale and 2 lab-scale membrane bioreactor (MBR) systems. Compared with the overall estrogenicities of sewage treatment plant (STP) effluents from references, the MBR systems studied have relatively good performance in the removal of estrogenicity. Estrone (E1) was removed with relatively high efficiency (80.2-91.4%), but 17beta-estradiol (E2) was removed with moderate efficiency (49.3-66.5%) by the MBRs. However, the experimental results indicated that after the treatment by MBR, substantial amounts of E1, estrone-3-sulfate (E1-3S), estrone-3-glucuronide (E1-3G), and 17beta-estradiol-glucuronides (E2-G) passed through treatment systems and entered into the aquatic environment. The reduction in the levels of overall equivalent E1 (68.4%) and that of overall equivalent E2 (80.8%) was demonstrated for the pilot-scale MBR-B. For alkylphenol compounds, bisphenol A (BPA) was removed well with a removal efficiency of 68.9 -90.1%, but 4-nonylphenol (4-NP) concentration was amplified (removal efficiency of -439.5 to -161.1%) after MBR treatment which could be caused by the transformation of its parent compounds, nonylphenol polyethoxylates (NPnEOs). The amounts of adsorbed estrogens per kg dry mass was relatively low, due to short hydraulic retention time and high mixed liquor suspended solids in MBRs, compared to that in STPs. PMID:17612196

  4. Potentiating effect of an endocrine disruptor, paranonylphenol, on the generation of reactive oxygen species (ROS) in human venous blood -- association with the activation of signal transduction pathway.

    PubMed

    Okai, Yasuji; Sato, Eisuke F; Higashi-Okai, Kiyoka; Inoue, Masayasu

    2007-09-01

    An endocrine disruptor, para-nonylphenol (NP), caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human whole blood from 50 to 1000 microM, which was measured by chemiluminescence generation. ROS-scavenging enzymes such as catalase and superoxide dismutase, and the lipophilic antioxidative agents, alpha-tocopherol and beta-carotene, showed preventive effects on NP-induced ROS generation. To analyze the biochemical mechanism of NP-induced ROS generation in human blood, we investigated the effects of different types of metabolic inhibitors on the activation pathways of ROS generation. An NADPH-dependent oxidase inhibitor, diphenyl iodonium chloride (DPI), and a myeloperoxidase inhibitor, sodium azide (NaN3), showed remarkable inhibitory effects on ROS generation induced by NP, but an inhibitor against mitochondrial respiratory function, potassium cyanide (KCN), did not exhibit a significant effect. Furthermore, a phosphatidylinositol-3 (PI3) kinase inhibitor, wortmannin, and a tyrosine kinase inhibitor, protein phosphorylation inhibitor 1 (PP1), caused a strong suppression of NP-induced ROS generation. Selective protein kinase C inhibitor, Ro-32-0432, p38 MAP kinase inhibitor, SB-203580, and ERK MAP kinase inhibitor, PD 98059, showed significant suppressive effects on NP-induced ROS generation. In addition, when human blood was exposed to lower concentrations (5-50 microM) of NP, they did not cause the significant ROS generation by themselves, but the priming and synergistic effects of NP were detected by the addition of secondary stimulants, opsonized zymosan (OZ) or phorbol myristate acetate (PMA). The analysis of the priming and synergistic effects of NP on OZ- or PMA-dependent ROS generation by antioxidative substances and metabolic inhibitors showed similar results compared with those of human blood treated with NP alone. These results suggest that NP causes an enhancing effect by itself, or priming and synergistic

  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. 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.

  7. Influence of endocrine active compounds on the developing rodent brain.

    PubMed

    Patisaul, Heather B; Polston, Eva K

    2008-03-01

    Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure. Using this more comprehensive approach we have demonstrated that the disruption of nuclear volume does not necessarily coincide with disruption of cellular phenotype or neuroendocrine function in two sexually dimorphic brain nuclei: the anteroventral periventricular nucleus of the hypothalamus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN). These results demonstrate that nuclear volume is likely not an appropriate biomarker for EAC exposure. We further demonstrated that neonatal exposure to the EACs genistein (GEN) and Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal phenotypes in adulthood with regional and cellular specificity suggesting that effects observed in one brain region may not be predictive of effects within neighboring regions. Finally, developmental EAC exposure has been shown to affect a variety of sexually dimorphic behaviors including reproductive behavior. These effects are likely to have a broad impact as maladaptive behavior could translate to decreased fitness of entire populations. Collectively, these findings emphasize the need to employ a comprehensive approach that addresses anatomical, functional and behavioral endpoints when evaluating the potential effects of EAC exposure.

  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. PMID:26391401

  9. Enantioselective metabolism of the endocrine disruptor pesticide methoxychlor by human cytochromes P450 (P450s): major differences in selective enantiomer formation by various P450 isoforms.

    PubMed

    Hu, Yiding; Kupfer, David

    2002-12-01

    Methoxychlor, a currently used pesticide that in mammals elicits proestrogenic/estrogenic activity and reproductive toxicity, has been classified as a prototype endocrine disruptor. Methoxychlor is prochiral, and its metabolites 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-M); 1,1,1-trichloro- 2-(4-methoxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (catechol-M); and 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (tris-OH-M) are chiral; whereas 1,1,1-trichloro-2, 2-bis(4-hydroxyphenyl)ethane (bis-OH-M) is achiral. These metabolites are formed during methoxychlor incubation with liver microsomes or recombinant cytochrome p450s (rp450s). Since methoxychlor-metabolite enantiomers may have different estrogenic/antiestrogenic/antiandrogenic activities than corresponding racemates, the possibility that p450s preferentially generate or use R or S enantiomers, was examined. Indeed, rCYP1A2 and r2A6 mono-demethylated methoxychlor primarily into (R)-mono-OH-M at 91 and 75%, respectively, whereas rCYP1A1, 2B6, 2C8, 2C9, 2C19, and 2D6 formed the (S)-enantiomer at 69, 66, 75, 95, 96, and 80%, respectively. However, rCYP3A4, 3A5, and 2B1(rat) weakly demethylated methoxychlor without enantioselectivity. Human liver microsomes generated (S)-mono-OH-M (77-87%), suggesting that CYP1A2 and 2A6 display only minor catalytic contribution. P450 inhibitors demonstrated that CYP2C9 and possibly 2C19 are major hepatic catalysts forming (S)-mono-OH-M, and CYP1A2 is primarily involved in forming the (R)-mono-OH-M. Demethylation rate of (S)-mono-OH-M versus (R)-mono-OH-M forming achiral bis-OH-M by rCYP1A2 was 97/3, compared with 15/85 and 17/83 for rCYP2C9 and 2C19, respectively, indicating opposite substrate enantioselectivity of rCYP1A2 versus 2C9 and 2C19. Also, rCYP1A2 preferentially O-demethylated (R)-catechol-M into (R)-tris-OH-M (at 80%), contrasting r2C9 and r2C19 that yielded (S)-tris-OH-M at 80 and 77%, respectively. Ortho-hydroxylation of

  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. Endocrine disruptors in sewage treatment plants, receiving river waters, and sediments: integration of chemical analysis and biological effects on feral carp.

    PubMed

    Petrovic, Mira; Solé, Montserrat; López de Alda, María J; Barceló, Damià

    2002-10-01

    Occurrence of alkylphenol ethoxylates or their metabolites (alkylphenols and carboxylated derivatives), as well as natural and synthetic steroids in sewage treatment plant (STP) effluents and in their receiving waters, has been related to biological effects, measured as alterations of plasma vitellogenin (VTG) concentration in natural fish populations. Water composites of STP influents, effluents, sludge, river water, sediment, and feral carps (Cyprinus carpio) were analyzed over a seven-month period in two tributaries of the Llobregat River (NE Spain). Solid-phase extraction/liquid chromatography/mass spectrometry (SPE-LC-MS) analysis revealed concentrations of up to 31 microg/L for nonylphenol ethoxylates (NPEOs), 15 microg/L for nonylphenol (NP), and 35 microg/L for nonylphenoxy carboxylate (NPE1C) in river water downstream of STPs. These compounds were also found to accumulate in river sediment with concentrations ranging from 10 to 820 microg/kg of NPEOs and from 22 to 645 microg/kg for NP. Natural and synthetic estrogens and progestogens also occurred in the water and sediments analyzed but in the ng/L and microg/kg range, respectively. Vitellogenin fluctuated among sites and sampling periods, but it was found to be increased in male carp collected downstream of the main STP. A correlation between endocrine-disrupting compounds (EDCs) in water and sediment and plasma VTG concentration in male carp was observed, especially for alkylphenolic compounds in water and sediment samples (r = 0.83-0.84 for n = 24) and for estriol and estrone in water (r = 0.78 and 0.94 for n = 9 and 8, respectively). PMID:12371491

  12. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

    Numerous manmade chemicals released into the environment can interfere with normal, hormonally regulated biological processes to adversely affect the development and reproductive functions of living species. Various in vivo and in vitro tests have been designed for detecting endocrine disruptors, but the number of chemicals to test is so high that to save time and money, (quantitative) structure-activity relationship ((Q)SAR) models are increasingly used as a surrogate for these laboratory assays. However, most of them focus only on a specific target (e.g. estrogenic or androgenic receptor) while, to be more efficient, endocrine disruption modelling should preferentially consider profiles of activities to better gauge this complex phenomenon. In this context, an attempt was made to evaluate the endocrine disruption profile of 220 structurally diverse pesticides using the Endocrine Disruptome simulation (EDS) tool, which simultaneously predicts the probability of binding of chemicals on 12 nuclear receptors. In a first step, the EDS web-based system was successfully applied to 16 pharmaceutical compounds known to target at least one of the studied receptors. About 13% of the studied pesticides were estimated to be potential disruptors of the endocrine system due to their high predicted affinity for at least one receptor. In contrast, about 55% of them were unlikely to be endocrine disruptors. The simulation results are discussed and some comments on the use of the EDS tool are made.

  13. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

    Numerous manmade chemicals released into the environment can interfere with normal, hormonally regulated biological processes to adversely affect the development and reproductive functions of living species. Various in vivo and in vitro tests have been designed for detecting endocrine disruptors, but the number of chemicals to test is so high that to save time and money, (quantitative) structure-activity relationship ((Q)SAR) models are increasingly used as a surrogate for these laboratory assays. However, most of them focus only on a specific target (e.g. estrogenic or androgenic receptor) while, to be more efficient, endocrine disruption modelling should preferentially consider profiles of activities to better gauge this complex phenomenon. In this context, an attempt was made to evaluate the endocrine disruption profile of 220 structurally diverse pesticides using the Endocrine Disruptome simulation (EDS) tool, which simultaneously predicts the probability of binding of chemicals on 12 nuclear receptors. In a first step, the EDS web-based system was successfully applied to 16 pharmaceutical compounds known to target at least one of the studied receptors. About 13% of the studied pesticides were estimated to be potential disruptors of the endocrine system due to their high predicted affinity for at least one receptor. In contrast, about 55% of them were unlikely to be endocrine disruptors. The simulation results are discussed and some comments on the use of the EDS tool are made. PMID:26548639

  14. Fast and simultaneous determination of endocrine disrupting compounds by ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Esteve, C; Herrero, L; Gómara, B; Quintanilla-López, J E

    2016-01-01

    A rapid and sensitive analytical method for the simultaneous determination of thirteen endocrine disruptors (five phthalates, seven parabens, and bisphenol A) in a single chromatographic run has been developed for the first time. The separation method, based on ultra-high performance liquid chromatography (UHPLC), allows the separation of all compounds (including isobaric pairs) in less than 4.1 min. The fast polarity switching mode of the triple quadrupole mass spectrometer used enables the registration of positive (phthalates) and negative (parabens and BPA) ions in the same acquisition run. A Response Surface Methodology was used for the optimization of the method. The optimum elution program starts with 0.2 min in isocratic conditions (79.8% water; 20% acetonitrile, 0.2% ammonium formate 5mM at pH 10.2), then the content of acetonitrile is linearly increased in 2 min up to 42%, and later up to 98% in 1.1 min. The analytical characteristics of the developed method were satisfactory. The method is robust and showed a linear response with determination coefficients (R(2)) higher than 0.991 in the range 5.0-2000 pg on column (or higher) for all the compounds investigated. Instrumental intra- and inter-day precision (expressed as relative standard deviation) were lower than 12% for parabens and bisphenol A, and between 5.9% and 27% for phthalates. Instrumental detection and quantification limits (iLODs and iLOQs) were in the range of medium-high femtograms (270-1300 pg on column for iLODs). Finally, the suitability of the developed method was demonstrated through its application to the analysis of commercial personal care products (shower gels) without any sample treatment, only a simple dilution, being possible to determine the simultaneous presence of phthalates, parabens, and bisphenol A in almost all the gels analyzed. PMID:26695271

  15. 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. PMID:23109571

  16. 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...

  17. 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. PMID:24552621

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. 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…

  3. Biological and enzymatic treatment of bisphenol A and other endocrine disrupting compounds: a review.

    PubMed

    Husain, Qayyum; Qayyum, Shariq

    2013-09-01

    Bisphenol A is predominantly used as an intermediate in the production of polycarbonate plastics and epoxy resins. Traces of bisphenol A released into the environment can reach into the wastewater and soil via application of sewage sludge from wastewater treatment systems that receive water containing bisphenol A, or from leachate from uncontrolled landfills. In this study we have made an effort to review the work on the presence of bisphenol A and other related endocrine disrupting compounds in the environment and their impact on the life of living organisms including human beings. Bisphenol A has several implications on the health of human beings as well it can also affect the growth of plants and animals. Number of physicochemical methods such as adsorption, membrane based filtration, ozonation, fenton, electrochemical and photochemical degradation has been used for the removal of bisphenol A. However, these methods have some inherent limitations and therefore cannot be used for large scale treatment of such pollutants. The alternative procedures have attracted the attention of environmental scientists. Biological methods are looking quite promising and these procedures are helpful in the complete degradation of bisphenol A and related compounds. Several bacterial, fungal, and algal strains and mixed cultures have successfully been employed for the degradation of bisphenol A. Recently, enzymatic methods have attracted the attention of the environmentalists for the treatment of bisphenol A and other endocrine disrupting compounds. Numerous types of oxidoreductases; laccases, tyrosinases, manganese peroxidase, lignin peroxidase, polyphenol oxidases, horseradish peroxidase and bitter gourd peroxidase have exhibited their potential for the remediation of such types of compounds. The cytochrome P 450 monooxygenases and hemoglobin have also participated in the degradation of bisphenol A and other related endocrine disrupting compounds. Various redox mediators

  4. Nitrate (NO3(-)) and nitrite (NO2(-)) are endocrine disruptors to downregulate expression of tyrosine hydroxylase and motor behavior through conversion to nitric oxide in early development of zebrafish.

    PubMed

    Jannat, Meshkatul; Fatimah, Ratu; Kishida, Mitsuyo

    2014-09-26

    With a view to consider the increasing concern over nitrogen pollution in the aquatic environment, we investigated effects of nitrate (NO3(-)) and nitrite (NO2(-)) on the activity of dopaminergic neuron in zebrafish embryos and larvae. Both nitrate and nitrite exposure decreased the expression of tyrosine hydroxylase (TH) in dopaminergic neurons at 48hpf. Only nitrite decreased the response to tactile stimulation at 72hpf, whereas both nitrate and nitrite decreased the swimming activity at 6dpf. When the embryos were exposed to nitrate or nitrite together with an estrogen receptor blocker (ICI 182,780), the decreases in TH expression and motor behavior caused by nitrate or nitrite alone were reversed suggesting the effects of nitrate and nitrite were mediated through estrogen receptor (ER). The result of co-incubation with an oxidoreductase inhibitor, diphenyleneiodonium, indicated the conversion to nitric oxide (NO) is likely to be responsible for the effects of nitrate and nitrite, which was further supported by the increased staining for NO after exposure. The present study demonstrates that nitrate and nitrite are neurotoxicants acting as an endocrine disruptor possibly through conversion to NO to downregulate the activity of dopaminergic neuron in early development of zebrafish. PMID:25173937

  5. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity. PMID:24650234

  6. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity.

  7. Restricted access property supramolecular solvents for combined microextraction of endocrine disruptors in sediment and sample cleanup prior to their quantification by liquid chromatography-tandem mass spectrometry.

    PubMed

    López-Jiménez, F J; Rosales-Marcano, M; Rubio, S

    2013-08-16

    A supramolecular solvent (SUPRAS) made up of inverted hexagonal aggregates of decanol was here proposed for the simultaneous microextraction of representative estrogenic disruptors (EDs) [viz. estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2) and bisphenol A (BPA)] in sediments and sample cleanup. The SUPRAS contains aqueous cavities, the size of which can be tailored by controlling the environment for decanol self-assembly. The method involved the stirring of the sample (0.3g of sediment) with 0.4mL of SUPRAS for 10min, subsequent centrifugation for extract separation from solid matrix components and direct analysis of the extract by liquid chromatography/triple quadrupole mass spectrometry (LC/QQQMS-MS). Driving forces for the microextraction of EDs in the SUPRAS involved both dispersion and hydrogen bond interactions. This mixed-mode mechanism resulted in high extraction efficiencies for EDs (viz. recoveries between 93 and 104%) and that allowed to reach low method detection limits (viz. 0.03, 0.3, 0.28, 0.4 and 0.08ngg(-1) for E1, E2, E3, EE2 and BPA, respectively) without the need for extract evaporation. The size of the aqueous cavities of the SUPRAS selected was no large enough to allow humic acids to efficiently diffuse through them. So the SUPRAS behaved as a restricted access material for these macromolecules thus facilitating sample cleanup. The method was applied to the determination of the targeted EDs in sediments from three rivers in the Southern Spain. The concentrations found ranged between below the MDL and 6.4ngg(-1). The sample treatment here proposed greatly simplifies the procedures currently used for the determination of EDs in sediments using LC/MS-MS.

  8. 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

  9. 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

  10. Occurrence and analysis of endocrine-disrupting compounds in a water supply system.

    PubMed

    Carvalho, A R M; Cardoso, V V; Rodrigues, A; Ferreira, E; Benoliel, M J; Duarte, E A

    2015-03-01

    This paper presents the study of the occurrence of 10 endocrine-disrupting compounds (EDCs) in 60 water samples using a method for simultaneous quantification and confirmation of the presence of these emerging compounds, using ultra-performance liquid chromatography with electrospray ionization and tandem mass spectrometry (UPLC-ESI-MS/MS). All samples were previously extracted by solid-phase extraction (SPE). Several natural and synthetic hormones (17-β-estradiol, ethinylestradiol, estriol, estrone, progesterone, mestranol, and diethylstilbestrol) and some industrial products (4-n-nonylphenol, 4-tert-octylphenol, and bisphenol A) were chosen for this survey. The analytical limits were calculated for each compound and were used in the identification and quantification of these target compounds in EPAL's water supply system. In this study, several samples were taken from the main intakes of water (surface and groundwater) used for production of water for human consumption and from different sampling points of the drinking water distribution system (piping, nets, and reservoirs). Some target compounds, such as estriol, 4-tert-octylphenol, mestranol, and nonylphenol, were found in trace amounts in several water samples. However, the studied endocrine-disrupting appeared in very low concentrations when compared with the assessed analytical limits.

  11. 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.

  12. 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

  13. CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identification.

    PubMed

    Hu, Y; Krausz, K; Gelboin, H V; Kupfer, D

    2004-02-01

    1. The endocrine disruptor pesticide methoxychlor undergoes O-demethylation by mammalian liver microsomes forming chiral mono-phenolic (1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane, i.e. mono-OH-M) and achiral bis-phenolic oestrogenic metabolites. Human liver microsomes (HLM) generated primarily the S-mono-OH-M. 2. Inhibitory monoclonal antibodies (MAb) identified those P450s catalysing the enantioselective O-demethylation of methoxychlor. In HLM, O-demethylation was inhibited by MAb anti-2C9 (30-40%), diminishing the per cent of S-mono-OH-M from about 80 to 55-60%. MAb anti-CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6 and 3A4 did not affect the demethylation rate in HLM. Nevertheless, MAb anti-CYP1A2 decreased the formation of R-mono-OH-M from 21-23 to 10-17%, indicating that CYP1A2 exhibits a role in generating the R-enantiomer. 3. Among cDNA-expressed human P450s (supersomes), CYP2C19 was the most active in demethylation, but in HLM, CYP2C19 appeared inactive (no inhibition by MAb anti-CYP2C19). There was a substantial difference in the per cent inhibition of demethylation by MAb anti-CYP2C9 and anti-rat CYP2C (MAb inhibiting all human CYP2C forms) and in altering the enantioselectivity, suggesting that demethylation by combined CYP2C8, 2C18 and 2C19 was significant (20-30%). 4. Polymorphism of methoxychlor demethylation was examined with supersomes and HLM-expressing CYP2C9 allelic variants. CYP2C9*1 and 2C9*2 were highly active; however, CYP2C9*3 appeared inactive.

  14. 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

  15. Analysis of endocrine disrupters and related compounds in sediments and sewage sludge using on-line turbulent flow chromatography-liquid chromatography-tandem mass spectrometry.

    PubMed

    Gorga, Marina; Insa, Sara; Petrovic, Mira; Barceló, Damià

    2014-07-25

    A novel fully automated method based on dual column switching using turbulent flow chromatography followed by liquid chromatography coupled to tandem mass spectrometry (TFC-LC-MS/MS) was applied for the determination of endocrine disruptors (EDCs) and related compounds in sediment and sewage sludge samples. This method allows the unequivocal identification and quantification of the most relevant environmental EDCs such as natural and synthetic estrogens and their conjugates, antimicrobials, parabens, bisphenol A (BPA), alkylphenolic compounds, benzotriazoles, and organophosphorus flame retardants, minimizing time of analysis and alleviating matrix effects. Applying this technique, after the extraction of the target compounds by pressurized liquid extraction (PLE), sediment and sewage sludge extracts were directly injected to the chromatographic system and the analytes were concentrated into the clean-up loading column. Using six-port switching system, the analytes were transferred to the analytical column for subsequent detection by MS-MS (QqQ). In order to optimize this multiplexing system, a comparative study employing six types of TurboFlow™ columns, with different chemical modifications, was performed to achieve the maximum retention of analytes and best elimination of matrix components. Using the optimized protocol low limits of quantification (LOQs) were obtained ranging from 0.0083 to 1.6 ng/g for sediment samples and from 0.10 to 125 ng/g for sewage sludge samples (except for alkylphenol monoethoxylate). The method was used to evaluate the presence and fate of target EDCs in the Ebro River which is the most important river in Spain with intensive agricultural and industrial activities in the basin that contribute to deteriorating soil and water quality. PMID:24909438

  16. 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

  17. 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. PMID:23178835

  18. 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.

  19. Determination of endocrine disrupting compounds using temperature-dependent inclusion chromatography: I. Optimization of separation protocol.

    PubMed

    Zarzycki, Paweł K; Włodarczyk, Elzbieta; Baran, Michał J

    2009-10-30

    In the present work we optimised the separation of battery of key UV non-transparent low-molecular-mass compounds having possible endocrine disrupting compounds (EDCs) activity or which may be used as the endocrine effect biomarkers. Simple optimization strategy was based on strong temperature effect that is driven by electrostatic interactions between macrocyclic mobile phase additives like cyclodextrins and eluted components of interest under C18 stationary phase and acetonitrile/water mobile phase conditions. Particularly, the effect of temperature involving native beta-cyclodextrin and its hydroxypropyl derivative to improve separation of number of natural (d-equilenin, equilin, estetrol, estriol, estrone, 17beta-estradiol, 17alpha-hydroxyprogesterone, 20alpha-hydroxyprogesterone, cortisol, cortisone, progesterone, testosterone, tetrahydrocortisol and tetrahydrocortisone) and artificial steroids (ethynylestradiol, norgestrel isomers, medroxyprogesterone, mestranol, methyltestosterone, norethindrone, 17alpha-estradiol) as well as non-steroidal compounds (diethylstilbesterol, bisphenol A, 4-tert-butylphenol, dimethyl phthalate, dibutyl phthalate and dioctyl phthalate) was investigated. It has been found that successful isocratic separation of 27 chemicals can be achieved using acetonitrile/water eluents modified with beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin at concentration of 10 mM and temperature of 47 degrees C. Separation protocol is simple, reliable, direct and non-radioactive and may be easily adapted for rapid separation and quantification of wide range of given steroids and related EDCs in environmental samples, particularly those that are characterised by unstable biological matrix and components of interest load. PMID:19362314

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

    PubMed

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    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 (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 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 embryos. 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 plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages 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. PMID:24713117

  1. 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.

  2. 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.

  3. 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.

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

    PubMed

    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. 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. PMID:23709001

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

    PubMed

    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. PMID:23977686

  7. The methods of identification, analysis, and removal of endocrine disrupting compounds (EDCs) in water.

    PubMed

    Chang, Hyun-Shik; Choo, Kwang-Ho; Lee, Byungwhan; Choi, Sang-June

    2009-12-15

    The information regarding endocrine disrupting compounds (EDCs) was reviewed, including the definition and characteristics, the recent research trends concerning identification and analytical methods, and the applicable removal processes. EDCs include various types of natural and synthetic chemical compounds presenting the mimicking or inhibition of the reproductive action of the endocrine system in animals and humans. The ubiquitous presence with trace level concentrations and the wide diversity are the reported characteristics of EDCs. Biologically based assays seem to be a promising method for the identification of EDCs. On the other hand, mass-based analytical methods show excellent sensitivity and precision for their quantification. Several extraction techniques for the instrumental analysis have been developed since they are crucial in determining overall analytical performances. Conventional treatment techniques, including coagulation, precipitation, and activated sludge processes, may not be highly effective in removing EDCs, while the advanced treatment options, such as granular activated carbon (GAC), membrane, and advanced oxidation processes (AOPs), have shown satisfactory results. The oxidative degradation of some EDCs was associated with aromatic moieties in their structure. Further studies on EDCs need to be conducted, such as source reduction, limiting exposure to vulnerable populations, treatment or remediation of contaminated sites, and the detailed understanding of transport mechanisms in the environment. PMID:19632774

  8. Development and Characterization of a Human Reporter Cell Line for the Assessment of Thyroid Receptor Transcriptional Activity: A Case of Organotin Endocrine Disruptors.

    PubMed

    Illés, Peter; Brtko, Július; Dvořák, Zdeněk

    2015-08-12

    We developed and characterized the human luciferase reporter cell line PZ-TR for the assessment of thyroid receptor (TR) transcriptional activity. Triiodothyronine (T3) induced luciferase activity in a dose-dependent manner, and the sensitivity of assay allowed for the detection of nanomolar T3 concentrations. The luciferase activity was induced by a maximum of (2.42 ± 0.14)-(2.73 ± 0.23)-fold after 24 h of exposure to 10 nM T3. We did not observe a nonspecific induction of luciferase activity by other steroid hormones and VDR ligands, with the exception of partial activation by retinoic acids. Cryopreservation of PZ-TR cells did not influence their functionality, responsivity to T3, or cell morphology, even after long-term cultivation. PZ-TR cells were used to evaluate the effects of organic tin compounds on TR. We found that the tributyltin and triphenyltin derivatives induced luciferase activity and that application of organotins in combination with T3 enhanced the effect of T3. These findings indicate that organic tin compounds have potential to interfere with TR-mediated regulation of gene expression and influence the physiological activity of thyroid hormones. PMID:26208032

  9. [Hormonal disruptors and farm animals].

    PubMed

    van Os, J L

    1998-01-01

    A number of man made environmental contaminants displays a weak hormonal, usually oestrogenic, activity. Currently such contaminants are termed hormone disruptors, a terminology that also includes natural compounds with hormonal activity, such as phyto and fungal oestrogens. Fertility and morphological defects in wildlife are related to high exposure to man made hormone disruptors. The potential threat of such exposure for human reproductive health is widely discussed. A possible decline in sperm counts in men is one of the subjects related to such environmental factors. There are no firm indications for this threat. Additional research is needed, however, for a more complete assessment. Farm animals so far played a minor role in the discussion. Therefore, in a study published elsewhere, long term trends in sperm counts of Dutch Dairy Bulls have been evaluated (27). No decline was found in 75,238 ejaculates collected between 1977 and 1996 from 2,314 bulls of the centre for artificial insemination (AI) NOORDWEST. Results of this study, published elsewhere, formed the reason to broader go into the relation between hormone disruptors and farm animals, observed effects of phyto-oestrogens in such animal and the role these animals could play in further research. PMID:9537066

  10. Glucuronidation of the oxidative cytochrome P450-mediated phenolic metabolites of the endocrine disruptor pesticide: methoxychlor by human hepatic UDP-glucuronosyl transferases.

    PubMed

    Hazai, Eszter; Gagne, Peter V; Kupfer, David

    2004-07-01

    Methoxychlor, a currently used pesticide, is a proestrogen exhibiting estrogenic activity in mammals in vivo. Methoxychlor undergoes oxidative metabolism by cytochromes P450, yielding 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-M) and 1,1,1-trichloro-2,2-bis(4-hydroxyphenyl)ethane (bis-OH-M) as main metabolites. Since humans may be exposed to these estrogenic metabolites, which are potential substrates of UDP-glucuronosyltransferases (UGTs), their glucuronide conjugation was investigated with human liver preparations and individual UGTs. Incubation of both mono-OH-M and bis-OH-M with human liver microsomes formed monoglucuronides. The structures of the glucuronides were identified by liquid chromatography/tandem mass spectometry. Examination of cDNA-expressed recombinant human hepatic UGTs revealed that several catalyze glucuronidation of both compounds. Among the cDNA-expressed UGT1A enzymes, UGT1A9 seemed to be the main catalyst of formation of mono-OH-M-glucuronide, whereas UGT1A3 seemed to be the most active in bis-OH-M-glucuronide formation. Furthermore, the chiral selectivity of mono-OH-M glucuronidation was examined. The results of the incubation of single enantiomers generally agreed with the chiral analyses of mono-OH-M derived from the glucuronidase digestion of the glucuronides of the racemic mono-OH-M. There was a relatively slight but consistent enantioselective preference of individual UGT1A1, UGT1A3, UGT1A9, and UGT2B15 enzymes for glucuronidation of the S- over the R-mono-OH-M, whereas in human liver microsomes differences were observed among donors in generating the respective R/S-mono-OH-M ratio. Since it was previously shown that human liver microsomes demethylate methoxychlor mainly into S-mono-OH-M, the observation that UGT1A isoforms preferentially glucuronidate the S-mono-OH-M suggests a suitable mechanism for eliminating this major enantiomer. This enantiomeric preference, however, is not extended to all samples of

  11. 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.

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

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter 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. 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. PMID:19350922

  13. A new analytical protocol for the determination of 62 endocrine-disrupting compounds in indoor air.

    PubMed

    Laborie, Stéphanie; Moreau-Guigon, Elodie; Alliot, Fabrice; Desportes, Annie; Oziol, Lucie; Chevreuil, Marc

    2016-01-15

    The objective of this study was to develop and validate a new analytical protocol for simultaneous determination of 62 semi-volatile organic compounds in both phases of indoor air. Studied compounds belong to several families: polybrominated diphenyl ethers, polychlorinated biphenyls, hexachlorobenzene, pentachlorobenzene, phthalates, polyaromatic hydrocarbons, parabens, tetrabromobisphenol A, bisphenol A, hexabromocyclododecane, triclosan, alkylphenols, alkylphenol ethoxylates, synthetic musks (galaxolide and tonalide) and pesticides (lindane and cypermethrin). A medium volume sampling system was used to collect simultaneously these endocrine-disrupting compounds (EDCs) from the gaseous and particulate phases. An accelerated solvent extraction method was optimized to obtain all EDCs in a single extract by atmospheric phase. Their extraction from the sorbents and their analysis by liquid and gas chromatography-mass spectrometry (LC/MS/MS, GC/MS and GC/MS/MS) was validated using spiked sorbents (recovery study and analytical uncertainty analysis by fully nested design). The developed protocol achieved low limits of quantification (<0.5ng m(-3)) and low uncertainty values (<5ng m(-3)) for all compounds. Once validated, the method was applied to indoor air samples from four locations (a house, an apartment, a day nursery and an office) and compared to literature to confirm its efficiency. All target EDCs were quantified in the samples and were primarily present in the gaseous phase. The major contaminants found in indoor air were, in descending order, phthalates, synthetic musks, alkylphenols and parabens. PMID:26592587

  14. 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.

  15. 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

  16. 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

  17. Mugilid fish are sentinels of exposure to endocrine disrupting compounds in coastal and estuarine environments.

    PubMed

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

    2014-09-01

    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

  18. 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...

  19. 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.

  20. Semivolatile Endocrine-Disrupting Compounds in Paired Indoor and Outdoor Air in Two Northern California Communities

    PubMed Central

    2010-01-01

    Interest in the health effects of potential endocrine-disrupting compounds (EDCs) that are high production volume chemicals used in consumer products has made exposure assessment and source identification a priority. We collected paired indoor and outdoor air samples in 40 nonsmoking homes in urban, industrial Richmond, CA, and 10 in rural Bolinas, CA. Samples were analyzed by GC-MS for 104 analytes, including phthalates (11), alkylphenols (3), parabens (3), polybrominated diphenyl ether (PBDE) flame retardants (3), polychlorinated biphenyls (PCBs) (3), polycyclic aromatic hydrocarbons (PAHs) (24), pesticides (38), and phenolic compounds (19). We detected 39 analytes in outdoor air and 63 in indoor air. For many of the phenolic compounds, alkylphenols, phthalates, and PBDEs, these represent some of the first outdoor measures and the first analysis of the relative importance of indoor and outdoor sources in paired samples. Data demonstrate higher indoor concentrations for 32 analytes, suggesting primarily indoor sources, as compared with only 2 that were higher outdoors. Outdoor air concentrations were higher in Richmond than Bolinas for 3 phthalates, 10 PAHs, and o-phenylphenol, while indoor air levels were more similar between communities, except that differences observed outdoors were also seen indoors. Indoor concentrations of the most ubiquitous chemicals were generally correlated with each other (4-t-butylphenol, o-phenylphenol, nonylphenol, several phthalates, and methyl phenanthrenes; Kendall correlation coefficients 0.2−0.6, p < 0.05), indicating possible shared sources and highlighting the importance of considering mixtures in health studies. PMID:20681565

  1. Fate of selected pharmaceuticals and synthetic endocrine disrupting compounds during wastewater treatment and sludge anaerobic digestion.

    PubMed

    Samaras, Vasilios G; Stasinakis, Athanasios S; Mamais, Daniel; Thomaidis, Nikolaos S; Lekkas, Themistokles D

    2013-01-15

    The concentrations of nine emerging contaminants, including pharmaceutically active compounds (PhACs) (ibuprofen, IBF; naproxen, NPX; diclofenac, DCF; ketoprofen, KFN) and endocrine disrupting chemicals (triclosan, TCS; bisphenol, BPA; nonylphenol, NP; nonylphenol monoethoxylate, NP1EO; nonylphenol diethoxylate, NP2EO), were determined in wastewater and sludge samples of two wastewater treatment plants (WWTPs) in Greece. Average concentrations in raw and treated wastewater ranged from 0.39 (KFN) to 12.52 μg L(-1) (NP) and from compounds during wastewater treatment ranged between 39% (DCF) and 100% (IBF). Except of DCF and BPA, similar removal efficiencies were observed in both WWTPs and no effect of WWTP's size and operational conditions was noticed. Use of mass balances showed that accumulation on sludge was a significant removal mechanism for NPs and TCS, while biodegradation/biotransformation was the major mechanism for the other compounds. Sampling of raw and digested sludge demonstrated that IBF and NPX are significantly removed (>80%) during anaerobic digestion, whereas removal of EDCs was lower, ranging up to 55% for NP1EO. PMID:23257325

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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.

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

    PubMed

    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. PMID:27056047

  8. Monitoring of environmental phenolic endocrine disrupting compounds in treatment effluents and river waters, Korea.

    PubMed

    Ko, Eun-Joung; Kim, Kyoung-Woong; Kang, Seo-Young; Kim, Sang-Don; Bang, Sun-Baek; Hamm, Se-Yeong; Kim, Dong-Wook

    2007-10-15

    The last two decades have witnessed growing scientific and public concerns over endocrine disrupting compounds (EDCs) that have the potential to alter the normal structure or functions of the endocrine system in wildlife and humans. In this study, the phenolic EDCs such as alkylphenol, chlorinated phenol and bisphenol A were considered. They are commonly found in wastewater discharges and in sewage treatment plant. In order to monitor the levels and seasonal variations of phenolic EDCs in various aquatic environments, a total of 15 water samples from the discharged effluent from sewage and wastewater treatment plants and river water were collected for 3 years. Ten environmental phenolic EDCs were determined by GC-MS and laser-induced fluorescence (LIF). GC-MS analysis revealed that most abundant phenolic EDCs were 4-n-heptylphenol, followed by nonlyphenol and bisphenol A during 2002-2003, while 4-t-butylphenol and 4-t-octylphenol were newly detected in aquatic environments in 2004. The category of phenolic EDCs showed similar fluorescence spectra and nearly equal fluorescence decay time. This makes it hard to distinguish each phenolic EDC from the EDCs mixture by LIF. Therefore, the results obtained from LIF analysis were expressed in terms of the fluorescence intensity of the total phenolic EDCs rather than that of the individual EDC. However, LIF monitoring and GC-MS analysis showed consistent result in that the river water samples had lower phenolic EDCs concentration compared to the effluent sample. This revealed a lower fluorescence intensity and the phenolic EDCs concentration in summer was lower than that in winter. For the validation of LIF monitoring for the phenolic EDCs, the correlation between EDCs concentration acquired from GC-MS and fluorescence intensity from LIF was obtained (R=0.7379). This study supports the feasibility of the application of LIF into EDCs monitoring in aquatic systems. PMID:19073088

  9. 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.

  10. 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; 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.

  11. 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.

  12. Determination of endocrine disrupting compounds and their metabolites in fish bile.

    PubMed

    Ros, Oihana; Izaguirre, Jon Kepa; Olivares, Maitane; Bizarro, Cristina; Ortiz-Zarragoitia, Maren; Cajaraville, Miren Pilar; Etxebarria, Nestor; Prieto, Ailette; Vallejo, Asier

    2015-12-01

    This work describes a new methodology for the simultaneous determination of a large variety of emerging and persistent organic compounds and some of their metabolites in fish bile samples. The target compounds were musk fragrances, alkyl phenols, hormones, pesticides, phthalate esters and bisphenol-A, all of them with a known endocrine disrupting effect. To achieve the determination these three steps were optimized: i) an enzymatic hydrolysis of the metabolites to render the unconjugated compounds; ii) the solid phase extraction of the target analytes (Plexa cartridges 200-mg); and, iii) a clean-up of the extracts (Florisil cartridges 1-g). The samples were analyzed by gas-chromatography-mass spectrometry (GC-MS), though the polar fraction required a previous derivatization with O-bis (trimethylsilyl) trifluoroacetamide. Good apparent recoveries (63-122%), repeatability (<20%) and limits of detection (LODs) ranging between 0.04 and 459 ng/mL were obtained. This method was applied to the analysis of the target analytes in bile samples of thicklip grey mullets (Chelon labrosus) from five different populations of the Basque Coast (South East Bay of Biscay) during the period of May-June 2012. The target analytes were found at concentrations ranging from

  13. 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.'

  14. 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.

  15. Quantitative mechanistically based dose-response modeling with endocrine-active compounds.

    PubMed Central

    Andersen, M E; Conolly, R B; Faustman, E M; Kavlock, R J; Portier, C J; Sheehan, D M; Wier, P J; Ziese, L

    1999-01-01

    A wide range of toxicity test methods is used or is being developed for assessing the impact of endocrine-active compounds (EACs) on human health. Interpretation of these data and their quantitative use in human and ecologic risk assessment will be enhanced by the availability of mechanistically based dose-response (MBDR) models to assist low-dose, interspecies, and (italic)in vitro(/italic) to (italic)in vivo(/italic) extrapolations. A quantitative dose-response modeling work group examined the state of the art for developing MBDR models for EACs and the near-term needs to develop, validate, and apply these models for risk assessments. Major aspects of this report relate to current status of these models, the objectives/goals in MBDR model development for EACs, low-dose extrapolation issues, regulatory inertia impeding acceptance of these approaches, and resource/data needs to accelerate model development and model acceptance by the research and the regulatory community. PMID:10421774

  16. Endocrine disrupting compounds in gaseous and particulate outdoor air phases according to environmental factors.

    PubMed

    Teil, Marie-Jeanne; Moreau-Guigon, Elodie; Blanchard, Martine; Alliot, Fabrice; Gasperi, Johnny; Cladière, Mathieu; Mandin, Corinne; Moukhtar, Sophie; Chevreuil, Marc

    2016-03-01

    This study investigated, for the first time in France, the spatial and temporal patterns of 55 endocrine disrupting chemicals (EDCs) in ambient air at three sites (urban, suburban and forest) under two climatic periods (warm/cold) for 2 successive years. All EDCs, except tetrabromobisphenol A (TBBPA), were encountered with various frequencies of up to 100%. Phthalate diesters (PAEs) were the most abundant chemicals with total concentrations as the sum of compounds, ranging from 10 to 100 ng m(-3) of total air, followed by alkylphenols (APs) and polycyclic aromatic hydrocarbons (PAHs), which were both approximately 1 ng m(-3). Polychlorinated biphenyl (PCBs) and bisphenol A (BPA) concentrations were notably lower (approximately 0.1 ng m(-3)). Air concentrations, depending on the considered compounds, were from 1.2 to 2 times higher in the urban than the suburban area and from 2 to 5 times higher in the urban than the forest site. PAH emissions were higher in the cold period, due to combustion processes. This finding is contrary to the other EDCs that are more abundant in the summer and governed by volatilisation. Most of the EDCs were largely distributed in the gaseous phase (>80% in the summer). The octanol/air partition coefficient (KOA) and vapour pressure (Vp) were relevant parameters for predicting EDC partitioning and direct relationships (p < 0.001) were observed i) between log K particle/gas partitioning (log Kp) and log KOA and ii) between EDC ratios in the gaseous phase and log vapour pressure (log Vp). PMID:26714291

  17. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars.

    PubMed

    Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

    2013-12-15

    Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0-45 ppm), methoxyl (45-63 ppm), O-alkyl (63-108 ppm), and carboxyl carbon (165-187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (Kow) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of adsorbates steadily throughout the study. PMID:24231319

  18. 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

  19. 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

  20. 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...

  1. 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...

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. 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. PMID:22885596

  5. 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

  6. Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

    PubMed

    Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

    2016-01-01

    This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms. PMID:27533865

  7. 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.

  8. 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.

  9. Relationship between biomarkers and endocrine-disrupting compounds in wild Girardnichthys viviparus from two lakes with different degrees of pollution.

    PubMed

    Olivares-Rubio, Hugo F; Dzul-Caamal, Ricardo; Gallegos-Rangel, María Esperanza; Madera-Sandoval, Ruth L; Domínguez-López, María Lilia; García-Latorre, Ethel; Vega-López, Armando

    2015-04-01

    Despite great efforts worldwide to evaluate the effects of endocrine-disrupting compounds (EDCs) in fish, there is little information available about the interactions of EDCs with the disruption of the sexual endocrine axis in fish species with matrotrophic viviparity and intraluminal gestation. To understand these interactions, six sampling campaigns were performed within a period of 1 year in two lakes with different degrees of pollution. A battery of biomarkers of the oestrogenic response was assessed in the liver [vitellogenin, CYP 1A1, epoxide hydrolase activity, and metallothioneins (MT)] and MT in the head of Girardinichthys viviparus. Linear correlation analysis and canonical correspondence analysis were performed to explore the relationship between the oestrogenic response with EDCs and with metals. The biomarker responses were assessed using the water content of EDCs (oestrone, 17-β-oestradiol, oestriol, 17-α-ethinyl oestradiol, total phenols, bisphenol A, nonyl phenol, octyl phenol), as well as the PAHs indene[1,2,3-c,d]pyrene, naphthalene, pyrene, benzo[a]anthracene, benzo[k]fluoranthene and benzo[a]pyrene) and metals (Cu, Fe, Mn, Pb and Zn). Greater disruption of the sexual endocrine axis occurred in fish of both sexes inhabiting the polluted lake whose effects were apparently influenced by CYP 1A1 activity and by 17-α-ethinyl oestradiol. In addition, non-estrogenic mechanisms in the hypothalamus and pituitary glands in male fish were observed, elicited by endogenous levels and the water concentration of Pb. In contrast, in females from the less polluted lake, VTG induction was related to exogenous oestrogens. The disruption of the hypothalamic-pituitary-gonadal axis is a complex process influenced by both endogenous and exogenous factors and contributes to male feminisation by exposure to EDCs.

  10. Relationship between biomarkers and endocrine-disrupting compounds in wild Girardnichthys viviparus from two lakes with different degrees of pollution.

    PubMed

    Olivares-Rubio, Hugo F; Dzul-Caamal, Ricardo; Gallegos-Rangel, María Esperanza; Madera-Sandoval, Ruth L; Domínguez-López, María Lilia; García-Latorre, Ethel; Vega-López, Armando

    2015-04-01

    Despite great efforts worldwide to evaluate the effects of endocrine-disrupting compounds (EDCs) in fish, there is little information available about the interactions of EDCs with the disruption of the sexual endocrine axis in fish species with matrotrophic viviparity and intraluminal gestation. To understand these interactions, six sampling campaigns were performed within a period of 1 year in two lakes with different degrees of pollution. A battery of biomarkers of the oestrogenic response was assessed in the liver [vitellogenin, CYP 1A1, epoxide hydrolase activity, and metallothioneins (MT)] and MT in the head of Girardinichthys viviparus. Linear correlation analysis and canonical correspondence analysis were performed to explore the relationship between the oestrogenic response with EDCs and with metals. The biomarker responses were assessed using the water content of EDCs (oestrone, 17-β-oestradiol, oestriol, 17-α-ethinyl oestradiol, total phenols, bisphenol A, nonyl phenol, octyl phenol), as well as the PAHs indene[1,2,3-c,d]pyrene, naphthalene, pyrene, benzo[a]anthracene, benzo[k]fluoranthene and benzo[a]pyrene) and metals (Cu, Fe, Mn, Pb and Zn). Greater disruption of the sexual endocrine axis occurred in fish of both sexes inhabiting the polluted lake whose effects were apparently influenced by CYP 1A1 activity and by 17-α-ethinyl oestradiol. In addition, non-estrogenic mechanisms in the hypothalamus and pituitary glands in male fish were observed, elicited by endogenous levels and the water concentration of Pb. In contrast, in females from the less polluted lake, VTG induction was related to exogenous oestrogens. The disruption of the hypothalamic-pituitary-gonadal axis is a complex process influenced by both endogenous and exogenous factors and contributes to male feminisation by exposure to EDCs. PMID:25567190

  11. 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...

  12. Removal of selected pharmaceuticals, fragrances and endocrine disrupting compounds in a membrane bioreactor and conventional wastewater treatment plants.

    PubMed

    Clara, M; Strenn, B; Gans, O; Martinez, E; Kreuzinger, N; Kroiss, H

    2005-11-01

    Eight pharmaceuticals, two polycyclic musk fragrances and nine endocrine disrupting chemicals were analysed in several waste water treatment plants (WWTPs). A membrane bioreactor in pilot scale was operated at different solid retention times (SRTs) and the results obtained are compared to conventional activated sludge plants (CASP) operated at different SRTs. The SRT is an important design parameter and its impact on achievable treatment efficiencies was evaluated. Different behaviours were observed for the different investigated compounds. Some compounds as the antiepileptic drug carbamazepine were not removed in any of the sampled treatment facilities and effluent concentrations in the range of influent concentrations were measured. Other compounds as bisphenol-A, the analgesic ibuprofen or the lipid regulator bezafibrate were nearly completely removed (removal rates >90%). The operation of WWTPs with SRTs suitable for nitrogen removal (SRT>10 days at 10 degrees C) also increases the removal potential regarding selected micropollutants. No differences in treatment efficiencies were detected between the two treatment techniques. As in conventional WWTP also the removal potential of MBRs depends on the SRT. Ultrafiltration membranes do not allow any additional detention of the investigated substances due to size exclusion. However, MBRs achieve a high SRT within a compact reactor. Nonylphenolpolyehtoxylates were removed in higher extend in very low-loaded conventional WWTPs, due to variations of redox conditions, necessary for the degradation of those compounds.

  13. 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.

  14. Atrazine is an immune disruptor in adult northern leopard frogs (Rana pipiens).

    PubMed

    Brodkin, Marc A; Madhoun, Hareth; Rameswaran, Muthuramanan; Vatnick, Itzick

    2007-01-01

    Atrazine, the most widely used herbicide in the United States, has been shown in several studies to be an endocrine disruptor in adult frogs. Results from this study indicate that atrazine also functions as an immune disruptor in frogs. Exposure to atrazine (21 ppb for 8 d) affects the innate immune response of adult Rana pipiens in similar ways to acid exposure (pH 5.5), as we have previously shown. Atrazine exposure suppressed the thioglycollate-stimulated recruitment of white blood cells to the peritoneal cavity to background (Ringer exposed) levels and also decreased the phagocytic activity of these cells. Unlike acid exposure, atrazine exposure did not cause mortality. Our results, from a dose-response study, indicate that atrazine acts as an immune disruptor at the same effective doses that it disrupts the endocrine system.

  15. Seasonal and spatial distribution of several endocrine-disrupting compounds in the Douro River Estuary, Portugal.

    PubMed

    Ribeiro, Cláudia; Tiritan, Maria Elizabeth; Rocha, Eduardo; Rocha, Maria João

    2009-01-01

    Recent studies in the Douro River estuary show signs of pollution in the area and of fish endocrine disruption. However, the chemical nature of the local contamination has not been fully investigated nor have studies checking for the simultaneous presence of endocrine-disrupting chemicals (EDCs), either of animal (estrone, E1; estradiol, E2), pharmaceutical (17alpha-ethynylestradiol, EE2), vegetal (daidzein, DAID; genistein, GEN; biochanin A, BIO-A), or industrial (bisphenol A, BPA; 4-octylphenol, 4-OP; 4-nonylphenol, 4-NP) origins. Thus, the main objective of this study was to examine the presence of these EDCs in estuarine water samples collected, in every season of the year, at nine sampling stations along the estuarine gradient. All samples were processed by two-step solid-phase extraction (Oasis HLB followed by silica) prior to high-performance liquid chromatography with diode-array detection (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS) analyses. The current data showed that E1 and EE2, all phytoestrogens, and BPA were identified and measured in this estuary. In contrast, 4-OP was only detected by GC-MS and E2 and 4-NP were not found. Additionally, E1 (up to 112.9 ng/L) and EE2 (up to 101.9 ng/L) were both measured in biologically hazardous amounts in winter. In the year sampled, the phytoestrogens suggested a possible seasonal pattern of fluctuation. Both DAID (up to 888.4 ng/L) and GEN (183.6 ng/L) were maximal in early summer, whereas BIO-A (up to 191.4 ng/L) reached its highest concentrations in winter. BPA (up to 10.7 microg/L) also attained highest levels in winter. In December 2005, it is hypothesized that E1, EE2, and BPA concentrations were atypically high due to current drought conditions. Almost all assayed EDCs existed in all seasons and, therefore, might have contributed to endocrine disruption of aquatic animals, previously documented by the high rate of ovotestis in fish caught in this estuary. PMID:18368434

  16. 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...

  17. 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.

  18. THE INFLUENCE OF SERUM BINDING PROTEINS AND FEEDBACK CONTROL OF SERUM ESTRADIOL LEVELS ON THE COMPARATIVE POTENCY OF ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    THE INFLUENCE OF SERUM BINDING PROTEINS ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS. JG Teeguarden1 and HA Barton2. 1ICF Consulting, Research Triangle Park NC; 2US EPA, ORD, NHEERL, ETD, Pharmacokinetics Branch, RTP, NC.

    Accurate comparison of...

  19. 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. PMID:23445418

  20. 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.

  1. From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting compounds across biological scales.

    PubMed

    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

  2. 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.

  3. The occurrence of endocrine disrupting compounds in off-shore sediments from the southern Baltic Sea.

    PubMed

    Ruczyńska, Wiesława; Szlinder-Richert, Joanna; Drgas, Aleksander

    2016-09-14

    This paper presents the study on the occurrence and spatial distribution of polybrominated diphenyl ethers (PBDEs), butyltin compounds (BTCs), bisphenol A (BPA), and alkylphenols (APs) in sediments. The study focused mainly on off-shore surface sediments collected from the southern Baltic Sea. The pollutant concentrations were as follows: compounds was highly related to the organic matter content in the sediments. Only BDE-209 concentrations were the highest in sandy sediments collected near the point source of pollution. This suggests the fresh anthropogenic input of BDE-209 into the marine environment. The principal component analysis (PCA) confirms these observations-the distribution of ∑BTCs, NPs, and ∑9PBDEs was mainly determined by the physicochemical properties of the sediments, while the distribution of BDE-209 was also related to other factors, such as proximity to the pollution source. According to the environmental standards applied in this work, NPs, and to a lesser extent TBT, might pose a risk to aquatic life in the present study area as they occur in some sediments in concentrations higher than those that might cause adverse effects on biota. PMID:27461960

  4. The occurrence of endocrine disrupting compounds in off-shore sediments from the southern Baltic Sea.

    PubMed

    Ruczyńska, Wiesława; Szlinder-Richert, Joanna; Drgas, Aleksander

    2016-09-14

    This paper presents the study on the occurrence and spatial distribution of polybrominated diphenyl ethers (PBDEs), butyltin compounds (BTCs), bisphenol A (BPA), and alkylphenols (APs) in sediments. The study focused mainly on off-shore surface sediments collected from the southern Baltic Sea. The pollutant concentrations were as follows: compounds was highly related to the organic matter content in the sediments. Only BDE-209 concentrations were the highest in sandy sediments collected near the point source of pollution. This suggests the fresh anthropogenic input of BDE-209 into the marine environment. The principal component analysis (PCA) confirms these observations-the distribution of ∑BTCs, NPs, and ∑9PBDEs was mainly determined by the physicochemical properties of the sediments, while the distribution of BDE-209 was also related to other factors, such as proximity to the pollution source. According to the environmental standards applied in this work, NPs, and to a lesser extent TBT, might pose a risk to aquatic life in the present study area as they occur in some sediments in concentrations higher than those that might cause adverse effects on biota.

  5. Refinement of the ECETOC approach to identify endocrine disrupting properties of chemicals in ecotoxicology.

    PubMed

    Weltje, Lennart; Wheeler, James R; Weyers, Arnd; Galay-Burgos, Malyka

    2013-12-16

    To use and implement an assessment scheme for the evaluation of endocrine disrupting properties of chemicals in ecotoxicology, the types of effect need to be agreed. Effects that merit further consideration in this context should fulfil the following three criteria: caused by an endocrine mode of action, be adverse, and be relevant at the population level to reflect the protection goal of ecotoxicological assessments. Thereafter, a comparison of effect values, regardless of the causative mechanisms, should be made, firstly to determine if endocrine toxicity generates the lowest endpoint within a taxon, and secondly if it is the lowest endpoint compared to that of other taxa living in the same compartment. These comparisons inform on two levels of specificity and determine if endocrine-mediated side-effects determine the ecotoxicological profile of a chemical. Various quantitative measures for the assessment of potency are also presented, which could assist in determining how to handle substances in the risk assessment when a regulatory concern is identified. Finally, derogation criteria should be defined for compounds that were designed as endocrine disruptors for non-vertebrates and those for which there is 'negligible exposure'. This paper discusses and provides proposals on how to apply these concepts for assessment of substances.

  6. Synthesis of surface plasmon resonance (SPR) triggered Ag/TiO2 photocatalyst for degradation of endocrine disturbing compounds

    NASA Astrophysics Data System (ADS)

    Leong, Kah Hon; Gan, Bee Ling; Ibrahim, Shaliza; Saravanan, Pichiah

    2014-11-01

    Surface deposition of silver nanoparticles (Ag NPs) onto the 100% anatase titania (Ag/TiO2) for evolution of surface plasmon resonance (SPR) was achieved sustainably with the assistance of solar energy. The preparation resulted in Ag/TiO2 photocatalyst with varied Ag depositions (0.5 wt%, 1.0 wt%, 3.0 wt% and 5.0 wt%). All obtained photocatalysts were characterized for the evolution of SPR via crystalline phase analysis, morphology, lattice fringes, surface area and pore size characteristics, chemical composition with chemical and electronic state, Raman scattering, optical and photoluminescence properties. The deposition of synthesized Ag NPs exhibited high uniformity and homogeneity and laid pathway for effective utilization of the visible region of electromagnetic spectrum through SPR. The depositions also lead for suppressing recombination rates of electron-hole. The photocatalytic evaluation was carried out by adopting two different class of endocrine disturbing compound (EDC) i.e., amoxicillin (pharmaceutical) and 2,4-dichlorophenol (pesticide) excited with artificial visible light source. Ag/TiO2 with Ag > 0.5 wt% exhibited significant degradation efficiency for both amoxicillin and 2,4-dichlorophenol. Thus synthesized Ag/TiO2 revealed the implication of plasmonics on TiO2 for the enhanced visible light photocatalytic activity.

  7. 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.

  8. 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.

  9. Anthropogenic pressure in a Portuguese river: Endocrine-disrupting compounds, trace elements and nutrients.

    PubMed

    Ribeiro, Cláudia M R; Maia, Alexandra S; Ribeiro, Ana R; Couto, Cristina; Almeida, Agostinho A; Santos, Mariana; Tiritan, Maria E

    2016-10-14

    Natural organic compounds such as phytoestrogens and phytosterols found in various plants, as well as mycotoxins produced by fungi, can be found in aquatic environments. The aim of this study was to investigate the occurrence of three different classes of natural estrogenic compounds, i.e., phytoestrogens, phytosterols and mycotoxins, in estuarine water samples from the Ave River estuary. For that, water samples were collected at five sampling points distributed along the estuary at low tide, during 1 year, processed by solid-phase extraction (SPE) and analyzed by gas chromatography coupled to mass spectrometry (GC-MS). To correlate the presence of phytoestrogens and phytosterols in the estuarine water, local flora was collected on riverside. Trace elements content and physicochemical parameters such as nutrients and dissolved oxygen were also determined seasonally at each sampling point, to give insights for the evaluation of water quality and anthropogenic pressure. Both phytoestrogens and phytosterols showed a seasonal variation, with the highest values observed in spring and summer and the lowest in winter. Daidzein (DAID) was found up to 404.0 ng L(-1) in spring and coumestrol (COUM) was found up to 165.0 ng L(-1) in summer. The mycotoxin deoxynivalenol (DON) was ubiquitously determined with values ranging from 59.5 to 642.4 ng L(-1). Nutrients and metals distribution and concentration varied among sampling stations and seasons. This study revealed for the first time the presence of mycotoxins, various classes of phytoestrogens and stigmasterol (STG) in estuarine water from the Ave River (Portugal), and the evaluation of the water quality confirmed that this estuary is still highly impacted by anthropogenic activities.

  10. Anthropogenic pressure in a Portuguese river: Endocrine-disrupting compounds, trace elements and nutrients.

    PubMed

    Ribeiro, Cláudia M R; Maia, Alexandra S; Ribeiro, Ana R; Couto, Cristina; Almeida, Agostinho A; Santos, Mariana; Tiritan, Maria E

    2016-10-14

    Natural organic compounds such as phytoestrogens and phytosterols found in various plants, as well as mycotoxins produced by fungi, can be found in aquatic environments. The aim of this study was to investigate the occurrence of three different classes of natural estrogenic compounds, i.e., phytoestrogens, phytosterols and mycotoxins, in estuarine water samples from the Ave River estuary. For that, water samples were collected at five sampling points distributed along the estuary at low tide, during 1 year, processed by solid-phase extraction (SPE) and analyzed by gas chromatography coupled to mass spectrometry (GC-MS). To correlate the presence of phytoestrogens and phytosterols in the estuarine water, local flora was collected on riverside. Trace elements content and physicochemical parameters such as nutrients and dissolved oxygen were also determined seasonally at each sampling point, to give insights for the evaluation of water quality and anthropogenic pressure. Both phytoestrogens and phytosterols showed a seasonal variation, with the highest values observed in spring and summer and the lowest in winter. Daidzein (DAID) was found up to 404.0 ng L(-1) in spring and coumestrol (COUM) was found up to 165.0 ng L(-1) in summer. The mycotoxin deoxynivalenol (DON) was ubiquitously determined with values ranging from 59.5 to 642.4 ng L(-1). Nutrients and metals distribution and concentration varied among sampling stations and seasons. This study revealed for the first time the presence of mycotoxins, various classes of phytoestrogens and stigmasterol (STG) in estuarine water from the Ave River (Portugal), and the evaluation of the water quality confirmed that this estuary is still highly impacted by anthropogenic activities. PMID:27411033

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept.

    PubMed

    Ashton, Kate S; Andrews, Kristin L; Bryan, Marian C; Bryan, Marion C; Chen, Jie; Chen, Kui; Chen, Michelle; Chmait, Samer; Croghan, Michael; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Jordan, Steve R; Kurzeja, Robert J M; Michelsen, Klaus; Pennington, Lewis D; Poon, Steve F; Sivits, Glenn; Van, Gwyneth; Vonderfecht, Steve L; Wahl, Robert C; Zhang, Jiandong; Lloyd, David J; Hale, Clarence; St Jean, David J

    2014-01-23

    Small molecule activators of glucokinase have shown robust efficacy in both preclinical models and humans. However, overactivation of glucokinase (GK) can cause excessive glucose turnover, leading to hypoglycemia. To circumvent this adverse side effect, we chose to modulate GK activity by targeting the endogenous inhibitor of GK, glucokinase regulatory protein (GKRP). Disrupting the GK-GKRP complex results in an increase in the amount of unbound cytosolic GK without altering the inherent kinetics of the enzyme. Herein we report the identification of compounds that efficiently disrupt the GK-GKRP interaction via a previously unknown binding pocket. Using a structure-based approach, the potency of the initial hit was improved to provide 25 (AMG-1694). When dosed in ZDF rats, 25 showed both a robust pharmacodynamic effect as well as a statistically significant reduction in glucose. Additionally, hypoglycemia was not observed in either the hyperglycemic or normal rats.

  16. Endocrine glands

    MedlinePlus

    Endocrine glands release (secrete) hormones into the bloodstream. The endocrine glands include: Adrenal Hypothalamus Islets of Langerhans in the pancreas Ovaries Parathyroid Pineal Pituitary Testes Thyroid

  17. Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits.

    PubMed

    Dudgeon, Drew D; Shinde, Sunita; Hua, Yun; Shun, Tong Ying; Lazo, John S; Strock, Christopher J; Giuliano, Kenneth A; Taylor, D Lansing; Johnston, Patricia A; Johnston, Paul A

    2010-08-01

    In recent years, advances in structure-based drug design and the development of an impressive variety of high-throughput screening (HTS) assay formats have yielded an expanding list of protein-protein interaction inhibitors. Despite these advances, protein-protein interaction targets are still widely considered difficult to disrupt with small molecules. The authors present here the results from screening 220,017 compounds from the National Institute of Health's small-molecule library in a novel p53-hDM2 protein-protein interaction biosensor (PPIB) assay. The p53-hDM2 positional biosensor performed robustly and reproducibly throughout the high-content screening (HCS) campaign, and analysis of the multiparameter data from images of the 3 fluorescent channels enabled the authors to identify and eliminate compounds that were cytotoxic or fluorescent artifacts. The HCS campaign yielded 3 structurally related methylbenzo-naphthyridin-5-amine (MBNA) hits with IC(50)s between 30 and 50 microM in the p53-hDM2 PPIB. In HCT116 cells with wild-type (WT) p53, the MBNAs enhanced p53 protein levels, increased the expression of p53 target genes, caused a cell cycle arrest in G1, induced apoptosis, and inhibited cell proliferation with an IC(50) ~4 microM. The prototype disruptor of p53-hDM2 interactions Nutlin-3 was more potent than the MBNAs in the p53-hDM2 PPIB assay but produced equivalent biological results in HCT116 cells WT for p53. Unlike Nutlin-3, however, MBNAs also increased the percentage of apoptosis in p53 null cells and exhibited similar potencies for growth inhibition in isogenic cell lines null for p53 or p21. Neither the MBNAs nor Nutin-3 caused cell cycle arrest in p53 null HCT116 cells. Despite the relatively modest size of the screening library, the combination of a novel p53-hDM2 PPIB assay together with an automated imaging HCS platform and image analysis methods enabled the discovery of a novel chemotype series that disrupts p53-hDM2 interactions in cells.

  18. 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...

  19. Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism.

    PubMed

    Norrgran, Jessica; Jones, Bernt; Lindquist, Nils-Gunnar; Bergman, Ake

    2012-07-01

    The incidence of cats being diagnosed with feline hyperthyroidism (FH) has increased greatly since it was first described in 1979. The cause of FH has not been established. Hypothetically, there is a link between increasing FH and exposure to brominated flame retardants. Much greater polybrominated diphenyl ethers (PBDE) concentrations have been reported in cat serum compared with human serum, likely due to cat licking behaviour. This study aimed to extend the present identification of brominated compounds in cat serum, with a focus on hydroxylated metabolites of PBDE, to improve the understanding of feline metabolism of PBDEs. A pooled serum sample from 30 Swedish pet cats with FH was analysed, and brominated species were identified. The results showed exposure to the discontinued flame retardant decabromobiphenyl (BB-209) and technical penta- and octa-BDEs. Altogether 12 PBDE congeners were identified along with 2'-MeO-BDE68. Furthermore, 2,4-dibromophenol, 2,4,6-, 2,4,5- and 2,3,4-tribromophenol plus 2'-OH-BDE68, 6-OH-BDE47, 5-OH-BDE47, 4'-OH-BDE49 were identified. 2,4,6-tribromophenol and 6-OH-BDE47 were the most prominent species in cat serum. Considering that these are natural products, it can be concluded that metabolism of PBDEs to OH-PBDEs is not a major route of PBDE elimination in cats. It is notable that BB-209, 6-OH-BDE47, and 2,4,6-tribromophenol all suggested that endocrine-disrupting chemicals were present in high concentrations in cat serum.

  20. 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.

  1. Biological regulation of receptor-hormone complex concentrations in relation to dose-response assessments for endocrine-active compounds.

    PubMed

    Andersen, M E; Barton, H A

    1999-03-01

    Some endocrine-active compounds (EACs) act as agonists or antagonists of specific hormones and may interfere with cellular control processes that regulate gene transcription. Many mechanisms controlling gene expression are universal to organisms ranging from unicellular bacteria to more complex plants and animals. One mechanism, coordinated control of batteries of gene products, is critical in adaptation of bacteria to new environments and for development and tissue differentiation in multi-cellular organisms. To coordinately activate sets of genes, all living organisms have devised molecular modules to permit transitions, or switching, between different functional states over a small range of hormone concentration, and other modules to stabilize the new state through homeostatic interactions. Both switching and homeostasis are regulated by controlling concentrations of hormone-receptor complexes. Molecular control processes for switching and homeostasis are inherently nonlinear and often utilize autoregulatory feedback loops. Among the biological processes contributing to switching phenomena are receptor autoinduction, induction of enzymes for ligand synthesis, mRNA stabilization/activation, and receptor polymerization. This paper discusses a variety of molecular switches found in animal species, devises simple quantitative models illustrating roles of specific molecular interactions in creating switching modules, and outlines the impact of these switching processes and other feedback loops for risk assessments with EACs. Quantitative simulation modeling of these switching mechanisms made it apparent that highly nonlinear dose-response curves for hormones and EACs readily arise from interactions of several linear processes acting in concert on a common control point. These nonlinear mechanisms involve amplification of response, rather than multimeric molecular interactions as in conventional Hill relationships. PMID:10330682

  2. 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

  3. 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...

  4. 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...

  5. 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...

  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. 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...

  8. 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

    2016-04-01

    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

  9. 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

  10. 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. PMID:25613412

  11. 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. PMID

  12. 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.

  13. 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...

  14. 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. PMID:22739065

  15. 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...

  16. Endocrine-Disrupting Chemicals and Reproductive Health.

    PubMed

    Zlatnik, Marya G

    2016-07-01

    This review discusses the evidence linking industrial chemicals to a variety of health and reproductive outcomes. Industrial chemical production has increased over the past 30 to 40 years. Basic science, animal models, and epidemiologic data suggest that certain chemicals may act as endocrine disruptors (substances that interfere with normal hormonal action) and may play an etiologic role in a number of conditions whose incidence has also increased during this same period. These include low birth weight, gestational diabetes, obesity, certain cancers, certain birth defects, and neurodevelopmental disorders such as attention deficit disorder and autism. In addition, some environmental chemicals may have epigenetic effects, resulting in transgenerational health impacts. The epidemiologic and experimental evidence that links chemicals such as plasticizers (eg, phthalates and phenols), flame retardants, perfluorinated compounds, and pesticides with adverse reproductive health outcomes is reviewed. Women's health care providers are the liaison between scientific research and their patients; they should educate themselves on the significance of environmental toxins to health. They are ideally positioned, not only to counsel and reassure pregnant women, but also to suggest practicable changes in dietary and lifestyle habits to improve their health. Furthermore, women's health care providers should advocate for regulatory changes that protect women and their families from the health effects of environmental toxins. PMID:27391253

  17. Endocrine-Disrupting Chemicals and Reproductive Health.

    PubMed

    Zlatnik, Marya G

    2016-07-01

    This review discusses the evidence linking industrial chemicals to a variety of health and reproductive outcomes. Industrial chemical production has increased over the past 30 to 40 years. Basic science, animal models, and epidemiologic data suggest that certain chemicals may act as endocrine disruptors (substances that interfere with normal hormonal action) and may play an etiologic role in a number of conditions whose incidence has also increased during this same period. These include low birth weight, gestational diabetes, obesity, certain cancers, certain birth defects, and neurodevelopmental disorders such as attention deficit disorder and autism. In addition, some environmental chemicals may have epigenetic effects, resulting in transgenerational health impacts. The epidemiologic and experimental evidence that links chemicals such as plasticizers (eg, phthalates and phenols), flame retardants, perfluorinated compounds, and pesticides with adverse reproductive health outcomes is reviewed. Women's health care providers are the liaison between scientific research and their patients; they should educate themselves on the significance of environmental toxins to health. They are ideally positioned, not only to counsel and reassure pregnant women, but also to suggest practicable changes in dietary and lifestyle habits to improve their health. Furthermore, women's health care providers should advocate for regulatory changes that protect women and their families from the health effects of environmental toxins.

  18. Development of a fast liquid chromatography-tandem mass spectrometry method for the determination of endocrine-disrupting compounds in waters.

    PubMed

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

    2010-09-01

    A fast liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method was developed to study five endocrine-disrupting compounds (4-n-nonylphenol, bisphenol A, estrone, 17β-estradiol and 17α-ethinylestradiol) in water. Different columns were tested; the chromatographic separation of the analytes was optimized on a Pinnacle DB biphenylic column with a water-acetonitrile gradient elution, which allowed the separation of the selected endocrine-disrupting compounds (EDCs) in less than 6 min. Quantitative analysis was performed in selected reaction monitoring (SRM) mode; two transitions were chosen for each compound, using the most abundant for quantitation. Calibration curves using bisphenol A-d (16) as internal standard were drawn, showing good correlation coefficients (0.9993-0.9998). All figures of merit of the method were satisfactory; limits of detection were in the low pg range for all analytes. The method was then applied to the determination of the analytes in real water samples: to this aim, polar organic chemical integrative samplers (POCIS) were deployed in the influent and in the effluent of a drinking water treatment plant in Liguria (Italy). The EDC level was rather low in the influent and negligible in the outlet, reflecting the expected function of the treatment plant.

  19. 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

  20. 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

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

    PubMed

    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.

  2. Evaluation of the presence of endocrine-disrupting compounds in dissolved and solid wastewater treatment plant samples of Gran Canaria Island (Spain).

    PubMed

    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

  3. Endocrine glands

    MedlinePlus

    The endocrine system is primarily composed of glands that produce chemical messengers called hormones. Glands of the endocrine system include the pituitary gland, the thyroid gland, the parathyroid glands, the thymus, ...

  4. 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

  5. Combining passive samplers and biomonitors to evaluate endocrine disrupting compounds in a wastewater treatment plant by LC/MS/MS and bioassay analyses.

    PubMed

    Liscio, C; Magi, E; Di Carro, M; Suter, M J-F; Vermeirssen, E L M

    2009-10-01

    Two types of integrative sampling approaches (passive samplers and biomonitors) were tested for their sampling characteristics of selected endocrine disrupting compounds (EDCs). Chemical analyses (LC/MS/MS) were used to determine the amounts of five EDCs (nonylphenol, bisphenol A, estrone, 17beta-estradiol and 17alpha-ethinylestradiol) in polar organic chemical integrative samplers (POCIS) and freshwater mussels (Unio pictorum); both had been deployed in the influent and effluent of a municipal wastewater treatment plant (WWTP) in Genoa, Italy. Estrogenicity of the POCIS samples was assessed using the yeast estrogen screen (YES). Estradiol equivalent values derived from the bioassay showed a positive correlation with estradiol equivalents calculated from chemical analyses data. As expected, the amount of estrogens and EEQ values in the effluent were lower than those in the influent. Passive sampling proved to be the preferred method for assessing the presence of these compounds since employing mussels had several disadvantages both in sampling efficiency and sample analyses.

  6. Combined effects of dietary phytoestrogen and synthetic endocrine-active compound on reproductive development in Sprague-Dawley rats: genistein and methoxychlor.

    PubMed

    You, Li; Casanova, Mercedes; Bartolucci, Erika J; Fryczynski, Mary W; Dorman, David C; Everitt, Jeffrey I; Gaido, Kevin W; Ross, Susan M; Heck Hd, Henry d'A

    2002-03-01

    Humans and wildlife are frequently exposed to mixtures of endocrine active-compounds (EAC). The objective of the present study was to investigate the potential of the phytoestrogen genistein to influence the reproductive developmental toxicity of the endocrine-active pesticide methoxychlor. Three levels of genistein (0, 300, or 800 ppm) and two levels of methoxychlor (0 or 800 ppm) were used in this study. Sprague-Dawley rats were exposed to the two compounds, either alone or in combinations, through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning. Both compounds, methoxychlor in particular, were associated with reduced body growth at 800 ppm, but pregnancy outcome was not affected by either treatment. An acceleration of vaginal opening (VO) in the exposed female offspring was the only observed effect of genistein at 300 ppm. Exposure to 800 ppm genistein or 800 ppm methoxychlor caused accelerated VO and also altered estrous cyclicity toward persistent estrus in the female offspring. The estrogenic responses to genistein and methoxychlor administered together were apparently accumulative of the effects associated with each compound alone. Methoxychlor, but not genistein, delayed preputial separation (PPS) in the male rats. When administered with methoxychlor, genistein at 800 ppm enhanced the effect of methoxychlor on delaying PPS. Genistein and methoxychlor treatment did not change gender-specific motor activity patterns in either sex. To explore possible mechanisms for interaction between the two compounds on development, we performed estrogen receptor (ER)- and androgen receptor (AR)-based in vitro transcriptional activation assays using genistein and the primary methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). While the in vitro assays supported the estrogenic effects of genistein and methoxychlor and the antiandrogenic effects of methoxychlor, the reactivity of these

  7. 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.