Science.gov

Sample records for environmental estrogenic compounds

  1. Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples.

    PubMed

    Vanparys, Caroline; Depiereux, Sophie; Nadzialek, Stéphanie; Robbens, Johan; Blust, Ronny; Kestemont, Patrick; De Coen, Wim

    2010-09-15

    In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC(50) value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R(2)=0.98), the estrogen receptor (ER) binding (R(2)=0.84) and the ER transcription activation assay (R(2)=0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of

  2. Assessing the energy and environmental performance of algae-mediated tertiary treatment of estrogenic compounds.

    PubMed

    Colosi, Lisa M; Resurreccion, Eleazer P; Zhang, Yongli

    2015-02-01

    This study uses a systems-level modeling approach to illustrate a novel synergy between municipal wastewater treatment and large-scale algaculture for production of bio-energy, whereby algae-mediated tertiary treatment provides efficient removal of unregulated, strongly estrogenic steroid hormones from the secondary effluent. Laboratory results from previously published studies suggested that algae-mediated treatment could deliver roughly 75-85% removal of a model estrogen (17β-estradiol) within typical algae pond residence times. As such, experimental results are integrated into a comprehensive life cycle assessment (LCA) framework, to assess the environmental performance of an algae-based tertiary treatment system relative to three conventional tertiary treatments: ozonation, UV irradiation, and adsorption onto granular activated carbon. Results indicate that the algae-mediated tertiary treatment is superior to the selected benchmarks on the basis of raw energy return on investment (EROI) and normalized energy use per mass of estrogenic toxicity removed. It is the only tertiary treatment system that creates more energy than it consumes, and it delivers acceptable effluent quality for nutrient and coliform concentrations while rendering a significant reduction in estrogenic toxicity. These results highlight the dual water and energy sustainability benefits that accrue from the integration of municipal wastewater treatment and large-scale algae farming.

  3. The role of environmental estrogens and autoimmunity.

    PubMed

    Chighizola, Cecilia; Meroni, Pier Luigi

    2012-05-01

    The prevalence of autoimmune diseases has significantly increased over the recent years. It has been proposed that this epidemiological evidence could be in part attributable to environmental estrogens, compounds that display estrogen-like activity and are ubiquitously present in the environment. Environmental estrogens can be found in a wide variety of foods: phytoestrogens occur in plants such as clover and soy, while mycoestrogens are food contaminants produced by fungi. Meat, eggs and dairy products from animals given exogenous hormones contain relatively high concentration of estrogens. Among xenoestrogens, industrial estrogens are synthetic chemicals produced for specific purposes (pesticides, plastics, surfactants and detergents) while metalloestrogens are found in heavy metals. Estrogens can be also administered through medications (contraceptive pill, hormone replacement therapy, genistein, cimetidine, creams). There is a considerable burden of evidence in vitro and in animal models that these compounds may exert immunotoxic effects. However, to date there is no convincing data that exposure to environmental estrogens can be regarded as a risk for human health. In particular, there is no consensus whether prolonged exposure to relatively low concentrations of different estrogenic chemicals can affect the human immune system and induce clinically evident diseases in real-life scenario. Moreover, the effects on human health of the synergistic interactions between natural, medical, dietary and environmental estrogens have not been fully elucidated yet. Here we provide an extensive review of the in vivo and in vitro effects of environmental estrogens on the immune system, focusing on the evidences of association between exposure and autoimmune disorders.

  4. Synergistic activation of estrogen receptor with combinations of environmental chemicals

    SciTech Connect

    Arnold, S.F.; Klotz, D.M.; Collins, B.M.

    1996-06-07

    Certain chemicals in the environment are estrogenic. The low potencies of the compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen potencies of combination of such chemicals were screened in a simple yeast estrogen systems (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 100 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses. 32 refs., 3 figs., 3 tabs.

  5. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc)

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  6. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  7. Quantum chemical studies of estrogenic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantum chemical methods are potent tools to provide information on the chemical structure and electronic properties of organic molecules. Modern computational chemistry methods have provided a great deal of insight into the binding of estrogenic compounds to estrogenic receptors (ER), an important ...

  8. Characterizing the Estrogenic Potential of 1060 Environmental ...

    EPA Pesticide Factsheets

    In order to detect environmental chemicals that pose a risk of endocrine disruption, high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals are needed. Alteration of estrogen signaling has been implicated in a variety of adverse health effects including cancer promotion, reproductive deficits, and vascular effects. Here we investigate the estrogenic potential of 1060 chemicals of environmental relevance using a real-time measure of growth kinetics by electrode impedance in the estrogen-responsive human ductal carcinoma, T47D cell line. Cells were treated in concentration response and measurements of cellular impedance were recorded every hour for six days. Progestens, androgens, and mineralocortocoids (progesterone, dihydrotestosterone, aldosterone) invoked a biphasic impedance signature that contrasted with the anticipated exponential impedance observed in response to known estrogen receptor agonists (17β-estradiol, genestein, bisphenol-A, nonylphenol, 4-tert-octylphenol). Several compounds, including bisphenol-A, and genestein caused impedance comparable to that of 17β-estradiol, although at much higher concentrations. Additionally, trenbolone and cyproterone acetate invoked the characteristic biphasic signature observed with other endogenous steroid hormones. The continuous real-time nature of this assay allows for the rapid detection of differential growth characteristics not easily detected by traditional cell prol

  9. Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.

    PubMed

    Pinto, Caroline L; Mansouri, Kamel; Judson, Richard; Browne, Patience

    2016-09-19

    The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites. We used commercially available software to predict metabolites of 50 parent compounds, out of which 38 chemicals are known to have estrogenic metabolites, and 12 compounds and their metabolites are negative for estrogenic activity. Three ER QSAR models were used to determine potential estrogen bioactivity of the parent compounds and predicted metabolites, the outputs of the models were averaged, and the chemicals were then ranked based on the total estrogenicity of the parent chemical and metabolites. The metabolite prediction software correctly identified known estrogenic metabolites for 26 out of 27 parent chemicals with associated metabolite data, and 39 out of 46 estrogenic metabolites were predicted as potential biotransformation products derived from the parent chemical. The QSAR models estimated stronger estrogenic activity for the majority of the known estrogenic metabolites compared to their parent chemicals. Finally, the three models identified a similar set of parent compounds as top ranked chemicals based on the estrogenicity of putative metabolites. This proposed in silico approach is an inexpensive and rapid strategy for the detection of chemicals with estrogenic metabolites and may reduce potential false negative results from in vitro assays.

  10. Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

    SciTech Connect

    Shyu, Conrad; Cavileer, Timothy D.; Nagler, James J.; Ytreberg, F. Marty

    2011-02-01

    Environmental estrogens have been the subject of intense research due to their documented detrimental effects on the health of fish and wildlife and their potential to negatively impact humans. A complete understanding of how these compounds affect health is complicated because environmental estrogens are a structurally heterogeneous group of compounds. In this work, computational molecular dynamics simulations were utilized to predict the binding affinity of different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors (ERs) as a model. Specifically, this study presents a comparison of the binding affinity of the natural ligand estradiol-17{beta} to the four rainbow trout ER isoforms with that of three known environmental estrogens 17{alpha}-ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine and testosterone, that are known to be very weak or non-binders to ERs were tested. The binding affinity of these compounds to the human ER{alpha} subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17{beta}, bisphenol A binds less strongly to all four receptors, 17{alpha}-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the {alpha} subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of the results are in excellent qualitative agreement with the known in vivo estrogenicity of these compounds in the rainbow trout and other fishes. Computational estimation of binding affinities could be a valuable tool for predicting the impact of environmental estrogens in fish and other animals.

  11. Functional associations between two estrogen receptors, environmental estrogens, and sexual disruption in the roach (Rutilus rutilus).

    PubMed

    Katsu, Yoshinao; Lange, Anke; Urushitani, Hiroshi; Ichikawa, Rie; Paull, Gregory C; Cahill, Laura L; Jobling, Susan; Tyler, Charles R; Iguchi, Taisen

    2007-05-01

    Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with estrogenic effluents from wastewater treatment works show feminized responses and have a reduced reproductive capability, but the chemical causation of sexual disruption in the roach has not been established. Feminized responses were induced in male roach exposed to environmentally relevant concentrations of the pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during early life (from fertilization to 84 days posthatch, dph), and these effects were signaled by altered patterns of expression of two cloned roach estrogen receptor (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver. Transactivation assays were developed for both roach ER subtypes and the estrogenic potencies of steroidal estrogens differed markedly at the different ER subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most prevalent environmental steroid in wastewater discharges) was equipotent with estradiol (E2) in activating the ERs. Comparison of the EC50 values for the compounds tested showed that ERbeta was 3-21-fold more sensitive to natural steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha. These findings add substantial support to the hypothesis that steroidal estrogens play a significant role in the induction of intersex in roach populations in U.K. rivers and that the molecular approach described could be usefully applied to understand interspecies sensitivity to xenoestrogens.

  12. Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors

    SciTech Connect

    Pinto, Caroline; Grimaldi, Marina; Boulahtouf, Abdelhay; Pakdel, Farzad; Brion, François; Aït-Aïssa, Sélim; Cavaillès, Vincent; Bourguet, William; Gustafsson, Jan-Ake; and others

    2014-10-01

    Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared to 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology. - Highlights: • Zebrafish is increasingly used to study the effects of estrogens. • We assessed the activity of pharmaceutical and environmental estrogens on zfERs. • Environmental estrogens displayed greater potency for zfERα compared to zfERβs. • hERβ selective agonists displayed greater potency for zf

  13. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

    Robert J. Kavlock, Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.

    Over the past several decades a hypothesis has been put forth that a numb...

  14. PCBs as environmental estrogens: Turtle sex determination as a biomarker of environmental contamination

    SciTech Connect

    Bergeron, J.M.; Crews, D. ); McLachlan, J.A. )

    1994-09-01

    Polychlorinated biphenyls (PCBs) are widespread, low-level environmental pollutants associated with adverse health effects such as immune suppression and teratogenicity. There is increasing evidence that some PCB compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans, particularly during development. Research on the mechanism through which these compounds act to alter reproductive function indicates estrogenic activity, whereby the compounds may be altering sexual differentiation. Here we demonstrate the estrogenic effect of some PCBs by reversing gonadal sex in a reptile species that exhibits temperature-dependent sex determination. 17 refs., 1 fig., 1 tab.

  15. Effects of Estrogens and Estrogenic Disrupting Compounds on Fish Mineralized Tissues

    PubMed Central

    Pinto, Patricia I. S.; Estêvão, Maria D.; Power, Deborah M.

    2014-01-01

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities. PMID:25196834

  16. Effects of estrogens and estrogenic disrupting compounds on fish mineralized tissues.

    PubMed

    Pinto, Patricia I S; Estêvão, Maria D; Power, Deborah M

    2014-08-15

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities.

  17. Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.

    PubMed

    Pinto, Caroline; Grimaldi, Marina; Boulahtouf, Abdelhay; Pakdel, Farzad; Brion, François; Aït-Aïssa, Sélim; Cavaillès, Vincent; Bourguet, William; Gustafsson, Jan-Ake; Bondesson, Maria; Balaguer, Patrick

    2014-10-01

    Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.

  18. MODELING THE EFFECTS OF FLEXIBILITY ON THE BINDING OF ENVIRONMENTAL ESTROGENS TO THE ESTROGEN RECEPTOR

    EPA Science Inventory

    Modeling the effects of flexibility on the binding of environmental estrogens to the estrogen receptor
    There are many reports of environmental endocrine disruption in the literature, yet it has been difficult to identify the specific chemicals responsible for these effects. ...

  19. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    SciTech Connect

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck . E-mail: khchung@skku.edu

    2006-08-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect.

  20. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds.

    PubMed

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2006-08-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect.

  1. Immunomodulation of Mytilus hemocytes by individual estrogenic chemicals and environmentally relevant mixtures of estrogens: in vitro and in vivo studies.

    PubMed

    Canesi, Laura; Lorusso, Lucia Cecilia; Ciacci, Caterina; Betti, Michele; Rocchi, Marco; Pojana, Giulio; Marcomini, Antonio

    2007-02-15

    Endocrine disrupting compounds (EDCs) are almost ubiquitous in the aquatic environment. In the marine bivalve Mytilus the natural estrogen 17beta-estradiol (E2) and different EDCs have been recently demonstrated to affect the function of the immune cells, the hemocytes. The effects were Tamoxifen-sensitive and were mediated by rapid modulation of kinase-mediated transduction pathways. In this work we compared the in vitro effects of individual estrogenic chemicals (E2, EE: 17alpha-ethynyl estradiol; MES: mestranol; NP: nonylphenol; NP1EC: nonylphenol monoethoxylate carboxylate; BPA: bisphenol A; BP: benzophenone) on hemocyte parameters: lysosomal membrane stability (LMS), phagocytosis, lysozyme release. LMS was the most sensitive effect parameter, showing a decreasing trend at increasing concentrations of estrogens. EC50 values obtained from LMS data were utilized to calculate the estradiol equivalency factor (EEF) for each compound; these EEFs allowed for an estimation of the estrogenic potential of a synthetic mixture with a composition very similar to that previously found in waters of the Venice lagoon. Concentrated mixtures significantly affected hemocyte parameters in vitro and the effects were prevented by Tamoxifen. Significant effects of the mixture were also observed in vivo, at longer exposure times and at concentrations comparable with environmental exposure levels. The results indicate that Mytilus immune parameters can be suitably utilized to evaluate the estrogenic potential of environmental samples.

  2. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic.

    PubMed Central

    Jobling, S; Reynolds, T; White, R; Parker, M G; Sumpter, J P

    1995-01-01

    Sewage, a complex mixture of organic and inorganic chemicals, is considered to be a major source of environmental pollution. A random screen of 20 organic man-made chemicals present in liquid effluents revealed that half appeared able to interact with the estradiol receptor. This was demonstrated by their ability to inhibit binding of 17 beta-estradiol to the fish estrogen receptor. Further studies, using mammalian estrogen screens in vitro, revealed that the two phthalate esters butylbenzyl phthalate (BBP) and di-n-butylphthalate (DBP) and a food antioxidant, butylated hydroxyanisole (BHA) were estrogenic; however, they were all less estrogenic than the environmental estrogen octylphenol. Phthalate esters, used in the production of various plastics (including PVC), are among the most common industrial chemicals. Their ubiquity in the environment and tendency to bioconcentrate in animal fat are well known. Neither BBP nor DBP were able to act as antagonists, indicating that, in the presence of endogenous estrogens, their overall effect would be cumulative. Recently, it has been suggested that environmental estrogens may be etiological agents in several human diseases, including disorders of the male reproductive tract and breast and testicular cancers. The current finding that some phthalate compounds and some food additives are weakly estrogenic in vitro, needs to be supported by further studies on their effects in vivo before any conclusions can be made regarding their possible role in the development of these conditions. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:7556011

  3. Biochar as potential adsorptive media for estrogenic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endocrine disrupting chemicals are an emerging problem in water pollution due to their toxic effects on humans and wildlife. Estrogenic compounds are a subset of endocrine disrupting chemicals that are particularly dangerous since they are very potent and can affect fish at concentrations as low as ...

  4. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

    USGS Publications Warehouse

    Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  5. Environmental signaling: from environmental estrogens to endocrine-disrupting chemicals and beyond.

    PubMed

    McLachlan, J A

    2016-07-01

    The landmark report (Herbst et al. 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed that DES was the carcinogen and exposure to DES caused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero. DES was also being used in agriculture and we discovered, at the first meeting on Estrogens in the Environment in 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated how DES and other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At the Wingspread Conference on the Human-Wildlife Connection in 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals

  6. Modulation of estrogenic effects by environmental temperature and food availability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endocrine-disrupting chemicals (EDCs), in combination with environmental influences, interfere with endocrine function in humans and wildlife. Estrogens are a type of EDC that may alter the hypothalamic-pituitary-gonadal axis in male fathead minnows, Pimephales promelas. The impact of estrogens on P...

  7. Modeling environmental loading rates of municipal wastewater contaminants: steroidal estrogens

    EPA Science Inventory

    Estrogenic compounds in municipal wastewater are of substantial interest because of suspicion that they may cause reproductive disruption in aquatic invertebrates, and because of their potential to contaminate human drinking water sources. Previous work suggests the primary contr...

  8. Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples

    PubMed Central

    Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki S.; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to

  9. Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence for cross-linking and redox cycling activities.

    PubMed

    Bennetts, L E; De Iuliis, G N; Nixon, B; Kime, M; Zelski, K; McVicar, C M; Lewis, S E; Aitken, R J

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (beta-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17beta-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  10. 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

  11. Use of Saccharomyces cerevisiae BLYES Expressing Bacterial Bioluminescence for Rapid, Sensitive Detection of Estrogenic Compounds

    PubMed Central

    Sanseverino, John; Gupta, Rakesh K.; Layton, Alice C.; Patterson, Stacey S.; Ripp, Steven A.; Saidak, Leslie; Simpson, Michael L.; Schultz, T. Wayne; Sayler, Gary S.

    2005-01-01

    An estrogen-inducible bacterial lux-based bioluminescent reporter was developed in Saccharomyces cerevisiae for applications in chemical sensing and environmental assessment of estrogen disruptor activity. The strain, designated S. cerevisiae BLYES, was constructed by inserting tandem estrogen response elements between divergent yeast promoters GPD and ADH1 on pUTK401 (formerly pUA12B7) that constitutively express luxA and luxB to create pUTK407. Cotransformation of this plasmid with a second plasmid (pUTK404) containing the genes required for aldehyde synthesis (luxCDE) and FMN reduction (frp) yielded a bioluminescent bioreporter responsive to estrogen-disrupting compounds. For validation purposes, results with strain BLYES were compared to the colorimetric-based estrogenic assay that uses the yeast lacZ reporter strain (YES). Strains BLYES and YES were exposed to 17β-estradiol over the concentration range of 1.2 × 10−8 through 5.6 × 10−12 M. Calculated 50% effective concentration values from the colorimetric and bioluminescence assays (n = 7) were similar at (4.4 ± 1.1) × 10−10 and (2.4 ± 1.0) × 10−10 M, respectively. The lower and upper limits of detection for each assay were also similar and were approximately 4.5 × 10−11 to 2.8 × 10−9 M. Bioluminescence was observed in as little as 1 h and reached its maximum in 6 h. In comparison, the YES assay required a minimum of 3 days for results. Strain BLYES fills the niche for rapid, high-throughput screening of estrogenic compounds and has the ability to be used for remote, near-real-time monitoring of estrogen-disrupting chemicals in the environment. PMID:16085836

  12. Environmental estrogens and reproductive health: a discussion of the human and environmental data.

    PubMed

    Daston, G P; Gooch, J W; Breslin, W J; Shuey, D L; Nikiforov, A I; Fico, T A; Gorsuch, J W

    1997-01-01

    Estrogenic activity of certain xenobiotics is an established mechanism of toxicity that can impair reproductive function in adults of either sex, lead to irreversible abnormalities when administered during development, or cause cancer. The concern has been raised that exposure to ambient levels of estrogenic xenobiotics may be having widespread adverse effects on reproductive health of humans and wildlife. The purpose of this review is to evaluate (a) the nature of the evidence supporting this concern, and (b) the adequacy of toxicity screening to detect, and risk assessment procedures to establish safe levels for, agents acting by this mechanism. Observations such as adverse developmental effects after maternal exposure to therapeutic levels of the potent estrogen diethylstilbestrol or male fertility problems after exposure to high levels of the weak estrogen chlordecone clearly demonstrate that estrogenicity is active as a toxic mechanism in humans. High level exposures to estrogenic compounds have also been shown to affect specific wildlife populations. However, there is little direct evidence to indicate that exposures to ambient levels of estrogenic xenobiotics are affecting reproductive health. Reports of historical trends showing decreasing reproductive capacity (e.g., decreased sperm production over the last 50 years) are either inconsistent with other data or have significant methodologic inadequacies that hinder interpretation. More reliable historical trend data show an increase in breast cancer rate, but the most comprehensive epidemiology study to data failed to show an association between exposure to persistent, estrogenic organochlorine compounds and breast cancer. Clearly, more work needs to be done to characterize historical trends in humans and background incidence of abnormalities in wildlife populations, and to test hypotheses about ambient exposure to environmental contaminants and toxic effects, before conclusions can be reached about the

  13. Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.

    PubMed

    Ruh, M F; Bi, Y; Cox, L; Berk, D; Howlett, A C; Bellone, C J

    1998-10-01

    Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity. 17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner. The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM. Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2

  14. 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...

  15. Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value.

    PubMed

    Punt, Ans; Brand, Walter; Murk, Albertinka J; van Wezel, Annemarie P; Schriks, Merijn; Heringa, Minne B

    2013-02-01

    With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability. In vitro estrogenic potencies of three model compounds (bisphenol A, genistein, and 4-nonylphenol) relative to ethinylestradiol (EE2), determined with the estrogen receptor alpha (ERα) transcriptional activation assay using hER-HeLa-9903 cells, were taken from literature and used to calculate the EE2 equivalent (EE2EQ) effect doses in the predominantly ERα-dependent rat uterotrophic assay. Compound-specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated. The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6-25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1.6-2.1 for especially genistein and bisphenol A. Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance. For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites.

  16. Potencies of estrogenic compounds in in vitro screening assays and in life cycle tests with zebrafish in vivo.

    PubMed

    Segner, H; Navas, J M; Schäfers, C; Wenzel, A

    2003-03-01

    The objective of this study was to compare the estrogenic potency of environmental estrogens at two testing tiers: at the initial level of in vitro screening assays, and at the level of definitive fish reproduction tests in vivo. The in vitro tests included a recombinant yeast estrogen receptor (ER) assay, a competitive radioreceptor assay using the hepatic ER of carp (Cyprinus carpio), and assays on vitellogenin induction in cultured hepatocytes of rainbow trout (Oncorhynchus mykiss) and carp. In vivo, full life cycle tests with zebrafish (Danio rerio) were performed, using fertilization success as estrogen-sensitive reproductive endpoint. The test compounds included the natural estrogen 17beta-estradiol (E2) (only applied in the in vitro assays); the synthetic estrogen ethynylestradiol (EE2); and two xenoestrogens, 4-tert-octylphenol (OP) and bisphenol A (BPA). Among the in vitro assays, differences were observed in the relative ranking of the test substances, and in the absolute sensitivity (EC50 values), although the interassay differences of EC50 values were within one order of magnitude. The in vivo activity of the test compounds was not accurately predicted by the in vitro assays, with respect to neither sensitivity nor ranking. The in vitro assays tended to overestimate the relative potency of the xenoestrogens; i.e. the ratio between the activity of the reference compound, EE2, and that of the test compound. The best prediction of the in vivo fish test results was obtained from the recombinant yeast assay.

  17. Environmental factors affecting ultraviolet photodegradation rates and estrogenicity of estrone and ethinylestradiol in natural waters.

    PubMed

    Atkinson, Susanna K; Marlatt, Vicki L; Kimpe, Lynda E; Lean, David R S; Trudeau, Vance L; Blais, Jules M

    2011-01-01

    The environmental fate and persistence of steroidal estrogens is influenced by their photodegradation. This can potentially occur both in the presence of the ultraviolet (UV) portion of solar radiation and in tertiary wastewater treatment plants that use UV radiation for disinfection purposes. To determine patterns of UV photodegradation for estrone (E1) and 17α-ethinylestradiol (EE2), water samples containing these compounds were exposed to levels of UVB radiation that would simulate exposure to ambient sunlight. E1 degraded with a pseudo-first-order rate law constant that was directly proportional to UVB radiation intensity (R² = 0.999, P < 0.001) and inversely proportional to dissolved organic carbon (DOC) concentration (R² = 0.812, P = 0.037). DOC acted as a competitive inhibitor to direct photolysis of E1 by UV. In contrast to E1, EE2 was more persistent under similar UVB treatment. A reporter gene assay showed that the estrogenicity of UVB-exposed estrogens did not decrease relative to non-UVB-exposed estrogens, suggesting that some of the photoproducts may also have estrogenic potency. These results show that environmental degradation rates of steroidal estrogens are predictable from the UV intensity reaching surface waters, and the DOC concentrations in these surface waters.

  18. [Estrogenic activity of ultraviolet absorbers and the related compounds].

    PubMed

    Matsumoto, Hisashi; Adachi, Shinichi; Suzuki, Yasuhiko

    2005-08-01

    The estrogenic activities of ultraviolet absorbers and their related compounds were investigated using MCF-7 cell proliferation assay. Nine of 33 chemicals (benzophenone, 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 4-hydroxybenzophenone, 3-(4-methylbenzylidene) camphor, ethyl 2-cyano-3,3-diphenylacrylate (etocrylene) and 2-ethylhexyl-2-cyano-3,3-diphenylacrylate (octocrylene)) were positive compared with the vehicle control. Benzhydrol, ethyl cinnamate and 2,2'-dihydroxy-4-methoxybenzophenone were weakly active. When each xenoestrogen was added to the cells along with ICI 182780, an estrogen receptor (ER) antagonist, the cell growth was reduced according to its doses. Therefore, the cell proliferation was suggested to generate through ER. Most of these chemicals were also positive using CHOOSER assay, a new method of testing estrogenic activity of xenoestrogen. Each xenoestrogen was also confirmed to bind to ERalpha and ERbeta using a human ER competitive binding assay against 17beta-estradiol. The concentration order of the strength of its inhibitory effect using both ERalpha and ERbeta was similar to that of MCF-7 cell proliferation assay, except for benzyl 4-hydroxybenzoate (B4HB). B4HB showed a stronger activity on CHOOSER assay and the competitive binding assay using both ERalpha and ERbeta, although there was no activity observed on MCF-7 cell proliferation assay. Our findings were to detect the estrogenic activity of etocrylene and octocrylene in vitro, in addition to confirming the activities of some ultraviolet absorbers as previously reported.

  19. Binding and transactivation of the largemouth bass estrogen receptors by model compounds

    EPA Science Inventory

    Environmental estrogens (EEs) are chemicals in the environment that can elicit adverse effects on estrogen (E2) signaling by binding with the estrogen receptors (ERs). In largemouth bass (LMB), the physiological actions of E2 are primarily mediated via three receptors (ERα, ERßb ...

  20. Analytical strategies based on chromatography-mass spectrometry for the determination of estrogen-mimicking compounds in food.

    PubMed

    Capriotti, Anna Laura; Cavaliere, Chiara; Colapicchioni, Valentina; Piovesana, Susy; Samperi, Roberto; Laganà, Aldo

    2013-10-25

    Food safety can be compromised by the presence of a wide variety of substances, deriving from both natural and anthropogenic sources. Among these substances, compounds exhibiting various degrees of estrogenic activity have been widely studied in environmental samples, whereas less attention has been devoted to food matrices. The aim of the present review is to give a general overview on the recent analytical methods based on gas or liquid chromatography coupled to mass spectrometry for the determination of estrogen-like compounds in foods, including new developments, improvements and upcoming trends in the field. Attention will be focused on four representative groups of compounds, i.e. natural and synthetic estrogens, mycoestrogens, phytoestrogens, and alkylphenols.

  1. Estrogenic & antiestrogenic properties of e-492, a nonsteroidal compound.

    PubMed

    Mehrotra, P K; Karkun, J N

    1975-01-01

    Estrogenic and antiestrogenic properties of E-492, a nonsteroidal compound (3 methyl-4'-(beta-pyrrolidinoethoxy)-2,3-diphenyl propiophenone), were assessed on the basis of ponderal, histologic, and biochemical changes in the uterus, cervix, and vagina of ovariectomized adult rats. This compound was studied at its maximum effective antifertility dose of .5 mg/kg/day for 5 days. Estradiol-dipropionate (EDP) was studied at a dose of 1 mcg/kg/day. EDP and E-492 separately increased the weight of the 3 genital accessories. Histologically, the organs presented an infantile condition characterized by atrophic epithelia, compact stroma, and inconspicious muscularis. The uterine glycogen level was raised by EDP (p less than .01) but not by E-492 (p greater than .05). Lactic acid was increased by EDP in all target organs (p less than .01) and by E-492 in the uterus and vagina (p less than .01) but not in the cervix (p greater than .05). Combined therapy antagonized EDP effect at the uterine and vaginal levels. Alkaline phosphatase was enhanced by EDP in all 3 organs (p less than .01) and by E-492 in the uterus and cervix (p less than .01). These results indicate that on the basis of changes in weight and histology, E-492 has both estrogenic and antiestrogenic potencies.

  2. ENVIRONMENTAL ENRICHMENT REDUCES THE MNEMONIC AND NEURAL BENEFITS OF ESTROGEN

    PubMed Central

    GRESACK, J. E.; FRICK, K. M.

    2006-01-01

    The degree to which memory is enhanced by estrogen replacement in postmenopausal women may depend on environmental factors such as education. The present study utilized an animal model of environmental enrichment to determine whether environmental factors influence the mnemonic and neural response to estrogen. Female mice were raised in standard (SC) or enriched (EC) conditions from weaning until adulthood (7 months). All mice were ovariectomized at 10 weeks, and tested in object recognition and water-escape motivated radial arm maze (WRAM) tasks at 6 months. Each day at the completion of training, mice received injections of 0.1 mg/kg cyclodextrin-encapsulated 17-β-estradiol (E2), 0.2 mg/kg E2, or cyclodextrin vehicle (VEH). At the completion of behavioral testing, hippocampal levels of the presynaptic protein synaptophysin and of brain-derived neurotrophic factor (BDNF) were measured. Enrichment effects were evident in VEH-treated mice; relative to SC-VEH females, EC-VEH females committed fewer working memory errors in the WRAM and exhibited increased hippocampal synaptophysin levels. Estrogen effects depended on environmental conditions. E2 (0.2 mg/kg) improved object memory only in SC females. The same dose improved working memory in SC females, but somewhat impaired working memory in EC females. Furthermore, both doses reduced hippocampal synaptophysin levels in EC, but not SC, females. In contrast, E2 reduced hippocampal BDNF levels in SC, but not EC, females. This study is the first to compare the effects of estrogen on memory and hippocampal function in enriched and non-enriched female mice. The results suggest that: (1) estrogen benefits object and working memory more in mice raised in non-enriched environments than in those raised in enriched environments, and (2) the changes induced by estrogen and/or enrichment may be associated with alterations in hippocampal synaptic plasticity. PMID:15381276

  3. Biomonitoring of estrogenic exposure and identification of responsible compounds in bream from Dutch surface waters.

    PubMed

    Houtman, Corine J; Booij, Petra; van der Valk, Karin M; van Bodegom, Peter M; van den Ende, Frank; Gerritsen, Anton A M; Lamoree, Marja H; Legler, Juliette; Brouwer, Abraham

    2007-05-01

    The exposure to and effects of estrogenic compounds in male breams from Dutch freshwater locations were investigated. Ovotestis was observed infrequently (maximum frequency 16%). However, plasma vitellogenin (VTG) concentration was elevated highly at some locations. Estrogenic activities in male bream plasma, liver, and in gastrointestinal content were measured in the estrogen-responsive chemical-activated luciferase gene expression (ER-CALUX) assay. Plasma concentrations of vitellogenin correlated very well with the estrogenic activities in gastrointestinal content. The ER-CALUX activity in gastrointestinal content thus could provide a biomarker for recent exposure to estrogenic compounds, and the gastrointestinal content was chosen as investigative matrix for the toxicity identification and evaluation ([TIE]; bioassay-directed fractionation) of estrogenic compounds in bream. The approach consisted of a reversed-phase high-performance liquid chromatography fractionation of gastrointestinal content extract, directed by ER-CALUX and followed by gas chromatography analysis. The estrogenic hormones 17beta-estradiol and its metabolite estrone were identified as major contributors to the activity at all locations (except the reference location), independent of the presence or absence of a known source of estrogenic activity, such as a sewage treatment plant. Chemical screening showed the presence of other pollutants, such as a lower chlorinated dioxin and the disinfectants clorophene and triclosan. However, these compounds did not have high estrogenic potencies and their concentrations were not high enough to contribute significantly to the observed estrogenic activity.

  4. In vitro assessment of estrogenic bioactivity in complex environmental effluents**

    EPA Science Inventory

    Environmental effluents contain a diversity of chemicals, can originate from a variety of sources, and have been found to contain estrogenic and/or androgenic activity. In this study, samples were collected from targeted sites or as runoff from an agriculture field that was spray...

  5. In vitro assessment of estrogenic bioactivity in complex environmental effluents

    EPA Science Inventory

    Environmental effluents contain a diversity of chemicals, can originate from a variety of sources, and have been found to contain estrogenic and/or androgenic activity. In this study, samples were collected from targeted sites or as runoff from an agriculture field that was spray...

  6. Zearalenone, an estrogenic mycotoxin, is an immunotoxic compound.

    PubMed

    Hueza, Isis M; Raspantini, Paulo Cesar F; Raspantini, Leonila Ester R; Latorre, Andreia O; Górniak, Silvana L

    2014-03-13

    The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.

  7. Identification of estrogenic compounds in fish bile using bioassay-directed fractionation.

    PubMed

    Houtman, Corine J; Van Oostveen, Annemiek M; Brouwer, Abraham; Lamoree, Marja H; Legler, Juliette

    2004-12-01

    Conjugates of estrogenic chemicals, endogenous as well as xenobiotic, are mainly excreted via bile into the intestine. Therefore, measurement of estrogenic activity in bile yields useful information about an organism's internal exposure to (xeno-)estrogens. Although previous studies in The Netherlands have reported estrogenic activity in male fish bile, the contribution of natural hormones and xenobiotic substances to this activity is unknown. To identify compounds responsible for estrogenic activity in fish bile, we developed a bioassay-directed fractionation method for estrogenic chemicals. In this approach, the in vitro reporter gene assay ER-CALUX (Estrogen Responsive Chemical Activated Luciferase Gene Expression) was used to assess estrogenic activity in deconjugated bile samples and to direct RP-HPLC fractionation and chemical analysis (by GC-MS) of estrogenic compounds. The method was applied to bile from male breams (Abramis brama) collected at three locations in The Netherlands. At one of these locations, the River Dommel, extremely high levels of plasma vitellogenin and a high incidence of intersex gonads in these male breams have previously been observed, indicating the exposure to estrogens. In this study, the natural hormones 17beta-estradiol, estrone, and estriol accounted for the majority of estrogenic activity in male bream bile. At the River Dommel, the synthetic contraceptive pill component ethynylestradiol was found in effective concentrations as well. The detected natural and synthetic hormones may be responsible forthe estrogenic effects observed in wild bream from this location. Furthermore, a large number of xenobiotic chemicals was detected at relatively high levels in bile, including triclosan, chloroxylenol, and clorophene. Although chloroxylenol was shown for the first time to be weakly estrogenic, these compounds did not contribute significantly to the estrogenic activity observed.

  8. Estrogenicity of food-associated estrogenic compounds in the fetuses of female transgenic mice upon oral and IP maternal exposure.

    PubMed

    Ter Veld, Marcel G R; Zawadzka, E; Rietjens, Ivonne M C M; Murk, Albertinka J

    2009-04-01

    The present study investigated to what extent seven food-associated in vitro estrogenic compounds can induce estrogenic effects in the fetuses of pregnant female mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc-induction was determined either 8h after maternal dosing with a single intraperitoneal (IP) dose or 24h after the last of a series of 8 daily oral dosages. Three known estrogens, 17beta-estradiol (E(2)), 17 alpha-ethynylestradiol (EE) and 17beta-estradiol 3,17-dipropionate (EP) were used as positive controls at 1mg/kgbw and DMSO as solvent control. The food-associated estrogenic compounds tested were: bisphenol A (BPA), nonylphenol (NP) both at 50mg/kgbw, dichlorodiphenyldichloroethylene (p,p'-DDE) at 50mg/kgbw, quercetin at 16.6 mg/kgbw, and di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 100mg/kgbw. Exposure to E(2), EE and EP resulted in significant luc inductions upon both oral and/or IP dosing in a variety of tissues including liver, tibia and femurs, and upon IP dosing also in fetuses. BPA, NP, DEHA, DEHP, DIHP, DDE and quercetin were unable to significantly induce luc activity in fetuses. However, after maternal oral exposure during gestation to NP, BPA and DIHP placental luc activity was significantly lowered. The results indicate that at the current levels of exposure to food-associated estrogenic compounds, estrogenic effects to the fetus are not expected. The significant luc reduction in the placenta, should be further studied for its significance for fetal development and relevance for the human situation.

  9. Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent.

    PubMed

    Jobling, S; Casey, D; Rodgers-Gray, T; Oehlmann, J; Schulte-Oehlmann, U; Pawlowski, S; Baunbeck, T; Turner, A P; Tyler, C R

    2003-10-29

    . Plasma vitellogenin concentrations in two species of male fish (the rainbow trout and the carp) also increased over the same time period. These data indicate that both the nature of the response and the relative sensitivities to environmental estrogens in P. antipodarum and three different fish species fish are comparable. P. antipodarum is thus, potentially a sensitive test organism for assessing estrogenicity of chemicals with a relevance to their activity in vertebrates.

  10. Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels

    PubMed Central

    Smiley, Dia A.; Khalil, Raouf A.

    2010-01-01

    The cardiovascular benefits of menopausal hormone therapy (MHT) remain controversial. The earlier clinical observations that cardiovascular disease (CVD) was less common in MHT users compared to non-users suggested cardiovascular benefits of MHT. Also, experimental studies have identified estrogen receptors ERα, ERβ and GPR30, which mediate genomic or non-genomic effects in vascular endothelium, smooth muscle, and extracellular matrix (ECM). However, data from randomized clinical trials (RCTs), most notably the Women's Health Initiative (WHI) study, have challenged the cardiovascular benefits and highlighted adverse cardiovascular events with MHT. The discrepancies have been attributed to the design of RCTs, the subjects' advanced age and preexisting CVD, and the form of estrogen used. The discrepancies may also stem from age-related changes in vascular ER amount, distribution, integrity, and post-receptor signaling pathways as well as structural changes in the vasculature. Age-related changes in other sex hormones such as testosterone may also alter the hormonal environment and influence the cardiovascular effects of estrogen. Investigating the chemical properties, structure-activity relationship and pharmacology of natural and synthetic estrogens should improve the effectiveness of conventional MHT. Further characterization of phytoestrogens, selective estrogen-receptor modulators (SERMs), and specific ER agonists may provide substitutes to conventional MHT. Conditions with excess or low estrogen levels such as polycystic ovary syndrome (PCOS) and Turner syndrome may provide insight into the development and regulation of ER and the mechanisms of aberrant estrogen-ER interactions. The lessons learned from previous RCTs have led to more directed studies such as the Kronos Early Estrogen Prevention Study (KEEPS). Careful design of experimental models and RCTs, coupled with the development of specific ER modulators, hold the promise of improving the actions of

  11. Detection of estrogenic activity in sediment-associated compounds using in vitro reporter gene assays.

    PubMed

    Legler, Juliette; Dennekamp, Martine; Vethaak, A Dick; Brouwer, Abraham; Koeman, Jan H; van der Burg, Bart; Murk, Albertinka J

    2002-07-03

    Sediments may be the ultimate sink for persistent (xeno-)estrogenic compounds released into the aquatic environment. Sediment-associated estrogenic potency was measured with an estrogen receptor-mediated luciferase reporter gene (ER-CALUX) assay and compared with a recombinant yeast screen. The ER-CALUX assay was more sensitive to 17beta-estradiol (E2) than the recombinant yeast screen, with an EC50 of 6 pM E2 compared to 100 pM in the yeast screen. Yeast cells were unable to distinguish the anti-estrogens ICI 182,780 and (4-hydroxy)tamoxifen, which were agonistic in the yeast. Acetone-soluble fractions of hexane/acetone extracts of sediments showed higher estrogenic potency than hexane-soluble extracts in the ER-CALUX assay. Sediments obtained from industrialized areas such as the Port of Rotterdam showed the highest estrogenic potency of the 12 marine sediments tested (up to 40 pmol estradiol equivalents per gram sediment). The estrogenic activity of individual chemicals that can be found in sediments including: alkylphenol ethoxylates and carboxylates; phthalates; and pesticides, was tested. Increasing sidechain length of various nonylphenol ethoxylates resulted in decreased estrogenic activity. Of the phthalates tested, butylbenzylphthalate was the most estrogenic, though with a potency approximately 100,000 times less than E2. The organochlorine herbicides atrazine and simazine failed to induce reporter gene activity. As metabolic activation may be required to induce estrogenic activity, a metabolic transformation step was added to the ER-CALUX assay using incubation of compounds with liver microsomes obtained from PCB-treated rats. Results indicate that metabolites of E2, NP and bisphenol A were less active than the parent compounds, while metabolites of methoxychlor were more estrogenic following microsomal incubations.

  12. Biosensor Zebrafish Provide New Insights into Potential Health Effects of Environmental Estrogens

    PubMed Central

    Lee, Okhyun; Takesono, Aya; Tada, Masazumi; Kudoh, Tetsuhiro

    2012-01-01

    Background: Environmental estrogens alter hormone signaling in the body that can induce reproductive abnormalities in both humans and wildlife. Available testing systems for estrogens are focused on specific systems such as reproduction. Crucially, however, the potential for significant health impacts of environmental estrogen exposures on a variety of body systems may have been overlooked. Objective: Our aim was to develop and apply a sensitive transgenic zebrafish model to assess real-time effects of environmental estrogens on signaling mechanisms in a whole body system for use in integrated health assessments. Methods: We created a novel transgenic biosensor zebrafish containing an estrogen-inducible promoter derived with multiple tandem estrogen responsive elements (EREs) and a Gal4ff-UAS system for enhanced response sensitivity. Results: Using our novel estrogen-responsive transgenic (TG) zebrafish, we identified target tissues for environmental estrogens; these tissues have very high sensitivity even at environmentally relevant concentrations. Exposure of the TG fish to estrogenic endocrine-disrupting chemicals (EDCs) induced specific expression of green fluorescent protein (GFP) in a wide variety of tissues including the liver, heart, skeletal muscle, otic vesicle, forebrain, lateral line, and ganglions, most of which have not been established previously as targets for estrogens in fish. Furthermore, we found that different EDCs induced GFP expression with different tissue response patterns and time trajectories, suggesting different potential health effects. Conclusion: We have developed a powerful new model for understanding toxicological effects, mechanisms, and health impacts of environmental estrogens in vertebrates. PMID:22510978

  13. Food-associated estrogenic compounds induce estrogen receptor-mediated luciferase gene expression in transgenic male mice.

    PubMed

    Ter Veld, Marcel G R; Zawadzka, E; van den Berg, J H J; van der Saag, Paul T; Rietjens, Ivonne M C M; Murk, Albertinka J

    2008-07-30

    The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8h after dosing the ER-luc male mice intraperitoneally (IP) or 14h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50mg/kgbw), dichlorodiphenyldichloroethylene (p,p'-DDE; at 5 and 25mg/kgbw), quercetin (at 1.66 and 16.6mg/kgbw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100mg/kgbw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50mg/kgbw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 10(4) times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high.

  14. Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).

    EPA Science Inventory

    There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipa...

  15. Missing links in our understanding of estrogenic compounds; chemical quantitation vs. biological assessment – where do we go from here?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The literature has become replete with reports quantifying estrogenic chemicals in the environment ranging from natural hormones to plasticizers. Laboratories have developed in vitro assays to assess estrogenic activity of both environmental samples and pure chemicals. Information pertaining to th...

  16. Anti-proliferative effects of estrogen receptor-modulating compounds isolated from Rheum palmatum.

    PubMed

    Kang, Se Chan; Lee, Chang Min; Choung, Eui Su; Bak, Jong Phil; Bae, Jong Jin; Yoo, Hyun Sook; Kwak, Jong Hwan; Zee, Ok Pyo

    2008-06-01

    The Rheum palmatum L., a traditional medicine in Korea, was screened for their estrogenic activity in a recombinant yeast system with a human estrogen receptor (ER) expression plasmid and a reporter plasmid used in a previous study. The EC50 values of the n-hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions of the methanolic extract of R. palmatum in the yeast-based estrogenicity assay system were 0.145, 0.093, 0.125, 1.459, 2.853 microg/mL, respectively, with marked estrogenic activity in the dichloromethane fraction. Using an activity-guided fractionation approach, five known anthraquinones, chrysophanol (1), physcion (2), emodin (3), aloe-emodin (4) and rhein (5), were isolated from the dichloromethane fraction. Compound 3 had the highest estrogenic relative potency (RP, 17bestradiol = 1.00) (6.3 x 10(-2)), followed by compound 4 (3.8 x 10(-3)), compound 5 (2.6 x 10(-4)), a compound 1 (2.1 x 10(-4)). Also, compound 3 and fraction 3 (which contained compound 3) of the dichloromethane fraction of R. palmatum showed strong cytotoxicity in both ER-positive (MCF-7) and-negative (MDA-MB-231) breast cancer cell lines.

  17. [Mixture effects to vitellogenin induction by four environmental estrogens in freshwater fish].

    PubMed

    Zhang, Hui; Kong, Fan-Xiang; Wang, Shi-He; Yu, Yang; Zhang, Min; Chen, Mei-Jun; Tan, Xiao; Qian, Shan-Qin

    2008-07-01

    Combined effects of estrogenic compounds to high risk life-form were demonstrated, and the study method on combined effects of environmental contaminant mixture and environmental risk assessment were also discussed. A nonlinear aggression was determined on the changes of plasma vitellogenin concentration in crucian carp via the environmental pollutant exposure concentration, and the concentration-response relationship was determined for the single chemical of estradiol, ethynylestradiol, bisphenol A, and octylphenol, and that of the mixed compounds at equipotent concentrations. The combined effects of the four xenoestrogens were tested using indices of mixture toxicity and the biomathematical models of concentration addition or independent action. Weibull function was indicated as the best-fit function (R2 > or = 0.92) with curve estimation, the 95% confidence limits of effect concentration was achieved using the bootstrap method, the media effective concentration (EC50) with 95% confidence interval was 0.007 9 (0.006 8-0.010 0), 0.098 7 (0.090 0-0.111 0), 63.50 (56.58-70.62) and 250.59 (228.46-271.99) Mg x L(-1) respectively. Results suggested that estrogenic chemicals acted together in an additive manner and the combined effects can be accurately predicted in whole range of exposure concentration by the concept of similar joint action or concentration addition.It is proved as a scientific and feasible method to apply the model of joint action whereas the outcome of indices with a great deal of indetermination.

  18. Universal assay of vitellogenin as a biomarker for environmental estrogens.

    PubMed Central

    Heppell, S A; Denslow, N D; Folmar, L C; Sullivan, C V

    1995-01-01

    Vitellogenin (VTG), the serum phospholipoglycoprotein precursor to egg yolk, is potentially an ideal biomarker for environmental estrogens. This study was undertaken to develop antibodies against conserved regions on the VTG molecule that could form the basis for establishing bioassays to detect estrogen exposure in any oviparous vertebrate. We developed monoclonal antibodies (mAbs) generated against purified rainbow trout (Oncorhynchus mykiss) VTG and selected for the property of specifically recognizing VTG purified from two phylogenetically distant vertebrates, trout and striped bass (Morone saxatilis). Results of enzyme-linked immunosorbent assay and Western blotting indicated that these mAbs specifically recognize purified VTG and VTG or other estrogen-inducible proteins in plasma or serum from representative species of four vertebrate classes (fish, amphibians, reptiles, and birds). All of the mAbs generated were IgM class. A polyclonal antiserum was raised against a synthetic consensus peptide representing the conserved N-terminal amino acid sequence of VTG. The results of Western blotting indicate that this antiserum specifically recognizes VTG in plasma or serum from teleost fish of diverse families. It was used to detect VTG in Western blots of serum from brown bullhead (Ameiurus nebulosus) with cancer (hepatocellular and cholangio-carcinoma) collected from a contaminated industrial site outside of their normal vitellogenic season. Our results indicate that it is feasible to generate antibodies capable of recognizing VTG without regard to species and that development of a universal VTG assay is an achievable goal. Images Figure 4. Figure 5. Figure 6. Figure 7. PMID:8593883

  19. ANALYSIS OF SWINE LAGOONS AND GROUND WATER FOR ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    A method was developed for analysis of low levels of natural (estradiol, estrone, estriol) and synthetic (ethinyl estradiol) estrogens in ground water and swine waste lagoon effluent. The method includes solid phase extraction of the estrogens, preparation of pentafluorobenzyl de...

  20. ANALYSIS OF SWINE LAGOONS AND GROUND WATER FOR ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    A method was developed for analysis of low levels of natural (estradiol, estrone, estriol) and synthetic (ethynylestradiol) estrogens in ground water and swine waste lagoon effluent. The method includes solid phase extraction of the estrogens, preparation of pentafluorobenzyl der...

  1. Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

    SciTech Connect

    Boehme, Kathleen; Simon, Stephanie

    2009-04-01

    Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.

  2. Balancing the budget of environmental estrogen exposure: the contribution of recycled water.

    PubMed

    Leusch, Frederic D L; Moore, Michael R; Chapman, Heather F

    2009-01-01

    Estrogenic endocrine disrupting compounds (e-EDCs) are present in treated sewage and there is concern about estrogenicity of potable recycled water. However e-EDCs are also present in other environmental media and intake from water needs to be considered in relation to these other sources. The concentrations of 13 e-EDCs in foodstuffs and drinking water are reviewed, their predicted concentrations in recycled water are estimated, and the daily estrogenic intake as 17beta-estradiol equivalent (EEq) based on both in vitro and in vivo potencies is calculated as 1.39 and 9.65 microg EEq/d, respectively. Dietary intake accounts for more than 99.8% of that total, and more than 84.2% is due to phytosterols. Drinking 2 L of recycled water per day is expected to add 0.001 to 0.016 microg EEq/d based on in vitro and in vivo potencies, respectively. Exposure to e-EDCs in recycled water is therefore likely to be insignificant compared to current dietary intakes.

  3. Occurrence of compounds estrogenic to freshwater mussels in surface waters in an urban area.

    PubMed

    Gagné, F; Marcogliese, D J; Blaise, C; Gendron, A D

    2001-06-01

    Estrogens play a major role in the sexual differentiation, gonad development, and oocyte growth of most oviparous organisms. They also stimulate vitellogenesis, the formation of high-density glycolipophosphoprotein that serves as an energy source for the developing embryo. Surface waters from the St. Lawrence River, obtained in the vicinity of an urban area (Montreal, Quebec, Canada), were studied with respect to their estrogenic potential to the freshwater mussel Elliptio complanata. Estrogenicity was measured in water extracts by means of a competitive assay of estradiol binding to cytosolic proteins and by the vitellin-inducing ability of mussel hemolymph following direct extract injection. Surface-water samples drawn downstream of a municipal outfall plume and in a river draining a large farming and agricultural area had high levels of total and fecal coliform bacteria. High levels of estrogen competitors were also found and were able to induce vitellins in injected mussels. Moreover, the estrogen-competing potential of the extracts was found to be significantly correlated with total and fecal coliform bacteria (R = 0.9, p < 0.01) and with the levels of vitellins in the hemolymph (R = 0.62, p = 0.03). The results indicate that water samples drawn from within the municipal effluent plume and from a river draining an agricultural area are estrogenic to freshwater mussels. Thus, the environmental inputs of estrogens are likely to be associated with human sewage and pesticide products.

  4. EXPRESSION PROFILING OF ESTROGENIC COMPOUNDS USING A SHEEPSHEAD MINNOW CDNA MACROARRAY

    EPA Science Inventory

    Larkin, Patrick, Leroy C. Folmar, Michael J. Hemmer, Arianna J. Poston and Nancy D. Denslow. 2003. Expression Profiling of Estrogenic Compounds Using a Sheepshead Minnow cDNA Macroarray. Environ. Health Perspect. 111(6):839-846. (ERL,GB 1171).

    A variety of anthropogenic c...

  5. Comparison of five in vitro bioassays to measure estrogenic activity in environmental waters.

    PubMed

    Leusch, Frederic D L; de Jager, Christiaan; Levi, Yves; Lim, Richard; Puijker, Leo; Sacher, Frank; Tremblay, Louis A; Wilson, Vickie S; Chapman, Heather F

    2010-05-15

    Bioassays are well established in the pharmaceutical industry and single compound analysis, but there is still uncertainty about their usefulness in environmental monitoring. We compared the responses of five bioassays designed to measure estrogenic activity (the yeast estrogen screen, ER-CALUX, MELN, T47D-KBluc, and E-SCREEN assays) and chemical analysis on extracts from four different water sources (groundwater, raw sewage, treated sewage, and river water). All five bioassays displayed similar trends and there was good agreement with analytical chemistry results. The data from the ER-CALUX and E-SCREEN bioassays were robust and predictable, and well-correlated with predictions from chemical analysis. The T47D-KBluc appeared likewise promising, but with a more limited sample size it was less compelling. The YES assay was less sensitive than the other assays by an order of magnitude, which resulted in a larger number of nondetects. The MELN assay was less predictable, although the possibility that this was due to laboratory-specific difficulties cannot be discounted. With standardized bioassay data analysis and consistency of operating protocols, bioanalytical tools are a promising advance in the development of a tiered approach to environmental water quality monitoring.

  6. Rapid effects of estrogens on behavior: environmental modulation and molecular mechanisms

    PubMed Central

    Laredo, Sarah A.; Landeros, Rosalina Villalon; Trainor, Brian C.

    2014-01-01

    Estradiol can modulate neural activity and behavior via both genomic and nongenomic mechanisms. Environmental cues have a major impact on the relative importance of these signaling pathways with significant consequences for behavior. First we consider how photoperiod modulates nongenomic estrogen signaling on behavior. Intriguingly, short days permit rapid effects of estrogens on aggression in both rodents and song sparrows. This highlights the importance of considering photoperiod as a variable in laboratory research. Next we review evidence for rapid effects of estradiol on ecologically-relevant behaviors including aggression, copulation, communication, and learning. We also address the impact of endocrine disruptors on estrogen signaling, such as those found in corncob bedding used in rodent research. Finally, we examine the biochemical mechanisms that may mediate rapid estrogen action on behavior in males and females. A common theme across these topics is that the effects of estrogens on social behaviors vary across different environmental conditions. PMID:24685383

  7. Rapid effects of estrogens on behavior: environmental modulation and molecular mechanisms.

    PubMed

    Laredo, Sarah A; Villalon Landeros, Rosalina; Trainor, Brian C

    2014-10-01

    Estradiol can modulate neural activity and behavior via both genomic and nongenomic mechanisms. Environmental cues have a major impact on the relative importance of these signaling pathways with significant consequences for behavior. First we consider how photoperiod modulates nongenomic estrogen signaling on behavior. Intriguingly, short days permit rapid effects of estrogens on aggression in both rodents and song sparrows. This highlights the importance of considering photoperiod as a variable in laboratory research. Next we review evidence for rapid effects of estradiol on ecologically-relevant behaviors including aggression, copulation, communication, and learning. We also address the impact of endocrine disruptors on estrogen signaling, such as those found in corncob bedding used in rodent research. Finally, we examine the biochemical mechanisms that may mediate rapid estrogen action on behavior in males and females. A common theme across these topics is that the effects of estrogens on social behaviors vary across different environmental conditions.

  8. VITELLOGENIN GENE TRANSCRIPTION: A RELATIVE QUANTITATIVE EXPOSURE INDICATOR OF ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    We report the development of a quantifiable exposure indicator for measuring the presence of environmental estrogens in aquatic systems. Synthetic oligonucleotides, designed specifically for the vitellogenin gene (Vg) transcription product, were used in a Reverse Transcription Po...

  9. FIELD DEPLOYABLE TECHNIQUES TO MONITOR EXPOSURE TO ENVIRONMENTAL ESTROGENS THROUGHOUT THE REPRODUCTIVE CYCLE OF WILD BIRDS

    EPA Science Inventory

    Concern about potential for endocrine disrupting chemicals to interfere with normal breeding behaviors of wildlife prompted this study of effects of exposure to environmental estrogens during the breeding cycle of wild birds. The house finch (Carpodacus mexicanus) was selected as...

  10. DEVELOPMENT OF A QUANTITATIVE ASSAY FOR VITELLOGENIN TO MONITOR ESTROGEN-LIKE ENVIRONMENTAL CONTAMINANTS

    EPA Science Inventory

    Many environmental contaminants have the potential to disrupt endocrine systems of wildlife and humans resulting in impairment of reproductive and other systems. A subset of these contaminants may initiate these effects by binding to the estrogen receptor. In oviparous vertebrate...

  11. Environmentally Friendly Corrosion Preventative Compounds

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Montgomery, Eliza; Kolody, Mark; Curran, Jerry; Back, Teddy; Balles, Angela

    2012-01-01

    The objective of the Ground Systems Development and Operations Program Environmentally Friendly Corrosion Protective Coatings and Corrosion Preventive Compounds (CPCs) project is to identify, test, and develop qualification criteria for the use of environmentally friendly corrosion protective coatings and CPCs for flight hardware and ground support equipment. This document is the Final Report for Phase I evaluations, which included physical property, corrosion resistance, and NASA spaceport environment compatibility testing and analysis of fifteen CPC types. The CPCs consisted of ten different oily film CPCs and five different wax or grease CPC types. Physical property testing encompassed measuring various properties of the bulk CPCs, while corrosion resistance testing directly measured the ability of each CPC material to protect various metals against corrosion. The NASA spaceport environment compatibility testing included common tests required by NASA-STD-6001, "Flammability, Odor, Offgassing, and Compatibility Requirements and Test Procedures for Materials in Environments that Support Combustion". At the end of Phase I, CPC materials were down-selected for inclusion in the next test phases. This final report includes all data and analysis of results obtained by following the experimental test plan that was developed as part of the project. Highlights of the results are summarized by test criteria type.

  12. Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types.

    PubMed

    Bovee, Toine F H; Helsdingen, Richard J R; Rietjens, Ivonne M C M; Keijer, Jaap; Hoogenboom, Ron L A P

    2004-07-01

    Previously, we described the construction of a rapid yeast bioassay stably expressing human estrogen receptor (hERalpha) and yeast enhanced green fluorescent protein (yEGFP) in response to estrogens. In the present study, the properties of this assay were further studied by testing a series of estrogenic compounds. Furthermore, a similar assay was developed based on the stable expression of human estrogen receptor beta (hERbeta). When exposed to 17beta-estradiol, the maximum transcriptional activity of the ERbeta cytosensor was only about 40% of the activity observed with ERalpha, but the concentration where half-maximal activation is reached (EC50), was about five times lower. The relative estrogenic potencies (REP), defined as the ratio between the EC50 of 17beta-estradiol and the EC50 of the compound, of the synthetic hormones dienestrol, hexestrol and especially mestranol were higher with ER, while DES was slightly more potent with ERbeta. The gestagens progesterone and medroxyprogesterone-acetate showed no response, whereas the androgen testosterone showed a very weak response. The anabolic agent, 19-nortestosterone showed a clear dose-related response with estrogen receptor but not beta. The phytoestrogens coumestrol, genistein, genistin, daidzein, daidzin and naringenin were relatively more potent with ERbeta. Ranking of the estrogenic potency with ER was: 17beta-estradiol > 8-prenylnaringenin > coumestrol > zearalenone > genistein > genistin > naringenin. The ranking with the ERbeta was: 17beta-estradiol > coumestrol > genistein > zearalenone > 8-prenylnaringen > daidzein > naringenin > genistin > daidzin. The hop estrogen 8-prenylnaringenin is relatively more potent with ERalpha. These data show that the newly developed bioassays are valuable tools for the rapid and high-throughput screening for estrogenic activity.

  13. Estrogenic effects of natural and synthetic compounds including tibolone assessed in Saccharomyces cerevisiae expressing the human estrogen alpha and beta receptors.

    PubMed

    Hasenbrink, Guido; Sievernich, André; Wildt, Ludwig; Ludwig, Jost; Lichtenberg-Fraté, Hella

    2006-07-01

    The human estrogen receptors (hER)alpha and hERbeta, differentially expressed and localized in various tissues and cell types, mediate transcriptional activation of target genes. These encode a variety of physiological reproductive and nonreproductive functions involved in energy metabolism, salt balance, immune system, development, and differentiation. As a step toward developing a screening assay for the use in applications where significant numbers of compounds or complex matrices need to be tested for (anti) estrogenic bioactivity, hERalpha and hERbeta were expressed in a genetically modified Saccharomyces cerevisiae strain, devoid of three endogenous xenobiotic transporters (PDR5, SNQ2, and YOR1). By using receptor-mediated transcriptional activation of the green fluorescent protein optimized for expression in yeast (yEGFP) as reporter 17 natural, comprising estrogens and phytoestrogens or synthetic compounds among which tibolone with its metabolites, gestagens, and antiestrogens were investigated. The reporter assay deployed a simple and robust protocol for the rapid detection of estrogenic effects within a 96-well microplate format. Results were expressed as effective concentrations (EC50) and correlated to other yeast based and cell line assays. Tibolone and its metabolites exerted clear estrogenic effects, though considerably less potent than all other natural and synthetic compounds. For the blood serum of two volunteers, considerable higher total estrogenic bioactivity than single estradiol concentrations as determined by immunoassay was found. Visualization of a hERalpha/GFP fusion protein in yeast revealed a sub cellular cytosolic localization. This study demonstrates the versatility of (anti) estrogenic bioactivity determination using sensitized S. cerevisiae cells to assess estrogenic exposure and effects.

  14. Occurrence and in vitro bioactivity of estrogen, androgen, and glucocorticoid compounds in a nationwide screen of United States stream waters

    USGS Publications Warehouse

    Conley, Justin M.; Evans, Nicola; Cardon, Mary C.; Rosenblum, Laura; Iwanowicz, Luke; Hartig, Phillip C.; Schenck, Kathleen M.; Bradley, Paul M.; Wilson, Vickie S.

    2017-01-01

    In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a broad suite of chemical analytes, in streamwater from 35 well-characterized sites (3 reference and 32 impacted) across 24 states and Puerto Rico. ER agonism was the most frequently detected with nearly all sites (34/35) displaying activity (range, 0.054–116 ng E2Eq L–1). There was a strong linear relationship (r2 = 0.917) between in vitro ER activity and concentrations of steroidal estrogens after correcting for the in vitro potency of each compound. AR agonism was detected in 5/35 samples (range, 1.6–4.8 ng DHTEq L–1) but concentrations of androgenic compounds were largely unable to account for the in vitro activity. Similarly, GR agonism was detected in 9/35 samples (range, 6.0–43 ng DexEq L–1); however, none of the recognized GR-active compounds on the target-chemical analyte list were detected. The utility of in vitro assays in water quality monitoring was evident from both the quantitative agreement between ER activity and estrogen concentrations, as well as the detection of AR and GR activity for which there were limited or no corresponding target-chemical detections to explain the bioactivity. Incorporation of in vitro bioassays as complements to chemical analyses in standard water quality monitoring efforts would allow for more complete assessment of the chemical mixtures present in many surface waters.

  15. Fate and transport of selected estrogen compounds in Hawaii soils: Effect of soil type and macropores

    NASA Astrophysics Data System (ADS)

    D'Alessio, Matteo; Vasudevan, Dharni; Lichwa, Joseph; Mohanty, Sanjay K.; Ray, Chittaranjan

    2014-10-01

    The fate and transport of estrogen compounds in the environment is of increasing concern due to their potential impact on freshwater organisms, ecosystems and human health. The behavior of these compounds in batch experiments suggests low mobility, while field studies indicate the persistence of estrogen compounds in the soil with the possibility of migration to surface water as well as groundwater. To better understand the movement of these chemicals through soils, we examined their transport in three different Hawaiian soils and two aqueous matrices. The three different soils used were an Oxisol, a Mollisol and a cinder, characterized by different mineralogical properties and collected at depths of 60-90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water containing calcium chloride (CaCl2), and recycled water collected from a wastewater treatment facility. The experiments were conducted in packed and structured columns. Non-equilibrium conditions were observed during the study, especially in the structured soil. This is believed to be primarily related to the presence of macropores in the soil. The presence of macropores resulted in reduced contact time between soil and estrogens, which facilitated their transport. We found that the organic carbon content and mineralogical composition of the soils had a profound effect on the transport of the estrogens. The mobility of estrone (E1) and 17β-estradiol (E2) was greater in cinder than in the other soils. In column experiments with recycled water, earlier breakthrough peaks and longer tails of estrogens were produced compared to those observed using DI water. The use of recycled water for agricultural purposes and the siting of septic tanks and cesspools should be critically reviewed in light of these findings, especially in areas where groundwater is the primary source of potable water, such as Hawaii.

  16. Fate and transport of selected estrogen compounds in Hawaii soils: effect of soil type and macropores.

    PubMed

    D'Alessio, Matteo; Vasudevan, Dharni; Lichwa, Joseph; Mohanty, Sanjay K; Ray, Chittaranjan

    2014-10-01

    The fate and transport of estrogen compounds in the environment is of increasing concern due to their potential impact on freshwater organisms, ecosystems and human health. The behavior of these compounds in batch experiments suggests low mobility, while field studies indicate the persistence of estrogen compounds in the soil with the possibility of migration to surface water as well as groundwater. To better understand the movement of these chemicals through soils, we examined their transport in three different Hawaiian soils and two aqueous matrices. The three different soils used were an Oxisol, a Mollisol and a cinder, characterized by different mineralogical properties and collected at depths of 60-90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water containing calcium chloride (CaCl2), and recycled water collected from a wastewater treatment facility. The experiments were conducted in packed and structured columns. Non-equilibrium conditions were observed during the study, especially in the structured soil. This is believed to be primarily related to the presence of macropores in the soil. The presence of macropores resulted in reduced contact time between soil and estrogens, which facilitated their transport. We found that the organic carbon content and mineralogical composition of the soils had a profound effect on the transport of the estrogens. The mobility of estrone (E1) and 17β-estradiol (E2) was greater in cinder than in the other soils. In column experiments with recycled water, earlier breakthrough peaks and longer tails of estrogens were produced compared to those observed using DI water. The use of recycled water for agricultural purposes and the siting of septic tanks and cesspools should be critically reviewed in light of these findings, especially in areas where groundwater is the primary source of potable water, such as Hawaii.

  17. Estrogenic potencies of several environmental pollutants, as determined by vitellogenin induction in a carp hepatocyte assay.

    PubMed

    Smeets, J M; van Holsteijn, I; Giesy, J P; Seinen, W; van den Berg, M

    1999-08-01

    Estrogenic potencies of several xenoestrogens were determined in vitro, using cultured hepatocytes from a genetically uniform male carp strain (Cyprinus carpio). Estrogenicity was measured as induction of the yolk protein precursor vitellogenin (Vtg), and compared to Vtg induction by 17beta-estradiol (E2). The order of estrogenic potency was: methoxychlor (MXCL) > o,p-DDT > chlordecone approximately/= bisphenol-A approximately/= 4-t-pentylphenol. Estrogenic potencies of these compounds varied from 1 x 10(-3) to 1 x 10(-4) relative to E2. The synthetic estrogen DES had a relative estrogenic potency of 0.5, whereas dieldrin, beta-endosulfan, o,p-DDE, and toxaphene (technical mixture) did not induce vitellogenesis at concentrations up to 100 microM. Experiments in which cells were simultaneously exposed to E2 and these xenoestrogens showed that the Vtg-inducing activities of E2 and 4-t-pentylphenol or bisphenol-A were (partially) additive, whereas E2 antagonized the estrogenic effects of MXCL and o,p-DDT. The effect of cytochrome P4501A (CYP1A)-induction on the estrogenicity of MXCL was studied by co-exposing cells to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD (10 pM) caused a greater than 50-fold induction of CYP1A, measured as ethoxyresorufin O-deethylase (EROD) activity, but Vtg induction by MXCL was not significantly affected. This indicates that CYP1A is not involved in the bioactivation of MXCL to more potent estrogenic metabolites in carp. The CARP-HEP (hepatocyte) assay can detect xenoestrogens with a potency > or = 2 x 10(-5) relative to E2. It allows simultaneous testing of more than 10 compounds for both estrogenic and antiestrogenic effects, which makes it a promising tool for the screening of suspected xenoestrogens.

  18. Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

    SciTech Connect

    Iwase, Yumiko . E-mail: Iwase.Yumiko@mg.m-pharma.co.jp; Fukata, Hideki . E-mail: fukata@faculty.chiba-u.jp; Mori, Chisato . E-mail: cmori@faculty.chiba-u.jp

    2006-05-01

    Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17{beta}-estradiol (E{sub 2}, a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 {mu}M DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 {mu}M E{sub 2} and 25 {mu}M GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at {mu}M level between DES and E{sub 2} on GJIC inhibition was observed, but not between GEN and E{sub 2}. DES and E{sub 2} showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 {mu}M was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E{sub 2} (10 pM and 20 {mu}M) and GEN (25 {mu}M) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E{sub 2} and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development.

  19. Cross-talk between non-genomic and genomic signalling pathways - Distinct effect profiles of environmental estrogens

    SciTech Connect

    Silva, Elisabete; Kabil, Alena; Kortenkamp, Andreas

    2010-06-01

    Estrogen receptor (ER) transcriptional cross-talk after activation by 17{beta}-estradiol (E2) has been studied in considerable detail, but comparatively little is known about the ways in which synthetic estrogen-like chemicals, so-called xenoestrogens, interfere with these signalling pathways. E2 can stimulate rapid, non-genomic signalling events, such as activation of the Src/Ras/Erk signalling pathway. We investigated how activation of this pathway by E2, the estrogenic environmental contaminants o,p'-DDT, {beta}-HCH and p,p'-DDE, and epidermal growth factor (EGF) influences the expression of ER target genes, such as TFF1, ER, PR, BRCA1 and CCND1, and the proliferation of breast cancer cells. Despite commonalities in their estrogenicity as judged by cell proliferation assays, the environmental contaminants exhibited striking differences in their non-genomic and genomic signalling. The gene expression profiles of o,p'-DDT and {beta}-HCH resembled the effects observed with E2. In the case of {beta}-HCH this is surprising, considering its reported lack of affinity to the 'classical' ER. The expression profiles seen with p,p'-DDE showed some similarities with E2, but overall, p,p'-DDE was a fairly weak transcriptional inducer of TFF1, ER, PR, BRCA1 and CCND1. We observed distinct differences in the non-genomic signalling of the tested compounds. p,p'-DDE was unable to stimulate Src and Erk1/Erk2 activations. The effects of E2 on Src and Erk1/Erk2 phosphorylation were transient and weak when compared to EGF, but {beta}-HCH induced strong and sustained activation of all tested kinases. Transcription of TFF1, ER, PR and BRCA1 by E2, o,p'-DDT and {beta}-HCH could be suppressed partially by inhibiting the Src/Ras/Erk pathway with PD 98059. However, this was not seen with p,p'-DDE. Our investigations show that the cellular activities of estrogens and xenoestrogens are the result of a combination of extranuclear (non-genomic) and nuclear (genomic) events and highlight the

  20. In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds.

    PubMed Central

    Meerts, I A; Letcher, R J; Hoving, S; Marsh, G; Bergman, A; Lemmen, J G; van der Burg, B; Brouwer, A

    2001-01-01

    Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens. PMID:11335189

  1. A low-density DNA microchip for the detection of (anti-)estrogenic compounds and their relative potencies.

    PubMed

    Wang, Si; Rijk, Jeroen C W; Pen, Marieke J; Aarts, Jac M M J G; Peijnenburg, Ad A C M; Rietjens, Ivonne M C M; Bovee, Toine F H

    2013-04-01

    In the current study, a set of 12 reference compounds was tested in a low-density DNA microchip that contains probes for 11 different estrogen-responsive marker genes. Our results show that the seven most informative marker genes on the chip resulted in fingerprints that correctly predicted the (anti-)estrogenic activity of the model compounds except that of the negative control testosterone. Two marker genes, myeloid leukemia factor-1 interacting protein and ubiquitin-conjugating enzyme E2C, were even capable of correctly predicting the estrogenic potency of all five estrogen receptor (ER) agonists tested and correlated well with the potencies as determined in the MCF-7/BOS proliferation assay and the in vivo uterotrophic assay. In addition, it was demonstrated that the estrogenic responses of testosterone, both in the array tube assay and in the proliferation assay, were partially due to the conversion of testosterone into 17β-estradiol by aromatase but also due to formation of other estrogenic metabolites, the presence and estrogenic potency of which were confirmed by gas chromatography-tandem mass spectrometry analysis and a yeast-based reporter gene assay, respectively. It is concluded that low-density DNA microchip-based fingerprinting in MCF-7/BOS cells for estrogenicity marker genes provides a faster in vitro alternative to the current MCF-7/BOS cell proliferation assay (E-screen).

  2. Rapid assessment of estrogenic compounds by CXCL-test illustrated by the screening of the UV-filter derivative benzophenones.

    PubMed

    Habauzit, Denis; Martin, Catherine; Kerdivel, Gwenneg; Pakdel, Farzad

    2017-04-01

    CXCL-test is a method that uses the estrogen-dependent secretion of the natural endogenous chemokine CXCL12 to evaluate the estrogenic activity of molecules. CXCL12 chemokine is involved in the estrogen dependent proliferation of breast cancer cells. Its measure is an indicator of cell proliferation and is used as an alternative test to classical proliferation test. Here we aimed to optimize this test, first to increase the number of tested molecules in a single assay and then to decrease the number of intermediate steps. The optimized CXCL-test was finally used for the evaluation of the estrogenic potency of emerging chemical pollutants: the UV filter benzophenones (BPs). The effect of BPs on CXCL12 secretion was also validated by real time quantitative RT-PCR. The optimized CXCL-test allowed a fast and direct assessment of estrogenic potency of molecules. The estrogenic activities of benzophenones were characterized and divided in two groups. The first one contains weak estrogenic compounds (BP, BP1, BP2, BP3, 234BP and 2344'BP). The second one contains medium estrogenic compounds (4BP, 44'BP, BP8, THB).

  3. The Natural Estrogenic Compound Diarylheptanoid (D3): In Vitro Mechanisms of Action and in Vivo Uterine Responses via Estrogen Receptor α

    PubMed Central

    Winuthayanon, Wipawee; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Burns, Katherine A.; Arao, Yukitomo; Hewitt, Sylvia C.; Pedersen, Lars C.

    2013-01-01

    Background: Diarylheptanoid (D3) isolated from the medicinal plant, Curcuma comosa, has estrogenic activity. Objective: We aimed to elucidate the mechanism(s) of D3 action and compare it with that of 17β-estradiol (E2) using both in vitro and in vivo uterine models. Methods: We used human uterine (Ishikawa) cells to determine the estrogenic action of D3 on the activation and nuclear translocation of estrogen receptor α (ERα). In addition, we further characterized the uterine response to D3 treatment in vivo. Results: D3 activated an estrogen responsive element (ERE) luciferase reporter through ERα, and molecular modeling suggested that D3 could be accommodated in the ERα binding pocket. Using modified ERα to assay ligand-dependent nuclear translocation, we observed D3-dependent ERα interaction and translocation. In mouse uteri, early- and late-phase estrogen-regulated gene responses were increased in D3-treated ovariectomized wild-type animals, in a manner similar to that of E2; no response was seen in ERα knockout animals. We observed a divergence in estrogen responses after D3 treatment: D3 induced robust DNA synthesis in uterine epithelial cells, linked to an increase in cell-cycle–related genes; however, no increase in uterine weight was observed 24 hr after treatment. D3 also affected uterine progesterone receptor expression patterns similar to E2. When D3 and E2 were administered together, we observed no additive or antagonistic effects of D3 on E2. Our findings suggest that D3 is a weak estrogenic agonist compound. Conclusion: D3 is a weakly acting phytoestrogen that mimics the mitogenic responses produced by E2 in an ERα-dependent manner, but it is unable to increase uterine weight or enhance or antagonize the effects of estrogen. PMID:23552522

  4. Estrogenic activity of isolated compounds and essential oils of Pimpinella species from Turkey, evaluated using a recombinant yeast screen.

    PubMed

    Tabanca, Nurhayat; Khan, Shabana I; Bedir, Erdal; Annavarapu, Srinivas; Willett, Kristine; Khan, Ikhlas A; Kirimer, Nese; Baser, K Husnu Can

    2004-08-01

    Several plants and plant-derived pure compounds, designated as phytoestrogens, have been reported to cause estrogenic effects. They have been used for alleviation of menopausal symptoms, prevention of osteoporosis, heart disease and cancer. There is an increased interest in studying phytoestrogens such as isoflavones and lignans for their use as replacements for synthetic estrogens. In this study, the estrogenic activity of essential oils of eleven Pimpinella species and the compounds isolated from these species were evaluated using the yeast estrogen screen (YES) assay. The essential oils containing (E)-anethole as major compound showed estrogenic activity in the YES assay, except for the aerial parts without fruits of P. anisetum and P. flabellifolia. The percent maximal response produced by most anethole-containing oils was 30-50%. Fruits of P. isaurica and P. peucedanifolia were estrogenic in spite of the absence or trace amount of anethole, respectively. This study indicates that the estrogenic activity of Pimpinella oils is not solely due to the presence of anethole. Components other than anethole may be responsible for contributing towards the estrogenic activity. The essential oils from different species varied in their estrogenic potencies (relative potency from 8.3 x 10(-8) to 1.2 x 10(-6) compared to 17 beta-estradiol) and among the different plant parts, the fruit oils of most species were estrogenic followed by the aerial parts without fruits and the root oils and their EC50 values varied from 45 micrograms/mL to 650 micrograms/mL.

  5. In vitro biomonitoring in polar extracts of solid phase matrices reveals the presence of unknown compounds with estrogenic activity.

    PubMed

    Legler, J; Leonards, P; Spenkelink, A; Murk, A J

    2003-01-01

    Determination of estrogenic activity has so far mainly concentrated on the assessment of compounds in surface water and effluent. This study is one of the first to biomonitor (xeno-)estrogens in sediment, suspended particulate matter and aquatic organisms. The relatively polar acetone extracts from these solid phase matrices do not contain the well-known estrogenic compounds such as hormones, alkylphenols and phthalates. An in vitro 'estrogen receptor-mediated chemical activated luciferase gene expression' (ER-CALUX) assay was applied to samples from various locations in the Netherlands. Estrogenic activity measured in polar fractions of particulate matter and sediment extracts ranged from below detection limit to up to 4.5 pmol estradiol equivalents (EEQ)/g dry weight. Estrogenic activity in freshwater river sediments was up to five times higher compared to sediments from large lakes and coastal locations. Tissue extracts EEQs were determined in bream (Abramis brama), flounder (Platichthysflesus), freshwater mussels (Dreissena polymorpha) and marine mussels (Mytilus edulis). The highest biota EEQ levels were found in the freshwater zebra mussel (30 pmol EEQ/g lipid). One sample site showed greatly elevated EEQs in sediment and biota, which correlated with effects found in the wild populations of bream. The EEQ activity of the unknown compounds in the polar fraction mostly was much higher than the calculated EEQ levels based on known estrogens in the non-polar fraction (previously published data).

  6. Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia.

    PubMed

    Al-Rifai, Jawad H; Gabelish, Candace L; Schäfer, Andrea I

    2007-10-01

    The discovery that natural and synthetic chemicals, in the form of excreted hormones and pharmaceuticals, as well as a vast array of compounds with domestic and industrial applications, can enter the environment via wastewater treatment plants and cause a wide variety of environmental and health problems even at very low concentrations, suggests the need for improvement of water recycling. Three Australian wastewater recycling schemes, two of which employ reverse osmosis (RO) technology, the other applying ozonation and biological activated carbon filtration, have been studied for their ability to remove trace organic contaminants including 11 pharmaceutically active compounds and two non-steroidal estrogenic compounds. Contaminant concentrations were determined using a sensitive analytical method comprising solid phase extraction, derivatization and GC with MS using selected ion monitoring. In raw wastewater, concentrations of analgesics and non-steroidal anti-inflammatory medications were comparable to those found in wastewaters around the world. Remarkably, removal efficiencies for the three schemes were superior to literature values and RO was responsible for the greatest proportion of contaminant removal. The ability of RO membranes to concentrate many of the compounds was demonstrated and highlights the need for continued research into monitoring wastewater treatment, concentrate disposal, improved water recycling schemes and ultimately, safer water and a cleaner environment.

  7. Assays for endocrine-disrupting chemicals: Beyond environmental estrogens

    SciTech Connect

    Folmar, L.C.

    1999-07-01

    Recent popular and scientific articles have reported the presence of estrogenic and other hormone mimicking chemicals in the environment and their potential for causing reproductive dysfunction in humans and wildlife. The purpose of this session was to present the best available, if not standard, analytical methods to assay for the effects of xenobiotic chemicals on a broad range of endocrine-mediated events, including reproduction, growth, development and stress responses in aquatic vertebrate and invertebrate animals.

  8. Molecular and Biochemical Analysis of the Estrogenic and Proliferative Properties of Vitamin E Compounds

    PubMed Central

    Khallouki, Farid; de Medina, Philippe; Caze-Subra, Stéphanie; Bystricky, Kerstin; Balaguer, Patrick; Poirot, Marc; Silvente-Poirot, Sandrine

    2016-01-01

    Tocols are vitamin E compounds that include tocopherols (TPs) and tocotrienols (TTs). These lipophilic compounds are phenolic antioxidants and are reportedly able to modulate estrogen receptor β (ERβ). We investigated the molecular determinants that control their estrogenicity and effects on the proliferation of breast cancer cells. Docking experiments highlighted the importance of the tocol phenolic groups for their interaction with the ERs. Binding experiments confirmed that they directly interact with both ERα and ERβ with their isoforms showing potencies in the following order: δ-tocols > γ-tocols > α-tocols. We also found that tocols activated the transcription of an estrogen-responsive reporter gene that had been stably transfected into cells expressing either ERα or ERβ. The role of the phenolic group in tocol–ER interaction was further established using δ-tocopherylquinone, the oxidized form of δ-TP, which had no ER affinity and did not induce ER-dependent transcriptional modulation. Tocol activity also required the AF1 transactivation domain of ER. We found that both δ-TP and δ-TT stimulated the expression of endogenous ER-dependent genes. However, whereas δ-TP induced the proliferation of ER-positive breast cancer cells but not ER-negative breast cancer cells, δ-TT inhibited the proliferation of both ER-positive and ER-negative breast cancer cells. These effects of δ-TT were found to act through the down regulation of HMG-CoA reductase (HMGR) activity, establishing that ERs are not involved in this effect. Altogether, these data show that the reduced form of δ-TP has estrogenic properties which are lost when it is oxidized, highlighting the importance of the redox status in its estrogenicity. Moreover, we have shown that δ-TT has antiproliferative effects on breast cancer cells independently of their ER status through the inhibition of HMGR. These data clearly show that TPs can be discriminated from TTs according to their

  9. Occurrence of selected estrogenic compounds and estrogenic activity in surface water and sediment of Langat River (Malaysia).

    PubMed

    Praveena, Sarva Mangala; Lui, Tang Seok; Hamin, Nur'Aqilah; Razak, Siti Quistina Noorain Abdul; Aris, Ahmad Zaharin

    2016-07-01

    The occurrence and estrogenic activities of steroid estrogens, such as the natural estrone (E1), 17β estradiol (E2), and estriol (E3), as well as the synthetic 17α-ethynylestradiol (EE2), were investigated in eight sampling points along the Langat River (Malaysia). Surface water samples were collected at 0.5 m and surface sediment 0-5 cm from the river surface. Instrument analysis of steroid estrogens was determined by UPLC-ESI-MS with an ultra-performance liquid chromatograph (Perkin Elmer FX15) coupled to a Q Trap function mass spectrophotometer (model 3200: AB Sciex). Steroid estrogen concentrations were higher in the Langat River sediments than those in its surface water. In surface water, E1 was not detected in any sampling point, E2 was only detected in two midstream sampling points (range 0-0.004 ng/L), E3 in three sampling points (range 0-0.002 ng/L), and EE2 in four sampling points (range 0-0.02 ng/L). E1 and E2 were detected in sediments from all sampling points, E3 in five sampling points, while EE2 only in one midstream sample (3.29E-4 ng/g). Sewage treatment plants, farming waste, and agricultural activities particularly present midstream and downstream were identified as potential sources of estrogens. Estrogenic activity expressed as estradiol equivalents (EEQs) was below 1 ng/L in all samples for both surface water and sediment, indicating therefore a low potential estrogenic risk to the aquatic environment. Although the health risks are still uncertain for drinking water consumers exposed to low levels of steroid estrogen concentrations, Langat River water is unacceptable for direct drinking purposes without treatment. Further studies of endocrine disruptors in Malaysian waters are highly recommended.

  10. Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

    USGS Publications Warehouse

    Lerner, Darren T.; Sheridan, Mark A.; McCormick, Stephen D.

    2012-01-01

    Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 μg g−1 17β-estradiol (E2) or 150 μg g−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 μg g−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

  11. Environmental Estrogens Differentially Engage the Histone Methyltransferase EZH2 to Increase Risk of Uterine Tumorigenesis

    PubMed Central

    Greathouse, K. Leigh; Bredfeldt, Tiffany; Everitt, Jeffrey I.; Lin, Kevin; Berry, Tia; Kannan, Kurunthachalam; Mittelstadt, Megan L.; Ho, Shuk-mei; Walker, Cheryl L.

    2013-01-01

    Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol (DES) during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyper-responsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein (GEN), a soy phytoestrogen, and the plasticizer bisphenol A (BPA), differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. While both GEN and BPA induce genomic estrogen receptor (ER) signaling in the developing uterus, only GEN induced PI3K/AKT non-genomic ER signaling to the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2). As a result, this “pre-genomic” signaling phosphorylates and represses EZH2, and reduces levels of H3K27 repressive mark in chromatin. Furthermore, only GEN caused estrogen-responsive genes in the adult myometrium to become hyper-responsive to hormone; estrogen-responsive genes were repressed in BPA exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by GEN promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, while BPA did not. These data demonstrate that environmental estrogens have distinct non-genomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis. PMID:22504913

  12. Optimization and prevalidation of the in vitro ERalpha CALUX method to test estrogenic and antiestrogenic activity of compounds.

    PubMed

    van der Burg, Bart; Winter, Roos; Weimer, Marc; Berckmans, Pascale; Suzuki, Go; Gijsbers, Linda; Jonas, Arjen; van der Linden, Sander; Witters, Hilda; Aarts, Jac; Legler, Juliette; Kopp-Schneider, Annette; Bremer, Susanne

    2010-08-01

    Estrogenicity of chemicals has received significant attention and is linked to endocrine-disrupting activities. However, there is a paucity of validated methods to assess estrogenicity in vitro. We have established a robust method to test estrogenic and antiestrogenic activity of compounds in vitro, as an alternative to using animal models such as the uterotrophic assay. To this end we optimized protocols to be used in combination with CALUX reporter gene assays and carried out an in house prevalidation, followed by two rounds of tests to establish transferability. Problems in the initial test with transferability were solved by isolation of a novel cell clone of the ERalpha CALUX line with greatly improved stability and luciferase levels. This cell line proved to be a very suitable and reliable predictor of estrogenicity of chemicals and was able to readily rank a range of chemicals on the basis of their EC50 values.

  13. New insights into fetal mammary gland morphogenesis: differential effects of natural and environmental estrogens

    PubMed Central

    Speroni, Lucia; Voutilainen, Maria; Mikkola, Marja L.; Klager, Skylar A.; Schaeberle, Cheryl M.; Sonnenschein, Carlos; Soto, Ana M.

    2017-01-01

    An increased breast cancer risk during adulthood has been linked to estrogen exposure during fetal life. However, the impossibility of removing estrogens from the feto-maternal unit has hindered the testing of estrogen’s direct effect on mammary gland organogenesis. To overcome this limitation, we developed an ex vivo culture method of the mammary gland where the direct action of estrogens can be tested during embryonic days (E)14 to 19. Mouse mammary buds dissected at E14 and cultured for 5 days showed that estrogens directly altered fetal mammary gland development. Exposure to 0.1 pM, 10 pM, and 1 nM 17 β-estradiol (E2) resulted in monotonic inhibition of mammary buds ductal growth. In contrast, Bisphenol-A (BPA) elicited a non-monotonic response. At environmentally relevant doses (1 nM), BPA significantly increased ductal growth, as previously observed in vivo, while 1 μM BPA significantly inhibited ductal growth. Ductal branching followed the same pattern. This effect of BPA was blocked by Fulvestrant, a full estrogen antagonist, while the effect of estradiol was not. This method may be used to study the hormonal regulation of mammary gland development, and to test newly synthesized chemicals that are released into the environment without proper assessment of their hormonal action on critical targets like the mammary gland. PMID:28102330

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

    PubMed

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

    2009-05-01

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

  15. Growth hormone secretion and clearance rates in growing beef steers implanted with estrogenic anabolic compounds.

    PubMed

    Gopinath, R; Kitts, W D

    1984-01-01

    The effect of estrogenic anabolic compounds on the kinetic parameters of metabolism of growth hormone (GH) was studied in growing beef steers. Twenty-four beef steers were randomly placed into four groups and assigned to one of the following four treatment groups: zeranol, diethylstilbestrol (DES), Synovex-S and an unimplanted control. GH metabolism was studied from eight steers on day 20 following the implantation of anabolic compounds. The animals were rapidly injected with a solution of bGH (NIH-GH-B18) and the disappearance of injected GH from the plasma was monitored up to 120 min following the injection. The plasma GH disappearance curve displayed an initial rapid phase lasting 5 min and a slow disappearance phase lasting 42 min; the fractional turnover rate from the two compartments were 0.167 and 0.017 min-1, respectively. The average volume of distribution of GH in steers was 6% of the body weight. Mean values of metabolic clearance and secretion rates of GH in steers were 21 liters/h and 252 micrograms/h or 74.5 ml/kg/h and 0.91 microgram/kg/h, respectively. Steers implanted with anabolic compounds gained more rapidly (P less than 0.05) than the controls. Plasma basal GH concentration appeared to be higher in all the implanted than in the control steers. The secretion rate of GH was increased (P less than 0.05) in steers implanted with anabolic compounds when compared to control steers. The secretion rate (microgram/kg/h) was about 96% (P less than 0.05), 107% (P less than 0.05) and 81% (P less than 0.05) higher in steers implanted with DES, zeranol and Synovex-S, respectively, than in the control steers. All the compounds studied were equally effective in increasing the secretion of GH on day 20 following their implantation. Metabolic clearance rate of GH was not affected by anabolic compound implantation in steers. There was, however, a slight reduction in metabolic clearance rate due to DES and a slight elevation due to zeranol and Synovex-S when

  16. Spatiotemporal variations in estrogenicity, hormones, and endocrine-disrupting compounds in influents and effluents of selected wastewater-treatment plants and receiving streams in New York, 2008-09

    USGS Publications Warehouse

    Baldigo, Barry P.; Phillips, Patrick J.; Ernst, Anne G.; Gray, James L.; Hemming, Jocelyn D.C.

    2014-01-01

    Endocrine-disrupting compounds (EDCs) in wastewater effluents have been linked to changes in sex ratios, intersex (in males), behavioral modifications, and developmental abnormalities in aquatic organisms. Yet efforts to identify and regulate specific EDCs in complex mixtures are problematic because little is known about the estrogen activity (estrogenicity) levels of many common and emerging contaminants. The potential effects of EDCs on the water quality and health of biota in streams of the New York City water supply is especially worrisome because more than 150 wastewater-treatment plants (WWTPs) are permitted to discharge effluents into surface waters and groundwaters of watersheds that provide potable water to more than 9 million people. In 2008, the U.S. Geological Survey (USGS), the New York State Department of Environmental Conservation (NYSDEC), New York State Department of Health (NYSDOH), and New York City Department of Environmental Protection (NYCDEP) began a pilot study to increase the understanding of estrogenicity and EDCs in effluents and receiving streams mainly in southeastern New York. The primary goals of this study were to document and assess the spatial and temporal variability of estrogenicity levels; the effectiveness of various treatment-plant types to remove estrogenicity; the concentrations of hormones, EDCs, and pharmaceuticals, personal care products (PPCPs); and the relations between estrogenicity and concentrations of hormones, EDCs, and PPCPs. The levels of estrogenicity and selected hormones, non-hormone EDCs, and PPCPs were characterized in samples collected seasonally in effluents from 7 WWTPs, once or twice in effluents from 34 WWTPs, and once in influents to 6 WWTPs. Estrogenicity was quantified, as estradiol equivalents, using both the biological e-screen assay and a chemical model. Results generally show that (1) estrogenicity levels in effluents varied spatially and seasonally, (2) a wide range of known and unknown EDCs

  17. Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

    PubMed Central

    Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

    2014-01-01

    Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

  18. Freeze-drying as suitable method to achieve ready-to-use yeast biosensors for androgenic and estrogenic compounds.

    PubMed

    Jarque, Sergio; Bittner, Michal; Hilscherová, Klára

    2016-04-01

    Recombinant yeast assays (RYAs) have been proved to be a suitable tool for the fast screening of compounds with endocrine disrupting activities. However, ready-to-use versions more accessible to less equipped laboratories and field studies are scarce and far from optimal throughputs. Here, we have applied freeze-drying technology to optimize RYA for the fast assessment of environmental compounds with estrogenic and androgenic potencies. The effects of different cryoprotectants, initial optical density and long-term storage were evaluated. The study included detailed characterization of sensitivity, robustness and reproducibility of the new ready-to-use versions, as well as comparison with the standard assays. Freeze-dried RYAs showed similar dose-responses curves to their homolog standard assays, with Lowest Observed Effect Concentration (LOEC) and Median effective Concentration (EC50) of 1 nM and 7.5 nM for testosterone, and 0.05 nM and 0.5 nM for 17β-estradiol, respectively. Freeze-dried cells stored at 4 °C retained maximum sensitivity up to 2 months, while cells stored at -18 °C showed no decrease in sensitivity throughout the study (10 months). This ready-to-use RYA is easily accessible and may be potentially used for on-site applications.

  19. Physiological and biochemical perturbations in Daphnia magna following exposure to the model environmental estrogen diethylstilbestrol

    SciTech Connect

    Baldwin, W.S.; Milam, D.L.; LeBlanc, G.A.

    1995-06-01

    The estrogenic properties of many environmental contaminants, such as DDE and PCBs, have been associated with reproductive failure in a variety of vertebrate species. While estrogens have been measured in many invertebrate species, the function of this hormone in invertebrates is controversial. The objective of the present study was to identify possible physiological and biochemical target sites for the estrogenic effects of some xenobiotics on the freshwater crustacean Daphnia magna using the model environmental estrogen diethylstilbestrol (DES). Chronic exposure of daphnids to 0.50 mg/L DES reduced molting frequency among first-generation juveniles and decreased fecundity of second-generation daphnids. Adult first-generation daphnids chronically exposed to DES, as well as adult daphnids acutely exposed to DES for only 48 h, were examined for steroid hormone metabolic capabilities using testosterone as the model steroid. The rate of elimination of two major hydroxylated metabolites of testosterone was significantly reduced, and elimination of glucose conjugates of testosterone was significantly elevated from exposure to 0.50 mg/L DES. These results demonstrate that multigeneration exposure of daphnids to DES results in reduced fecundity and altered steroid metabolic capabilities. Thus, some arthropods, like vertebrates, are sensitive to the effects of endocrine-disrupting chemicals.

  20. Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway

    PubMed Central

    Huang, Ruili; Sakamuru, Srilatha; Martin, Matt T.; Reif, David M.; Judson, Richard S.; Houck, Keith A.; Casey, Warren; Hsieh, Jui-Hua; Shockley, Keith R.; Ceger, Patricia; Fostel, Jennifer; Witt, Kristine L.; Tong, Weida; Rotroff, Daniel M.; Zhao, Tongan; Shinn, Paul; Simeonov, Anton; Dix, David J.; Austin, Christopher P.; Kavlock, Robert J.; Tice, Raymond R.; Xia, Menghang

    2014-01-01

    The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα β-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERα agonists and antagonists was evaluated using a set of 39 reference compounds with known ERα activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERα binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERα active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals. PMID:25012808

  1. INTRODUCTION OF THE VITELLOGENIN GENE IN EARLY LIFE STAGE FATHEAD MINNOWS AS AN EFFECTIVE EXPOSURE INDICATOR FOR ESTROGENIC COMPOUNDS

    EPA Science Inventory

    Vitellogenin (Vg) gene expression in adult male fathead minnows (FHM) has previously been used successfully to detect exposures to estrogenic compounds in aquatic systems; however, sample volume(s)required for >24h exposure durations and the logistics of sampling pose some limita...

  2. INTERACTION OF PAH-RELATED COMPOUNDS WITH THE ALPHA AND BETA ISOFORMS OF ESTROGEN RECEPTOR. (R826192)

    EPA Science Inventory

    The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs), heterocyclic PAHs, and their monohydroxy derivatives to interact with the estrogen receptor (ER) alpha and beta isoforms was examined. Only compounds possessing a hydroxyl group were able to compete wit...

  3. Alkyllead compounds and their environmental toxicology.

    PubMed

    Abadin, Henry G; Pohl, Hana R

    2010-01-01

    Alkyllead compounds are man-made compounds in which a carbon atom of one or more organic molecules is bound to a lead atom. Tetraethyllead and tetramethyllead are the most common alkyllead compounds that were used primarily as gasoline additives for many years. Consequently, auto emissions have accounted for a major part of lead environmental pollution. Alkyllead compounds can readily enter living organisms as they are well absorbed via all major routes of entry. Because of their lipid solubility, the alkylleads can also readily cross the blood-brain barrier. The toxicokinetic information on organic lead can be used as biomarkers of exposure for monitoring exposed individuals. The organic alkyllead compounds are more toxic than the inorganic forms of lead. Neurotoxicity is the predominant effect of lead (both for organic and inorganic forms), although lead affects almost every organ of the body. The use of alkyllead compounds has declined over the last 20 years, due to the worldwide effort to eliminate the use of leaded gasoline. This achievement can be viewed as a great accomplishment of public health preventive measures.

  4. RAPID SCREENING OF ENVIRONMENTAL CHEMICALS FOR ESTROGEN RECEPTOR BINDING CAPACITY

    EPA Science Inventory

    Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wide range of environmental and industrial chemical...

  5. DNA damage and estrogenic activity induced by the environmental pollutant 2-nitrotoluene and its metabolite

    PubMed Central

    Watanabe, Chigusa; Egami, Takashi; Midorikawa, Kaoru; Hiraku, Yusuke; Oikawa, Shinji; Kawanishi, Shosuke

    2010-01-01

    Objectives The environmental pollutant 2-nitrotoluene (2-NO2-T) is carcinogenic and reproductively toxic in animals. In this study, we elucidated the mechanisms of its carcinogenicity and reproductive toxicity. Methods We examined DNA damage induced by 2-NO2-T and its metabolite, 2-nitrosotoluene (2-NO-T), using 32P-5′-end-labeled DNA. We measured 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in calf thymus DNA and cellular DNA in cultured human leukemia (HL-60) cells treated with 2-NO2-T and 2-NO-T. 8-Oxoguanine DNA glycosylase (OGG1) gene expression in HL-60 cells was measured by real-time polymerase chain reaction (PCR). We examined estrogenic activity using an E-screen assay and a surface plasmon resonance (SPR) sensor. Results In experiments with isolated DNA fragments, 2-NO-T induced oxidative DNA damage in the presence of Cu (II) and β-nicotinamide adenine dinucleotide disodium salt (reduced form) (NADH), while 2-NO2-T did not. 2-NO-T significantly increased levels of 8-oxodG in HL-60 cells. Real-time polymerase chain reaction (PCR) analysis revealed upregulation of OGG1 gene expression induced by 2-NO-T. An E-screen assay using the human breast cancer cell line MCF-7 revealed that 2-NO2-T induced estrogen-dependent cell proliferation. In contrast, 2-NO-T decreased the cell number and suppressed 17β-estradiol-induced cell proliferation. The data obtained with the SPR sensor using estrogen receptor α and the estrogen response element supported the results of the E-screen assay. Conclusions Oxidative DNA damage caused by 2-NO-T and estrogen-disrupting effects caused by 2-NO2-T and 2-NO-T may play a role in the reproductive toxicity and carcinogenicity of these entities. PMID:21432561

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

    PubMed

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

    2005-01-26

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

  7. BPA and environmental estrogen in potable water sources in Enugu municipality, South-East, Nigeria.

    PubMed

    Ignatius, C Maduka; Francis, E Ezeonu; Emeka, E Neboh; Elvis, N Shu; Ebele, J Ikekpeazu

    2010-11-01

    BPA and environmental estrogen levels were assayed in potable water samples (38 tap water, 36 well water, 18 river water and 24 rain water samples) that were randomly collected from the different parts of Enugu metropolis, south-east Nigeria. The mean ± SD estrogen levels in tap, well, river and rain water samples were 0.10 ± 0.09, 0.05 ± 0.02, 0.05 ± 0.02 and 0.05 ± 0.02 μg/L respectively. Also, the mean BPA levels (μg/L) in the different water sources were 0.20 ± 0.07, 0.21 ± 0.07, 0.18 ± 0.04, and 0.40 ± 0.16, respectively. There was statistically significant difference (p = 0.0227) in BPA levels between the harvested rain water and the drinking tap water.

  8. Isolation and Characterization of New Phenolic Compounds with Estrogen Biosynthesis-Inhibiting and Antioxidation Activities from Broussonetia papyrifera Leaves

    PubMed Central

    Yang, Chunyan; Li, Fu; Du, Baowen; Chen, Bin; Wang, Fei; Wang, Mingkui

    2014-01-01

    Broussonetia papyrifera leaves (BPL) as a traditional Chinese medicine are also used in livestock feed for stimulating reproduction, adipose tissue and muscle development; however, the mechanism of their action is still unknown. Through estrogen biosynthesis-guided fractionation in human ovarian granulosa-like KGN cells, five new phenolic glycosides, broussoside A–E(1–5), along with fifteen known dietary phenolic compounds, were isolated from the n-butanol extract of BPL, and their structures were elucidated on the basis of NMR spectra analysis and chemical evidence. New compounds 3, 4, 5 and the known compounds 9 and 10 were found to potently inhibit estrogen biosynthesis in KGN cells. In addition, compounds 9, 17, 18, and 20 showed strong antioxidant activity against ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and DPPH (1, 1′-diphenyl -2-picryl-hydrazyl radical) assays. These findings suggest that BPL may improve meat quality through the regulation of estrogen biosynthesis. Furthermore, they may be useful for the discovery of potential aromatase modulators from natural products. Finally, they could be considered as a new source for natural antioxidants. PMID:24714659

  9. Simultaneous analysis of eight phenolic environmental estrogens in blood using dispersive micro-solid-phase extraction combined with ultra fast liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Yong-Gang; Chen, Xiao-Hong; Pan, Sheng-Dong; Zhu, Hao; Shen, Hao-Yu; Jin, Mi-Cong

    2013-10-15

    A novel, simple and sensitive method was developed for the simultaneous determination of eight phenolic environmental estrogens in blood by using the dispersive micro-solid-phase extraction (d-µ-SPE) procedure combined with ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS). The excellent nanomaterials tetraethylenepentamine-functionalized magnetic polymer was used as an adsorbent, and the main factors affecting the extraction efficiency were investigated in detail. All target compounds showed good linearities in the tested range with correlation coefficients (r) higher than 0.999. The mean recoveries were in the range of 85.0-105.0%. The intra-day and inter-day relative standard deviations (RSDs) were lower than 4.9% and 5.2%, respectively. The limits of quantification for the eight phenolic environmental estrogens were between 0.075 and 0.42 µg L(-1). The developed method can be applied to the routine analyses for the determination of the eight phenolic environmental estrogens in blood samples.

  10. Ethanolic extract of Coelogyne cristata Lindley (Orchidaceae) and its compound coelogin promote osteoprotective activity in ovariectomized estrogen deficient mice.

    PubMed

    Sharma, Chetan; Mansoori, Mohd Nizam; Dixit, Manisha; Shukla, Priyanka; Kumari, Tejaswita; Bhandari, S P S; Narender, T; Singh, Divya; Arya, K R

    2014-10-15

    Coelogyne cristata Lindley (CC) family Orchidaceae is an Indian medicinal plant used for the treatment of fractured bones in folk-tradition of Kumaon region, Uttarakhand, India. In continuation of our drug discovery program, feeding of ethanolic extract to ovariectomized estrogen deficient mice led to significant restoration of trabecular micro architecture in both femoral and tibial bones, better bone quality and also devoid of any uterine estrogenicity. Subsequently, coelogin, a pure compound was isolated from ethyl acetate fraction of C. cristata and evaluated in in vitro osteoblast cell cultures. Treatment of coelogin to osteoblasts led to enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen and RUNX-2. Based on these results, we propose that ethanolic extract of C. cristata and its pure compound coelogin have potential in the management of post menopausal osteoporosis.

  11. Electrochemical detection of phenolic estrogenic compounds at clay modified carbon paste electrode

    NASA Astrophysics Data System (ADS)

    Belkamssa, N.; Ouattara, L.; Kawachi, A.; Tsujimura, M.; Isoda, H.; Chtaini, A.; Ksibi, M.

    2015-04-01

    A simple and sensitive electroanalytical method was developed to determine the Endocrine Disrupting chemical 4-tert-octylphenol on clay modified carbon paste electrode (Clay/CPE). The electrochemical response of the proposed electrode was studied by means of cyclic and square wave voltammetry. It has found that the oxidation of 4-tert-octylphenol on the clay/CPE displayed a well-defined oxidation peak. Under these optimal conditions, a linear relation between concentrations of 4-tert-octylphenol current response was obtained over range of 7.26×10-6 to 3.87×10-7 with a detection and quantification limit of 9.2×10-7 M and 3.06×10-6 M, respectively. The correlation coefficient is 0.9963. The modified electrode showed suitable sensitivity, high stability and an accurate detection of 4-tert-octylphenol. The modified electrode also relevant suitable selectivity for various phenolic estrogenic compounds.

  12. From pure compounds to complex exposure: Effects of dietary cadmium and lignans on estrogen, epidermal growth factor receptor, and mitogen activated protein kinase signaling in vivo.

    PubMed

    Ali, Imran; Hurmerinta, Teija; Nurmi, Tarja; Berglund, Marika; Rüegg, Joelle; Poutanen, Matti; Halldin, Krister; Mäkelä, Sari; Damdimopoulou, Pauliina

    2016-06-24

    Exposure to environmental endocrine active compounds correlates with altered susceptibility to disease in human populations. Chemical risk assessment is single compound based, although exposure often takes place as heterogeneous mixtures of man-made and natural substances within complex matrices like diet. Here we studied whether the effects of cadmium and enterolactone on endocrine endpoints in dietary exposure can be predicted based on pure compound effects. Ovariectomized estrogen reporter ERE-luciferase (ERE-luc) mice were maintained on diets that intrinsically contain increasing concentrations of cadmium and enterolactone precursors for three and 21 days. The activation of the ERE-luc, epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK)-ERK1/2, and classical estrogen responses were measured. Interactions between the diets and endogenous hormone were evaluated by challenging the animals with 17β-estradiol. Compared to animals on basal purified diet, mice consuming experimental diets were exposed to significantly higher levels of cadmium and enterolactone, yet the exposure remained comparable to typical human dietary intake. Surprisingly, we could not detect effects on endpoints regulated by pure enterolactone, such as ERE-luc activation. However, cadmium accumulation in the liver was accompanied with activation of EGFR and MAPK-ERK1/2 in line with our earlier CdCl2 studies. Further, attenuation of 17β-estradiol-induced ERE-luc response in liver by experimental diets was observed. Our findings indicate that the exposure context can have substantial effects on the activity of endocrine active compounds in vivo. Thus, whenever possible, a context that mimics human exposure should be tested along with pure compounds.

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

    SciTech Connect

    CGCampbell@lbl.gov

    2004-01-30

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

  14. Evaluation of estrogenic, antiestrogenic and genotoxic activity of nemorosone, the major compound found in brown Cuban propolis

    PubMed Central

    2013-01-01

    Background Brown propolis is the major type of propolis found in Cuba; its principal component is nemorosone, the major constituent of Clusia rosea floral resins. Nemorosone has received increasing attention due to its strong in vitro anti-cancer action. The citotoxicity of nemorosone in several human cancer cell lines has been reported and correlated to the direct action it has on the estrogen receptor (ER). Breast cancer can be treated with agents that target estrogen-mediated signaling, such as antiestrogens. Phytoestrogen can mimic or modulate the actions of endogenous estrogens and the treatment of breast cancer with phytoestrogens may be a valid strategy, since they have shown anti-cancer activity. Methods The aim of the present investigation was to assess the capacity of nemorosone to interact with ERs, by Recombinant Yeast Assay (RYA) and E-screen assays, and to determine by comet assay, if the compound causes DNA-damaging in tumoral and non-tumoral breast cells. Results Nemorosone did not present estrogenic activity, however, it inhibited the 17-β-estradiol (E2) action when either of both methods was used, showing their antiestrogenicity. The DNA damage induced by the benzophenone in cancer and normal breast cells presented negative results. Conclusion These findings suggest that nemorosone may have therapeutic application in the treatment of breast cancer. PMID:23902919

  15. Estrogen receptor positive breast cancers and their association with environmental factors

    PubMed Central

    2011-01-01

    Background Epidemiological studies to assess risk factors for breast cancer often do not differentiate between different types of breast cancers. We applied a general linear model to determine whether data from the Surveillance, Epidemiology, and End Results Program on annual county level age-adjusted incidence rates of breast cancer with and without estrogen receptors (ER+ and ER-) were associated with environmental pollutants. Results Our final model explained approximately 38% of the variation in the rate of ER+ breast cancer. In contrast, we were only able to explain 14% of the variation in the rate of ER- breast cancer with the same set of environmental variables. Only ER+ breast cancers were positively associated with the EPA's estimated risk of cancer based on toxic air emissions and the proportion of agricultural land in a county. Meteorological variables, including short wave radiation, temperature, precipitation, and water vapor pressure, were also significantly associated with the rate of ER+ breast cancer, after controlling for age, race, premature mortality from heart disease, and unemployment rate. Conclusions Our findings were consistent with what we expected, given the fact that many of the commonly used pesticides and air pollutants included in the EPA cancer risk score are classified as endocrine disruptors and ER+ breast cancers respond more strongly to estrogen than ER- breast cancers. The findings of this study suggest that ER+ and ER- breast cancers have different risk factors, which should be taken into consideration in future studies that seek to understand environmental risk factors for breast cancer. PMID:21569288

  16. Characterizing the Estrogenic Potential of 1060 Environmental Chemicals by Assessing Growth Kinetics in T47D Cells

    EPA Science Inventory

    In order to detect environmental chemicals that pose a risk of endocrine disruption, high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals are needed. Alteration of estrogen signaling has been implicated in a variety of adverse health effec...

  17. INVESTIGATION OF TRANSFORMATION PRODUCTS FROM THE CHLORINATION OF ESTROGENIC AND ANDROGENIC COMPOUNDS

    EPA Science Inventory

    Drinking water sources are increasingly impacted by upstream anthropogenic activities, including wastewater discharge, concentrated animal feeding operations (CAFOs) and landfill leachate. Androgenic and estrogenic activities have been detected in surface waters downstream from ...

  18. Estrogenic compounds in Tunisian urban sewage treatment plant: occurrence, removal and ecotoxicological impact of sewage discharge and sludge disposal.

    PubMed

    Belhaj, Dalel; Athmouni, Khaled; Jerbi, Bouthaina; Kallel, Monem; Ayadi, Habib; Zhou, John L

    2016-12-01

    The occurrence, fate and ecotoxicological assessment of selected estrogenic compounds were investigated at Tunisian urban sewage treatment plant. The influents, effluents, as well as primary, secondary and dehydrated sludge, were sampled and analyzed for the target estrogens to evaluate their fate. All target compounds were detected in both sewage and sludge with mean concentrations from 0.062 to 0.993 μg L(-1) and from 11.8 to 792.9 μg kg(-1)dry weight, respectively. A wide range of removal efficiencies during the treatment processes were observed, from 6.3 % for estrone to 76.8 % for estriol. Ecotoxicological risk assessment revealed that the highest ecotoxicological risk in sewage effluent and dehydrated sludge was due to 17β-estradiol with a risk quotient (RQ) of 4.6 and 181.9, respectively, and 17α-ethinylestradiol with RQ of 9.8 and 14.85, respectively. Ecotoxicological risk after sewage discharge and sludge disposal was limited to the presence of 17β-estradiol in dehydrated-sludge amended soil with RQ of 1.38. Further control of estrogenic hormones in sewage effluent and sludge is essential before their discharge and application in order to prevent their introduction into the natural environment.

  19. Estrogenic compounds determination in water samples by dispersive liquid-liquid microextraction and micellar electrokinetic chromatography coupled to mass spectrometry.

    PubMed

    D'Orazio, Giovanni; Asensio-Ramos, María; Hernández-Borges, Javier; Fanali, Salvatore; Rodríguez-Delgado, Miguel Ángel

    2014-05-30

    In this work, a group of 12 estrogenic compounds, i.e., four natural sexual hormones (estrone, 17β-estradiol, 17α-estradiol and estriol), an exoestrogen (17α-ethynylestradiol), a synthetic stilbene (dienestrol), a mycotoxin (zearalenone) and some of their major metabolites (2-methoxyestradiol, α-zearalanol, β-zearalanol, α-zearalenol and β-zearalenol) have been separated and determined by micellar electrokinetic chromatography (MEKC) coupled to electrospray ion trap mass spectrometry. For this purpose, a background electrolyte containing an aqueous solution of 45 mM of perfluorooctanoic acid (PFOA) adjusted to pH 9.0 with an ammonia solution, as MS friendly surfactant, and methanol (10% (v/v)), as organic modifier, was used. To further increase the sensitivity, normal stacking mode was applied by injecting the sample dissolved in an aqueous solution of 11.5mM of ammonium PFO (APFO) at pH 9.0 containing 10% (v/v) of methanol for 25s. Dispersive liquid-liquid microextraction, using 110 μL of chloroform and 500 μL of acetonitrile as extraction and dispersion solvents, respectively, was employed to extract and preconcentrate the target analytes from different types of environmental water samples (mineral, run-off and wastewater) containing 30% (w/v) NaCl and adjusted to pH 3.0 with 1M HCl. The limits of detection achieved were in the range 0.04-1.10 μg/L. The whole method was validated in terms of linearity, precision, recovery and matrix effect for each type of water, showing determination coefficients higher than 0.992 for matrix-matched calibration and absolute recoveries in the range 43-91%.

  20. Vitamin D modulation of the activity of estrogenic compounds in bone cells in vitro and in vivo.

    PubMed

    Somjen, Dalia

    2007-01-01

    Vitamin D analogs modulate different organs, including modulation of energy metabolism, through the induction of creatine kinase (CK) activity. Skeletal organs from vitamin D-depleted rats showed lower constituent CK than those from vitamin D-replete rats. Moreover, estradiol-17beta (E2) or dihydrotestosterone (DHT), which increased CK in organs from intact female or male rats, respectively, stimulated much less CK in vitamin D-depleted rats. Treatment of intact female rats with noncalcemic vitamin D analogs significantly upregulated E2- and DHT-induced CKresponse. These analogs upregulated the CK response to selective estrogen receptor modulators (SERMs) in organs from intact or ovariectomized (Ovx) female rats but abolished SERMs' inhibitory effect on E2-induced CK. These analogs significantly increased estradiol receptor alpha (ERalpha) protein in skeletal organs as well as histomorphological and biochemical changes due to this treatment followed by E2 or DHT. The analogs alone markedly altered the growth plate and the trabeculae and increased trabecular bone volume (%TB V) and trabecular width. The addition of E2 or DHT to this treatment restored all parameters as well as increased %TBV and cell proliferation. Treatment of Ovx female rats with JK 1624 F2-2 (JKF) decreased growth-plate width and increased %TB V, whereas QW1624 F2-2 (QW) restored growth-plate width and %TB V. Treatment of E2 with JKF restored %TBV and growth-plate width, whereas E2 with QW restored all parameters, including cortical width. There was also upregulation of the response of CK to E2 in both combined treatments. Our human-derived osteoblast (hObs)-like cell cultures respond to estrogenic compounds, and pretreating them with JKF upregulated the CK response to E2, raloxifene (Ral), and some phytoestrogens. ERalpha and ERbeta proteins, as well as mRNA, were modulated by CB 1093 (CB) and JKF. JKF increased specific nuclear E2 binding in female hObs but inhibited specific membranal E2

  1. Calculation methods to perform mass balance of endocrine disrupting compounds in a submerged membrane bioreactor: fate and distribution of estrogens during the biological treatment.

    PubMed

    Estrada-Arriaga, E B; Mijaylova, P

    2011-01-01

    The purpose of this paper is to report the study of the fate and distribution of three endocrine disrupting compounds (estrogens); Estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) in a laboratory scale submerged membrane bioreactor (SMBR). For this matter, both aqueous and solids phases were analyzed for the presence of E1, E2 and EE2. The outcome of this study was that three SMBRs showed enhanced elimination of estrogens in different operational conditions; the estrogen removal was close to 100% in SMBR. Additionally, E1, E2 and EE2 were detected in SMBR sludge at concentrations of up to 41.2, 37.3 and 36.9 ng g(-1) dry weight, respectively. The estrogen removal in the SMBRs was directly influenced by a combination of simultaneous biodegradation-adsorption processes, indicating that the main removal mechanism of the estrogens in the SMBRs is the biodegradation process. The E1, E2 and EE2 were biologically degraded in the SMBR (87-100%). The sorption of estrogens onto activated sludge was from 2%. Therefore, a high potential for estrogen removal by biodegradation in the SMBR was observed, allowing less estrogen concentration in the dissolved phase available for the adsorption of these compounds onto biological flocs. Two different methods were carried out for mass balance calculations of estrogens in SMBR. For the first method, the measured data was used in both liquid and solid phases, whereas for the second one, it was in aqueous phase and solid-water distribution coefficients (K(d)) value of E1, E2 and EE2. The purpose of these methodologies is to make easier the identification of the main mechanisms involved in the removal of E1, E2 and EE2 in a SMBR. Both methods can be applied in order to determine the mechanism, fate and distribution of estrogens in a SMBR.

  2. Effects of natural and synthetic estrogens and various environmental contaminants on vitellogenesis in fish primary hepatocytes: comparison of bream (Abramis brama) and carp (Cyprinus carpio).

    PubMed

    Rankouhi, T Rouhani; Sanderson, J T; van Holsteijn, I; van Leeuwen, C; Vethaak, A D; van den Berg, M

    2004-09-01

    Interaction of environmental estrogens with the estrogen receptor (ER) has been shown in various fish species. Our objective was to compare the sensitivity of bream (Abramis brama) to (xeno-)estrogens with that of the carp (Cyprinus carpio), by measuring the effects of 17beta-estradiol (E2), estrone (E1), ethynylestradiol (EE2), bisphenol A (BPA), nonylphenol (NP), methoxychlor (MXCL), and halogenated aromatic hydrocarbons (HAHs) such as polychlorinated biphenyls (PCB126, PCB118), 2,3,7,8-tetrachlorodibenzo-dioxin (TCDD), and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) on vitellogenesis in primary hepatocytes. Comparing the EC50 values in bream hepatocytes: EE2 (0.1-0.2 microM) < E1 (0.6-0.2 microM) < E2 (1.9 microM) with those of carp hepatocytes EE2 (0.03-0.06 microM) < E2 (0.3 microM) approximately E1 (0.2-0.3 microM) we found differences in sensitivity and ranking of the estrogenic potency of E2 and E1, indicating interspecies differences. Exposure to BPA, NP, MXCL, and HAHs did not or only weakly induce vitellogenesis. Bream hepatocytes coexposed to E2 and TCDD, PCB126 or PCDF showed a concentration-dependent inhibition of E2-induced vitellogenesis. IC50 (concentration of a compound that elicits 50% inhibition of E2-induced vitellogenesis) values determined in bream were: TCDD (0.02-0.09 nM) < PCB126 (0.35-0.1 nM) < PCDF (2.0-0.1) and in carp were: TCDD (0.01 nM) < PCB126 (0.4 nM). PCB118 showed no (anti-)estrogenic response. IC50 values and benchmark-concentration for TCDD and PCB126 in bream and carp hepatocytes were in the same range, indicating similar sensitivity to these compounds. Due to their anti-estrogenic capacity with benchmark-concentrations in the pM range TCDD, PCDF, and PCB126 may form a potential hazard for the reproductive success of fish species by inhibition of vitellogenesis.

  3. Is there an association between exposure to environmental estrogens and breast cancer?

    PubMed Central

    Safe, S H

    1997-01-01

    It was initially reported that levels of polychlorinated biphenyls (PCBs) or p,p'-DDE were elevated in breast cancer patients (serum or tissue) versus controls. These results, coupled with reports that selected environmental estrogens decreased 17beta-estradiol (E2) 2-hydroxylase activity and increased the ratio of 16alpha-hydroxyestrone/2-hydroxyestrone metabolites in MCF-7 human breast cancer cells, have led to the hypothesis that xenoestrogens are a preventable cause of breast cancer. More recent studies and analysis of organochlorine levels in breast cancer patients versus controls show that these contaminants are not elevated in the latter group. Moreover, occupational exposure to relatively high levels of PCBs and DDT/DDE are not associated with an increased incidence of breast cancer. A reexamination of the radiometric E2 2-hydroxylase assay in MCF-7 cells with diverse estrogens, antiestrogens, and carcinogens showed that the mammary carcinogen benzo[a]pyrene induced this response and the antiestrogen ICI 164,384 decreased E2 2-hydroxylase activity. Thus, E2 2-hydroxylase activity and the 16alpha-hydroxyestrone/2-hydroxyestrone metabolite ratio in MCF-7 cells does not predict xenoestrogens or mammary carcinogens. PMID:9168013

  4. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

    SciTech Connect

    Penza, M.; Jeremic, M.; Marrazzo, E.; Maggi, A.; Ciana, P.; Rando, G.; Grigolato, P.G.; Di Lorenzo, D.

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to

  5. Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood.

    PubMed Central

    Fisher, J S; Turner, K J; Brown, D; Sharpe, R M

    1999-01-01

    Neonatal exposure to diethylstilbestrol (DES) can alter the structure of the testicular excurrent ducts in rats. We characterized these changes according to dose and time posttreatment and established whether potent estrogens (ethinyl estradiol), environmental estrogens (genistein, octylphenol, bisphenol A, parabens), and tamoxifen induce such changes. Rats were administered these compounds neonatally and assessed at several time points during (day 10, or day 18 for some treatments) and after (days 18, 25, 35, and 75) the treatment period to detect any changes in testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water channel aquaporin-1 (AQP-1). Treatment with DES (10, 1, or 0.1 microg/injection; equivalent to 0.37, 0.037, or 0.0037 mg/kg/day, respectively) induced dose-dependent changes in testis weight and all parameters. These effects were most pronounced at days 18 and 25 and appeared to lessen with time, although some persisted into adulthood. Neonatal treatment with ethinyl estradiol (10 microg/injection; equivalent to 0.37 mg/kg/day) caused changes broadly similar to those induced by 10 mg DES. Administration of tamoxifen (2 mg/kg/day) caused changes at 18 days that were similar to those induced by 1 microg DES. Treatment with genistein (4 mg/kg/day), octylphenol (2 mg/injection; equivalent to 150 mg/kg/day), or bisphenol A (0.5 mg/injection; equivalent to 37 mg/kg/day) caused minor but significant (p<0.05) decreases in epithelial cell height of the efferent ducts at days 18 and/or 25. In animals that were followed through to 35 days and/or adulthood, these changes were no longer obvious; other parameters were either unaffected or were affected only marginally and transiently. Administration of parabens (2 mg/kg/day) had no detectable effect on any parameter at day 18. To establish whether these effects of estrogens were direct or indirect (i.e., resulting from reduced

  6. INVESTIGATION OF TRANSFORMATION PRODUCTS FROM THE CHLORINATION OF ESTROGENIC AND ANDROGENIC COMPOUNDS- Poster

    EPA Science Inventory

    The objective of this research is to investigate chlorinated by-products of a selected number of steroids representing both estrogens and androgens. Highly controlled reaction conditions were used to ascertain product distribution. Bench-scale studies were conducted to identify...

  7. Characterizing the Growth Kinetics in Estrogen Responsive T47D Cells After Exposure to 2000 Environmental Chemicals

    EPA Science Inventory

    There is a need to develop high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals for endocrine disrupting potential. The estrogen signaling pathway is a known xenobiotic target that has been implicated in a variety of adverse health effects...

  8. ANALYSIS OF CHANGES IN GENE EXPRESSION PATTERNS IN FISH EXPOSED TO NATURAL PHARMACEUTICAL AND ENVIRONMENTAL ESTROGENS USING GENE ARRAYS.

    EPA Science Inventory

    Denslow, N.D., P. Larkin, T.L. Sabo-Attwood, J. Kocerha, K.J. Kroll, M.J. Hemmer and L.C. Folmar. 2004. Analysis of Changes in Gene Expression Patterns in Fish Exposed to Natural, Pharmaceutical and Environmental Estrogens Using Gene Arrays (Abstract). Mar. Environ. Res. 58(2-5):...

  9. Magnetic solid-phase extraction based on a triethylenetetramine-functionalized magnetic graphene oxide composite for the detection of ten trace phenolic environmental estrogens in environmental water.

    PubMed

    Chen, Xiao-Hong; Pan, Sheng-Dong; Ye, Mei-Jun; Li, Xiao-Ping; Zhao, Yong-Gang; Jin, Mi-Cong

    2016-02-01

    A novel triethylenetetramine-functionalized magnetic graphene oxide composite was prepared and used as a magnetic solid-phase extraction adsorbent for the fast detection of ten trace-level phenolic environmental estrogens in environmental water. The synthesized material was carefully characterized by scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and X-ray photoelectron spectroscopy to confirm the structure and components. The adsorption and desorption conditions of the adsorbent toward phenolic environmental estrogens were optimized in detailed to obtain the best extraction recovery and elution efficiency. Under the optimum conditions, the limits of detection of the method for ten phenolic environmental estrogens were in range of 0.15-1.5 ng/L, which was lower than the reported methods for phenolic environmental estrogens detection in literatures. This could be contributed to the unique structure and property of the as-prepared material. The developed method was successfully applied for the determination of environmental water samples with recoveries ranging from 88.5 to 105.6%.

  10. 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

  11. A 155-plex high-throughput in vitro coregulator binding assay for (anti-)estrogenicity testing evaluated with 23 reference compounds.

    PubMed

    Wang, Si; Houtman, René; Melchers, Diana; Aarts, Jac; Peijnenburg, Ad; van Beuningen, Rinie; Rietjens, Ivonne; Bovee, Toine F

    2013-01-01

    To further develop an integrated in vitro testing strategy for replacement of in vivo tests for (anti-)estrogenicity testing, the ligand-modulated interaction of coregulators with estrogen receptor α was assessed using a PamChip® plate. The relative estrogenic potencies determined, based on ERα binding to coregulator peptides in the presence of ligands on the PamChip® plate, were compared to the relative estrogenic potencies as determined in the in vivo uterotrophic assay. The results show that the estrogenic potencies predicted by the 57 coactivators on the peptide microarray for 18 compounds that display a clear E2 dose-dependent response (goodness of fit of a logistic dose-response model of 0.90 or higher) correlated very well with their in vivo potencies in the uterotrophic assay, i.e., coefficient of determination values for 30 coactivators higher than or equal to 0.85. Moreover, this coregulator binding assay is able to distinguish ER agonists from ER antagonists: profiles of selective estrogen receptor modulators, such as tamoxifen, were distinct from those of pure ER agonists, such as dienestrol. Combination of this coregulator binding assay with other types of in vitro assays, e.g., reporter gene assays and the H295R steroidogenesis assay, will frame an in vitro test panel for screening and prioritization of chemicals, thereby contributing to the reduction and ultimately the replacement of animal testing for (anti-)estrogenic effects.

  12. Environmentally friendly organic synthesis using bismuth(III) compounds.

    PubMed

    Krabbe, Scott W; Mohan, Ram S

    2012-01-01

    With increasing environmental concerns, the need for environmentally friendly organic synthesis has gained increased importance. In this regard, bismuth(III) compounds are especially attractive as "green" reagents and catalysts for organic synthesis. Bismuth(III) compounds are remarkably nontoxic, relatively air and moisture stable, and easy to handle. The contributions from our laboratory in the last 5 years in the field of applications of bismuth(III) compounds as catalysts are presented.

  13. Selective pressurized liquid extraction of estrogenic compounds in soil and analysis by gas chromatography-mass spectrometry.

    PubMed

    Zhang, Zulin; Rhind, Stewart M; Kerr, Christine; Osprey, Mark; Kyle, Carol E

    2011-01-24

    A selective pressurized liquid extraction (SPLE) method, followed by gas chromatography-mass spectrometry (GC-MS), for the simultaneous extraction and clean-up of estrone (E1), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), estriol (E3) and bisphenol A (BPA) from soil samples is described. The on-line clean-up of soil by SPLE was achieved using different organic matter retainers, including silica, alumina and Florisil, the most effective being silica. Thus, different amounts of silica, in conjunction with different extraction solvents (acetone, ethyl acetate, isohexane and dichloromethane), either alone or in combination, were used to extract the target chemicals from spiked soil samples. It was shown that 3g silica resulted in satisfactory rates of recovery of target compounds and acetone:dichloromethane (1:3, v/v) was efficient in extracting and eluting estrogenic compounds for SPLE. Variables affecting the SPLE efficiency, including temperature and pressure were studied; the optimum parameters were 60°C and 1500 psi, respectively. The limits of detection (LODs) of the proposed method were 0.02-0.37 ng g(-1) for the different estrogenic chemicals studied. The outputs using the proposed method were linear over the range from 0.1 to 120 ng g(-1) for E1, E2, EE2, 0.2-120 ng g(-1) for E3, and 0.5-120 ng g(-1) for BPA. The optimized method was further verified by performing spiking experiments in natural soil matrices; good rates of recovery and reproducibility were achieved for all selected compounds and the method was successfully applied to soil samples from Northeast Scotland, for the determination of the target compounds.

  14. Environmental Exposure, Estrogen and Two X Chromosomes are Required for Disease Development in an Epigenetic Model of Lupus

    PubMed Central

    Strickland, Faith M.; Hewagama, Anura; Lu, Qianjian; Wu, Ailing; Hinderer, Robert; Webb, Ryan; Johnson, Kent; Sawalha, Amr H.; Delaney, Colin; Yung, Raymond; Richardson, Bruce C.

    2011-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6 × SJL)F1 mice transgenic for a dominant-negative MEK (dnMEK) that was previously shown to be inducibly and selectively expressed in T cells. In this model, induction of the dnMEK by doxycycline treatment suppresses T cell ERK signaling, decreasing DNA methyltransferase expression and resulting in DNA demethylation, overexpression of immune genes Itgal (CD11a) and Tnfsf7 (CD70), and anti-dsDNA antibody. To examine the role of gender and estrogen in this model, male and female transgenic mice were neutered and implanted with time-release pellets delivering placebo or estrogen. Doxycycline induced IgG anti-dsDNA antibodies in intact and neutered, placebo-treated control female but not male transgenic mice. Glomerular IgG deposits were also found in the kidneys of female but not male transgenic mice, and not in the absence of doxycycline. Estrogen enhanced anti-dsDNA IgG antibodies only in transgenic, ERK-impaired female mice. Decreased ERK activation also resulted in overexpression and demethylation of the X-linked methylation-sensitive gene CD40lg in female but not male mice, consistent with demethylation of the second X chromosome in the females. The results show that both estrogen and female gender contribute to the female predisposition in lupus susceptibility through hormonal and epigenetic X chromosome effects and through suppression of ERK signaling by environmental agents. PMID:22142890

  15. Environmental exposure, estrogen and two X chromosomes are required for disease development in an epigenetic model of lupus.

    PubMed

    Strickland, Faith M; Hewagama, Anura; Lu, Qianjian; Wu, Ailing; Hinderer, Robert; Webb, Ryan; Johnson, Kent; Sawalha, Amr H; Delaney, Colin; Yung, Raymond; Richardson, Bruce C

    2012-05-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for a dominant-negative MEK (dnMEK) that was previously shown to be inducibly and selectively expressed in T cells. In this model, induction of the dnMEK by doxycycline treatment suppresses T cell ERK signaling, decreasing DNA-methyltransferase expression and resulting in DNA demethylation, overexpression of immune genes Itgal (CD11a) and Tnfsf7 (CD70), and anti-dsDNA antibody. To examine the role of gender and estrogen in this model, male and female transgenic mice were neutered and implanted with time-release pellets delivering placebo or estrogen. Doxycycline induced IgG anti-dsDNA antibodies in intact and neutered, placebo-treated control female but not male transgenic mice. Glomerular IgG deposits were also found in the kidneys of female but not male transgenic mice, and not in the absence of doxycycline. Estrogen enhanced anti-dsDNA IgG antibodies only in transgenic, ERK-impaired female mice. Decreased ERK activation also resulted in overexpression and demethylation of the X-linked methylation-sensitive gene CD40lg in female but not male mice, consistent with demethylation of the second X chromosome in the females. The results show that both estrogen and female gender contribute to the female predisposition in lupus susceptibility through hormonal and epigenetic X-chromosome effects and through suppression of ERK signaling by environmental agents.

  16. EFFECTS OF EXPOSURE TO ENVIRONMENTAL ESTROGENS ON REPRODUCTIVE PARAMETERS IN A MARINE FISH, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    Estradiol (E2), ethynylestradiol (EE2) and estrone (E4) are steroidal estrogens that are released into the aquatic environment in sewage treatment effluent. To determine whether these estrogens could impact reproductive parameters in a model fish species, actively spawning male ...

  17. No evidence of exposure to environmental estrogens in two feral fish species sampled from the Yarra River, Australia: A comparison with Northern Hemisphere studies.

    PubMed

    Hassell, Kathryn; Pettigrove, Vincent; Beresford, Nicola; Jobling, Susan; Kumar, Anu

    2016-09-01

    Environmental estrogens originate from a variety of sources including sewage treatment plant (STP) effluents and adverse physiological effects (endocrine disruption) have been observed in several fish species sampled downstream of STP discharges. In this study we examined common carp (Cyprinus carpio) and roach (Rutilis rutilis) for signs of exposure to environmental estrogens in the iconic Yarra River, Melbourne, Australia. The Yarra River flows through the city of Melbourne and more than 2 million people live within the catchment. Two STPs discharge water into the Yarra River within the middle reaches, and the areas immediately downstream of these discharge locations were the focus of this study. Carp and roach were chosen as test species since both have been utilised extensively for endocrine disruption research throughout Europe, North America and Asia, and data from various international studies was used for comparison with the results of the present study. Neither species showed evidence of exposure to environmental estrogens, with no elevation of plasma vitellogenin levels in males and no incidence of intersex gonads. Most physiological endpoints in both species from this study were within ranges reported in carp and roach from reference sites in other studies, however some degenerative histological changes in both male and female gonads were observed. Surface water samples showed no estrogenic activity (measured by the yeast-estrogen screen, YES), but did display strong anti-estrogenic and weak androgenic activity (measured by the yeast-androgen screen, YAS). Whilst the results show no evidence of impacts from environmental estrogens in the Yarra River, the presence of both anti-estrogenic and androgenic activity in water samples, as well as some gonadal changes in carp is concerning and indicates that our focus needs to broaden, in order to look for biological impacts in resident fauna that might be due to environmental pollutants other than environmental

  18. Endocrine-disrupting chemical exposure and the American alligator: a review of the potential role of environmental estrogens on the immune system of a top trophic carnivore.

    PubMed

    Finger, John W; Gogal, Robert M

    2013-11-01

    Endocrine-disrupting chemicals (EDCs) alter cellular and organ system homeostasis by interfering with the body's normal physiologic processes. Numerous studies have identified environmental estrogens as modulators of EDC-related processes in crocodilians, notably in sex determination. Other broader studies have shown that environmental estrogens dysregulate normal immune function in mammals, birds, turtles, lizards, fish, and invertebrates; however, the effects of such estrogenic exposures on alligator immune function have not been elucidated. Alligators occupy a top trophic status, which may give them untapped utility as indicators of environmental quality. Environmental estrogens are also prevalent in the waters they occupy. Understanding the effects of these EDCs on alligator immunity is critical for managing and assessing changes in their health and is thus the focus of this review.

  19. Estrogenic and dioxin-like compounds in sediment from Zierikzee harbour identified with CALUX assay-directed fractionation combined with one and two dimensional gas chromatography analyses.

    PubMed

    Houtman, Corine J; Booij, Petra; Jover, Eric; Pascual del Rio, David; Swart, Kees; van Velzen, Martin; Vreuls, Rene; Legler, Juliette; Brouwer, Abraham; Lamoree, Marja H

    2006-12-01

    The identity of compounds responsible for estrogenic and dioxin-like activities in sediment from the harbour of the small town Zierikzee in Zeeland, The Netherlands, was investigated using a bioassay directed fractionation approach with the in vitro estrogen and dioxin responsive reporter gene assays ER- and DR-CALUX. For identification of compounds exhibiting activity in the bioassays, either one or two-dimensional GC in combination with quadrupole (MSD), ion trap (ITD) or time-of-flight mass spectrometric detection (ToF-MS) was used, depending on the biological and chemical characteristics and the complexity of the fractions. The natural estrogenic hormone 17-beta-estradiol and its metabolite estrone were identified with GC-ITD as the main contributors to the estrogenic activity. After successive rounds of fractionation, the dioxin-like activity could be explained by the presence of various polycyclic aromatic hydrocarbons identified with GC-MSD and two-dimensional comprehensive GC x GC-ToF-MS. Some estrogenic activity of a relatively non-polar nature remained unidentified.

  20. PERINATAL EXPOSURE TO ESTROGENIC COMPOUNDS AND THE SUBSEQUENT EFFECTS ON THE PROSTRATE OF THE ADULT RAT: EVALUATION OF INFLAMMATION IN THE VENTRAL AND LATERAL LOBES

    EPA Science Inventory

    Perinatal exposure to estrogenic compounds and the subsequent effects on the prostate of the adult rat: evaluation of inflammation in the ventral and lateral lobes.

    Stoker TE, Robinette CL, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National ...

  1. Environmental Chemistry Compound Identification Using High ...

    EPA Pesticide Factsheets

    There is a growing need for rapid chemical screening and prioritization to inform regulatory decision-making on thousands of chemicals in the environment. We have previously used high-resolution mass spectrometry to examine household vacuum dust samples using liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS). Using a combination of exact mass, isotope distribution, and isotope spacing, molecular features were matched with a list of chemical formulas from the EPA’s Distributed Structure-Searchable Toxicity (DSSTox) database. This has further developed our understanding of how openly available chemical databases, together with the appropriate searches, could be used for the purpose of compound identification. We report here on the utility of the EPA’s iCSS Chemistry Dashboard for the purpose of compound identification using searches against a database of over 720,000 chemicals. We also examine the benefits of QSAR prediction for the purpose of retention time prediction to allow for alignment of both chromatographic and mass spectral properties. This abstract does not reflect U.S. EPA policy presentation at the Eastern Analytical Symposium.

  2. Construction of a Bacterial Assay for Estrogen Detection Based on an Estrogen-Sensitive Intein ▿ †

    PubMed Central

    Liang, Rubing; Zhou, Jing; Liu, Jianhua

    2011-01-01

    Escherichia coli strain DIER was constructed for estrogen detection by inserting an estrogen-sensitive intein (VMAER intein) into the specific site of the constitutively expressed chromosomal lacZ gene. This VMAER intein was generated by replacing the endonuclease region of the Saccharomyces cerevisiae VMA intein with the estrogen binding region of the human estrogen receptor α (hERα). When there were estrogens or analogs, the splicing of the VMAER intein was induced to produce the mature LacZ protein, which was detected through a β-galactosidase colorimetric assay. Eight typical chemicals (17-β-estradiol, bisphenol A, chrysene, 6-OH-chrysene, benz[a]anthracene, pyrene, progesterone, and testosterone) were detected using this DIER strain, and the whole detection procedure was accomplished in 2 h. Their 50% effective concentrations (EC50), relative estrogenic activities, and estradiol equivalency factors were calculated and were quite consistent with those detected with the yeast estrogen screening (YES) system. Furthermore, the estrogenic activities of the synthetic musk samples extracted from the wastewater and waste sludge of a sewage treatment plant of Shanghai (China) were detected, and their results were comparable to those obtained from the YES system and gas chromatography-mass spectrometry (GC-MS). In conclusion, the DIER bioassay could fill a niche for the efficient, rapid, high-throughput screening of estrogenic compounds and has potential for the remote, near-real-time monitoring of environmental estrogens. PMID:21317264

  3. Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

    SciTech Connect

    Mao, Haoping; Wang, Hong; Ma, Shangwei; Xu, Yantong; Zhang, Han; Wang, Yuefei; Niu, Zichang; Fan, Guanwei; Zhu, Yan; Gao, Xiu Mei

    2014-01-01

    Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p < 0.01), while it reduced 300 μM acetylcholine (ACh) (p < 0.01), 100 μM veratridine (Ver) (p < 0.01) and 56 mM K{sup +} (p < 0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p < 0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56 mM K{sup +} induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion

  4. Polydopamine-coated magnetic nanoparticles for isolation and enrichment of estrogenic compounds from surface water samples followed by liquid chromatography-tandem mass spectrometry determination.

    PubMed

    Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Piovesana, Susy; Samperi, Roberto; Zenezini Chiozzi, Riccardo; Laganà, Aldo

    2016-06-01

    Estrogens, phytoestrogens, and mycoestrogens may enter into the surface waters from different sources, such as effluents of municipal wastewater treatment plants, industrial plants, and animal farms and runoff from agricultural areas. In this work, a multiresidue analytical method for the determination of 17 natural estrogenic compounds, including four steroid estrogens, six mycoestrogens, and seven phytoestrogens, in river water samples has been developed. (Fe3O4)-based magnetic nanoparticles coated by polydopamine (Fe3O4@pDA) were used for dispersive solid-phase extraction, and the final extract was analyzed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The Fe3O4 magnetic nanoparticles were prepared by a co-precipitation procedure, coated by pDA, and characterized by scanning electron microscopy, infrared spectroscopy, and elemental analysis. The sample preparation method was optimized in terms of extraction recovery, matrix effect, selectivity, trueness, precision, method limits of detection, and method limits of quantification (MLOQs). For all the 17 analytes, recoveries were >70 % and matrix effects were below 30 % when 25 mL of river water sample was treated with 90 mg of Fe3O4@pDA nanoparticles. Selectivity was tested by spiking river water samples with 50 other compounds (mycotoxins, antibacterials, conjugated hormones, UV filters, alkylphenols, etc.), and only aflatoxins and some benzophenones showed recoveries >60 %. This method proved to be simple and robust and allowed the determination of natural estrogenic compounds belonging to different classes in surface waters with MLOQs ranging between 0.003 and 0.1 μg L(-1). Graphical Abstract Determination of natural estrogenic compounds in water by magnetic solid phase extraction followed by liquid chromatography-tandem mass spectrometry analysis.

  5. Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study.

    PubMed

    Shughrue, P J; Lane, M V; Merchenthaler, I

    1997-12-01

    Progesterone receptor (PR) messenger RNA (mRNA) is concentrated in neurons of the preoptic area and other regions of the rat hypothalamus where it is colocalized with the estrogen receptor and regulated by changes in the steroid hormonal milieu. To date, little is known about the regulation of PR mRNA by estrogens and whether antiestrogenic compounds are capable of modulating its expression. The present studies used in situ hybridization to ascertain the time course of PR mRNA regulation in the medial preoptic nucleus by 17beta-estradiol, determine the effective dose required to elicit a response, and compare the efficacy of 17beta-estradiol with a variety of estrogenic or antiestrogenic compounds. The first series of studies revealed that the treatment of ovariectomized rats with 17beta-estradiol resulted in an increase in PR expression within 2 h, after which it remained elevated until 10 h postinjection and then returned to baseline levels. When ovariectomized rats were injected with 25-1000 ng/kg of 17beta-estradiol and euthanized 6 h later, a dose-dependent increase in the level of PR mRNA was observed, with a maximal response at 1000 ng/kg and an EC50 of 93.5 ng/kg. Subsequent studies evaluated the efficacy of a variety of estrogenic and antiestrogenic compounds in the rat preoptic nucleus. 17Beta-estradiol, diethylstilbestrol, and 17alpha-estradiol all significantly increased the level of PR mRNA, although the degree of induction varied with each compound. The injection of tamoxifen, raloxifene, toremifene, droloxifene, clomiphene, GW 5638, or ICI 182,780 had no significant estrogenic effect on PR gene expression at the dose evaluated. In contrast, when tamoxifen or raloxifene, but not ICI 182,780, was administered in the antagonist mode, a significant dose-related decrease in the estradiol-induced level of PR mRNA was seen in the preoptic area. The results of these studies clearly demonstrate that PR mRNA expression in the rat preoptic area is rapidly

  6. Interference of xenoestrogen o,p'-DDT on the action of endogenous estrogens at environmentally realistic concentrations.

    PubMed

    Zhong, Lingying; Xiang, Xiao; Lu, Wei; Zhou, Pei; Wang, Lumei

    2013-05-01

    Estrogenic effects of individual chemicals and mixtures of 17β-estradiol (E2) and o,p'-DDT were examined using pS2 and PR gene expressions in MCF-7 cells. Interactions between E2 and o,p'-DDT were evaluated by a statistical method based on factorial design. At levels close to environmentally realistic concentrations, no significant interactions between E2 and o,p'-DDT were observed, suggesting that the xenoestrogen (o,p'-DDT) could act in an additive way with the endogenous estrogen (E2). These results demonstrated the utility of this statistical method in a mixture study, and highlight the potential interference and health risk of low-level xenoestrogens, such as o,p'-DDT.

  7. Highly Selective Screening of Estrogenic Compounds in Consumer-Electronics Plastics by Liquid Chromatography in Parallel Combined with Nanofractionation-Bioactivity Detection and Mass Spectrometry.

    PubMed

    Jonker, Willem; Ballesteros-Gómez, Ana; Hamers, Timo; Somsen, Govert W; Lamoree, Marja H; Kool, Jeroen

    2016-11-15

    The chemical safety of consumer products is an issue of emerging concern. Plastics are widely used, e.g. as casings of consumer electronics (TVs, computers, routers, etc.), which are present in houses and offices in continuously increasing numbers. In this study, we investigate the estrogenic activity of components of plastics coming from electronics' casings. A recently developed fractionation platform for effect-directed analysis (EDA) was used. This platform combines reversed-phase liquid chromatography in parallel with bioassay detection via nanofractionation and with online high-resolution time-of-flight mass spectrometry (TOFMS) for the identification of bioactives. Four out of eight of the analyzed plastics samples showed the presence of estrogenic compounds. Based on the MS results these were assigned to bisphenol A (BPA), 2,4-di-tert-butylphenol, and a possible bisphenol A analog. All samples contained flame retardants, but these did not show any estrogenicity. The observed BPA, however, could be an impurity of tetrabromo-BPA (TBBPA) or TBBPA-based flame retardants. Due to the plausible migration of additives from plastics into the environment, plastics from consumer electronics likely constitute a source of estrogenic compound contamination in the indoor environment.

  8. Removal of Estrogens and Estrogenicity through Drinking Water Treatment

    EPA Science Inventory

    Estrogenic compounds have been shown to be present in surface waters, leading to concerns over their possible presence in finished drining waters. In this work, two in vitro human cell line bioassays for estrogenicity were used to evaluate the removal of estrogens through conven...

  9. Regulation of Growth and Metastases in an Estrogen Independent Breast Cancer Cell by Vitamin D Compounds

    DTIC Science & Technology

    2000-08-01

    micrometastases in the nude mouse, we used the EGFP fluorescent marker gene, cloned from the bioluminescent jellyfish Aequorea Victoria (previously...Utilizing our SUM-159PT GFP model system in vivo we can more efficiently examine the effects of vitamin D compounds to modulate invasion and metastasis...cells in nude mice. We previously reported that use of SUM-159PT cells expressing GFP enabled visualization of cancer cells in the mammary fat pad as

  10. THE USE OF DNA MACROARRAYS TO EVALUATE THE EFFECTS OF ENVIRONMENTAL ESTROGENS ON WILDLIFE

    EPA Science Inventory

    During the mid-1990s, several investigations in the United States and United Kingdom showed that wild fish of several species collected downstream of sewage treatment plants or industrial discharges presented expression of estrogen-responsive genes, or phenotypic sex reversal. Su...

  11. Pyrolysis of wastewater biosolids significantly reduces estrogenicity.

    PubMed

    Hoffman, T C; Zitomer, D H; McNamara, P J

    2016-11-05

    Most wastewater treatment processes are not specifically designed to remove micropollutants. Many micropollutants are hydrophobic so they remain in the biosolids and are discharged to the environment through land-application of biosolids. Micropollutants encompass a broad range of organic chemicals, including estrogenic compounds (natural and synthetic) that reside in the environment, a.k.a. environmental estrogens. Public concern over land application of biosolids stemming from the occurrence of micropollutants hampers the value of biosolids which are important to wastewater treatment plants as a valuable by-product. This research evaluated pyrolysis, the partial decomposition of organic material in an oxygen-deprived system under high temperatures, as a biosolids treatment process that could remove estrogenic compounds from solids while producing a less hormonally active biochar for soil amendment. The estrogenicity, measured in estradiol equivalents (EEQ) by the yeast estrogen screen (YES) assay, of pyrolyzed biosolids was compared to primary and anaerobically digested biosolids. The estrogenic responses from primary solids and anaerobically digested solids were not statistically significantly different, but pyrolysis of anaerobically digested solids resulted in a significant reduction in EEQ; increasing pyrolysis temperature from 100°C to 500°C increased the removal of EEQ with greater than 95% removal occurring at or above 400°C. This research demonstrates that biosolids treatment with pyrolysis would substantially decrease (removal>95%) the estrogens associated with this biosolids product. Thus, pyrolysis of biosolids can be used to produce a valuable soil amendment product, biochar, that minimizes discharge of estrogens to the environment.

  12. Identification of alkylphenols and other estrogenic compounds in wastewater, septage, and groundwater on Cape Cod, Massachusetts

    USGS Publications Warehouse

    Rudel, Ruthann A.; Melly, Steven J.; Geno, Paul W.; Sun, Gang; Brody , Julia G.

    1998-01-01

    As part of a larger effort to characterize the impacts to Cape Cod drinking water supplies from on-site wastewater disposal, we developed two analytical methods using HPLC and GC/MS for a range of compounds identified as endocrine-disrupting chemicals (EDCs), including the nonionic surfactants alkylphenol polyethoxylates (APEOs) and their degradation products. We analyzed samples for nonylphenol, octylphenol, and their ethoxylates up to the hexaethoxylate using an HPLC method, with detection limits ranging from 2 to 6 μg/L. A set of phenolic compounds including bisphenol A and nonylphenol were derivatized and analyzed by GC/MS with detection limits from 0.001 to 0.02 μg/L. Total APEOs in untreated wastewater and septage samples ranged from 1350 to 11 000 μg/L by the HPLC method. Nonylphenol was detected in all septage samples at concentrations above 1000 μg/L. Phenylphenol and bisphenol A were detected in septage and wastewater at about 1 μg/L. In groundwater downgradient of an infiltration bed for secondary treated effluent, nonyl/octylphenol and ethoxylates were present at about 30 μg/L. Bisphenol A, nonylphenol monoethoxycarboxylate, and nonyl/octylphenol tetraethoxylate were detected in some drinking water wells at concentrations ranging from below the quantitation limit to 32.9 μg/L. Results suggest that septic systems may be a significant source of APEOs to groundwater.

  13. Estrogenic environmental contaminants alter the mRNA abundance profiles of genes involved in gonadal differentiation of the American bullfrog

    PubMed Central

    Wolff, Stephanie E.; Veldhoen, Nik; Helbing, Caren C.; Ramirez, Claire A.; Malpas, Janae M.; Propper, Catherine R.

    2015-01-01

    Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring for endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17β-estradiol (E2; 10−9 M) or 4-tert-octylphenol (OP; 10−9 M, 10−8 M, and 10−7 M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10−7 M OP increased testicular transcript levels. Treatment with 10−9 and 10−8 M OP, but not 10−7 M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed

  14. Estrogenic environmental contaminants alter the mRNA abundance profiles of genes involved in gonadal differentiation of the American bullfrog.

    PubMed

    Wolff, Stephanie E; Veldhoen, Nik; Helbing, Caren C; Ramirez, Claire A; Malpas, Janae M; Propper, Catherine R

    2015-07-15

    Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring of endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17β-estradiol (E2; 10(-9)M) or 4-tert-octylphenol (OP; 10(-9)M, 10(-8)M, and 10(-7)M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10(-7)M OP increased testicular transcript levels. Treatment with 10(-9) and 10(-8)M OP, but not 10(-7)M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed within

  15. Environmental occurrence, analysis, and toxicology of toxaphene compounds.

    PubMed Central

    de Geus, H J; Besselink, H; Brouwer, A; Klungsøyr, J; McHugh, B; Nixon, E; Rimkus, G G; Wester, P G; de Boer, J

    1999-01-01

    Toxaphene production, in quantities similar to those of polychlorinated biphenyls, has resulted in high toxaphene levels in fish from the Great Lakes and in Arctic marine mammals (up to 10 and 16 microg g-1 lipid). Because of the large variabiliity in total toxaphene data, few reliable conclusions can be drawn about trends or geographic differences in toxaphene concentrations. New developments in mass spectrometric detection using either negative chemical ionization or electron impact modes as well as in multidimensional gas chromatography recently have led researchers to suggest congener-specific approaches. Recently, several nomenclature systems have been developed for toxaphene compounds. Although all systems have specific advantages and limitations, it is suggested that an international body such as the International Union of Pure and Applied Chemistry make an attempt to obtain uniformity in the literature. Toxicologic information on individual chlorobornanes is scarce, but some reports have recently appeared. Neurotoxic effects of toxaphene exposure such as those on behavior and learning have been reported. Technical toxaphene and some individual congeners were found to be weakly estrogenic in in vitro test systems; no evidence for endocrine effects in vivo has been reported. In vitro studies show technical toxaphene and toxaphene congeners to be mutagenic. However, in vivo studies have not shown genotoxicity; therefore, a nongenotoxic mechanism is proposed. Nevertheless, toxaphene is believed to present a potential carcinogenic risk to humans. Until now, only Germany has established a legal tolerance level for toxaphene--0.1 mg kg-1 wet weight for fish. PMID:10229713

  16. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose.

    PubMed

    Penza, M; Jeremic, M; Marrazzo, E; Maggi, A; Ciana, P; Rando, G; Grigolato, P G; Di Lorenzo, D

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5μg/kg). At higher doses (50-500μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed.

  17. Determination of estrogenic compounds in milk and yogurt samples by hollow-fibre liquid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry.

    PubMed

    D'Orazio, Giovanni; Hernández-Borges, Javier; Herrera-Herrera, Antonio Vicente; Fanali, Salvatore; Rodríguez-Delgado, Miguel Ángel

    2016-10-01

    An environmentally friendly method based on hollow-fibre liquid-phase microextraction (HF-LPME) was developed for the extraction of selected estrogenic compounds (i.e. four natural sexual hormones: estrone, 17β-estradiol, 17α-estradiol and estriol; two exoestrogens: 17α-ethynylestradiol and 2-methoxyestradiol; two synthetic stilbenes: dienestrol and hexestrol; and five resorcylic acid lactones: zearalenone, α-zearalanol, β-zearalanol, α-zearalenol and β-zearalenol), from whole cow and semi-skimmed goat milk and whole natural yogurt. After the optimization of the sample preparation procedure, spiked extracts were derivatized to their trimethylsilyl products using N,O-bis(trimethylsilyl)trifluoroacetamide reagent and then analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS). Once optimum extraction conditions were established (protein precipitation with acetonitrile, extraction and the back-extraction in acetonitrile following the HF-LPME procedure), the method was validated and the calibration range, precision and accuracy were studied. The RSD values for the intra- and inter-day precision of the peak areas were in the range 0.65-9.69 and 1.00-11.47 %, respectively. The determination coefficients were higher than 0.991 for method calibration curves while LOD and LOQ values were between 0.06-2.55 and 0.16-6.11 μg/L for whole cow milk, 0.04-1.70 and 0.11-4.86 μg/L for semi-skimmed goat milk and 0.07-3.73 and 0.23-9.81 μg/L for natural yogurt, respectively. Finally, the accuracy and precision of the method were evaluated, obtaining a value in the range 84 81-119 % and RSD values lower than 20 % in all cases.

  18. Occupational asphyxiation by unknown compound(s): environmental and toxicological approach.

    PubMed

    Poli, D; Solarino, B; Di Vella, G; Tattoli, L; Strisciullo, G; Goldoni, M; Mutti, A; Gagliano-Candela, R

    2010-04-15

    During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death. Environmental results indicated that H(2)S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks. These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H(2)S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2 mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction. This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s).

  19. Do estrogenic compounds in drinking water migrating from plastic pipe distribution system pose adverse effects to human? An analysis of scientific literature.

    PubMed

    Liu, Ze-Hua; Yin, Hua; Dang, Zhi

    2017-01-01

    With the widespread application of plastic pipes in drinking water distribution system, the effects of various leachable organic chemicals have been investigated and their occurrence in drinking water supplies is monitored. Most studies focus on the odor problems these substances may cause. This study investigates the potential endocrine disrupting effects of the migrating compound 2,4-di-tert-butylphenol (2,4-d-t-BP). The summarized results show that the migration of 2,4-d-t-BP from plastic pipes could result in chronic exposure and the migration levels varied greatly among different plastic pipe materials and manufacturing brands. Based on estrogen equivalent (EEQ), the migrating levels of the leachable compound 2,4-d-t-BP in most plastic pipes were relative low. However, the EEQ levels in drinking water migrating from four out of 15 pipes may pose significant adverse effects. With the increasingly strict requirements on regulation of drinking water quality, these results indicate that some drinking water transported with plastic pipes may not be safe for human consumption due to the occurrence of 2,4-d-t-BP. Moreover, 2,4-d-t-BP is not the only plastic pipe-migrating estrogenic compound, other compounds such as 2-tert-butylphenol (2-t-BP), 4-tert-butylphenol (4-t-BP), and others may also be leachable from plastic pipes.

  20. Toxicity identification fractionation of environmental estrogens in waste water and sludge using gas and liquid chromatography coupled to mass spectrometry and recombinant yeast assay.

    PubMed

    Fernandez, Marc P; Noguerol, Tania-Noelia; Lacorte, Silvia; Buchanan, Ian; Piña, Benjamin

    2009-02-01

    We developed a toxicity identification fractionation (TIF) procedure to determine estrogenic compounds in wastewaters and sludge. The procedure consisted in fractionation of samples through a C(18) solid-phase extraction cartridge, in which Fraction I contained nonylphenol (NP) and its mono (NPEO(1)) and diethoxylate (NPEO(2)) and the markers of faecal exposure, Fraction II contained bisphenol A (BPA) and synthetic and natural hormones, and Fraction III contained the hormone conjugates. These three fractions were analyzed in parallel using gas or liquid chromatography coupled to mass spectrometry and recombinant yeast assay (RYA). Water samples collected daily throughout a whole week contained from 0.45 to 7.22 microg L(-1) of NP > NPEO(1) > NPEO(2) and were responsible for the estrogenicity of these samples. Fractions II and III were not estrogenic and that was due to the low ng L(-1) level of hormones and hormone conjugates found, respectively. The biological treatment sewage treatment plant (STP) was capable to eliminate from 52 to 100% of the compounds, with bisphenol A being the least removed. Only alkylphenols were accumulated in sludge with concentrations from 8.69 to 26.3 mg kg(-1) dw of NPEO(1) > NPEO(2) > NP. The integrated procedure herein proposed can be used as a screening method to evaluate estrogenic compounds in STPs and to survey faecal elimination.

  1. Relationship between sex steroid and vitellogenin concentrations in flounder (Platichthys flesus) sampled from an estuary contaminated with estrogenic endocrine-disrupting compounds.

    PubMed

    Scott, Alexander P; Katsiadaki, Ioanna; Kirby, Mark F; Thain, John

    2006-04-01

    High concentrations of vitellogenin (VTG; egg yolk protein) have previously been found in male flounder (Platichthys flesus) from several UK estuaries; these levels have been ascribed to the presence of estrogenic endocrine-disrupting compounds (EDCs). Gonadal abnormalities, including intersex, have also been recorded in these estuaries. However, there is no firm evidence to date that these two findings are causally linked or that the presence of estrogenic EDCs has any adverse population effects. In the present study, we examined the relationship between concentrations of VTG and sex steroids (11-oxo-testosterone in males and 17beta-estradiol in females) in specimens of flounder captured from the estuary of the River Mersey. We first questioned whether the high concentrations of VTG in male and immature female flounder were indeed caused by a direct effect of exogenous EDCs and not indirectly via the endogenous secretion of 17beta-estradiol. The data favored the direct involvement of estrogenic EDCs. We then questioned whether the presence of estrogenic EDCs not only stimulated inappropriate VTG synthesis but whether it might also have had a negative effect on endogenous steroid secretion. It should be noted that the predicted consequences of a drop in steroid secretion include smaller gonads, smaller oocytes, fewer numbers of sperm, and depressed spawning behavior. This question was more difficult to answer because of the strong effect of the seasonal reproductive cycle and stage of maturation on steroid concentrations. However, matched by month of capture and stage of maturation, both 17beta-estradiol in females and 11-keto-testosterone in males were in most cases significantly lower in those years when VTG concentrations were higher.

  2. Fate and removal of estrogens in municipal wastewater.

    PubMed

    Racz, LeeAnn; Goel, Ramesh K

    2010-01-01

    Natural and synthetic estrogens are some of the most potent endocrine disrupting compounds found in municipal wastewater. Much research has been conducted on the source and fate of estrogens in wastewater treatment plants. Sorption and biodegradation are the primary removal mechanisms for estrogens in activated sludge systems, which are widely used biological treatment techniques for municipal wastewater treatment. However, when removal of estrogens in a wastewater treatment plant is incomplete, these compounds enter the environment through wastewater discharges or waste activated sludge at concentrations that can cause endocrine-reproductive system alterations in birds, reptiles and mammals. Therefore, studies have also focused on potential advanced treatment technologies with the aim of removing the compounds before discharging wastewater effluent or disposing waste sludge. This review discusses the physiological effects of these estrogens and the degree of problems estrogens pose as they enter the wastewater stream. Thereafter, this review also analyzes their fate in wastewater treatment systems and how they may reach drinking water sources. Furthermore, this review includes a discussion on various treatment technologies being investigated and future research trends for this pressing environmental issue.

  3. Environmental assessment of a site contaminated by organic compounds.

    PubMed

    Riccardi, C; Berardi, S; Di Basilio, M; Gariazzo, C; Giardi, P; Villarini, M

    2001-01-01

    This paper presents a study on environmental assessment of an abandoned industrial area located in central Italy. Main production was refractory materials and compounds for treatment of industrial wastewater. The present work deals with a methodology for development of a sound sampling design, chemical characterization of soil samples, definition of the degree of site contamination according to law limits and evaluation of the fate and transport of contaminants by EPA simulation model (VLEACH 2.2a). Results indicate that toxic compounds (polycyclic aromatic hydrocarbons and plasticizers) are uniformly distributed in the contaminated site and only in one sampling point their concentrations exceed law limits. Modeling results confirm that contaminants migration to groundwater can be excluded, addressing for a site remediation limited to the surface layer.

  4. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    EPA Science Inventory

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  5. The use of a whole animal biophotonic model as a screen for the angiogenic potential of estrogenic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular endothelial growth factor (VEGF) is essential for normal vascular growth and development during wound repair. VEGF is estrogen responsive and capable of regulating its own receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). Several agricultural pesticides (e.g., methoxychlor)...

  6. Detecting estrogenic activity in water samples withestrogen-sensitive yeast cells using spectrophotometry and fluorescencemicroscopy

    SciTech Connect

    Wozei, E.; Holman, H-Y.N.; Hermanowicz, S.W.; Borglin S.

    2006-03-15

    Environmental estrogens are environmental contaminants that can mimic the biological activities of the female hormone estrogen in the endocrine system, i.e. they act as endocrine disrupters. Several substances are reported to have estrogen-like activity or estrogenic activity. These include steroid hormones, synthetic estrogens (xenoestrogens), environmental pollutants and phytoestrogens (plant estrogens). Using the chromogenic substrate ortho-nitrophenyl-{beta}-D-galactopyranoside (ONPG) we show that an estrogen-sensitive yeast strain RMY/ER-ERE, with human estrogen receptor (hER{alpha}) gene and the lacZ gene which encodes the enzyme {beta}-galactosidase, is able to detect estrogenic activity in water samples over a wide range of spiked concentrations of the hormonal estrogen 17{beta}-estradiol (E2). Ortho-nitrophenol (ONP), the yellow product of this assay can be detected using spectrophotometry but requires cell lysis to release the enzyme and allow product formation. We improved this aspect in a fluorogenic assay by using fluorescein di-{beta}-D-galactopyranoside (FDG) as a substrate. The product was visualized using fluorescence microscopy without the need to kill, fix or lyse the cells. We show that in live yeast cells, the uptake of E2 and the subsequent production of {beta}-galactosidase enzyme occur quite rapidly, with maximum enzyme-catalyzed fluorescent product formation evident after about 30 minutes of exposure to E2. The fluorogenic assay was applied to a selection of estrogenic compounds and the Synchrotron-based Fourier transform infrared (SR-FTIR) spectra of the cells obtained to better understand the yeast whole cell response to the compounds. The fluorogenic assay is most sensitive to E2, but the SR-FTIR spectra suggest that the cells respond to all the estrogenic compounds tested even when no fluorescent response was detected. These findings are promising and may shorten the duration of environmental water screening and monitoring regimes using

  7. Estimation of environmental properties for inorganic compounds using LSER

    USGS Publications Warehouse

    Hickey, James P.

    1999-01-01

    The Great Lakes Science Center has devised values for inorganic species for use in the environmental property- predictive quantitative structure-activity relationships (QSAR) Linear Solvation Energy Relationship (LSER). Property estimation has been difficult for inorganic species. In this presentation aqueous solubility, bioconcentration and acute aquatic toxicity are estimated for inorganic compounds using existing LSER equations. The best estimations arise from the most accurate description of predominant solution species, many within an order of magnitude. The toxicities also depend on an estimation of the bioactive amount and configuration. A number of anion/cation combinations (salts) still resist accurate property estimation, and the reasons currently are not understood. These new variable values will greatly extend the application and utility of LSER for the estimation of environmental properties.

  8. Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense).

    PubMed

    Overk, Cassia R; Yao, Ping; Chadwick, Lucas R; Nikolic, Dejan; Sun, Yongkai; Cuendet, Muriel A; Deng, Yunfan; Hedayat, A S; Pauli, Guido F; Farnsworth, Norman R; van Breemen, Richard B; Bolton, Judy L

    2005-08-10

    Because the prevailing form of hormone replacement therapy is associated with the development of cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL. (hops) have been reported to contain the prenylflavanone, 8-prenylnaringenin (8-PN), as the most estrogenic constituent, and this was confirmed using an estrogen receptor ligand screening assay utilizing ultrafiltration mass spectrometry. Extracts of hops and red clover and their individual constituents including 8-PN, 6-prenylnaringenin (6-PN), isoxanthohumol (IX), and xanthohumol (XN) from hops and daidzein, formononetin, biochanin A, and genistein from red clover were compared using a variety of in vitro estrogenic assays. The IC50 values for the estrogen receptor alpha and beta binding assays were 15 and 27 microg/mL, respectively, for hops and 18.0 and 2.0 microg/mL, respectively, for the red clover extract. Both of the extracts, genistein, and 8-PN activated the estrogen response element (ERE) in Ishikawa cells while the extracts, biochanin A, genistein, and 8-PN, significantly induced ERE-luciferase expression in MCF-7 cells. Hop and red clover extracts as well as 8-PN up-regulated progesterone receptor (PR) mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR mRNA was significantly up-regulated by the extracts, biochanin A, genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 microg/mL, respectively, in the alkaline phosphatase induction assay. On the basis of these data, hops and red clover could be attractive for the development as herbal dietary supplements to alleviate menopause-associated symptoms.

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

    PubMed

    Meeker, John D

    2010-07-01

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

  10. Environmentally Friendly Corrosion Preventative Compounds for Ground Support Structures

    NASA Technical Reports Server (NTRS)

    Montgomery Eliza L.; Calle, Luz, Marina; Curran, Jerome P.; Kolody, Mark R.

    2013-01-01

    The need to use environmentally friendly technologies throughout future space-related launch programs prompted a study aimed at replacing current petroleum and solvent-based Corrosion Preventive Compounds (CPCs) with environmentally friendly alternatives. The work in this paper focused on the identification and evaluation of environmentally friendly CPCs for use in protecting flight hardware and ground support equipment from atmospheric corrosion. CPCs are used as temporary protective coatings and must survive in the aggressive coastal marine environment that exists throughout the Kennedy Space Center, Florida. The different protection behaviors of fifteen different oily film CPCs, both common petroleum-based and newer environmentally friendly types, were evaluated on various steel and aluminum substrates. CPC and substrate systems were subjected to atmospheric testing at the Kennedy Space Center's Beachside Atmospheric Corrosion Test Site, as well as cyclic accelerated corrosion testing. Each CPC also underwent physical characterization and launch-related compatibility testing. The results for the fifteen CPC systems are presented in this paper.

  11. In Vitro Assessment of Estrogenic Activity in Source and Treated Drinking Water Extracts from 25 U.S. Drinking Water Plants

    EPA Science Inventory

    The presence of estrogenic compounds in environmental water samples and their potential impact on fish, wildlife and human reproductive health has been of concern for some time. In vitro assays have been successfully used to screen for estrogenic activity in many types of water s...

  12. The Measurement of Estrogens

    NASA Astrophysics Data System (ADS)

    Holder, Geoff; Makin, Hugh L. J.; Bradlow, H. Leon

    Biologists use the word ‘estrogen' when referring to molecules which have the ability to induce uterine growth or vaginal cornification in the immature or ovariectomized rodent. The word estrogen was derived from two Greek words - oistros meaning frenzy and gennein - to beget. Chemists and biochemists, however, often restrict their use of this term to molecules that contain a characteristic 18-carbon steroid nucleus with an aromatic (phenolic) A-ring, both those that are biologically active estrogens and those without biologic activity but which are of intrinsic interest, such as the estrogen conjugates. This chapter is concerned only with these steroid compounds. The structure and inter-relationship of some common estrogens are given in Fig. 8.1. In addition to the biological estrogens, there are a wide variety of both natural and synthetic compounds which have estrogenic activity when measured by one or another parameter. While many of the assay procedures described in this review are applicable to these compounds, their application to non C18-steroids will not be discussed here. Methodology for these non-steroidal compounds can be found in reviews by Wang et al. (2002), Wu et al. (2004), Muir (2006), and Delmonte and Rader (2006). While not wishing to downgrade the importance of previous work in the estrogen field, the authors have taken a deliberate decision to exclude most publications prior to 1975, not because these do not have value but simply because space is not unlimited and readers of the present chapter might be expected to be seeking information about methodology which is less than 30 years old. Readers seeking pre-1975 information in this area can find it in Oakey and Holder (1995).

  13. Environmental estrogen Bisphenol A adsorption/oxidation on Graphene oxide/MnO2 (GO/MnO2) nanocomposite

    NASA Astrophysics Data System (ADS)

    Bele, Sotiria I.; Deliyanni, Eleni A.

    2015-04-01

    The environmental fate and decontamination of Bisphenol A (BPA), an environmental estrogen that is used as a monomer in plastic industry, are of emerging concern. This study focused on the kinetics, influencing factors and pathways of its adsorption and oxidative decomposition by MnO2. Additionally, Graphene oxide/MnO2 (GO/MnO2) nanocomposite was prepared and tested as a kind of adsorbent and/or catalysts for oxidative decomposition of Bisphenol A (BPA). A suspension of graphene oxide/manganese sulfate (GO/MnSO4) produced by the modified Hummers method was in situ transformed into GO/MnO2 nanocomposite in combination with KMnO4. It is found that MnO2 nanoparticles are uniformly distributed in the structure of GO. The surface chemistry and the porous texture of the prepared nanocomposite were characterized by thermal analysis (DTA), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM) and Nitrogen adsorption (BET). The nanocomposite presented superior catalytic activities, much higher than that of the bare MnO2 for the decomposition of BPA in the presence of H2O2. The high activity of GO/MnO2 nanocomposite for the decomposition of BPA could be related to the synergistic effect of GO and MnO2 with the assistance of H2O2 according to the adsorption-oxidation-desorption mechanism.

  14. Estrogen Injection

    MedlinePlus

    ... forms of estrogen injection are used to treat hot flushes (hot flashes; sudden strong feelings of heat and sweating) ... If you are using estrogen injection to treat hot flushes, your symptoms should improve within 1 to ...

  15. Nitroaromatic munition compounds: environmental effects and screening values.

    PubMed

    Talmage, S S; Opresko, D M; Maxwell, C J; Welsh, C J; Cretella, F M; Reno, P H; Daniel, F B

    1999-01-01

    Available data on the occurrence, transport, transformation, and toxicity of eight nitroaromatic munition compounds and their degradation products, TNT, TNB, DNB, DNA, 2-ADNT, RDX, HMX, and tetryl were used to identify potential fate in the environment and to calculate screening benchmarks or safe environmental levels for aquatic and terrestrial organisms. Results of monitoring studies revealed that some of these compounds persist at sites where they were produced or processed. Most of the compounds are present in soil, sediment, and surface water or groundwater at military sites. Soil adsorption coefficients indicate that these chemicals are only moderately adsorbed to soil and may leach to groundwater. Most of these compounds are transformed by abiotic or biotic mechanisms in environmental media. Primary transformation mechanisms involve photolysis (TNT, RDX, HMX, tetryl), hydrolysis (tetryl), and microbial degradation (TNT, TNB, DNB, DNA, 2-ADNT, and HMX). Microbial degradation for both nitro and nitramine aromatic compounds involves rapid reduction of nitro groups to amino groups, but further metabolism is slow. With the exception of DNB, complete mineralization did not usually occur under the conditions of the studies. RDX was resistant to microbial degradation. Available ecotoxicological data on acute and chronic studies with freshwater fish and invertebrates were summarized, and water quality criteria or ecotoxicological screening benchmarks were developed. Depending on the available data, criteria/benchmarks were calculated according to USEPA Tier I or Tier II guidelines. The munitions chemicals are moderately to highly toxic to freshwater organisms, with chronic screening values < 1 mg/L. For some chemicals, these low values are caused by inherent toxicity; in other cases, they result from the conservative methods used in the absence of data. For nonionic organic munitions chemicals, sediment quality benchmarks were calculated (based on Kow values and the

  16. The influence of a surfactant, linear alkylbenzene sulfonate, on the estrogenic response to a mixture of (xeno)estrogens in vitro and in vivo.

    PubMed

    Harris, Catherine A; Brian, Jayne V; Pojana, Giulio; Lamoree, Marja; Booy, Petra; Marcomini, Antonio; Sumpter, John P

    2009-01-18

    The effect of the presence of a surfactant on the activity of a mixture of environmental estrogens was assessed. In their natural habitat, fish are subject not only to exposure to mixtures of estrogenic compounds, as has been addressed in previous publications, but also to other confounding factors (chemical, physical and biological), which may, in theory, affect their responses to such compounds. To assess the potential for such interference, the commonly occurring surfactant, linear alkylbenzene sulfonate (LAS), was applied to the yeast estrogen screen at various concentrations, independently and together with a mixture of estrogens at constant concentrations. LAS enhanced the estrogenic activity of the mixture, an effect which became less pronounced over the course of time. This information was used to design an in vivo study to assess induction of vitellogenin in fathead minnows exposed to the same mixture of estrogens plus LAS. A similar trend was observed, that is, the response was enhanced, but the effect became less pronounced as the study progressed. However, the enhanced response in vivo occurred only at the highest concentration of LAS tested (362microg/L), and was transient because it was no longer apparent by the end of the study. Although LAS is a significant contaminant in terms of both concentration and frequency of detection in the aquatic environment, these data do not suggest that it will have a significant impact on the response of fish to environmental estrogens.

  17. Mixture interactions of xenoestrogens with endogenous estrogens.

    EPA Science Inventory

    There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. These environmental estrogens originate from various sources including concentrated animal feedlot operations (CAFO), m...

  18. Integration of GC-MSD and ER-Calux® assay into a single protocol for determining steroid estrogens in environmental samples.

    PubMed

    Avberšek, Miha; Žegura, Bojana; Filipič, Metka; Heath, Ester

    2011-11-01

    There are many published studies that use either chemical or biological methods to investigate steroid estrogens in the aquatic environment, but rarer are those that combine both. In this study, gas chromatography with mass selective detection (GC-MSD) and the ER-Calux(®) estrogenicity assay were integrated into a single protocol for simultaneous determination of natural (estrone--E1, 17β-estradiol--E2, estriol--E3) and synthetic (17α-ethinylestradiol--EE2) steroid estrogens concentrations and the total estrogenic potential of environmental samples. For integration purposes, several solvents were investigated and the commonly used dimethyl sulphoxide (DMSO) in the ER-Calux(®) assay was replaced by ethyl acetate, which is more compatible with gas chromatography and enables the same sample to be analysed by both GC-MSD and the ER-Calux(®) assay. The integrated protocol was initially tested using a standard mixture of estrogens. The results for pure standards showed that the estrogenicity calculated on the basis of GC-MSD and the ER-Calux(®) assay exhibited good correlation (r(2)=0.96; α=0.94). The result remained the same when spiked waste water extracts were tested (r(2)=0.92, α=1.02). When applied to real waste water influent and effluent samples the results proved (r(2)=0.93; α=0.99) the applicability of the protocol. The main advantages of this newly developed protocol are simple sample handling for both methods, and reduced material consumption and labour. In addition, it can be applied as either a complete or sequential analysis where the ER-Calux(®) assay is used as a pre-screening method prior to the chemical analysis.

  19. Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: A combined synthesis, binding and docking study

    PubMed Central

    McCullough, Christopher; Neumann, Terrence S.; Gone, Jayapal Reddy; He, Zhengjie; Herrild, Christian; Wondergem, Julie; Pandey, Rajesh K.; Donaldson, William A.; Sem, Daniel S.

    2014-01-01

    Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule. PMID:24315190

  20. Characterizing the Growth Kinetics in Estrogen Responsive ...

    EPA Pesticide Factsheets

    There is a need to develop high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals for endocrine disrupting potential. The estrogen signaling pathway is a known xenobiotic target that has been implicated in a variety of adverse health effects including reproductive deficits and cancer promotion. Using real-time measurements of growth kinetics by electrode impedance, the estrogen-responsive human ductal carcinoma cell line, T47D, was treated with 2000 chemicals of environmental relevance. Cells were treated in concentration response and measurements of cellular impedance were recorded every hour for six days. Exponential impedance, signifying increased proliferation, was observed by prototypical estrogen receptor agonists (17β-estradiol, genestein, bisphenol-A, nonylphenol, 4-tert-octylphenol). Several compounds, including bisphenol-A and genestein, induced cell proliferation at comparable levels to 17β-estradiol, although at much higher concentrations. Progestins, and mineralocortocoids (progesterone, dihydrotestosterone, aldosterone) invoked a biphasic impedance signature. In conclusion, the real-time nature of this assay allows for rapid detection of differential growth characteristics shows potential, in combination with other ToxCast HTS assays, to detect environmental chemicals with potential endocrine activity. [This abstract does not necessarily reflect Agency policy]. Several compounds, including bisphenol-A and

  1. Polydimethylsiloxane/metal-organic frameworks coated stir bar sorptive extraction coupled to high performance liquid chromatography-ultraviolet detector for the determination of estrogens in environmental water samples.

    PubMed

    Hu, Cong; He, Man; Chen, Beibei; Zhong, Cheng; Hu, Bin

    2013-10-04

    In this work, three kinds of metal-organic frameworks (MOFs), MOF-5, MOF-199 and IRMOF-3, were introduced in stir bar sorptive extraction (SBSE) and novel polydimethylsiloxane (PDMS)/MOFs (including PDMS/MOF-5, PDMS/MOF-199 and PDMS/IRMOF-3) coated stir bars were prepared by sol-gel technique. These PDMS/MOFs coatings were characterized and critically compared for the extraction of seven target estrogens (17-β-estradiol, dienestrol, diethylstilbestrol, estrone, 4-t-octylphenol, bisphenol-A and 17α-ethynylestradiol) by SBSE, and the results showed that PDMS/IRMOF-3 exhibited highest extraction efficiency. Based on the above facts, a novel method of PDMS/IRMOF-3 coating SBSE-high performance liquid chromatography ultraviolet (HPLC-UV) detection was developed for the determination of seven target estrogens in environmental waters. Several parameters affecting extraction of seven target estrogens by SBSE (PDMS/IRMOF-3) including extraction time, stirring rate, pH, ionic strength, desorption solvent and desorption time were investigated. Under the optimal experimental conditions, the limits of detection (LODs, S/N=3) were found to be in the range of 0.15-0.35 μg/L. The linear range was 2-2,500 μg/L for 17α-ethynylestradiol and 1-2,500 μg/L for other estrogens. The relative standard deviations (RSDs) were in the range of 3.7-9.9% (n=8, c=20 μg/L) and the enrichment factors were from 30.3 to 55.6-fold (theoretical enrichment factor was 100-fold). The proposed method was successfully applied to the analysis of estrogens in environmental water samples, and quantitative recoveries were obtained for the spiking experiments.

  2. Selective estrogen receptor-beta (SERM-beta) compounds modulate raphe nuclei tryptophan hydroxylase-1 (TPH-1) mRNA expression and cause antidepressant-like effects in the forced swim test.

    PubMed

    Clark, J A; Alves, S; Gundlah, C; Rocha, B; Birzin, E T; Cai, S-J; Flick, R; Hayes, E; Ho, K; Warrier, S; Pai, L; Yudkovitz, J; Fleischer, R; Colwell, L; Li, S; Wilkinson, H; Schaeffer, J; Wilkening, R; Mattingly, E; Hammond, M; Rohrer, S P

    2012-11-01

    Estrogen acts through two molecularly distinct receptors termed estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which bind estradiol with similar affinities and mediate the effects of estrogen throughout the body. ERα plays a major role in reproductive physiology and behavior, and mediates classic estrogen signaling in such tissues as the uterus, mammary gland, and skeleton. ERβ, however, modulates estrogen signaling in the ovary, the immune system, prostate, gastrointestinal tract, and hypothalamus, and there is some evidence that ERβ can regulate ERα activity. Moreover, ERβ knockout studies and receptor distribution analyses in the CNS suggest that this receptor may play a role in the modulation of mood and cognition. In recent years several ERβ-specific compounds (selective estrogen receptor beta modulators; SERM-beta) have become available, and research suggests potential utility of these compounds in menopausal symptom relief, breast cancer prevention, diseases that have an inflammatory component, osteoporosis, cardiovascular disease, and inflammatory bowel disease, as well as modulation of mood, and anxiety. Here we demonstrate an antidepressant-like effect obtained using two SERM-beta compounds, SERM-beta1 and SERM-beta2. These compounds exhibit full agonist activity at ERβ in a cell based estrogen response element (ERE) transactivation assay. SERM-beta1 and 2 are non-proliferative with respect to breast as determined using the MCF-7 breast cancer cell-based assay and non-proliferative in the uterus as determined by assessing the effects of SERM-beta compounds on immature rat uterine weight and murine uterine weight. In vivo SERM-beta1 and 2 are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein. These compounds show activity in the murine forced swim test and promote hippocampal neurogenesis acutely in rats. Taken

  3. Exposure to an environmental estrogen breaks down sexual isolation between native and invasive species

    PubMed Central

    Ward, Jessica L; Blum, Michael J

    2012-01-01

    Environmental change can increase the likelihood of interspecific hybridization by altering properties of mate recognition and discrimination between sympatric congeners. We examined how exposure to an environmentally widespread endocrine-disrupting chemical (EDC), bisphenol A (BPA), affected visual communication signals and behavioral isolation between an introduced freshwater fish and a native congener (genus: Cyprinella). Exposure to BPA induced changes in the expression of male secondary traits as well as male and female mate choice, leading to an overall reduction in prezygotic isolation between congeners. Changes in female mate discrimination were not tightly linked to changes in male phenotypic traits, suggesting that EDC exposure may alter female choice thresholds independently of the effects of exposure on males. These findings indicate that environmental exposure to EDCs can lead to population declines via the erosion of species boundaries and by promoting the establishment and spread of non-native species via hybridization. PMID:23346234

  4. Estrogenic flavonoids: structural requirements for biological activity.

    PubMed

    Miksicek, R J

    1995-01-01

    A systematic survey of polycyclic phenols has been performed to identify members of this chemical group with estrogenic activity. Twelve compounds were found to be able to stimulate the transcriptional activity of the human estrogen receptor expressed in cultured cells by transient transfection. These natural estrogens belong to several distinct, but chemically related classes including chalcones, flavanones, flavones, flavonols, and isoflavones. Selected examples of estrogenic flavonoids were further analyzed to determine their biological potencies and their relative affinities for binding to the estrogen receptor. These data are interpreted with respect to the molecular structure of polycyclic phenols required for hormonal activity as nonsteroidal estrogens.

  5. Population responses of the freshwater amphipod Gammarus pulex (L.) to an environmental estrogen, 17alpha-ethinylestradiol.

    PubMed

    Watts, Matthew M; Pascoe, David; Carroll, Kathleen

    2002-02-01

    The effects of the environmental estrogen 17alpha-ethinylestradiol (EE) on mixed populations of 90 individual Gammarus pulex were examined following a 100-d exposure in a flow-through system. Counts of total animal numbers revealed that, in all treatment groups, population size dramatically increased due to recruitment, with neonate and juvenile gammarids the most abundant. At concentrations of 1 and 10 microg/L EE, the recorded mean population sizes of 385 and 411, respectively, were significantly greater (p = 0.018) than the control (169). Mean population sizes in the solvent control (257) and 100 ng/L EE treatment (267) were not significantly different (p > 0.05) from the control. In addition to total counts, detailed image analysis of each individual animal allowed the assessment of length-frequency distributions, adult sex ratio, number of precopula pairs/ovigerous females, and measurement of secondary antenna and gnathopod length (secondary sex characteristics). The sex ratio of adults at 100 ng, 1 microg, and 10 microg/L EE was greater than 2:1 (female:male), and significantly more females (p = 0.008) were recorded at these concentrations compared with the control. The number of male adults, precopula guarding pairs, and ovigerous females did not differ between treatments (p > 0.05). Secondary antennal and gnathopod length in males was consistently greater than in females (p < or = 0.001), but comparison between groups revealed no difference in these parameters.

  6. Dispersive liquid-liquid microextraction for four phenolic environmental estrogens in water samples followed by determination using capillary electrophoresis.

    PubMed

    Liu, Junying; Lu, Wenhui; Liu, Huitao; Wu, Xiaqing; Li, Jinhua; Chen, Lingxin

    2016-10-01

    Dispersive liquid-liquid microextraction (DLLME) coupled with CE was successfully developed for simultaneous determination of four types of phenolic environmental estrogens (PEEs), namely hexestrol (HS), bisphenol A (BPA), diethylstilbestrol (DES) and dienestrol (DS). Several parameters affecting DLLME and CE conditions were systematically investigated including the type and volume of extraction solvent and dispersive solvent, extraction time, salt, pH value, surfactant, buffer solution and so on. Under the optimal conditions, DLLME-CE exhibited strong enrichment ability, presenting high enrichment factors of 467, 241, 367 and 362 for HS, BPA, DES and DS, respectively, as well as low detection limits of 0.3, 0.6, 0.6 and 0.3 μg/L, respectively. Excellent linearity was achieved in the range of 2.0-150 μg/L for HS and DS, and 4.0-300 μg/L for BPA and DES, with correlation coefficients R>0.9983. Recoveries ranging from 70.4 to 108.1% were obtained with tap water, lake water and seawater samples spiked at three concentration levels and the relative standard deviations (RSDs, for n = 5) were 2.1-9.7%. This DLLME-CE method with high selectivity and sensitivity, high stability, simplicity, cost-effectiveness, eco-friendliness was proved potentially applicable for the rapid and simultaneous determination of PEEs in complicated water samples.

  7. Estrogenic effects from household stoves.

    PubMed

    Wu, W Z; Chen, J; Rehmann, K; Schramm, K W; Kettrup

    2002-09-01

    With the application of a genetically modified yeast, estrogen receptor-activating compounds were detected in the soot and emission gas of a wood-burning household stove. The EC50 value of 17beta-estradiol was divided by the EC50 value of soot, and the obtained relative estrogenic value for raw soot was 2.37E-5, indicating that soot was about 100,000 times less estrogenic than 17beta-estradiol. Chemical analysis revealed that alkyl phenol, benzonic acid, and PAHs represented the major constituents in the most potent fractions of the soot. Along with PAHs, other constituents might also contribute to the estrogenicity of soot.

  8. Molecular Modeling for Screening Environmental Chemicals for Estrogenicity: Use of the Toxicant-Target Approach

    EPA Science Inventory

    There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the pre...

  9. ASSESSMENT OF DIFFERENTIAL GENE EXPRESSION IN SHEEPSHEAD MINNOWS EXPOSED TO ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    Gene arrays and quantitative real-time PCR (Q-PRC) are sensitive methods for assessing exposure of fish and other wildlife to environmental contaminants by measuring changes in gene expression. Several genes normally induced by estradiol in female fish, those for vitellogenins (...

  10. Antiestrogenicity and estrogenicity in leachates from solid waste deposits.

    PubMed

    Svenson, Anders; Sjöholm, Sofia; Allard, Ann-Sofie; Kaj, Lennart

    2011-06-01

    A great deal of effort has been devoted to developing new in vitro and in vivo methods to identify and classify endocrine disrupting chemicals that have been identified in environmental samples. In this study an in vitro test based on recombinant yeast strains transfected with genes for the human estrogen receptor α was adapted to examine the presence of estrogenic and antiestrogenic substances in six Swedish landfill leachates. Antiestrogenic effects were measured as inhibition of the estradiol induced response with the human estrogen receptor α, and quantified by comparison with the corresponding inhibitory effects of a known antiestrogen, hydroxytamoxifen. The estrogenicity was within the range of that determined in domestic sewage effluents, from below the limit of detection to 29 ng estradiol units L(-1). Antiestrogenicity was detected in some of the investigated landfill leachates, ranging between <38 and 3800 μg hydroxytamoxifen equivalents L(-1). There was no apparent relation between the type of waste deposited on the landfills and the antiestrogenic effect. Fractionation of a landfill leachate showed that estrogenic compounds were located in two dominant fractions. Three estrogenic compounds were found that accounted for the estrogenic activity in extracts of leachates: bisphenol A, estradiol, and ethinylestradiol. The bisphenol may have been released from decomposing plastic waste and the estrogenic steroids from earlier deposits of municipal sewage sludge and pharmaceutical waste. Fractionation of leachates from three parts of a landfill showed that the antiestrogenic activity was distributed in at least four fractions and somewhat different in different flows of leachate. This indicated a heterogeneous mixture of antiestrogenic substances.

  11. Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons

    SciTech Connect

    Davisson, M L; Love, A H; Vance, A; Reynolds, J G

    2005-02-08

    Man-made organophosphorus compounds have been widely distributed throughout our environment as pesticides since their development during and after WWII. Many important studies have documented their relative persistence and toxicity. Development and use of some organophosphorus compounds as nerve agents gave rise to a separate but parallel effort to understand environmental persistence. In this latter case, the experiments have focused mainly on evaporation rates and first-order reaction kinetics. However, because organophosphorus compounds are easily polarized, the ionic content of a surrounding media directly factors into these reaction rates, but limited work in this regard has been done under environmentally relevant conditions. Furthermore, limited experiments investigating persistence of these agents on soil has resulted in widely varying degradation rates. Not surprisingly, no studies have investigated affinities of organophosphorus nerve agents to mineral or organic matter typically found in soil. As a result, we initiated laboratory experiments on dilute concentrations of nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) to quantify persistence in simulated environmental aqueous conditions. A quantitative analytical method was developed for VX and its degradation products using High Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). VX hydrolysis rate is known to have a pH-dependency, however, the type of buffer and the relative proportion of different nucleophiles in solution significantly affect the overall rate and mechanism of degradation. For example, dissolved carbonate, a weak nucleophile dominating natural water, yielded pseudo-first order rate constants of {approx} 8 x 10{sup -3}/hr at pH 5 and 2 x 10{sup -2}/hr at pH 11. This small pH-dependent variation departs significantly from widely accepted rates at this pH range (4 x 10{sup -4}/hr to 8 x 10{sup -2}/hr) that were based on

  12. Fluorescence spectroscopy of polynuclear aromatic compounds in environmental monitoring.

    PubMed

    Kumke, M U; Löhmannsröben, H G; Roch, T

    1995-06-01

    The occurrence of polynuclear aromatic compounds (PAC) in the environment and experimental techniques suitable for the detection of PAC in environmental compartments are briefly reviewed. The specific requirements for on-site andin situ environmental analysis are outlined. Particular emphasis is given to fluorescence spectroscopic techniques for the investigation of humic acid- and soil-containing samples. Some examples of studies in the literature on Shpol'skii and jet spectroscopy and on laser-induced fluorescence (OF) measurements of PAC and mineral oils are highlighted. Contaminants in the environment are usually encountered as multicomponent mixtures in very complex matrices. Total fluorescence analysis in combination with the chemometrical technique of rank annihilation factor analysis (RAFA) was employed for the evaluation of a six-component PAC mixture in toluene. It was shown that even in the presence of strong spectral overlap the qualitative identification of all compounds and the reliable quantification of five substances was possible. Results are presented from our stationary and time-resolved fluorescence investigations of the interactions between pyrene and humic acid in water. The Stern-Volmer analysis showed a significant effect of pH on the static quenching efficiency which can be explained by the pH-dependent macromolecular structure of humic acids. Preliminary results from studies of the deactivation of triplet PAC and quenching of delayed fluorescence by humic acid are reported. LIF measurements of mineral oils directly from soil surfaces and of a model oil in a soil column were performed with a fiber-optic coupled multichannel spectrometer. The fluorescence intensity/ concentration relationships were established for a crude and a fuel oil; the corresponding lower limits of detection (LOD) were determined to be 0.025 and 0.125% m/m (mass/mass percentages). These detection limits are compared with realistic oil contaminations of soils. In a soil

  13. Evaluating Cost when Selecting Performance Reference Compounds for the Environmental Deployment of Polyethylene Passive Samplers

    EPA Science Inventory

    A challenge in environmental passive sampling is determining when equilibrium is achieved between the sampler, target contaminants, and environmental phases. A common approach is the use of performance reference compounds (PRCs) to indicate degree of equilibrium. One logistical...

  14. Capillary electrochromatography and nano-liquid chromatography coupled to nano-electrospray ionization interface for the separation and identification of estrogenic compounds.

    PubMed

    D'Orazio, Giovanni; Hernández-Borges, Javier; Asensio-Ramos, María; Rodríguez-Delgado, Miguel Ángel; Fanali, Salvatore

    2016-01-01

    Nano-LC and CEC were coupled to MS through a nanospray or a pressurized liquid-junction interface for the simultaneous separation and determination of 11 estrogenic compounds. Different stationary phases, that is, phenyl, C18, and C18 bidentate silica hydrate, were studied. For both techniques, the phenyl stationary phase was the best option, considering separation efficiency, selectivity, and resolution. Under the optimized conditions, the baseline separation of the target compounds (including estradiol and zearalanol epimers) was achieved in less than 20 min in nano-LC-MS and less than 13 min in CEC-MS. Molecular imprinted polymer SPE was used for extracting the target compounds from mineral water samples with the analysis of nano-LC-MS. The whole molecular imprinted polymer SPE nano-LC-MS method was validated through a recovery study at two levels of concentration. Sensitivity was improved by on-column focusing technique obtaining LODs in the range 1.4-55.4 ng/L.

  15. Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green.

    PubMed

    Jiao, Baowei; Yeung, Eric K C; Chan, Chi Bun; Cheng, Christopher H K

    2008-12-15

    Endocrine disruptors refer to chemical compounds in the environment which interfere with the endocrine systems of organisms. Among them, environmental estrogens pose serious problems to aquatic organisms, in particular fish. It is therefore important and necessary to have a fast and low-cost system to screen the large number of different chemical compounds in the aquatic environment for their potential endocrine disrupting actions. In this study, a screening platform was developed to detect xenoestrogens in the aquatic environment using the fission yeast Schizosaccharomyces pombe, and applied for compound screening. The aim was to demonstrate any significant potential differences between the fish screening system and the human screening system. To this end, a yeast expression vector harboring a fish estrogen receptor alpha and a reporter vector containing the estrogen responsive element fused with the Escherichia coli LacZ gene were constructed. After transformation with these two vectors, the transformed yeast clones were confirmed by Western blotting and selected on the basis of the beta-galactosidase activity. In this transgenic yeast system, the natural estrogen (estradiol) and other known xenoestrogens such as diethylstilbestrol, bisphenol A, genistein and dichloro-diphenyl-trichloroethane exhibited dose-dependent activities. Using this system, more than 40 putative endocrine disruptors including phytoestrogens, pesticides, herbicides, industrial dyes and other industrial chemicals were screened. Ten of them were demonstrated to exhibit estrogenic actions. Industrial dyes such as malachite green (MG) that disrupt thyroid hormone synthesis are extensively used and are widely distributed in the aquatic environment. Using this system, MG did not show any estrogenic action, but was demonstrated to exhibit anti-estrogenic activity.

  16. Detection and occurrence of chlorinated byproducts of bisphenol a, nonylphenol, and estrogens in drinking water of china: comparison to the parent compounds.

    PubMed

    Fan, Zhanlan; Hu, Jianying; An, Wei; Yang, Min

    2013-10-01

    This study applied a sensitive dansylation LC-MS/MS method to the investigation on the occurrence of bisphenol A (BPA), nonylphenol (NP), estrogens (E1 and E2), and their 11 chlorinated byproducts in 62 drinking water treatment plants (DWTPs) of 31 major cities across China. BPA (4.7-512 ng/L), NP (8.2-918 ng/L), and E1 (ND-9.9 ng/L) were widely detected in source waters, E2 was detected in less than half of the samples (ND-3.2 ng/L), while chlorinated byproducts were only detected in source waters of two DWTPs. In drinking water, chlorinated BPAs and monochloro-NP (MCNP) were detected in more than half of the samples with concentrations of 0.2-26.7 ng/L for monochloro-BPA (MCBPA), ND-6.3 ng/L for dichloro-BPA (DCBPA), ND-7.7 ng/L for trichloro-BPA (TCBPA), ND-4.8 ng/L for tetrachloro-BPA (TBBPA), and ND-13.3 ng/L for MCNP, while dichloro-E1 (DCE1, ND-0.2 ng/L) and dichloro-NP (DCNP, ND-1.6 ng/L) were less frequently detected (10/62 and 4/62). The production of chlorinated NPs in DWTPs was mainly influenced by the amount of NP in source water and chlorine added, while the concentrations of chlorinated BPAs in drinking waters were only found to be significantly correlated with those of BPA in source waters. Advanced treatment processes could be effective techniques for reducing target chlorinated byproducts in drinking water. This is the first report on the occurrence of chlorinated byproducts of BPA, NP, and estrogens in drinking water, and these chemicals should be considered when assessing the human risk of their parent compounds.

  17. Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines.

    PubMed

    van Duursen, Majorie B M; Sanderson, J Thomas; van der Bruggen, Marieke; van der Linden, Jeroen; van den Berg, Martin

    2003-08-01

    In human breast tissue, estrone (E(1)) and estradiol (E(2)) are mainly hydroxylated by cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) to 2-hydroxyestrogens (2-OHE(1/2)) and 4-hydroxyestrogens (4-OHE(1/2)), respectively. Several studies show that 4-OHE(1/2), but not 2-OHE(1/2), may act as a carcinogen and a high estrogen 4-/2-hydroxylation ratio appears to be a marker for the presence of neoplasms. In this study, we investigated the effects of several dioxin-like compounds on estrogen 2- and 4-hydroxylation in a malignant (MCF-7) and a nontumorigenic (MCF-10A) human mammary epithelial cell line. 2- and 4-methoxyestrogen (MeOE(1/2)) formations were used as measures of the 2- and 4-hydroxylation pathways, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3'4,4',5,5'-hexachlorobiphenyl (PCB 169) concentration dependently induced 2-MeOE(1/2) formation and ethoxyresorufin-O-deethylation (EROD) activity through induced CYP1A1 expression in MCF-7 and MCF-10A cells. 2,3',4,4',5-pentachlorobiphenyl (PCB 118) had no such effect. Effects on CYP1B1 expression and 4-MeOE(1/2) formation were less pronounced; only TCDD caused an induction, whereas PCB 169 was a potent and selective inhibitor of 4-MeOE(1/2) formation (IC(50) 0.7 and 2.2 nM PCB 169 in MCF-7 and MCF-10A cells, respectively). MCF-10A cells were less responsive toward dioxin-like compounds and the apparent EC(50) values for CYP1A1 and CYP1B1 induction in this study were 10-100 fold higher than in MCF-7 cells. The constitutive 4-/2-MeOE(1/2) ratios were 2.99 +/- 0.78 and 0.93 +/- 0.40 in MCF-7 and MCF-10A, respectively. Incubation with dioxin-like compounds resulted in a concentration-dependent decrease in the 4-/2-MeOE(1/2) ratio, but an increase in potentially carcinogenic estrogen metabolites in both MCF-7 and MCF-10A cells. This indicates that even though the 4-/2-OHE(1/2) ratio may be used as indicator for the presence

  18. Estrogen supplements in menopause.

    PubMed

    Booher, D L

    1990-01-01

    The number of women aged 65 and older is expected to double by the year 2000, increasing the need for effective management of symptoms related to menopause. Contemporary management of menopause addresses the continuum of events associated with the effects of estrogen deprivation on quality and duration of life, including neuroendocrine changes, urogenital atrophy, sexual dysfunction, skin and hair changes, osteoporosis, and cardiovascular disease. The risks and benefits of management strategies, including hormone replacement therapy, must be weighted carefully by both physician and patient. The use of estrogens and progestins, alterative compounds, dosages, routes of administration, and their advantages and disadvantages must be analyzed.

  19. EMISSION OF VOLATILE COMPOUNDS BY SEEDS UNDER DIFFERENT ENVIRONMENTAL CONDITIONS

    EPA Science Inventory

    Small mammals locate buried wet seeds more efficiently than buried dry seeds. This may be attributable to emission of volatile compounds by the seeds. To test this hypothesis I measured emission of volatile compounds from seeds of three plant species (Pinus contorta, Purshia tr...

  20. Sex differences and effects of estrogenic compounds on the expression of inflammatory molecules by astrocytes exposed to the insecticide dimethoate.

    PubMed

    Astiz, Mariana; Acaz-Fonseca, Estefania; Garcia-Segura, Luis M

    2014-04-01

    A low dose of the organophosphorus insecticide dimethoate (DMT) produces oxidation of lipids and proteins and impairs mitochondrial function in the brain of male rats, together with a reduction of gonadal hormones in plasma. Here, we have assessed whether DMT affected the expression of inflammatory molecules, the production of reactive oxygen species (ROS), and the expression of steroidogenic proteins and estrogen receptors in cortical astrocyte-enriched cultures obtained separately from male and female CD1 mice pups. Furthermore, we have analyzed whether estradiol may counteract the effects of DMT. A dose of DMT (2 μg/mL) did not affect cell viability, increased interleukin (IL) 6, IL1β, tumor necrosis factor (TNF)α, interferon-γ-inducible protein 10 (IP10), ERβ, steroidogenic acute regulatory protein, and aromatase mRNA levels and ERα protein levels in male but not in female cultures. Estradiol decreased the mRNA levels of IL6, IP10, TNFα, and IL1β in male but not in female cultures treated with DMT. The effect of estradiol was prevented by the ER antagonist ICI 182,780, fully imitated by an ERβ agonist and partially imitated by an ERα agonist. Furthermore, DMT increased the production of ROS in male astrocytes while estradiol reduced ROS production to control levels. These findings indicate that a sublethal dose of DMT alters astrocyte function. The selective action of estradiol on male astrocytes and the sexually dimorphic action of DMT suggest that the pesticide may have different neurological outcomes in males and females.

  1. Presence of estrogenic activity from emission of fossil fuel combustion as detected by a recombinant yeast bioassay

    NASA Astrophysics Data System (ADS)

    Wang, Jingxian; Wu, Wenzhong; Henkelmann, Bernhard; You, Li; Kettrup, Antonius; Schramm, Karl-Werner

    Estrogenic activities of emission samples generated by fossil fuel combustion were investigated with human estrogen receptor (ER) recombinant yeast bioassay. The results showed that there were weak but clear estrogenic activities in combustion emissions of fossil fuels including coal, petroleum, and diesel. The estrogenic relative potency (RP) of fossil fuel combustion was the highest in petroleum-fired car, followed by coal-fired stove, diesel-fired agrimotor, coal-fired electric power station. On the other hand, the estrogenic relative inductive efficiency (RIE) was the highest in coal-fired stove and coal-fired electric power station, followed by petroleum-fired car and diesel-fired agrimotor. The estrogenic activities in the sub-fractions from chromatographic separation of emitted materials were also determined. The results indicated that different chemical fractions in these complex systems have different estrogenic potencies. The GC/MS analysis of the emission showed that there were many aromatic carbonyls, big molecular alcohol, PAHs and derivatives, and substituted phenolic compounds and derivatives which have been reported as environmental estrogens. The existence of estrogenic substances in fossil fuel combustion demands further investigation of their potential adverse effects on human and on the ecosystem. The magnitude of pollution due to global usage of fossil fuels makes it imperative to understand the issue of fossil fuel-derived endocrine activities and the associated health risks, particularly the aggregated risks stemmed from exposure to toxicants of multiple sources.

  2. Validation and application of a rapid in vitro assay for assessing the estrogenic potency of halogenated phenolic chemicals.

    PubMed

    Körner, W; Hanf, V; Schuller, W; Bartsch, H; Zwirner, M; Hagenmaier, H

    1998-01-01

    The E-Screen assay serves as an in vitro tool for the detection of estrogenic activity of chemicals and extracts of environmental samples. Based on the induction of proliferation in human estrogen receptor-positive MCF-7 breast cancer cells we could substantially simplify the assay. As one important step of validation we applied the modified assay for testing nine known xenoestrogens. We could confirm the results of other groups assuring the reproducibility of the E-Screen assay. The results provide evidence that the E-Screen assay is suitable for determination of estradiol equivalency factors (EEFs) for environmental estrogens to rank their estrogenic potency relative to the natural estrogen 17 beta-estradiol. Further, we used the optimized proliferation test to screen nine halogenated phenolic compounds for their possible estrogenic potency. Three widely applied chemicals expressed a weak receptor-mediated estrogenic activity: the flame retardant Tetrabromo-Bisphenol-A, the disinfectant 4-chloro-3-methylphenol, and the herbicide educt 4-chloro-2-methylphenol. Their estrogenic potencies were five to six orders of magnitude lower than that of 17 beta-estradiol.

  3. Species comparisons in molecular and functional attributes of the androgen and estrogen receptor

    EPA Science Inventory

    While endocrine disrupting compounds (EDCs) have the potential to act via several mechanisms of action, one of the most widely studied is the ability of environmental chemicals to interact directly with either the estrogen (ER) or androgen receptor (AR). In vitro screening assay...

  4. ENVIRONMENTAL ESTROGENS AND CANCER

    EPA Science Inventory

    One in eight women is predicted to be diagnosed with breast cancer this year. Of those afflicted with the disease, only about one-quarter will have a family history that helps to explain their diagnosis. The rest have what is termed sporadic cancer, potentially influenced by l...

  5. Co-occurrence of estrogenic and antiestrogenic activities in wastewater: quantitative evaluation of balance by in vitro ERα reporter gene assay and chemical analysis.

    PubMed

    Ihara, Masaru; Ihara, Mariko O; Kumar, Vimal; Narumiya, Masanori; Hanamoto, Seiya; Nakada, Norihide; Yamashita, Naoyuki; Miyagawa, Shinichi; Iguchi, Taisen; Tanaka, Hiroaki

    2014-06-03

    Endocrine-disrupting chemicals are exogenous substances that alter the function of the endocrine system, with adverse health effects on organisms or their progeny. In vitro estrogen receptor (ER) reporter gene assays have long been used to measure estrogenic activity in wastewater. Nevertheless, there is still uncertainty about their usefulness in environmental monitoring on account of a discrepancy between the estrogenic response of the in vitro assay and concentrations of estrogenic compounds determined by chemical analysis. Here, we measured estrogenic and antiestrogenic activities in wastewater by ERα reporter gene assay. All samples were simultaneously analyzed for estrone, 17β-estradiol, estriol, and 17α-ethynylestradiol, and the concentrations were used to predict estrogenic activity. All samples in which measured estrogenic activity was significantly lower than predicted showed strong antiestrogenic activity. In addition, we confirmed that the fraction that did not have antiestrogenic activity showed stronger estrogenic activity than the unfractionated wastewater extract. These results indicate that antiestrogenic compounds in wastewater suppress the activity of natural estrogens, and the reporter gene assay represents the net activity.

  6. Estrogenic compounds, chemical quantitation, biological assessment – What we know, what we don’t, and what should our future priorities be?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over the last two decades, the literature has become replete with reports quantifying estrogenic chemicals in the environment ranging from natural hormones to plasticizers. In addition to measuring concentrations, laboratories have developed various in vitro assays to assess estrogenic activity of ...

  7. Influences of sex, incubation temperature, and environmental quality on gonadal estrogen and androgen receptor messenger RNA expression in juvenile American alligators (Alligator mississippiensis).

    PubMed

    Moore, Brandon C; Milnes, Matthew R; Kohno, Satomi; Katsu, Yoshinao; Iguchi, Taisen; Guillette, Louis J

    2010-01-01

    Gonadal steroid hormone receptors play a vital role in transforming ligand signals into gene expression. We have shown previously that gonads from wild-caught juvenile alligators express greater levels of estrogen receptor 1 (ESR1) than estrogen receptor 2 (ESR2). Furthermore, sexually dimorphic ESR2 mRNA expression (female > male) observed in animals from the reference site (Lake Woodruff, FL, USA) was lost in alligators from the contaminated Lake Apopka (FL, USA). We postulated that environmental contaminant exposure could influence gonadal steroid hormone receptor expression. Here, we address questions regarding gonadal estrogen and androgen receptor (AR) mRNA expression in 1-yr-old, laboratory-raised alligators. What are relative expression levels within gonads? Do these levels vary between sexes or incubation temperatures? Can contaminant exposure change these levels? We observed a similar pattern of expression (ESR1 > AR > ESR2) in ovary and testis. However, both incubation temperature and environment modulated expression. Males incubated at 33.5 degrees C expressed greater AR levels than females incubated at 30 degrees C; dimorphic expression was not observed in animals incubated at 32 degrees C. Compared to Lake Woodruff alligators, Lake Apopka animals of both sexes showed lesser ESR2 mRNA expression levels. Employing cluster analyses, we integrated these receptor expression patterns with those of steroidogenic factors. Elevated ESR2 and CYP19A1 expressions were diagnostic of alligator ovary, whereas elevated HSD3B1, CYP11A1, and CYP17A1 expressions were indicative of testis. In contrast, AR, ESR1, and NR5A1 showed variable expressions that were not entirely associated with sex. These findings demonstrate that the mRNA expression of receptors required for steroid hormone signaling are modified by exposure to environmental factors, including temperature and contaminants.

  8. The environmental impact of growth-promoting compounds employed by the United States beef cattle industry: history, current knowledge, and future directions.

    PubMed

    Kolok, Alan S; Sellin, Marlo K

    2008-01-01

    The current state of knowledge regarding the environmental impact of growth-promoting compounds associated with the U.S. beef cattle industry is extensive in some areas but virtually nonexistent in others. The compounds administered to the cattle are quite well understood, as are bovine metabolism and excretion. If the sex and age of the cattle on the feedlot are known, the metabolites excreted by the cattle should be predictable with a great deal of accuracy. The fate, transport, and biological effects of growth-promoting compounds are just beginning to be studied. Most of the research conducted on the fate and transport of growth-promoting compounds has focused on 17beta-E2; however, much of this research was not conducted using feedlot runoff or manure. Studies are needed that focus specifically on manures and runoff from experimental or commercial feedlots. To date, the degree to which growth-promoting compounds are released from feedlots in a bioavailable form remains a point of speculation. The environmental fate and transport of TBA, P, and MGA have not been well studied. Comparisons between the fate and transport of T and 17beta-E2, however, make it clear that compounds with similar structure may behave very differently once released into the environment. Considering that 17beta-E2 is a naturally occurring estrogen and that TBA is a nonaromatizable androgen, it is not surprising that these compounds directly impact the reproductive physiology of fishes. The effects of these two compounds have been well documented, as has been described here; however, the effects of P and MGA exposures have gone largely uninvestigated. This is a serious critical gap in our knowledge base because progestogins play an important role in sex steroid synthesis and reproduction. Clearly, additional research on the consequences of exposures to P and MGA is warranted. The majority of research investigating the effects of 17beta-E2 and TBA metabolites on fish has been conducted in

  9. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

    A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet.

  10. Effect of diet on fecal and urinary estrogenic activity.

    PubMed

    Tucker, H A; Knowlton, K F; Meyer, M T; Khunjar, W O; Love, N G

    2010-05-01

    The United States Environmental Protection Agency has identified estrogens from animal feeding operations as a major environmental concern, but few data are available to quantify the excretion of estrogenic compounds by dairy cattle. The objectives of this study were to quantify variation in estrogenic activity in feces and urine due to increased dietary inclusion of phytoestrogens. Ten Holstein heifers were assigned to 2 groups balanced for age and days pregnant; groups were randomly assigned to treatment sequence in a 2-period crossover design. Dietary treatments consisted of grass hay or red clover hay, and necessary supplements. Total collection allowed for sampling of feed refusals, feces, and urine during the last 4 d of each period. Feces and urine samples were pooled by heifer and period, and base extracts were analyzed for estrogenic activity (estrogen equivalents) using the yeast estrogen screen bioassay. Feces and urine samples collected from 5 heifers were extracted and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify excretion of 7 phytoestrogenic compounds. Excretion of 17-beta estradiol equivalents in urine was higher and tended to be higher in feces for heifers fed red clover hay (84.4 and 120.2 mg/d for feces and urine, respectively) compared with those fed grass hay (57.4 and 35.6 mg/d). Analysis by LC-MS/MS indicated greater fecal excretion of equol, genistein, daidzein, coumestrol, and formononetin by heifers fed red clover hay (1634, 29.9, 96.3, 27.8, and 163 mg/d, respectively) than heifers fed grass hay (340, 3.0, 46.2, 8.8, and 18.3 mg/d, respectively). Diet had no effect on fecal biochanin A or 2-carbethoxy-5, 7-dihydroxy-4'-methoxyisoflavone. Four phytoestrogens were detected in urine (2-carbethoxy-5, 7-dihydroxy-4'-methoxyisoflavone, daidzein, equol, and formononetin) and their excretion was not affected by diet. Identifying sources of variation in estrogenic activity of manure will aid in the

  11. Modeling the photocatalytic mineralization in water of commercial formulation of estrogens 17-β estradiol (E2) and nomegestrol acetate in contraceptive pills in a solar powered compound parabolic collector.

    PubMed

    Colina-Márquez, José; Machuca-Martínez, Fiderman; Li Puma, Gianluca

    2015-07-22

    Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove commercial estradiol formulations (17-β estradiol and nomegestrol acetate) from water. Photolysis alone degraded up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm of TOC as initial concentration of the commercial estradiols formulation. The adsorption of estrogens over the catalyst was insignificant and was modeled by the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was modeled considering the reactor fluid-dynamics, the radiation field, the estrogens mass balance, and a modified Langmuir-Hinshelwood rate law, that was expressed in terms of the rate of photon adsorption. The optimum removal of the estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm diameter tubular CPC reactors which approached the optimum catalyst concentration and optical thickness determined from the modeling of the absorption of solar radiation in the CPC, by the six-flux absorption-scattering model (SFM).

  12. BIOCHEMICAL AND ANALYTICAL CHARACTERIZATION OF ESTROGENICALLY ACTIVE WASTEWATER: COMPARISON OF FIELD EXTRAPOLATIONS TO THE MEASURED CONCENTRATION OF ESTROGENS IN SEWAGE EFFLUENT

    EPA Science Inventory

    Estrogenically active wastewater was observed at two municipal wastewater treatment plants (WWTPs) utilizing caged male channel catfish in a previous study. The focus of this investigation was to identify and characterize the compound(s) responsible for this estrogenic response. ...

  13. Mathematical classification of regulatory logics for compound environmental changes.

    PubMed

    Tanaka, Reiko J; Kimura, Hidenori

    2008-03-21

    This paper is concerned with biological regulatory mechanisms in response to the simultaneous occurrence of a huge number of environmental changes. The restricted resources of cells strictly limit the number of their regulatory methods; hence, cells must adopt, as compensation, special mechanisms to deal with the simultaneous occurrence of environmental changes. We hypothesize that cells use various control logics to integrate information about independent environmental changes related to a cell task and represent the resulting effects of the different ways of integration by logical functions. Using the notion of equivalence classes in set theory, we describe the mathematical classification of the effects into biologically unequivalent ones realized by different control logics. Our purely mathematical and systematic classification of logical functions reveals three elementary control logics with different biological relevance. To better understand their biological significance, we consider examples of biological systems that use these elementary control logics.

  14. Interferences of an environmental pollutant with estrogen-like action in the male reproductive system of the terrestrial vertebrate Podarcis sicula.

    PubMed

    Verderame, Mariailaria; Limatola, Ermelinda

    2015-03-01

    Nonylphenol (NP) is classified among the endocrine disruptor chemicals with estrogen-like properties. It is widely used in many industries and to dilute pesticides in agriculture, and is known to affect the reproductive system of many aquatic and semi-aquatic organisms. This study aimed to verify how NP, administered via food and water, may interfere with the reproductive cycle of a terrestrial vertebrate. Our model was the male Italian wall lizard Podarcis sicula, a seasonal breeding species that may be naturally exposed to environmental pollution. From our findings it emerges that an NP-polluted diet administered during the mating period causes in this lizard a slowdown of spermatogenesis and affects the testicular and epididymal structure, making it similar to that of the non-reproductive period. The distribution in the testis and epididymis of mRNA for steroid hormone receptors, i.e., estrogen α and β and androgen receptors, was also investigated. NP treatment inhibits the expression of AR, ERα, and ERβ-mRNA in spermatogonia and primary spermatocytes and causes a switch-off of the secretory activity of the epididymal corpus by inducing the expression of ERα.

  15. Biological validation of a sample preparation method for ER-CALUX bioanalysis of estrogenic activity in sediment using mixtures of xeno-estrogens.

    PubMed

    Houtman, Corine J; Van Houten, Yoni K; Leonards, Pim E G; Brouwer, Abraham; Lamoree, Marja H; Legler, Juliette

    2006-04-01

    The combined estrogenic effects of mixtures of environmental pollutants in the in vitro ER-CALUX (chemical activated luciferase gene expression) bioassaywere examined to biologically validate a sample preparation method for the analysis of estrogenic compounds in sediment. The method used accelerated solvent extraction (ASE) and gel permeation chromatography (GPC) and was validated with respect to recovery of biological response taking mixture effects into account. Four mixtures of three to six xenoestrogenic compounds (bisphenol A, 4-nonylphenol, (4,4'-dichlorodiphenyl)trichloroethane, (2,4'-dichlorodiphenyl)trichloroethane, dieldrin, 4-n-octylphenol, alpha-chlordane, dibutylphthalate, (4,4'-dichlorodiphenyl)dichloroethylene, and 2,4,5-trichlorobiphenyl) were prepared. Experimentally determined mixture effects were well described by the concept of concentration addition (CA), as expected for similarly acting compounds. Observed estradiol equivalence factors of the mixtures (on average 1.2 +/- 0.3) agreed very well with the value predicted according to CA. The sample preparation method was then applied to pure mixtures of standards and to sediment spiked with one of the mixtures. Recoveries of estrogenic compounds were estimated by determination of their mixture potencies in ER-CALUX and compared to the mixture effects predicted by CA. Recoveries of estrogenic activity were between 80 and 129%, indicating that the additive behavior of mixtures of xeno-estrogens is well conserved during sample preparation. Together with an average repeatability of 18.3%, low average limit of detection (2.6 +/- 1.8 pg of EEQ/ g), and coefficient of variance (3.5 +/- 3.3%),this demonstrated the suitability of the sample preparation method for the analysis of mixtures of (xeno-)estrogenic compounds in sediment with the ER-CALUX assay.

  16. Environmental fate of the antifouling compound zinc pyrithione in seawater.

    PubMed

    Grunnet, Katja S; Dahllöf, Ingela

    2005-12-01

    To perform a thorough risk assessment of the new antifouling compound zinc pyrithione (ZnPT2), additional information regarding the fate of the compound is needed. The present study examined the recovery and transchelation of ZnPT2 in controlled laboratory experiments, photodegradation experiments, and a fate study in a large-scale field experiment. Chemical analyses were performed using a newly developed method for simultaneous analyses of ZnPT2 and copper pyrithione (CuPT2). Furthermore, two antifouling paints containing ZnPT2 were examined for the fate of leaching biocide. Naturally occurring ligands and metals in seawater influence the stability of ZnPT2. The presence of free Cu2+, which is present naturally in the seawater or is released from copper-containing paints, results in a partial transchelation of ZnPT2 into CuPT2. A complete transchelation of ZnPT2 into CuPT2 was observed when Cu2+ was present at an equimolar concentration in the absence of interfering ligands. When ZnPT2 was leached from antifouling paints containing both ZnPT2 and Cu2O, CuPT2 was found, with no trace of ZnPT2. Photodegradation was low in natural waters and absent from 1 m or more below the surface. The results show that ZnPT2 has a low persistence in seawater when leached from antifouling paints. However, the more stable and toxic transchelation product CuPT2 is formed, which has the potential to accumulate in the sediments and, therefore, should be included in both chemical analysis and risk assessment of ZPT2.

  17. Transport capabilities of environmental Pseudomonads for sulfur compounds.

    PubMed

    Zerbs, Sarah; Korajczyk, Peter J; Noirot, Philippe H; Collart, Frank R

    2017-04-01

    Sulfur is an essential element in plant rhizospheres and microbial activity plays a key role in increasing the biological availability of sulfur in soil environments. To better understand the mechanisms facilitating the exchange of sulfur-containing molecules in soil, we profiled the binding specificities of eight previously uncharacterized ABC transporter solute-binding proteins from plant-associated Pseudomonads. A high-throughput screening procedure indicated eighteen significant organosulfur binding ligands, with at least one high-quality screening hit for each protein target. Calorimetric and spectroscopic methods were used to validate the best ligand assignments and catalog the thermodynamic properties of the protein-ligand interactions. Two novel high-affinity ligand-binding activities were identified and quantified in this set of solute-binding proteins. Bacteria were cultured in minimal media with screening library components supplied as the sole sulfur sources, demonstrating that these organosulfur compounds can be metabolized and confirming the relevance of ligand assignments. These results expand the set of experimentally validated ligands amenable to transport by this ABC transporter family and demonstrate the complex range of protein-ligand interactions that can be accomplished by solute-binding proteins. Characterizing new nutrient import pathways provides insight into Pseudomonad metabolic capabilities which can be used to further interrogate bacterial survival and participation in soil and rhizosphere communities.

  18. The Expression of Leptin, Estrogen Receptors, and Vitellogenin mRNAs in Migrating Female Chum Salmon, Oncorhynchus keta: The Effects of Hypo-osmotic Environmental Changes.

    PubMed

    Choi, Young Jae; Kim, Na Na; Shin, Hyun Suk; Choi, Cheol Young

    2014-04-01

    Leptin plays an important role in energy homeostasis and reproductive function in fish, especially in reproduction. Migrating fish, such as salmonoids, are affected by external environmental factors, and salinity changes are a particularly important influence on spawning migrations. The aim of this study was to test whether changes in salinity affect the expression of leptin, estrogen receptors (ERs), and vitellogenin (VTG) in chum salmon (Oncorhynchus keta). The expression and activity of leptin, the expression of ERs and VTG, and the levels of estradiol-17β and cortisol increased after the fish were transferred to FW, demonstrating that changes in salinity stimulate the HPG axis in migrating female chum salmon. These findings reveal details about the role of elevated leptin levels and sex steroid hormones in stimulating sexual maturation and reproduction in response to salinity changes in chum salmon.

  19. Investigation of the estrogenic activities of pesticides from Pal-dang reservoir by in vitro assay.

    PubMed

    Oh, Young Jin; Jung, Yeon Jung; Kang, Joon-Wun; Yoo, Young Sook

    2007-12-15

    Endocrine disruptors, when absorbed into the body, interfere with the normal function by mimicking or blocking the hormone system. To investigate compounds mimicking estrogen in the drinking water source of the residence of Seoul, the Pal-dang reservoir was monitored over a period of 5 years, between 2000 and 2004. Nine kinds of pesticide (carbaryl, DBCP, diazinon, fenitrothion, fenobucarb, flutolanil, iprobenphos, isoprothiolane and parathion) were found to exist in the river water sample. These compounds were detected at low concentrations in the water samples. The total concentration and those of each of these pesticides were below the permissible limits of the National Institute of Environmental Research (NIER), Korea. The estrogenic potencies of the nine pesticides were examined using an E-screen assay with MCF-7 BUS estrogen receptor (ER)-positive human breast cancer cells, with ER-negative MDA MB 231 cell lines also used to compare the results. From this, flutolanil and isoprothiolane were confirmed to have estrogenic activities as shown by the increasing MCF-7 BUS cell growth on their addition. In addition, the estrogen receptor alpha (ERalpha) protein, estrogen receptor-regulated progesterone receptor (PR) and pS2 mRNA levels on the addition of flutolanil and isoprothiolane were measured with MCF-7 BUS cells. It was observed that the levels of ERalpha protein decreased and those of the PR and pS2 genes increased on the addition of either flutolanil or isoprothiolane at concentrations of 10(-4) M, in the same manner as with the addition of 17beta-estradiol, which was used as the positive control. From these results, it was confirmed that flutolanil and isoprothiolane exhibit estrogenic activities, suggesting they might act through estrogen receptors.

  20. HOMOLOGY MODELING OF THE ESTROGEN RECEPTOR SUBTYPE BETA (ER-BETA) AND CALCULATION OF LIGAND BINDING AFFINITIES. (R826133)

    EPA Science Inventory

    Abstract

    Estrogen is a steroid hormone playing critical roles in physiological processes such as sexual differentiation and development, female and male reproductive processes, and bone health. Numerous natural and synthetic environmental compounds have been shown capa...

  1. Separations of compounds of biological and environmental interest by micellar electrokinetic capillary chromatography

    SciTech Connect

    Balchunas, A.T.; Swaile, D.F.; Powell, A.C.; Sepaniak, M.J.

    1988-10-01

    Important criteria for the effective separation of compounds of biological or environmental interest by micellar electrokinetic capillary chromatography are discussed. Efficiencies of approximately 100,000 plates/meter are achieved in the separations of samples of derivatized amines, aflatoxins, and hydroxy aromatic compounds. Laser fluorometric detection is shown to be capable of detecting subpicogram injected quantities. Organic solvents such as 2-propanol and acetonitrile are added to the aqueous mobile phases normally used to improve the separation of hydrophobic compounds, impart different selectivities, and provide a means for gradient programming. Column diameter is found to influence efficiency, analysis time, and detection.

  2. Detection, transport and degradation of free and conjugated estrogens in soils

    NASA Astrophysics Data System (ADS)

    Goeppert, Nadine; Dror, Ishai; Berkowitz, Brian

    2010-05-01

    The behavior of Estradiol (E2), Estrone (E1) and Estrone-Sulfate (E1-3S) in a natural soil is analyzed in terms of transport and metabolic degradation properties. These compounds are released into the environment in significant amounts and have been shown to potentially contribute to endocrine disruption in humans and wildlife. Although literature data demonstrate that hormones sorb strongly to soil and also degrade quickly, significant amounts, especially of conjugated estrogens, can be still detected in various environmental media. Moreover, several recent studies note that hormones bind to colloidal organic carbon, which can facilitate hormone transport and decrease the degree of hormone degradation. These findings thus suggest a moderate mobility and persistence of estrogen compounds and their metabolites. However, many uncertainties regarding the transport and fate of estrogen compounds remain, which are complicated by difficulties in sampling and detection. Most research is performed at the catchment scale where large volumes of water are available for analysis. In addition, laboratory batch tests usually involve estrogen concentrations that are large and unrealistic for environmental conditions, or require use of labeled compounds for which it is unclear whether the substance measured is parent or metabolite. There is a serious lack of transport studies under controlled conditions, using small water volumes and low detection limits, which are crucial to understand the basic transport processes of estrogen transport and degradation. Here, we present a protocol for hormone measurement using an online-SPE LC-MS/MS for detection. We use the method to quantify free estrogens and metabolites at low concentrations in small sample volumes (~mL) of water and soil extracts. The study includes batch (sorption) and transport tests in flow-through columns, using natural clay-rich soil from Bet Dagan, Israel. Consideration of sorption and transport experiments using both

  3. Rapid CE-UV binding tests of environmentally hazardous compounds with polymer-modified magnetic nanoparticles.

    PubMed

    Iqbal, Zafar; Alsudir, Samar; Miah, Musharraf; Lai, Edward P C

    2011-08-01

    Hazardous compounds and bacteria in water have an adverse impact on human health and environmental ecology. Polydopamine (or polypyrrole)-coated magnetic nanoparticles and polymethacrylic acid-co-ethylene glycol dimethacrylate submicron particles were investigated for their fast binding kinetics with bisphenol A, proflavine, naphthalene acetic acid, and Escherichia coli. A new method was developed for the rapid determination of % binding by sequential injection of particles first and compounds (or E. coli) next into a fused-silica capillary for overlap binding during electrophoretic migration. Only nanolitre volumes of compounds and particles were sufficient to complete a rapid binding test. After heterogeneous binding, separation of the compounds from the particles was afforded by capillary electrophoresis. % binding was influenced by applied voltage but not current flow. In-capillary coating of particles affected the % binding of compounds.

  4. Determination of estrogenic activity by LYES-assay (yeast estrogen screen-assay assisted by enzymatic digestion with lyticase).

    PubMed

    Schultis, T; Metzger, J W

    2004-12-01

    In order to enhance the sensitivity and the speed of the yeast estrogen screen (YES)-assay, which has been established in many laboratories for the determination of estrogenic activity of compounds and environmental samples, the LYES-assay, a modified version of the YES-assay including a digestion step with the enzyme lyticase, was developed. With the LYES-assay the estrogenic activities of natural (17beta-estradiol E2 and estrone), synthetic (17alpha-ethinylestradiol EE2) and pharmaceutical estrogens (diethylstilbestrol DES) as well as xenoestrogens (4-nonylphenol NP and five parabens) were determined and compared with the results obtained by other in vitro-assays namely the conventional YES-assay, the E-Screen-assay (MCF-7 breast tumor cell proliferation) and a receptor binding-assay (RB) with human estrogen receptors hER-alpha and hER-beta. In the case of E2 the LYES-assay had a significantly lower limit of quantification (LOQ) than the conventional YES-assay and even two orders of magnitude lower than the RB-assay. Compared to the E-Screen-assay the LOQ of the LYES-assay was almost one order of magnitude higher. The time required to perform the LYES-assay was as little as seven hours compared to three to five days for the conventional YES-assay. Thus, the LYES-assay is a very good alternative to existing estrogenic in vitro-assays, since it has a good sensitivity, is cheap and much faster than the other assays.

  5. 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.

  6. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TOOL FOR IDENTIFYING ORGANIC COMPOUNDS IN COMPLEX EXTRACTS OF ENVIRONMENTAL SAMPLES

    EPA Science Inventory


    Unidentified Organic Compounds. For target analytes, standards are purchased, extraction and clean-up procedures are optimized, and mass spectra and retention times for the chromatographic separation are obtained for comparison to the target compounds in environmental sample ...

  7. The anti-estrogenic activity of sediments from agriculturally-intense watersheds: Assessment using in vivo and in vitro assays

    PubMed Central

    Sellin Jeffries, Marlo K.; Conoan, Nicholas H.; Cox, Marc B.; Sangster, Jodi L.; Balsiger, Heather A.; Bridges, Andrew A.; Cowman, Tim; Knight, Lindsey A.; Bartelt-Hunt, Shannon L.; Kolok, Alan S.

    2015-01-01

    compound in these extracts. Chemical analysis revealed the presence of a variety of steroid hormones, including those associated with the production of beef cattle (ie: β-trenbolone, α-zearalanol and α-zearalenol), in sediments indicating that compounds utilized by local beef cattle operations are capable of entering nearby watersheds. Overall, the results of this study indicate that an environmentally-relevant anti-estrogenic compound is present in sediments from agriculturally-intense watersheds and that this compound is bioavailable to fish. Furthermore, the presence of steroid hormones in sediments from these watersheds provides evidence indicating that steroids are capable of sorbing to sediments. Clearly, sediments are capable of acting as a source of endocrine-disrupting compounds in the aquatic environment. PMID:21723217

  8. Estrogens in the daily diet: in vitro analysis indicates that estrogenic activity is omnipresent in foodstuff and infant formula.

    PubMed

    Behr, Maximilian; Oehlmann, Jörg; Wagner, Martin

    2011-10-01

    Food is a main source of exposure to endocrine active compounds, many of which have been linked to adverse health effects. Phytoestrogens, especially from soy, are the major dietary source of estrogenicity. However, foodstuff contains a variety of estrogen-like compounds that might not be detected analytically. To assess the total estrogenic activity of foodstuff, we employed the Yeast Estrogen Screen (YES). We analyzed 18 food samples and five milk-based infant formulas. Soy-based products contained potent estrogenicity of 100-1500ng estradiol equivalents per kilogram (EEQ/kg). The estrogenicity in soy-free products was far lower (10-40ng EEQ/kg). We also detected significant estrogenic activity in three infant formulas (14-22ng EEQ/kg). Furthermore, we found soy lecithin to be strongly estrogenic. It might, therefore, be a major contributor to total estrogenicity. We conclude that dietary estrogens are omnipresent and not limited to soy-based food. In an exposure assessment we calculated a total dietary intake of 27.5 and 34.0ng EEQ/d for adults and 1.46ng EEQ/d for infants. While the dietary exposure to estrogenic activity is lower than previously estimated, our results demonstrate that many food types are a source of unidentified estrogen-like compounds still awaiting toxicological evaluation.

  9. Assessment of Environmental Effects of Ordnance Compounds and their Transformation Products in Coastal Ecosystems

    DTIC Science & Technology

    2003-12-01

    common sediment bacteria Enterobacter aerogenes, Pseudomonas fluorescens, Escherichia coli, Klebsiella sp. and Aeromonas sp. before and after... Pseudomonas fluorescens, Enterobacter aerogenes, Escherichia coli, Klebsiella sp. and Aeromonas sp. are known important decomposers in sediments and...including some compounds of environmental concern such as substituted azobenzenes or phenazines (Haderlein and Schwarzenbach 1995). Aminonitrotoluenes

  10. Volatile Organic Sulfur Compounds of Environmental Interest: Dimethyl Sulfide and Methanethiol

    ERIC Educational Resources Information Center

    Chasteen, Thomas G.; Bentley, Ronald

    2004-01-01

    Volatile organic sulfur compounds (VOSCs) have been assigned environmental roles in global warming, acid precipitation, and cloud formation where two important members dimethyl sulfide (CH3)2 S, DMS, and methanethiol, CH3SH, MT, of VOSC group are involved.

  11. Determination of estrogenic activity in the river Chienti (Marche Region, Italy) by using in vivo and in vitro bioassays.

    PubMed

    Cocci, Paolo; Palermo, Francesco Alessandro; Quassinti, Luana; Bramucci, Massimo; Miano, Antonino; Mosconi, Gilberto

    2016-05-01

    Environmental estrogen-like compounds (i.e. xenoestrogens) are a variety of pollutants, ranging from synthetic to natural occurring molecules, that are found in surface and waste waters over a wide range of concentrations. In aquatic environment, the overall estrogenic activity is often due to the presence of a mixture of chemicals and their degraded products which can induce synergistic effects. Current strategies for monitoring estrogen-like chemicals are based on the use of a battery of in vivo and in vitro ecotoxicological tests. In this regard, the aim of the present work was to carry out a bio-monitoring study for testing estrogenicity of the Chienti river (Marche Region, Italy) by using both an E-screen and a vitellogenin (Vtg) induction assay in juvenile goldfish. Three sites were used for analysis, localized at the mouth (sampling point 1), in the middle (sampling point 2) and at the origin (sampling point 3) of Chienti river. For most of the water samples (i.e. samples collected at sampling points 2 and 3), clear estrogenic activity was detected in the E-screen assay suggesting different proliferation activities in function of the collecting site. In contrast, the Vtg ELISA demonstrated that water samples collected from each sampling point were estrogenic. Overall, we showed for the first time that the estrogenic activities in water samples from the Chienti river were significant in both in vivo and in vitro; we also observed a different sensitivity between bioassays.

  12. Bioactivation of dibrominated biphenyls by cytochrome P450 activity to metabolites with estrogenic activity and estrogen sulfotransferase inhibition capacity.

    PubMed

    van Lipzig, Marola M H; Commandeur, Jan N; de Kanter, Frans J J; Damsten, Micaela C; Vermeulen, Nico P E; Maat, Evelina; Groot, Ed J; Brouwer, Abraham; Kester, Monique H A; Visser, Theo J; Meerman, John H N

    2005-11-01

    Exposure of humans and wildlife to xenobiotics, such as halogenated biphenyls, that interfere with the endogenous estrogen balance may lead to endocrine disruption. Such compounds may either mimic or block estradiol's action by agonistic or antagonistic action, respectively. They may also affect endogenous estradiol concentrations by induction or inhibition of enzymes that metabolize estradiol. In the present study, we demonstrate that estrogenic metabolites of two brominated biphenyls, 2,2'-dibromobiphenyl (2,2'-DBB) and 4,4'-dibromobiphenyl (4,4'-DBB), are formed by rat liver microsomal cytochrome P450 (CYP) activity. Bioactivation of 2,2'-DBB and 4,4'-DBB yielded various mono- and dihydroxylated bromobiphenyl metabolites, which were collected by preparative HPLC and analyzed by LC/MS. Several of the metabolites bound to the estrogen receptor (ER) activated the ER and inhibited human estrogen sulfotransferase (hEST). Seven monohydroxylated metabolites were positively identified using synthetic monohydroxylated reference compounds. These synthetic monohydroxylated bromobiphenyls also bound to and activated the ER and inhibited hEST. The highest ER affinity was observed for 4-OH-2,2'-DBB, with an EC50 of 6.6 nM. The highest ER activation was observed for 4-OH-3,4'-DBB (EC50 of 74 nM) while 4-OH-4'-MBB and 4-OH-2,2'-DBB induced a supramaximal (as compared to estradiol) ER activation. The strongest hEST inhibition was found with 4-OH-3,4'-DBB (EC50 = 40 nM). In conclusion, we show that two dibrominated biphenyls are bioactivated by CYP activity into very potent estrogenic metabolites and inhibitors of hEST. These findings are of vital importance for accurate risk assessment of exposure to environmental contaminants, such as halogenated biphenyls. Neglecting bioactivation through biotransformation will lead to underestimation of health risks of this class of xenobiotics.

  13. Volatile Organic Sulfur Compounds of Environmental Interest: Dimethyl Sulfide and Methanethiol. An Introductory Overview

    NASA Astrophysics Data System (ADS)

    Chasteen, Thomas G.; Bentley, Ronald

    2004-10-01

    Volatile organic sulfur compounds and their degradation products play important environmental roles in global warming, acid precipitation, and cloud formation. Two important members of this group, dimethyl sulfide, DMS, and methanethiol, MT, are formed by living organisms as well as by abiotic processes. DMS is synthesized by various organisms in the marine environment and large quantities of it are released to the atmosphere. One key precursor for DMS synthesis is the sulfonium salt, dimethylsulfoniopropionate. MT, also formed in marine environments, can be further converted to DMS. The chemical reactions responsible for the biosynthesis of DMS and MT are emphasized here, as well as means for their degradation. Since sulfur compounds are often ignored in normal course work, this article provides a basic foundation for an understanding of these interesting and environmentally significant compounds.

  14. Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

    PubMed

    Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

    2014-09-01

    Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive.

  15. The anti-estrogenic activity of sediments from agriculturally intense watersheds: assessment using in vivo and in vitro assays.

    PubMed

    Sellin Jeffries, Marlo K; Conoan, Nicholas H; Cox, Marc B; Sangster, Jodi L; Balsiger, Heather A; Bridges, Andrew A; Cowman, Tim; Knight, Lindsey A; Bartelt-Hunt, Shannon L; Kolok, Alan S

    2011-09-01

    compound in these extracts. Chemical analysis revealed the presence of a variety of steroid hormones, including those associated with the production of beef cattle (i.e. β-trenbolone, α-zearalanol and α-zearalenol), in sediments indicating that compounds utilized by local beef cattle operations are capable of entering nearby watersheds. Overall, the results of this study indicate that an environmentally relevant anti-estrogenic compound is present in sediments from agriculturally intense watersheds and that this compound is bioavailable to fish. Furthermore, the presence of steroid hormones in sediments from these watersheds provides evidence indicating that steroids are capable of sorbing to sediments.

  16. Estrogens and Cognition: Friends or Foes?

    PubMed Central

    Korol, Donna L.; Pisani, Samantha L.

    2015-01-01

    Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings that show the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. PMID:26149525

  17. Estrogen potency of oral contraceptive pills.

    PubMed

    Chihal, H J; Peppler, R D; Dickey, R P

    1975-01-01

    The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.

  18. Enzymatic electrochemical detection coupled to multivariate calibration for the determination of phenolic compounds in environmental samples.

    PubMed

    Hernandez, Silvia R; Kergaravat, Silvina V; Pividori, Maria Isabel

    2013-03-15

    An approach based on the electrochemical detection of the horseradish peroxidase enzymatic reaction by means of square wave voltammetry was developed for the determination of phenolic compounds in environmental samples. First, a systematic optimization procedure of three factors involved in the enzymatic reaction was carried out using response surface methodology through a central composite design. Second, the enzymatic electrochemical detection coupled with a multivariate calibration method based in the partial least-squares technique was optimized for the determination of a mixture of five phenolic compounds, i.e. phenol, p-aminophenol, p-chlorophenol, hydroquinone and pyrocatechol. The calibration and validation sets were built and assessed. In the calibration model, the LODs for phenolic compounds oscillated from 0.6 to 1.4 × 10(-6) mol L(-1). Recoveries for prediction samples were higher than 85%. These compounds were analyzed simultaneously in spiked samples and in water samples collected close to tanneries and landfills.

  19. A ternary classification using machine learning methods of distinct estrogen receptor activities within a large collection of environmental chemicals.

    PubMed

    Zhang, Quan; Yan, Lu; Wu, Yan; Ji, Li; Chen, Yuanchen; Zhao, Meirong; Dong, Xiaowu

    2017-02-15

    Endocrine-disrupting chemicals (EDCs), which can threaten ecological safety and be harmful to human beings, have been cause for wide concern. There is a high demand for efficient methodologies for evaluating potential EDCs in the environment. Herein an evaluation platform was developed using novel and statistically robust ternary models via different machine learning models (i.e., linear discriminant analysis, classification and regression tree, and support vector machines). The platform is aimed at effectively classifying chemicals with agonistic, antagonistic, or no estrogen receptor (ER) activities. A total of 440 chemicals from the literature were selected to derive and optimize the three-class model. One hundred and nine new chemicals appeared on the 2014 EPA list for EDC screening, which were used to assess the predictive performances by comparing the E-screen results with the predicted results of the classification models. The best model was obtained using support vector machines (SVM) which recognized agonists and antagonists with accuracies of 76.6% and 75.0%, respectively, on the test set (with an overall predictive accuracy of 75.2%), and achieved a 10-fold cross-validation (CV) of 73.4%. The external predicted accuracy validated by the E-screen assay was 87.5%, which demonstrated the application value for a virtual alert for EDCs with ER agonistic or antagonistic activities. It was demonstrated that the ternary computational model could be used as a faster and less expensive method to identify EDCs that act through nuclear receptors, and to classify these chemicals into different mechanism groups.

  20. Detection of estrogenic activity in Flemish surface waters using an in vitro recombinant assay with yeast cells.

    PubMed

    Witters, H E; Vangenechten, C; Berckmans, P

    2001-01-01

    Numerous environmental chemicals possess estrogen-like properties. At elevated doses, natural estrogens and environmental estrogen-like chemicals are known to produce adverse effects on humans and wildlife. Sources of potential exposure to endocrine disrupting compounds have to be identified for risk and hazard assessment. Extracts prepared from 16 selected water samples taken in Flemish rivers, effluents of municipal wastewater treatment plants and reservoirs for drinking water production were analysed for estrogenic activity with a cellular bioassay. Yeast cells, which are stably transfected with the DNA sequence of hER and which contain expression plasmids with the reporter gene lac-Z, encoding the enzyme beta-galactosidase, were used to measure receptor binding. Flemish rivers showed the highest estrogenic potency, compared to effluents of waste water treatment plants and reservoirs which showed low induction factors (beta-galactosidase production) relative to solvent control conditions. By comparison with a standard curve for 17 beta-estradiol (E2), estrogenic potency in water samples was calculated as E2-equivalents and ranged from below detection limit (approximately 2.75 ng E2/l) up to 81.4 ng/l E2-equivalents. About 7 water samples had more than 10 ng/l E2-equivalents. These elevated levels of E2-equivalents are likely to exert significant adverse effects on reproduction success of wildlife, which should be verified with in vivo studies.

  1. Solving practical problems in environmental sampling for chemical agents and their degradation compounds

    SciTech Connect

    Williams, K.E.; Sheely, M.V.

    1995-06-01

    The analyses of environmental samples for chemical agent degradation products were conducted using analytical test methods designed for evaluation of solid waste samples. All methods are found in the 3rd Edition of EPA`s compendium of analytical methods (SW-846) dated July 1992. These EPA methods are recommended for compliance testing required by the Resource Conservation and Recovery Act (RCRA) and are routinely used for the analysis of environmental samples. In the past several years, these same methods were used to support the survey of areas suspected of having chemical agent or chemical agent degradation compound contamination. An overview is presented of the U.S. Army Center for Health Promotion and Preventive Medicine`s (previously the U.S. Army Environmental Hygiene Agency) involvement with the analysis of samples for chemical agents and their degradation compounds collected from sites such as Tooele Army Depot, Rocky Mt. Arsenal, Newport Army Depot, Johnston Island, and Spring Valley, (a residential site near American University in Washington D.C.) Discussed are practical problems encountered during a quick response of a non-surety laboratory to analyze environmental samples for agents and their degradation compounds.

  2. In Vitro Assays for Assessment of Androgenic and Estrogenic Activity of Defined Mixtures and Complex Environmental Samples

    EPA Science Inventory

    Point sources of endocrine active compounds to aquatic environments such as waste water treatment plants, pulp and paper mills, and animal feeding operations invariably contain complex mixtures of chemicals. The current study investigates the use of targeted in vitro assays des...

  3. Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment.

    PubMed Central

    Vesell, E S; Passananti, G T

    1977-01-01

    Compared to laboratory animals, humans are extremely heterogenous with respect to the many factors that can influence the distribution and biological effects of toxic chemicals. This heterogeneity can prevent an accurate assessment of the impact of a particular toxic compound on the health of an individual subject. Some of the factors that can significantly modify the host response to certain drugs, which serve in this review as a model for environmental chemicals, are enumerated and discussed. Although the mechanisms by which many of these factors modify the biological effects of certain environmental chemicals and drugs have been determined in some cases, better definition of the nature of interactions between these factors and environmental chemicals in a particular individual is required at a biochemical and molecular level. Recommendations are offered for the further development of our knowledge concerning interactions between environmental chemicals and such factors in a particular individual. PMID:598349

  4. Methodologies for the extraction of phenolic compounds from environmental samples: new approaches.

    PubMed

    Mahugo Santana, Cristina; Sosa Ferrera, Zoraida; Esther Torres Padrón, M; Juan Santana Rodríguez, José

    2009-01-09

    Phenolic derivatives are among the most important contaminants present in the environment. These compounds are used in several industrial processes to manufacture chemicals such as pesticides, explosives, drugs and dyes. They also are used in the bleaching process of paper manufacturing. Apart from these sources, phenolic compounds have substantial applications in agriculture as herbicides, insecticides and fungicides. However, phenolic compounds are not only generated by human activity, but they are also formed naturally, e.g., during the decomposition of leaves or wood. As a result of these applications, they are found in soils and sediments and this often leads to wastewater and ground water contamination. Owing to their high toxicity and persistence in the environment, both, the US Environmental Protection Agency (EPA) and the European Union have included some of them in their lists of priority pollutants. Current standard methods of phenolic compounds analysis in water samples are based on liquid-liquid extraction (LLE) while Soxhlet extraction is the most used technique for isolating phenols from solid matrices. However, these techniques require extensive cleanup procedures that are time-intensive and involve expensive and hazardous organic solvents, which are undesirable for health and disposal reasons. In the last years, the use of news methodologies such as solid-phase extraction (SPE) and solid-phase microextraction (SPME) have increased for the extraction of phenolic compounds from liquid samples. In the case of solid samples, microwave assisted extraction (MAE) is demonstrated to be an efficient technique for the extraction of these compounds. In this work we review the developed methods in the extraction and determination of phenolic derivatives in different types of environmental matrices such as water, sediments and soils. Moreover, we present the new approach in the use of micellar media coupled with SPME process for the extraction of phenolic

  5. Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics

    SciTech Connect

    Meeuwen, J.A. van Son, O. van; Piersma, A.H.; Jong, P.C. de; Berg, M. van den

    2008-08-01

    There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E{sub 2}) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden.

  6. [Estrogen receptors and the mammary gland].

    PubMed

    Barrón, A; Bermejo, L; Castro, I

    1997-01-01

    For several decades it has been known that steroid hormones, estrogen and progesterone, regulate some genes involved in the growth, proliferation and differentiation of the mammary-gland in animals and humans. In the last years, the presence or absence of the nuclear estrogen receptor has been used by clinicians as a marker for tumor malignancy, as a prognostic index or as an important parameter for hormonal therapy with anti-estrogenic compounds of some hormone-dependent breast cancers. This review shows some advances in the knowledge of the structure, function, molecular mechanisms of estrogenic activity, and interaction with proteins like protooncogenes and growth factors. Also, we refer to the role of the estrogen receptor in the physiophatology of breast cancer.

  7. The Behavior of Environmentally Friendly Corrosion Preventative Compounds in an Aggressive Coastal Marine Environment

    NASA Technical Reports Server (NTRS)

    Montgomery, Eliza L.; Calle, Luz Marina; Curran Jerome C.; Kolody, Mark R.

    2013-01-01

    The shift to use environmentally friendly technologies throughout future space-related launch programs prompted a study aimed at replacing current petroleum and solvent-based Corrosion Preventive Compounds (CPCs) with environmentally friendly alternatives. The work in this paper focused on the identification and evaluation of environmentally friendly CPCs for use in protecting flight hardware and ground support equipment from atmospheric corrosion. The CPCs, while a temporary protective coating, must survive in the aggressive coastal marine environment that exists throughout the Kennedy Space Center, Florida. The different protection behaviors of fifteen different soft film CPCs, both common petroleum-based and newer environmentally friendly types, were evaluated on various steel and aluminum substrates. The CPC and substrate systems were subjected to atmospheric testing at the Kennedy Space Center's Beachside Atmospheric Corrosion Test Site, as well as cyclic accelerated corrosion testing. Each CPC also underwent physical characterization and launch-related compatibility testing . The initial results for the fifteen CPC systems are reported : Key words: corrosion preventive compound, CPC, spaceport, environmentally friendly, atmospheric exposure, marine, carbon steel, aluminum alloy, galvanic corrosion, wire on bolt.

  8. In Vivo Imaging of Activated Estrogen Receptors in Utero by Estrogens and Bisphenol A

    PubMed Central

    Lemmen, Josephine G.; Arends, Roel J.; van der Saag, Paul T.; van der Burg, Bart

    2004-01-01

    Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that, using this in vivo model in combination with the IVIS imaging system, activation of estrogen receptors (ERs) by maternally applied BPA and other estrogens can be detected in living embryos in utero. Eight hours after exposure to 1 mg/kg BPA, ER transactivation could be significantly induced in the embryos. This was more potent than would be estimated from in vitro assays, although its intrinsic activity is still lower than that of diethylstilbestrol and 17β-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using in vitro assays might underestimate its estrogenic potential in embryos. PMID:15531440

  9. In vivo imaging of activated estrogen receptors in utero by estrogens and bisphenol A.

    PubMed

    Lemmen, Josephine G; Arends, Roel J; van der Saag, Paul T; van der Burg, Bart

    2004-11-01

    Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that, using this in vivo model in combination with the IVIS imaging system, activation of estrogen receptors (ERs) by maternally applied BPA and other estrogens can be detected in living embryos in utero. Eight hours after exposure to 1 mg/kg BPA, ER transactivation could be significantly induced in the embryos. This was more potent than would be estimated from in vitro assays, although its intrinsic activity is still lower than that of diethylstilbestrol and 17beta-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using in vitro assays might underestimate its estrogenic potential in embryos.

  10. A structural perspective on nuclear receptors as targets of environmental compounds

    PubMed Central

    Delfosse, Vanessa; Maire, Albane le; Balaguer, Patrick; Bourguet, William

    2015-01-01

    Nuclear receptors (NRs) are members of a large superfamily of evolutionarily related transcription factors that control a plethora of biological processes. NRs orchestrate complex events such as development, organ homeostasis, metabolism, immune function, and reproduction. Approximately one-half of the 48 human NRs have been shown to act as ligand-regulated transcription factors and respond directly to a large variety of endogenous hormones and metabolites that are generally hydrophobic and small in size (eg, retinoic acid or estradiol). The second half of the NR family comprises the so-called orphan receptors, for which regulatory ligands are still unknown or may not exist despite the presence of a C-terminal ligand-binding domain, which is the hallmark of all NRs. Several chemicals released into the environment (eg, bisphenols, phthalates, parabens, etc) share some physicochemical properties with natural ligands, allowing them to bind to NRs and activate or inhibit their action. Collectively referred to as endocrine disruptors or endocrine-disrupting chemicals (EDCs), these environmental pollutants are highly suspected to cause a wide range of developmental, reproductive, neurological, or metabolic defects in humans and wildlife. Crystallographic studies are revealing unanticipated mechanisms by which chemically diverse EDCs interact with the ligand-binding domain of NRs. These studies thereby provide a rational basis for designing novel chemicals with lower impacts on human and animal health. In this review, we provide a structural and mechanistic view of endocrine disrupting action using estrogen receptors α and β, (ERα/β), peroxisome proliferator activated receptor γ (PPARγ), and their respective environmental ligands as representative examples. PMID:25500867

  11. Comparative endpoint sensitivity of in vitro estrogen agonist assays.

    PubMed

    Dreier, David A; Connors, Kristin A; Brooks, Bryan W

    2015-07-01

    Environmental and human health implications of endocrine disrupting chemicals (EDCs), particularly xenoestrogens, have received extensive study. In vitro assays are increasingly employed as diagnostic tools to comparatively evaluate chemicals, whole effluent toxicity and surface water quality, and to identify causative EDCs during toxicity identification evaluations. Recently, the U.S. Environmental Protection Agency (USEPA) initiated ToxCast under the Tox21 program to generate novel bioactivity data through high throughput screening. This information is useful for prioritizing chemicals requiring additional hazard information, including endocrine active chemicals. Though multiple in vitro and in vivo techniques have been developed to assess estrogen agonist activity, the relative endpoint sensitivity of these approaches and agreement of their conclusions remain unclear during environmental diagnostic applications. Probabilistic hazard assessment (PHA) approaches, including chemical toxicity distributions (CTD), are useful for understanding the relative sensitivity of endpoints associated with in vitro and in vivo toxicity assays by predicting the likelihood of chemicals eliciting undesirable outcomes at or above environmentally relevant concentrations. In the present study, PHAs were employed to examine the comparative endpoint sensitivity of 16 in vitro assays for estrogen agonist activity using a diverse group of compounds from the USEPA ToxCast dataset. Reporter gene assays were generally observed to possess greater endpoint sensitivity than other assay types, and the Tox21 ERa LUC BG1 Agonist assay was identified as the most sensitive in vitro endpoint for detecting an estrogenic response. When the sensitivity of this most sensitive ToxCast in vitro endpoint was compared to the human MCF-7 cell proliferation assay, a common in vitro model for biomedical and environmental monitoring applications, the ERa LUC BG1 assay was several orders of magnitude less

  12. Comparison of European and American techniques for the analysis of volatile organic compounds in environmental matrices.

    PubMed

    Voice, T C; Kolb, B

    1994-08-01

    The United States Environmental Protection Agency has promulgated methods for analysis of volatile organic compounds by purge and trap, or dynamic headspace, gas chromatography. In western Europe, where environmental analyses are less heavily regulated, static headspace is widely used. In this paper, these two approaches are compared and contrasted for use with different environmental matrices. The theoretical basis and state of application for purge and trap and headspace analysis are discussed, and data are presented on the accuracy and precision of both approaches. Data are reported on the use of headspace analysis for different aqueous matrix types with different sample preparation procedures. A new method for direct headspace analysis of soil samples is presented and compared with the EPA-approved purge and trap method.

  13. Environmental Aspects of Two Volatile Organic Compound Groundwater Treatment Designs at the Rocky Flats Site - 13135

    SciTech Connect

    Michalski, Casey C.; DiSalvo, Rick; Boylan, John

    2013-07-01

    DOE's Rocky Flats Site in Colorado is a former nuclear weapons production facility that began operations in the early 1950's. Because of releases of hazardous substances to the environment, the federally owned property and adjacent offsite areas were placed on the CERCLA National Priorities List in 1989. The final remedy was selected in 2006. Engineered components of the remedy include four groundwater treatment systems that were installed before closure as CERCLA-accelerated actions. Two of the systems, the Mound Site Plume Treatment System and the East Trenches Plume Treatment System, remove low levels of volatile organic compounds using zero-valent iron media, thereby reducing the loading of volatile organic compounds in surface water resulting from the groundwater pathway. However, the zero-valent iron treatment does not reliably reduce all volatile organic compounds to consistently meet water quality goals. While adding additional zero-valent iron media capacity could improve volatile organic compound removal capability, installation of a solar powered air-stripper has proven an effective treatment optimization in further reducing volatile organic compound concentrations. A comparison of the air stripper to the alternative of adding additional zero-valent iron capacity to improve Mound Site Plume Treatment System and East Trenches Plume Treatment System treatment based on several key sustainable remediation aspects indicates the air stripper is also more 'environmentally friendly'. These key aspects include air pollutant emissions, water quality, waste management, transportation, and costs. (authors)

  14. [Corrected Title: Solid-Phase Extraction of Polar Compounds from Water] Automated Electrostatics Environmental Chamber

    NASA Technical Reports Server (NTRS)

    Sauer, Richard; Rutz, Jeffrey; Schultz, John

    2005-01-01

    A solid-phase extraction (SPE) process has been developed for removing alcohols, carboxylic acids, aldehydes, ketones, amines, and other polar organic compounds from water. This process can be either a subprocess of a water-reclamation process or a means of extracting organic compounds from water samples for gas-chromatographic analysis. This SPE process is an attractive alternative to an Environmental Protection Administration liquid-liquid extraction process that generates some pollution and does not work in a microgravitational environment. In this SPE process, one forces a water sample through a resin bed by use of positive pressure on the upstream side and/or suction on the downstream side, thereby causing organic compounds from the water to be adsorbed onto the resin. If gas-chromatographic analysis is to be done, the resin is dried by use of a suitable gas, then the adsorbed compounds are extracted from the resin by use of a solvent. Unlike the liquid-liquid process, the SPE process works in both microgravity and Earth gravity. In comparison with the liquid-liquid process, the SPE process is more efficient, extracts a wider range of organic compounds, generates less pollution, and costs less.

  15. Structure and estrogenic activity of new lignans from Iryanthera lancifolia.

    PubMed

    Mesa-Siverio, Dulce; Machín, Rubén P; Estévez-Braun, Ana; Ravelo, Angel G; Lock, Olga

    2008-03-15

    Five new dibenzylbutane type lignans (1-5) were isolated from the stem bark of Iryanthera lancifolia. Their structures were determined by extensive 1D and 2D NMR spectroscopic studies and chemical evidence. Seventeen of the isolated compounds were tested for their estrogenic activities in the estrogen responsive human breast cancer cell line MCF-7 BUS using the E-Screen proliferation assay. Cell proliferation was evaluated by the SRB assay to calculate the estrogenic parameters. The majority of the compounds induced a mitogenic response. This effect, given as Relative Proliferative Effect (RPE) to reference estrogen 17beta-estradiol (E(2)), ranged between 14% and 84%.

  16. Estrogens and aging skin

    PubMed Central

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies. PMID:24194966

  17. Toxic volatile organic compounds in environmental tobacco smoke: Emission factors for modeling exposures of California populations

    SciTech Connect

    Daisey, J.M.; Mahanama, K.R.R.; Hodgson, A.T.

    1994-10-01

    The primary objective of this study was to measure emission factors for selected toxic air contaminants in environmental tobacco smoke (ETS) using a room-sized environmental chamber. The emissions of 23 volatile organic compounds (VOCs), including, 1,3-butadiene, three aldehydes and two vapor-phase N-nitrosamines were determined for six commercial brands of cigarettes and reference cigarette 1R4F. The commercial brands were selected to represent 62.5% of the cigarettes smoked in California. For each brand, three cigarettes were machine smoked in the chamber. The experiments were conducted over four hours to investigate the effects of aging. Emission factors of the target compounds were also determined for sidestream smoke (SS). For almost all target compounds, the ETS emission factors were significantly higher than the corresponding SS values probably due to less favorable combustion conditions and wall losses in the SS apparatus. Where valid comparisons could be made, the ETS emission factors were generally in good agreement with the literature. Therefore, the ETS emission factors, rather than the SS values, are recommended for use in models to estimate population exposures from this source. The variabilities in the emission factors ({mu}g/cigarette) of the selected toxic air contaminants among brands, expressed as coefficients of variation, were 16 to 29%. Therefore, emissions among brands were Generally similar. Differences among brands were related to the smoked lengths of the cigarettes and the masses of consumed tobacco. Mentholation and whether a cigarette was classified as light or regular did not significantly affect emissions. Aging was determined not to be a significant factor for the target compounds. There were, however, deposition losses of the less volatile compounds to chamber surfaces.

  18. Vitellogenin induction by xenobiotic estrogens in the red-eared turtle and African clawed frog.

    PubMed Central

    Palmer, B D; Palmer, S K

    1995-01-01

    Many environmental pollutants have estrogenic activity in animals. Xenobiotic estrogens include many pesticides and industrial chemicals that biocumulate. The impact of these common pollutants on the reproductive success of wildlife may be considerable, particularly in threatened or endangered species. This research examined the use of plasma vitellogenin in males as a biomarker for estrogenic xenobiotics in reptiles and amphibians. Adult male turtles (Trachemys scripta) and frogs (Xenopus laevis) were given ip injections of estradiol-17 beta (E2), diethylstilbestrol (DES), or o,p'-DDT (1-chloro-2-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl)benzene) daily for 7 days, and plasma was collected on day 14. The estrogenic activity of each compound was determined by measuring the induction of plasma vitellogenin. Vitellogenin was identified by precipitation, electrophoresis, Western blot, and enzyme-linked immunosorbant assay (ELISA). In both species, estradiol and DES treatments induced the most vitellogenin, whereas DDT treatments induced smaller amounts of vitellogenin in a dose-dependent fashion. These data indicate that induction of plasma vitellogenin in males may be a useful biomarker of xenobiotic estrogen activity in wild populations of reptiles and amphibians. Images Figure 1. Figure 3. PMID:7556019

  19. Reduced embryonic survival in rainbow trout resulting from paternal exposure to the environmental estrogen 17 alpha- ethynylestradiol during late sexual maturation

    SciTech Connect

    Brown, Kim H.; Schultz, Irvin R.; Nagler, James J.

    2007-11-01

    Exposure of fishes to environmental estrogens is known to affect sexual development and spawning, but little information exists regarding effects on gametes. This study evaluated embryonic survival of offspring from male rainbow trout (Oncorhynchus mykiss) exposed to 17a-ethynylestradiol (EE2)using an in vitro fertilization protocol. Males were exposed at either 1800 or 6700 degree days (8d) (i.e. 161 or 587 days post-fertilization (dpf)) to test for effects on testes linked to reproductive ontogeny. At 18008d, fish were beginning testicular differentiation and were exposed to 109 ng EE2/l for 21 days. At 67008d, fish have testes containing spermatocytes and spermatids and were exposed for 56 days to either 0.8, 8.3, or 65 ng EE2/l. Semen was collected at full sexual maturity in each group and used to fertilize eggs pooled from several non-exposed females. Significant decreases in embryonic survival were observed only with the 67008d exposure. In 0.8 and 8.3 ng EE2/l treatments, embryo survival was significantly reduced at 19 dpf when compared with the control. In contrast, an immediate decrease in embryonic survival at 0.5 dpf was observed in the 65 ng EE2/l treatment. Blood samples collected at spawning from 67008d exposed males revealed a significant decrease in 11-ketotestosterone and a significant increase in luteinizing hormone levels for the 65 ng EE2/l treatment when compared with the other treatment groups. Results indicate that sexually maturing male rainbow trout are susceptible to EE2 exposure with these fish exhibiting two possible mechanisms of reduced embryonic survival through sperm varying dependant

  20. Reduced embryonic survival in rainbow trout resulting from paternal exposure to the environmental estrogen 17α-ethynylestradiol during late sexual maturation

    PubMed Central

    Brown, Kim H; Schultz, Irvin R; Nagler, James J

    2007-01-01

    Exposure of fishes to environmental estrogens is known to affect sexual development and spawning, but little information exists regarding effects on gametes. This study evaluated embryonic survival of offspring from male rainbow trout (Oncorhynchus mykiss) exposed to 17α-ethynylestradiol (EE2) using an in vitro fertilization protocol. Males were exposed at either 1800 or 6700 degree days (°d) (i.e. 161 or 587 days post-fertilization (dpf)) to test for effects on testes linked to reproductive ontogeny. At 1800°d, fish were beginning testicular differentiation and were exposed to 109 ng EE2/l for 21 days. At 6700°d, fish have testes containing spermatocytes and spermatids and were exposed for 56 days to either 0.8, 8.3, or 65 ng EE2/l. Semen was collected at full sexual maturity in each group and used to fertilize eggs pooled from several non-exposed females. Significant decreases in embryonic survival were observed only with the 6700°d exposure. In 0.8 and 8.3 ng EE2/l treatments, embryo survival was significantly reduced at 19 dpf when compared with the control. In contrast, an immediate decrease in embryonic survival at 0.5 dpf was observed in the 65 ng EE2/l treatment. Blood samples collected at spawning from 6700°d exposed males revealed a significant decrease in 11-ketotestosterone and a significant increase in luteinizing hormone levels for the 65 ng EE2/l treatment when compared with the other treatment groups. Results indicate that sexually maturing male rainbow trout are susceptible to EE2 exposure with these fish exhibiting two possible mechanisms of reduced embryonic survival through sperm varying dependant on EE2 exposure concentrations experienced. PMID:17965256

  1. Different formats of imprinted polymers for determining organotin compounds in environmental samples.

    PubMed

    Gallego-Gallegos, Mercedes; Muñoz-Olivas, Riansares; Cámara, Carmen

    2009-02-01

    Organotin compounds and their degradation products enter the environment mainly as a result of their use as biocides and antifouling paints. Analysis of these compounds in environmental samples has to be very sensitive and selective so that their concentrations corresponding to the low environmental target values can also be detected. Generally, analysis of a complex matrix leads to high interferences during the different process steps; clean-up procedures are recommended to overcome this problem. For the past many years, solid phase extraction by employing imprinted materials has been extensively used for many organic substances that are used for pre-concentration and clean-up purposes with excellent results. Here, we present three different imprinted polymers prepared via bulk, precipitation, and emulsion polymerization methods that use similar compositions. The synthesized polymer particles were characterized morphologically by employing scanning electron microscopy and Brunauer-Emmett-Teller analysis. Binding properties were calculated using the Langmuir-Freundlich isotherm. Depending on the properties of the materials, different analytical applications for complex matrices are proposed. These applications are mainly used on tributyltin and its degradation products for environmental analysis.

  2. Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides.

    PubMed

    Kucinska, Malgorzata; Giron, Maria-Dolores; Piotrowska, Hanna; Lisiak, Natalia; Granig, Walter H; Lopez-Jaramillo, Francisco-Javier; Salto, Rafael; Murias, Marek; Erker, Thomas

    2016-01-01

    The cytotoxicity of 27 benzanilides and dithiobenzanilides built on a stilbene scaffold and possessing various functional groups in aromatic rings previously described for their spasmolytic properties was assayed on three human cancer cell lines (A549 -lung adenocarcinoma, MCF-7 estrogen dependent breast adenocarcinoma and MDA-MB-231 estrogen independent breast adenocarcinoma) and 2 non-tumorigenic cell lines (CCD39Lu-lung fibroblasts, MCF-12A - breast epithelial). Three compounds (6, 15 and 18) showed selective antiproliferative activity against estrogen dependent MCF-7 cancer cells and their estrogenic activity was further confirmed in MCF-7 transfected with an estrogen receptor reporter plasmid and in HEK239 cells over-expressing the estrogen receptor alpha (ERα). Compound 18 is especially interesting as a potential candidate for therapy since it is highly toxic and selective towards estrogen dependent MCF7 cell lines (IC50 = 5.07 μM versus more than 100 μM for MDA-MB-231) and almost innocuous for normal breast cells (IC50 = 91.46 μM for MCF-12A). Docking studies have shown that compound 18 interacts with the receptor in the same cavity as estradiol although the extra aromatic ring is involved in additional binding interactions with residue W383. The role of W383 and the extended binding mode were confirmed by site-directed mutagenesis.

  3. Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides

    PubMed Central

    Kucinska, Malgorzata; Giron, Maria-Dolores; Piotrowska, Hanna; Lisiak, Natalia; Granig, Walter H.; Lopez-Jaramillo, Francisco-Javier; Salto, Rafael; Murias, Marek; Erker, Thomas

    2016-01-01

    The cytotoxicity of 27 benzanilides and dithiobenzanilides built on a stilbene scaffold and possessing various functional groups in aromatic rings previously described for their spasmolytic properties was assayed on three human cancer cell lines (A549 –lung adenocarcinoma, MCF-7 estrogen dependent breast adenocarcinoma and MDA-MB-231 estrogen independent breast adenocarcinoma) and 2 non-tumorigenic cell lines (CCD39Lu–lung fibroblasts, MCF-12A - breast epithelial). Three compounds (6, 15 and 18) showed selective antiproliferative activity against estrogen dependent MCF-7 cancer cells and their estrogenic activity was further confirmed in MCF-7 transfected with an estrogen receptor reporter plasmid and in HEK239 cells over-expressing the estrogen receptor alpha (ERα). Compound 18 is especially interesting as a potential candidate for therapy since it is highly toxic and selective towards estrogen dependent MCF7 cell lines (IC50 = 5.07 μM versus more than 100 μM for MDA-MB-231) and almost innocuous for normal breast cells (IC50 = 91.46 μM for MCF-12A). Docking studies have shown that compound 18 interacts with the receptor in the same cavity as estradiol although the extra aromatic ring is involved in additional binding interactions with residue W383. The role of W383 and the extended binding mode were confirmed by site-directed mutagenesis. PMID:26730945

  4. Survey of estrogenic activity in fish feed by yeast estrogen-screen assay.

    PubMed

    Matsumoto, Takeru; Kobayashi, Makito; Moriwaki, Toshihisa; Kawai, Shin'ichiro; Watabe, Shugo

    2004-10-01

    Fishes have been used as laboratory animal for research of estrogenic endocrine disrupters by many researchers. However, much less attention was paid to the possibility that compounds with estrogenic activity are present in fish diets. In order to examine this possibility, we measured the estrogenic activity in commercial fish feed by in vitro yeast estrogen-screen (YES) assay based on the binding ability of tested compounds to estrogen receptors. Estrogenic activity was detected in all the commercial fish feed examined (0.2-6.2 ng estradiol equivalent/g fish feed), some phytoestrogens (genistein, formononetin, equol and coumestrol; relative activity to estradiol, 8.6 x 10(-6)-1.1 x 10(-4) by giving a value of 1.0 to estradiol) and some androgens (testosterone, 11-ketotestosterone and 5 alpha-dihydrotestosterone; relative activity to estradiol, 3.0 x 10(-6)-1.2 x 10(-4)). Therefore, it is possible that these compounds could affect the results of in vivo estrogen assay, such as vitellogenin production in male fish, especially when fish are fed commercial feed.

  5. Bioluminescent yeast estrogen assay (BLYES) as a sensitive tool to monitor surface and drinking water for estrogenicity.

    PubMed

    Bergamasco, Ana Marcela Di Dea; Eldridge, Melanie; Sanseverino, John; Sodré, Fernando Fabriz; Montagner, Cassiana Carolina; Pescara, Igor Cardoso; Jardim, Wilson Figueiredo; Umbuzeiro, Gisela de Aragão

    2011-11-01

    Estrogenic Endocrine Disrupting Chemicals (EDCs) are a concern due to their ubiquity and recognized adverse effects to humans and wildlife. Methods to assess exposure to and associated risks of their presence in aquatic environment are still under development. The aim of this work is to assess estrogenicity of raw and treated waters with different degrees of pollution. Chemical analyses of selected EDCs were performed by liquid chromatography-tandem mass spectrometry, and estrogenic activity was evaluated using in vitro bioluminescent yeast estrogen assay (BLYES). Most raw water samples (18/20) presented at least one EDC and 16 rendered positive in BLYES. When EDCs were detected, the bioassay usually provided a positive response, except when only bisphenol A was detected at low concentrations. The highest values of estrogenic activity were detected in the most polluted sites. The maximum estrogenic activity observed was 8.7 ng equiv. of E2 L(-1). We compared potencies observed in the bioassay to the relative potency of target compounds and their concentrations failed to fully explain the biological response. This indicates that bioassay is more sensitive than the chemical approach either detecting estrogenic target compounds at lower concentrations, other non-target compounds or even synergistic effects, which should be considered on further investigations. We have not detected either estrogenic activity or estrogenic compounds in drinking water. BLYES showed good sensitivity with a detection limit of 0.1 ng equiv. E2 L(-1) and it seems to be a suitable tool for water monitoring.

  6. Environmental chamber study of maximum incremental reactivities of volatile organic compounds

    NASA Astrophysics Data System (ADS)

    Carter, William P. L.; Pierce, John A.; Luo, Dongmin; Malkina, Irina L.

    The effects of 26 individual volatile organic compounds (VOCs) on ozone formation, NO oxidation, and OH radical levels were measured by adding them to reactive organic gas (ROG)-NO x-air environmental chamber irradiations representing a simplified model photochemical smog system. These experiments had relatively low ROG/NOx ratios to represent conditions where ozone formation is most sensitive to VOC additions. The compounds studied included representative alkanes, alkenes, aromatic hydrocarbons, aldehydes, alcohols, and CO. The addition of formaldehyde, methylbenzenes, alkenes and methanol all caused increased integrated OH radical concentrations, and caused the most NO oxidation and ozone formation per molecule reacted. The C 6+n-alkanes had the most inhibiting effects on OH radicals, and caused reduced NO oxidation and ozone formation in these experiments. The other compounds had smaller negative effects on OH radicals, but moderate positive effects on ozone formed and NO oxidized. The implications of these results in terms of the atmospheric reaction mechanisms of these compounds are discussed.

  7. Estrogenic activity in Finnish municipal wastewater effluents.

    PubMed

    Välitalo, Pia; Perkola, Noora; Seiler, Thomas-Benjamin; Sillanpää, Markus; Kuckelkorn, Jochen; Mikola, Anna; Hollert, Henner; Schultz, Eija

    2016-01-01

    Effluents from wastewater treatment plants (WWTPs) are a major source of estrogenic compounds to the aquatic environment. In the present work, estrogenic activities of effluents from eight municipal WWTPs in Finland were studied. The main objectives of the study were to quantify the concentrations of selected estrogenic compounds, to evaluate their contribution to estrogenic potency and to test the feasibility of the commercial bioassays for wastewater analysis. The effluent samples were analyzed by two in vitro tests, i.e. ERα-CALUX(®) and ELISA-E2, and by liquid chromatography mass spectrometry for six estrogenic compounds: estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), 17α-estradiol and bisphenol A (BPA). Estrogenic effects were found in all of the effluent samples with both of the bioassays. The concentrations measured with ELISA-E2 (8.6-61.6 ng/L) were clearly higher but exhibited a similar pattern than those with chemical analysis (E2 estrogenic potency was possible only for E1 and BPA, which contributed less than 10% to the observed effects, except in one sample with a high BPA contribution (17%). The contribution of E2 was significant in two samples where it was detected (28% and 67%). The results demonstrated that more comprehensive information on potential estrogenic activity of wastewater effluents can be achieved by using in vitro biotests in addition to chemical analysis and their use would be beneficial in monitoring and screening purposes.

  8. Estrogen and Osteoporosis.

    ERIC Educational Resources Information Center

    Lindsay, Robert

    1987-01-01

    This article reviews the use of estrogen in the prevention and treatment of osteoporosis. Dosage levels, interactions with other factors, side effects, and the mechanism of estrogen action are discussed. (Author/MT)

  9. MEASUREMENT OF VOLATILE ORGANIC COMPOUNDS BY THE US ENVIRONMENTAL PROTECTION AGENCY COMPENDIUM METHOD TO-17 - EVALUATION OF PERFORMANCE CRITERIA

    EPA Science Inventory

    An evaluation of performance criteria for US Environmental Protection Agency Compendium Method TO-17 for monitoring volatile organic compounds (VOCs) in air has been accomplished. The method is a solid adsorbent-based sampling and analytical procedure including performance crit...

  10. ESTROGEN INDUCED VITELLOGENIN MRNA AND PROTEIN IN SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS)

    EPA Science Inventory

    Many environmentally persistent xenobiotic chemicals appear to disrupt normal endocrine function by acting as ligands for endogenous steroid receptors, including the estrogen receptor. Xenobiotics that bind to the estrogen receptor may elicit several effects, one of which is acti...

  11. Adaptive Significance of ERα Splice Variants in Killifish (Fundulus heteroclitus) Resident in an Estrogenic Environment

    EPA Science Inventory

    The possibility that chronic, multigenerational exposure to environmental estrogens selects for adaptive hormone response phenotypes is a critical unanswered question. Embryos/larvae of killifish from an estrogenic polluted environment (New Bedford Harbor, NBH), as compared to th...

  12. Comparison of the sensitivities of common in vitro and in vivo assays of estrogenic activity: application of chemical toxicity distributions.

    PubMed

    Dobbins, Laura L; Brain, Richard A; Brooks, Bryan W

    2008-12-01

    A number of contaminants in municipal effluent discharges are estrogen agonists to fish. Whereas several in vitro and in vivo techniques have been developed to assess the estrogenic activity of these compounds or ambient environmental samples, previous comparisons of the relative sensitivities of these approaches remain inconclusive. We employed a probabilistic hazard assessment approach using chemical toxicity distributions (CTDs) to perform a novel evaluation of relative sensitivities of six common in vitro and in vivo assays. We predicted that there was an 8.3% (human breast ademocarcinoma cell line, MCF-7, assay), 6.3% (yeast estrogen screen assay), or 1.9% (fish hepatocyte vitellogenin, VTG, assay) probability of detecting a compound in aquatic systems that will elicit an estrogenic response at concentrations at or below 0.1 microg/L, suggesting that the MCF-7 assay was the most sensitive in vitro assay evaluated in this study. The probabilities of eliciting the estrogenic response of VTG induction at a concentration less than 0.1 microg/L in rainbow trout, fathead minnow, and Japanese medaka were determined at 29.9, 26.2, and 18.8%, respectively. Thus, rainbow trout VTG induction was the most sensitive in vivo assay assessed. Subsequently, CTDs may provide a useful technique for hazard assessment of chemical classes for which exposure data are limited and for chemicals with common toxicological mechanisms and modes of action.

  13. Identification of an estrogenic hormone receptor in Caenorhabditis elegans

    SciTech Connect

    Mimoto, Ai; Fujii, Madoka; Usami, Makoto; Shimamura, Maki; Hirabayashi, Naoko; Kaneko, Takako; Sasagawa, Noboru; Ishiura, Shoichi

    2007-12-28

    Changes in both behavior and gene expression occur in Caenorhabditis elegans following exposure to sex hormones such as estrogen and progesterone, and to bisphenol A (BPA), an estrogenic endocrine-disrupting compound. However, only one steroid hormone receptor has been identified. Of the 284 known nuclear hormone receptors (NHRs) in C. elegans, we selected nhr-14, nhr-69, and nhr-121 for analysis as potential estrogenic hormone receptors, because they share sequence similarity with the human estrogen receptor. First, the genes were cloned and expressed in Escherichia coli, and then the affinity of each protein for estrogen was determined using a surface plasmon resonance (SPR) biosensor. All three NHRs bound estrogen in a dose-dependent fashion. To evaluate the specificity of the binding, we performed a solution competition assay using an SPR biosensor. According to our results, only NHR-14 was able to interact with estrogen. Therefore, we next examined whether nhr-14 regulates estrogen signaling in vivo. To investigate whether these interactions actually control the response of C. elegans to hormones, we investigated the expression of vitellogenin, an estrogen responsive gene, in an nhr-14 mutant. Semi-quantitative RT-PCR showed that vitellogenin expression was significantly reduced in the mutant. This suggests that NHR-14 is a C. elegans estrogenic hormone receptor and that it controls gene expression in response to estrogen.

  14. Estrogen and Bazedoxifene

    MedlinePlus

    ... estrogen that controls your symptoms and only taking estrogen as long as needed can help reduce these risks. Talk to your doctor from time to time to decide if you should take a lower dose of estrogen or should stop taking the medication.Talk to ...

  15. Estrogens Can Disrupt Amphibian Mating Behavior

    PubMed Central

    Hoffmann, Frauke; Kloas, Werner

    2012-01-01

    The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline. PMID:22355410

  16. Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency.

    PubMed

    Beresford, Nicola; Baynes, Alice; Kanda, Rakesh; Mills, Matthew R; Arias-Salazar, Karla; Collins, Terrence J; Jobling, Susan

    2016-09-11

    Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters. Much of the estrogenic potency of wastewater treatment plant (WWTP) effluents can be attributed to the discharge of steroid estrogens including estradiol (E2), EE2 and E1 due to incomplete removal of these substances at the treatment plant. An evaluation of the efficacy of wastewater treatment processes requires the quantitative determination of individual substances most often undertaken using chemical analysis methods. Most frequently used methods include Gas Chromatography-Mass Spectrometry (GCMS/MS) or Liquid Chromatography-Mass Spectrometry (LCMS/MS) using multiple reaction monitoring (MRM). Although very useful for regulatory purposes, targeted chemical analysis can only provide data on the compounds (and specific metabolites) monitored. Ecotoxicology methods additionally ensure that any by-products produced or unknown estrogenic compounds present are also assessed via measurement of their biological activity. A number of in vitro bioassays including the Yeast Estrogen Screen (YES) are available to measure the estrogenic activity of wastewater samples. Chemical analysis in conjunction with in vivo and in vitro bioassays provides a useful toolbox for assessment of the efficacy and suitability of wastewater treatment processes with respect to estrogenic endocrine disrupting compounds. This paper utilizes a battery of chemical and ecotoxicology tests to assess conventional, advanced and emerging wastewater treatment processes in laboratory and field studies.

  17. Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency

    PubMed Central

    Beresford, Nicola; Baynes, Alice; Kanda, Rakesh; Mills, Matthew R.; Arias-Salazar, Karla; Collins, Terrence J.; Jobling, Susan

    2016-01-01

    Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters. Much of the estrogenic potency of wastewater treatment plant (WWTP) effluents can be attributed to the discharge of steroid estrogens including estradiol (E2), EE2 and E1 due to incomplete removal of these substances at the treatment plant. An evaluation of the efficacy of wastewater treatment processes requires the quantitative determination of individual substances most often undertaken using chemical analysis methods. Most frequently used methods include Gas Chromatography-Mass Spectrometry (GCMS/MS) or Liquid Chromatography-Mass Spectrometry (LCMS/MS) using multiple reaction monitoring (MRM). Although very useful for regulatory purposes, targeted chemical analysis can only provide data on the compounds (and specific metabolites) monitored. Ecotoxicology methods additionally ensure that any by-products produced or unknown estrogenic compounds present are also assessed via measurement of their biological activity. A number of in vitro bioassays including the Yeast Estrogen Screen (YES) are available to measure the estrogenic activity of wastewater samples. Chemical analysis in conjunction with in vivo and in vitro bioassays provides a useful toolbox for assessment of the efficacy and suitability of wastewater treatment processes with respect to estrogenic endocrine disrupting compounds. This paper utilizes a battery of chemical and ecotoxicology tests to assess conventional, advanced and emerging wastewater treatment processes in laboratory and field studies. PMID:27684328

  18. The epigenetics of estrogen

    PubMed Central

    Zhao, Zaorui; Fan, Lu

    2011-01-01

    Epigenetic processes have been implicated in everything from cell proliferation to maternal behavior. Epigenetic alterations, including histone alterations and DNA methylation, have also been shown to play critical roles in the formation of some types of memory, and in the modulatory effects that factors, such as stress, drugs of abuse and environmental stimulation, have on the brain and memory function. Recently, we demonstrated that the ability of the sex-steroid hormone 17β-estradiol (E2) to enhance memory formation is dependent on histone acetylation and DNA methylation, a finding that has important implications for understanding how hormones influence cognition in adulthood and aging. In this article, we provide an overview of the literature demonstrating that epigenetic processes and E2 influence memory, describe our findings indicating that epigenetic alterations regulate E2-induced memory enhancement, and discuss directions for future work on the epigenetics of estrogen. PMID:21593594

  19. Environmental behavior of organotin compounds in the coastal environment of Xiamen, China.

    PubMed

    Wang, Xinhong; Hong, Huasheng; Zhao, Dongmei; Hong, Liyu

    2008-01-01

    In 2006, organotins pollution were investigated in the coastal environment of Xiamen, China. Six species of organotin compounds including tributyltin, triphenyltin and their degradation compounds were quantified in the dissolved and particulate phases of the water, and in the sediment using GC-FPD. The concentrations of organotin compounds ranged from 2.2 to 160 ng (Sn) L(-1) dissolved in the water, 0.14-6.7 ng (Sn) L(-1) in suspended particulate matter and nd approximately 26 ng (Sn) g(-1) (dry weight) in the sediment. The highest concentration of total organotin or tributyltin in water was found in a shipyard and at a station near the inlet of the harbor, indicating fresh inputs of antifouling paints to Xiamen's coastal environment. Organotin speciation was performed on sediment cores to investigate contamination trends over the past ten years in the harbor. The results of (210)Pb dating indicated that Xiamen western harbor suffered contamination during 2000. The environmental behavior of organotins such as the enhancement of the microlayer, partitioning between water/suspended particulate matter and between water/sediment are also discussed in this paper.

  20. Environmental diagnostic analysis of ground water bacteria and their involvement in utilization of aromatic compounds

    SciTech Connect

    Wear, J.E. Jr.

    1993-05-01

    The objective of this study was to examine the hypothesis that select functional groups of bacteria from pristine sites have an innate ability to degrade synthetic aromatics that often contaminate groundwater environments,due to exposure to naturally occurring recalcitrant aromatics in their environment. This study demonstrates that subsurface microbial communities are capable of utilizing lignin and humic acid breakdown products. Utilizers of these compounds were found to be present in most all the wells tested. Even the deepest aquifer tested had utilizers present for all six of the aromatics tested. Highest counts for the aromatics tested were observed with the naturally occurring breakdown products of either lignin or humic acid. Carboxylic acids were found to be an important sole carbon source for groundwater bacteria possibly explained by the fact that they are produced by the oxidative cleavage of aromatic ring structures. The carbohydrate sole carbon sources that demonstrated the greatest densities were ones commonly associated with humics. This study indicates that utilization of naturally occurring aromatic compounds in the subsurface is an important nutritional source for groundwater bacteria. In addition, it suggests that adaptation to naturally occurring recalcitrant substrates is the origin of degradative pathways for xenobiotic compounds with analogous structure. This work has important implications for in situ bioremediation as a method of environmental cleanup.

  1. The Interplay between Estrogen and Fetal Adrenal Cortex

    PubMed Central

    Kaludjerovic, Jovana; Ward, Wendy E.

    2012-01-01

    Estrogen is a steroid hormone that regulates embryogenesis, cell proliferation and differentiation, organogenesis, the timing of parturition, and fetal imprinting by carrying chemical messages from glands to cells within tissues or organs in the body. During development, placenta is the primary source of estrogen production but estrogen can only be produced if the fetus or the mother supplies dehydroepiandrosterone (DHEA), the estrogen prohormone. Studies show that the fetal zone of the fetal adrenal cortex supplies 60% of DHEA for placental estrogen production, and that placental estrogen in turn modulates the morphological and functional development of the fetal adrenal cortex. As such, in developed countries where humans are exposed daily to environmental estrogens, there is concern that the development of fetal adrenal cortex, and in turn, placental estrogen production may be disrupted. This paper discusses fetal adrenal gland development, how endogenous estrogen regulates the structure and function of the fetal adrenal cortex, and highlights the potential role that early life exposure to environmental estrogens may have on the development and endocrinology of the fetal adrenal cortex. PMID:22536492

  2. Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens.

    PubMed

    Gutendorf, B; Westendorf, J

    2001-09-14

    Many chemicals in surface waters and sediments have recently been discovered to have estrogenic/antiestrogenic activity. Among these compounds, known as 'endocrine disrupters', are natural and synthetic hormones, phytoestrogenes and a variety of industrial chemicals, such as certain detergents and pesticides. These substances are supposed to affect the development and reproduction in wildlife and humans and may also be involved in the induction of cancer. In order to assess the estrogenic/antiestrogenic potential of pure compounds and complex environmental samples we compared an array of in vitro test systems, (i) two luciferase reporter gene assays using transgenic human MVLN cells (derived from MCF-7 cells) and HGELN cells (derived from HeLa cells); (ii) a competitive binding assay with recombinant human estrogen receptors (ER) alpha and beta; and (iii) a proliferation assay with MCF7-cells (E-Screen). The sensitivity of the assays for 17-beta-estradiol decreased in the order: MVLN-cells=E-Screen>HGELN-cells>binding to ER-alpha>binding to ER-beta. A good correlation was obtained between the estrogenic potencies of 11 compounds (17-beta-estradiol (E(2)), estrone (E(1)), estriol (E(3)), ethinylestradiol (EE(2)), diethylstilbestrol (DES), coumestrol, beta-sitosterol, genistein, 4-nonylphenol, 4-octylphenol, bisphenol A) in the three tissue culture assays. The relative potencies of the compounds obtained by the cell free binding assays were one to two orders of magnitude higher compared with the cell culture assays. The phytoestrogens showed a preference to bind to ER-beta, but only genistein showed a much lower activity in the E-Screen (growth induction in breast cancer cells) compared with the luciferase induction in MVLN and HGELN-cells.

  3. An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens: studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor.

    PubMed

    Sheen, Y Y; Simpson, D M; Katzenellenbogen, B S

    1985-08-01

    Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10(-11)-10(-6) M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day X 50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.

  4. Anti-estrogenic activity of lignans from Acanthopanax chiisanensis root.

    PubMed

    Lee, Sanghyun; Yoo, Hye Hyun; Piao, Xiang Lan; Kim, Ju Sun; Kang, Sam Sik; Shin, Kuk Hyun

    2005-02-01

    Anti-estrogenic activity of (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), and 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrolactone (5) isolated from the root of Acanthopanax chiisanensis was tested using Ishikawa cells. Among them, compound 3 exhibited anti-estrogenic activity (IC50 = 4.86 microM).

  5. Postmenopausal skin and estrogen.

    PubMed

    Archer, David F

    2012-10-01

    The aging global population continues to drive increasing demand for cosmaceuticals and cosmetic surgery among older men and women. Since the discovery in the 1990s that estrogen receptors are present in skin cells and decline in number from the onset of menopause in women, researchers have explored a number of ways in which estrogen can improve skin condition. Skin is estrogen responsive, and several studies now exist to support the antiaging properties of estrogen replacement therapies in postmenopausal women. Both systemic and topical estrogens appear to have positive effects on hormonal aging, increasing skin collagen content, thickness, elasticity and hydration. Estrogen therapies may also improve wound healing and reduce the incidence of wound complications. This review explores the potential for targeted estrogen replacement as a therapeutic option for long-term skin management in postmenopausal women.

  6. Estrogenic alkylphenols in fish tissues, sediments, and waters from the U.K. Tyne and Tees estuaries

    SciTech Connect

    Lye, C.M.; Frid, C.L.J.; Gill, M.E.; Cooper, D.W.; Jones, D.M.

    1999-04-01

    Nonylphenols and related compounds are common products of biodegradation of a large group of nonionic surfactants, the nonylphenol polyethoxylates. Many of these compounds are known to be environmentally persistent and to elicit estrogenic response in both mammals and fish. In this study, nonylphenol (NP), nonylphenol monoethoxylate (NP1EO), and octylphenol (OP) were found in tissues of mature male flounder, Platichthys flesus, and in tissues of juvenile flounder. These fish also showed detectable levels of the yolk protein vitellogenin in their plasma, indicative of estrogenic exposure. The compounds were also found in discharges from a major sewage treatment works and in sediments from two estuaries in north-east England; the highest levels from the highly industrialized Tees and lower levels from the industrialized/urbanized Tyne estuary. The implications of these findings for fish populations are discussed.

  7. EVALUATION OF THE EFFECTS OF ENVIRONMENTAL COMPOUNDS ON STEROID HORMONE PRODUCTION IN H295R CELLS

    EPA Science Inventory

    H295R cells constitute a pluripotent cell line that has retained the enzymatic ability to produce steroids along the entire steroidogenic pathway, including C19 androgens and C18 estrogens. For this reason, they have been a valued research tool, and have been employed in an ever...

  8. Country-specific chemical signatures of persistent environmental compounds in breast milk.

    PubMed

    Krysiak-Baltyn, K; Toppari, J; Skakkebaek, N E; Jensen, T S; Virtanen, H E; Schramm, K-W; Shen, H; Vartiainen, T; Kiviranta, H; Taboureau, O; Brunak, S; Main, K M

    2010-04-01

    Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

  9. Compound

    NASA Astrophysics Data System (ADS)

    Suzumura, Akitoshi; Watanabe, Masaki; Nagasako, Naoyuki; Asahi, Ryoji

    2014-06-01

    Recently, Cu-based chalcogenides such as Cu3SbSe4, Cu2Se, and Cu2SnSe3 have attracted much attention because of their high thermoelectric performance and their common feature of very low thermal conductivity. However, for practical use, materials without toxic elements such as selenium are preferable. In this paper, we report Se-free Cu3SbS4 thermoelectric material and improvement of its figure of merit ( ZT) by chemical substitutions. Substitutions of 3 at.% Ag for Cu and 2 at.% Ge for Sb lead to significant reductions in the thermal conductivity by 37% and 22%, respectively. These substitutions do not sacrifice the power factor, thus resulting in enhancement of the ZT value. The sensitivity of the thermal conductivity to chemical substitutions in these compounds is discussed in terms of the calculated phonon dispersion and previously proposed models for Cu-based chalcogenides. To improve the power factor, we optimize the hole carrier concentration by substitution of Ge for Sb, achieving a power factor of 16 μW/cm K2 at 573 K, which is better than the best reported for Se-based Cu3SbSe4 compounds.

  10. Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother-newborn pairs.

    PubMed

    Pedersen, Marie; Halldorsson, Thorhallur I; Mathiesen, Line; Mose, Tina; Brouwer, Abraham; Hedegaard, Morten; Loft, Steffen; Kleinjans, Jos C S; Besselink, Harrie; Knudsen, Lisbeth E

    2010-05-01

    In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX(R)-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother-newborns (0.10 versus 0.18ng CALUX(R)-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX(R)-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rsestrogenic and androgenic exposures during fetal development of humans.

  11. Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.

    PubMed Central

    Hopert, A C; Beyer, A; Frank, K; Strunck, E; Wünsche, W; Vollmer, G

    1998-01-01

    Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9721258

  12. Assessment of SPME Partitioning Coefficients: Implications for Passive Environmental Sampling of Hydrophobic Organic Compounds

    NASA Astrophysics Data System (ADS)

    Difilippo, E. L.; Eganhouse, R. P.

    2009-12-01

    Solid-phase microextraction (SPME) has shown potential as an in situ passive sampling technique in aqueous environments. The reliability of this method depends upon accurate determination of the partitioning coefficient between the fiber coating and water (Kf) for the compounds of interest. Kf values for poly(dimethylsiloxane) (PDMS) and water spanning 4 orders of magnitude have been reported for hydrophobic organic compounds (HOCs). However, most of the published data (86%) do not pass the criterion for negligible depletion (Vw > 100KfVf , where Vw is the sample volume [μl] and Vf is the fiber coating volume [μl]), resulting in erroneous Kf values. The range in reported Kf values is reduced to just over 2 orders of magnitude for some polychlorinated biphenyls (PCBs) when these erroneous values are removed. We conducted a two-tailed t-test comparing Kf values for the same compounds (polycyclic aromatic hydrocarbons (PAHs) and PCBs) measured with different fiber coating thicknesses and fiber manufacturers; the majority (85%) of these Kf values are not statistically different (p = 0.10). In addition to an accurate measurement of Kf, the impact of environmental factors on partitioning, such as temperature and ionic strength, are essential in applying laboratory-measured Kf values to field samples. To date, few studies have measured Kf at conditions other than at 25° C in distilled water. While the available data indicate slight differences in Kf at different temperatures and ionic strength, the data are too limited to make an accurate assessment of the impact of these factors on the accuracy of in situ concentration measurements. Because of the challenges in measuring Kf for HOCs, it may be useful to develop predictive models for calculating Kf using known or measured physico-chemical properties. A multi-parameter linear solvation energy relationship (LSER) was developed to estimate Kf in distilled water at 25° C for HOCs based on published physico

  13. Processing, phase equilibria and environmental degradation of molybdenum (silicom,aluminum)(2) intermetallic compound

    NASA Astrophysics Data System (ADS)

    Eason, Paul Duane

    The Mo(Si,Al)2 C40 compound was chosen for investigation as a possible high temperature structural material. To produce the C40 phase, several processing routes were explored with emphasis on obtaining microstructure/property relationships (i.e. control of grain size and minimization of secondary phases). To facilitate processing of single phase material, the phase equilibria of the Mo-Si-Al ternary system were reevaluated with respect to the phases adjacent to the C40 compound. An anomalous environmental degradation appeared to be the primary obstacle to further study of the compound and was investigated accordingly. Several processing routes were assessed for the production of dense, nearly single-phase Mo(Si,Al)2. Hot powder compaction was chosen as the method of sample production as is the case with many refractory silicide based materials. Therefore, variations in the processing techniques came from the choice of precursor materials and methods of powder production. Mechanical alloying, arc-melting and comminution, and blending of both elemental and compound powders were all employed to produce charges for hot uniaxial pressing. The final compacts were compared on the basis of density, grain size and presence of secondary phases. Establishment of a Mo-Si-Al ternary isothermal phase diagram at 1400°C was performed. Multiphase alloy compositions were selected to identify the phase boundaries of the C40, C54, T1 and Mo3Al8 phase fields, as well as to verify the existence of the C54 phase at 1400°C. The alloys were equilibrated by heat treatment and analyzed for phase identification and quantitative compositional information. The environmental degradation phenomenon was approached as a classical "pest" with an emphasis of study on grain boundary chemistry and atmospheric dependence of attack. Both Auger spectroscopy and electron microscopy revealed carbon-impurity-induced grain boundary segregation responsible for the embrittlement and material loss. Means of

  14. Estrogen Deficiency and the Origin of Obesity during Menopause

    PubMed Central

    Lizcano, Fernando; Guzmán, Guillermo

    2014-01-01

    Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women. PMID:24734243

  15. Assessment of PDMS-water partition coefficients: implications for passive environmental sampling of hydrophobic organic compounds

    USGS Publications Warehouse

    DiFilippo, Erica L.; Eganhouse, Robert P.

    2010-01-01

    Solid-phase microextraction (SPME) has shown potential as an in situ passive-sampling technique in aquatic environments. The reliability of this method depends upon accurate determination of the partition coefficient between the fiber coating and water (Kf). For some hydrophobic organic compounds (HOCs), Kf values spanning 4 orders of magnitude have been reported for polydimethylsiloxane (PDMS) and water. However, 24% of the published data examined in this review did not pass the criterion for negligible depletion, resulting in questionable Kf values. The range in reported Kf is reduced to just over 2 orders of magnitude for some polychlorinated biphenyls (PCBs) when these questionable values are removed. Other factors that could account for the range in reported Kf, such as fiber-coating thickness and fiber manufacturer, were evaluated and found to be insignificant. In addition to accurate measurement of Kf, an understanding of the impact of environmental variables, such as temperature and ionic strength, on partitioning is essential for application of laboratory-measured Kf values to field samples. To date, few studies have measured Kf for HOCs at conditions other than at 20 degrees or 25 degrees C in distilled water. The available data indicate measurable variations in Kf at different temperatures and different ionic strengths. Therefore, if the appropriate environmental variables are not taken into account, significant error will be introduced into calculated aqueous concentrations using this passive sampling technique. A multiparameter linear solvation energy relationship (LSER) was developed to estimate log Kf in distilled water at 25 degrees C based on published physicochemical parameters. This method provided a good correlation (R2 = 0.94) between measured and predicted log Kf values for several compound classes. Thus, an LSER approach may offer a reliable means of predicting log Kf for HOCs whose experimental log Kf values are presently unavailable. Future

  16. Predicting the environmental distribution of compounds with unknown physicochemical properties from known pesticide properties

    SciTech Connect

    Prasad, S.S.

    1991-01-01

    This study examines how pesticide characteristics such as water solubility, molecular weight, bioconcentration, volatility, and soil absorption affect soil-to-water mobility, water-to-air dissipation, and water-to-biota accumulation when present in the environmental medium of preferred residence. The study concludes that chemicals that have low water solubilities tend to adsorb to soil, those that have low vapor pressures tend to dissipate slowly from water, and those that have relatively high octanol-to-water partition coefficients or low water solubility have a high potential for bioconcentration. Based on these findings, researchers should be able to predict the mobility of pesticides belonging to a particular category or family of compounds with unknown physicochemical properties and recommend ways to restore the environment. 13 refs., 13 figs., 4 tabs.

  17. Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

    PubMed Central

    Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

    2015-01-01

    Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment. PMID:26333997

  18. Environmental guideline for the reduction of volatile organic compound emissions from the plastics processing industry

    SciTech Connect

    1997-12-31

    The purpose of this document is to provide guidance to environmental regulatory agencies, manufacturers, and operators of plastics processing plants regarding the means of reducing emissions containing volatile organic compounds (VOCs) which are released to the environment in the course of production. Sectors covered by the guideline are expanded polystyrene, cellular polyethylene foams, polyvinyl chloride, and reinforced plastics and composites made from thermoset polyester resins. The guideline focuses on the reduction of VOC emissions from processing and clean-up operations, the handling and storage of VOC-containing materials, and the handling and disposal of wastes. The guideline contains material, equipment, process, and operating standards for plastics processing facilities, record keeping and training standards, recommended operating practices, and testing protocols.

  19. A wireless hybrid chemical sensor for detection of environmental volatile organic compounds.

    PubMed

    Chen, Cheng; Tsow, Francis; Campbell, Katherine Driggs; Iglesias, Rodrigo; Forzani, Erica; Tao, N J

    2013-05-01

    A hybrid sensor for monitoring volatile organic compounds (VOCs) in air is developed. The device combines two orthogonal sensing principles, selective molecular binding with a microfabricated quartz tuning fork detector and separation of analytes with a column. The tuning fork detector is functionalized with molecular imprinted polymers for selective binding to benzene, toluene, ethylbenzene, and xylenes (BTEX), and the separation column provides further discrimination of the analytes for real world complex sample analysis. The device is wireless, portable, battery-powered, and cell-phone operated, and it allows reliable detection in parts per billion (ppb) by volume-levels of BTEX in the presence of complex interferents. The hybrid device is suitable for occupational, environmental health, and epidemiological applications.

  20. Determination of aromatic tracer compounds for environmental tobacco smoke aerosol by two step laser mass spectrometry

    NASA Astrophysics Data System (ADS)

    Morrical, Brad D.; Zenobi, Renato

    Cigarette smoking is a major cause of indoor aerosol pollution. Determination of exposure to environmental tobacco smoke (ETS) aerosol is critical to understanding health effects. Sizing studies have shown that ETS has a size distribution that is efficiently deposited into the lungs and can therefore provide effective delivery of carcinogenic compounds into the human body. Two-step laser mass spectrometry is used to analyze aromatic compounds on aerosols collected from a smoking lobby. The determination and suitability of ETS tracers on aerosols is examined. Additionally, the transport of aerosol from the smoking lobby is examined to determine what effect deposition and dilution have on the mass spectrum observed. Results from the analysis of ETS, both from lobby samples and direct cigarette sampling, show that several unique peaks are present in the mass spectrum when compared to other combustion sources, such as automobiles and diesel trucks. In particular, ions at m/ z 118, 132, 146, and 160 are consistently present and are not found in other combustion sources. For the indoor environment, where chemical transformation is much less rapid than in the outdoor environment, these ions were found to be present as soon as the first smokers appeared and persisted over the course of the day. Aerosol samples taken in the morning prior to the presence of smokers in the lobby reveal the presence of skeletal PAHs, indicative of outdoor urban traffic aerosol penetration into the building.

  1. Effect of genotype and environmental conditions on health-promoting compounds in Brassica rapa.

    PubMed

    Francisco, Marta; Cartea, María Elena; Soengas, Pilar; Velasco, Pablo

    2011-03-23

    It is well-known that a variety of factors (genetic and environmental) affect the ultimate metabolite levels in brassica vegetables, although there is still little information about the role that genetics and environment play on glucosinolates and phenolic levels. Total glucosinolates were more abundant in turnip tops (26.02 μmol g(-1) dw) than in turnip greens (17.78 μmol g(-1) dw). On the other hand, total phenolic content was found in higher quantities in turnip greens (43.81 μmol g(-1) dw) than in turnip tops (37.53 μmol g(-1) dw). Aliphatic glucosinolates were clearly regulated by genotype; in contrast, the effects of environment and genotype×environment interaction on the indolic glucosinolate and phenolic compounds content appeared to be the main effects of variation. Identification of genotypes with enhanced and stable levels of these compounds would provide a value-added opportunity for marketing this crop with superior health promotion to consumers.

  2. Bioassay- versus analytically-derived estrogen equivalents: Ramifications for monitoring

    EPA Science Inventory

    Due to concern for possible endocrine-related effects on aquatic vertebrates, environmental estrogens (EEs) are a growing focus of surface water contaminant monitoring programs. Some efforts utilize measurement of a targeted set of chemicals known to act as estrogen receptor (ER)...

  3. Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

    PubMed

    Xin, D; Wang, H; Yang, J; Su, Y-F; Fan, G-W; Wang, Y-F; Zhu, Y; Gao, X-M

    2010-02-01

    The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

  4. The Estrogen Hypothesis of Obesity

    PubMed Central

    Grantham, James P.; Henneberg, Maciej

    2014-01-01

    The explanation of obesity as a simple result of positive energy balance fails to account for the scope of variable responses to diets and lifestyles. It is postulated that individual physiological and anatomical variation may be responsible for developing obesity. Girls in poor families develop greater adiposity than their male siblings, a trend not present in richer environments. This indicates strong influence of estrogen on fat accumulation irrespective of poor socioeconomic conditions. Obesity rates in males and females of developed nations are similar, while in poorer nations obesity is much more prevalent in females. Female to male ratio of obesity correlates inversely with gross domestic product. Therefore, the parity of male and female obesity in developed countries may result from male exposure to environmental estrogen-like substances associated with affluence. These hormonally driven mechanisms may be equally active within both sexes in more developed areas, thereby increasing overall obesity. PMID:24915457

  5. Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

    PubMed Central

    S Katzenellenbogen, Benita; A Katzenellenbogen, John

    2000-01-01

    Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents. PMID:11250726

  6. Assessment and Molecular Actions of Endocrine-Disrupting Chemicals That Interfere with Estrogen Receptor Pathways

    PubMed Central

    Kerdivel, Gwenneg; Habauzit, Denis; Pakdel, Farzad

    2013-01-01

    In all vertebrate species, estrogens play a crucial role in the development, growth, and function of reproductive and nonreproductive tissues. A large number of natural or synthetic chemicals present in the environment and diet can interfere with estrogen signaling; these chemicals are called endocrine disrupting chemicals (EDCs) or xenoestrogens. Some of these compounds have been shown to induce adverse effects on human and animal health, and some compounds are suspected to contribute to diverse disease development. Because xenoestrogens have varying sources and structures and could act in additive or synergistic effects when combined, they have multiple mechanisms of action. Consequently, an important panel of in vivo and in vitro bioassays and chemical analytical tools was used to screen, evaluate, and characterize the potential impacts of these compounds on humans and animals. In this paper, we discuss different molecular actions of some of the major xenoestrogens found in food or the environment, and we summarize the current models used to evaluate environmental estrogens. PMID:23737774

  7. The effects of abiotic and biotic environmental components on the microbial mineralization of selected xenobiotic compounds in soils

    SciTech Connect

    Knaebel, D.B.

    1990-01-01

    This research investigated the effects of environmental components on the microbial mineralization of xenobiotic compounds in soils. The soils' chemical and physical characteristics, microbial community structure, organic and inorganic components, and other associated biota (plants) were examined for their effects on the biodegradation process. The biodegradation of {sup 14}C foreign, synthetic ({double bond} xenobiotic) compounds was measured by quantifying {sup 14} CO{sub 2} production over time. Mineralization kinetics were estimated by first-order and 3/2 order mineralization models. The compounds displayed different mineralization kinetics in the different soils, which were due to nature of the xenobiotic chemical and to abiotic and biotic soil characteristics. Specific soil components (montmorillonite, humic acids and fulvic acids) inhibited mineralization. Other soil components (sand, illite, kaolinite) had less effect on the biodegradation process. Modified soil microbial communities mineralized the compounds differently. Bacteria-enhanced soils metabolized the compounds to greater extents than the fungi-enhanced soils, which both mineralized the compounds more than actinomycete-enhanced soils. However, the rates of mineralization were only significantly different between the bacteria-enhanced soils and the actinomycete-enhanced soil. Plants significantly increased soil microbial biomass and activity, and stimulated the rate of microbial mineralization of xenobiotic compounds. However, they had no effect on the total amounts of mineralization. In summary, these diverse abiotic and biotic environmental components exerted tremendous influences on the microbial turnover of xenobiotic compounds in soils. Therefore, these components should be considered when modeling the fate of xenobiotic chemicals in the environment.

  8. Genome Sequence of Pseudomonas citronellolis SJTE-3, an Estrogen- and Polycyclic Aromatic Hydrocarbon-Degrading Bacterium

    PubMed Central

    Zheng, Daning; Wang, Xiuli; Wang, Pingping; Peng, Wanli; Ji, Nannan

    2016-01-01

    Pseudomonas citronellolis SJTE-3, isolated from the active sludge of a wastewater treatment plant in China, can utilize a series of environmental estrogens and estrogen-like toxicants. Here, we report its whole-genome sequence, containing one circular chromosome and one circular plasmid. Genes involved in estrogen biodegradation in this bacterium were predicted. PMID:27932659

  9. Flow analysis techniques as effective tools for the improved environmental analysis of organic compounds expressed as total indices.

    PubMed

    Maya, Fernando; Estela, José Manuel; Cerdà, Víctor

    2010-04-15

    The scope of this work is the accomplishment of an overview about the current state-of-the-art flow analysis techniques applied to the environmental determination of organic compounds expressed as total indices. Flow analysis techniques are proposed as effective tools for the quick obtention of preliminary chemical information about the occurrence of organic compounds on the environment prior to the use of more complex, time-consuming and expensive instrumental techniques. Recently improved flow-based methodologies for the determination of chemical oxygen demand, halogenated organic compounds and phenols are presented and discussed in detail. The aim of the present work is to demonstrate the highlight of flow-based techniques as vanguard tools on the determination of organic compounds in environmental water samples.

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

    PubMed

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

    2009-11-01

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

  11. Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density

    PubMed Central

    Luine, Victoria N.; Frankfurt, Maya

    2012-01-01

    Estrogens exert sustained, genomically mediated effects on memory throughout the female life cycle, but here we review new studies documenting rapid effects of estradiol on memory, which are exerted through membrane-mediated mechanisms. Use of recognition memory tasks in rats, shows that estrogens enhance memory consolidation within one hour. 17α-estradiol is more potent than 17β-estradiol, and the dose response relationship between estrogens and memory is an inverted U shape. Use of specific estrogen receptor (ER) agonists suggests mediation by an ERβ-like membrane receptor. Enhanced memory is associated with increased spine density and altered noradrenergic activity in the medial prefrontal cortex and hippocampus within 30 min. of administration. The environmental chemical, bisphenol-A, rapidly antagonizes enhancements in memory in both sexes possibly through actions on spines. Thus, estradiol and related compounds exert rapid alterations in cognition through non-genomic mechanisms, a finding which may provide a basis for better understanding and treating memory impairments. PMID:22981654

  12. In vitro estrogenic activity of Achillea millefolium L.

    PubMed

    Innocenti, G; Vegeto, E; Dall'Acqua, S; Ciana, P; Giorgetti, M; Agradi, E; Sozzi, A; Fico, G; Tomè, F

    2007-02-01

    Isolation and biological characterization of pure compounds was used to identify and characterize estrogenic activity and estrogen receptors (ER) preference in chemical components of Achillea millefolium. This medicinal plant is used in folk medicine as an emmenagogue. In vitro assay, based on recombinant MCF-7 cells, showed estrogenic activity in a crude extract of the aerial parts of A. millefolium. After fractionation of the crude extract with increasing polar solvents, estrogenic activity was found in the methanol/water fraction. Nine compounds were isolated and characterized by HR-MS spectra and 1D- and 2D-NMR techniques. In particular, dihydrodehydrodiconiferyl alcohol 9-O-beta-D-glucopyranoside - a glycosyl-neolignan - was isolated for the first time from the genus Achillea in addition to six flavone derivatives, apigenin, apigenin-7-O-beta-D-glucopyranoside, luteolin, luteolin-7-O-beta-D-glucopyranoside, luteolin-4'-O-beta-D-glucopyranoside, rutin, and two caffeic acid derivatives, 3,5-dicaffeoylquinic acid and chlorogenic acid. Apigenin and luteolin, the most important estrogenic compounds among those tested, were studied for their ability to activate alpha or beta estrogen receptors (ERalpha, ERbeta) using transiently transfected cells. Our results suggest that isolation and biological characterization of estrogenic compounds in traditionally used medicinal plants could be a first step in better assessing further (e.g. in vivo) tests of nutraceutical and pharmacological strategies based on phytoestrogens.

  13. A demonstration of the uncertainty in predicting the estrogenic activity of individual chemicals and mixtures from an in vitro estrogen receptor transcriptional activation assay (T47D-KBluc) to the in vivo uterotrophic assay using oral exposure

    EPA Science Inventory

    In vitro estrogen receptor assays are valuable screening tools for identifying environmental samples and chemicals that display estrogenic activity. However, in vitro potency cannot necessarily be extrapolated to estimates of in vivo potency because in vitro assays are currently...

  14. Visualization of Estrogen Receptor Transcriptional Activation in Zebrafish

    PubMed Central

    Halpern, Marnie E.

    2011-01-01

    Estrogens regulate a diverse range of physiological processes and affect multiple tissues. Estrogen receptors (ERs) regulate transcription by binding to DNA at conserved estrogen response elements, and such elements have been used to report ER activity in cultured cells and in transgenic mice. We generated stable, transgenic zebrafish containing five consecutive elements upstream of a c-fos minimal promoter and green fluorescent protein (GFP) to visualize and quantify transcriptional activation in live larvae. Transgenic larvae show robust, dose-dependent estrogen-dependent fluorescent labeling in the liver, consistent with er gene expression, whereas ER antagonists inhibit GFP expression. The nonestrogenic steroids dexamethasone and progesterone fail to activate GFP, confirming ER selectivity. Natural and synthetic estrogens activated the transgene with varying potency, and two chemicals, genistein and bisphenol A, preferentially induce GFP expression in the heart. In adult fish, fluorescence was observed in estrogenic tissues such as the liver, ovary, pituitary gland, and brain. Individual estrogen-responsive neurons and their projections were visualized in the adult brain, and GFP-positive neurons increased in number after 17β-estradiol exposure. The transgenic estrogen-responsive zebrafish allow ER signaling to be monitored visually and serve as in vivo sentinels for detection of estrogenic compounds. PMID:21540282

  15. Estrogen Receptor Ligands: A Review (2013–2015)

    PubMed Central

    Farzaneh, Shabnam; Zarghi, Afshin

    2016-01-01

    Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high

  16. QSAR prediction of estrogen activity for a large set of diverse chemicals under the guidance of OECD principles.

    PubMed

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2006-11-01

    A large number of environmental chemicals, known as endocrine-disrupting chemicals, are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones, and such chemicals may pose a serious threat to the health of humans and wildlife. They are thought to act through a variety of mechanisms, mainly estrogen-receptor-mediated mechanisms of toxicity. However, it is practically impossible to perform thorough toxicological tests on all potential xenoestrogens, and thus, the quantitative structure--activity relationship (QSAR) provides a promising method for the estimation of a compound's estrogenic activity. Here, QSAR models of the estrogen receptor binding affinity of a large data set of heterogeneous chemicals have been built using theoretical molecular descriptors, giving full consideration to the new OECD principles in regulation for QSAR acceptability, during model construction and assessment. An unambiguous multiple linear regression (MLR) algorithm was used to build the models, and model predictive ability was validated by both internal and external validation. The applicability domain was checked by the leverage approach to verify prediction reliability. The results obtained using several validation paths indicate that the proposed QSAR model is robust and satisfactory, and can provide a feasible and practical tool for the rapid screening of the estrogen activity of organic compounds.

  17. Estrogens and Prostate Cancer: Etiology, Mediators, Prevention, and Management

    PubMed Central

    Ho, Shuk-Mei; Lee, Ming-tsung; Lam, Hung-Ming; Leung, Yuet-Kin

    2011-01-01

    The relationship between hormones and the pathogenesis of prostate cancer (PCa) has been studied extensively. All the mainstay targets for hormonal PCa therapies are based on negating androgen action. Recent epidemiologic and experimental data have clearly pinpointed the key roles of estrogens in PCa development and progression. Racial and geographical differences, as well as age-associated changes, in estrogen synthesis and metabolism contribute significantly to the etiology by increasing the ratio of circulating estrogen to androgen, sex hormone binding globulin synthesis, and aromatase activity and reducing androgen glucuronidation and tissue bioactivation. Promotion of aberrant cell growth, evasion of apoptosis, increased oxidative stress and inflammation, and gains in adiposity and bioactivation to genotoxic carcinogens during adulthood are probable mechanisms of estrogen carcinogenicity, while “estrogen imprinting” via epigenetics in early-life also determines PCa risk. Although the effects of estrogens are known to be mediated by genomic actions of the two estrogen receptor (ER) subtypes (ERα and ERβ), other non-canonical mediators, including the different ERβ isoforms, membrane and mitochondrial ERs, and G protein-coupled receptor 30, may have major actions diverging from classical ER actions. These new discoveries have led to renewed interest among the public and the medicinal field in estrogens and antiestrogens as singular and adjuvant PCa treatment and prevention regimens. This review summarizes current knowledge on how different estrogens/antiestrogens/estrogen mimics contribute to prostate carcinogenesis, the roles of the different mediators of estrogen in the process, and the potentials of new estrogenic/antiestrogenic compounds as targeted therapies for prevention and treatment of PCa. PMID:21889723

  18. Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory.

    PubMed

    Korol, Donna L; Pisani, Samantha L

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions.

  19. Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species.

    PubMed

    Bhandari, Ramji K; Deem, Sharon L; Holliday, Dawn K; Jandegian, Caitlin M; Kassotis, Christopher D; Nagel, Susan C; Tillitt, Donald E; Vom Saal, Frederick S; Rosenfeld, Cheryl S

    2015-04-01

    Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered.

  20. Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species

    USGS Publications Warehouse

    Bhandari, Ramji K.; Deem, Sharon L.; Holliday, Dawn K.; Jandegian, Caitlin M.; Kassotis, Christopher D.; Nagel, Susan C.; Tillitt, Donald E.; vom Saal, Frederick S.; Rosenfeld, Cheryl S.

    2015-01-01

    Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered.

  1. Are oral contraceptives a significant contributor to the estrogenicity of drinking water?

    PubMed

    Wise, Amber; O'Brien, Kacie; Woodruff, Tracey

    2011-01-01

    Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.

  2. Emissions of volatile organic compounds from new carpets measured in a large-scale environmental chamber

    SciTech Connect

    Hodgson, A.T.; Wooley, J.D.; Daisey, J.M. )

    1993-03-01

    This study was undertaken to quantify the emissions of volatile organic compounds (VOCs) released by new carpets. Samples of four typical carpets, including two with styrene-butadiene rubber (SBR) latex adhesive and two with different backings, were collected from the finish lines at manufacturers' mills. Individual VOCs released from these samples were identified, and their concentrations, emission rates and mass emissions were measured under simulated indoor conditions in a 20 m[sup 3] environmental chamber over one week periods. Concentrations and emission rates of VOCs emitted by a new SBR carpet were also measured in a house. The carpets emitted a variety of VOCs. The two SBR carpets primarily emitted 4-phenylcyclohexene (4-PCH), the source of [open quotes]new carpet[close quotes] odor, and styrene. The concentrations and emission rates of 4-PCH were similar for the two carpets, while the styrene values varied significantly. The carpet with a polyvinyl chloride backing emitted formaldehyde, vinyl acetate, isooctane, 1,2-propanediol, and 2-ethyl-1-hexanol. Of these, vinyl acetate and propanediol had the highest concentrations and emission rates. The carpet with a polyurethane backing primarily emitted butylated hydroxytoluene. With the exception of formaldehyde, little is known about the health effects of these VOCs at low concentrations. 23 refs., 3 figs., 6 tabs.

  3. Emissions of volatile organic compounds from new carpets measured in a large-scale environmental chamber.

    PubMed

    Hodgson, A T; Wooley, J D; Daisey, J M

    1993-03-01

    This study was undertaken to quantify the emissions of volatile organic compounds (VOCs) released by new carpets. Samples of four typical carpets, including two with styrene-butadiene rubber (SBR) latex adhesive and two with different backings, were collected from the finish lines at manufacturers' mills. Individual VOCs released from these samples were identified, and their concentrations, emission rates and mass emissions were measured under simulated indoor conditions in a 20 m3 environmental chamber over one week periods. Concentrations and emission rates of VOCs emitted by a new SBR carpet were also measured in a house. The carpets emitted a variety of VOCs. The two SBR carpets primarily emitted 4-phenylcyclohexene (4-PCH), the source of "new carpet" odor, and styrene. The concentrations and emission rates of 4-PCH were similar for the two carpets, while the styrene values varied significantly. The carpet with a polyvinyl chloride backing emitted formaldehyde, vinyl acetate, isooctane, 1,2-propanediol, and 2-ethyl-1-hexanol. Of these, vinyl acetate and propanediol had the highest concentrations and emission rates. The carpet with a polyurethane backing primarily emitted butylated hydroxytoluene. With the exception of formaldehyde, little is known about the health effects of these VOCs at low concentrations.

  4. Volatile trace compounds released from municipal solid waste at the transfer stage: Evaluation of environmental impacts and odour pollution.

    PubMed

    Zhao, Yan; Lu, Wenjing; Wang, Hongtao

    2015-12-30

    Odour pollution caused by municipal solid waste is a public concern. This study quantitatively evaluated the concentration, environmental impacts, and olfaction of volatile trace compounds released from a waste transfer station. Seventy-six compounds were detected, and ethanol presented the highest releasing rate and ratio of 14.76 kg/d and 12.30 g/t of waste, respectively. Life cycle assessment showed that trichlorofluoromethane and dichlorodifluoromethane accounted for more than 99% of impact potentials to global warming and approximately 70% to human toxicity (non-carcinogenic). The major contributor for both photochemical ozone formation and ecotoxicity was ethanol. A detection threshold method was also used to evaluate odour pollution. Five compounds including methane thiol, hydrogen sulphide, ethanol, dimethyl disulphide, and dimethyl sulphide, with dilution multiples above one, were considered the critical compounds. Methane thiol showed the highest contribution to odour pollution of more than 90%, as indicated by its low threshold. Comparison of the contributions of the compounds to different environmental aspects indicated that typical pollutants varied based on specific evaluation targets and therefore should be comprehensively considered. This study provides important information and scientific methodology to elucidate the impacts of odourant compounds to the environment and odour pollution.

  5. TyPol - a new methodology for organic compounds clustering based on their molecular characteristics and environmental behavior.

    PubMed

    Servien, Rémi; Mamy, Laure; Li, Ziang; Rossard, Virginie; Latrille, Eric; Bessac, Fabienne; Patureau, Dominique; Benoit, Pierre

    2014-09-01

    Following legislation, the assessment of the environmental risks of 30000-100000 chemical substances is required for their registration dossiers. However, their behavior in the environment and their transfer to environmental components such as water or atmosphere are studied for only a very small proportion of the chemical in laboratory tests or monitoring studies because it is time-consuming and/or cost prohibitive. Therefore, the objective of this work was to develop a new methodology, TyPol, to classify organic compounds, and their degradation products, according to both their behavior in the environment and their molecular properties. The strategy relies on partial least squares analysis and hierarchical clustering. The calculation of molecular descriptors is based on an in silico approach, and the environmental endpoints (i.e. environmental parameters) are extracted from several available databases and literature. The classification of 215 organic compounds inputted in TyPol for this proof-of-concept study showed that the combination of some specific molecular descriptors could be related to a particular behavior in the environment. TyPol also provided an analysis of similarities (or dissimilarities) between organic compounds and their degradation products. Among the 24 degradation products that were inputted, 58% were found in the same cluster as their parents. The robustness of the method was tested and shown to be good. TyPol could help to predict the environmental behavior of a "new" compound (parent compound or degradation product) from its affiliation to one cluster, but also to select representative substances from a large data set in order to answer some specific questions regarding their behavior in the environment.

  6. Bioaccumulation of photoprotective compounds in copepods: environmental triggers and sources of intra-specific variability

    NASA Astrophysics Data System (ADS)

    Zagarese, H. E.; García, P.; Diéguez, M. D.; Ferraro, M. A.

    2012-12-01

    Ultraviolet radiation (UVR) and temperature are two globally important abiotic factors affecting freshwater ecosystems. Planktonic organisms have developed a battery of counteracting mechanisms to minimize the risk of being damaged by UVR, which respond to three basic principles: avoid, protect, repair. Copepods are among the most successful zooplankton groups. They are highly adaptable animals, capable of displaying flexible behaviors, physiologies, and life strategies. In particular, they are well equipped to cope with harmful UVR. Their arsenal includes vertical migration, accumulation of photoprotective compounds, and photorepair. The preference for a particular strategy is affected by a plethora of environmental (extrinsic) parameters, such as the existence of a depth refuge, the risk of visual predation, and temperature. Temperature modifies the environment (e.g. the lake thermal structure), and animal metabolism (e.g., swimming speed, bioaccumulation of photoprotective compounds). In addition, the relative weight of UVR-coping strategies is also influenced by the organism (intrinsic) characteristics (e.g., inter- and intra-specific variability). The UV absorbing compounds, mycosporine-like amino acids (MAAs), are widely distributed among freshwater copepods. Animals are unable to synthesize MAAs, and therefore depend on external sources for accumulating these compounds. Although copepods may acquire MAAs from their food, for the few centropagic species investigated so far, the main source of MAAs are microbial (most likely prokaryotic) organisms living in close association with the copepods. Boeckella gracilipes is a common centropagic copepod in Patagonian lakes. We suspected that its occurrence in different types of lakes, hydrologically unconnected, but within close geographical proximity, could have resulted in different microbial-copepod associations (i.e., different MAAs sources) that could translate into intra-specific differences in the accumulation

  7. MEMBRANE ESTROGEN RECEPTOR REGULATION OF HYPOTHALAMIC FUNCTION

    PubMed Central

    Micevych, Paul E.; Kelly, Martin J.

    2012-01-01

    Over the decades, our understanding of estrogen receptor (ER) function has evolved. Today we are confronted by at least two nuclear ERs: ERα and ERβ; and a number of putative membrane ERs, including ERα, ERβ, ER-X, GPR30 and Gq-mER. These receptors all bind estrogens or at least estrogenic compounds and activate intracellular signaling pathways. In some cases, a well-defined pharmacology, and physiology has been discovered. In other cases, the identity or the function remains to be elucidated. This mini-review attempts to synthesize our understanding of 17β-estradiol membrane signaling within hypothalamic circuits involved in homeostatic functions focusing on reproduction and energy balance. PMID:22538318

  8. Selective determination of estrogenic compounds in water by microextraction by packed sorbents and a molecularly imprinted polymer coupled with large volume injection-in-port-derivatization gas chromatography-mass spectrometry.

    PubMed

    Prieto, A; Vallejo, A; Zuloaga, O; Paschke, A; Sellergen, B; Schillinger, E; Schrader, S; Möder, M

    2011-10-03

    A fully automated protocol consisting of microextraction by packed sorbents (MEPS) coupled with large volume injection-in-port-derivatization-gas chromatography-mass spectrometry (LVI-derivatization-GC-MS) was developed to determine endocrine disrupting compounds (EDCs) such as alkylphenols, bisphenol A, and natural and synthetic hormons in river and waste water samples. During method optimization, the extraction parameters as ion strength of the water sample, the MEPS extraction regime, the volume of organic solvent used for the elution/injection step, the type of elution solvents and the selectivity of the sorbents were studied. For optimum in-port-derivatization, 10 μL of the derivatization reagent N,O-bis(trimethylsilyl)triufloroacetamide with 1% of trimethylchlorosilane (BSTFA+1% TMCS) was used. 17β-Estradiol-molecularly imprinted polymer (MIP) and silica gel (modified with C-18) sorbents were examined for the enrichment of the target analytes from water samples and the obtained results revealed the high selectivity of the MIP material for extraction of substances with estrogen-like structures. Recovery values for most of the analytes ranged from 75 to 109% for the C18 sorbent and from 81 to 103% for the MIP material except for equilin (on C18 with only 57-66% recovery). Precision (n=4) of the entire analysis protocol ranged between 4% and 22% with both sorbents. Limits of detection (LODs) were at the low ngL(-1) level (0.02-87, C18 and 1.3-22, MIP) for the target analytes.

  9. Breast cancer survivors who use estrogenic botanical supplements have lower serum estrogen levels than non users

    PubMed Central

    Wayne, Sharon J; Neuhouser, Marian L; Koprowski, Carol; Ulrich, Cornelia M; Wiggins, Charles; Gilliland, Frank; Baumgartner, Kathy B; Baumgartner, Richard N; McTiernan, Anne; Bernstein, Leslie; Ballard-Barbash, Rachel

    2014-01-01

    Objective To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors. Methods 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements. Results Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 v 23.6 pg/mL), estradiol (12.8 v 14.7 pg/mL), free estradiol (0.29 v 0.35 pg/mL), and DHEAS (47.7 v 56.2 ug/dL) compared to women reporting no use. Conclusion Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis. PMID:18931907

  10. Comparison of in vitro and in vivo estrogenic activity of UV filters in fish.

    PubMed

    Kunz, Petra Y; Galicia, Hector F; Fent, Karl

    2006-04-01

    In this work, we evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. We focus on UV filters being used in sunscreens and in UV stabilization of materials. First, we determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made comparisons with yeast carrying the human hERalpha for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose-response curves with maximal responses of 81-115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone-4 displayed lower maximal responses of 15-74%. Whereas the activity of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the activities of UV filters were similar or relatively higher in rtERalpha, indicating different relative binding activities of both ER. Subsequently, we analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 microg/l) than BP1 (4919 microg/l) and BP2 (8783 microg/l). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus we propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.

  11. Estrogenic activity of the phytoestrogens naringenin, 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin.

    PubMed

    Zierau, Oliver; Gester, Sven; Schwab, Pia; Metz, Peter; Kolba, Susanne; Wulf, Marina; Vollmer, Günter

    2002-05-01

    Chemically synthesized naringenin derivatives, identical to natural occurring compounds, were tested for their estrogenic activity using two independent estrogen screening assays. Using a yeast based estrogen receptor assay, strong estrogenic activities were demonstrated for 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin, while the parent compound naringenin did not show recognizable estrogenic activity. In MVLN cells, a bioluminescent MCF-7-derived cell line, the estrogenic activity of 8-prenylnaringenin and 6-(1,1-dimethylallyl)naringenin was detected at concentrations of 10(-6) M and 5 x 10(-6) M respectively. Naringenin demonstrated estrogenic activity but only at a concentration of 10(-5) M. These estrogenic effects are mediated by the ER, as the antiestrogen 4-hydroxytamoxifen inhibited these activities. In summary, this study provides the further confirmation that 8-prenylnaringenin demonstrates high estrogenic activity, and demonstrated for the first time for 6-(1,1-dimethylallyl)naringenin a reasonable high estrogenic activity, while naringenin exhibit low or no estrogenic activity.

  12. Dietary Estrogens Act through Estrogen Receptor-Mediated Processes and Show No Antiestrogenicity in Cultured Breast Cancer Cells.

    PubMed Central

    Makela, S; Davis, VL; Tally, WC; Korkman, J; Salo, L; Vihko, R; Santti, R; Korach, KS

    1994-01-01

    Dietary estrogens are believed to exert their estrogenic or antiestrogenic (chemopreventive) action in estrogen responsive cells by interacting with the estrogen receptor (ER). The present study was undertaken to evaluate a direct role of ER in estrogenic or antiestrogenic activities of three dietary estrogens (coumestrol, genistein and zearalenone). HeLa cells were transiently co-transfected with an expression vector for ER and an estrogen-responsive reporter gene construct. Coumestrol, genistein, and zearalenone all increased the activity of the reporter gene, only in the presence of the ER, and the activation was blocked with the ER antagonist ICI 164,384, demonstrating an ER-specific, agonist response. In addition, in MCF-7 cells, coumestrol and zearalenone increased the expression of the estrogen-responsive pS2 gene. Coumestrol and genistein inhibited the purified estrogen-specific 17ß-hydroxysteroid oxidoreductase enzyme and the conversion of estrone to 17ß-estradiol in T-47D cells, which contain this enzyme. However, they did not inhibit the estrone-induced proliferation of T-47D cells. In conclusion, coumestrol, genistein, and zearalenone are all potent estrogens in vitro, and they act through ER mediated mechanism. Our findings give no evidence to support the idea that these compounds act as antiestrogens through competition for the binding sites of ER or by inhibition of the conversion of estrone to 17ß-estradiol in breast cancer cells, since this effect was nullified by their agonist action on cell proliferation. Therefore, their suggested chemopreventive action in estrogen-related cancers must be mediated through other mechanisms. Images Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 2. E Figure 3. A Figure 3. B Figure 4. A Figure 4. B Figure 4. C Figure 4. D Figure 4. E Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. A Figure 9. B Figure 9. C PMID:9679118

  13. Occurrence and removal of estrogens, progesterone and testosterone in three constructed wetlands treating municipal sewage in the Czech Republic.

    PubMed

    Vymazal, Jan; Březinová, Tereza; Koželuh, Milan

    2015-12-01

    Estrogenic hormones, progesterone and testosterone are endocrine-disrupting chemicals and their presence in aquatic environments represents a potentially adverse environmental and public health impact. There is a considerable amount of information about removal of estrogens, progesterone and testosterone in conventional wastewater treatment plants, namely activated sludge systems. However, the information about removal of these compounds in constructed wetlands is very limited. Three constructed wetlands with horizontal subsurface flow in the Czech Republic have been selected to evaluate removal of estrogens (estrone, estriol, 17β-estradiol, 17α-ethinylestradiol), testosterone and progesterone. Monitored constructed wetlands for 100, 150 and 200 PE have been in operation for more than 10 years and all systems exhibit very high treatment efficiency for organics and suspended solids. The results indicate that removal of all estrogens, progesterone and testosterone was high and only estrone was found in the outflow from one constructed wetland in concentrations above the limit of quantification 1 ng l(-1). The limits of quantification for other estrogens, i.e., 10 ng l(-1) for estriol, 1 ng l(-1) for 17β-estradiol and 2 ng l(-1) for 17α-ethinylestradiol were not exceeded in the outflow of all monitored constructed wetlands. Also, for progesterone and testosterone, all outflow concentrations were below the LOQ of 0.5 ng l(-1). The results indicated that constructed wetlands with horizontal subsurface flow are a promising technology for elimination of estrogens, progesterone and testosterone from municipal sewage but more information is needed to confirm this finding.

  14. Multiple hormonal activities of UV filters and comparison of in vivo and in vitro estrogenic activity of ethyl-4-aminobenzoate in fish.

    PubMed

    Kunz, Petra Y; Fent, Karl

    2006-10-12

    UV filters have been detected in surface water, wastewater and fish, and some of them are estrogenic in fish. At present, little is known about their additional hormonal activities in different hormonal receptor systems despite their increasing use and environmental persistence. Besides estrogenic activity, UV filters may have additional activities, both agonistic and antagonistic in aquatic organisms. In our study, we investigate a series of UV filters for multiple hormonal activities in vitro in human receptor systems and evaluate the predictive value of these findings for the activity in fish in vitro and in vivo. First we systematically analysed the estrogenic, antiestrogenic, androgenic, and antiandrogenic activity of 18 UV filters and one metabolite in vitro at non-cytotoxic concentrations with recombinant yeast systems carrying either a human estrogen (hERalpha) or androgen receptor (hAR). All 19 compounds elicited hormonal activities, surprisingly most of them multiple activities. We found 10 UV-filters having agonistic effects towards the hERalpha. Surprisingly, we identified for the first time six UV filters with androgenic activities and many of them having pronounced antiestrogenic and antiandrogenic activities. As much as 17 compounds inhibited 4,5-dihydrotestosterone activity in the hAR assay, while 14 compounds inhibited estradiol activity in the hERalpha assay, indicating antiandrogenic and antiestrogenic activity, respectively. In particular, the antiandrogenic activities of phenyl- and benzyl salicylate, benzophenone-1 and -2, and of 4-hydroxybenzophenone were higher than that of flutamide, a known hAR antagonist. In a second series of experiments, we investigated the predictive power of the hERalpha assay for aquatic organisms by further investigating the estrogenic UV filter ethyl 4-aminobenzoate (Et-PABA) in vitro and in vivo in fish. Et-PABA showed estrogenic activity in a recombinant yeast system carrying the rainbow trout estrogen receptor

  15. Environmental contaminants in pathogenesis of breast cancer.

    PubMed

    Mukherjee, Shyamali; Koner, Bidhan Chandra; Ray, Sanhita; Ray, Amitabha

    2006-08-01

    This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors. Estrogens are closely related to the pathogenesis of breast cancer. Oxidative catabolism of estrogen, mediated by various cytochrome P450 enzymes, generates reactive free radicals that can cause oxidative damage. The same enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (xenobiotic) chemicals. Xenobiotic chemicals may exert their pathological effects through generation of reactive free radicals. Breast tissue can be a target of several xenobiotic agents. DNA-reactive metabolites of different xenobiotic compounds have been detected in breast tissue. Many phase I and II xenobiotic metabolizing enzymes are expressed in both normal and cancerous breast tissues. These enzymes play a significant role in the activation/detoxification of xenobiotic and endogenous compounds including estrogens. More than 30 carcinogenic chemicals are present in tobacco smoke; many of them are fat-soluble, resistant to metabolism and can be stored in breast adipose tissue. Similarly, pesticides are also known to cause oxidative stress; while some act as endocrine disruptor, some are shown to suppress apoptosis in estrogen sensitive cell lines. Reports have shown an association of smoking (both active and passive) and pesticides with breast cancer risk. However, the issues have remained controversial. Different mutagenic substances that are generated in the cooking process e.g., heterocyclic amines and polycyclic aromatic hydrocarbons (PAHs) can be a threat to breast tissue. PAHs and dioxins exert their adverse effects through the aryl hydrocarbon receptor (AhR), which activates several genes involved in the metabolisms of xenobiotic compounds and endogenous

  16. Effect of estrogenic binary mixtures in the yeast estrogen screen (YES).

    PubMed

    Ramirez, Tzutzuy; Buechse, Andreas; Dammann, Martina; Melching-Kollmuß, Stephanie; Woitkowiak, Claudia; van Ravenzwaay, Bennard

    2014-10-01

    Endocrine disrupting compounds (EDCs) of natural or synthetic origin can interfere with the balance of the hormonal system, either by altering hormone production, secretion, transport, or their binding and consequently lead to an adverse outcome in intact animals. An important aspect is the prediction of effects of combined exposure to two or more EDCs at the same time. The yeast estrogen assay (YES) is a broadly used method to assess estrogenic potential of chemicals. Besides exhibiting good predictivity to identify compounds which interfere with the estrogen receptor, it is easy to handle, rapid and therefore allows screening of a large number of single compounds and varying mixtures. Herein, we applied the YES assay to determine the potential combination effects of binary mixtures of two estrogenic compounds, bisphenol A and genistein, as well as one classical androgen that in vitro also exhibits estrogenic activity, trenbolone. In addition to generating data from combined exposure, we fitted these to a four-parametric logistic dose-response model. As all compounds tested share the same mode of action dose additivity was expected. To assess this, the Loewe model was utilized. Deviations between the Loewe additivity model and the observed responses were always small and global tests based on the whole dose-response data set indicated in general a good fit of the Loewe additivity model. At low concentrations concentration additivity was observed, while at high concentrations, the observed effect was lower than additivity, most likely reflecting receptor saturation. In conclusion, our results suggest that binary combinations of genistein, bisphenol A and trenbolone in the YES assay do not deviate from expected additivity.

  17. Potency and characterization of estrogen-receptor agonists in United Kingdom estuarine sediments.

    PubMed

    Thomas, Kevin V; Balaam, Jan; Hurst, Mark; Nedyalkova, Zoya; Mekenyan, Ovanes

    2004-02-01

    The activity of estrogen-receptor (ER) agonists in sediments collected from the United Kingdom (UK) estuaries was assessed using the in vitro recombinant yeast estrogen screen (YES assay). The YES assay was successfully used to determine the in vitro ER agonist potency of pore waters and solvent extracts of sediments collected from UK estuaries. Estrogen-receptor agonists were detected in 66% of the pore water samples and in 91% of the sediment solvent extracts tested. The pore waters tested had ER agonist potencies from less than 2 to 68 ng 17beta-estradiol (E2) L(-1), whereas sediment extracts had potencies from less than 0.2 to 13 microg E2 kg(-1). A toxicity identification evaluation approach using bioassay-directed fractionation was used in an attempt to identify the ER agonists in extracts of sediments collected from the Tyne and Tees estuaries (UK). Gas chromatography-mass spectrometry was used to provide lists of compounds in the fractions obtained that were evaluated for known ER agonist activity using published data and an ER quantitative structure-activity relationship model. Toxicity identification evaluation characterization failed to identify any ER agonists in pore water extracts; however, three compounds in sediment solvent extracts were identified as ER agonists. Nonylphenol, cinnarizine, and cholesta-4,6-dien-3-one were identified in the sample collected from the Tyne estuary. Important ER agonist substances that contaminate marine sediments remain unidentified. The present study as well as previous work on effluents point toward the involvement of natural products in the estrogenic burdens of marine sediments. Further work is required to establish the relative contribution of natural products and anthropogenic chemicals to current environmental impacts in the context of the Oslo and Paris Commission strategy to eliminate hazardous substances by 2020.

  18. Cloning, expression and functional characterization of carp, Cyprinus carpio, estrogen receptors and their differential activations by estrogens.

    PubMed

    Katsu, Yoshinao; Lange, Anke; Miyagawa, Shinichi; Urushitani, Hiroshi; Tatarazako, Norishisa; Kawashima, Yukio; Tyler, Charles R; Iguchi, Taisen

    2013-01-01

    Sex-steroid hormones are essential for normal reproductive activity in both sexes. Estrogens are necessary for ovarian differentiation during a critical developmental stage in vertebrates and promote the growth and differentiation of the female reproductive system. Importantly, environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. To understand the molecular mechanisms of estrogen actions and to evaluate estrogen receptor ligand interactions in the carp, Cyprinus carpio, a species used widely for both field- and laboratory-based studies, we cloned all three carp estrogen receptors (ER; ERα, ERβ1 and ERβ2) and applied an estrogen-responsive (ERE)-luciferase reporter assay system to characterize the interactions of these receptors with steroidal and synthetic estrogens. DNA fragments encoding all three ERs in carp, ERα, ERβ1 and ERβ2, were obtained from the ovary using degenerate primer sets and PCR techniques, and full-length carp ER (cER) cDNAs were then obtained using RACE (rapid amplification of the cDNA end) techniques. Amino acid sequences of cERs showed overall homology of 46% (α vs β1), 49% (α vs β2) and 53% (β1 vs β2). In the transient transfection ERE-luciferase reporter assay system (using mammalian cells) the cER proteins displayed estrogen-dependent activation of transcription and cERβ2 showed a higher sensitivity to the natural steroid oestrogen, 17β-estradiol, than cERα. The assay system developed is a powerful assay for toxicology and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen-disrupting mechanisms in carp. The data presented also expand our knowledge of estrogen receptor evolution.

  19. Estrogenic activity of glyceollins isolated from soybean elicited with Aspergillus sojae.

    PubMed

    Kim, Hyo Jung; Suh, Hwa-Jin; Kim, Jeong Hwan; Kang, Sun Chul; Park, Sunmin; Lee, Choong Hwan; Kim, Jong-Sang

    2010-04-01

    Glyceollins, which are synthesized from daidzein in soybeans cultured with fungi, have been shown to have antifungal effects and cancer preventive properties. Several studies have proposed that isoflavones and their metabolites act as a mixed agonist/antagonist for estrogen. Although glyceollins were reported to suppress some cancer cells via anti-estrogenic activity, it is not clear whether the compounds possess estrogenic potential. In contrast to the anti-estrogenic action reported thus far, we observed estrogenic effects of glyceollins using E-screen assay and pS2 expression, whereas glyceollins showed higher affinity for estrogen receptor (ER) beta than ERalpha. We also found that glyceollins were more efficiently produced de novo in minced than in half-sliced soybean, following infection with Aspergillus sojae. In conclusion, glyceollins may be useful in the prevention or amelioration of postmenopausal complications because they had strong estrogenic activity, and their production could be variable depending upon processing prior to fungal inoculation.

  20. A novel mechanism of non-feminizing estrogens in neuroprotection.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Covey, Douglas F; Simpkins, James W

    2016-11-03

    Estrogens are potent and efficacious neuroprotectants both in vitro and in vivo in a variety of models of neurotoxicity. We determined the structural requirements for neuroprotection in an in vitro assay using a panel of >70 novel estratrienes, synthesized to reduce or eliminate estrogen receptor (ER) binding. We observed that neuroprotection could be enhanced by as much as 200-fold through modifications that positioned a large bulky group at the C2 or C4 position of the phenolic A ring of the estratriene. Further, substitutions on the B, C or D rings either reduced or did not markedly change neuroprotection. Collectively, there was a negative correlation between binding to ERs and neuroprotection with the more potent compounds showing no ER binding. In an in vivo model for neuroprotection, transient cerebral ischemia, efficacious compounds were active in protection of brain tissue from this pro-oxidant insult. We demonstrated that these non-feminizing estrogens engage in a redox cycle with glutathione, using the hexose monophosphate shunt to apply cytosolic reducing potential to cellular membranes. Together, these results demonstrate that non-feminizing estrogens are neuroprotective and protect brain from the induction of ischemic- and Alzheimer's disease (AD)-like neuropathology in an animal model. These features of non-feminizing estrogens make them attractive compounds for assessment of efficacy in AD and stroke, as they are not expected to show the side effects of chronic estrogen therapy that are mediated by ER actions in the liver, uterus and breast.

  1. Studies on the hypolipdemic and estrogenic activities of 2,8-dibenzylcyclooctanone and its analogues.

    PubMed

    Cayen, M N; Dubuc, J; Givner, M L; Greselin, E; Revesz, C

    1976-07-01

    The effects of 2,8-dibenzylcyclooctanone (DBCO) and a series of its analogues on serum lipids and on estrogenic activity in rats were studied. Assays of the estrogenicity of DBCO showed that although the compound is a very weak estrogen, it exhibited estrogenic activity at doses that were hypolipidemic. Among the analogues, only those containing the dibenzylcyclooctanone system were active. All compounds demonstrating hypocholesterolemic activity, except the weakly active compound 15, also reduced the weights of the seminal vesicles and ventral prostate and increased the weight of the adrenal gland. Compounds containing a benzylidene group or reduced ketone group did not exhibit any activity. It is concluded that the hypocholesterolemic activity of the structural analogues of DBCO is correlated with their estrogenicity.

  2. Removal and Transformation of Estrogens During the Coagulation Process

    EPA Science Inventory

    Estrogenic compounds have been shown to be present in surface waters, leading to concerns over the possible presence of endocrine disrupting compounds in finished drinking waters. Bench-scale studies (jar tests) simulating coagulation were conducted to evaluate the ability of tw...

  3. EVALUATION OF THE REMOVAL OF ESTROGENS THROUGH THE COAGULATION PROCESS

    EPA Science Inventory

    A number of estrogenic compounds have been shown to be present in surface waters in the U.S. These compounds have the potential to act as potent endocrine disrupting chemicals (EDCs), leading to a growing concern over the possible presence of EDCs in finished drinking waters. C...

  4. EVALUATION OF THE REMOVAL OF ESTROGENS THROUGH THE COAGULATION PROCESS

    EPA Science Inventory

    A number of estrogenic compounds have been shown to be present in surface waters in the U.S. These compounds have the potential to act as endocrine disrupting chemicals (EDCs), leading to concern over the possible presence of EDCs in finished drinking waters. Consequently, it is ...

  5. EVALUATION OF THE REMOVAL OF ESTROGENS THROUGH THE COAGULATION PROCESS

    EPA Science Inventory

    A number of estrogenic compounds have been shown to be present in surface waters in the U.S. These compounds have the potential to act as potent endocrine disrupting chemicals (EDCs), leading to a growing concern over the possible presence of EDCs in finished drinking waters. Con...

  6. EVALUATION OF THE REMOVAL OF ESTROGENS FOLLOWING CHLORINATION

    EPA Science Inventory

    A number of estrogenic compounds have been shown to be present in surface waters in the U.S. These compounds have the potential to act as potent endocrine disrupting chemicals (EDCs). Although there has not yet been a determination of risks posed by EDCs in finished drinking wat...

  7. Screening Estrogenic Activities of Chemicals or Mixtures In Vivo Using Transgenic (cyp19a1b-GFP) Zebrafish Embryos

    PubMed Central

    Brion, François; Le Page, Yann; Piccini, Benjamin; Cardoso, Olivier; Tong, Sok-Keng; Chung, Bon-chu; Kah, Olivier

    2012-01-01

    The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent protein) under the control of the cyp19a1b gene, encoding brain aromatase. This gene has two major characteristics: (i) it is only expressed in radial glial progenitors in the brain of fish and (ii) it is exquisitely sensitive to estrogens. Based on these properties, we demonstrate that natural or synthetic hormones (alone or in binary mixture), including androgens or progestagens, and industrial chemicals induce a concentration-dependent GFP expression in radial glial progenitors. As GFP expression can be quantified by in vivo imaging, this model presents a very powerful tool to screen and characterize compounds potentially acting as estrogen mimics either directly or after metabolization by the zebrafish embryo. This study also shows that radial glial cells that act as stem cells are direct targets for a large panel of endocrine disruptors, calling for more attention regarding the impact of environmental estrogens and/or certain pharmaceuticals on brain development. Altogether these data identify this in vivo bioassay as an interesting alternative to detect estrogen mimics in hazard and risk assessment perspective. PMID:22586461

  8. Screening estrogenic activities of chemicals or mixtures in vivo using transgenic (cyp19a1b-GFP) zebrafish embryos.

    PubMed

    Brion, François; Le Page, Yann; Piccini, Benjamin; Cardoso, Olivier; Tong, Sok-Keng; Chung, Bon-chu; Kah, Olivier

    2012-01-01

    The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent protein) under the control of the cyp19a1b gene, encoding brain aromatase. This gene has two major characteristics: (i) it is only expressed in radial glial progenitors in the brain of fish and (ii) it is exquisitely sensitive to estrogens. Based on these properties, we demonstrate that natural or synthetic hormones (alone or in binary mixture), including androgens or progestagens, and industrial chemicals induce a concentration-dependent GFP expression in radial glial progenitors. As GFP expression can be quantified by in vivo imaging, this model presents a very powerful tool to screen and characterize compounds potentially acting as estrogen mimics either directly or after metabolization by the zebrafish embryo. This study also shows that radial glial cells that act as stem cells are direct targets for a large panel of endocrine disruptors, calling for more attention regarding the impact of environmental estrogens and/or certain pharmaceuticals on brain development. Altogether these data identify this in vivo bioassay as an interesting alternative to detect estrogen mimics in hazard and risk assessment perspective.

  9. Estrogen and the cardiovascular system.

    PubMed

    Knowlton, A A; Lee, A R

    2012-07-01

    Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone.

  10. Fish population failure caused by an environmental estrogen is long-lasting and regulated by direct and parental effects on survival and fecundity

    USGS Publications Warehouse

    Schwindt, Adam R.; Winkelman, Dana L.

    2013-01-01

    Despite significant research demonstrating effects of estrogens such as 17α - ethinylestradiol (EE2) on fish, the underlying mechanisms regulating population failure are unknown. Projected water shortages could leave waterways increasingly dominated by wastewater effluent and understanding mechanisms is necessary for conservation and management. Here we identify mechanisms of population failure in three generations of fathead minnows including direct and parental effects on survival and fecundity. EE2 concentrations, as low as 3.2 ng/L, reduced F0 male survival to 17% and juvenile production by 40%. F1 offspring continuously exposed to EE2 failed to reproduce and offspring transferred to clean water reproduced 70 - 99% less than controls. Furthermore, survival of F2s was reduced 51% - 97% compared to controls, despite the absence of direct embryonic exposure. The indirect effect on F2 survival suggests the possibility of transgenerational effects of EE2. Our results suggest that chronically exposed populations may not be able to recover in the absence of immigration.

  11. Bioassays for estrogenic activity: development and validation of estrogen receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studies.

    PubMed

    Li, J; Lee, L; Gong, Y; Shen, P; Wong, S P; Wise, Stephen D; Yong, E L

    2009-02-01

    Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly popular phytoestrogen formulations are commonly prescribed to improve menopausal health. These drugs are metabolized to numerous bioactive compounds, known or unknown, which may exert combinatorial estrogenic effects in vivo. The aim of this study is to develop and validate estrogen receptor (ER) alpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify serum estrogenic activities in a clinical trial setting. We measured changes in serum estrogenicity following ingestion of E2V and compared this to mass spectrometric measurements of its bioactive metabolites, estrone and 17beta-stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%) with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood ratio test, P < 0.0001), suggesting that the ERalpha assay reflects summated activity of compounds in serum. ERbeta correlated moderately (R = 0.52) with estrone and 17beta-estradiol, with an estrone/17beta-estradiol coefficient ratio that was twice that of ERalpha, indicating estrone was more active on a molar basis in the ERbeta assay. Unlike the ERalpha and ERbeta bioassays, MCF-7 cell proliferation was driven by 17beta-estradiol, and addition of estrone did not increase the predictive value of the model, suggesting that the driver or drivers for breast cancer cell proliferation were not the same as for ERalpha and ERbeta transactivation. In contrast, a decoction of the traditional Chinese medicinal herb Epimedium pubescens did not induce significant changes in estrogenic bioactivity over baseline. These data indicate that ERalpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays reflect different aspects of estrogenic activity and that these assays suggest that the Epimedium formulation tested is unlikely to exert significant estrogenic effects in humans.

  12. EARLY LIFE EXPOSURES TO ENVIRONMENTAL COMPOUNDS: LESSONS LEARNED FROM ANIMAL MODELS

    EPA Science Inventory

    Abstract: This article was an invited submission by the Cornell University Breast Cancer & Environmental Risk Factors group, who publish the newsletter, The Ribbon. A recent paper on low dose effects of an atrazine metabolite mixture in Environmental Health Perspectives by the ...

  13. Toxic Volatile Organic Compounds in Environmental Tobacco Smoke:Emission Factors for Modeling Exposures of California Populations

    SciTech Connect

    Daisey, J.M.; Mahanama, K.R.R.; Hodgson, A.T.

    1994-10-01

    The primary objective of this study was to measure emission factors for selected toxic air in environmental tobacco smoke (ETS) using a room-sized environmental chamber. The emissions of 23 volatile organic compounds (VOCs), including 1,3-butadiene, three aldehydes and two vapor-phase N-nitrosarnines were determined for six commercial brands of cigarettes and reference cigarette 1R4F. The commercial brands were selected to represent 62.5% of the cigarettes smoked in California. For each brand, three cigarettes were machine smoked in the chamber. The experiments were conducted over four hours to investigate the effects of aging. Emission factors of the target compounds were also determined for sidestream smoke (SS). For almost all target compounds, the ETS emission factors were significantly higher than the corresponding SS values probably due to less favorable combustion conditions and wall losses in the SS apparatus. Where valid comparisons could be made, the ETS emission factors were generally in good agreement with the literature. Therefore, the ETS emission factors, rather than the SS values, are recommended for use in models to estimate population exposures from this source. The variabilities in the emission factors (pgkigarette) of the selected toxic air contaminants among brands, expressed as coefficients of variation, were 16 to 29%. Therefore, emissions among brands were generally similar. Differences among brands were related to the smoked lengths of the cigarettes and the masses of consumed tobacco. Mentholation and whether a cigarette was classified as light or regular did not significantly affect emissions. Aging was determined not to be a significant factor for the target compounds. There were, however, deposition losses of the less volatile compounds to chamber surfaces.

  14. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites.

    PubMed

    Van de Wiele, Tom; Vanhaecke, Lynn; Boeckaert, Charlotte; Peru, Kerry; Headley, John; Verstraete, Willy; Siciliano, Steven

    2005-01-01

    Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastrointestinal simulator, we show that human intestinal microbiota can also bioactivate PAHs, more in particular to estrogenic metabolites. PAH compounds are not estrogenic, and indeed, stomach and small intestine digestions of 62.5 nmol naphthalene, phenanthrene, pyrene, and benzo(a)pyrene showed no estrogenic effects in the human estrogen receptor bioassay. In contrast, colon digests of these PAH compounds displayed estrogenicity, equivalent to 0.31, 2.14, 2.70, and 1.48 nmol 17alpha-ethynylestradiol (EE2), respectively. Inactivating the colon microbiota eliminated these estrogenic effects. Liquid chromatography-mass spectrometry analysis confirmed the microbial PAH transformation by the detection of PAH metabolites 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene in colon digests of pyrene and benzo(a)pyrene. Furthermore, we show that colon digests of a PAH-contaminated soil (simulated ingestion dose of 5 g/day) displayed estrogenic activity equivalent to 0.58 nmol EE2, whereas stomach or small intestine digests did not. Although the matrix in which PAHs are ingested may result in lower exposure concentrations in the gut, our results imply that the PAH bioactivation potency of colon microbiota is not eliminated by the presence of soil. Moreover, because PAH toxicity is also linked to estrogenicity of the compounds, the PAH bioactivation potency of colon microbiota suggests that current risk assessment may underestimate the risk from ingested PAHs.

  15. Comparison of in vitro estrogenic activity and estrogen concentrations in source and treated waters from 25 U.S. drinking water treatment plants.

    PubMed

    Conley, Justin M; Evans, Nicola; Mash, Heath; Rosenblum, Laura; Schenck, Kathleen; Glassmeyer, Susan; Furlong, Ed T; Kolpin, Dana W; Wilson, Vickie S

    2017-02-01

    In vitro bioassays have been successfully used to screen for estrogenic activity in wastewater and surface water, however, few have been applied to treated drinking water. Here, extracts of source and treated water samples were assayed for estrogenic activity using T47D-KBluc cells and analyzed by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) for natural and synthetic estrogens (including estrone, 17β-estradiol, estriol, and ethinyl estradiol). None of the estrogens were detected above the LC-FTMS quantification limits in treated samples and only 5 source waters had quantifiable concentrations of estrone, whereas 3 treated samples and 16 source samples displayed in vitro estrogenicity. Estrone accounted for the majority of estrogenic activity in respective samples, however the remaining samples that displayed estrogenic activity had no quantitative detections of known estrogenic compounds by chemical analyses. Source water estrogenicity (max, 0.47ng 17β-estradiol equivalents (E2Eq) L(-1)) was below levels that have been linked to adverse effects in fish and other aquatic organisms. Treated water estrogenicity (max, 0.078ngE2EqL(-1)) was considerably below levels that are expected to be biologically relevant to human consumers. Overall, the advantage of using in vitro techniques in addition to analytical chemical determinations was displayed by the sensitivity of the T47D-KBluc bioassay, coupled with the ability to measure cumulative effects of mixtures, specifically when unknown chemicals may be present.

  16. Hygrometers and thermohygrometers: environmental monitoring ensures the potency and stability of compounding agents.

    PubMed

    Allen, Loyd V; McKenzie, Robert; Ainsworth, Ron; Kastango, Eric S; Kaestner, Rick; Rebelo, Andre; Burnside, Paul; Schultz, Gerald

    2010-01-01

    Although the terms humidity and relative humidity are often used interchangeably, they are not synonymous. Humidity is the amount of water in the air, and relative humidity is the ratio of the amount of water vapor in the air at a specific temperature to the maximum possible amount of water vapor in the air at that temperature. Thus humidity and temperature are inextricably bound in their effects on the environment. In a compounding pharmacy, humidity can affect the stability and quality of the compounds prepared, as well as equipment, chemicals, and polymers. Devices that measure relative humidity (hygrometers) or humidity and temperature (thermohygrometers) are essential instruments in a compounding pharmacy. They must be chosen carefully, however, to ensure that the measurements they yield are accurate, that they are reliable over time. Most desirable are devices that alert the pharmacist immediately at any time if levels of humidity or temperature at a designated site differ from a specific norm. In this report, we discuss the effects of humidity on the process of compounding and on the agents used in customized preparations. A Table that lists essential features of a variety of hygrometers and thermohygrometers appropriate for use in a compounding pharmacy is presented for easy reference.

  17. In vitro estrogenicity of polybrominated flame retardants.

    PubMed

    Nakari, Tarja; Pessala, Piia

    2005-09-10

    Estrogenicity of five brominated flame retardants (BFRs), namely BDE-47, BDE-99, BDE-205, PBB-153 and technical Firemaster BP-6, were assessed by in vitro assays developed to detect chemicals with estrogenic properties. Recombinant yeast cells containing a human estrogen receptor gene failed to give any response to the chemicals tested. However, the positive control compound, estradiol-17beta, showed that the yeast cell assays had worked properly. The freshly separated fish hepatocyte assay based on the synthesis and secretion of vitellogenin from the isolated liver cells produced a clear dose-response curve in the presence of all tested flame retardants except Firemaster BP-6. The toxicity of the BFRs was detected by determining the cell ethoxyresorufin-O-deethylase activity (EROD). The BFRs tested induced hepatic EROD activity at low test concentrations, but started to inhibit activity at higher concentrations. The decreased detoxification capacity of the hepatocytes resulted in a decrease in the vitellogenin production of the cells. The capability of in vitro assays to detect estrogenic properties of chemicals seems to vary. Thus, further work is needed to understand the mechanisms responsible for these reactions.

  18. Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors

    PubMed Central

    POP, ANCA; LUPU, DIANA IOANA; CHERFAN, JULIEN; KISS, BELA; LOGHIN, FELICIA

    2015-01-01

    Background and aims Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed classes of psychotropics. Even though the SSRI class consists of 6 molecules (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), only fluoxetine was intensively studied for endocrine disruptive effects, while the other SSRIs received less attention. This study was designed to evaluate the estrogenic/antiestrogenic effect of fluoxetine, sertraline and paroxetine. Methods The in vitro (anti)estrogenic activity was assessed using a firefly luciferase reporter construct in the T47D-KBluc breast cancer cell line. These cells express nuclear estrogen receptors that can activate the transcription of the luciferase reporter gene upon binding of estrogen receptor agonists. Results All three compounds were found to interact with the estrogen receptor. Fluoxetine had dual properties, weak estrogenic at lower concentrations and antiestrogenic effect at higher concentrations. Sertraline shared the same properties with fluoxetine, but also increased the estradiol-mediated transcriptional activity. Paroxetine presented only one type of effect, the ability to increase the estradiol-mediated transcriptional activity. Conclusions Overall, our results indicate a possible interaction of SSRIs with the estrogen receptor. As SSRIs are being used by all categories of population, including pregnant women or children, establishing whether they can affect the endocrine mediated mechanisms should be a priority. PMID:26609273

  19. In vitro estrogen receptor binding of PCBs: measured activity and detection of hydroxylated metabolites in a recombinant yeast assay.

    PubMed

    Layton, Alice C; Sanseverino, John; Gregory, Betsy W; Easter, James P; Sayler, Gary S; Schultz, T Wayne

    2002-05-01

    The estrogenic activities of 17beta-estradiol, biphenyl, chlorinated biphenyls, and Aroclor mixtures 1221, 1242, and 1248 were measured with a modified recombinant yeast estrogen assay (i.e., a Saccharomyces cerevisiae-based lac-Z (beta-galactosidase) reporter assay). Modifications of the assay included the use of glass vials instead of plastic microtiter plates and the addition of the medium and yeast before the test substrate. 14C-labeled compounds were used to follow improvements in the assay procedures. 14C-17beta-estradiol recovery from plastic microtiter plates and glass vials using the standard or the modified procedure was approximately 89%. However, 14C-4-CB (4-chlorobiphenyl) recovery was considerably less, ranging from 3% in plastic microtiter plates using the standard procedure to 26% in vials using the modified procedure. These results suggest that the toxicity of strongly hydrophobic chemicals may be underestimated. Using the modified yeast estrogen assay, full agonist activity was observed for 4-CB, 2,4,6-CB, and 2,5-CB while each of the Aroclor mixtures were only partial agonists. The equivalent EC50 values in ppm were in environmentally relevant concentrations for biphenyl (19 ppm), 4-CB (4.5 ppm), 2,5-CB (21 ppm), 2,4,6-CB (0.8 ppm), Aroclor 1221 (2.9 ppm), Aroclor 1242 (0.65 ppm), and Aroclor 1248 (2.3 ppm). Estrogen receptor binding for the individual PCB congeners was 25- to 650-fold less than the reported estrogen binding for the corresponding hydroxylated PCB metabolite. Gas chromatographic/mass spectrometric analysis of yeast extracts indicated that S. cerevisiae hydroxylated the individual PCB congeners in the ppb range. With the exception of biphenyl, the concentration of hydroxylated metabolites obtained from incubation of S. cerevisiae with PCB congeners was consistent with the concentration necessary to elicit a positive estrogen receptor-binding response. This work provides evidence that S. cerevisiae are capable of metabolic

  20. Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells

    SciTech Connect

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2013-06-01

    Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3β-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (p < 0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-α activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways. - Highlights: • Tributyltin chloride is agonistic to ER-α in MCF-7 cell line at low doses. • Tributyltin chloride up regulated aromatase activity and estradiol production. • Tributyltin chloride also activates MAPK pathway inducing ERK activation.

  1. Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.

    PubMed

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2013-06-01

    Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3β-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (p<0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-α activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways.

  2. HUMAN BLOOD AND ENVIRONMENTAL MEDIA SCREENING METHOD FOR PESTICIDES AND POLYCHLORINATED BIPHENYL COMPOUNDS USING LIQUID EXTRACTION AND GAS CHROMATOGRAPHY-MASS SPECTROMETRY ANALYSIS

    EPA Science Inventory

    Screening assessment methods have been developed for semi- and non-volatile persistent organic pollutants (POPs) for human blood and solid environmental media. The specific methodology is developed for measuring the presence of "native" compounds, specifically, a var...

  3. Tandem Extraction/Liquid Chromatography-Mass Spectrometry Protocol for the Analysis of Acrylamide and Surfactant-related Compounds in Complex Aqueous Environmental Samples

    EPA Science Inventory

    The development of a liquid chromatography‐mass spectrometry (LC‐MS)‐based strategy for the detection and quantitation of acrylamide and surfactant‐related compounds in aqueous complex environmental samples.

  4. Dietary estrogens stimulate human breast cells to enter the cell cycle.

    PubMed Central

    Dees, C; Foster, J S; Ahamed, S; Wimalasena, J

    1997-01-01

    It has been suggested that dietary estrogens neutralize the effect of synthetic chemicals that mimic the effects of estrogen (i.e., xenoestrogens, environmental estrogens). Genistein, a dietary estrogen, inhibits the growth of breast cancer cells at high doses but additional studies have suggested that at low doses, genistein stimulates proliferation of breast cancer cells. Therefore, if dietary estrogens are estrogenic at low doses, one would predict that they stimulate estrogen-receptor positive breast cancer cells to enter the cell cycle. Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells. The steroidal antiestrogen ICI 182,780 suppressed dietary estrogen-mediated activation of Cdk2. Dietary estrogens not only failed to suppress DDT-induced Cdk2 activity, but were found to slightly increase enzyme activity. Both zearalenone and genistein were found to stimulate the expression of a luciferase reporter gene under the control of an estrogen response element in MVLN cells. Our findings are consistent with a conclusion that dietary estrogens at low concentrations do not act as antiestrogens, but act like DDT and estradiol to stimulate human breast cancer cells to enter the cell cycle. Images Figure 2. Figure 3. A Figure 3. B Figure 4. Figure 5. PMID:9168007

  5. The environmental compartments of environmental hormones.

    PubMed

    Shore, Laurence S; Bar-El, Cohen Keren

    2010-01-01

    Compounds with estrogenic activity are ubiquitous in nature. Phytoestrogens and steroidal estrogens are found naturally in the food, in particular legumes and milk products. Naturally occurring steroidal estrogens and synthetic estrogens such as ethinylestradiol are constantly excreted into the environment as the result of the release of animal and human waste. As the result of this constant exposure, testosterone, estrogens, and ethinylestradiol are readily detectable in every stream examined in Israel. The concentrations observed of the estrogenic compounds are physiological, i.e., at these concentrations fish reproductive function can be affected. Estrogenic compounds do not usually reach the groundwater but testosterone percolates through the soil and is frequently found in the groundwater. In the dry season, there are no natural or synthetic steroids in the streams of the Jordan River watershed. However, at the beginning of the rainy season, both estrogen and testosterone reach the surface waters in the runoff from fields with manure, whereas ethinylestradiol reaches the streams in overflows from oxygenation ponds used to treat sewage prior to irrigation.

  6. Developmental synergism of steroidal estrogens in sex determination.

    PubMed

    Bergeron, J M; Willingham, E; Osborn, C T; Rhen, T; Crews, D

    1999-02-01

    Gonadal sex in the red-eared slider turtle, Trachemys scripta, is determined by incubation temperature during embryonic development. Evidence suggests that temperature determines sex by influencing steroid hormone metabolism and/or sensitivity: steroidogenic enzyme inhibitors or exogenous sex steroid hormones and their man-made analogs override (or enhance) temperature effects on sex determination. Specifically, nonaromatizable androgens and aromatase inhibitors induce testis differentiation at female-producing temperatures, whereas aromatizable androgens and estrogens induce ovary differentiation at male-producing temperatures. Moreover, natural estrogens and temperature synergize to produce more females than would be expected if estrogens and temperature had purely additive effects on sex determination. In this study, we use sex reversal of turtle embryos incubated at a male-producing temperature to examine synergism among steroidal estrogens: estrone, 17ss-estradiol, and estriol. A low dose of 17ss-estradiol (200 ng) showed significant synergism when administered with a single low dose of estriol (10 ng). Likewise, a single low dose of estrone (250 ng) had a synergistic effect when combined with the same low dose of estriol (10 ng). We conclude that the weak natural estrogens estrone and 17ss-estradiol synergize with a low dose of the more potent estriol to reverse gonadal sex during the critical period of sexual differentiation. These results suggest that weak environmental estrogens may also synergize with stronger natural estrogens.

  7. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    PubMed

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

  8. Use of response biomarkers in milk for assessing exposure to environmental contaminants: the case for dioxin-like compounds.

    PubMed

    Diehl-Jones, W L; Bols, N C

    2000-01-01

    Screening for environmental contaminants in milk is generally conducted by chemical analysis, yet such an approach may be time-consuming and expensive, and is not indicative of the physiological consequences of such exposure. The focus of this review is to summarize those constituents of milk that may be altered by maternal exposure to one of the most biologically active environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and to develop the case for their use as biomarkers of response. Several chemical and/or cellular components of milk are potentially useful as biomarkers, and may be developed as convenient, biologically relevant indicators of maternal exposure to dioxin-like compounds.

  9. Saccharomyces cerevisiae Produces a Yeast Substance that Exhibits Estrogenic Activity in Mammalian Systems

    NASA Astrophysics Data System (ADS)

    Feldman, David; Stathis, Peter A.; Hirst, Margaret A.; Price Stover, E.; Do, Yung S.; Kurz, Walter

    1984-06-01

    Partially purified lipid extracts of Saccharomyces cerevisiae contain a substance that displaces tritiated estradiol from rat uterine cytosol estrogen receptors. The yeast product induces estrogenic bioresponses in mammalian systems as measured by induction of progesterone receptors in cultured MCF-7 human breast cancer cells and by a uterotrophic response and progesterone receptor induction after administration to ovariectomized mice. The findings raise the possibility that bakers' yeast may be a source of environmental estrogens.

  10. Current trends in green liquid chromatography for the analysis of pharmaceutically active compounds in the environmental water compartments.

    PubMed

    Shaaban, Heba; Górecki, Tadeusz

    2015-01-01

    Green analytical chemistry is an aspect of green chemistry which introduced in the late nineties. The main objectives of green analytical chemistry are to obtain new analytical technologies or to modify an old method to incorporate procedures that use less hazardous chemicals. There are several approaches to achieve this goal such as using environmentally benign solvents and reagents, reducing the chromatographic separation times and miniaturization of analytical devices. Traditional methods used for the analysis of pharmaceutically active compounds require large volumes of organic solvents and generate large amounts of waste. Most of them are volatile and harmful to the environment. With the awareness about the environment, the development of green technologies has been receiving increasing attention aiming at eliminating or reducing the amount of organic solvents consumed everyday worldwide without loss in chromatographic performance. This review provides the state of the art of green analytical methodologies for environmental analysis of pharmaceutically active compounds in the aquatic environment with special emphasis on strategies for greening liquid chromatography (LC). The current trends of fast LC applied to environmental analysis, including elevated mobile phase temperature, as well as different column technologies such as monolithic columns, fully porous sub-2 μm and superficially porous particles are presented. In addition, green aspects of gas chromatography (GC) and supercritical fluid chromatography (SFC) will be discussed. We pay special attention to new green approaches such as automation, miniaturization, direct analysis and the possibility of locating the chromatograph on-line or at-line as a step forward in reducing the environmental impact of chromatographic analyses.

  11. Compounding Effects of Agricultural Land Use and Water Use in Free-Flowing Rivers: Confounding Issues for Environmental Flows.

    PubMed

    Hardie, Scott A; Bobbi, Chris J

    2017-03-03

    Defining the ecological impacts of water extraction from free-flowing river systems in altered landscapes is challenging as multiple stressors (e.g., flow regime alteration, increased sedimentation) may have simultaneous effects and attributing causality is problematic. This multiple-stressor context has been acknowledged in environmental flows science, but is often neglected when it comes to examining flow-ecology relationships, and setting and implementing environmental flows. We examined the impacts of land and water use on rivers in the upper Ringarooma River catchment in Tasmania (south-east Australia), which contains intensively irrigated agriculture, to support implementation of a water management plan. Temporal and spatial and trends in river condition were assessed using benthic macroinvertebrates as bioindicators. Relationships between macroinvertebrate community structure and environmental variables were examined using univariate and multivariate analyses, focusing on the impacts of agricultural land use and water use. Structural changes in macroinvertebrate communities in rivers in the catchment indicated temporal and spatial declines in the ecological condition of some stretches of river associated with agricultural land and water use. Moreover, water extraction appeared to exacerbate impairment associated with agricultural land use (e.g., reduced macroinvertebrate density, more flow-avoiding taxa). The findings of our catchment-specific bioassessments will underpin decision-making during the implementation of the Ringarooma water management plan, and highlight the need to consider compounding impacts of land and water use in environmental flows and water planning in agricultural landscapes.

  12. Environmental Effects in Niobium Base Alloys and Other Selected Intermetallic Compounds

    DTIC Science & Technology

    1988-12-15

    Niobium aluminides and silicides as well as other intermetallic corn unds have potential for use in advanced gas turbines where increased operating...diffusion aluminide coatings on Ni-base alloys(10), Fe- silicides (l 1), and Ni- ’ silicides (12) indicate similar behavior to that in Figure 8. Typical... Niobium W MAR- 2 7 1983 Base Alloys and Other Selected Intermetallic Compounds &Simukx Defense Advanced Research Projects Agency . DARPA Order No. 6155

  13. The removal of estrogenic activity with UV/chlorine technology and identification of novel estrogenic disinfection by-products.

    PubMed

    Li, Man; Xu, Bi; Liungai, Zhiqi; Hu, Hong-Ying; Chen, Chao; Qiao, Juan; Lu, Yun

    2016-04-15

    As a recently developed disinfection technology, ultraviolet (UV)/chlorine treatment has received much attention. Many studies have evaluated its effects on pathogen inactivation, contaminant removal, and formation of disinfection by-products (DBPs), but its potential for environmental estrogen removal and estrogenic DBP generation, which can also be a risk to both ecosystem and human health, have not been evaluated. In this study, UV/chlorine treatment resulted in a greater removal of estrogenic activity in synthetic effluent samples containing 17β-estradiol (E2) than did UV or chlorine treatment alone regardless of the water quality. For both the UV/chlorine and chlorine treatments, there was significant interference from NH3-N, although the UV/chlorine treatment was less affected. Estrogen receptor based affinity chromatography was used to isolate the specific estrogenic DBPs, and a novel product, with high estrogenic activity compared to E2, Δ9(11)-dehydro-estradiol, was identified. It was generated by all three treatments, and might be previously mistakenly recognized as estrone (E1). This study demonstrated that UV/chlorine is a better treatment for the removal of 17β-estradiol than chlorine and UV alone. The new identified estrogenic DBP, Δ9(11)-dehydro-estradiol, which can be isolated by affinity chromatography, could be an emerging concern in the future.

  14. Binary Classification of a Large Collection of Environmental Chemicals from Estrogen Receptor Assays by Quantitative Structure-Activity Relationship and Machine Learning Methods

    EPA Science Inventory

    ABSTRACT: There are thousands of environmental chemicals subject to regulatory decisions for endocrine disrupting potential. A promising approach to manage this large universe of untested chemicals is to use a prioritization filter that combines in vitro assays with in silico QSA...

  15. Non-Feminizing Estrogens Do Not Exhibit Antidepressant-like Activity

    PubMed Central

    Prokai-Tatrai, Katalin; Nguyen, Vien; Prokai, Laszlo

    2016-01-01

    In this exploratory study, we performed an evaluation of non-feminizing estrogens as lead compounds for the safe treatment of menopausal symptoms. Despite confirming an enhancement of antioxidant potency as a consequence of increased lipophilicity of the prototype structures, our analyses have revealed serious shortcomings regarding pharmaceutically important properties and drug-likeness. In addition, our assessment in an animal model of estrogen deprivation has confirmed that genomic mechanisms are required for the alleviation of menopause-associated depression. Therefore, non-feminizing estrogens are not suitable to fulfill their implicated premise to address unmet needs to treat neurological and psychiatric conditions associated with estrogen deprivation of the brain.

  16. Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

    PubMed

    Brueggemeier, R W; Gu, X; Mobley, J A; Joomprabutra, S; Bhat, A S; Whetstone, J L

    2001-12-01

    -tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

  17. Estrogenic Activities of Fatty Acids and a Sterol Isolated from Royal Jelly

    PubMed Central

    Isohama, Yoichiro; Maruyama, Hiroe; Yamada, Yayoi; Narita, Yukio; Ohta, Shozo; Araki, Yoko; Miyata, Takeshi; Mishima, Satoshi

    2008-01-01

    We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera) has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER) β. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17β-estradiol to ERβ, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17β-estradiol to ERα. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ. PMID:18830443

  18. Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

    PubMed

    Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

    2015-09-01

    In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships.

  19. The German Environmental Survey 1990/92 (GerES II): sources of personal exposure to volatile organic compounds.

    PubMed

    Hoffmann, K; Krause, C; Seifert, B; Ullrich, D

    2000-01-01

    In the framework of the second German Environmental Survey carried out in the Western part of Germany in 1990/91 (GerES IIa) 113 adults aged 25-69 years were selected at random from the total study population of about 2500 to investigate personal exposure to about 70 volatile organic compounds (VOCs). Each subject wore a diffusive badge-type sampler for 1 week. The VOCs determined included alkanes, aromatics, aliphatic halocarbons, terpenes, and oxygen-containing compounds. Multivariate regression analysis was carried out to determine and quantify the major sources of personal exposure to various VOCs. In this paper, results are given for benzene, and C8- and C9-aromatics. Being subject to environmental tobacco smoke was found to be the most important determinant of benzene exposure, but automobile-related activities such as driving a car or refuelling, were also associated with significantly increased levels of benzene. The major determinant of C8- and C9-aromatics concentrations was occupational exposure. Emissions from paints, lacquers, newspapers, magazines and print-works were also important contributors to C8-aromatics exposure. Renovation, painting and smoking were associated with a significant increase of the exposure to C9-aromatics.

  20. Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

    PubMed Central

    Auger, Jacques; Le Denmat, Dominique; Berges, Raymond; Doridot, Ludivine; Salmon, Benjamin; Canivenc-Lavier, Marie Chantal; Eustache, Florence

    2013-01-01

    Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D–5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans. PMID:23926155

  1. Sensing Estrogen with Electrochemical Impedance Spectroscopy

    PubMed Central

    Li, Jing; Kim, Byung Kun; Im, Ji-Eun; Choi, Han Nim; Kim, Dong-Hwan; Cho, Seong In

    2016-01-01

    This study demonstrates the application feasibility of electrochemical impedance spectroscopy (EIS) in measuring estrogen (17β-estradiol) in gas phase. The present biosensor gives a linear response (R2 = 0.999) for 17β-estradiol vapor concentration from 3.7 ng/L to 3.7 × 10−4 ng/L with a limit of detection (3.7 × 10−4 ng/L). The results show that the fabricated biosensor demonstrates better detection limit of 17β-estradiol in gas phase than the previous report with GC-MS method. This estrogen biosensor has many potential applications for on-site detection of a variety of endocrine disrupting compounds (EDCs) in the gas phase. PMID:27803838

  2. An approach toward quantification of organic compounds in complex environmental samples using high-resolution electrospray ionization mass spectrometry

    SciTech Connect

    Nguyen, Tran B.; Nizkorodov, Sergey; Laskin, Alexander; Laskin, Julia

    2013-01-07

    Quantitative analysis of individual compounds in complex mixtures using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) is complicated by differences in the ionization efficiencies of analyte molecules in the mixture, resulting in signal suppression during ionization. However, the ability to obtain concentration estimates of compounds in an environmental sample is important for data interpretation and comparison. We introduce an approach for estimating mass concentrations of analytes observed in a multicomponent mixture by HR-ESI-MS, without prior separation. The approach relies on a calibration of the instrument using appropriate standards added to the mixture of studied analytes. An illustration of how the proposed calibration can be applied in practice is provided for aqueous extracts of isoprene photooxidation organic aerosol, with multifunctional organic acids standards. We show that the observed ion sensitivities in ESI-MS are positively correlated with the “adjusted mass,” defined as a product of the molecular mass and the H/C ratio in the molecule (adjusted mass = H/C x molecular mass). The correlation of the observed ESI sensitivity with adjusted mass is justified by considering trends of the physical and chemical properties of organic compounds that affect ionization in the positive ion mode, i.e., gas-phase basicity, polarizability, and molecular size.

  3. Tracing the Holocene environmental evolution on the island of South Georgia by lipid biomarkers and compound-specific radiocarbon analysis

    NASA Astrophysics Data System (ADS)

    Jivcov, S.; Berg, S.; Kusch, S.; Viehberg, F. A.; Rethemeyer, J.; Melles, M.

    2015-12-01

    We present lipid biomarker data of a sedimentary record that spans the entire Holocene and was recovered from a marine inlet located at the northern coast of South Georgia (Cumberland West Bay) to adress two major objectives, namely: a) the identification of temporal variations in reservoir effects and b) the reconstruction of regional environmental changes during the last deglaciation. For objective a) we compare compound-specific radiocarbon ages of terrigeneous lipid biomarkers (n-alcohols) with 14C ages of bulk sedimentary organic matter to detect potential reservoir effects and changes over time. The study site experienced different environmental conditions following the retreat of the local glaciers in the early Holocene. After an initial freshwater stage when the inlet was separated from the sea, it passed into brackish and finally fully marine conditions. These hydrological changes probably resulted in variable reservoir ages. For objective b) we investigate biomarkers, comprising n-alkanes (C15-C35) and n-alcohols (C14-C28), including high molecular weight compounds typically derived from land plants and low molecular weight compounds like C17 n-alkanes and C16 n-alcohols, mostly originating from aquatic organisms. We noticed an abrupt increase in TOC values and sums of biomarkers after the glacier retreat, culminating in highest concentrations at the transition from freshwater to brackish conditions. Subsequently, the concentrations decline and vary at low levels until the inlet becomes fully marine. The marine stage is characterized by relatively constant TOC values but variable biomarker concentrations. Lowest biomarker levels occur around 1870±134 cal yr BP and between 6204±115 and 9666±161 cal yr BP and correspond to phases of glacier advance as suggested by studies of lake and peat deposits from South Georgia.

  4. Environmental assessment of the compounds from creosote-treated pilings in marine environment

    SciTech Connect

    Jop, K.M.; Butala, J.H.; Webb, D.A.; Wade, T.L.

    1995-12-31

    A comprehensive ecological risk assessment was conducted to evaluate the environmental impact of creosote-treated pilings in the marine environment at Moss Landing Harbor, Moss Landing, California. The chemical composition of creosote is critical to its fate and effects in the environment. Therefore, a multiple-stage methodology utilizing column gas chromatography with mass spectrometer detector was used for the identification and quantification of polycyclic aromatic hydrocarbons (PAHs) in neat creosote and environmental samples. The risk assessment of 46 PAHs (water soluble fraction) in the marine environment was based on bioaccumulation studies with caged mussels Mytilus californianus and a testing program with the surface sheen, water column, sediment elutriate, pore waters and bulk sediment. Water samples were evaluated using 7-day chronic exposures with Mysidopsis bahia, while bulk sediments were evaluated with 10-day tests with Ampelisca abdita. Testing program included exposure to normal and UV fluorescent lights. The results of this environmental assessment program allow to characterize the extent and magnitude of toxicity of PAHs released from creosote treated pilings and the risk associated with using creosote in marine environment.

  5. A Bayesian network model for assessing natural estrogen fate and transport in a swine waste lagoon.

    PubMed

    Lee, Boknam; Kullman, Seth W; Yost, Erin; Meyer, Michael T; Worley-Davis, Lynn; Williams, C Michael; Reckhow, Kenneth H

    2014-10-01

    Commercial swine waste lagoons are regarded as a major reservoir of natural estrogens, which have the potential to produce adverse physiological effects on exposed aquatic organisms and wildlife. However, there remains limited understanding of the complex mechanisms of physical, chemical, and biological processes that govern the fate and transport of natural estrogens within an anaerobic swine lagoon. To improve lagoon management and ultimately help control the offsite transport of these compounds from swine operations, a probabilistic Bayesian network model was developed to assess natural estrogen fate and budget and then compared against data collected from a commercial swine field site. In general, the model was able to describe the estrogen fate and budget in both the slurry and sludge stores within the swine lagoon. Sensitivity analysis within the model demonstrated that the estrogen input loading from the associated barn facility was the most important factor in controlling estrogen concentrations within the lagoon slurry storage, whereas the settling rate was the most significant factor in the lagoon sludge storage. The degradation reactions were shown to be minor in both stores based on prediction of average total estrogen concentrations. Management scenario evaluations demonstrated that the best possible management options to reduce estrogen levels in the lagoon are either to adjust the estrogen input loading from swine barn facilities or to effectively enhance estrogen bonding with suspended solids through the use of organic polymers or inorganic coagulants.

  6. Environmental impact of ionic liquids: Automated evaluation of chemical oxygen demand of photochemical degraded compounds.

    PubMed

    Saraiva, M Lúcia Mfs; Costa, Susana; Passos, Marieta

    2017-02-19

    A novel automated fluorimetric technique was developed for the assessment of ionic liquids (ILs) chemical oxygen demand (COD). It was combined a photodegradation step with the perspective of promote ILs degradation. The method was implemented on a sequential injection analysis (SIA) system and based on the reduction of cerium (IV) in the presence of irradiated ILs. The obtained results demonstrated higher COD values for compounds incorporating the chloride anion. Bmim [Cl], bmpyr [Cl] and hmim [Cl] also exhibiting considerable photodegradability ratio. Cholinium cation and methanesulfonate and tetrafluoroborate anions seem to confer resistance to photolysis. The developed methodology proved to be a simple, affordable and robust method. Additionally, it showed a good repeatability under the tested conditions (rsd < 3.5%, n = 10). Therefore, it is expected that the developed approach can be used as screening method for preliminary evaluation of compounds potential impact in the aquatic field. Additionally, the photolysis seems to be an attractive option to promote ILs degradation before their release to wastewater.

  7. Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its major components: in vitro and in vivo studies.

    PubMed

    Kang, Hyun Ku; Choi, Yun-Ho; Kwon, Hyosuk; Lee, Sang-Bum; Kim, Dong-Hyun; Sung, Chung Ki; Park, Young In; Dong, Mi-Sook

    2012-08-01

    The estrogenic and antiestrogenic activities of Epimedii Herba, which is a traditional medicinal herb used in Korea and China were investigated in this study. The in vitro estrogen receptor (ER) mediated estrogenic/antiestrogenic activities of an Epimedii Herba extract (Epi ext) and its major components were determined using an estrogen responsive element driven reporter gene assay in MCF-7/ERE and HEK293T cells. The Epi ext exhibited ERα- and ERβ-mediated estrogenic activity with an EC(50) of 5.0 and 17.8 μM in HEK293T cells, respectively. Prenylflavonoid glycosides such as icariin (ICA), epimedin A, B, and C did not show any in vitro estrogenic or antiestrogenic activities. Icaritin (ICT) and quercetin exhibited in vitro ER mediated estrogenic activity with a more potent interaction with ERβ. In vivo estrogenic activities of the Epi ext, ICA and ICT were compared using an uterotrophic assay. Although the potency of in vitro estrogenic activity was in the order of ICT>Epi ext>ICA, ICA had the strongest estrogenic activity and next ICT in ovariectomized rats. These results collectively suggest that phytoestrogens possess both estrogenic and antiestrogenic activity, and that the differential expression of these two compounds with opposing activities is dependent on the physiological environment in terms of estrogen level, which may be the case in humans.

  8. Measurement of 16 volatile organic compounds in restaurant air contaminated with environmental tobacco smoke.

    PubMed

    Vainiotalo, S; Väänänen, V; Vaaranrinta, R

    2008-11-01

    Tobacco smoke-related air pollutant levels were studied in ten Finnish restaurants. Markers of tobacco smoke were measured together with other compounds typical of tobacco smoke and indoor air. The measurements were carried out at stationary sampling points in smoking and non-smoking areas of the restaurants in 2005-2006, when at least half of the service area had to be non-smoking according to the Finnish Tobacco Act. The average concentrations (geometric mean, microg/m3) of the 16 airborne contaminants measured in the smoking area were: nicotine 18.1; toluene 10.6; isoprene 10.2; m,p-xylene 5.0; limonene 4.8; benzene 3.3; furfuryl aldehyde 3.2; 1,3-butadiene 2.7; 3-ethenylpyridine (3-EP) 2.5; phenol 2.1; ethyl benzene 1.7; pyridine 1.6; o-xylene 1.5; 3-picoline 1.4; styrene 1.2; and naphthalene 0.45. A good correlation (r=0.90-0.99, p<0.001) was obtained between tobacco-specific markers (3-EP and nicotine) and 1,3-butadiene, isoprene, pyridine, furfuryl aldehyde, 3-picoline, phenol, and styrene. A poor or no correlation (r=0.19-0.60) was obtained between 3-EP or nicotine and the rest of the compounds. The average concentrations of all compounds were significantly lower in the non-smoking area than in the smoking area (p<0.05). In the non-smoking area, the average concentration of 3-EP was 0.35 microg/m3 and that of nicotine 1.6 microg/m3. In three restaurants, the area design and ventilation were effective: the average level of 3-EP in the non-smoking section was <3% from that in the smoking section. In the other restaurants, tobacco smoke was spreading more freely and the corresponding value was 14-76%. A sensitive method was applied for the measurement of airborne 1,3-butadiene. The air samples were collected into Carbopack X adsorption tubes and analysed by thermal desorption/gas chromatography/mass selective detection. The precision of the method was 4.2% (at 100 ng/sample) and the limit of quantification 0.02 microg/m3.

  9. In vitro estrogenicity of ambient particulate matter: contribution of hydroxylated polycyclic aromatic hydrocarbons.

    PubMed

    Wenger, Daniela; Gerecke, Andreas C; Heeb, Norbert V; Schmid, Peter; Hueglin, Christoph; Naegeli, Hanspeter; Zenobi, Renato

    2009-04-01

    Atmospheric particulate matter (PM1) was collected at an urban and a rural site in Switzerland during a hibernal high air pollution episode and was investigated for estrogenicity using an estrogen-sensitive reporter gene assay (ER-CALUX). All samples that were tested induced estrogen receptor-mediated gene expression in T47D human breast adenocarcinoma cells. Observed estrogenic activities corresponded to 17beta-estradiol (E2) CALUX equivalent concentrations ranging from 2 to 23 ng E2-CEQ per gram of PM1 (particulate matter of < or = 1 microm aerodynamic diameter) and from 0.07 to 1.25 pg E2-CEQ per m(3) of sampled air. There was a strong correlation between the PM1 estrogenicity of the urban and rural sites (r = 0.92). Five hydroxylated polycyclic aromatic hydrocarbons (hydroxy-PAHs), which show structural similarities to E2, were assessed for their estrogenic activity. The following order of estrogenic potency was found: 2-hydroxychrysene > 2-hydroxyphenanthrene > 1-hydroxypyrene > 2-hydroxynaphthalene > 1-hydroxynaphthalene. Three of these hydroxy-PAHs, namely 2-hydroxyphenanthrene, 2-hydroxynaphthalene and 1-hydroxynaphthalene, were detected in all PM1 extracts. However, they contributed only 0.01-0.2% to the overall estrogenic activity. Hence, mainly other estrogenic compounds not yet identified by chemical analysis must be responsible for the observed activity. The temporal trend of PM1 estrogenicity at the urban and rural site, respectively, was compared with the time course of several air pollutants (NO2, NO, SO2, O3, CO) and meteorological parameters (temperature, humidity, air pressure, solar irradiation, wind velocity). However, specific emission sources and formation processes of atmospheric xenoestrogens could not be elucidated. This study showed that ambient particulate matter contains compounds that are able to interact with estrogen receptors in vitro and potentially also interfere with estrogen-regulated pathways in vivo.

  10. Aromatase inhibitors: assessment of biochemical efficacy measured by total body aromatase inhibition and tissue estrogen suppression.

    PubMed

    Lønning, Per E; Geisler, Jürgen

    2008-02-01

    The implementation of aromatase inhibitors for treatment of early and metastatic breast cancer has been one of the major improvements in endocrine therapy of breast cancer. Measurement of endocrine effects of aromatase inhibition in vivo has been a major tool in the process of evaluating novel compounds. Biochemical efficacy of aromatase inhibitors in vivo may be determined from their effects on "total body aromatization" as well changes in plasma and tissue estrogen levels. Due to high sensitivity, tracer methods allowing calculation of whole body aromatase inhibition are still considered the gold standard. The method developed by our group in collaboration with the Royal Marsden Hospital and the results of this joint program are summarized and discussed. These studies allowed classification of the different aromatase inhibitors and their optimal dosage, selecting the best compounds for clinical evaluation. In vivo total body aromatase assessment is a work-consuming method, allowing such studies to be conducted in a limited number of patients only. In contrast, plasma estrogen measurement is a cruder but simpler method, allowing screening of larger groups of patients. As plasma estrogens arise through passive diffusion of estrogens synthesized in different body compartments, plasma estrogens, as well as total body aromatase assessment, present a rough estimate of total body tissue estrogen production, and changes associated with treatment with aromatase inhibitors reflect the effects on tissue estrogen production in general. However, plasma estrogen levels do not correlate to breast cancer tissue estrogen levels. This is due to the endocrine autonomy of breast cancer tissue with significant local estrogen production in some tumors. Thus, direct measurement of intratumor estrogens is demanded to evaluate the effects of aromatase inhibitors in malignant target tissues. Our group has developed a highly sensitive HPLC-RIA for the simultaneous measurement of estrone

  11. Lead: Aspects of its ecology and environmental toxicity. [physiological effects of lead compound contamination of environment

    NASA Technical Reports Server (NTRS)

    Siegel, S. M.

    1973-01-01

    An analysis of lead toxicity in the Hawaiian environment was conducted. It was determined that lead enters the environment as an industrial contaminant resulting from the combustion of leaded gasoline. The amount of lead absorbed by the plants in various parts of the Hawaiian Islands is reported. The disposition of lead in the sediments of canals and yacht basins was investigated. The methods for conducting the surveys of lead content are described. Possible consequences of continued environmental pollution by burning leaded gasoline are discussed.

  12. Environmental exposure to chromium compounds in the valley of León, México.

    PubMed Central

    Armienta-Hernández, M A; Rodríguez-Castillo, R

    1995-01-01

    The effects on the environment and health of the operation of a chromate compounds factory and tanneries in the León valley in central México are discussed. Sampling and analysis of chromium were performed in water, soil, and human urine. Groundwater has been polluted in an area of about 5 km2 by the leaching of a solid factory waste, which results in concentrations up to 50 mg/l of hexavalent chromium. The plume shape and extension appear to be controlled by the prevailing well extraction regime. Total chromium was detected in the soil around the factory as a result of both aerial transport and deposition of dust produced in the chromate process and irrigation with tannery-contaminated water. Analysis of the impact of chromium in air and water on populations with various degrees of exposure revealed that highly harmful health effects were not observed. PMID:7621799

  13. 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.

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

    PubMed

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

    2017-02-10

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

  15. Correlating environmental partitioning properties of organic compounds: The three solubility approach

    SciTech Connect

    Cole, J.G.; Mackay, D.

    2000-02-01

    It is suggested that in addition to correlating the environmental partitioning characteristics of chemicals as partition coefficients, it is also valuable to correlate them as solubilities or pseudo-solubilities. These solubilities are essentially convenient, readily understood, and in many cases, measurable expressions of single-phase activity coefficients. To illustrate this approach, a novel, three solubility, quantitative structure-property relationships (or QSAR) approach is described for correlating the physico-chemical parameters in which the solubilities or pseudo-solubilities of individual chemicals in the liquid or super-cooled liquid state, both individually and as homologous series, are compiled and correlated as a function of temperature in the three primary media of air, water, and octanol and possibly in other relevant media. These quantities, which are deduced from measured partition coefficients, solubilities, and vapor pressures, comprise a consistent data set that can be used to estimate a variety of environmentally relevant partition coefficients. The approach is demonstrated in detail for the chlorobenzenes and in a preliminary fashion for a variety of persistent and hydrophobic substances. The merits of this approach as a supplement to the conventional use of partition coefficients are discussed.

  16. Regulation of prolactin synthesis in vitro by estrogenic and antiestrogenic derivatives of estradiol and estrone.

    PubMed

    Jordan, V C; Koch, R

    1989-04-01

    The estrogenic and antiestrogenic activities of derivatives of estradiol and estrone were determined in vitro using the ability of primary cultures of immature rat pituitary cells to synthesize PRL. Estradiol derivatives were the most potent estrogens in the assay. Large ethinyl substitutions in the 17 alpha position generally caused a decrease in estrogenic potency (up to 1000-fold). The 3 phenolic hydroxyl was important, but not essential, for the estrogenic activity of the estradiol molecule. Estratriene was approximately 1000 times less potent than estradiol. However, significant estrogenic activity was observed with the compound anordin (EC50, 8 x 10(-9) M), which could potentially be converted to a dihydroxylated derivative but without an aromatic A ring. Similarly, the steroid androst-5-ene-3,17-diol was weakly estrogenic (EC50, 3 x 10(-8) M). Steriods with a ketone in the A and D rings were generally inactive as estrogens and antiestrogens. Estradiol derivatives with 17 beta amines were only weak estrogens. Estrone derivatives were less active than the corresponding estradiol derivatives. 4-Nitromethoxyestrone exhibited weak antiestrogenic properties; however, 4-nitroestrone and methoxyestrone were both estrogens. The reason for the antiestrogenic properties of 4-nitromethoxyestrone is obscure, as the compound does not have structural features similar to those of known nonsteroidal antiestrogens. Minor alterations to the estradiol molecule at the 11 beta (OH) or 6 (ketone) position had little effect on estrogenic potency; however, large substitutions at the 11 beta (RU 39,411) or 7 alpha (ICI 164384) position produced antiestrogenic compounds. RU 39,411 was approximately 10 times more active as an antiestrogen than 4-hydroxytamoxifen, whereas ICI 164,384 was approximately 10 times less active than 4-hydroxytamoxifen. A series of hypothetical models is proposed that could explain the antiestrogenic properties of RU 39,411 and ICI 164,384 by an interaction

  17. Impact of secondary treatment types and sludge handling processes on estrogen concentration in wastewater sludge.

    PubMed

    Marti, Erica J; Batista, Jacimaria R

    2014-02-01

    Endocrine-disrupting compounds (EDCs), such as estrogen, are known to be present in the aquatic environment at concentrations that negatively affect fish and other wildlife. Wastewater treatment plants (WWTPs) are major contributors of EDCs into the environment. EDCs are released via effluent discharge and land application of biosolids. Estrogen removal in WWTPs has been studied in the aqueous phase; however, few researchers have determined estrogen concentration in sludge. This study focuses on estrogen concentration in wastewater sludge as a result of secondary treatment types and sludge handling processes. Grab samples were collected before and after multiple treatment steps at two WWTPs receiving wastewater from the same city. The samples were centrifuged into aqueous and solid phases and then processed using solid phase extraction. Combined natural estrogens (estrone, estradiol and estriol) were measured using an enzyme-linked immunosorbent assay (ELISA) purchased from a manufacturer. Results confirmed that activated sludge treatments demonstrate greater estrogen removal compared to trickling filters and mass concentration of estrogen was measured for the first time on trickling filter solids. Physical and mechanical sludge treatment processes, such as gravity thickeners and centrifuges, did not significantly affect estrogen removal based on mass balance calculations. Dissolved air flotation thickening demonstrated a slight decrease in estrogen concentration, while anaerobic digestion resulted in increased mass concentration of estrogen on the sludge and a high estrogen concentration in the supernatant. Although there are no state or federally mandated discharge effluent standards or sludge application standards for estrogen, implications from this study are that trickling filters would need to be exchanged for activated sludge treatment or followed by an aeration basin in order to improve estrogen removal. Also, anaerobic digestion may need to be replaced

  18. High-valent iron (Fe(VI), Fe(V), and Fe(IV)) species in water: characterization and oxidative transformation of estrogenic hormones.

    PubMed

    MachalováŠišková, Karolína; Jančula, Daniel; Drahoš, Bohuslav; Machala, Libor; Babica, Pavel; Alonso, Paula Godoy; Trávníček, Zdeněk; Tuček, Jiří; Maršálek, Blahoslav; Sharma, Virender K; Zbořil, Radek

    2016-07-28

    This paper presents solid state synthesis and characterization of tetra-oxy iron(iv) and iron(v) species in their salt forms (Na4FeO4-Fe(IV) and K3FeO4-Fe(V)). Stability of the synthesized salts, commonly called ferrates, in water was determined by applying the (57)Fe Mössbauer spectroscopy technique. Within 2 s in water, Fe(IV) converted into Fe(III) while Fe(V) transformed into Fe(VI) and Fe(III) at pH = 8.2. Comparatively, Fe(VI) (bought as K2FeO4) remained stable in aqueous solution during the short time period. The oxidative removal efficiency of the high-valent iron species was then tested against five environmentally important estrogenic hormones (estron (E1), 17-β-estradiol (E2), estriol (E3), 17-α-ethinylestradiol (EE2), and diethylstibestrol (DES)) in effluent water of a wastewater treatment plant. Three dosages of iron species (1, 10, and 100 mg L(-1)) were applied to the effluent water. An increase in the concentration of dosages enhanced the removal of estrogens. Both Fe(V) and Fe(VI) were effective in degrading estrogens, but Fe(IV) showed limited oxidation capacity to transform estrogens. The oxidized products of the estrogens were analyzed using Raman spectroscopy and high-performance liquid chromatography-mass spectrometry (HPLC-MS) techniques. Results demonstrated the transformation of estrogens into low molecular weight oxygenated compounds such as quinone-like and opened-aromatic ring species. A detailed study on E1 by using excess Fe(VI) showed the mineralization of the parent compound. The results demonstrate great potential of high-valent iron species in the degradation of endocrine disruptor chemicals like estrogens with several superior aspects including fast reactions, complete degradation and/or formation of benign organic species, and environmentally-acceptable iron oxide by-products.

  19. Interaction of xenobiotics with estrogen receptors α and β and a putative plasma sex hormone-binding globulin from channel catfish (Ictalurus punctatus)

    USGS Publications Warehouse

    Gale, William L.; Patino, Reynaldo; Maule, Alec G.

    2004-01-01

    Estrogens are important regulators of physiological functions. Although environmental contaminants (xenoestrogens) which interfere with estrogen signaling are of increasing concern, there is only limited information about their ability to interact with estrogen-binding proteins (SHBG) or receptors (ER). Recombinant ER?? and ?? were obtained after transient transfection of COS-7 cells with channel catfish ER cDNA. Plasma from adult female channel catfish was the source of SHBG. Tritiated estradiol ( 3H-E2) was used in standard radioligand-binding assays to characterize the binding properties of channel catfish SHBG (ccfSHBG) and to estimate the inhibition constants for various estrogenic compounds. Binding of 3H-E2 to ccfSHBG was saturable and of high affinity with a Kd (??SE) of 1.9??0.14nM and a Bmax of 14.3??2.4pmol/mg protein (n=3 assays). Additionally, ccfSHBG displayed binding specificity for androgens and estrogens. Endosulfan, 4-nonylphenol, and 4-octylphenol displaced 3H-E2 binding to ccfSHBG albeit only at very high concentrations, whereas dieldrin and atrazine showed little displacement activity even at the highest concentrations used. The synthetic estrogen ethynylestradiol had higher affinity than E2 for ccfSHBG. This finding differs from results with human and rainbow trout SHBG. The alkylphenolic compounds (4-octylphenol and 4-nonylphenol) displayed some ability to displace 3H-E2 binding from ER?? and ?? at high concentrations, but dieldrin and atrazine had little binding activity for both ER subtypes and endosulfan for ER??. The xenobiotics tested generally showed equivalent or greater affinity for ER?? than ER??, whereas natural estrogens had much greater affinity for ER?? than ER??. These observations suggest that results of studies using fish tissue ER extracts must be interpreted with caution, since both ER subtypes may be present, and that the binding of xenoestrogens to SHBG must be taken into account for proper assessment of endocrine

  20. RNA Regulation of Estrogen

    DTIC Science & Technology

    2010-08-01

    contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or decision...Estrogen 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-09-1-0353 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) J. Andrew...ORGANIZATION NAME( S ) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Oregon Eugene OR 97403-5295

  1. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin.

    PubMed

    Brander, Susanne M; He, Guochun; Smalling, Kelly L; Denison, Michael S; Cherr, Gary N

    2012-12-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. The authors evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo response with an in vitro assay--chemical activated luciferase gene expression (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. Whereas the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells.

  2. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin

    PubMed Central

    Brander, Susanne M.; He, Guochun; Smalling, Kelly L.; Denison, Michael S.; Cherr, Gary N.

    2012-01-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. We evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid contaminated aquatic habitats. We then compared the in vivo response to an in vitro assay: CALUX (Chemical Activated Luciferase Gene Expression). Juvenile Menidia beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. While Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration-response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. While the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. Our results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, and/or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells. PMID:23007834

  3. Rapid control of male typical behaviors by brain-derived estrogens.

    PubMed

    Cornil, Charlotte A; Ball, Gregory F; Balthazart, Jacques

    2012-10-01

    Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanisms that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators.

  4. Role of pocket flexibility in the modulation of estrogen receptor alpha by key residue arginine 394.

    PubMed

    Mu, Yunsong; Peng, Sufen; Zhang, Aiqian; Wang, Liansheng

    2011-02-01

    Estradiol derivatives, with similar structures as estradiol (E2) or estradiol metabolites, have been recognized to have detrimental health effects on wildlife and humans. However, data at the molecular level about interactions of these compounds with biological targets are still lacking. Herein, a flexible docking approach was used to characterize the molecular interaction of nine estradiol derivatives with estrogen receptor alpha (ERα) in the ligand-binding domain. All ligands were docked in the buried hydrophobic cavity of the steroid hormone pocket. In addition, the plasticity of an active site was also identified by reversing amino acid arginine 394 for better ligand-receptor binding affinity. Finally, bioassays based on genetically modified yeast strains were used to validate the quality of molecular simulation because of their rapidity and high sensitivity. The experimental findings about logarithm values of the median effective concentration (EC50) value had a linear correlation with computational binding affinity from molecular docking, which described a pattern of interaction between estradiol derivatives and ER. The estrogenic activity of all compounds, although more or less lower than E2, was proved to possess high severe environmental risks. Considering the sidechain flexibility in the ligand binding pocket, 17α-ethylestradiol-3-cyclopentylether was reported to correlate highly significantly with known induced fit conformational changes based upon proof-of-principle calculations on human ERα with the preservation of a strong salt bridge between glutamic acid 353 and arginine 394.

  5. Evaluation of wetland and tertiary wastewater treatments for estrogenicity using in vivo and in vitro assays.

    PubMed

    Xie, L; Sapozhnikova, Y; Bawardi, O; Schlenk, D

    2005-01-01

    The effects of wetland wastewater treatment on estrogenic activity and estrogenic activity of water after tertiary treatment were evaluated using in vivo (rainbow trout vitellogenin [VTG] expression) and in vitro (yeast estrogen screening) assays. Juvenile rainbow trout exposed to tertiary-treated wastewater from the Green Acres Treatment Plant in Orange County Water District had increased plasma VTG levels compared with control fish. When trout were exposed to wastewater-dominated water before it entered into Prado Wetland (Riverside County, CA), VTG concentrations were increased above those of controls and were not significantly different from fish exposed to water exiting the wetland. VTG E2-equivalent concentrations (EEQs) of the water samples from the Green Acres Plant were 16.92 +/- 16.49 ng/L. Activity of water entering Prado Wetland was 29.80 +/- 28.41 ng/L EEQ, and water exiting was 24.34 +/- 23.17 ng/L EEQ. In vitro assays estimated that estrogenic activity of water from the Green Acres Plant was <1 ng/L EEQ, whereas water entering and exiting Prado Wetland had yeast estrogen screening EEQs of 2.57 and <1 ng/L, respectively. Our results suggest that environmental estrogens that are not potent estrogen-receptor ligands exist in wastewaters from the Green Acres Plant as well as water entering and exiting Prado Wetland. Wetland treatment did not remove environmental estrogens in the water. Our results also suggest that in vitro assays may underestimate estrogenic activity of sampled water.

  6. Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra).

    PubMed

    Simons, Rudy; Vincken, Jean-Paul; Mol, Loes A M; The, Susan A M; Bovee, Toine F H; Luijendijk, Teus J C; Verbruggen, Marian A; Gruppen, Harry

    2011-07-01

    The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography-mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E(2)). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20-60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E(2), not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.

  7. Preparation of four fluorine-18-labeled estrogens and their selective uptakes in target tissues of immature rats

    SciTech Connect

    Kiesewetter, D.O.; Kilbourn, M.R.; Landvatter, S.W.; Heiman, D.F.; Katzenellenbogen, J.A.; Welch, M.J.

    1984-11-01

    Four fluorine-18-labeled estrogens have been prepared by simple displacement reactions utilizing reactive trifluoromethane sulfonate (triflate) precursors and F-18 fluoride ion. All four fluoroestrogens have high affinity for the estrogen receptor. In immature female rats, they are taken up by target tissues, such as the uterus, with very high selectivity: uterus-to-blood ratios at 1 hr are: Compound 1, 39; Compound 2, 12; Compound 3, 13; and Compound 4, 19. That the uptake process involves an estrogen-specific binder of limited capacity is demonstrated by the suppressive effect of coadministered unlabeled estradiol on target tissue uptake.

  8. Aryl hydrocarbon receptor-mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments.

    PubMed

    Machala, M; Ciganek, M; Bláha, L; Minksová, K; Vondráck, J

    2001-12-01

    Reproductive dysfunction in wildlife populations can be a result of environmental contaminants binding to aryl hydrocarbon receptor (AhR) or estrogenic receptors. Signaling by both types of receptors can be affected by polycyclic aromatic hydrocarbons (PAHs), which are potential endocrine disruptors. However, our knowledge regarding the effects of oxygenated (oxy)-PAHs and azaarenes on AhR-mediated and estrogenic activities is incomplete. In the present study, we have identified 9-fluorenone, anthrone, anthraquinone, benzanthrone, benz[a]anthracene-7,12-dione, benz[c]acridine, and dibenz[a,h]acridine as prevalent oxy-PAHs and azaarenes found in river sediments. Their concentrations in sediment samples ranged from 2.1 to 165.2 ng g(-1) for oxy-PAHs and up to 27.3 ng g(-1) for azaarenes. Their relative AhR-inducing and estrogenic potencies were quantified in vitro using two cell lines that were stably transfected with a luciferase reporter gene system and expressed as induction equivalency factors (IEFs). The only oxy-PAHs with detectable levels of in vitro AhR-mediated activity were benzanthrone and benz[a]anthracene-7,12-dione. However, their IEFs were approximately three to four orders of magnitude lower than those of benzo[a]pyrene. On the other hand, azaarenes showed a strong AhR-mediated activity, with dibenzo[a,h]acridine being a far more potent inducer of activity than benzo[a]pyrene. Benzanthrone, benz[a]anthracene-7,12-dione, anthraquinone, and benz[a]acridine were weak inducers of in vitro estrogenic activity, with IEFs similar to that of benzo[a]pyrene. Based on concentrations and relative potencies, our results suggest that dibenzo[a,h]acridine can significantly contribute to the overall AhR-mediated activity in river sediments, whereas the remaining compounds do not. No studied compound was found to contribute significantly to estrogen receptor-mediated activity in vitro.

  9. ERα dimerization: a key factor for the weak estrogenic activity of an ERα modulator unable to compete with estradiol in binding assays.

    PubMed

    Leclercq, Guy; Laïos, Ioanna; Elie-Caille, Céline; Leiber, Denis; Laurent, Guy; Lesniewska, Eric; Tanfin, Zahra; Jacquot, Yves

    2017-04-01

    Estrothiazine (ESTZ) is a weak estrogen sharing structural similarities with coumestrol. ESTZ failed to compete with [(3)H]17β-estradiol ([(3)H]17β-E2) for binding to the estrogen receptor α (ERα), questioning its ability to interact with the receptor. However, detection by atomic force spectroscopy (AFS) of an ESTZ-induced ERα dimerization has eliminated any remaining doubts. The effect of the compound on the proliferation of ERα-positive and negative breast cancer cells confirmed the requirement of the receptor. The efficiency of ESTZ in MCF-7 cells was weak without any potency to modify the proliferation profile of estradiol and coumestrol. Growth enhancement was associated with a proteasomal degradation of ERα without substantial recruitment of LxxLL coactivators. This may be related to an unusual delay between the acquisition by the receptor of an ERE-binding capacity and the subsequent estrogen-dependent transcription. A complementary ability to enhance TPA-induced AP-1 transcription was observed, even at concentrations insufficient to activate the ERα, suggesting a partly independent mechanism. ESTZ also rapidly and transiently activated ERK1/2 likely through membrane estrogenic pathways provoking a reorganization of the actin network. Finally, the systematic absence of biological responses with an ESTZ derivative unable to induce ERα dimerization stresses the importance of this step in the action of the compound, as reported for conventional estrogens. In view of the existence of many other ERα modulators (endocrine disruptors such as, for example, pesticides, environmental contaminants or phytoestrogens) with extremely weak or similar apparent lack of binding ability, our work may appear as pilot investigation for assessing their mechanism of action.

  10. Exercise, Eating, Estrogen, and Osteoporosis.

    ERIC Educational Resources Information Center

    Brown, Jim

    1986-01-01

    Osteoporosis affects millions of people, especially women. Three methods for preventing or managing osteoporosis are recommended: (1) exercise; (2) increased calcium intake; and (3) estrogen replacement therapy. (CB)

  11. Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds.

    PubMed

    Thorsteinsson, Thorsteinn; Másson, Már; Kristinsson, Karl G; Hjálmarsdóttir, Martha A; Hilmarsson, Hilmar; Loftsson, Thorsteinn

    2003-09-11

    A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C.

  12. Characterization of pharmaceutically active compounds in Beijing, China: Occurrence pattern, spatiotemporal distribution and its environmental implication.

    PubMed

    Ma, Ruixue; Wang, Bin; Yin, Lina; Zhang, Yizhe; Deng, Shubo; Huang, Jun; Wang, Yujue; Yu, Gang

    2017-02-05

    Pharmaceutically active compounds (PhACs) as an important group of "emerging contaminants" (ECs), have been highlighted and received global attentions in last decade. China has tremendous consumption of PhACs and the most pharmaceutical manufacturers worldwide. In this study, 33 PhACs (19 antibiotics included) were monitored in the Beiyun River basin in Beijing, China. The seasonal occurrence, temporal-spatial distribution and potential source were investigated. The total levels were about 2μgL(-1). Non-antibiotics were more frequently detected. The highest median concentrations were observed for caffeine (558ngL(-1)) and erythromycin (319ngL(-1)). Acetaminophen, erythromycin, diclofenac and N,N-diethyl-meta-toluamide showed highly significant seasonal variation, while caffeine, carbamazepine, metoprolol and most sulfonamides were more stable. The burden was most heavy in Qing River in both seasons (up to 4μgL(-1)). Antibiotics from veterinary use accounted for minor contribution in this region. The characteristics and trends were overviewed by comparing with our previous survey. The total level of 15 PhACs dropped significantly by 37% on average from 2013 to 2015. The proportion of caffeine, once a major component in 2013, reduced from 77% to 47%. The burden of these ECs in surface water of Beijing is remarkably reduced, suggesting the overall situation has been improving.

  13. Polychlorinated diphenyl sulfides. Preparation of model compounds, chromatography, mass spectrometry, NMR, and environmental analysis

    SciTech Connect

    Sinkkonen, S.; Kolehmainen, E.; Laihia, K.; Koistinen, J.; Rantio, T.

    1993-07-01

    Some polychlorinated diphenyl sulfides were prepared by chlorination of diphenyl sulfide with sulfuryl chloride and by Friedel-Crafts-type reaction from 1,2-dichlorobenzene and sulfur. Individual isomers from the reaction mixtures were isolated by reversed-phase high-performance liquid chromatography. Mass spectra show the degree of chlorination of different compounds, and {sup 1}H and {sup 13}C NMR spectra verify their structures. Three trichloro isomers were shown to be 2,2{prime}, 4-, 2,4,4{prime}, and 2,4{prime},6-trichlorodiphenyl sulfides and two symmetric tetrachloro isomers bis(2,4-dichlorophenyl) and bis(3,4-dichlorophenyl) sulfides. Chlorine-induced {sup 13}C NMR substituent chemical shifts (SCS) have been calculated and compared with the experimental ones in the case of bis(2,4-dichlorophenyl) sulfide. Four stack gases from a waste incinerator and six pulp mill effluents from two bleaching plants were screened for the polychlorinated diphenyl sulfides. Trichlorodiphenyl sulfides were found from five pulp mill effluent samples and tri- and tetrachlorodiphenyl sulfides from two stack gas samples. 24 refs., 8 figs., 5 tabs.

  14. Atomic and molecular physics of plasma-based environmental technologies for abatement of volatile organic compounds

    SciTech Connect

    Penetrante, B.M.; Hsiao, M.C.; Bardsley, J.N.; Merritt, B.T.; Vogtlin, G.E.; Kuthi, A.; Burkhart, C.P.; Bayless, J.R.

    1996-08-01

    Non-thermal plasma techniques represent a new generation of air emission control technology that potentially could treat large-volume emissions containing dilute concentrations of volatile organic compounds (VOCs). In order to apply non-thermal plasmas in an industrial scale, it is important to establish the electrical power requirements and byproducts of the process. There is a need for reliable data concerning the primary decomposition mechanisms and subsequent chemical kinetics associated with non-thermal processing of VOCs. There are many basic atomic and molecular physics issues that are essential in evaluating the economic performance of non- thermal plasma reactors. These studies are important in understanding how the input electrical power is dissipated in the plasma and how efficiently it is converted to the production of the plasma species (radicals, ions, or electrons) responsible for the decomposition of the VOCs. This paper will present results from the basic experimental and theoretical studies aimed at identifying the reaction mechanisms responsible for the primary decomposition of various types of VOCs.

  15. Model estimates of the contributions of environmental tobacco smoke to volatile organic compound exposures in office buildings

    SciTech Connect

    Daisey, J.M.; Gadgil, A.; Hodgson, A.T.

    1990-01-01

    Volatile organic compounds (VOC) in office buildings originate from multiple sources, such as outdoor air, building materials, occupants, office supplies, and office equipment. Many of the VOC found in office buildings are also present in environmental tobacco smoke (ETS), e.g., benzene, toluene, formaldehyde. Measurements made to date in Office buildings have been interpreted by some to imply that the contributions to ETS to VOC exposures in office buildings are small. Four different ventilation-infiltration scenarios were modeled for a typical office building. The purpose of this investigation was to provide first-order estimate of the range of contributions of ETS to VOC contributions in office buildings under various ventilation conditions through the use of a mass-balance model and to evaluate the significance of such contributions relative to the VOC concentration measured in office buildings. 25 refs., 1 fig., 4 tabs.

  16. The environmental behavior and chemical fate of energetic compounds (TNT, RDX, tetryl) in soil and plant systems

    SciTech Connect

    Cataldo, D.A.; Harvey, S.D.; Fellows, R.J.

    1993-06-01

    Munitions materials can accumulate or cycle in terrestrial environs at production and manufacturing facilities and thus pose potential heath and environmental concerns. To address questions related to food chain accumulation, the environmental behavior of energetic compounds (2,4,6-trinitrotoluene,TNT; hexahydro-1,3,5-trinitro-1,3,5-triazine, RDX; 2,4,6-trinitrophenylmethylnitramine, tetryl) was evaluated. Emphasis was placed on determining the potential for soil/plant transfer of munitions residues, translocation and distribution within the plant, the extent to which compounds were metabolized following accumulation, and the chemical nature and form of accumulated residues. Both TNT and tetryl undergo extensive chemical transformation in soil, forming aminodinitrotoluene isomers and N-methyl-2,4,6-trinitroaniline residues, respectively, along with a series of unknowns. After 60 days, only 30% of the amended TNT and 8% of the amended tetryl remained unchanged in the soil. In contrast, 78% of the soil-amended RDX remained unchanged after 60 days. After 60 days, plants grown in soils containing 10 ppm residues contained from 5 {mu}g TNT/g to 600 {mu}g RDX/G fresh wt. tissue. TNT and tetryl residues were primarily accumulated in roots (75%), while RDX was concentrated in leaves and seed. The principal transport form for TNT (root to shoot) was an acid labile conjugate of aminodinitrotoluene; RDX was transported unchanged. On accumulation in roots and leaves, highly polar and non-extractable TNT metabolites dominated, with the aminodinitrotoluene isomers accounting for less than 20% of the residues present. Only a few percent were present as the parent TNT. RDX was partitioned similarly to TNT, with 8 to 30% of the RDX appearing as polar metabolites, 20--50% as parent RDX, and the balance as non-extractable residues. Tetryl was metabolized to N-methyl-2,4,6-trinitroaniline and a variety of polar metabolites.

  17. Role of hepatic monooxygenases in generating estrogenic metabolites from methoxychlor and from its identified contaminants.

    PubMed

    Bulger, W H; Feil, V J; Kupfer, D

    1985-01-01

    Previous investigations demonstrated that methoxychlor [1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane] contains estrogenic contaminants and that methoxychlor per se is not an estrogen but is a proestrogen being metabolized in vivo into estrogenic products. The present study examined structurally identified methoxychlor contaminants as to their estrogenic or proestrogenic properties. Also, the estrogenic activity of demethylated metabolites of methoxychlor and of one contaminant was determined. To examine these properties, we utilized an assay developed by us that monitors whether a given compound, incubated with isolated rat uteri, can diminish the uterine cytosolic estrogen receptor and elevate the nuclear estrogen receptor and whether metabolic intervention by hepatic microsomal monooxygenase(s) is required by the respective compound for this cellular redistribution of the receptor. Of the 15 compounds examined which constitute with methoxychlor 99.5% of total technical grade methoxychlor, two compounds, 1,1-dichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethene (mono-OH-MDDE) and 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-methoxychlor), were active per se and two compounds, 1,1-dichloro-2,2-bis(4-methoxyphenyl)ethene (MDDE) and methoxychlor, required metabolic transformation for estrogenic activity to be manifested. Subsequently, it was shown that the mono- and bis-OH metabolites of MDDE and of methoxychlor were active estrogens and that the order of activity, either by the above procedure or in terms of relative binding affinity to rat uterine cytosolic receptor, was as follows: bis-OH-MDDE much greater than bis-OH-methoxychlor greater than mono-OH-MDDE greater than mono-OH-methoxychlor. Following the in vitro observations, the activity of MDDE and bis-OH-MDDE was determined in vivo in immature rats. It appears that both compounds are estrogenic, yielding marked elevation in ornithine decarboxylase (EC 4.1.1.17) levels and moderate

  18. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.

    PubMed

    Halabalaki, Maria; Alexi, Xanthippi; Aligiannis, Nektarios; Lambrinidis, George; Pratsinis, Harris; Florentin, Ida; Mitakou, Sofia; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Alexis, Michael N

    2006-05-01

    Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.

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

    PubMed

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

    2015-09-01

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

  20. Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays.

    PubMed

    Sonneveld, Edwin; Jansen, Hendrina J; Riteco, Jacoba A C; Brouwer, Abraham; van der Burg, Bart

    2005-01-01

    We have established highly sensitive and specific androgen and estrogen reporter cell lines which we have named AR (androgen receptor) and ERalpha (estrogen receptor alpha) CALUX (Chemically Activated LUciferase eXpression), respectively. Both bioassays are member of a panel of CALUX reporter cell lines derived from the human U2-OS osteosarcoma cell line, all using highly selective reporter constructs based with a basal promoter element linked to multimerized response elements, allowing efficient and specific measurement of compounds interfering with androgen, estrogen, progesterone, and glucocorticoid receptors. The AR CALUX bioassay contains the human androgen receptor and a luciferase reporter construct containing three androgen-responsive elements coupled to a minimal TATA promoter. This cell line was characterized by its stable expression of AR protein, its highly selective response to low levels of different natural and synthetic androgens, and its insignificant response to other nuclear hormone receptor ligands such as estrogens, progestins, and glucocorticoids. The EC50 of dihydrotestosterone (DHT) was found to be 0.13 nM, consistent with the high affinity of this ligand to the human AR. Flutamide, cyproterone acetate, and the environmental contaminants vinclozolin, DDT, methoxychlor, its metabolite HPTE, and penta-BFR showed clear antagonistic activity in the AR CALUX bioassay, competitively inhibiting DHT-mediated transactivation. The established AR CALUX bioassay proved to excel in terms of easy cell line maintenance, high fold induction range (typical 30 times over solvent control), low minimal detection limit (3.6 pM), and high androgen selectivity. Potential applications such as testing the androgenic or estrogenic activity of pure chemicals and pharmaceuticals and complex mixtures (environmental, food, feed, and clinical) are discussed.

  1. Correlation between Odor Concentration and Volatile Organic Compounds (VOC) Composition of Environmental Tobacco Smoke (ETS).

    PubMed

    Noguchi, Miyuki; Tanaka, Saya; Watanabe, Kaede; Yamasaki, Akihiro

    2016-10-09

    We examined the correlation between the odor concentration and the chemical composition of environmental tobacco smoke (ETS). Three types of ETS samples were prepared: secondhand smoke (SHS), thirdhand smoke (THS), and field ETS samples from an outside smoking area. The odor concentrations of the ETS, SHS, and THS samples were determined by the triangle-odor-bag method, and the chemical compositions were determined by proton transfer mass spectrometry. The odor concentration of the SHS samples was three or four orders of magnitude higher than that of the field ETS samples, and three orders of magnitude higher than that of the THS samples. The concentration ratios of the constituent chemicals in THS to those in SHS were about 10(-4), corresponding to the ratio of the odor concentration. The concentration ratios of the constituent chemicals in the field ETS samples were much lower than the ratios of the odor concentrations. This suggests that the main contributing components to the odor of the field ETS samples are different from those in SHS and THS. The main contributors of the odor in the field ETS samples could be acetaldehyde, acetonitrile, acetic acid, and other unknown components with a mass-to-charge ratio (m/z) of 39 and 43.

  2. Correlation between Odor Concentration and Volatile Organic Compounds (VOC) Composition of Environmental Tobacco Smoke (ETS)

    PubMed Central

    Noguchi, Miyuki; Tanaka, Saya; Watanabe, Kaede; Yamasaki, Akihiro

    2016-01-01

    We examined the correlation between the odor concentration and the chemical composition of environmental tobacco smoke (ETS). Three types of ETS samples were prepared: secondhand smoke (SHS), thirdhand smoke (THS), and field ETS samples from an outside smoking area. The odor concentrations of the ETS, SHS, and THS samples were determined by the triangle-odor-bag method, and the chemical compositions were determined by proton transfer mass spectrometry. The odor concentration of the SHS samples was three or four orders of magnitude higher than that of the field ETS samples, and three orders of magnitude higher than that of the THS samples. The concentration ratios of the constituent chemicals in THS to those in SHS were about 10−4, corresponding to the ratio of the odor concentration. The concentration ratios of the constituent chemicals in the field ETS samples were much lower than the ratios of the odor concentrations. This suggests that the main contributing components to the odor of the field ETS samples are different from those in SHS and THS. The main contributors of the odor in the field ETS samples could be acetaldehyde, acetonitrile, acetic acid, and other unknown components with a mass-to-charge ratio (m/z) of 39 and 43. PMID:27735848

  3. Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenil fish (Spaurus aurata).

    PubMed

    Calò, M; Alberghina, D; Bitto, A; Lauriano, E R; Lo Cascio, P

    2010-01-01

    Vitellogenin (Vtg) is a phospho-lipo-glycoprotein produced by oviparous animals in response to estrogen receptor (ER) binding. The presence of Vtg in juvenile and male fish liver and plasma has been used as biomarker to evaluate levels of environmental contaminants as dioxin and PCBs. Interaction of dioxins and PCBs with aryl hydrocarbon receptor (AhR) may affect reproduction by recruitment of estrogen receptor alpha (ERalpha). The aim of this study was to investigate the effects of PCB-126, a co-planar PCB prototypical AhR agonist, and of PCB-153, a non-coplanar PCB lacking dioxine-like activity, on Vtg expression in young fish (Spaurus aurata) after a 12 or 24h exposure to PCBs as well as 48h following PCBs removal. Vtg expression was evaluated by immunohistochemistry and by Western-blot analysis. Our results showed an increased Vtg expression following PCBs administration, with a maximum level after 12h of exposure to either PCB-126, PCB-153 or a mixture of both PCBs. Following this estrogenic activity, an anti-estrogenic activity was detected after 24h of incubation with PCB-126 (alone or mixed with PCB-153), suggested by a decrease in Vtg expression likely through AhR, as a consequence of a hypothetic defence mechanism to endogenous or exogenous ligands.

  4. Estrogenic activity of polychlorinated biphenyls present in human tissue and the environment.

    PubMed

    DeCastro, B Rey; Korrick, Susan A; Spengler, John D; Soto, Ana M

    2006-04-15

    This study evaluated the estrogenicity of polychlorinated biphenyls (PCBs) present in environmental media and human tissue and assessed exposure pathways for PCB-derived estrogenic potency in air, soil, and dust from New Bedford, MA, an area with a PCB-contaminated Superfund site. Thirty-four PCB congeners were assayed for estrogenic potency using E-SCREEN, an assay based on the estrogen-dependent proliferation of MCF-7 cells in vitro. Childhood exposure to estradiol-equivalents via PCBs in environmental media was estimated byweighting previously reported New Bedford congener-specific concentrations by their relative estrogenic potency and published inhalation and soil ingestion rates. Thirteen congeners were weakly estrogenic in E-SCREEN: PCBs 17, 18, 30, 44, 49, 66, 74, 82, 99, 103, 110, 128, and 179. These PCBs were typically 6 orders of magnitude less potent than 17beta-estradiol, with proliferative potencies ranging from 0.0007% to 0.0040%. Of the environmental media assessed, air (inhalation) had the highest PCB-derived estradiol-equivalent exposure. PCB estrogenic potency information from this study provides an important resource both for preliminary estimation of routes of human exposure to xenoestrogens and for application to human health studies focused on estrogen-responsive health outcomes, such as reproductive development and related malignancies.

  5. Automated high-throughput in vitro screening of the acetylcholine esterase inhibiting potential of environmental samples, mixtures and single compounds.

    PubMed

    Froment, Jean; Thomas, Kevin V; Tollefsen, Knut Erik

    2016-08-01

    A high-throughput and automated assay for testing the presence of acetylcholine esterase (AChE) inhibiting compounds was developed, validated and applied to screen different types of environmental samples. Automation involved using the assay in 96-well plates and adapting it for the use with an automated workstation. Validation was performed by comparing the results of the automated assay with that of a previously validated and standardised assay for two known AChE inhibitors (paraoxon and dichlorvos). The results show that the assay provides similar concentration-response curves (CRCs) when run according to the manual and automated protocol. Automation of the assay resulted in a reduction in assay run time as well as in intra- and inter-assay variations. High-quality CRCs were obtained for both of the model AChE inhibitors (dichlorvos IC50=120µM and paraoxon IC50=0.56µM) when tested alone. The effect of co-exposure of an equipotent binary mixture of the two chemicals were consistent with predictions of additivity and best described by the concentration addition model for combined toxicity. Extracts of different environmental samples (landfill leachate, wastewater treatment plant effluent, and road tunnel construction run-off) were then screened for AChE inhibiting activity using the automated bioassay, with only landfill leachate shown to contain potential AChE inhibitors. Potential uses and limitations of the assay were discussed based on the present results.

  6. Bacteriostatics of volatile organic compounds of Crimean pine and environmental meteorological conditions

    NASA Astrophysics Data System (ADS)

    Chalaya, Elena; Slepykh, Victor; Efimenko, Natalia; Povolotckaia, Nina

    2015-04-01

    Sanitary and hygienic properties of air saturated with volatile organic compounds of plants (VOC) have a fundamental importance for the biosphere. In particular, they make such a feature as the freshness of the air. The energy contained in VOC and made by Earth vegetation can be compared with the energy of lightning discharges in the atmosphere during the year [1]. The influence of natural environment on the dynamics of VOC developed by plants is also of current interest and is, in particular, important for resort study because VOC produced by the vegetation of the resort regions can be seen as a self-contained resort resource [2]. Dynamics of VOC evolution by Crimean pine (Pinus Pallasiana D.Don.) that is the forest forming breed of the resort region Caucasus Mineral Waters (Russia) has been studied by a microbiological method [1]. Dynamics of bacteriostatics was qualified by the extent of oppression of the VOC test- culture (Staphylococcus aureus 209p) of the pine in % in comparison with control. The needles for the experience were selected at noon in the middle of the summer. At the time of the needle selection meteorological indicators were fixed. As the result of the researches we got an empirical equation of dynamics of VOC bacteriostatics of the Crimean pine under the influence of total solar radiation (kW/m2) and relative air humidity (%). The coefficient of the multiple correlation of the VOC bacteriostatics of the Crimean pine, total solar radiation and relative air humidity makes: R=0,83 at the importance of F=7,53>F0 05=3,49. The coefficient of the multiple determination is R2=0,69. The equation is: y = - 35,1020 + 1,7193x + 175,6638p- 0,0181x2 + 0,6054 (xp) - 191,1319p2, where Y - is bacteriostatics (%); x - is relative humidity (%); p - is total solar radiation (kW/m2). The fixed parameters of the equation are: air humidity - 90-30%; total solar radiation - 0.20-1.0 kW/m2; bacteriostatics - 0-61%. The obtained results can be used in the resort study

  7. Recent advances in occupational and environmental health hazards of workers exposed to gasoline compounds.

    PubMed

    Ekpenyong, Christopher E; Asuquo, Asuquo E

    2017-02-21

    The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity. These mechanisms include covalent binding to deoxyribonucleic acid (DNA), leading to oxidative damage, tumor-suppression gene activity, and activation of pro-oncogenes. Furthermore, it results in induction of autoimmunity and local inflammatory responses, disruption of multiple neurotransmitters and immune cell function, derangement of various enzyme activities (e.g., sodiumpotassium adenosine triphosphate (Na+/K+/ATPase) activity, cytochrome P450 (CYP450), nitric oxide synthase (NOS), antioxidant enzyme activities, etc.), conjugation of bile, and non-specific cell membrane interaction, leading to damage of the membrane lipid bilayer and proteins. Available data suggests that exposure to gasoline or gasoline constituents have the potential to cause different types of illnesses. The data highlights the need to maintain safety measures via suitable research, medical surveillance, regulatory control, life style modification, early detection, and intervention to minimize exposure and manage suspected cases. They also present novel opportunities to design and develop effective therapeutic strategies against gasoline-induced detrimental effects. Int J

  8. Concentrations of perfluoroalkyl compounds in the serum and milk of lactating North Carolina women

    EPA Science Inventory

    Perfluoroalkyl acids (PFAAs) and their derivatives are ubiquitous environmental contaminants that have been detected in a multitude of terrestrial and aquatic organisms. Some PFAAs bind the human estrogen receptors in vitro. Further, some PFAAs induce estrogen responsive genes a...

  9. Environmental exposure to volatile organic compounds among workers in Mexico City as assessed by personal monitors and blood concentrations.

    PubMed

    Romieu, I; Ramirez, M; Meneses, F; Ashley, D; Lemire, S; Colome, S; Fung, K; Hernandez-Avila, M

    1999-07-01

    Benzene, an important component in gasoline, is a widely distributed environmental contaminant that has been linked to known health effects in animals and humans, including leukemia. In Mexico City, environmental benzene levels, which may be elevated because of the heavy traffic and the poor emission control devices of older vehicles, may pose a health risk to the population. To assess the potential risk, portable passive monitors and blood concentrations were used to survey three different occupational groups in Mexico City. Passive monitors measured the personal exposure of 45 workers to benzene, ethylbenzene, toluene, o-xylene and m-/p-xylene during a work shift. Blood concentrations of the above volatile organic compounds (VOCs), methyl tert-butyl ether, and styrene were measured at the beginning and the end of a work shift. Passive monitors showed significantly higher (p > 0.0001) benzene exposure levels among service station attendants (median = 330 microg/m3; range 130-770) as compared to street vendors (median = 62 microg/m3; range 49-180) and office workers (median = 44 microg/m3, range 32-67). Baseline blood benzene levels (BBLs) for these groups were higher than those reported for similar populations from Western countries (median = 0.63 microg/L, n = 24 for service station attendants; median = 0.30 microg/L, n = 6 for street vendors; and median = 0.17 microgr;g/L, n = 7 for office workers). Nonsmoking office workers who were nonoccupationally exposed to VOCs had BBLs that were more than five times higher than those observed in a nonsmoking U.S. population. BBLs of participants did not increase during the work shift, suggesting that because the participants were chronically exposed to benzene, complex pharmacokinetic mechanisms were involved. Our results highlight the need for more complete studies to assess the potential benefits of setting environmental standards for benzene and other VOCs in Mexico.

  10. Environmental exposure to volatile organic compounds among workers in Mexico City as assessed by personal monitors and blood concentrations.

    PubMed Central

    Romieu, I; Ramirez, M; Meneses, F; Ashley, D; Lemire, S; Colome, S; Fung, K; Hernandez-Avila, M

    1999-01-01

    Benzene, an important component in gasoline, is a widely distributed environmental contaminant that has been linked to known health effects in animals and humans, including leukemia. In Mexico City, environmental benzene levels, which may be elevated because of the heavy traffic and the poor emission control devices of older vehicles, may pose a health risk to the population. To assess the potential risk, portable passive monitors and blood concentrations were used to survey three different occupational groups in Mexico City. Passive monitors measured the personal exposure of 45 workers to benzene, ethylbenzene, toluene, o-xylene and m-/p-xylene during a work shift. Blood concentrations of the above volatile organic compounds (VOCs), methyl tert-butyl ether, and styrene were measured at the beginning and the end of a work shift. Passive monitors showed significantly higher (p > 0.0001) benzene exposure levels among service station attendants (median = 330 microg/m3; range 130-770) as compared to street vendors (median = 62 microg/m3; range 49-180) and office workers (median = 44 microg/m3, range 32-67). Baseline blood benzene levels (BBLs) for these groups were higher than those reported for similar populations from Western countries (median = 0.63 microg/L, n = 24 for service station attendants; median = 0.30 microg/L, n = 6 for street vendors; and median = 0.17 microgr;g/L, n = 7 for office workers). Nonsmoking office workers who were nonoccupationally exposed to VOCs had BBLs that were more than five times higher than those observed in a nonsmoking U.S. population. BBLs of participants did not increase during the work shift, suggesting that because the participants were chronically exposed to benzene, complex pharmacokinetic mechanisms were involved. Our results highlight the need for more complete studies to assess the potential benefits of setting environmental standards for benzene and other VOCs in Mexico. Images Figure 1 PMID:10378996

  11. Application of the yeast-based reporter gene bioassay for the assessment of estrogenic activity in cow's milk from Poland.

    PubMed

    Stypuła-Trębas, Sylwia; Minta, Maria; Radko, Lidia; Żmudzki, Jan

    2015-11-01

    Milk contain compounds acting through the estrogen receptor signaling. The still open question whether such estrogens pose a risk for human health, encouraged us to measure the overall estrogenic activity of cow's milk in the in vitro yeast reporter bioassay. First, we assessed the ability of the bioassay to detect estrogens frequently detected in milk. The relative potencies of 16 compounds descended in the order: 17β-estradiol (17β-E2), 17α-ethinylestradiol, diethylstilbestrol, dienestrol, 17α-E2, estrone, zearalenone, estriol, equol, genistein, 17β-E2 glucuronide, bisphenol A, apigenin, daidzein. Flavone, 4-n-nonylphenol and 4-t-octylphenol shown no activity in the bioassay.The estrogenic activities of milk samples without hydrolysis were below the detection limit, whereas in 50% of the deconjugated samples they varied between 0.29 and 0.49 ng EEQ mL(-1). We also compared the estrogenic activity in raw cow's milk collected from rural and industrial locations in Poland. In our pilot study we did not observe statistically significant difference in estrogenic activities in milk collected from the two locations. We found that the daily intake of estrogens with milk may be higher than estrogen levels in human serum. Further studies are warranted to evaluate the significance of milk and dairy as a source of estrogens for humans.

  12. Effect of source-separated urine storage on estrogenic activity detected using bioluminescent yeast Saccharomyces cerevisiae.

    PubMed

    Jaatinen, Sanna; Kivistö, Anniina; Palmroth, Marja R T; Karp, Matti

    2016-09-01

    The objective was to demonstrate that a microbial whole cell biosensor, bioluminescent yeast, Saccharomyces cerevisiae (BMAEREluc/ERα) can be applied to detect overall estrogenic activity from fresh and stored human urine. The use of source-separated urine in agriculture removes a human originated estrogen source from wastewater influents, subsequently enabling nutrient recycling. Estrogenic activity in urine should be diminished prior to urine usage in agriculture in order to prevent its migration to soil. A storage period of 6 months is required for hygienic reasons; therefore, estrogenic activity monitoring is of interest. The method measured cumulative female hormone-like activity. Calibration curves were prepared for estrone, 17β-estradiol, 17α- ethinylestradiol and estriol. Estrogen concentrations of 0.29-29,640 μg L(-1) were detectable while limit of detection corresponded to 0.28-35 μg L(-1) of estrogens. The yeast sensor responded well to fresh and stored urine and gave high signals corresponding to 0.38-3,804 μg L(-1) of estrogens in different urine samples. Estrogenic activity decreased during storage, but was still higher than in fresh urine implying insufficient storage length. The biosensor was suitable for monitoring hormonal activity in urine and can be used in screening anthropogenic estrogen-like compounds interacting with the receptor.

  13. Evaluation of estrogenic activity and measurement of EDCs in wastewater treatment plants

    NASA Astrophysics Data System (ADS)

    Lee, B. C.; Jung, J. Y.; Kim, H. K.

    2006-10-01

    Correlations between estrogenic activity and DOC/UV260 ratio in wastewater treatment processes were investigated to propose a simple, reliable and comprehensive indicator for the presence of estrogenic substances. Contrary to this, when short-term bioassays such as the E-SCREEN, receptor binding and reporter gene expression assays are used for detecting estrogenic activity in the wastewater sample, they require a long time, at least a few days. The major factors contributing to the estrogenic activity were found to be 17β-estradiol (E2) and estrone (El). A good relationship between the DOC/ UV260 ratio and the concentration of estrogens (El and E2) in the effluent of the activated sludge process was found: the E2 concentration increased as the DOC/UV260 ratio increased while the El concentration decreased. The relative estrogenic activity and DOC/UV260 ratio showed a good correlation (R2=0.84) for all sewage samples except the ozonized samples in the sewage treatment plants. This study shows that the estrogenic compounds are hard to be mineralized by the conventional biological processes. Advanced oxidation processes are required to further remove estrogenic substances in the secondary effluent. By analysis of DOC and UV260, the estrogenic activity in the wastewater can be rapidly estimated.

  14. Measurement of estrogenic activity in sediments from Haihe and Dagu River, China.

    PubMed

    Song, Maoyong; Xu, Yan; Jiang, Qinting; Lam, Paul K S; O'Toole, Desmond K; Giesy, John P; Jiang, Guibin

    2006-07-01

    Sediments from two rivers in China, the Haihe and Dagu Rivers, were examined for estrogenic activity using an estrogen receptor (ER)-mediated in vitro bioassay system. ER-active compounds were isolated from sediments by Soxhlet extraction, and the crude extracts were fractionated using a florisil column into three fractions. The estrogenic activity of each extract was detected by measuring luciferase activity in the human breast cancer cell line MCF-7 transfected with a luciferase receptor gene. Significant estrogenic activity was observed in each total extract. The 17beta-estradiol equivalents (E2-EQs) ranged from 8.24 to 95.28 ng E2 g(-1) dw. As a result, the relative estrogenic potencies of three fractions in this study descended in the order of Fraction 3>Fraction 2>Fraction 1. The results of the bioassay analysis indicated the heavy pollution status of these sites with estrogenic contaminants. In this study, five selected chemicals, the natural estrogens 17beta-estradiol (E2) and estrone (E1), and the xeno-estrogens 4-octylphenol (OP), 4-nonylphenol (NP), and Bisphenol A (BPA) were also analyzed using the in vitro bioassay. The estrogenic activity of these chemicals were E2>E1>NP>OP>BPA.

  15. Free and conjugated estrogen exports in surface-runoff from poultry litter-amended soil.

    PubMed

    Dutta, Sudarshan; Inamdar, Shreeram; Tso, Jerry; Aga, Diana S; Sims, J Tom

    2010-01-01

    Land application of animal manures such as poultry litter is a common practice, especially in states with surplus manure. Past studies have shown that animal manure may contain estrogens, which are classified as endocrine-disrupting chemicals and may pose a threat to aquatic and wildlife species. We evaluated the concentrations of estrogens in surface runoff from experimental plots (5 x 12 m each) receiving raw and pelletized poultry litter. We evaluated the free (estrone, E1; 17beta-estradiol, E2beta; estriol, E3) and conjugate forms (glucuronides and sulfates) of estrogens, which differ in their toxicity. Sampling was performed for 10 natural storm events over a 4-mo period (April-July 2008). Estrogen concentrations were screened using enzyme-linked immunosorbent assay (ELISA), followed by quantification using liquid chromatography with tandem mass spectrometry (LC/MS/MS). Concentrations of estrogens from ELISA were much higher than the LC/MS/MS values, indicating crossreactivity with organic compounds. Exports of estrogens were much lower from soils amended with pelletized poultry litter than the raw form of the litter. No-tillage management practice also resulted in a lower export of estrogens with surface runoff compared with reduced tillage. The concentrations and exports of conjugate forms of estrogens were much higher than the free forms for some treatments, indicating that the conjugate forms should be considered for a comprehensive assessment of the threat posed by estrogens.

  16. Androgens and estrogens in benign prostatic hyperplasia: past, present and future

    PubMed Central

    Nicholson, Tristan M.; Ricke, William A.

    2011-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs. PMID:21620560

  17. Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

    PubMed Central

    Chen, Xueyan; Uzuner, Ugur; Li, Man; Shi, Weibing; Yuan, Joshua S.; Dai, Susie Y.

    2016-01-01

    Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors. PMID:27589781

  18. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells.

    PubMed

    Heneweer, Marjoke; Muusse, Martine; van den Berg, Martin; Sanderson, J Thomas

    2005-10-15

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 microM). Therefore, instead of using EC50 values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC50 value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 microM, 0.5 microM, 1.9 microM, and 1.0 microM for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol (E2

  19. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells

    SciTech Connect

    Heneweer, Marjoke . E-mail: M.Heneweer@iras.uu.nl; Muusse, Martine; Berg, Martin van den; Sanderson, J. Thomas

    2005-10-15

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 {mu}M). Therefore, instead of using EC{sub 50} values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC{sub 50} value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 {mu}M, 0.5 {mu}M, 1.9 {mu}M, and 1.0 {mu}M for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol

  20. Estrogen receptors in breast carcinoma.

    PubMed

    Huaman, A

    1979-11-01

    On the basis of estrogen receptor assays, breast carcinomas are presently classified as estrogen-dependent tumors, which respond to endocrine therapy, and autonomous tumors, for which endocrine therapy is useless. This paper presents a short review of the biochemical principles of estrogen dependence, the procedures used to determine estrogen receptors, and the clinical applications of the findings of these assay procedures. Biobhemically, the estroogen dependence of normal breast cells is explained as a biochemical reaction occurring between the circulating estradiol and the breast cell, which occurs in 3 steps: 1) circulating estradiol penetrates the cellular membrane by passive diffusion, followed by 2) combining of estradiol with the estrogen-binding protein (estrophilin) and formation of an estrogen receptor complex which undergoes activation and translocation into the nucleus, to result in 3) the activated steroid receptor which combines with the nuclear charomatin and stimulates ribonucleic acid synthesis for the formation of estradiol binding proteins or estradiol receptors. The cytosol method of Wittliff et al. is described in brief and entails radioactive competitive analysis; the other available laboratory procedure is immunofluorescence of tumor sections. Quantification of estrogen receptor content can be used clinically to decide on ablative endocrine therapy, to determine the effectiveness of anti-estrogen administration, to determine the primary site of metastatic carcinoma, and as a screenng device.

  1. Phytoestrogens and sterols in waters with cyanobacterial blooms - Analytical methods and estrogenic potencies.

    PubMed

    Procházková, Tereza; Sychrová, Eliška; Javůrková, Barbora; Večerková, Jaroslava; Kohoutek, Jiří; Lepšová-Skácelová, Olga; Bláha, Luděk; Hilscherová, Klára

    2017-03-01

    Compounds with estrogenic potencies and their adverse effects in surface waters have received much attention. Both anthropogenic and natural compounds contribute to overall estrogenic activity in freshwaters. Recently, estrogenic potencies were also found to be associated with cyanobacteria and their blooms in surface waters. The present study developed and compared the solid phase extraction and LC-MS/MS analytical approaches for determination of phytoestrogens (8 flavonoids - biochanin A, coumestrol, daidzein, equol, formononetin, genistein, naringenin, apigenin - and 5 sterols - ergosterol, β-sitosterol, stigmasterol, campesterol, brassicasterol) and cholesterol in water. The method was used for analyses of samples collected in stagnant water bodies dominated by different cyanobacterial species. Concentrations of individual flavonoids ranged from below the limit of detection to 3.58 ng/L. Sterols were present in higher amounts up to 2.25 μg/L. Biological potencies of these phytoestrogens in vitro were characterized using the hERα-HeLa-9903 cell line. The relative estrogenic potencies (compared to model estrogen - 17β-estradiol) of flavonoids ranged from 2.25E-05 to 1.26E-03 with coumestrol being the most potent. None of the sterols elicited estrogenic response in the used bioassay. Estrogenic activity was detected in collected field water samples (maximum effect corresponding to 2.07 ng/L of 17β-estradiol equivalents, transcriptional assay). At maximum phytoestrogens accounted for only 1.56 pg/L of 17β-estradiol equivalents, contributing maximally 8.5% of the total estrogenicity of the water samples. Other compounds therefore, most likely of anthropogenic origin such as steroid estrogens, are probably the major drivers of total estrogenic effects in these surface waters.

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

    PubMed

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

    2006-04-01

    The relevance of endocrine-disrupting compounds as potential contaminants of drinking water is reviewed, particularly in the reuse of wastewater. Growing populations and increasing intensification of land and water use for industry and agriculture have increased the