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Sample records for micropollutants endocrine disrupting

  1. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

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

  2. A hierarchical testing strategy for micropollutants in drinking water regarding their potential endocrine-disrupting effects-towards health-related indicator values.

    PubMed

    Kuckelkorn, Jochen; Redelstein, Regine; Heide, Timon; Kunze, Jennifer; Maletz, Sibylle; Waldmann, Petra; Grummt, Tamara; Seiler, Thomas-Benjamin; Hollert, Henner

    2017-09-21

    In Germany, micropollutants that (may) occur in drinking water are assessed by means of the health-related indicator value (HRIV concept), developed by the German Federal Environment Agency. This concept offers five threshold values (≤ 0.01 to ≤ 3 μg l(-1)) depending on availability and completeness of data regarding genotoxicity, neurotoxicity, and germ cell-damaging potential. However, the HRIV concept is yet lacking integration of endocrine disruptors as one of the most prominent toxicological concerns in water bodies, including drinking water. Thresholds and proposed bioassays hence urgently need to be defined. Since endocrine disruption of ubiquitary chemicals as pharmaceuticals, industrial by-products, or pesticides is a big issue in current ecotoxicology, the aim of this study was to explore endocrine effects, i.e., estrogenic and androgenic effects, as an important, additional toxicological mode of action for the HRIV concept using a hierarchical set of well-known but improved bioassays. Results indicate that all of the 13 tested substances, industrial chemicals and combustion products (5), pharmaceuticals and medical agents (4), and pesticides and metabolites (4), have no affinity to the estrogen and androgen receptor in human U2OS cells without metabolic activation, even when dosed at their water solubility limit, while in contrast some of these substances showed estrogenic effects in the RYES assay, as predicted in pre-test QSAR analysis. Using a specifically developed S9-mix with the U2OS cells, those micropollutants, i.e., Benzo[a]pyrene, 2,4-Dichlorophenol, 3,3-Dichlorbenzidin, 3,4-Dichloranilin, and diclofenac, they show estrogenic effects at the same concentration range as for the yeast cells. Three of the drinking water-relevant chemicals, i.e., atrazine, tributyltin oxide, and diclofenac, caused effects on hormone production in the H295R assay, which can be correlated with changes in the expression of steroidogenic genes. One chemical, 17

  3. [Xenoestrogens: endocrine disrupting compounds].

    PubMed

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  4. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity. PMID:19433244

  5. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  6. Endocrine Effects of Circadian Disruption.

    PubMed

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems.

  7. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

    ... metabolism (how the body converts food to fuel), reproduction, growth and development, and the way your body ... body. It controls overall endocrine system functions including reproduction, stress responses, growth, lactation (production and secretion of ...

  8. Endocrine disrupters and menopausal health.

    PubMed

    Holmes, Philip; Rumsby, Paul; Harrison, Paul T C

    2004-06-01

    Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

  9. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  10. Fungal Laccases Degradation of Endocrine Disrupting Compounds

    PubMed Central

    Macellaro, Gemma; Cicatiello, Paola; Sannia, Giovanni

    2014-01-01

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

  11. Endocrine disruption in aquatic vertebrates.

    PubMed

    Kloas, Werner; Urbatzka, Ralph; Opitz, Robert; Würtz, Sven; Behrends, Thomas; Hermelink, Björn; Hofmann, Frauke; Jagnytsch, Oana; Kroupova, Hana; Lorenz, Claudia; Neumann, Nadja; Pietsch, Constanze; Trubiroha, Achim; Van Ballegooy, Christoph; Wiedemann, Caterina; Lutz, Ilka

    2009-04-01

    Environmental compounds can interfere with endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disrupters (ED), are surface waters. Thus, aquatic vertebrates, such as fish and amphibians, are most endangered. ED can adversely affect reproductive biology and the thyroid system. ED act by (anti)estrogenic and (anti)androgenic modes of action, resulting in abnormal sexual differentiation and impaired reproduction. These effects are mainly driven by direct interferences of ED with sex steroid receptors rather than indirectly by impacting synthesis and bioavailability of sex steroids, which in turn might affect the hypothalamic-pituitary-gonadal axis. Recent findings reveal that, in addition to the human-produced waste of ED, natural sources, such as parasites and decomposition of leaves, also might act as ED, markedly affecting sexual differentiation and reproduction in fish and amphibians. Although the thyroid system has essential functions in both fish and amphibians, amphibian metamorphosis has been introduced as the most sensitive model to detect thyroidal ED; no suitable fish model exists. Whereas ED may act primarily on only one specific endocrine target, all endocrine systems will eventually be deregulated as they are intimately connected to each other. The recent ecotoxicological issue of pharmaceutically active compounds (PhACs) present in the aquatic environment indicates a high potential for further endocrine modes of action on aquatic vertebrates by ED derived from PhACs, such as glucocorticoids, progestins, and beta-agonists.

  12. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

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

  13. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

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

  14. Endocrine-Disrupting Compounds in Aquatic Ecosystems.

    EPA Science Inventory

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

  15. Endocrine-Disrupting Compounds in Aquatic Ecosystems.

    EPA Science Inventory

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

  16. Endocrine disruption in aquatic insects: a review.

    PubMed

    Soin, Thomas; Smagghe, Guy

    2007-02-01

    There is mounting evidence that a wide variety of compounds can have endocrine disrupting effects on humans and wildlife. However, investigations so far have focused primarily on exposure to human and other vertebrates, with invertebrate findings largely restricted to marine mollusks or to the ecdysteroid and juvenile hormone agonists as purposely synthesized endocrine disrupters for the pest management of insects. This article provides a brief description of the insect hormone system, a short sum-up of the relevant insect groups with aquatic life stages, and an overview of the additional evidence for endocrine disruption in aquatic insects from laboratory and field studies since 1999. In addition, the suitability of insects as sentinels for endocrine disrupting chemicals in aquatic ecosystems is discussed. Conclusions are drawn and research needs are defined.

  17. FIELD MONITORING FOR ENDOCRINE DISRUPTION IN INVERTEBRATES

    EPA Science Inventory

    The field monitoring chapter addresses the following issues: cases where endocrine disruption (ED) has been identified as causing effects in either individuals, populations, or communities in the field; practical...

  18. Endocrine Disrupting Contaminants—Beyond the Dogma

    PubMed Central

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  19. Endocrine disrupting contaminants--beyond the dogma.

    PubMed

    Guillette, Louis J

    2006-04-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p -DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms.

  20. Amphibians as model to study endocrine disrupters.

    PubMed

    Kloas, Werner; Lutz, Ilka

    2006-10-13

    Environmental compounds can interfere with endocrine systems of wildlife and humans. These so-called endocrine disrupters (ED) are known to affect reproductive biology and thyroid system. The classical model species for these endocrine systems are amphibians and therefore they can serve as sentinels for detection of the modes of action (MOAs) of ED. Recently, amphibians are being reviewed as suitable models to assess (anti)estrogenic and (anti)androgenic MOAs influencing reproductive biology as well as (anti)thyroidal MOAs interfering with the thyroid system. The development of targeted bioassays in combination with adequate chemical analyses is the prerequisite for a concise risk assessment of ED.

  1. Endocrine Disrupting Chemicals and Disease Susceptibility

    PubMed Central

    Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

    2011-01-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

  2. Endocrine disrupting chemicals and disease susceptibility.

    PubMed

    Schug, Thaddeus T; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J

    2011-11-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products--including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption.

  3. Behaviour of pharmaceuticals and endocrine disrupting chemicals in simplified sewage treatment systems.

    PubMed

    Brandt, Emanuel M F; de Queiroz, Fernanda B; Afonso, Robson J C F; Aquino, Sérgio F; Chernicharo, Carlos A L

    2013-10-15

    This work assessed the behaviour of nine pharmaceuticals and/or endocrine disrupting chemicals (EDCs) in demo-scale upflow anaerobic sludge blanket reactors (UASB reactors) coupled to distinct simplified post-treatment units (submerged bed, polishing ponds, and trickling filters) fed on raw sewage taken from a municipality in Brazil. The dissolved concentration of the studied micropollutants in the raw and treated sewage was obtained using solid phase extraction (SPE) followed by analysis in a liquid chromatography system coupled to a hybrid high resolution mass spectrometer consisting of an ion-trap and time of flight (LC-MS-IT-TOF). The UASB reactors demonstrated that they were not appropriate for efficiently removing the assessed compounds from the sewage. Furthermore, this study demonstrated that the hydraulic retention time (HRT) was an important parameter for the removal of the hydrophilic and less biodegradable compounds, such as trimethoprim and sulfamethoxazole. The post-treatment units substantially increased the removal of most target micropollutants present in the anaerobic effluents, with a greater removal of micropollutants in simplified systems that require a large construction area, such as the submerged bed and polishing ponds, probably because of the higher HRT employed. Alternatively, compact post-treatment systems, such as trickling filters, tended to be less effective at removing most of the micropollutants studied, and the type of packing proved to be crucial for determining the fate of such compounds using trickling filters. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes

    USGS Publications Warehouse

    Writer, J.H.; Barber, L.B.; Brown, G.K.; Taylor, H.E.; Kiesling, R.L.; Ferrey, M.L.; Jahns, N.D.; Bartell, S.E.; Schoenfuss, H.L.

    2010-01-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17??-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use. ?? 2010.

  5. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes.

    PubMed

    Writer, Jeffrey H; Barber, Larry B; Brown, Greg K; Taylor, Howard E; Kiesling, Richard L; Ferrey, Mark L; Jahns, Nathan D; Bartell, Steve E; Schoenfuss, Heiko L

    2010-12-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17β-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use.

  6. Emerging endocrine disrupters: perfluoroalkylated substances.

    PubMed

    Jensen, Allan Astrup; Leffers, Henrik

    2008-04-01

    In recent years, polyfluorinated chemicals (PFCs) have increasingly been used as surfactants in various industry- and consumer products, because of their unique properties as repellents of dirt, water and oils. The most well-known PFCs are perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their derivatives belonging to the group of perfluoroalkylated substances. The PFCs are very persistent in the environment, and some of them have been discovered as global pollutants of air, water, soil and wildlife and even found in remote polar areas. Bioaccumulation occurs also in humans, and everybody in our society has traces of these PFCs in their blood and internal organs such as the liver, kidneys, spleen, gall bladder and testes. In the blood, PFOS and PFOA are bound to serum proteins. The acute toxicity of the polyfluorinated substances is moderate but some substances can induce peroxisome proliferation in rat livers and may change the fluidity of cell membranes. Some of these PFCs, such as PFOS and PFOA, are potential developmental toxicants and are suspected endocrine disruptors with effects on sex hormone levels resulting in lower testosterone levels and higher oestradiol level. Other PFCs have oestrogenic effects in cell cultures. The industrial production of PFOS and its derivatives stopped in 2000, and the European Union has banned most uses from the summer of 2008. However, hundreds of related chemicals: homologues with shorter or longer alkyl chain, PFOA and telomers, which potentially may degrade to perfluoroalkanoic (carboxylic) acids, are not regulated.

  7. In vivo endocrine disruption assessment of wastewater treatment plant effluents with small organisms.

    PubMed

    Castillo, Luis; Seriki, Kemi; Mateos, Stéphanie; Loire, Nicolas; Guédon, Nathalie; Lemkine, Gregory F; Demeneix, Barbara A; Tindall, Andrew J

    2013-01-01

    Surface water receives a variety of micro-pollutants that could alter aquatic organisms' reproduction and development. It is known that a few nanograms per litre of these compounds can induce endocrine-disrupting effects in aquatic species. Many compounds are released daily in wastewater, and identifying the compounds responsible for inducing such disruption is difficult. Methods using biological analysis are therefore an alternative to chemical analysis, as the endocrine disruption potential of the stream as a whole is considered. To detect hormonal disruption of thyroid and oestrogenic functions, fluorescent Xenopus laevis tadpoles and medaka (Oryzias latipes) fish larvae bearing genetic constructs integrating hormonal responsive elements were used for physiological screens for potential endocrine disruption in streams from an urban wastewater treatment plant. The Xenopus model was used to assess thyroid disruption and the medaka model oestrogenic disruption in wastewater samples. Assays using the genetically modified organisms were conducted on 9 influent and 32 effluent samples. The thyroidal effect of wastewater was either reduced or removed by the treatment plant; no oestrogenic effect was detected in any of the wastewater samples.

  8. Endocrine-disrupting chemicals and skin manifestations.

    PubMed

    Ju, Qiang; Zouboulis, Christos C

    2016-09-01

    Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin. In addition, their effects on keratinocytes, melanocytes, sebocytes, inflammatory and immunological cells, and skin stem cells produce inflammatory and allergic skin diseases, chloracne, disorders of skin pigmentation, skin cancer, and skin aging. Mechanisms, which EDCs use to induce these skin disorders are complicated, and involve the interference of endogenous hormones and most importantly the activation of the aryl hydrocarbon receptor signal pathway. Further studies on EDCs and skin diseases are necessary to elucidate these mechanisms.

  9. Endocrine disrupters and female reproductive health.

    PubMed

    McLachlan, John A; Simpson, Erica; Martin, Melvenia

    2006-03-01

    There is growing evidence of the impact of estrogenic contaminants in the environment. Studies have shown that male fish in detergent-contaminated water express female characteristics, turtles are sex-reversed by polychlorinated biphenyls (PCBs), male frogs exposed to a common herbicide form multiple ovaries, pseudohermaphroditic offspring are produced by polar bears, and seals in contaminated water have an excess of uterine fibroids. Endocrine-disrupting chemicals (those found in the external environment that can mimic or inhibit endogenous hormones) mostly exhibit estrogenic effects, but a few are anti-estrogenic or anti-androgenic. Many of these compounds are industrial contaminants, such as pesticides and plasticizers, and others are natural phytoestrogens found in plants such as soy and in herbal supplements. Recent work shows that human development can also be feminized by exposure to estrogenic chemicals. Estrogen is the key hormone in the initiation (puberty) and the end (menopause) of reproductive life in women and thus of considerable importance in women's health. The same chemicals that affect wildlife may affect breast growth and lactation, and could have a role in uterine diseases such as fibroids and endometriosis. New studies provide a mechanism of action for estrogenic chemicals and other endocrine disrupters at the molecular level (called epigenetics) that may help explain the long-term effects of endocrine disruption.

  10. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  11. Endocrine-disrupting chemicals: an Endocrine Society scientific statement.

    PubMed

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C; Hauser, Russ; Prins, Gail S; Soto, Ana M; Zoeller, R Thomas; Gore, Andrea C

    2009-06-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

  12. The Intersection of Neurotoxicology and Endocrine Disruption

    PubMed Central

    Weiss, Bernard

    2012-01-01

    Endocrine disruption, the guiding theme of the 27th International Neurotoxicology Conference, merged into the neurotoxicology agenda largely because hormones help steer the process of brain development. Although the disruption motif first attracted public health attention because of reproductive anomalies in both wildlife and humans, the neurobehavioral implications had been planted decades earlier. They stemmed from the principle that sex differences in behavior are primarily the outcomes of differences in how the brain is sexually differentiated during early development by gonadal hormones (the Organizational Hypothesis). We also now understand that environmental chemicals are capable of altering these underlying events and processes. Among those chemicals, the group labeled as endocrine disrupting chemicals (EDCs) offers the clearest evidence of such selectivity, a consequence of their actions on the endogenous sex steroids, androgens and estrogens. Two EDCs in particular offer useful and intriguing examples. One is phthalate esters. The other is bisphenol A. Both agents are used extensively in plastics manufacture, and are pervasive in the environment. Both are produced in immense quantities. Both are found in almost all humans. Phthalates are considered to function in essence as anti-androgens, while bisphenol A is labeled as an estrogen. Their associations with brain sexual differentiation are reviewed and further questions noted. Both EDCs produce a wider spectrum of health effects, however, than would be extrapolated simply from their properties as anti-androgens and estrogens. Obesity is one example. Further complicating their assessment as health risks are questions about nonmonotonic dose-response functions and about transgenerational effects incurred via epigenetic mechanisms. All these facets of endocrine disruption are pieces of a puzzle that challenge neurotoxicologists for solutions. PMID:22659293

  13. Risk Evaluation of Endocrine-Disrupting Chemicals

    PubMed Central

    Gioiosa, Laura; Palanza, Paola; vom Saal, Frederick S.

    2015-01-01

    We review here our studies on early exposure to low doses of the estrogenic endocrine-disrupting chemical bisphenol A (BPA) on behavior and metabolism in CD-1 mice. Mice were exposed in utero from gestation day (GD) 11 to delivery (prenatal exposure) or via maternal milk from birth to postnatal day 7 (postnatal exposure) to 10 µg/kg body weight/d of BPA or no BPA (controls). Bisphenol A exposure resulted in long-term disruption of sexually dimorphic behaviors. Females exposed to BPA pre- and postnatally showed increased anxiety and behavioral profiles similar to control males. We also evaluated metabolic effects in prenatally exposed adult male offspring of dams fed (from GD 9 to 18) with BPA at doses ranging from 5 to 50 000 µg/kg/d. The males showed an age-related significant change in a number of metabolic indexes ranging from food intake to glucose regulation at BPA doses below the no observed adverse effect level (5000 µg/kg/d). Consistent with prior findings, low but not high BPA doses produced significant effects for many outcomes. These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable. PMID:26740806

  14. Human biological monitoring of suspected endocrine-disrupting compounds

    PubMed Central

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

    2014-01-01

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

  15. Fish and wildlife species as sentinels of environmental endocrine disruption

    USGS Publications Warehouse

    Sheffield, S.R.; Matter, J.M.; Rattner, B.A.; Guiney, P.D.; Kendall, Ronald J.; Dickerson, Richard L.; Giesy, John P.; Suk, William P.

    1998-01-01

    This chapter provides an overview of the history and criteria for use of captive and free-ranging fish and wildlife (amphibians, reptiles, birds, and mammals) species as sentinels of potential environmental endocrine disruption. Biochemical, behavioral, physiological, immunological, genetic, reproductive, developmental, and ecological correlates of endocrine disruption in these sentinels are presented and reviewed. In addition, data needs to promote better use of sentinel species in the assessment of endocrine disruption are discussed.

  16. Endocrine disrupting properties of perfluorooctanoic acid.

    PubMed

    White, Sally S; Fenton, Suzanne E; Hines, Erin P

    2011-10-01

    Perfluoroalkyl acids (PFAAs) have attracted attention in recent years for their environmental ubiquity, as well as their toxicity. Several PFAAs are found in human tissues globally, as humans are exposed on a daily basis through intake of contaminated food, water, and air, irrespective of proximity to industry. Perfluorooctanoic acid (PFOA) is a PFAA shown to be developmentally toxic in mice, with broad and varied health consequences that may include long-lasting effects in reproductive tissues and metabolic reprogramming. To date, the only demonstrated mode of action by which the health effects of PFOA are mediated is via the activation of the peroxisome proliferator-activated receptor alpha (PPARα). The endogenous roles for this receptor, as well as the adverse outcomes of activation by exogenous agents during development, are currently under investigation. Recent studies suggest that PFOA may alter steroid hormone production or act indirectly, via ovarian effects, as a novel means of endocrine disruption. Here we review the existing literature on the known health effects of PFOA in animal models, focusing on sensitive developmental periods. To complement this, we also present epidemiologic health data, with the caveat that these studies largely address only associations between adult exposures and outcomes, rarely focusing on endocrine-specific endpoints, susceptible subpopulations, or windows of sensitivity. Further research in these areas is needed. Published by Elsevier Ltd.

  17. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed Central

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-01-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter. PMID:9539004

  18. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-02-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

  19. The challenge posed by endocrine-disrupting chemicals.

    PubMed

    Ashby, J; Houthoff, E; Kennedy, S J; Stevens, J; Bars, R; Jekat, F W; Campbell, P; Van Miller, J; Carpanini, F M; Randall, G L

    1997-02-01

    Rapid regulatory developments in the area of environmental endocrine disruption present a series of potential problems that are identified and illustrated with examples taken from the recent literature. A list of priorities is provided, including the need for additional epidemiological and wildlife studies, the derivation of a coordinated testing strategy, agreement on the toxicities expected of endocrine disrupting agents, and acceptance that whole animal assays will be uniquely critical in this area of toxicology. The intrinsic difficulty of attempting to simultaneously study all aspects of endocrine disruption indicates the need to reduce the scope of the problem, which can be achieved by first studying toxicities mediated by sex hormone receptors.

  20. The challenge posed by endocrine-disrupting chemicals.

    PubMed Central

    Ashby, J; Houthoff, E; Kennedy, S J; Stevens, J; Bars, R; Jekat, F W; Campbell, P; Van Miller, J; Carpanini, F M; Randall, G L

    1997-01-01

    Rapid regulatory developments in the area of environmental endocrine disruption present a series of potential problems that are identified and illustrated with examples taken from the recent literature. A list of priorities is provided, including the need for additional epidemiological and wildlife studies, the derivation of a coordinated testing strategy, agreement on the toxicities expected of endocrine disrupting agents, and acceptance that whole animal assays will be uniquely critical in this area of toxicology. The intrinsic difficulty of attempting to simultaneously study all aspects of endocrine disruption indicates the need to reduce the scope of the problem, which can be achieved by first studying toxicities mediated by sex hormone receptors. PMID:9105789

  1. Integrated risk assessment and endocrine disrupters.

    PubMed

    Bridges, J W; Bridges, Olga

    2004-12-01

    1. The procedures currently employed for risk assessment are unlikely to be sustainable in the future for a variety of reasons. A number of actions are needed to remedy the situation and the most important of these actions are: * to improve access to existing data; * to introduce a prioritisation system based on exposure assessment; * to co-ordinate and harmonise approaches of different organisations involved in risk assessment. 2. Integration of information and methodologies between human health risk assessment and ecological risk assessment (integrated risk assessment) is advocated in this paper as one of the most important steps towards a holistic and effective way of conducting a risk assessment. 3. A framework is proposed for identification of agents for which an integrated risk assessment would be of particular value. Close collaboration across disciplines and across countries is necessary for the potential of integrated risk assessment to be realised in practice. The practicality of applying integrated risk assessment to endocrine disrupting agents is presently being investigated in an EU funded multi-laboratory collaborative study (CREDO).

  2. ENDOCRINE DISRUPTING CONTAMINANTS AND ALLIGATOR EMBRYOS: A LESSON FROM WILDLIFE?

    EPA Science Inventory

    Many xenobiotic compounds introduced into the environment by human activity adversely affect wildlife. A number of these contaminants have been hypothesized to induce non lethal, multigenerational effects by acting as endocrine disrupting agents. One case is that of the alligator...

  3. ENDOCRINE DISRUPTING CONTAMINANTS AND ALLIGATOR EMBRYOS: A LESSON FROM WILDLIFE?

    EPA Science Inventory

    Many xenobiotic compounds introduced into the environment by human activity adversely affect wildlife. A number of these contaminants have been hypothesized to induce non lethal, multigenerational effects by acting as endocrine disrupting agents. One case is that of the alligator...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  6. A RESEARCH AGENDA FOR RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    To date, research on suspected endocrine disrupting chemicals (EDCs) has focused on determining health effects in humans and wildlife and on occurrence of these chemicals in the environment. There is strong evidence that certain chemicals are causing endocrine-related effects in...

  7. Incorporation of endocrine disruption into chemical hazard scoring for pollution prevention and current list of endocrine disrupting chemicals.

    PubMed

    Whaley, D A; Keyes, D; Khorrami, B

    2001-11-01

    Research continues to support the theory of endocrine disruption. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. The University of Tennessee, Knoxville (UTN), developed a method for hazard scoring chemicals for the aquatic ecosystem. The Indiana Clean Manufacturing Technology and Safe Materials Institute at Purdue University (CMTI) later expanded the scoring system to include terms for worker hazard as well as terms for contamination of soil and air quality, and for stratospheric ozone depletion. We call the CMTI chemical hazard score the Purdue score. At West Virginia University, two improvements of the Purdue chemical hazard score are developed, a normalizing of the term for soil contamination, and addition of hazard score terms for ecosystem endocrine disruption. The results of incorporating endocrine disruption terms into the hazard scoring equations resulted in increased hazard rankings, often substantially increased, for 26 endocrine disrupting chemicals (EDCs) among 200 Superfund chemicals. Because data suggesting human endocrine disruption from such chemicals is still controversial, no endocrine disruptor term has been added to the human toxicity portions of the chemical hazard scoring system at this time. The third product of this work is assembly of a current consolidated list of (1) established or probable, mostly synthetic, industrial chemical and medication EDCs and (2) suspect (less certain) synthetic and natural (phytoestrogen) possible endocrine disrupting chemicals, with the goal of contributing to future development of quantitative structure activity

  8. ENDOCRINE-DISRUPTING CONTAMINANTS AND REPRODUCTION IN VERTEBRATE WILDLIFE.

    EPA Science Inventory

    The fields of toxicology, endocrinology, and reproductive physiology recently have combined resources to study the effects of endocrine-disrupting contaminants (EDCs) in wildlife populations. EDCs include a wide variety of chemicals that are only related by the ability to disrupt...

  9. ENDOCRINE-DISRUPTING CONTAMINANTS AND REPRODUCTION IN VERTEBRATE WILDLIFE.

    EPA Science Inventory

    The fields of toxicology, endocrinology, and reproductive physiology recently have combined resources to study the effects of endocrine-disrupting contaminants (EDCs) in wildlife populations. EDCs include a wide variety of chemicals that are only related by the ability to disrupt...

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

    PubMed Central

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. PMID:22991565

  11. Endocrine disrupting effects of butylated hydroxyanisole (BHA - E320)

    PubMed Central

    POP, ANCA; KISS, BELA; LOGHIN, FELICIA

    2013-01-01

    Butylated hydroxyanisole (BHA) is extensively used as antioxidant in foods, food packaging, cosmetics and pharmaceuticals. In the past years, it raised concerns regarding its possible endocrine disrupting effect. The existing in vitro studies indicate that BHA presents a weak estrogenic effect and also anti-androgenic properties while an in vivo study found it to have antiestrogenic properties. There is no sufficient data available at the moment to draw a conclusion regarding the safety of BHA when referring to its endocrine disrupting effect. Since a fraction of the population might be exposed to doses superior to the acceptable daily intake (ADI), it is important to gather more in vitro and in vivo data concerning the potential effects that BHA might have alone, but also in mixtures with natural hormones or other endocrine disrupting compounds. PMID:26527908

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

    PubMed

    Schantz, S L; Widholm, J J

    2001-12-01

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

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

    PubMed Central

    Schantz, S L; Widholm, J J

    2001-01-01

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

  14. CONTAMINANT-ASSOCIATED ENDOCRINE DISRUPTION IN REPTILES.

    EPA Science Inventory

    The data presented suggest that contaminants can alter the endocrine and reproductive system of reptiles by mimicking hormones and by various mechanisms other than direct hormonal mimicry. However, these data indicate, as do many other studies using various vertebrates, that a fo...

  15. Pesticides as endocrine-disrupting chemicals

    EPA Science Inventory

    Pesticides are designed to be bioactive against certain targets but can cause toxicity to nontarget species by a variety of other modes of action including disturbance of endocrine function. As such, pesticides have been found to bind and alter the function of hormone receptors, ...

  16. Pesticides as endocrine-disrupting chemicals

    EPA Science Inventory

    Pesticides are designed to be bioactive against certain targets but can cause toxicity to nontarget species by a variety of other modes of action including disturbance of endocrine function. As such, pesticides have been found to bind and alter the function of hormone receptors, ...

  17. CONTAMINANT-ASSOCIATED ENDOCRINE DISRUPTION IN REPTILES.

    EPA Science Inventory

    The data presented suggest that contaminants can alter the endocrine and reproductive system of reptiles by mimicking hormones and by various mechanisms other than direct hormonal mimicry. However, these data indicate, as do many other studies using various vertebrates, that a fo...

  18. Designing Endocrine Disruption Out of the Next Generation of Chemicals

    PubMed Central

    Schug, T.T; Abagyan, R.; Blumberg, B.; Collins, T.J.; Crews, D.; DeFur, P.L.; Dickerson, S.M.; Edwards, T.M.; Gore, A.C.; Guillette, L.J.; Hayes, T.; Heindel, J.J.; Moores, A.; Patisaul, H.B.; Tal, T.L.; Thayer, K.A.; Vandenberg, L.N.; Warner, J.; Watson, C.S.; Saal, F.S. vom; Zoeller, R.T.; O’Brien, K.P.; Myers, J.P.

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical’s potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at “the drawing board.” It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a ‘proof-of-principle’ test, we ran 6 endocrine disrupting chemicals (EDCs) that act

  19. Designing Endocrine Disruption Out of the Next Generation of Chemicals.

    PubMed

    Schug, T T; Abagyan, R; Blumberg, B; Collins, T J; Crews, D; DeFur, P L; Dickerson, S M; Edwards, T M; Gore, A C; Guillette, L J; Hayes, T; Heindel, J J; Moores, A; Patisaul, H B; Tal, T L; Thayer, K A; Vandenberg, L N; Warner, J; Watson, C S; Saal, F S Vom; Zoeller, R T; O'Brien, K P; Myers, J P

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via

  20. Exposure to endocrine disrupting chemicals and neurodevelopmental alterations.

    PubMed

    Pinson, A; Bourguignon, J P; Parent, A S

    2016-07-01

    The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling.

  1. Endocrine Disruption and Human Prostate Cancer

    DTIC Science & Technology

    2008-03-01

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

  2. Endocrine disruption, parasites and pollutants in wild freshwater fish.

    PubMed

    Jobling, S; Tyler, C R

    2003-01-01

    Disruption of the endocrine system has been shown to occur in wild freshwater fish populations across the globe. Effects range from subtle changes in the physiology and sexual behaviour of fish to permanently altered sexual differentiation, impairment of gonad development and/or altered fertility. A wide variety of adverse environmental conditions may induce endocrine disruption, including sub-optimal temperatures, restricted food supply, low pH, environmental pollutants, and/or parasites. Furthermore, it is conceivable that any/all of these factors could act simultaneously to cause a range of disparate or inter-related effects. Some of the strongest evidence for a link between an adverse health effect, as a consequence of endocrine disruption, and a causative agent(s) is between the condition of intersex in wild roach (Rutlius rutilus) in UK rivers and exposure to effluents from sewage treatment works. The evidence to indicate that intersex in roach (and other cyprinid fish living in these rivers) is caused by chemicals that mimic and/or disrupt hormone function/balance in treated sewage effluent is substantial. There are a few parasites that affect the endocrine system directly in fish, including the tape worm Ligula intestinalis and a few parasites from the micropsora phylum. L. intestinalis acts at the level of the hypothalamus restricting GnRH secretion (resulting in poorly developed gonads) and is one of the very few examples where an endocrine disrupting event has been shown to result in a population-level effect (reducing it). It is well established that many parasites affect the immune system and thus the most common effect of parasites on the endocrine system in fish is likely to be an indirect one.

  3. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

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

  4. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    Although these studies indicate that wastewater-treatment plant effluent is a conduit for endocrine active chemicals to surface waters, endocrine active chemicals also were present in surface waters with no obvious wastewater-treatment plant effluent sources. Endocrine active chemicals were detected and indicators of endocrine disruption in fish were measured at numerous sites upstream from discharge of wastewater-treatment plant effluent. These observations indicate that other unidentified sources of endocrine active chemicals exist, such as runoff from land surfaces, atmospheric deposition, inputs from onsite septic systems, or other groundwater sources. Alternatively, some endocrine active chemicals may not yet have been identified or measured. The presence of biological indicators of endocrine disruption in male fish indicates that the fish are exposed to endocrine active chemicals. However indicators of endocrine disruption in male fish does not indicate an effect on fish reproduction or changes in fish populations.

  5. Recent Advances on Endocrine Disrupting Effects of UV Filters

    PubMed Central

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-01-01

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. PMID:27527194

  6. Recent Advances on Endocrine Disrupting Effects of UV Filters.

    PubMed

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-08-03

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

  7. Assessing Risks of Endocrine-disrupting Chemicals: A Scientific Odyssey

    EPA Science Inventory

    In the mid-90s there was a marked increase in public awareness of, and concern for, endocrine-disrupting chemicals (EDCs). There have been a number of purported impacts of EDCs on both human and wildlife health; however, in some instances it has been challenging to relate observ...

  8. WASTEWATER TREATMENT AND ITS MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Research has shown that wastewater treatment (WWT) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WWT can include centralized wastewater treatment plants (WWTPs) or on-site WWT technologies. EDCs found in WWT effluents (aqueous and biosol...

  9. DEVELOPING TOOLS FOR EVALUATING RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    The goal of endocrine disrupting chemical (EDC) risk management (RM) is to minimize the release of EDCs into the environment or to minimize the exposure of humans or wildlife to EDCs already present in the environment. RM research projects may involve: substituting more innocuous...

  10. METABOLOMIC STUDIES OF ENDOCRINE DISRUPTION IN SMALL FISH MODELS

    EPA Science Inventory

    Metabolomics is now being widely used to obtain complementary information to genomic and proteomic studies. To better understand temporal, compensatory and dose responses to endocrine-disrupting chemicals (EDCs) within the hypothalamic-pituitary¬gonadal (HPG) axis, we have carrie...

  11. DEVELOPING TOOLS FOR EVALUATING RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    The goal of endocrine disrupting chemical (EDC) risk management (RM) is to minimize the release of EDCs into the environment or to minimize the exposure of humans or wildlife to EDCs already present in the environment. RM research projects may involve: substituting more innocuous...

  12. EFFECTIVE RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS WORKSHOP NEWMEDIA CD

    EPA Science Inventory

    This product is a CD-ROM version of the workshop, Effective Risk Management of Endocrine Disrupting Chemicals, held in January 2002, in Cincinnati, Ohio. The goal of this workshop was to introduce the science and engineering behind managing the potential risk of suspected endocri...

  13. BIOMARKERS OF ENDOCRINE DISRUPTION AT THE MRNA LEVEL

    EPA Science Inventory

    Denslow, Nancy D., Christopher J. Bowman, Gillian Robinson, H. Stephen Lee, Ronald J. Ferguson, Michael J. Hemmer and Leroy C. Folmar. 1999. Biomarkers of Endocrine Disruption at the mRNA Level. In: Environmental Toxicology and Risk Assessment: Standardization of Biomarkers for ...

  14. Assessing Risks of Endocrine-disrupting Chemicals: A Scientific Odyssey

    EPA Science Inventory

    In the mid-90s there was a marked increase in public awareness of, and concern for, endocrine-disrupting chemicals (EDCs). There have been a number of purported impacts of EDCs on both human and wildlife health; however, in some instances it has been challenging to relate observ...

  15. PROGRAM FOR THE IDENTIFICATION AND REPLACEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    A computer software program is being developed to aid in the identification and replacement of endocrine disrupting chemicals (EDC). This program will be comprised of two distinct areas of research: identification of potential EDC nd suggstions for replacing those potential EDC. ...

  16. WASTEWATER TREATMENT AND ITS MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Research has shown that wastewater treatment (WWT) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WWT can include centralized wastewater treatment plants (WWTPs) or on-site WWT technologies. EDCs found in WWT effluents (aqueous and biosol...

  17. BIOMARKERS OF ENDOCRINE DISRUPTION AT THE MRNA LEVEL

    EPA Science Inventory

    Denslow, Nancy D., Christopher J. Bowman, Gillian Robinson, H. Stephen Lee, Ronald J. Ferguson, Michael J. Hemmer and Leroy C. Folmar. 1999. Biomarkers of Endocrine Disruption at the mRNA Level. In: Environmental Toxicology and Risk Assessment: Standardization of Biomarkers for ...

  18. Endocrine disruption: fact or urban legend?

    PubMed

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

    2013-12-16

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

  19. 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...

  20. 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...

  1. Endocrine disrupters--testing strategies to assess human hazard.

    PubMed

    Baker, V A

    2001-01-01

    During the last decade an hypothesis has been developed linking certain chemicals (natural and synthetic) to observed and suspected adverse effects on reproduction in both wildlife and humans. The issue of 'endocrine disruption' originally focused on chemicals that mimic the action of the natural hormone oestrogen. However, the concern is now encompassing effects on the whole endocrine system. In response to public awareness, regulatory agencies (including the US EPA) and the OECD are formulating potential testing strategies and have begun the process of validating defined tests to systematically assess chemicals for their endocrine-disrupting activities. In order to investigate chemicals that have the potential to cause endocrine disruption, a large number of in vitro and in vivo assays have been identified. In vitro test systems (particularly when used in combination) offer the possibility of providing an early screen for large numbers of chemicals and can be useful in characterising the mechanism of action and potency. In vitro assays in widespread use for the screening/characterisation of endocrine disrupting potential include hormone receptor ligand binding assays (determination of the ability of a chemical to bind to the hormone receptor), cell proliferation assays (analysis of the ability of a chemical to stimulate growth of oestrogen sensitive cells), reporter gene assays in yeast or mammalian cells (analysis of the ability of a chemical to stimulate the transcription of a reporter gene construct in cell culture), and the analysis of the regulation of endogenous oestrogen sensitive genes in cell lines. However, in vitro assays do not always reliably predict the outcome in vivo due to differences in metabolic capabilities of the test systems used and the diverse range of mechanisms by which endocrine disrupting chemicals may act. Therefore a complementary battery of short- and long-term in vitro and in vivo assays (that assess both receptor and non

  2. Endocrine Disruption and In Vitro Ecotoxicology: Recent Advances and Approaches.

    PubMed

    Wagner, Martin; Kienle, Cornelia; Vermeirssen, Etiënne L M; Oehlmann, Jörg

    Endocrine-disrupting chemicals (EDCs) are man-made compounds interfering with hormone signaling. Omnipresent in the environment, they can cause adverse effects in a wide range of wildlife. Accordingly, Endocrine Disruption is one focal area of ecotoxicology. Because EDCs induce complex response patterns in vivo via a wide range of mechanisms of action, in vitro techniques have been developed to reduce and understand endocrine toxicity. In this review we revisit the evidence for endocrine disruption in diverse species and the underlying molecular mechanisms. Based on this, we examine the battery of in vitro bioassays currently in use in ecotoxicological research and discuss the following key questions. Why do we use in vitro techniques? What endpoints are we looking at? Which applications are we using in vitro bioassays for? How can we put in vitro data into a broader context? And finally, what is the practical relevance of in vitro data? In critically examining these questions, we review the current state-of-the-art of in vitro (eco)toxicology, highlight important limitations and challenges, and discuss emerging trends and future research needs.

  3. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    PubMed Central

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. PMID:26414233

  4. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.

    PubMed

    Gore, A C; Chappell, V A; Fenton, S E; Flaws, J A; Nadal, A; Prins, G S; Toppari, J; Zoeller, R T

    2015-12-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health.

  5. [Endocrine xenoestrogenics disrupters: molecular mechanisms and detection methods].

    PubMed

    Mnif, Wissem; Pillon, Arnaud; Balaguer, Patrick; Bartegi, Aghleb

    2007-01-01

    The attention paid to endocriniens modulators for purpose micropolluants (endocrine disrupters) has been increasingly studied these last years particularly on animals. The results of this study raised big concerns from Doctors and Biologists on the eventual risks human health can face. Indeed, endocrine systems of the body play an essential and pervasive role in both the short- and long-term regulation of metabolic processes. Nutritional, behavioural, and reproductive processes are intricately regulated by endocrine systems, as are growth (including bone growth/remodelling), gut, cardiovascular, and kidney function and responses to all forms of stress. Disorders of any of the endocrine system, involving both over- and under-active hormone secretion, result inevitably in disease, the effects of which may extend to many different organs and functions and are often debilitating or life-threatening. Viewed from this general perspective, the threat posed from environmental chemicals with endocrine activity (either agonist or antagonistic) is potentially serious. However, the fact that humans and wildlife are exposed to such chemicals does not necessarily mean that clinically manifest disturbance of the relevant endocrine system will result, because much depends on the level and duration of exposure and on the timing of exposure. Indeed, a large numbers of environmental estrogens are suspected of altering human health as well as the marine ecosystem balance. The objective of this review is to study the different molecular mechanisms of these xenoestrogenes micropolluants, in order to emphasize their potential risk and to present some of the different experimental methods for their detection.

  6. Effects of endocrine disrupters on sexual, gonadal development in fish.

    PubMed

    Scholz, S; Klüver, N

    2009-01-01

    Steroid sex hormones play an important role in the sexual differentiation of fish. Thus, it is not surprising that chemical contaminants with steroid-like activities were considered as responsible for the unusual occurrence of gonadal intersex conditions and other gonadal aberrations in feral fish. In this review, we give an overview about field data and summarise and categorise experimental evidence that links disruption of gonadal development in gonochoristic fish to contaminations by endocrine disrupting chemicals. A comprehensive overview on laboratory studies using water-borne exposures and histopathological analysis is given. Parameters ranging from simple quantitative characteristics such as sex ratio, number of sex reversed fish, and gonadosomatic index (GSI) to detailed morphometric analyses have been considered. Categorisation of the data indicates 2 major groups of chemicals with apparently conserved effects across species, i.e. estrogenic/anti-androgenic or androgenic/anti-estrogenic compounds. Since gross morphological parameters and histological analysis are often the first parameters measured in field campaigns for sampling of feral fish, the review supports the critical evaluation of present and future field studies and the confirmation or rejection of causative links to exposure with endocrine disrupting chemicals. Furthermore, in combination with the analysis of molecular endpoints the processed data will be useful to deduce mechanistic information on potential endocrine disrupting compounds.

  7. Chemical communication threatened by endocrine-disrupting chemicals.

    PubMed Central

    Fox, Jennifer E

    2004-01-01

    Communication on a cellular level--defined as chemical signaling, sensing, and response--is an essential and universal component of all living organisms and the framework that unites all ecosystems. Evolutionarily conserved signaling "webs," existing both within an organism and between organisms, rely on efficient and accurate interpretation of chemical signals by receptors. Therefore, endocrine-disrupting chemicals (EDCs), which have been shown to disrupt hormone signaling in laboratory animals and exposed wildlife, may have broader implications for disrupting signaling webs that have yet to be identified as possible targets. In this article, I explore common evolutionary themes of chemical signaling (e.g., estrogen signaling in vertebrates and phytoestrogen signaling from plants to symbiotic soil bacteria) and show that such signaling systems are targets of disruption by EDCs. Recent evolutionary phylogenetic data have shown that the estrogen receptor (ER) is the ancestral receptor from which all other steroid receptors have evolved. In addition to binding endogenous estrogens, ERs also bind phytoestrogens, an ability shared in common with nodulation D protein (NodD) receptors found in Rhizobium soil bacteria. Recent data have shown that many of the same synthetic and natural environmental chemicals that disrupt endocrine signaling in vertebrates also disrupt phytoestrogen-NodD receptor signaling in soil bacteria, which is necessary for nitrogen-fixing symbiosis. Bacteria-plant symbiosis is an unexpected target of EDCs, and other unexpected nontarget species may also be vulnerable to EDCs found in the environment. PMID:15121505

  8. Chemical communication threatened by endocrine-disrupting chemicals.

    PubMed

    Fox, Jennifer E

    2004-05-01

    Communication on a cellular level--defined as chemical signaling, sensing, and response--is an essential and universal component of all living organisms and the framework that unites all ecosystems. Evolutionarily conserved signaling "webs," existing both within an organism and between organisms, rely on efficient and accurate interpretation of chemical signals by receptors. Therefore, endocrine-disrupting chemicals (EDCs), which have been shown to disrupt hormone signaling in laboratory animals and exposed wildlife, may have broader implications for disrupting signaling webs that have yet to be identified as possible targets. In this article, I explore common evolutionary themes of chemical signaling (e.g., estrogen signaling in vertebrates and phytoestrogen signaling from plants to symbiotic soil bacteria) and show that such signaling systems are targets of disruption by EDCs. Recent evolutionary phylogenetic data have shown that the estrogen receptor (ER) is the ancestral receptor from which all other steroid receptors have evolved. In addition to binding endogenous estrogens, ERs also bind phytoestrogens, an ability shared in common with nodulation D protein (NodD) receptors found in Rhizobium soil bacteria. Recent data have shown that many of the same synthetic and natural environmental chemicals that disrupt endocrine signaling in vertebrates also disrupt phytoestrogen-NodD receptor signaling in soil bacteria, which is necessary for nitrogen-fixing symbiosis. Bacteria-plant symbiosis is an unexpected target of EDCs, and other unexpected nontarget species may also be vulnerable to EDCs found in the environment.

  9. Endocrine-disrupting chemicals and male reproductive health.

    PubMed

    Knez, Jure

    2013-05-01

    Endocrine-disrupting chemicals are substances present in the environment that can interfere with normal hormonal balance and thus exert potentially adverse health effects on the human organism. Male reproductive system development and function may be susceptible to the effects of such environmental toxicants. Bisphenol A, phthalates and alkylphenols are important components of multiple products and are thus ubiquitously present in the environment. It has been demonstrated under laboratory conditions that they can exert detrimental effects on the male reproductive system. However, human exposure data are scarce and do not uniformly support toxicity of these substances at environmental concentrations. Despite substantial research efforts, the final answer to the problem of endocrine-disrupting chemicals is not yet in sight. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Endocrine disrupters--a threat to women's health?

    PubMed

    Waring, R H; Harris, R M

    2011-02-01

    Endocrine disruption has been a topic of public concern for many years and its study remains high on the scientific agenda. Endocrine disrupters (EDs) are compounds which may be of industrial or natural origin and which act to dysregulate steroid function and metabolism. As well as their actions on nuclear steroid receptors, EDs can inhibit the pathways of steroid synthesis and degradation. They not only affect reproductive function but also affect a range of tissues which are steroid sensitive such as the central nervous system and thyroid. Results from the latest studies suggest that EDs may also affect the immune system, glucose homeostasis and can act as epigenetic modulators resulting in transgenerational effects. Research in this area has led to the development of drugs used in the treatment of several types of hormone-sensitive cancer. However, despite many years of effort, the effects on human health of long-term environmental exposure to EDs, whether singly or as mixtures, remain unknown.

  11. Endocrine-disrupting chemicals and the regulation of energy balance.

    PubMed

    Nadal, Angel; Quesada, Ivan; Tudurí, Eva; Nogueiras, Rubén; Alonso-Magdalena, Paloma

    2017-09-01

    Energy balance involves the adjustment of food intake, energy expenditure and body fat reserves through homeostatic pathways. These pathways include a multitude of biochemical reactions, as well as hormonal cues. Dysfunction of this homeostatic control system results in common metabolism-related pathologies, which include obesity and type 2 diabetes mellitus. Metabolism-disrupting chemicals (MDCs) are a particular class of endocrine-disrupting chemicals that affect energy homeostasis. MDCs affect multiple endocrine mechanisms and thus different cell types that are implicated in metabolic control. MDCs affect gene expression and the biosynthesis of key enzymes, hormones and adipokines that are essential for controlling energy homeostasis. This multifaceted spectrum of actions precludes compensatory responses and favours metabolic disorders. Herein, we review the main mechanisms used by MDCs to alter energy balance. This work should help to identify new MDCs, as well as novel targets of their action.

  12. An approach to assessment of endocrine disruption in the National Children's Study.

    PubMed Central

    Longnecker, Matthew P; Bellinger, David C; Crews, David; Eskenazi, Brenda; Silbergeld, Ellen K; Woodruff, Tracey J; Susser, Ezra S

    2003-01-01

    In this article we consider the importance of assessing endocrine disruption in a large new cohort that has been proposed, the National Children's Study (NCS). We briefly review evidence that endocrine disruption is a potentially important hypothesis for human studies and weigh the need to assess endocrine disruption in the NCS. We note the salient features of earlier, similar cohort studies that serve as reference points for the design of the NCS. Finally, we discuss features of the NCS that would allow or enhance assessment of endocrine disruption, even if endocrine disruption were not a primary hypothesis motivating the study. At this time, the evidence supporting endocrine disruption in humans with background-level exposures is not strong. Thus, a compelling rationale for the NCS will probably need to be based on core hypotheses that focus on other issues. Nonetheless, if properly designed, the NCS could serve as an excellent resource for investigating future hypotheses regarding endocrine disruption. PMID:14527852

  13. Modelling the interaction of steroid receptors with endocrine disrupting chemicals

    PubMed Central

    D'Ursi, Pasqualina; Salvi, Erika; Fossa, Paola; Milanesi, Luciano; Rovida, Ermanna

    2005-01-01

    Background The organic polychlorinated compounds like dichlorodiphenyltrichloroethane with its metabolites and polychlorinated biphenyls are a class of highly persistent environmental contaminants. They have been recognized to have detrimental health effects both on wildlife and humans acting as endocrine disrupters due to their ability of mimicking the action of the steroid hormones, and thus interfering with hormone response. There are several experimental evidences that they bind and activate human steroid receptors. However, despite the growing concern about the toxicological activity of endocrine disrupters, molecular data of the interaction of these compounds with biological targets are still lacking. Results We have used a flexible docking approach to characterize the molecular interaction of seven endocrine disrupting chemicals with estrogen, progesterone and androgen receptors in the ligand-binding domain. All ligands docked in the buried hydrophobic cavity corresponding to the hormone steroid pocket. The interaction was characterized by multiple hydrophobic contacts involving a different number of residues facing the binding pocket, depending on ligands orientation. The EDC ligands did not display a unique binding mode, probably due to their lipophilicity and flexibility, which conferred them a great adaptability into the hydrophobic and large binding pocket of steroid receptors. Conclusion Our results are in agreement with toxicological data on binding and allow to describe a pattern of interactions for a group of ECD to steroid receptors suggesting the requirement of a hydrophobic cavity to accommodate these chlorine carrying compounds. Although the affinity is lower than for hormones, their action can be brought about by a possible synergistic effect. PMID:16351736

  14. Modelling the interaction of steroid receptors with endocrine disrupting chemicals.

    PubMed

    D'Ursi, Pasqualina; Salvi, Erika; Fossa, Paola; Milanesi, Luciano; Rovida, Ermanna

    2005-12-01

    The organic polychlorinated compounds like dichlorodiphenyltrichloroethane with its metabolites and polychlorinated biphenyls are a class of highly persistent environmental contaminants. They have been recognized to have detrimental health effects both on wildlife and humans acting as endocrine disrupters due to their ability of mimicking the action of the steroid hormones, and thus interfering with hormone response. There are several experimental evidences that they bind and activate human steroid receptors. However, despite the growing concern about the toxicological activity of endocrine disrupters, molecular data of the interaction of these compounds with biological targets are still lacking. We have used a flexible docking approach to characterize the molecular interaction of seven endocrine disrupting chemicals with estrogen, progesterone and androgen receptors in the ligand-binding domain. All ligands docked in the buried hydrophobic cavity corresponding to the hormone steroid pocket. The interaction was characterized by multiple hydrophobic contacts involving a different number of residues facing the binding pocket, depending on ligands orientation. The EDC ligands did not display a unique binding mode, probably due to their lipophilicity and flexibility, which conferred them a great adaptability into the hydrophobic and large binding pocket of steroid receptors. Our results are in agreement with toxicological data on binding and allow to describe a pattern of interactions for a group of ECD to steroid receptors suggesting the requirement of a hydrophobic cavity to accommodate these chlorine carrying compounds. Although the affinity is lower than for hormones, their action can be brought about by a possible synergistic effect.

  15. 78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... determine the potential for a drug to disrupt the endocrine system. This draft guidance also discusses... compounds that have the potential to interfere with some aspect of the endocrine system of an organism or its progeny. Any component of the endocrine system can be a target of endocrine disruptors, although...

  16. 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.

  17. Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

    PubMed Central

    Brown, T. R.; Doan, L. L.; Gore, A. C.; Skakkebaek, N. E.; Soto, A. M.; Woodruff, T. J.; Vom Saal, F. S.

    2012-01-01

    An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures. PMID:22733974

  18. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society.

    PubMed

    Zoeller, R Thomas; Brown, T R; Doan, L L; Gore, A C; Skakkebaek, N E; Soto, A M; Woodruff, T J; Vom Saal, F S

    2012-09-01

    An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.

  19. Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs).

    PubMed

    Palioura, Eleni; Diamanti-Kandarakis, Evanthia

    2015-12-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unclear etiopathogenesis that is likely to involve genetic and environmental components synergistically contributing to its phenotypic expression. Endocrine disrupting chemicals (EDCs) and in particular Bisphenol A (BPA) represent a group of widespread pollutants intensively investigated as possible environmental contributors to PCOS pathogenesis. Substantial evidence from in vitro and animal studies incriminates endocrine disruptors in the induction of reproductive and metabolic aberrations resembling PCOS characteristics. In humans, elevated BPA concentrations are observed in adolescents and adult PCOS women compared to reproductively healthy ones and are positively correlated with hyperandrogenemia, implying a potential role of the chemical in PCOS pathophysiology, although a causal interference cannot yet be established. It is plausible that developmental exposure to specific EDCs could permanently alter neuroendocrine, reproductive and metabolic regulation favoring PCOS development in genetically predisposed individuals or it could accelerate and/or exacerbate the natural course of the syndrome throughout life cycle exposure.

  20. Environmental Endocrine Disruption of Energy Metabolism and Cardiovascular Risk

    PubMed Central

    Kirkley, Andrew G.; Sargis, Robert M.

    2014-01-01

    Rates of metabolic and cardiovascular diseases have increased at an astounding rate in recent decades. While poor diet and physical inactivity are central drivers, these lifestyle changes alone fail to fully account for the magnitude and rapidity of the epidemic. Thus, attention has turned to identifying novel risk factors, including the contribution of environmental endocrine disrupting chemicals. Epidemiological and preclinical data support a role for various contaminants in the pathogenesis of diabetes. In addition to the vascular risk associated with dysglycemia, emerging evidence implicates multiple pollutants in the pathogenesis of atherosclerosis and cardiovascular disease. Reviewed herein are studies linking endocrine disruptors to these key diseases that drive significant individual and societal morbidity and mortality. Identifying chemicals associated with metabolic and cardiovascular disease as well as their mechanisms of action is critical for developing novel treatment strategies and public policy to mitigate the impact of these diseases on human health. PMID:24756343

  1. CHARACTERIZATION OF ENDOCRINE-DISRUPTION AND CLINICAL MANIFESTATIONS IN LARGE-MOUTH BASS FROM FLORIDA LAKES

    EPA Science Inventory

    Previous efforts from this laboratory, have documented altered endocrine function and sexual differentiation for alligators and turtles from Lake Apopka in Central Florida. This lake has been exposed to a variety of contaminants which are potentially endocrine-disrupting. Therefo...

  2. CHARACTERIZATION OF ENDOCRINE-DISRUPTION AND CLINICAL MANIFESTATIONS IN LARGE-MOUTH BASS FROM FLORIDA LAKES

    EPA Science Inventory

    Previous efforts from this laboratory, have documented altered endocrine function and sexual differentiation for alligators and turtles from Lake Apopka in Central Florida. This lake has been exposed to a variety of contaminants which are potentially endocrine-disrupting. Therefo...

  3. Polycystic ovary syndrome: do endocrine disrupting chemicals play a role?

    PubMed Central

    Barrett, Emily S.; Sobolewski, Marissa

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by multiple endocrine disturbances and its underlying causes, although uncertain, are likely to be both genetic and environmental. Recently, there has been interest in whether endocrine disrupting chemicals (EDCs) in the environment, particularly Bisphenol A (BPA), may contribute to the disorder. In animal models, exposure to BPA during the perinatal period, dramatically disrupts ovarian and reproductive function in females, often at doses similar to typical levels of human exposure. BPA also appears to have obesogenic properties, disrupting normal metabolic activity and making the body prone to overweight. In humans, cross-sectional data suggests that BPA concentrations are higher in women with PCOS than in reproductively healthy women, but the direction of causality has not been established. As this research is in its infancy, additional work is needed to understand the mechanisms by which EDCs may contribute to PCOS as well as the critical periods of exposure, which may even be transgenerational. Future research should also focus on translating the promising work in animal models into longitudinal human studies and determining whether additional EDCs, beyond BPA, may be important to consider. PMID:24715511

  4. Identification of endocrine disrupting chemicals acting on human aromatase.

    PubMed

    Baravalle, Roberta; Ciaramella, Alberto; Baj, Francesca; Di Nardo, Giovanna; Gilardi, Gianfranco

    2017-06-01

    Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represents a possible solution to identify potential endocrine disrupting chemicals. Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP(+) released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100μM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA. Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting

  5. Removal of endocrine disrupting compounds during conventional wastewater treatment.

    PubMed

    Kanda, R; Churchley, J

    2008-03-01

    There is evidence that aquatic organisms downstream of some sewage treatment works show endocrine disruption as a result of exposure to substances in the effluent. As a result, the Environment Agency of England and Wales, in collaboration with the UK Government and the water industry, has started an intensive programme to determine the fate and behaviour of endocrine disrupting compounds in sewage treatment works. Sampling sites for the endocrine disruption demonstration programme are located throughout England and Wales. This paper presents data from Nuneaton sewage treatment works (Warwickshire, England), a modem nitrifying activated sludge plant serving an equivalent population of 98,000 and one of the selected sites for the demonstration programme. Results for the 24-hour survey carried out in June 2006 in which manual grab samples were taken hourly show excellent removal of estrone, estradiol, nonyl-phenol and the nonylphenolethoxylates (3-5 EO units) at 97, 99, 94 and 98% respectively. They also show excellent removal (99%) of estrogenicity, measured by the YES bioassay. However the removal of ethynylestradiol was poor at only 3%. In November 2006, a further survey was carried out comprising grab samples taken at 4-hourly intervals across a continuous 7-day period. This monitoring confirmed the good removal of estrone and estradiol, at 97.8% and 96.3% respectively as well as an excellent reduction in estrogenicity (98.3%), but again showed poor removal of ethynylestradiol of 5.6%. There was evidence of a diurnal pattern for estrone and estradiol concentrations and to a lesser extent for ethynylestradiol in samples of crude sewage with works returns. Peak concentrations tended to occur at around midday.

  6. Occurrence of endocrine-disrupting chemicals in indoor dust

    PubMed Central

    Hwang, Hyun-Min; Park, Eun-Kee; Young, Thomas M.; Hammock, Bruce D.

    2010-01-01

    Human exposure to indoor dust enriched with endocrine-disrupting chemicals released from numerous indoor sources has been a focus of increasing concern. Longer residence times and elevated contaminant concentrations in the indoor environment may increase chances of exposure to these contaminants by 1000-fold compared to outdoor exposure. To investigate the occurrence of semi-volatile endocrine-disrupting chemicals, including PBDEs (polybrominated diphenyl ethers), PCBs (polychlorinated biphenyls), phthalates, pyrethroids, DDT (dichlorodiphenyltrichloroethane) and its metabolites, and chlordanes, indoor dust samples were collected from household vacuum cleaner bags provided by 10 apartments and 1 community hall in Davis, California, USA. Chemical analyses show that all indoor dust samples are highly contaminated by target analytes measured in the present study. Di-(2-ethylhexyl)phthalate was the most abundant (104–7630 μg/g) in all samples and higher than other target analytes by 2 to 6 orders of magnitude. PBDEs were also found at high concentrations (1780–25,200 ng/g). Although the use of PCBs has been banned or restricted for decades, some samples had PCBs at levels that are considered to be concerns for human health, indicating that the potential risk posed by PCBs still remains high in the indoor environment, probably due to a lack of dissipation processes and continuous release from the sources. Although the use of some PBDEs is being phased out in some parts of the U.S., this trend may apply to PBDEs as well. We can anticipate that exposure to PBDEs will continue as long as the general public keeps using existing household items such as sofas, mattresses, and carpets that contain PBDEs. This study provides additional information that indoor dust is highly contaminated by persistent and endocrine-disrupting chemicals. PMID:18632138

  7. Study on Photocatalytic Degradation of Endocrine Disrupting Compound

    NASA Astrophysics Data System (ADS)

    Pralhad Parihar, Bhagwan; Gupta, Smita; Chakraborty, Mousumi

    2017-07-01

    Propylparaben (PP) is catagorized as endocrine disrupting compounds and is found to be present in urban wastewater comparatively at high concentrations. In the present work, propylparaben was degraded photo-catalytically by optimizing different process parameters such as initial concentration of propylparaben (25mgL-1 to 100 mgL-1), pH of the feed phase and concentration of photocatalyst TiO2 (50 mgL-1 to 200 mgL-1). Finally PP degraded and converted to CO2 and H2O and the degradation was found to follow the first order kinetics.

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

    PubMed

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

    2003-08-01

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

  9. Biomarkers of endocrine disruption at the mRNA level

    SciTech Connect

    Denslow, N.D.; Bowman, C.J.; Robinson, G.; Lee, H.S.; Ferguson, R.J.; Hemmmer, M.J.; Folmar, L.C.

    1999-07-01

    A large number of estrogen-mimicking, anthropogenic chemicals capable of disrupting normal reproductive function have been identified. The ubiquitous distribution of these compounds, many as components of complex industrial or municipal waste, has spurred an effort to develop methods to screen for chemicals which disrupt normal endocrine regulation of reproduction. The authors have developed assays that both allow exposure of animals in vivo and measure the response at the level of gene activation. The authors have developed a probe for measuring the induction of vitellogenin mRNA by Northern Blot in livers of sheepshead minnows treated with 17-{beta}-estradiol. The authors have also developed a strategy for using Differential Display Polymerase Chain Reaction for determining gene induction profiles following exposure to estradiol. These methods should be adaptable to a variety of structurally diverse estrogen mimics.

  10. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals.

    PubMed Central

    Fox, Jennifer E; Starcevic, Marta; Jones, Phillip E; Burow, Matthew E; McLachlan, John A

    2004-01-01

    Some organochlorine pesticides and other synthetic chemicals mimic hormones in representatives of each vertebrate class, including mammals, reptiles, amphibians, birds, and fish. These compounds are called endocrine-disrupting chemicals (EDCs). Similarly, hormonelike signaling has also been observed when vertebrates are exposed to plant chemicals called phytoestrogens. Previous research has shown the mechanism of action for EDCs and phytoestrogens is as unintended ligands for the estrogen receptor (ER). Although pesticides have been synthesized to deter insects and weeds, plants produce phytoestrogens to deter herbivores, as attractant cues for insects, and as recruitment signals for symbiotic soil bacteria. Our data present the first evidence that some of the same organochlorine pesticides and EDCs known to disrupt endocrine signaling through ERs in exposed wildlife and humans also disrupt the phytoestrogen signaling that leguminous plants use to recruit Sinorhizobium meliloti soil bacteria for symbiotic nitrogen fixation. Here we report that a variety of EDCs and pesticides commonly found in agricultural soils interfere with the symbiotic signaling necessary for nitrogen fixation, suggesting that the principles underlying endocrine disruption may have more widespread biological and ecological importance than had once been thought. PMID:15121509

  11. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals.

    PubMed

    Fox, Jennifer E; Starcevic, Marta; Jones, Phillip E; Burow, Matthew E; McLachlan, John A

    2004-05-01

    Some organochlorine pesticides and other synthetic chemicals mimic hormones in representatives of each vertebrate class, including mammals, reptiles, amphibians, birds, and fish. These compounds are called endocrine-disrupting chemicals (EDCs). Similarly, hormonelike signaling has also been observed when vertebrates are exposed to plant chemicals called phytoestrogens. Previous research has shown the mechanism of action for EDCs and phytoestrogens is as unintended ligands for the estrogen receptor (ER). Although pesticides have been synthesized to deter insects and weeds, plants produce phytoestrogens to deter herbivores, as attractant cues for insects, and as recruitment signals for symbiotic soil bacteria. Our data present the first evidence that some of the same organochlorine pesticides and EDCs known to disrupt endocrine signaling through ERs in exposed wildlife and humans also disrupt the phytoestrogen signaling that leguminous plants use to recruit Sinorhizobium meliloti soil bacteria for symbiotic nitrogen fixation. Here we report that a variety of EDCs and pesticides commonly found in agricultural soils interfere with the symbiotic signaling necessary for nitrogen fixation, suggesting that the principles underlying endocrine disruption may have more widespread biological and ecological importance than had once been thought.

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

    EPA Pesticide Factsheets

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

  13. Steroid hormones as biomarkers of endocrine disruption in wildlife

    SciTech Connect

    Guillette, L.J. Jr.; Rooney, A.A.; Crain, D.A.; Orlando, E.F.

    1999-07-01

    Xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect the endocrine system of wildlife. Various species exhibit abnormalities of (1) plasma sex steroid hormones, (2) altered steroid synthesis form the gonad in vitro and (3) altered steroidogenic enzyme function. These endpoints are sensitive and relatively easy to measure quantitatively with reliability and precision. These observations have led to the conclusion that sex steroid hormones could be markers of exposure to, and altered function from, endocrine disrupting contaminants (EDCs). However, there are serious limitations in the use of steroid hormones as generalized markers of EDC exposure. Steroid hormones exhibit seasonal, ontogenetic, gender and species-specific variation. Moreover, the regulation of sex steroid plasma concentrations is a relatively complex phenomenon capable of short-term (minutes-hours) alteration due to environmental inputs, such as acute stress--an activational response. Alterations in steroids synthesis and degradation also can be a response to altered embryonic development due to EDC exposure--an organizational response. If steroid hormones are to be used as biomarkers, then closely controlled, well designed sampling has to be performed. Additionally, an appreciation of the variation possible in endocrine responses among the species to be studied must be obtained.

  14. Retinoid metabolism in invertebrates: when evolution meets endocrine disruption.

    PubMed

    André, A; Ruivo, R; Gesto, M; Castro, L Filipe C; Santos, M M

    2014-11-01

    Recent genomic and biochemical evidence in invertebrate species pushes back the origin of the retinoid metabolic and signaling modules to the last common ancestor of all bilaterians. However, the evolution of retinoid pathways are far from fully understood. In the majority of non-chordate invertebrate lineages, the ongoing functional characterization of retinoid-related genes (metabolism and signaling pathways), as well as the characterization of the endogenous retinoid content (precursors and active retinoids), is still incomplete. Despite limited, the available data supports the presence of biologically active retinoid pathways in invertebrates. Yet, the mechanisms controlling the spatial and temporal distribution of retinoids as well as their physiological significance share similarities and differences with vertebrates. For instance, retinol storage in the form of retinyl esters, a key feature for the maintenance of retinoid homeostatic balance in vertebrates, was only recently demonstrated in some mollusk species, suggesting that such ability is older than previously anticipated. In contrast, the enzymatic repertoire involved in this process is probably unlike that of vertebrates. The suggested ancestry of active retinoid pathways implies that many more metazoan species might be potential targets for endocrine disrupting chemicals. Here, we review the current knowledge about the occurrence and functionality of retinoid metabolic and signaling pathways in invertebrate lineages, paying special attention to the evolutionary origin of retinoid storage mechanisms. Additionally, we summarize existing information on the endocrine disruption of invertebrate retinoid modules by environmental chemicals. Research priorities in the field are highlighted. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Endocrine disruption of the epigenome: a breast cancer link

    PubMed Central

    Knower, Kevin C; To, Sarah Q; Leung, Yuet-Kin; Ho, Shuk-Mei; Clyne, Colin D

    2015-01-01

    The heritable component of breast cancer accounts for only a small proportion of total incidences. Environmental and lifestyle factors are therefore considered to among the major influencing components increasing breast cancer risk. Endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment. The estrogenic property of EDCs has thus shown many associations between ongoing exposures and the development of endocrine-related diseases, including breast cancer. The environment consists of a heterogenous population of EDCs and despite many identified modes of action, including that of altering the epigenome, drawing definitive correlations regarding breast cancer has been a point of much discussion. In this review, we describe in detail well-characterized EDCs and their actions in the environment, their ability to disrupt mammary gland formation in animal and human experimental models and their associations with exposure and breast cancer risk. We also highlight the susceptibility of early-life exposure to each EDC to mediate epigenetic alterations, and where possible describe how these epigenome changes influence breast cancer risk. PMID:24532474

  16. Endocrine disruption in crustaceans due to pollutants: a review.

    PubMed

    Rodríguez, Enrique M; Medesani, Daniel A; Fingerman, Milton

    2007-04-01

    The main endocrine-regulated processes of crustaceans have been reviewed in relation to the effects of endocrine-disrupting compounds (EDCs). Molting has been shown to be inhibited by several organic pollutants, such as xenoestrogens and related compounds, as well as by some pesticides. Most of these disrupters are thought to interfere with ecdysone at target tissues, although only for a few has this action been demonstrated in vitro. The heavy metal cadmium appears to inhibit some ecdysone secretion. Juvenoid compounds have also been shown to inhibit molting, likely by interfering with the stimulatory effect of methyl farnesoate. A molt-promoting effect of emamectin benzoate, a pesticide, has also been reported. As for reproduction, a variety of organic compounds, including xenoestrogens, juvenoids and ecdysteroids, has produced abnormal development of male and female secondary sexual characters, as well as alteration of the sex ratio. Cadmium and copper have been shown to interfere with hormones that stimulate reproduction, such as methyl farnesoate, as well as with secretion of the gonad inhibiting hormone, therefore affecting, for example, ovarian growth. Several heavy metals were able to produce hyperglycemia in crustaceans during short times of exposure; while a hypoglycemic response was noted after longer exposures, due to inhibition of secretion of the crustacean hyperglycemic hormone. The ecological relevance of EDCs on crustaceans is discussed, mainly in relation to the identification of useful biomarkers and sentinel species. New experimental approaches are also proposed.

  17. Behavior of Selected Endocrine Disrupting Chemicals in Sewage Treatment Plant

    NASA Astrophysics Data System (ADS)

    Wang, Xinze; Lu, Jiaming; Ollivier, Natacha; Saturnino, Anais; Gomez, Elena; Casellas, Claude; Picot, Bernadette

    2010-11-01

    The behavior of endocrine disrupting chemicals in sewage treatment plant affects their final fate in water environment. We selected six endocrine disrupting chemicals: 4 alkylphenols (4-tert-octylphenol, octylphenol, 4-nonylphenol, bisphenol A) and 2 steroids (17α-ethinylestradiol and estriol) as targets, their removal and transformation in wastewater treatment plant were studied. Five mixed liquors were sampled respectively from different stages of Minhang wastewater treatment plant in Shanghai. EDCs concentration were analyzed with GC-MS. The main removal pathways of EDCs include initial adsorption by suspended solids and following biodegradation in biological sludge. The removal efficiency of six targets was more than 86%. The concentration of OP and 4-n-NP in water significantly increased in anoxic stage, the reason may be the releases of EDCs from sludge to water on the condition of low DO. And it was also found that the EDCs could be released to water phase in the secondary clarifier, which may cause potential risk of EDCs entering the environment with discharge.

  18. Endocrine disruption of the epigenome: a breast cancer link.

    PubMed

    Knower, Kevin C; To, Sarah Q; Leung, Yuet-Kin; Ho, Shuk-Mei; Clyne, Colin D

    2014-04-01

    The heritable component of breast cancer accounts for only a small proportion of total incidences. Environmental and lifestyle factors are therefore considered to among the major influencing components increasing breast cancer risk. Endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment. The estrogenic property of EDCs has thus shown many associations between ongoing exposures and the development of endocrine-related diseases, including breast cancer. The environment consists of a heterogenous population of EDCs and despite many identified modes of action, including that of altering the epigenome, drawing definitive correlations regarding breast cancer has been a point of much discussion. In this review, we describe in detail well-characterized EDCs and their actions in the environment, their ability to disrupt mammary gland formation in animal and human experimental models and their associations with exposure and breast cancer risk. We also highlight the susceptibility of early-life exposure to each EDC to mediate epigenetic alterations, and where possible describe how these epigenome changes influence breast cancer risk.

  19. Thyroid endocrine disruption of acetochlor on zebrafish (Danio rerio) larvae.

    PubMed

    Yang, Mei; Hu, Jingjin; Li, Shuying; Ma, Youning; Gui, Wenjun; Zhu, Guonian

    2016-06-01

    The herbicide acetochlor is widely used and detected in the environment and biota, and has been suspected to disrupt the thyroid endocrine system, but underlying mechanisms have not yet been clarified. In the present study, zebrafish larvae (7 days post-fertilization) were exposed to a series concentration of acetochlor (0, 1, 3, 10, 30, 100 and 300 µg l(-1) ) within a 14-day window until 21 days post-fertilization. Thyroid hormones and mRNA expression profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. Exposure to the positive control, 3,5,3'-triiodothyronine (T3 ), altered the mRNA expression, suggesting that the HPT axis in the critical window of zebrafish responded to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. The mRNA expressions of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tpo) were upregulated significantly with acetochlor treatment, which might be responsible for the increased thyroxine concentrations. The downregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) and transport (ttr) in zebrafish larvae exposed to acetochlor might further explain the increased thyroxine levels and decreased T3 levels. The mRNA expression of the thyroid hormone receptor (trα) was also upregulated upon acetochlor exposure. Results suggested that acetochlor altered mRNA expression of the HPT axis-related genes and changed the whole body thyroid hormone levels in zebrafish larvae. It demonstrated that acetochlor could cause endocrine disruption of the thyroid system by simulating the biological activity of T3 . Copyright © 2015 John Wiley & Sons, Ltd.

  20. Evaluation of Water Treatment Methods for Endocrine Disrupting Compounds

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

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

  1. RESEARCH ON ENDOCRINE DISRUPTERS IN THE AQUATIC ENVIRONMENT BY THE UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

    EPA Science Inventory

    Research on Endocrine Disrupters in the Aquatic Environment by the United States Environmental Protection Agency (Abstract). Presented at the Endocrine Disrupters Workshop sponsored by the UK Department of Environment, Food and Rural Affairs, 8-9 September 2001, Weymouth, UK. 1 p...

  2. [The concept of endocrine disruption and human health].

    PubMed

    Cravedi, Jean-Pierre; Zalko, Daniel; Savouret, Jean-François; Menuet, Arnaud; Jégou, Bernard

    2007-02-01

    state of knowledge about endocrine disruption, focusing in particular on the problem of food contaminants.

  3. Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network.

    PubMed

    Mueller, Johanna K; Heger, Sabine

    2014-04-01

    Endocrine disrupting chemicals have been shown to alter the pubertal process. The controlling levels of the Gonadotropin releasing hormone (GnRH) network involve GnRH itself, KiSS1, and the transcriptional regulators enhanced at puberty 1 (EAP1), Thyroid Transcription Factor 1 (TTF1), and Yin Yang 1 (YY1). While Genistein and Bisphenol A (BPA) have been shown to advance the advent of puberty, exposure to Dioxin delayed pubertal onset. Utilizing in vitro approaches, we observed that Genistein and BPA suppress inhibitory and activate stimulatory components of the GnRH network, while Dioxin exhibit an inhibitory effect at all regulatory hierarchical levels of the GnRH network. It repressed KiSS1, Gnrh, Ttf1 and Yy1 transcription via the xenobiotic response element (XRE), while EAP1 was not affected. Therefore, EDCs alter the neuroendocrine GnRH regulatory network at all hierarchical levels.

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

    PubMed

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

    2014-08-30

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

  5. Exposure to Endocrine Disrupting Chemicals and Male Reproductive Health

    PubMed Central

    Jeng, Hueiwang Anna

    2014-01-01

    Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs. PMID:24926476

  6. Environmental exposure to endocrine-disrupting chemicals and miscarriage.

    PubMed

    Krieg, Sacha A; Shahine, Lora K; Lathi, Ruth B

    2016-09-15

    Establishment of early pregnancy is the result of complex biochemical interactions between the decidua and blastocyst. Any alteration in this chemical dialogue has the potential to result in adverse pregnancy outcomes including miscarriage. Sporadic miscarriage is the most common complication of pregnancy and can be caused by multiple factors. While the most common cause of miscarriage is genetic abnormalities in the fetus, other contributing factors certainly can play a role in early loss. One such factor is environmental exposure, in particular to endocrine-disrupting chemicals, which has the potential to interfere with endogenous hormone action. These effects can be deleterious, especially in early pregnancy when the hormonal milieu surrounding implantation is in delicate balance. The purpose of this paper is to review the current evidence on the role of environmental toxins in reproduction.

  7. THE ESTROGENIC ENDOCRINE DISRUPTING CHEMICAL BISPHENOL A (BPA) AND OBESITY

    PubMed Central

    vom Saal, Frederick S.; Nagel, Susan C.; Coe, Benjamin L.; Angle, Brittany M.; Taylor, Julia A.

    2012-01-01

    There is increasing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent increase in adult obesity and other components of metabolic syndrome. In particular, there is evidence that epigenetic changes associated with the use of manmade chemicals may interact with other factors that influence fetal and postnatal growth in contributing to the current obesity epidemic. The focus of this review is on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA), on adipocytes and their function, and the ultimate impact on adult obesity; BPA exposure also results in impaired reproductive capacity. We discuss the interaction of EDCs with other factors that impact growth during fetal and neonatal life, such as placental blood flow and nutrient transport to fetuses, and how these influence fetal growth and abnormalities in homeostatic control systems required to maintain normal body weight throughout life. PMID:22249005

  8. Endocrine disrupting properties of perfluorooctanoic acid☆,☆☆

    PubMed Central

    White, Sally S.; Fenton, Suzanne E.; Hines, Erin P.

    2012-01-01

    Perfluoroalkyl acids (PFAAs) have attracted attention in recent years for their environmental ubiquity, as well as their toxicity. Several PFAAs are found in human tissues globally, as humans are exposed on a daily basis through intake of contaminated food, water, and air, irrespective of proximity to industry. Perfluorooctanoic acid (PFOA) is a PFAA shown to be developmentally toxic in mice, with broad and varied health consequences that may include long-lasting effects in reproductive tissues and metabolic reprogramming. To date, the only demonstrated mode of action by which the health effects of PFOA are mediated is via the activation of the peroxisome proliferator-activated receptor alpha (PPARα). The endogenous roles for this receptor, as well as the adverse outcomes of activation by exogenous agents during development, are currently under investigation. Recent studies suggest that PFOA may alter steroid hormone production or act indirectly, via ovarian effects, as a novel means of endocrine disruption. Here we review the existing literature on the known health effects of PFOA in animal models, focusing on sensitive developmental periods. To complement this, we also present epidemiologic health data, with the caveat that these studies largely address only associations between adult exposures and outcomes, rarely focusing on endocrine-specific endpoints, susceptible subpopulations, or windows of sensitivity. Further research in these areas is needed. PMID:21397692

  9. Endocrine disruption of oestrogen action and female reproductive tract cancers.

    PubMed

    Gibson, Douglas A; Saunders, Philippa T K

    2014-04-01

    Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.

  10. Effects of Endocrine-Disrupting Chemicals on the Ovary.

    PubMed

    Patel, Shreya; Zhou, Changqing; Rattan, Saniya; Flaws, Jodi A

    2015-07-01

    Endocrine-disrupting chemicals (EDCs) are found abundantly in the environment, resulting in daily human exposure. This is of concern because many EDCs are known to target the female reproductive system and, more specifically, the ovary. In the female, the ovary is the key organ responsible for reproductive and endocrine functions. Exposure to EDCs is known to cause many reproductive health problems such as infertility, premature ovarian failure, and abnormal sex steroid hormone levels. Some EDCs and their effects on adult ovarian function have been studied extensively over the years, whereas the effects of others remain unclear. This review covers what is currently known about the effects of selected EDCs (bisphenol A, methoxychlor, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phthalates, and genistein) on the adult ovary and the mechanisms by which they act upon the ovary, focusing primarily on their effects on folliculogenesis and steroidogenesis. Furthermore, this review discusses future directions needed to better understand the effects of EDCs, including the need to examine the effects of multiple and more consistent doses and to study different mechanisms of action. © 2015 by the Society for the Study of Reproduction, Inc.

  11. Impedance Measurements as a Tool for the Detection of Endocrine Disrupting Chemicals

    DTIC Science & Technology

    2007-11-02

    endocrine disruptors on human health has created a need for screening systems to detect xenoestrogens, a diverse group of chemicals that mimic...Impedance Measurements as a Tool for the Detection of Endocrine Disrupting Chemicals V. Sacks, J. Rishpon* Department of Molecular...sensitive and amenable to use on-site, providing an efficient and economic tool for measuring minuscule amounts of endocrine disrupting chemicals

  12. Endocrine disrupting chemicals in indoor and outdoor air.

    PubMed

    Rudel, Ruthann A; Perovich, Laura J

    2009-01-01

    The past 50 years have seen rapid development of new building materials, furnishings, and consumer products and a corresponding explosion in new chemicals in the built environment. While exposure levels are largely undocumented, they are likely to have increased as a wider variety of chemicals came into use, people began spending more time indoors, and air exchange rates decreased to improve energy efficiency. As a result of weak regulatory requirements for chemical safety testing, only limited toxicity data are available for these chemicals. Over the past 15 years, some chemical classes commonly used in building materials, furnishings, and consumer products have been shown to be endocrine disrupting chemicals-that is they interfere with the action of endogenous hormones. These include PCBs, used in electrical equipment, caulking, paints and surface coatings; chlorinated and brominated flame retardants, used in electronics, furniture, and textiles; pesticides, used to control insects, weeds, and other pests in agriculture, lawn maintenance, and the built environment; phthalates, used in vinyl, plastics, fragrances, and other products; alkylphenols, used in detergents, pesticide formulations, and polystyrene plastics; and parabens, used to preserve products like lotions and sunscreens. This paper summarizes reported indoor and outdoor air concentrations, chemical use and sources, and toxicity data for each of these chemical classes. While industrial and transportation-related pollutants have been shown to migrate indoors from outdoor sources, it is expected that indoor sources predominate for these consumer product chemicals; and some studies have identified indoor sources as the predominant factor influencing outdoor ambient air concentrations in densely populated areas. Mechanisms of action, adverse effects, and dose-response relationships for many of these chemicals are poorly understood and no systematic screening of common chemicals for endocrine disrupting

  13. Endocrine disrupting chemicals in indoor and outdoor air

    NASA Astrophysics Data System (ADS)

    Rudel, Ruthann A.; Perovich, Laura J.

    The past 50 years have seen rapid development of new building materials, furnishings, and consumer products and a corresponding explosion in new chemicals in the built environment. While exposure levels are largely undocumented, they are likely to have increased as a wider variety of chemicals came into use, people began spending more time indoors, and air exchange rates decreased to improve energy efficiency. As a result of weak regulatory requirements for chemical safety testing, only limited toxicity data are available for these chemicals. Over the past 15 years, some chemical classes commonly used in building materials, furnishings, and consumer products have been shown to be endocrine disrupting chemicals - that is they interfere with the action of endogenous hormones. These include PCBs, used in electrical equipment, caulking, paints and surface coatings; chlorinated and brominated flame retardants, used in electronics, furniture, and textiles; pesticides, used to control insects, weeds, and other pests in agriculture, lawn maintenance, and the built environment; phthalates, used in vinyl, plastics, fragrances, and other products; alkylphenols, used in detergents, pesticide formulations, and polystyrene plastics; and parabens, used to preserve products like lotions and sunscreens. This paper summarizes reported indoor and outdoor air concentrations, chemical use and sources, and toxicity data for each of these chemical classes. While industrial and transportation-related pollutants have been shown to migrate indoors from outdoor sources, it is expected that indoor sources predominate for these consumer product chemicals; and some studies have identified indoor sources as the predominant factor influencing outdoor ambient air concentrations in densely populated areas. Mechanisms of action, adverse effects, and dose-response relationships for many of these chemicals are poorly understood and no systematic screening of common chemicals for endocrine disrupting

  14. Endocrine disrupting chemicals in indoor and outdoor air

    PubMed Central

    Rudel, Ruthann A.; Perovich, Laura J.

    2009-01-01

    The past 50 years have seen rapid development of new building materials, furnishings, and consumer products and a corresponding explosion in new chemicals in the built environment. While exposure levels are largely undocumented, they are likely to have increased as a wider variety of chemicals came into use, people began spending more time indoors, and air exchange rates decreased to improve energy efficiency. As a result of weak regulatory requirements for chemical safety testing, only limited toxicity data are available for these chemicals. Over the past 15 years, some chemical classes commonly used in building materials, furnishings, and consumer products have been shown to be endocrine disrupting chemicals—that is they interfere with the action of endogenous hormones. These include PCBs, used in electrical equipment, caulking, paints and surface coatings; chlorinated and brominated flame retardants, used in electronics, furniture, and textiles; pesticides, used to control insects, weeds, and other pests in agriculture, lawn maintenance, and the built environment; phthalates, used in vinyl, plastics, fragrances, and other products; alkylphenols, used in detergents, pesticide formulations, and polystyrene plastics; and parabens, used to preserve products like lotions and sunscreens. This paper summarizes reported indoor and outdoor air concentrations, chemical use and sources, and toxicity data for each of these chemical classes. While industrial and transportation-related pollutants have been shown to migrate indoors from outdoor sources, it is expected that indoor sources predominate for these consumer product chemicals; and some studies have identified indoor sources as the predominant factor influencing outdoor ambient air concentrations in densely populated areas. Mechanisms of action, adverse effects, and dose-response relationships for many of these chemicals are poorly understood and no systematic screening of common chemicals for endocrine disrupting

  15. Thyroid endocrine disruption of azocyclotin to Xenopus laevis during metamorphosis.

    PubMed

    Li, Meng; Cao, Chuyan; Li, Shuying; Gui, Wenjun; Zhu, Guonian

    2016-04-01

    Organotin compounds are ubiquitous contaminants that are frequently detected in the environment and in biota, which raises concern about their risk to wildlife and human health. In the present study, Nieuwkoop & Faber stage 51 Xenopus laevis tadpoles were exposed to different concentrations of azocyclotin (0, 0.02, 0.1 and 0.5μg/L) for 21 days, during which time the tadpoles underwent morphological development. Exposure to azocyclotin caused an inhibitory effect on the pre-metamorphic development of X. laevis (e.g., a shortened hind limb length). Azocyclotin induced an alteration of the triiodothyronine (T3) content, which indicated thyroid endocrine disruption. Real-time PCR was performed to examine the expression levels of the genes involved in the thyroid hormone (TH) signaling pathway. Significant down-regulation of the type 2 deiodinase gene was observed, which may be partially responsible for the decreased T3 concentrations. Furthermore, the expression of T3 responsive genes, including thyroid hormone receptor, basic transcription element binding protein, 2tromelysins-3 and matrix metalloproteinase 2, were down-regulated in tadpoles, suggesting that azocyclotin induced a decrease in the T3 contents and, in turn, affected the mRNA expression of downstream genes involved in multiple physiological responses. Chemical analysis showed that azocyclotin could accumulate in X. laevis after 21 days of exposure. In conclusion, the results of the present study showed that azocyclotin could alter the mRNA expression of genes involved in TH signaling as well as the thyroid hormone concentrations in X. laevis tadpoles, leading to endocrine disruption of thyroid system, and that azocyclotin had obvious inhibitory effects on X. laevis metamorphosis.

  16. Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and ...

  17. SCREENING CALIFORNIA SURFACE WATERS FOR ESTROGENIC ENDOCRINE DISRUPTING CHEMICALS (EEDC) WITH A JUVENILE RAINBOW TROUT LIVER VITELLOGENIN MRNA PROCEDURE

    EPA Science Inventory

    Concern regarding the occurrence of chemicals that disrupt endocrine system functions in aquatic species has heightened over the last 15 years. However, little attention has been given to monitoring for estrogenic endocrine disrupting chemicals (EEDCs) in California's freshwater ...

  18. Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and ...

  19. SCREENING CALIFORNIA SURFACE WATERS FOR ESTROGENIC ENDOCRINE DISRUPTING CHEMICALS (EEDC) WITH A JUVENILE RAINBOW TROUT LIVER VITELLOGENIN MRNA PROCEDURE

    EPA Science Inventory

    Concern regarding the occurrence of chemicals that disrupt endocrine system functions in aquatic species has heightened over the last 15 years. However, little attention has been given to monitoring for estrogenic endocrine disrupting chemicals (EEDCs) in California's freshwater ...

  20. Bisphenol A, an endocrine-disrupting chemical, and brain development.

    PubMed

    Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2012-08-01

    Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in various industries and the field of dentistry. The consequent increase in BPA exposure among humans has led us to some concerns regarding the potential deleterious effects on reproduction and brain development. The emphasis of this review is on the effects of prenatal and lactational exposure to low doses of BPA on brain development in mice. We demonstrated that prenatal exposure to BPA affected fetal murine neocortical development by accelerating neuronal differentiation/migration during the early embryonic stage, which was associated with up- and down-regulation of the genes critical for brain development, including the basic helix-loop-helix transcription factors. In the adult mice brains, both abnormal neocortical architecture and abnormal corticothalamic projections persisted in the group exposed to the BPA. Functionally, BPA exposure disturbed murine behavior, accompanied with a disrupted neurotransmitter system, including monoamines, in the postnatal development period and in adult mice. We also demonstrated that epigenetic alterations in promoter-associated CpG islands might underlie some of the effects on brain development after exposure to BPA. © 2012 Japanese Society of Neuropathology.

  1. Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

    USGS Publications Warehouse

    Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

    2001-01-01

    Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

  2. In vitro profiling of endocrine disrupting effects of phenols.

    PubMed

    Li, Jian; Ma, Mei; Wang, Zijian

    2010-02-01

    Some phenols have been suspected to modulate the endocrine systems of wildlife and humans, but less is known about their interactions with different types of nuclear receptors. In this study, the ability of 2-tert-butylphenol, 2-isopropylphenol, 4-tert-octylphenol (4-t-OP), 2,4-dichlorophenol (2,4-DCP), 3,4-dichlorophenol (3,4-DCP), pentachlorophenol (PCP), bisphenols A (BPA), tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA) and 4-phenylphenol to activate estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR) and estrogen-related receptor (ERR) were determined using a set of recombined yeast strains. It was found that 4-t-OP, 3,4-DCP, PCP, BPA, TBBPA, TCBPA and 4-phenylphenol were ERalpha agonists, while 4-t-OP, PCP and 4-phenylphenol showed ERalpha antagonistic activities. 2-tert-Butylphenol, 4-t-OP, 2-isopropylphenol, 2,4-DCP, 3,4-DCP, BPA, TCBPA and 4-phenylphenol were antagonists for AR, whereas none of the compounds studied were found to be an AR agonist. TCBPA, TBBPA and PCP were PR antagonists, and 2-tert-butylphenol, 3,4-DCP, 4-t-OP, 4-phenylphenol and 2-isopropylphenol were weak inhibitors on expression under control of the PR. None of the phenols were PR agonists. 2-tert-Butylphenol, 4-t-OP and PCP were ERRgamma inverse agonists, while 2,4-DCP, 3,4-DCP, PCP, BPA, TBBPA and TCBPA exhibited the ability to reverse the ERR inhibition induced by 4-hydroxytamoxifen. Based on the functional agonistic or antagonistic receptor-mediated effects, we further discussed the possible action mechanisms of these phenols as endocrine disrupting chemicals.

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

    PubMed

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

    2004-05-01

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

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

    PubMed

    Falconer, Ian R

    2006-06-01

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

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

    PubMed Central

    Falconer, Ian R.

    2006-01-01

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

  6. Methodological issues in human studies of endocrine disrupting chemicals.

    PubMed

    Lee, Duk-Hee; Jacobs, David R

    2015-12-01

    Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non-existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half-lives among populations with a relatively low

  7. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.

    PubMed

    Gore, A C; Chappell, V A; Fenton, S E; Flaws, J A; Nadal, A; Prins, G S; Toppari, J; Zoeller, R T

    2015-12-01

    The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence

  8. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    PubMed Central

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans—especially during development—may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the

  9. Endocrine disrupters: the new players able to affect the epigenome

    PubMed Central

    Casati, Lavinia; Sendra, Ramon; Sibilia, Valeria; Celotti, Fabio

    2015-01-01

    Epigenetics represents the way by which the environment is able to program the genome; there are three main levels of epigenetic control on genome: DNA methylation, post-translational histone modification and microRNA expression. The term Epigenetics has been widened by NIH to include “both heritable changes in gene activity and expression but also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable.” These changes might be produced mostly by the early life environment and might affect health influencing the susceptibility to develop diseases, from cancer to mental disorder, during the entire life span. The most studied environmental influences acting on epigenome are diet, infections, wasting, child care, smoking and environmental pollutants, in particular endocrine disrupters (EDs). These are environmental xenobiotics able to interfere with the normal development of the male and female reproductive systems of wildlife, of experimental animals and possibly of humans, disrupting the normal reproductive functions. Data from literature indicate that EDs can act at different levels of epigenetic control, in some cases transgenerationally, in particular when the exposure to these compounds occurs during the prenatal and earliest period of life. Some of the best characterized EDs will be considered in this review. Among the EDs, vinclozolin (VZ), and methoxychlor (MXC) promote epigenetic transgenerational effects. Polychlorinated biphenils (PCBs), the most widespread environmental EDs, affect histone post-translational modifications in a dimorphic way, possibly as the result of an alteration of gene expression of the enzymes involved in histone modification, as the demethylase Jarid1b, an enzyme also involved in regulating the interaction of androgens with their receptor. PMID:26151052

  10. Thyroid endocrine disruption and external body morphology of Zebrafish

    USGS Publications Warehouse

    Sharma, Prakash; Grabowski, Timothy B.; Patino, Reynaldo

    2016-01-01

    This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15 mM)], combination of MZ (0.15 mM) and thyroxine (T4, 2 nM), T4 (2 nM), or control (reconstituted water) treatments until 33 dpf and subsequently maintained in reconstituted water until 45 dpf. Samples were taken at 33 and 45 dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45 dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45 dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45 dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45 dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45 dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects.

  11. Sorption of selected endocrine disrupting chemicals to different aquatic colloids.

    PubMed

    Zhou, J L; Liu, R; Wilding, A; Hibberd, A

    2007-01-01

    The sorption of seven endocrine disrupting chemicals (EDCs) to aquatic colloids was determined by cross-flow ultrafiltration (CFUF) followed by gas chromatography-mass spectrometry (GC-MS). Results show that the colloidal organic carbon normalized sorption coefficient (Kcoc) of EDCs to different aquatic colloids varies by a factor of 6-12 because such colloids are of different origin. Through characterization of colloidal samples, a significant relationship was established between Kcoc values and the molar extinction coefficient of colloids at 280 nm, whereas no other colloidal properties such as elemental ratios were correlated with Kcoc values. The results are consistent with other reports of the importance of the quality of sorbents such as their aromatic carbon content in sorbing various organic pollutants. The presence of a surfactant was found to increase Kcoc values for estrone (El) and 17alpha-ethynylestradiol (EE2). The method was subsequently applied for determining EDC concentrations in field samples, where both conventional and truly dissolved EDCs showed higher concentrations close to sewage outfalls than either upstream or downstream, confirming the sourceconcentration relationship. In addition, the truly dissolved EDC concentrations were lower than the conventional dissolved concentrations, confirming that there were interactions between aquatic colloids and EDCs. It is estimated that between 10 and 29% of EDCs are associated with aquatic colloids. As colloids are highly abundant in rivers and ocean, they will therefore play a significant role in the environmental behavior and fate of EDCs.

  12. Growth as a mirror: Is endocrine disruption challenging Tanner's concept?

    PubMed Central

    Schell, Lawrence M.; Burnitz, Kristopher K.; Gallo, Mia V.

    2012-01-01

    Background James Tanner coined the expression `Growth as a Mirror' and summarized in four words the results of more than a century of research on growth. Nineteenth century social reformers saw poor child growth as a reflection of terrible environmental conditions of the working class. Later investigators in anthropology and other fields clarified the connections between poor nutrition, disease, psychosocial stress and poor growth. Aim To evaluate the growth as a mirror concept in light of recent studies of endocrine disruption. Papers and Implications Pollution is recognized as a prominent component of the modern environment. From studies of many pollutants it is clear that some pollutants depress growth while others speed sexual maturation and increase growth, primarily in weight and fatness. While such unwelcome environmental features do not always suppress growth, growth still mirrors the environment in all its complexity and this relationship is key to understanding growth patterns today. For example, Akwesasne Mohawk adolescents are characterized by high rates of obesity and overweight. Their growth reflects the multiple intersecting influences of psychosocial stress, several pollutant exposures and limited dietary chokes. Conclusion Although Tanner did not anticipate the myriad influences of pollutants, the growth as a mirror concept continues to have great validity and utility. PMID:22780455

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

    PubMed

    Rissman, Emilie F; Adli, Mazhar

    2014-08-01

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

  14. Mate choice, sexual selection, and endocrine-disrupting chemicals.

    PubMed

    Gore, Andrea C; Holley, Amanda M; Crews, David

    2017-09-11

    Humans have disproportionately affected the habitat and survival of species through environmental contamination. Important among these anthropogenic influences is the proliferation of organic chemicals, some of which perturb hormone systems, the latter referred to as endocrine-disrupting chemicals (EDCs). EDCs are widespread in the environment and affect all levels of reproduction, including development of reproductive organs, hormone release and regulation through the life cycle, the development of secondary sexual characteristics, and the maturation and maintenance of adult physiology and behavior. However, what is not well-known is how the confluence of EDC actions on the manifestation of morphological and behavioral sexual traits influences mate choice, a process that requires the reciprocal evaluation of and/or acceptance of a sexual partner. Moreover, the outcomes of EDC-induced perturbations are likely to influence sexual selection; yet this has rarely been directly tested. Here, we provide background on the development and manifestation of sexual traits, reproductive competence, and the neurobiology of sexual behavior, and evidence for their perturbation by EDCs. Selection acts on individuals, with the consequences manifest in populations, and we discuss the implications for EDC contamination of these processes, and the future of species. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Intercalibration exercise using a stickleback endocrine disrupter screening assay.

    PubMed

    Allen, Yvonne T; Katsiadaki, Ioanna; Pottinger, Tom G; Jolly, Cecile; Matthiessen, Peter; Mayer, Ian; Smith, Andy; Scott, Alexander P; Eccles, Paul; Sanders, Matthew B; Pulman, Kim G T; Feist, Stephen

    2008-02-01

    The Organisation for Economic Cooperation and Development (OECD) is currently validating a short-term fish screening protocol for endocrine disrupters (estrogens, androgens, and their antagonists and aromatase inhibitors), using three core species: fathead minnow, Japanese medaka, and zebrafish. The main endpoints proposed for the first phase of validation of the screen are vitellogenin (VTG) concentration, gross morphology (secondary sexual characteristics and gonado-somatic index), and gonadal histopathology. A similar protocol is concurrently being developed in the United Kingdom using the three-spined stickleback, with identical endpoints to those for the core species and, in addition, a unique androgen-specific endpoint in the form of spiggin (glue protein) induction. To assess the suitability of this species for inclusion in the OECD protocol alongside the core species, an intercalibration was conducted using 17beta-estradiol (a natural estrogen) and trenbolone (a synthetic androgen), thus mimicking a previous intercalibration with the core species. All three participating laboratories detected statistically significant increases in VTG in males after 14 d exposure to nominal concentrations of 100 ng/L 17beta-estradiol and statistically significant increases in spiggin in females after 14 d exposure to nominal concentrations of 5,000 ng/L trenbolone. The stickleback screen is reliable, possessing both relevant and reproducible endpoints for the detection of potent estrogens and androgens. Further work is underway to assess the relevance and suitability of the screen for weakly acting estrogens, anti-androgens, and aromatase inhibitors.

  16. Enantioselective separation of defined endocrine-disrupting nonylphenol isomers.

    PubMed

    Acir, Ismail-Hakki; Wüst, Matthias; Guenther, Klaus

    2016-08-01

    Nonylphenol is in the focus of worldwide endocrine-disrupter research and accounted for as a priority hazardous substance of the Water Framework Directive of the European Union. Technical nonylphenol consists of a very complex mixture of isomers and enantiomers. As estrogenic effect and degradation behavior in environmental processes of single nonylphenols are heavily dependent on the structure of the nonyl side chain, it is absolutely necessary to consider the nonylphenol problem from an isomer and enantiomer-specific viewpoint. In this study, an enantiomer-specific separation of eight defined synthesized nonylphenol isomers by five different special chiral cyclodextrin columns was performed underivatized and after methylation, silylation, and acylation. This work demonstrates that three columns out of the investigated five show an excellent separation behavior for the studied different nonylphenol isomers and can be used for the enantiomer-specific determination of nonylphenols in food, other biological matrices, and environmental samples in the future. Graphical abstract Enantiomeric pair of 4-NP170 (4-[1-ethyl-1,3,3-trimethylbutyl]phenol).

  17. Endocrine basis for disruptive effects of cortisol on preovulatory events.

    PubMed

    Breen, Kellie M; Billings, Heather J; Wagenmaker, Elizabeth R; Wessinger, Emily W; Karsch, Fred J

    2005-04-01

    Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently inhibits gonadotropin secretion and disrupts ovarian cyclicity. Here we tested the hypothesis that stress-like concentrations of cortisol interfere with follicular phase endocrine events of the ewe by suppressing pulsatile LH secretion, which is essential for subsequent steps in the preovulatory sequence. Cortisol was infused during the early to midfollicular phase, elevating plasma cortisol concentrations to one third, one half, or the maximal value induced by isolation, a commonly used model of psychosocial stress. All cortisol treatments compromised at least some aspect of reproductive hormone secretion in follicular phase ewes. First, cortisol significantly suppressed LH pulse frequency by as much as 35%, thus attenuating the high frequency LH pulses typical of the preovulatory period. Second, cortisol interfered with timely generation of the follicular phase estradiol rise, either preventing it or delaying the estradiol peak by as much as 20 h. Third, cortisol delayed or blocked the preovulatory LH and FSH surges. Collectively, our findings support the hypothesis that stress-like increments in plasma cortisol interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges. Moreover, the suppression of LH pulse frequency provides indirect evidence that cortisol acts centrally to suppress pulsatile GnRH secretion in follicular-phase ewes.

  18. Toxicogenomics and ecotoxicogenomics for studying endocrine disruption and basic biology.

    PubMed

    Iguchi, Taisen; Watanabe, Hajime; Katsu, Yoshinao

    2007-01-01

    Chemicals released into the environment have the potential to disrupt the endocrine system in wild animals, mouse, and humans. To understand molecular mechanisms of chemical toxicity in various species, toxicogenomics/ecotoxicogenomics, describing the integration of genomics (trascriptomics, proteomics and metabolomics) into toxicology/ecotoxicology, needs to be established as a powerful tool for research. Ecotoxicogenomics is defined as the study of gene and protein expression in non-target organisms that is important in responses to environmental toxicant exposures. Estrogen-responsive genes and estrogen response element(s) in genes have been identified in the mouse reproductive tract by application of cDNA microarray technology. Additionally, functional mechanisms of tributyltin action via nuclear receptors such as retinoid X receptor alpha and peroxisome proliferator activated receptor gamma also have been identified using cDNA microarray. A microarray system has been established for Daphnia magna. Toxicogenomics/ecotoxicogenomics provide powerful tools to help us understand not only molecular mechanisms of chemical toxicity but also the basic biology of various animal species.

  19. Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

    PubMed Central

    Colborn, T; vom Saal, F S; Soto, A M

    1993-01-01

    Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans. PMID:8080506

  20. ENDOCRINE DISRUPTING CHEMICAL EMISSIONS FROM COMBUSTION SOURCES: DIESEL PARTICULATE EMISSIONS AND DOMESTIC WASTE OPEN BURN EMISSIONS

    EPA Science Inventory

    Emissions of endocrine disrupting chemicals (EDCs) from combustion sources are poorly characterized due to the large number of compounds present in the emissions, the complexity of the analytical separations required, and the uncertainty regarding identification of chemicals with...

  1. EFFECTIVE RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    The conventional drinking water treamtent processes of coagulation, flocculation, and filtration as well as specialized treatment processes have been examined for their capacity to remove endocrine disrupting chemicals (EDCs). A groupf od EDCs including 4-nonylphenol, diethylphth...

  2. Endocrine disrupting pesticides: a leading cause of cancer among rural people in Pakistan.

    PubMed

    Ejaz, Sohail; Akram, Waseem; Lim, Chae Woong; Lee, Jong Jin; Hussain, Imtiaz

    2004-06-01

    Evidence on the relationship between cancer and occupational exposure to pesticides and endocrine disrupting chemicals is reviewed. In animal studies it has been proved that majority of endocrine disrupting pesticides are carcinogenic. In humans, pesticides have been classified as carcinogens by the International Agency for Research on Cancer. Farmers may therefore be at higher risk for acute and chronic health effects associated with pesticides. Human data, however, are limited by the small number of studies that evaluate individual endocrine disrupting pesticide. Cancer of the breast, ovary, prostate, testis, and thyroid are hormone-dependent, which fostered research on the potential risk associated with occupational and environmental exposure to the so-called endocrine-disrupting pesticides. Professional as well as public exposure to pesticides raises cancer risk. Interaction with adjuvant and with other toxicants increases the actual risk. On the other hand, organochlorine pesticides and triazine herbicides require further investigation for a possible etiologic role in some hormone-dependent cancers.

  3. ENDOCRINE DISRUPTING CHEMICAL RISK MANAGEMENT RESEARCH IN THE US EPA'S OFFICE OF RESEARCH AND DEVELOPMENT

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are receiving increasing media and scientific attention. Concerns about these chemicals stem from the possibility of serious human and wildlife effects and environmental persistence. The US EPA Office of Research and Development's National ...

  4. Genotyping Sex in Fathead Minnows, Pimephales promelas, for Use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. Dete...

  5. EFFECTIVE RISK MANAGEMENT OF ENDOCRINE DISRUPTING CHEMICALS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    The conventional drinking water treamtent processes of coagulation, flocculation, and filtration as well as specialized treatment processes have been examined for their capacity to remove endocrine disrupting chemicals (EDCs). A groupf od EDCs including 4-nonylphenol, diethylphth...

  6. Genotyping Sex in Fathead Minnows, Pimephales promelas, for Use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. Dete...

  7. Webinar Presentation: Metals, Endocrine Disrupting Chemicals and Biomarkers of Metabolic Syndrome Risk in Adolescence

    EPA Pesticide Factsheets

    This presentation, Metals, Endocrine Disrupting Chemicals and Biomarkers of Metabolic Syndrome Risk in Adolescence, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series held on Feb. 11, 2015.

  8. Development of Methods of Genotyping Sex for use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. De...

  9. Removal of Selected Endocrine Disrupting Chemicals During On-Site Wastewater Treatment Using A Constructed Wetland

    EPA Science Inventory

    Significant research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants. These plants have been show...

  10. BENCH-SCALE STUDIES ON THE FORMATION OF ENDOCRINE DISRUPTING CHEMICALS FROM COMBUSTION SOURCES

    EPA Science Inventory

    The paper discusses the formsation of endocrine disrupting compounds (EDCs) from precursors, such as phenol and chlorobenzens, under various combustion conditions. It gives results of an exploration of the effects of precursor and catalysys composition on homologue production an...

  11. MATHEMATICAL MODEL OF METABOLIC PATHWAYS OF STEROIDOGENESIS TO PREDICT MOLECULAR RESPONSE FOR ENDOCRINE DISRUPTING CHEMICALS.

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals (EDCs) in the environment can induce adverse effects on reproduction and development in both humans and wildlife, mediated through hormonal disturbances.

  12. Genotyping Sex in Fathead Minnows, Pimephales promelas, for Use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. De...

  13. ENDOCRINE DISRUPTING CHEMICAL RISK MANAGEMENT RESEARCH IN THE US EPA'S OFFICE OF RESEARCH AND DEVELOPMENT

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are receiving increasing media and scientific attention. Concerns about these chemicals stem from the possibility of serious human and wildlife effects and environmental persistence. The US EPA Office of Research and Development's National ...

  14. MATHEMATICAL MODEL OF METABOLIC PATHWAYS OF STEROIDOGENESIS TO PREDICT MOLECULAR RESPONSE FOR ENDOCRINE DISRUPTING CHEMICALS.

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals (EDCs) in the environment can induce adverse effects on reproduction and development in both humans and wildlife, mediated through hormonal disturbances.

  15. Development of Methods of Genotyping Sex for use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. De...

  16. Removal of Selected Endocrine Disrupting Chemicals During On-Site Wastewater Treatment Using A Constructed Wetland

    EPA Science Inventory

    Significant research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants. These plants have been show...

  17. Genotyping Sex in Fathead Minnows, Pimephales promelas, for Use in Endocrine Disruption Assays

    EPA Science Inventory

    Endocrine disrupting compounds have been shown to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In many cases these sex-reversed individuals are morphologically indistinguishable from normal individuals. De...

  18. ENDOCRINE DISRUPTER SCREENING PROGRAMS TO PROTECT WILDLIFE: ONLY AS STRONG AS THE WEAKEST LINK

    EPA Science Inventory

    As global efforts move towards the establishment of screening programs for endocrine disrupters (EDs) in wildlife, a number of unresolved questions demand attention if such efforts are to strengthen the...

  19. Assessing Endocrine Disrupting Chemicals In Landfills, Solid Waste Sites and Wastewater

    EPA Pesticide Factsheets

    EPA researchers are assessing waste water effluents to measure their effects on ecosystems and aquatic animals while also developing innovative solutions to reduce concentrations of potential endocrine disrupting chemicals.

  20. RELATIVE BINDING AFFINITY OF ENDOCRINE DISRUPTING CHEMICALS TO ESTROGEN RECEPTOR IN TWO SPECIES OF FRESHWATER FISH

    EPA Science Inventory

    The US EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. To evaluate the potential for chemicals to cause endocrine disruption in fish we have previously measured the affinity of a number of chemicals for the rainbow trout estr...

  1. ENDOCRINE-DISRUPTING CHEMICALS IN THE ENVIRONMENT: ASSESSING POTENTIAL EFFECTS IN WILDLIFE

    EPA Science Inventory

    Recent evidence suggests that xenobiotic chemicals which mimic/block the action of key hormones in a variety of endocrine pathways may be responsible for adverse effects both in humans and wildlife. This talk will provide an overview of instances in which endocrine-disrupting che...

  2. ENDOCRINE-DISRUPTING CHEMICALS IN THE ENVIRONMENT: ASSESSING POTENTIAL EFFECTS IN WILDLIFE

    EPA Science Inventory

    Recent evidence suggests that xenobiotic chemicals which mimic/block the action of key hormones in a variety of endocrine pathways may be responsible for adverse effects both in humans and wildlife. This talk will provide an overview of instances in which endocrine-disrupting che...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  5. An approach to the identification and regulation of endocrine disrupting pesticides.

    PubMed

    Ewence, Annette; Brescia, Susy; Johnson, Ian; Rumsby, Paul C

    2015-04-01

    Recent decades have seen an increasing interest in chemicals that interact with the endocrine system and have the potential to alter the normal function of this system in humans and wildlife. Chemicals that produce adverse effects caused by interaction with endocrine systems are termed Endocrine Disrupters (EDs). This interest has led regulatory authorities around the world (including the European Union) to consider whether potential endocrine disrupters should be identified and assessed for effects on human health and wildlife and what harmonised criteria could be used for such an assessment. This paper reviews the results of a study whereby toxicity data relating to human health effects of 98 pesticides were assessed for endocrine disruption potential using a number of criteria including the Specific Target Organ Toxicity for repeat exposure (STOT-RE) guidance values used in the European Classification, Labelling and Packaging (CLP) Regulation. Of the pesticides assessed, 27% required further information in order to make a more definitive assessment, 14% were considered to be endocrine disrupters, more or less likely to pose a risk, and 59% were considered not to be endocrine disrupters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Metabolic disruption in context: Clinical avenues for synergistic perturbations in energy homeostasis by endocrine disrupting chemicals

    PubMed Central

    Sargis, Robert M

    2015-01-01

    The global epidemic of metabolic disease is a clear and present danger to both individual and societal health. Understanding the myriad factors contributing to obesity and diabetes is essential for curbing their decades-long expansion. Emerging data implicate environmental endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases such as obesity and diabetes. The phenylsulfamide fungicide and anti-fouling agent tolylfluanid (TF) was recently added to the list of EDCs promoting metabolic dysfunction. Dietary exposure to this novel metabolic disruptor promoted weight gain, increased adiposity, and glucose intolerance as well as systemic and cellular insulin resistance. Interestingly, the increase in body weight and adipose mass was not a consequence of increased food consumption; rather, it may have resulted from disruptions in diurnal patterns of energy intake, raising the possibility that EDCs may promote metabolic dysfunction through alterations in circadian rhythms. While these studies provide further evidence that EDCs may promote the development of obesity and diabetes, many questions remain regarding the clinical factors that modulate patient-specific consequences of EDC exposure, including the impact of genetics, diet, lifestyle, underlying disease, pharmacological treatments, and clinical states of fat redistribution. Currently, little is known regarding the impact of these factors on an individual’s susceptibility to environmentally-mediated metabolic disruption. Advances in these areas will be critical for translating EDC science into the clinic to enable physicians to stratify an individual’s risk of developing EDC-induced metabolic disease and to provide direction for treating exposed patients. PMID:27011951

  7. Fish endocrine disruption responses to a major wastewater treatment facility upgrade.

    PubMed

    Barber, Larry B; Vajda, Alan M; Douville, Chris; Norris, David O; Writer, Jeffery H

    2012-02-21

    The urban-water cycle modifies natural stream hydrology, and domestic and commercial activities increase the burden of endocrine-disrupting chemicals, such as steroidal hormones and 4-nonylphenol, that can disrupt endocrine system function in aquatic organisms. This paper presents a series of integrated chemical and biological investigations into the occurrence, fate, and effects of endocrine-disrupting chemicals in the City of Boulder Colorado's WWTF and Boulder Creek, the receiving stream. Results are presented showing the effects of a full-scale upgrade of the WWTF (that treats 0.6 m(3) s(-1) of sewage) from a trickling filter/solids contact process to an activated sludge process on the removal of endocrine-disrupting compounds and other contaminants (including nutrients, boron, bismuth, gadolinium, and ethylenediaminetetraacetic acid) through each major treatment unit. Corresponding impacts of pre- and postupgrade effluent chemistry on fish reproductive end points were evaluated using on-site, continuous-flow experiments, in which male fathead minnows (Pimephales promelas) were exposed for 28 days to upstream Boulder Creek water and WWTF effluent under controlled conditions. The upgrade of the WWTF resulted in improved removal efficiency for many endocrine-disrupting chemicals, particularly 17β-estradiol and estrone, and fish exposed to the postupgrade effluent indicated reduction in endocrine disruption relative to preupgrade conditions.

  8. Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring.

    PubMed

    Giordano, Felice; Abballe, Annalisa; De Felip, Elena; di Domenico, Alessandro; Ferro, Fabio; Grammatico, Paola; Ingelido, Anna Maria; Marra, Valentina; Marrocco, Giacinto; Vallasciani, Santiago; Figà-Talamanca, Irene

    2010-04-01

    Prenatal exposures to endocrine-disrupting chemicals (EDCs) are suspected risk factors in the etiology of hypospadias. The aim of this case-control study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring. Detailed questionnaire data on occupational and dietary exposures to EDCs in the perinatal period were collected from 80 mothers with hypospadiac infants and from 80 mothers with healthy controls within 24 months of childbirth. Maternal exposure to selected EDCs was also ascertained by measuring the concentration of dichlorodiphenyldichloroethylene, hexachlorobenzene, and several polychlorinated biphenyl congeners in the serum of primiparous mothers of 37 cases and 21 controls. The risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a job-exposure matrix: jobs with exposure to one class of EDCs (odds ratios [OR](crude), 2.83; 95% confidence intervals [CI], 1.32-6.07; OR(adjusted), 2.44; 95% CI, 1.06-5.61) and jobs with exposure to more than one group of EDCs (OR(crude), 4.27; 95% CI, 1.43-12.78; OR(adjusted), 4.11; 95%CI, 1.34-12.59). Increase in risk was also found among mothers consuming a diet rich in fish or shellfish (OR(crude), 3.41; 95% CI, 1.42-8.23; OR(adjusted), 2.73; 95%CI, 1.09-6.82). Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias (OR(adjusted), 5.50; 95% CI, 1.24-24.31). This study, although based on a limited number of cases, for the first time provides evidence of an association between maternal exposure to EDCs, in particular elevated plasma hexachlorobenzene concentration, and the development of hypospadias in the offspring. (c) 2010 Wiley-Liss, Inc.

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

    PubMed

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

    2010-09-01

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

  10. Reproductive endocrine-disrupting effects of triclosan: Population exposure, present evidence and potential mechanisms.

    PubMed

    Wang, Cai-Feng; Tian, Ying

    2015-11-01

    Triclosan has been used as a broad-spectrum antibacterial agent for over 40 years worldwide. Increasing reports indicate frequent detection and broad exposure to triclosan in the natural environment and the human body. Current laboratory studies in various species provide strong evidence for its disrupting effects on the endocrine system, especially reproductive hormones. Multiple modes of action have been suggested, including disrupting hormone metabolism, displacing hormones from hormone receptors and disrupting steroidogenic enzyme activity. Although epidemiological studies on its effects in humans are mostly negative but conflicting, which is typical of much of the early evidence on the toxicity of EDCs, overall, the evidence suggests that triclosan is an EDC. This article reviews human exposure to triclosan, describes the current evidence regarding its reproductive endocrine-disrupting effects, and discusses potential mechanisms to provide insights for further study on its endocrine-disrupting effects in humans.

  11. Developmental effects of endocrine-disrupting chemicals in wildlife and humans

    SciTech Connect

    Colborn, T. ); vom Saal, F.S. ); Soto, A.M. )

    1993-10-01

    Large numbers and large quantities of endoncrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, trangenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistent of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  14. Disruption of the endocrine control of final oocyte maturation in teleosts by xenobiotic chemicals

    SciTech Connect

    Thomas, P.

    1999-07-01

    Final oocyte maturation (FOM) in fish and other vertebrates is under precise endocrine control and involves changes in hormone secretion at all levels of the hypothalamus-pituitary-gonadal axis. Several potential sites and mechanisms of chemical disruption of the endocrine system controlling FOM by are discussed. Neurotoxic chemicals such as lead and PCBs can alter monoamine neurotransmitter function and xenoestrogens can interfere with steroid feedback mechanisms at the hypothalamus and pituitary to impair the neuroendocrine control of gonadotropin secretion. Chemicals which disrupt calcium homeostasis such as cadmium can interfere with calcium-dependent signal transduction pathway activated by reproductive hormones in the pituitary and gonads. Other xenobiotics may disrupt maturation-inducing steroid (MIS) function by impairing its synthesis or receptor binding. The problems in assessing endocrine disruption of FOM are discussed. The relatively few investigations reported in the literature on endocrine disruption of FOM in fishes by chemicals indicate that organochlorine and organophosphorus pesticides at concentrations less than one ppb can impair induction of FOM in response to gonadotropin and the MIS. Moreover, evidence is presented that certain organochlorine pesticides block MIS action by binding to the MIS receptor which is localized on the oocyte plasma membrane. Steroid membrane receptor function may be particularly susceptible to interference by hydrophilic chemicals. Finally, an in vitro bioassay capable of screening many chemicals simultaneously for their ability to disrupt the endocrine control of FOM is described.

  15. EVALUATION OF TRICLOSAN AS A POTENTIAL ENDOCRINE DISRUPTING CHEMICAL

    EPA Science Inventory

    Triclosan is an industrial antibacterial agent commonly used in soaps, toothpaste and cleaners. The present investigation was designed to examine the endocrine modulating potential of Triclosan because its chemical structure closely resembles known non-steroidial estrogens (e.g. ...

  16. EVALUATION OF TRICLOSAN AS A POTENTIAL ENDOCRINE DISRUPTING CHEMICAL

    EPA Science Inventory

    Triclosan is an industrial antibacterial agent commonly used in soaps, toothpaste and cleaners. The present investigation was designed to examine the endocrine modulating potential of Triclosan because its chemical structure closely resembles known non-steroidial estrogens (e.g. ...

  17. Developing a laboratory animal model for perinatal endocrine disruption: the hamster chronicles.

    PubMed

    Hendry, William J; Sheehan, Daniel M; Khan, Shafiq A; May, Jeffrey V

    2002-10-01

    At the biomedical, regulatory, and public level, considerable concern surrounds the concept that inappropriate exposure to endocrine-disrupting chemicals, especially during the prenatal and/or neonatal period, may disrupt normal reproductive tract development and adult function. The intent of this review was to 1. Describe some unique advantages of the hamster for perinatal endocrine disruptor (ED) studies, 2. Summarize the morphological and molecular consequences of exposure to the established perinatal ED, diethylstilbestrol, in the female and male hamster, 3. Present some new, histomorphological insight into the process of neonatal diethylstilbestrol-induced disruption in the hamster uterus, and 4. Introduce recent efforts and future plans to evaluate the potency and mechanism of action of other putative EDs in the hamster experimental system. Taken together, the findings indicate that the hamster represents a unique and sensitive in vivo system to probe the phenomenon of endocrine disruption. The spectrum of candidate endpoints includes developmental toxicity, neoplasia, and more subtle endpoints of reproductive dysfunction.

  18. CUMULATIVE DEVELOPMENTAL EFFECTS OF ENDOCRINE DISRUPTERS: SYNERGY OR ADDITIVITY?

    EPA Science Inventory

    Exposure to chemicals with hormonal activity during critical developmental periods can disrupt reproductive function and development. Within the last decade, several classes of pesticides and toxic substances have been shown to disrupt differentiation of the male rat reproductive...

  19. CUMULATIVE DEVELOPMENTAL EFFECTS OF ENDOCRINE DISRUPTERS: SYNERGY OR ADDITIVITY?

    EPA Science Inventory

    Exposure to chemicals with hormonal activity during critical developmental periods can disrupt reproductive function and development. Within the last decade, several classes of pesticides and toxic substances have been shown to disrupt differentiation of the male rat reproductive...

  20. Experimental designs to assess endocrine disrupting effects in invertebrates. A review.

    PubMed

    Barata, Carlos; Porte, Cinta; Baird, Donald J

    2004-08-01

    In order to gain basic understanding of the ecological effects of vertebrate Endocrine Disrupting Chemicals (EDCs), many research groups are currently testing these chemicals using aquatic invertebrates. Small crustaceans, such as cladocerans and copepods, are of particular interest since they are ecologically important and their short life cycles allow obtaining information on demographic parameters. Despite the existence of diverse literature on the development, growth and reproductive effects of EDCs on these crustaceans, only a few studies have unambiguously assessed a truly endocrine disrupting effect. This review discusses new experimental designs to differentiate between endocrine disruption and other causes of reproductive and developmental impairment. Our findings clearly illustrate that many studies may have falsely concluded that chemicals have endocrine disrupting modes of action when in fact a much simpler explanation was not previously ruled out (e.g., egg mortality, feeding inhibition). This means that there is an urgent need for integration of toxic effects on energy intake to toxicity assessments. Such an approach would permit different ectotoxicological models of action, including endocrine disrupting effects, to be distinguished and their relative roles in the overall toxic response to be clarified.

  1. Contamination and toxic effects of persistent endocrine disrupters in marine mammals and birds.

    PubMed

    Tanabe, Shinsuke

    2002-01-01

    In recent years, several species of marine mammals and birds have been affected by uncommon diseases and unusual mortalities. While several possible causative factors have been attributed for these events, a prominent suspect is exposure to man-made toxic contaminants. Particularly, some of these man-made chemicals can disrupt normal endocrine physiology in animals. At CMES, our studies focus on exposure and toxic effects of endocrine disrupting chemicals, particularly organochlorines, in higher trophic level wildlife. Endocrine disrupting chemicals, such as organochlorine insecticides, polychlorinated biphenyls, organotins etc. are found in tissues of a wide variety of wildlife. Extremely high concentrations have been found in animals afflicted with diseases and/or victims of mass mortalities. Elevated contamination by organochlorines has been found in open sea animals such as cetaceans and albatrosses, which seemed to be attributable to their low capacity to metabolize toxic persistent contaminants. Significant correlations between biochemical parameters (serum hormone concentrations and cytochrome P450 enzyme activities) and residues of endocrine disrupting chemicals were found in some species of marine animals, which indicates that these chemicals may impose toxic effects in animals even at the current levels of exposure. In general, water birds and marine mammals accumulated the dioxin-like compounds with much higher concentrations than humans, implying higher risk from exposure in wildlife. The future issues of endocrine disrupting chemicals in humans and wildlife will have to be focused in developing countries.

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

    SciTech Connect

    1997-01-01

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

  3. Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

    PubMed

    Rutkowska, Aleksandra; Rachoń, Dominik; Milewicz, Andrzej; Ruchała, Marek; Bolanowski, Marek; Jędrzejuk, Diana; Bednarczuk, Tomasz; Górska, Maria; Hubalewska-Dydejczyk, Alicja; Kos-Kudła, Beata; Lewiński, Andrzej; Zgliczyński, Wojciech

    2015-01-01

    With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

  4. Probiotic removal of herbicides with endocrine disrupting potential from aqueous matrices.

    PubMed

    Wouters, R; Lardenoit, R; De Boever, P; Verstraete, W

    2001-01-01

    Water dosed with 50 mg/L of 2,4-D and atrazine was treated to remove the herbicides which both are reported to have endocrine disrupting potential. Both chemicals could be removed effectively with activated carbon. Yet, traces of endocrine disrupter remained in the water and are able to enter the food chain. The further biological elimination of these compounds was investigated. Milk alone did not decrease the amount of chemicals present in the aqueous supernatant. Yet, the probiotic products Bifidus yoghurt (GB), Actimel (Danone) and Yakult (Yakult Honsha) appeared to bind a substantial amount of the endocrine disrupting chemicals to the particulate fraction and thus render them potentially less bio-available in the aqueous phase.

  5. Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio).

    PubMed

    Jianjie, Chen; Wenjuan, Xue; Jinling, Cao; Jie, Song; Ruhui, Jia; Meiyan, Li

    2016-02-01

    Excessive fluoride in natural water ecosystem has the potential to detrimentally affect thyroid endocrine system, but little is known of such effects or underlying mechanisms in fish. In the present study, we evaluated the effects of fluoride on growth performance, thyroid histopathology, thyroid hormone levels, and gene expressions in the HPT axis in male zebrafish (Danio rerio) exposed to different determined concentrations of 0.1, 0.9, 2.0 and 4.1 M of fluoride to investigate the effects of fluoride on thyroid endocrine system and the potential toxic mechanisms caused by fluoride. The results indicated that the growth of the male zebrafish used in the experiments was significantly inhibited, the thyroid microtrastructure was changed, and the levels of T3 and T4 were disturbed in fluoride-exposed male fish. In addition, the expressional profiles of genes in HPT axis displayed alteration. The expressions of all studied genes were significantly increased in all fluoride-exposed male fish after exposure for 45 days. The transcriptional levels of corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroglobulin (TG), sodium iodide symporter (NIS), iodothyronine I (DIO1), and thyroid hormone receptor alpha (TRα) were also elevated in all fluoride-exposed male fish after 90 days of exposure, while the inconsistent expressions were found in the mRNA of iodothyronineⅡ (DIO2), UDP glucuronosyltransferase 1 family a, b (UGT1ab), transthyretin (TTR), and thyroid hormone receptor beta (TRβ). These results demonstrated that fluoride could notably inhibit the growth of zebrafish, and significantly affect thyroid endocrine system by changing the microtrastructure of thyroid, altering thyroid hormone levels and endocrine-related gene expressions in male zebrafish. All above indicated that fluoride could pose a great threat to thyroid endocrine system, thus detrimentally affected the normal function of thyroid of male zebrafish. Copyright © 2015

  6. Science based guidance for the assessment of endocrine disrupting properties of chemicals.

    PubMed

    Bars, Remi; Broeckaert, Fabrice; Fegert, Ivana; Gross, Melanie; Hallmark, Nina; Kedwards, Tim; Lewis, Dick; O'Hagan, Sue; Panter, Grace H; Weltje, Lennart; Weyers, Arnd; Wheeler, James R; Galay-Burgos, Malyka

    2011-02-01

    The European legislation on plant protection products (Regulation (EC) No. 1107/2009) and biocides (Directive 98/8/EC), as well as the regulation concerning chemicals (Regulation (EC) No. 1907/2006 'REACH') only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or non-target species. However, there is currently no agreed guidance on how to identify and evaluate endocrine activity and disruption. Consequently, an ECETOC task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. Specific scientific criteria for the determination of endocrine disrupting properties that integrate information from both regulatory (eco)toxicity studies and mechanistic/screening studies are proposed. These criteria combine the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. The criteria developed are presented in the form of flow charts for assessing relevant effects for both humans and wildlife species. In addition, since not all chemicals with endocrine disrupting properties are of equal hazard, assessment of potency is also proposed to discriminate chemicals of high concern from those of lower concern. The guidance presented in this paper includes refinements made to an initial proposal following discussion of the criteria at a workshop of invited regulatory, academic and industry scientists.

  7. The Use of MS-based Metabolomics to Determine Markers Associated with Endocrine Disruption in Small Fish Species

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are exogenous substances that disrupt the physiological function of endogenous hormones. In fish, these xenobiotics are capable of interfering with the dynamic equilibrium of the hypothalamic-pituitary-gonadal (HPG) axis resulting in adverse ...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  10. The Use of MS-based Metabolomics to Determine Markers Associated with Endocrine Disruption in Small Fish Species

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are exogenous substances that disrupt the physiological function of endogenous hormones. In fish, these xenobiotics are capable of interfering with the dynamic equilibrium of the hypothalamic-pituitary-gonadal (HPG) axis resulting in adverse ...

  11. Parasitism as a source of potential distortion in studies on endocrine disrupting chemicals in molluscs.

    PubMed

    Morley, Neil J

    2006-11-01

    The effects of endocrine disrupting chemicals (EDC) on molluscs in both marine and freshwater polluted environments are a continuing area of concern resulting in many field and laboratory studies. However, molluscs are commonly infected with trematode parasites which, in order to obtain sufficient nutrients for their own development, naturally disrupt the functioning of the endocrine system of the host. The physiological effects of parasitisation on the reproduction and immune response of molluscs are summarised, using a number of examples, and the implications for EDC studies are discussed.

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    2010-01-01

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

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

    EPA Science Inventory

    Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.

    Stoker TE, Parks LG, Gray LE, Cooper RL.

  15. Toxicological profiling of sediments using in vitro bioassays, with emphasis on endocrine disruption.

    PubMed

    Houtman, Corine J; Cenijn, Peter H; Hamers, Timo; Lamoree, Marja H; Legler, Juliette; Murk, Albertinka J; Brouwer, Abraham

    2004-01-01

    In vitro bioassays are valuable tools for screening environmental samples for the presence of bioactive (e.g., endocrine-disrupting) compounds. They can be used to direct chemical analysis of active compounds in toxicity identification and evaluation (TIE) approaches. In the present study, five in vitro bioassays were used to profile toxic potencies in sediments, with emphasis on endocrine disruption. Nonpolar total and acid-treated stable extracts of sediments from 15 locations in the Rhine Meuse estuary area in The Netherlands were assessed. Dioxin-like and estrogenic activities (using dioxin-responsive chemical-activated luciferase gene expression [DR-CALUX] and estrogen-responsive chemical-activated luciferase gene expression [ER-CALUX] assays) as well as genotoxicity (UMU test) and nonspecific toxic potency (Vibrio fischeri assay) were observed in sediment extracts. For the first time, to our knowledge, in vitro displacement of thyroid hormone thyroxine (T4) from the thyroid hormone transport protein thransthyretin by sediment extracts was observed, indicating the presence of compounds potentially able to disrupt T4 plasma transport processes. Antiestrogenic activity was also observed in sediment. The present study showed the occurrence of endocrine-disrupting potencies in sediments from the Dutch delta and the suitability of the ER- and DR-CALUX bioassays to direct endocrine-disruption TIE studies.

  16. Hormone-activated estrogen receptors in annelid invertebrates: implications for evolution and endocrine disruption.

    PubMed

    Keay, June; Thornton, Joseph W

    2009-04-01

    As the primary mediators of estrogen signaling in vertebrates, estrogen receptors (ERs) play crucial roles in reproduction, development, and behavior. They are also the major mediators of endocrine disruption by xenobiotic pollutants that mimic or block estrogen action. ERs that are sensitive to estrogen and endocrine disrupters have long been thought to be restricted to vertebrates: although there is evidence for estrogen signaling in invertebrates, the only ERs studied to date, from mollusks and cephalochordates, have been insensitive to estrogen and therefore incapable of mediating estrogen signaling or disruption. To determine whether estrogen sensitivity is ancestral or a unique characteristic of vertebrate ERs, we isolated and characterized ERs from two annelids, Platynereis dumerilii and Capitella capitata, because annelids are the sister phylum to mollusks and have been shown to produce and respond to estrogens. Functional assays show that annelid ERs specifically activate transcription in response to low estrogen concentrations and bind estrogen with high affinity. Furthermore, numerous known endocrine-disrupting chemicals activate or antagonize the annelid ER. This is the first report of a hormone-activated invertebrate ER. Our results indicate that estrogen signaling via the ER is as ancient as the ancestral bilaterian animal and corroborate the estrogen sensitivity of the ancestral steroid receptor. They suggest that the taxonomic scope of endocrine disruption by xenoestrogens may be very broad and reveal how functional diversity evolved in a gene family central to animal endocrinology.

  17. Toxicogenomic approach to endocrine disrupters: identification of a transcript profile characteristic of chemicals with estrogenic activity.

    PubMed

    Naciff, Jorge M; Daston, George P

    2004-01-01

    Public concerns have been raised in recent years over the possible adverse effects that may result from exposure to chemicals in the environment that have the potential to interfere with the normal function of the endocrine system in wildlife and humans ("endocrine disrupters"). Regulations have been established that require the testing of pesticides used in food crops and drinking water contaminants, for estrogenicity and other hormonal activities. In the United States, the U.S. EPA proposed the Endocrine Disrupter Screening Program, which consists of a Tier 1 screening battery of tests that is designed to identify chemicals capable of interacting with various hormonal systems, and different Tier 2 testing assays that are designed to verify and broaden the Tier 1 results. We identify 2 main problems with this approach: (1) the fact that the developmental stages that are the most susceptible to endocrine disruption are not represented in the screening tier, mainly because developmental effects tend to be latent, and there is no way to economically screen in developing models; and (2) the expense to screen each chemical to be included in this program. Thus, the need arises for an accurate, rapid, and cost effective method for assessing the potential endocrine activity of multiple chemicals during development. We hypothesize that the largely latent developmental effects of some endocrine disruptors are preceded by immediate changes in gene expression in the embryo and fetus. Therefore, an approach to assess the potential estrogenic (and other steroid hormonal) activity of different compounds is to identify those patterns of gene expression elicited in a tissue/organ exposed to these particular classes of chemicals. In this paper, the potential utility of such an approach for screening and better understanding of mechanism of action for specific chemicals with endocrine disrupter activities is presented, using as an example chemicals with estrogenic activity.

  18. 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.

  19. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours.

    PubMed

    Patisaul, Heather B

    2016-07-08

    A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.

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

    PubMed Central

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

    2016-01-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

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

    PubMed

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

    2016-03-25

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

  2. The Japanese Quail as an avian model for testing endocrine disrupting chemicals: endocrine and behavioral end points

    USGS Publications Warehouse

    Ottinger, M.A.; Abdelnabi, M.A.; Thompson, N.; Wu, J.; Henry, K.; Humphries, E.; Henry, P.F.P.

    2000-01-01

    Birds have extremely varied reproductive strategies. As such, the impact of endocrine disrupting chemicals (EDCs) can greatly differ across avian species. Precocial species, such as Japanese quail appear to be most sensitive to EDC effects during embryonic development, particularly sexual differentiation. A great deal is known about the ontogeny of Japanese quail (Coturnix japonica) relative to endocrine, neuro-endocrine, and behavioral components of reproduction. Therefore, this species provides an excellent model for understanding effects of EDCs on reproductive biology with exposure at specific stages of the life cycle. The purpose of these experiments was to conduct a 1- or 2- generation experiment with positive or negative control chemicals and to determine changes in selected end points. Japanese quail embryos were exposed to estradiol benzoate (EB; positive control) in a 2-generation design or to fadrozole (FAD; negative control) in a 1-generation design. Embryonic EB treatment resulted in significant reductions (p< 0.5) in hen day production (90.2 vs 54.1; control vs EB, resp.) and fertility (85.3 vs 33.4%, control vs EB, resp.). Males showed sharply reduced courtship and mating behaviors as well as increased lag time (26 vs 148 sec; control vs EB) in behavioral tests. Fadrozole exposure resulted in reduced hatchability of fertile eggs, particularly at higher doses. There were no significant effects on courtship and mating behavior of males although males showed an increased lag time in their responses, nally, a behavioral test for studying motor and fear responses in young chicks was used; chicks exposed to an estrogenic pesticide (methoxychlor) showed some deficits. In summary, the use of appropriate and reliable end points that are responsive to endocrine disruption are critical for assessment of EDCs. Supported in part by EPA grant R826134.

  3. SETAC Focused Topic Meeting on endocrine-disrupting chemicals: Overview and outcomes

    EPA Science Inventory

    A SETAC North America Focused Topic Meeting (FTM), “Endocrine Disruption: Chemical testing, Risk Assessment Approaches and Implications”, was held 4-6 February, 2014 at the US Environmental Protection Agency (USEPA) conference facility in Research Triangle Park, NC. The meeting,...

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

    EPA Science Inventory

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

    Suzanne E. Fenton1, and Jennifer Rayner1,2

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

  5. MANAGING ENDOCRINE DISRUPTING CHEMICALS USING EXISTING AND INNOVATIVE WASTEWATER TREATMENT TECHNOLOGIES

    EPA Science Inventory

    Research has shown that wastewater (WW) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WW treatment (WWT) may include centralized wastewater treatment plants (WWTPs) or smaller on-site WWT technologies. EDCs found in WWT effluents (aqueou...

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

    EPA Science Inventory

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

  7. SOURCES, TEMPORAL VARIATIONS, AND FATE AND TRANSPORT OF SELECTED ENDOCRINE DISRUPTING COMPOUNDS AND PHARMACEUTICALS, NEBRASKA, USA

    EPA Science Inventory

    Known or suspected endocrine disrupting compounds have been detected in water from streams, groundwater, and drinking water. In 2001 and 2002, the U.S. Geological Survey in cooperation with the U.S./ Environmental Protection Agency and the City of Lincoln, Nebraska, collected va...

  8. ASSESSING ENDOCRINE-DISRUPTING CHEMICAL EXPOSURE IN INDIGENOUS AQUATIC POPULATIONS IN THE OHIO RIVER

    EPA Science Inventory

    The NERL has launched a collaborative study with the ORSANCO to determine the degree of ecologically relevant endocrine-disrupting chemical (EDC) exposure in the New Cumberland Pool of the Ohio River under the Environmental Monitoring and Assessment Program - Great Rivers Project...

  9. Considerations in the Derivation of Water Quality Criteria for Endocrine-disrupting Chemicals

    EPA Science Inventory

    When the USEPA’s 1985 guidelines for deriving numerical water quality criteria (WQC) for the protection of aquatic life were developed there was little anticipation that endocrine-disrupting chemicals (EDCs) would be come a widespread environmental issue. While the basic guidelin...

  10. STEROID HORMONES AS BIOMARKERS OF ENDOCRINE DISRUPTION IN WILDLIFE. IN: ENVIRONMENTAL TOXICOLOGY AND RISK ASSESSMENT

    EPA Science Inventory

    Standardization of Biomarkers for Endocrine Disruption and Environmental Assessment. 8th Volume, ASTM STP 1364. D.S. Henshel, M.C. Black, and M.C. Harrass, Editors. American Society for Testing and Materials, West Conshohocken, PA. Pp. 254-270.

  11. MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES

    EPA Science Inventory

    MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL
    ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES.
    Authors: L E Gray 1 , J Furr 1 , M G Price 2 , C J Wolf 3 and J S Ostby 1
    Institutions: 1. Endocrinology Branch, Reproductive Toxicology Division, NH...

  12. MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES

    EPA Science Inventory

    MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL
    ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES.
    Authors: L E Gray 1 , J Furr 1 , M G Price 2 , C J Wolf 3 and J S Ostby 1
    Institutions: 1. Endocrinology Branch, Reproductive Toxicology Division, NH...

  13. Early homeostatic disturbances of human growth and maturation by endocrine disrupters.

    PubMed

    Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2010-08-01

    We attempt to delineate and integrate aspects of growth and development that could be affected by endocrine disrupters [endocrine-disrupting compounds (EDC)], an increasing public health concern. Epidemiological and experimental data substantiate that fetal and early postnatal life are critical periods of exposure to endocrine disrupters, with possible transgenerational effects. The EDC effects include several disorders of the reproductive system throughout life (abnormalities of sexual differentiation, infertility or subfertility and some neoplasia) and disorders of energy balance (obesity and metabolic syndrome). The mechanisms are consistent with the concept of 'developmental origin of adult disease'. They could involve cross-talk between the factors controlling reproduction and those controlling energy balance, both in the hypothalamus and peripherally. Due to ubiquity of endocrine disrupters and lifelong stakes of early exposure, individual families should be provided by pediatricians with recommendations following the precautionary principle, that is prevention or attenuation of conditions possibly detrimental to health before the evidence of such adverse effects is complete and undisputable.

  14. Using biological endpoints for assessing exposures to endocrine disrupting contaminants of emerging concern

    EPA Science Inventory

    Most of what is known about the implications of endocrine disrupting chemicals (EDCs) in the environment is site- or compound-specific. There are numerous reports of gonadal histological abnormalities, alterations in sex ratios, and high vitellogenin protein levels in fish below ...

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

    EPA Science Inventory

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

  16. A dissection of biological pathways underlying transcriptional responses to endocrine disrupting chemicals in zebrafish

    EPA Science Inventory

    Genome-wide gene expression profiling under a variety of perturbations is a powerful tool to explore the dynamics of fish responses to exposures of endocrine disrupting chemicals (EDCs). Using Agilent zebrafish two-color genome microarryas, we profiled zebrafish responses under ...

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

    EPA Science Inventory

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

  18. Analysis of synthetic endocrine-disrupting chemicals in food: a review.

    PubMed

    Mezcua, M; Martínez-Uroz, M A; Gómez-Ramos, M M; Gómez, M J; Navas, J M; Fernández-Alba, A R

    2012-10-15

    This work focuses on a revision of analytical methodologies for the determination of industrial chemicals that have an endocrine-disrupting effect on food commodities. These food commodities have been divided into two major categories: crops and food of animal origin. The reviewed methods have been commented on in terms of sample preparation, analytical methods, and the occurrence of the studied compounds.

  19. PROJECTING POPULATION-LEVEL RESPONSES OF MYSIDS EXPOSED TO AN ENDOCRINE DISRUPTING CHEMICAL

    EPA Science Inventory

    Raimondo, Sandy and Charles L. McKenney, Jr. Submitted. Projecting Population-Level Responses of Mysids Exposed to an Endocrine-Disrupting Chemical. Integr. Comp. Biol. 23 p. (ERL,GB 1203).

    To fully understand the implications of a chemical's effect on the conservation of...

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

    EPA Science Inventory

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

    Suzanne E. Fenton1, and Jennifer Rayner1,2

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

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

    EPA Science Inventory

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

  2. Removal Of Endocrine Disrupting Chemicals By A Constructed Wetland For On-Site Domestic Wastewater Treatment

    EPA Science Inventory

    Research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants (WWTPs). These WWTPs have been shown to ...

  3. Development of a Computational Model for Female Fathead Minnows exposed to Two Endocrine Disrupting Chemicals

    EPA Science Inventory

    Endocrine disrupting chemicals (e.g., estrogens and androgens) are known to affect reproductive functions in fish. A synthetic estrogen used in birth control pills, 17á-ethynylestradiol (EE2), is discharged from wastewater treatment plants into water bodies throughout the United ...

  4. EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS (EDCS) ON FETAL TESTES HORMONE PRODUCTION

    EPA Science Inventory

    Effects of Endocrine Disrupting Chemicals (EDCs) on Fetal Testes Hormone Production
    CS Lambright, VS Wilson, JR Furr, CJ Wolf, N Noriega, LE Gray, Jr
    US EPA, ORD/NHEERL/RTD, RTP, NC 27711

    Exposure to EDCs during critical periods of fetal sexual development can have...

  5. Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

    EPA Science Inventory

    Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal? The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncanc...

  6. MANAGING ENDOCRINE DISRUPTING CHEMICALS USING EXISTING AND INNOVATIVE WASTEWATER TREATMENT TECHNOLOGIES

    EPA Science Inventory

    Research has shown that wastewater (WW) can be a significant source of endocrine disrupting chemicals (EDCs) to the environment. WW treatment (WWT) may include centralized wastewater treatment plants (WWTPs) or smaller on-site WWT technologies. EDCs found in WWT effluents (aqueou...

  7. SETAC Focused Topic Meeting on endocrine-disrupting chemicals: Overview and outcomes

    EPA Science Inventory

    A SETAC North America Focused Topic Meeting (FTM), “Endocrine Disruption: Chemical testing, Risk Assessment Approaches and Implications”, was held 4-6 February, 2014 at the US Environmental Protection Agency (USEPA) conference facility in Research Triangle Park, NC. The meeting,...

  8. Using biological endpoints for assessing exposures to endocrine disrupting contaminants of emerging concern

    EPA Science Inventory

    Most of what is known about the implications of endocrine disrupting chemicals (EDCs) in the environment is site- or compound-specific. There are numerous reports of gonadal histological abnormalities, alterations in sex ratios, and high vitellogenin protein levels in fish below ...

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

    EPA Science Inventory

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

  10. PROJECTING POPULATION-LEVEL RESPONSES OF MYSIDS EXPOSED TO AN ENDOCRINE DISRUPTING CHEMICAL

    EPA Science Inventory

    Raimondo, Sandy and Charles L. McKenney, Jr. Submitted. Projecting Population-Level Responses of Mysids Exposed to an Endocrine-Disrupting Chemical. Integr. Comp. Biol. 23 p. (ERL,GB 1203).

    To fully understand the implications of a chemical's effect on the conservation of...

  11. ASSESSING ENDOCRINE-DISRUPTING CHEMICAL EXPOSURE IN INDIGENOUS AQUATIC POPULATIONS IN THE OHIO RIVER

    EPA Science Inventory

    The NERL has launched a collaborative study with the ORSANCO to determine the degree of ecologically relevant endocrine-disrupting chemical (EDC) exposure in the New Cumberland Pool of the Ohio River under the Environmental Monitoring and Assessment Program - Great Rivers Project...

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

    EPA Science Inventory

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

  13. Removal Of Endocrine Disrupting Chemicals By A Constructed Wetland For On-Site Domestic Wastewater Treatment

    EPA Science Inventory

    Research has shown that domestic and industrial wastewater can be a source of endocrine disrupting chemicals (EDCs) to the environment. Much of this research has focused on municipal and industrial centralized wastewater treatment plants (WWTPs). These WWTPs have been shown to ...

  14. Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

    EPA Science Inventory

    Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal? The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncanc...

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

    EPA Science Inventory

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

  16. Development of a Computational Model for Female Fathead Minnows exposed to Two Endocrine Disrupting Chemicals

    EPA Science Inventory

    Endocrine disrupting chemicals (e.g., estrogens and androgens) are known to affect reproductive functions in fish. A synthetic estrogen used in birth control pills, 17á-ethynylestradiol (EE2), is discharged from wastewater treatment plants into water bodies throughout the United ...

  17. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation.

    PubMed

    Vos, J G; Dybing, E; Greim, H A; Ladefoged, O; Lambré, C; Tarazona, J V; Brandt, I; Vethaak, A D

    2000-01-01

    Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most

  18. Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones

    EPA Science Inventory

    Endocrine disruption is considered a highly relevant endpoint for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening for endocrine disruption – with focus on vertebrates (fish and amphibians) and estrogen, and...

  19. Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians – interactions with estrogens, androgens, and thyroid hormones

    EPA Science Inventory

    Endocrine disruption is considered a highly relevant endpoint for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening for endocrine disruption – with focus on vertebrates (fish and amphibians) and estrogen, and...

  20. Receptors mediating toxicity and their involvement in endocrine disruption.

    PubMed

    Rüegg, Joëlle; Penttinen-Damdimopoulou, Pauliina; Mäkelä, Sari; Pongratz, Ingemar; Gustafsson, Jan-Ake

    2009-01-01

    Many toxic compounds exert their harmful effects by activating of certain receptors, which in turn leads to dysregulation of transcription. Some of these receptors are so called xenosensors. They are activated by external chemicals and evoke a cascade of events that lead to the elimination of the chemical from the system. Other receptors that are modulated by toxic substances are hormone receptors, particularly the ones of the nuclear receptor family. Some environmental chemicals resemble endogenous hormones and can falsely activate these receptors, leading to undesired activity in the cell. Furthermore, excessive activation of the xenosensors can lead to disturbances of the integrity of the system as well. In this chapter, the concepts of receptor-mediated toxicity and hormone disruption are introduced. We start by describing environmental chemicals that can bind to xenosensors and nuclear hormone receptors. We then describe the receptors most commonly targeted by environmental chemicals. Finally, the mechanisms by which receptor-mediated events can disrupt the system are depicted.

  1. Polychlorinated biphenyls, mercury, and potential endocrine disruption in fish from the Hudson River, New York, USA

    USGS Publications Warehouse

    Baldigo, Barry P.; Sloan, R.J.; Smith, S.B.; Denslow, N.D.; Blazer, V.S.; Gross, T.S.

    2006-01-01

    Tissue residues of total mercury (Hg), total polychlorinated biphenyls (PCBs), and lipid-based PCBs; plasma concentrations of endocrine biomarkers; and reproductive and histologic biomarkers were assessed in 460 carp (Cyprinus carpio), bass (Micropterus salmoides and Micropterus dolomieui), and bullhead (Ameiurus nebulosus) collected from eight sites across the Hudson River Basin in the spring of 1998 to determine if endocrine disruption was evident in resident fish species and to evaluate contaminant-biomarker interrelations. Total PCBs in bed sediments (maximum 2,500 ??g kg-1) could explain 64 to 90% of the variability in lipid-based PCB residues in tissues (maximum 1,250 ??g PCB g-lipid-1) of the four species. The 17??-estradiol to 11-ketotestosterone ratio, typically less than 1.0 in male fish and greater than 1.0 in females, exceeded 1.4 in all male largemouth bass and 35% of male carp and bullhead at one site 21 km downstream from a major PCB source. Endocrine biomarkers were significantly correlated with total Hg in female smallmouth bass and carp, and with lipid-based PCBs in males of all four species. Empirical evidence of endocrine modulation in blood plasma of male and female fish from sites with and without high PCB residues in bed sediments and fish tissues suggest that PCBs, Hg, or other contaminants may disrupt normal endocrine function in fish of the Hudson River. ?? Eawag, 2006.

  2. Proteomic response of Macrobrachium rosenbergii hepatopancreas exposed to chlordecone: Identification of endocrine disruption biomarkers?

    PubMed

    Lafontaine, Anne; Baiwir, Dominique; Joaquim-Justo, Célia; De Pauw, Edwin; Lemoine, Soazig; Boulangé-Lecomte, Céline; Forget-Leray, Joëlle; Thomé, Jean-Pierre; Gismondi, Eric

    2017-07-01

    The present work is the first study investigating the impacts of chlordecone, an organochlorine insecticide, on the proteome of the decapod crustacean Macrobrachium rosenbergii, by gel-free proteomic analysis. The hepatopancreas protein expression variations were analysed in organisms exposed to three environmental relevant concentrations of chlordecone (i.e. 0.2, 2 and 20µg/L). Results revealed that 62 proteins were significantly up- or down-regulated in exposed prawns compared to controls. Most of these proteins are involved in important physiological processes such as ion transport, defense mechanisms and immune system, cytoskeleton dynamics, or protein synthesis and degradation. Moreover, it appears that 6% of the deregulated protein are involved in the endocrine system and in the hormonal control of reproduction or development processes of M. rosenbergii (e.g. vitellogenin, farnesoic acid o-methyltransferase). These results indicate that chlordecone is potentially an endocrine disruptor compound for decapods, as already observed in vertebrates. These protein modifications could lead to disruptions of M. rosenbergii growth and reproduction, and therefore of the fitness population on the long-term. Besides, these disrupted proteins could be suggested as biomarkers of exposure for endocrine disruptions in invertebrates. However, further investigations are needed to complete understanding of action mechanisms of chlordecone on proteome and endocrine system of crustaceans. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish.

    PubMed

    Niemuth, Nicholas J; Jordan, Renee; Crago, Jordan; Blanksma, Chad; Johnson, Rodney; Klaper, Rebecca D

    2015-02-01

    Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms.

  4. Metformin Exposure at Environmentally Relevant Concentrations Causes Potential Endocrine Disruption in Adult Male Fish

    PubMed Central

    Niemuth, Nicholas J; Jordan, Renee; Crago, Jordan; Blanksma, Chad; Johnson, Rodney; Klaper, Rebecca D

    2015-01-01

    Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms. Environ Toxicol Chem 2014;9999:1–6. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of SETAC. PMID:25358780

  5. Endocrine disrupting potential of PAHs and their alkylated analogues associated with oil spills.

    PubMed

    Lee, Sangwoo; Hong, Seongjin; Liu, Xiaoshan; Kim, Cheolmin; Jung, Dawoon; Yim, Un Hyuk; Shim, Won Joon; Khim, Jong Seong; Giesy, John P; Choi, Kyungho

    2017-09-20

    Polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs are known to be major toxic contaminants in spills of petroleum hydrocarbons (oil). Spilled oil undergoes weathering and over time, PAHs go through a series of compositional changes. PAHs can disrupt endocrine functions, and the type of functions affected and associated potencies vary with the type and alkylation status of PAH. In this study, the potential of five major PAHs of crude oil, i.e., naphthalene, fluorene, dibenzothiophene, phenanthrene, and chrysene, and their alkylated analogues (n = 25), to disrupt endocrine functions was evaluated by use of MVLN-luc and H295R cell lines. In the MVLN-luc bioassay, seven estrogen receptor (ER) agonists were detected among 30 tested PAHs. The greatest ER-mediated potency was observed for 1-methylchrysene (101.4%), followed by phenanthrene and its alkylated analogues (range of %-E2max from 1.6% to 47.3%). In the H295R bioassay, significantly greater syntheses of steroid hormones were observed for 20 PAHs. For major PAHs and their alkylated analogues, disruption of steroidogenesis appeared to be more significant than ER-mediated effects. The number and locations of alkyl-moieties alone could not explain differences in the types or the potencies of toxicities. This observation shows that disruption of endocrine functions by some constituents of oil spills could be underestimated if only parent compounds are considered in assessments of hazard and risk.

  6. Removal of trace organic micropollutants by drinking water biological filters.

    PubMed

    Zearley, Thomas L; Summers, R Scott

    2012-09-04

    The long-term removal of 34 trace organic micropollutants (<1 μg L(-1)) was evaluated and modeled in drinking water biological filters with sand media from a full-scale plant. The micropollutants included pesticides, pharmaceuticals, and personal care products, some of which are endocrine disrupting chemicals, and represent a wide range of uses, chemical structures, adsorbabilities, and biodegradabilities. Micropollutant removal ranged from no measurable removal (<15%) for 13 compounds to removal below the detection limit and followed one of four trends over the one year study period: steady state removal throughout, increasing removal to steady state (acclimation), decreasing removal, or no removal (recalcitrant). Removals for all 19 nonrecalcitrant compounds followed first-order kinetics when at steady state with increased removal at longer empty bed contact times (EBCT). Rate constants were calculated, 0.02-0.37 min(-1), and used in a pseudo-first-order rate model with the EBCT to predict removals in laboratory biofilters at a different EBCT and influent conditions. Drinking water biofiltration has the potential to be an effective process for the control of many trace organic contaminants and a pseudo-first-order model can serve as an appropriate method for approximating performance.

  7. Detecting endocrine disrupting compounds in water using sulfur-oxidizing bacteria.

    PubMed

    Van Ginkel, Steven W; Hassan, Sedky H A; Oh, Sang-Eun

    2010-09-01

    For the rapid and reliable detection of endocrine disrupting compounds in water, a novel toxicity detection methodology based on sulfur-oxidizing bacteria (SOB) has been developed. The methodology exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid in the presence of oxygen. The reaction results in an increase in electrical conductivity (EC) and a decrease in pH. When endocrine disrupting compounds were added to the system, the effluent EC decreased and the pH increased due to the inhibition of the SOB. We found that the system can detect these chemicals in the 50-200 ppb range, which is lower than many whole-cell biosensors to date. The SOB biosensor can detect toxicity on the order of min to h which can serve as an early warning so as to not pollute the environment and affect public health. (c) 2010 Elsevier Ltd. All rights reserved.

  8. Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife.

    PubMed Central

    Guillette, L J; Crain, D A; Rooney, A A; Pickford, D B

    1995-01-01

    Many environmental contaminants disrupt the vertebrate endocrine system. Although they may be no more sensitive to endocrine-disrupting contaminants (EDCs) than other vertebrates, reptiles are good sentinels of exposure to EDCs due to the lability in their sex determination. This is exemplified by a study of alligators at Lake Apopka, Florida, showing that EDCs have altered the balance of reproductive hormones resulting in reproductive dysfunction. Such alterations may be activationally or organizationally induced. Much research emphasizes the former, but a complete understanding of the influence of EDCs in nature can be generated only after consideration of both activational and organizational alterations. The organizational model suggests that a small quantity of an EDC, administered during a specific period of embryonic development, can permanently modify the organization of the reproductive, immune, and nervous systems. Additionally, this model helps explain evolutionary adaptations to naturally occurring estrogenic compounds, such as phytoestrogens. PMID:8593864

  9. Endocrine disruption of sexual selection by an estrogenic herbicide in the mealworm beetle (Tenebrio molitor).

    PubMed

    McCallum, Malcolm L; Matlock, Makensey; Treas, Justin; Safi, Barroq; Sanson, Wendy; McCallum, Jamie L

    2013-12-01

    The role that endocrine disruption could play in sexual selection remains relatively untested, and although estrogens occur in insects, little information exists about their biological role in insect reproduction. Atrazine is a commonly applied herbicide that mimics estrogen in vertebrates. Tenebrio molitor were raised from egg to adult under a gradation of environmentally relevant atrazine exposures and a non-treated control. Atrazine was delivered in the drinking water ad libitum. Female T. molitor were provided with a choice between unrelated males raised under three levels of atrazine exposures. Female preference for males demonstrated a non-monotonic inverted U-shaped response to atrazine exposure. There was no significant difference between the control and the high exposure to atrazine. Excluding the control, female preference increased as exposure concentration increased. These results have important repercussions for nonlethal effects of endocrine disruption on populations, their capacity to interfere with sexual selection, and the role of estrogen in pheromone communication among insects.

  10. Identification of Endocrine Disrupting Chemicals using a Virus-Based Colorimetric Sensor.

    PubMed

    Moon, Jong-Sik; Lee, Yujin; Shin, Dong-Myeong; Kim, Chuntae; Kim, Won-Geun; Park, Minji; Han, Jiye; Song, Hyerin; Kim, Kyujung; Oh, Jin-Woo

    2016-11-07

    A simple and portable colorimetric sensor based on M13 bacteriophage (phage) was devised to identify a class of endocrine disrupting chemicals, including benzene, phthalate, and chlorobenzene derivatives. Arrays of structurally and genetically modified M13 bacteriophage were fabricated so as to produce a biomimetic colorimetric sensor, and color changes in the phage arrays in response to several benzene derivatives were characterized. The sensor was also used to classify phthalate and chlorobenzene derivatives as representatives of endocrine disrupting chemicals. The characteristic color patterns obtained on exposure to various benzene derivatives enabled similar chemical structures in the vapor phase to be classified. Our sensing approach based on the use of a genetically surface modified M13 bacteriophage offers a promising platform for portable, simple environmental monitors that could be extended for use in numerous application areas, including food monitoring, security monitoring, explosive risk assessment, and point of care testing.

  11. The application of membrane bioreactors as decentralised systems for removal of endocrine disrupting chemicals and pharmaceuticals.

    PubMed

    Le-Minh, N; Coleman, H M; Khan, S J; van Luer, Y; Trang, T T T; Watkins, G; Stuetz, R M

    2010-01-01

    The concentrations of some important endocrine disrupting chemicals and pharmaceuticals after various stages of wastewater treatment were investigated. The endocrine disrupting chemicals included natural and synthetic estrogenic and androgenic steroids. The pharmaceuticals included a series of sulfonamide antibiotics and trimethoprim. The removal efficiency of a membrane bioreactor (MBR) was investigated and compared with a conventional activated sludge (CAS) system. Samples were analysed by liquid chromatography tandem mass spectrometry. Results showed that the MBR and CAS systems effectively removed steroidal estrogens and androgens, but only partially eliminated the target antibiotics from wastewater. The MBR was shown to be more effective than the CAS system which was possibly attributed to the high solid retention time and concentration of biosolids in the MBR. The results highlight the potential wider application of MBRs for the removal of trace chemical contaminants in wastewater and their potential for use as decentralised wastewater treatment systems.

  12. Sex differences in microglial colonization and vulnerabilities to endocrine disruption in the social brain.

    PubMed

    Rebuli, Meghan E; Gibson, Paul; Rhodes, Cassie L; Cushing, Bruce S; Patisaul, Heather B

    2016-11-01

    During development, microglia, the resident immune cells of the brain, play an important role in synaptic organization. Microglial colonization of the developing brain is sexually dimorphic in some regions, including nuclei critical for the coordination of social behavior, suggesting steroid hormones have an influencing role, particularly estrogen. By extension, microglial colonization may be vulnerable to endocrine disruption. Concerns have been raised regarding the potential for endocrine disrupting compounds (EDCs) to alter brain development and behavior. Developmental exposure to Bisphenol A (BPA), a ubiquitous EDC, has been associated with altered sociosexual and mood-related behaviors in various animal models and children. Through a comparison of the promiscuous Wistar rat (Rattus norvegicus) and the socially monogamous prairie vole (Microtus ochrogaster), we are the first to observe that developmental exposure to the synthetic estrogen ethinyl estradiol (EE) or BPA alters the sex-specific colonization of the hippocampus and amygdala by microglia.

  13. Advancing research on endocrine disrupting chemicals in breast cancer: Expert panel recommendations.

    PubMed

    Teitelbaum, Susan L; Belpoggi, Fiorella; Reinlib, Les

    2015-07-01

    Breast cancer incidence continues to increase in the US and Europe, a reflection of the growing influence of environment factors that interact with personal genetics. The US Environmental Protection Agency estimates that there are approximately 10,000 endocrine disrupting chemicals among the common daily exposures that could affect the risk of disease. The daunting tasks of identifying, characterizing, and elucidating the mechanisms of endocrine disrupting chemicals in breast cancer need to be addressed to produce a comprehensive model that will facilitate preventive strategies and public policy. An expert panel met to describe and bring attention to needs linking common environmental exposures, critical windows of exposure, and optimal times of assessment in investigating breast cancer risk. The group included investigators with extensive experience in the use of rodent models and in leading population studies and produced a set of recommendations for effective approaches to gaining insights into the environmental origins of breast cancer across the lifespan.

  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. Hypospadias and endocrine disruption: is there a connection?

    PubMed Central

    Baskin, L S; Himes, K; Colborn, T

    2001-01-01

    Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention. PMID:11713004

  16. Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals

    PubMed Central

    Wan, HT; Mruk, Dolores D; Wong, Chris KC; Cheng, C Yan

    2014-01-01

    Introduction Exposure to endocrine disrupting chemicals (EDCs) has recently been linked to declining fertility in men in both developed and developing countries. Since many EDCs possess intrinsic estrogenic or androgenic activities, thus, the gonad is one of the major targets of EDCs. Areas covered For the past 2 decades, studies found in the literature regarding the disruptive effects of these EDCs on reproductive function in human males and also rodents were mostly focused on oxidative stress-induced germ cell apoptosis, disruption of steroidogenesis, abnormal sperm production and disruption of spermatogenesis in particular cell adhesion function and the blood–testis-barrier (BTB) function. Herein, we highlight recent findings in the field illustrating testis-specific proteins are also targets of EDCs. Expert opinion This information should be helpful in developing better therapeutic approach to manage ECD-induced reproductive toxicity. This information is also helpful to identify potential targets for male contraceptive development. PMID:23600530

  17. Removal of an endocrine disrupting chemical (17alpha-ethinyloestradiol) from wastewater effluent by activated carbon adsorption: effects of activated carbon type and competitive adsorption.

    PubMed

    Ifelebuegu, A O; Lester, J N; Churchley, J; Cartmell, E

    2006-12-01

    Granular activated carbon has been extensively used for the adsorption of organic micropollutants for potable water production. In this study the removal of an endocrine disrupting chemical from wastewater final effluent by three types of granular activated carbon (wood, coconut and coal based) has been investigated in batch adsorption experiments and correlated with the removal of chemical oxygen demand (COD), total organic carbon (TOC) and ultraviolet absorbance (UV). The results obtained demonstrated 17alpha-ethinyloestradiol (EE2) removals of 98.6%, 99.3%, and 96.4% were achieved by the coal based (ACo), coconut based (ACn) and wood based (AWd) carbons respectively at the lowest dose of carbon (0.1gl(-1)). The other adsorbates investigated all exhibited good removal. At an equilibrium concentration of 7mgl(-1) the COD adsorption capacities were 3.16mg g(-1), 4.8 mg g(-1) and 7.1 mg g(-1) for the wood, coconut and coal based carbons respectively. Overall, the order of removal efficiency of EE2 and the other adsorbates for the three activated carbons was ACn > ACo > AWd. The adsorption capacities of the carbons were found to be reduced by the effects of other competing adsorbates in the wastewater effluent.

  18. Construction of amphiphilic segments on polypropylene nonwoven surface and its application in removal of endocrine disrupting compounds (EDCs) from aqueous solution

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Wei, Junfu; Zhou, Xiangyu; Liu, Nana

    2015-05-01

    The amphiphilic segments on polypropylene nonwoven (PP nonwoven) surface were constructed using the ultraviolet (UV) irradiation graft polymerization for the removal of endocrine disrupting compounds (EDCs) with different polarity from aqueous solution. The stearyl acrylate (SA) as hydrophobic functional monomer was introduced onto the surface of PP nonwoven fabric at first stage and then the hydroxyethyl acrylate (HEA) as hydrophilic functional monomer was introduced subsequently. The effect of functional monomer concentration and UV irradiation time on grafting ratio was studied and discussed. The novel amphiphilic structure was designed and constructed based on adsorption capacity for the target micropollutants. The structure and composition of the amphiphilic adsorption materials were characterized by Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and contact angle (CA). The adsorption behaviors for EDCs of the amphiphilic adsorption materials were studied and the results indicated that the adsorption capacity and adsorption rate were superior to single SA grafted PP nonwoven (PP-g-SA) and single HEA grafted PP nonwoven (PP-g-HEA). The novel amphiphilic adsorption material was efficient for the removal of EDCs with different polarity and could be utilized as a potential adsorption material for removing EDCs from aqueous solution.

  19. Endocrine disrupting chemicals in pesticides and herbicide in Fars Province, Iran.

    PubMed

    Ebrahimi, M; Shamabadi, N

    2007-09-15

    Recent studies have shown that certain man-made compounds (including some pesticides and herbicide) through interfering with endocrine system, have the capability to induce developmental and reproductive abnormalities in humans and animals. Pesticides are currently being used in large scales in many developed and developing countries (including Iran), so this study has been conducted to determine the percentage of endocrine disruptor agents in pesticides used in Fars province. The results showed that more than 1,581,690 L of pesticides, in 86 different brands, have been used in Fars province during year 1380 and 25.93% (34 types) of them had at least one carcinogenic agents. At least 30 pesticides (711720 L, 44.99%) had one endocrine disruptor agent and therefore can be classified as environmental hormones or endocrine disrupting chemicals. The percentage of pesticides whom interfering with normal endocrine system activity were, 7.82% (66572 L), 4.54% (39975 L), 22.02% (348400 L), 5.12% (81000 L) and 21.18% (34500 L) of pesticides were antiestrogenic, antiandorgenic, antityroidic, antigonadotropin and anitestroid hormones, respectively. The results showed that about 50% of pesticides which currently being used in Fars province should be banned.

  20. Twenty-Five Years of Endocrine Disruption Science: Remembering Theo Colborn

    PubMed Central

    Kwiatkowski, Carol F.; Bolden, Ashley L.; Liroff, Richard A.; Rochester, Johanna R.; Vandenbergh, John G.

    2016-01-01

    Summary: For nearly 30 years, Dr. Theo Colborn (1927–2014) dedicated herself to studying the harmful effects of endocrine-disrupting chemicals on wildlife, humans, and the environment. More recently, she extended this effort to address the health impacts of unconventional oil and gas development. Colborn was a visionary leader who excelled at synthesizing scientific findings across disciplines. Using her unique insights and strong moral convictions, she changed the face of toxicological research, influenced chemical regulatory policy, and educated the public. In 2003, Colborn started a nonprofit organization—The Endocrine Disruption Exchange (TEDX). As we celebrate the 25th anniversary of endocrine disruption science, TEDX continues her legacy of analyzing the extensive body of environmental health research and developing unique educational resources to support public policy and education. Among other tools, TEDX currently uses the systematic review framework developed by the National Toxicology Program at the National Institute of Environmental Health Sciences, to answer research questions of pressing concern. In this article, we pay homage to the tenacious woman and the exemplary contribution she made to the field of environmental health. Recommendations for the future of the field are drawn from her wisdom. PMID:27580976

  1. Endocrine disruption in wild populations of chub (Leuciscus cephalus) in contaminated French streams.

    PubMed

    Hinfray, Nathalie; Palluel, Olivier; Piccini, Benjamin; Sanchez, Wilfried; Aït-Aïssa, Selim; Noury, Patrice; Gomez, Elena; Geraudie, Perrine; Minier, Christophe; Brion, François; Porcher, Jean-Marc

    2010-04-01

    The aim of this study was to assess endocrine disruptive effects in wild population of fish in five French rivers selected to represent different pollution contexts at two seasons (summer and fall). For that purpose, a panel of biometrical parameters (length, weight, and gonado-somatic index: GSI) and biochemical (ethoxyresorufin-O-deethylase: EROD, vitellogenin: VTG, and brain aromatase) and histological biomarkers (gonads histology) were used in chub (Leuciscus cephalus), a common cyprinid fish species. In fish from the reference site, EROD activity and VTG levels were low at the two seasons. Brain aromatase activities (AAs) were similar to other species and increased with increasing GSI and gonad maturation. Among the four contaminated sites, the Jalle d'Eysines River was the most impacted site. At this site, fish were exposed to estrogenic substances as demonstrated by the VTG induction in males and the arrest of development of the gonads that led to lower brain AA compared to fish from the reference site. In fish from other contaminated sites, EROD activity was induced as compared to fish from the reference site and some males had elevated concentrations of VTG. Moreover, the presence of aromatase-inhibiting compounds was demonstrated in the sediments of three contaminated sites, even if the precise nature of contaminants is not known. This study provides new data concerning endocrine disruption in wild fish populations inhabiting French rivers and demonstrates that measurements of in vivo and in vitro aromatase could be used as biomarkers of endocrine disruption in field studies.

  2. Endocrine disrupting chemicals in the atmosphere: Their effects on humans and wildlife.

    PubMed

    Annamalai, Jayshree; Namasivayam, Vasudevan

    2015-03-01

    Endocrine disrupting chemicals (EDCs) are exogenous agents that interfere or disrupt the normal synthesis, secretion, transportation, binding and metabolism of natural hormones; eventually dysregulating homeostatic mechanisms, reproduction and development. They are emitted into the atmosphere during anthropogenic activities and physicochemical reactions in nature. Inhalation of these EDCs as particulate and gaseous vapors triggers their interaction with endocrine glands and exerts agonist or antagonists actions at hormone receptors. The endocrine disruption at nanogram levels of EDC's has gained concern in the last decade, due to infertility among men and women, early puberty, obesity, diabetes and cancer. Thus, the review explores the literature that addresses the major occurring EDCs in the atmosphere including phthalates, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), brominated flame retardants (BFRs), dioxins, alkylphenols (APs) and perfluorinated chemicals (PFCs). Sources, fate, half-life, mechanism, measured concentrations in air, bioaccumulation in tissues, laboratory exposures correlating to toxicological effects of these EDCs in humans and wildlife are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Endocrine disrupting chemicals in Minnesota lakes - Water-quality and hydrological data from 2008 and 2010

    USGS Publications Warehouse

    Barber, Larry B.; Writer, Jeffrey H.; Keefe, Steffanie K.; Brown, Greg K.; Ferrey, Mark L.; Jahns, Nathan D.; Kiesling, Richard L.; Lundy, James R.; Poganski, Beth H.; Rosenberry, Donald O.; Taylor, Howard E.; Woodruff, Olivia P.; Schoenfuss, Heiko L.

    2012-01-01

    Understanding the sources, fate, and effects of endocrine disrupting chemicals in aquatic ecosystems is important for water-resource management. This study was conducted during 2008 and 2010 to establish a framework for assessing endocrine disrupting chemicals, and involved a statewide survey of their occurrence in 14 Minnesota lakes and a targeted study of different microhabitats on a single lake. The lakes ranged in size from about 0.1 to 100 square kilometers, varied in trophic status from oligotrophic to eutrophic, and spanned a range of land-uses from wetlands and forest to agricultural and urban use. Water and sediment samples were collected from the near-shore littoral environment and analyzed for endocrine disrupting chemicals, including trace elements, acidic organic compounds, neutral organic compounds, and steroidal hormones. In addition, polar organic compound integrative samplers were deployed for 21 days and analyzed for the same organic compounds. One lake was selected for a detailed microhabitat study of multiple near-shore environments. This report compiles the results from the field measurements and laboratory chemical analysis of water, sediment, and polar organic compound integrative sampler samples collected during 2008 and 2010. Most of the organic compounds measured were not detected in any of the water samples, although a few compounds were detected in several of the lakes.

  4. Pulp and paper mill effluent treatments have differential endocrine-disrupting effects on rainbow trout.

    PubMed

    Orrego, Rodrigo; Guchardi, John; Hernandez, Victor; Krause, Rachelle; Roti, Lucia; Armour, Jeffrey; Ganeshakumar, Mathumai; Holdway, Douglas

    2009-01-01

    Endocrine disruption (ED) effects due to pulp and paper mill effluents extracts involving different industrial procedures and effluent treatments (nontreated, primary, and secondary treated) were evaluated using immature triploid rainbow trout in a pulse-exposure toxicity experiment. The protocol involved the use of intraperitoneal injection of mill extracts (solid-phase extraction [SPE]) corrected for individual fish weight and included several laboratory standards (steroidal hormones and phytosterols). Biological endpoints at two different levels of biological organization were analyzed (molecular and individual organism). Results indicated that nonsignificant changes were observed in the individual physiological indices represented by condition factor, liver somatic index, and gonad somatic index during the experiment. Significant induction of liver ethoxyresorufin-O-deethylase activity was observed between different effluent treatments and experimental controls. Significant endocrine-disrupting effects at the reproductive level were observed in all effluent treatments involving significant increments in plasma vitellogenin (VTG) levels. Fish exposed to untreated effluent extracts had significantly higher VTG levels compared to fish exposed to primary and secondary treatment effluent extracts, indicating a decrease of the estrogenic effect due to the effluent treatment. The present study has shown that for the Chilean pulp and paper mill SPE extracts evaluated, an endocrine disruption effect was induced in immature triploid rainbow, reaffirming the significant estrogenic effects demonstrated previously in laboratory and field experiments.

  5. Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways

    EPA Pesticide Factsheets

    Event page for the upcoming Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) meeting to consider and review Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption

  6. USE OF POPULATION STUDIES TO IDENTIFY ASSOCIATIONS BETWEEN ADVERSE HEALTH EFFECTS AND ENVIRONMENTAL EXPOSURES TO ENDOCRINE DISRUPTING HERBICIDES

    EPA Science Inventory

    Not only animal studies, but also population (ecologic) studies can contribute to the identification of endocrine disrupting chemicals. Population studies are fundamental in identifying public health hazards, and provide hypotheses for more targeted studies. Chlorophenoxy herb...

  7. USE OF POPULATION STUDIES TO IDENTIFY ASSOCIATIONS BETWEEN ADVERSE HEALTH EFFECTS AND ENVIRONMENTAL EXPOSURES TO ENDOCRINE DISRUPTING HERBICIDES

    EPA Science Inventory

    Not only animal studies, but also population (ecologic) studies can contribute to the identification of endocrine disrupting chemicals. Population studies are fundamental in identifying public health hazards, and provide hypotheses for more targeted studies. Chlorophenoxy herb...

  8. Multi-tiered Approach to Development of Increased Throughput Assay Models to Assess Endocrine-Disrupting Activity of Chemicals

    EPA Science Inventory

    Screening for endocrine-disrupting chemicals (EDCs) requires sensitive, scalable assays. Current high-throughput screening (HTPS) approaches for estrogenic and androgenic activity yield rapid results, but many are not sensitive to physiological hormone concentrations, suggesting ...

  9. Multi-tiered Approach to Development of Increased Throughput Assay Models to Assess Endocrine-Disrupting Activity of Chemicals

    EPA Science Inventory

    Screening for endocrine-disrupting chemicals (EDCs) requires sensitive, scalable assays. Current high-throughput screening (HTPS) approaches for estrogenic and androgenic activity yield rapid results, but many are not sensitive to physiological hormone concentrations, suggesting ...

  10. SCREENING AND TESTING FOR ENDOCRINE DISRUPTION IN FISH - BIOMARKERS AS "SIGNPOSTS," NOT "TRAFFIC LIGHTS," IN RISK ASSESSMENT

    EPA Science Inventory

    Biomarkers provide important tools for addressing the impacts of endocrine disrupting chemicals (EDCs) in fish. Presently, biomarkers are best used as mechanistic "signposts" rather than as "red traffic lights" in the environmental risk assessment of EDCs. In field studies, bio...

  11. Effects of endocrine disrupters on the expression of growth hormone and prolactin mRNA in the rainbow trout pituitary.

    USDA-ARS?s Scientific Manuscript database

    It is now widely accepted that chemical pollutants in the environment can interfere with the endocrine system of animals, thus affecting development and reproduction. Some of these endocrine disrupters (EDs) can have estrogenic or antiestrogenic effects. Most studies to date have focused on the ef...

  12. Racial/ethnic disparities in environmental endocrine disrupting chemicals and women's reproductive health outcomes: epidemiological examples across the life course.

    PubMed

    James-Todd, Tamarra M; Chiu, Yu-Han; Zota, Ami R

    2016-06-01

    Disparities in women's reproductive health outcomes across the life course have been well-documented. Endocrine disrupting chemicals may be one factor driving disparities, as studies suggest exposure to certain environmental endocrine disrupting chemicals, such as certain phthalates, bisphenol A, parabens and polybrominated diphenyl ethers are higher in non-whites. Yet, a limited amount of research has focused on these chemical exposures as a potential mediator of racial/ethnic differences in women's reproductive health outcomes, such as pubertal development, fibroids, infertility, and pregnancy complications. Given that race/ethnicity is a social construct, the purpose of this review was to present the current state of the literature on racial/ethnic disparities in both environmental endocrine disrupting chemicals, as well as associations between these chemicals and selected women's reproductive health outcomes. Our goal was to evaluate literature from populations based in the United States to: 1) characterize racial/ethnic differences in environmental endocrine disrupting chemicals and 2) systematically review literature on environmental endocrine disrupting chemicals and selected women's health outcomes in populations containing more than one racial/ethnic group. This review highlights the need for future work in determining whether higher exposures to some environmental endocrine disrupting chemicals might partly explain differences in women's reproductive health outcomes in these higher-exposure and high-risk groups.

  13. Endocrine-disrupting effect of the ultraviolet filter benzophenone-3 in zebrafish, Danio rerio.

    PubMed

    Kinnberg, Karin L; Petersen, Gitte I; Albrektsen, Mette; Minghlani, Mita; Awad, Suad Mohamud; Holbech, Bente F; Green, John W; Bjerregaard, Poul; Holbech, Henrik

    2015-12-01

    The chemical ultraviolet (UV) filter benzophenone-3 (BP-3) is suspected to be an endocrine disruptor based on results from in vitro and in vivo testing. However, studies including endpoints of endocrine adversity are lacking. The present study investigated the potential endocrine-disrupting effects of BP-3 in zebrafish (Danio rerio) in the Fish Sexual Development Test (Organisation for Economic Co-operation and Development TG 234) and a 12-d adult male zebrafish study. In TG 234, exposure from 0 d to 60 d posthatch caused a monotone dose-dependent skewing of the phenotypic sex ratio toward fewer males and more female zebrafish (no observed effect concentration [NOEC]: 191 μg/L, lowest observed effect concentration [LOEC]: 388 μg/L). Besides, gonad maturation was affected in both female fish (NOEC 191 μg/L, LOEC 388 μg/L) and male fish (NOEC 388 μg/L, LOEC 470 μg/L). Exposure to BP-3 did not affect the vitellogenin concentration in TG 234. After 12 d exposure of adult male zebrafish, a slight yet significant increase in the vitellogenin concentration was observed at 268 μg/L but not at 63 μg/L and 437 μg/L BP-3. Skewing of the sex ratio is a marker of an endocrine-mediated mechanism as well as a marker of adversity, and therefore the conclusion of the present study is that BP-3 is an endocrine-disrupting chemical in accordance with the World Health Organization's definition. © 2015 SETAC.

  14. European Union's strategy on endocrine disrupting chemicals and the current position of Slovenia.

    PubMed

    Perharič, Lucija; Fatur, Tanja; Drofenik, Jernej

    2016-06-01

    In view of the European Union regulations 1107/2009 and 528/2012, which say that basic substances in plant protection and biocidal products marketed in the European Union (EU) should not have an inherent capacity to cause endocrine disruption, an initiative was started to define scientific criteria for the identification of endocrine disruptors (EDs). The objectives of the EU strategy on EDs are to protect human health and the environment, to assure the functioning of the market, and to provide clear and coherent criteria for the identification of EDs that could have broad application in the EU legislation. Policy issues were to be addressed by the Ad-hoc group of Commission Services, EU Agencies and Member States established in 2010, whereas the scientific issues were to be addressed by the Endocrine Disruptors Expert Advisory Group (ED EAG), established in 2011. The ED EAG adopted the 2002 World Health Organization (WHO) definition of endocrine disruptor and agreed that for its identification it is necessary to produce convincing evidence of a biologically plausible causal link between an adverse effect and endocrine disrupting mode of action. In 2014, the European Commission proposed four ED identification criteria options and three regulatory options, which are now being assessed for socio-economic, environmental, and health impact. Slovenia supports the establishing of identification criteria and favours option 4, according to which ED identification should be based on the WHO definition with the addition of potency as an element of hazard characterisation. As for regulatory options, Slovenia favours the risk-based rather than hazard-based regulation.

  15. Personal care products and endocrine disruption: A critical review of the literature.

    PubMed

    Witorsch, Raphael J; Thomas, John A

    2010-11-01

    This article reviews laboratory and epidemiological research into the endocrine disruptive effects of components of personal care products, namely, phthalate esters, parabens, ultraviolet (UV) filters, polycyclic musks, and antimicrobials. High doses of phthalates in utero can produce “phthalate syndrome,” demasculinizing effects in male rat offspring due to impaired testosterone production by fetal testes. However, evidence linking phthalate exposure to similar effects in humans appears inconclusive. Furthermore, phthalate exposure derived from personal care products is within safe limits and its principal bioavailable phthalate, diethyl phthalate (DEP), does not produce “phthalate syndrome.” Parabens exhibit very weak estrogen activity in vitro and in vivo, but evidence of paraben-induced developmental and reproductive toxicity in vivo lacks consistency and physiological coherence. Evidence attempting to link paraben exposure with human breast cancer is nonexistent. Select UV filters at high doses produce estrogenic, antithyroid, and other effects in rats in vivo. Again, no evidence links UV filter exposure to endocrine disruptive effects in humans. Some polycyclic musks weakly bind to estrogen, androgen, or progestin receptors and exhibit primarily antagonistic activity in vitro, which for the most part, has yet to be confirmed in vivo in mammals. The antimicrobials triclocarban and triclosan evoke weak responses mediated by aryl hydrocarbon, estrogen, and androgen receptors in vitro, which require confirmation in vivo. Preliminary observations suggest a novel interaction between triclocarban and testosterone. In conclusion, although select constituents exhibit interactions with the endocrine system in the laboratory, the evidence linking personal care products to endocrine disruptive effects in humans is for the most part lacking.

  16. Environmental analysis of endocrine disrupting effects from hydrocarbon contaminants in the ecosystem. 1998 annual progress report

    SciTech Connect

    McLachlan, J.

    1998-06-01

    'The objective of this project is to determine how environmental contaminants, namely hydrocarbons, can act as hormones or anti-hormones (i.e., environmental hormones) in different species present in aquatic ecosystems. Species of particular focus are those which can serve as sentinel species (e.g., amphibians) and, thus, provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. This reports the progress of 1.5 years of a three-year grant awarded to the Tulane/Xavier Center for Bioenvironmental Research (CBR). A growing body of evidence suggests that chemicals in the environment can disrupt the endocrine system of animals (i.e., wildlife and humans) and adversely impact the development of these species. Because of the multitude of known endocrine-disrupting chemicals and the numerous industrial and government sectors producing these chemicals, almost every federal agency has initiated research on the endocrine effects of chemicals relevant to their operations. This study represents the Department of Energy (DOE) Basic Energy Sciences'' only research on the impacts of endocrine-disrupting chemicals. The activities employed by this project to determine these impacts include development of biotechnology screens (in vitro), animal screens (in vivo), and other analyses of aquatic ecosystem biomarkers of exposure. The results from this study can elucidate how chemicals in the environment, including those from DOE activities, can signal (and alter) the development of a number of species in aquatic ecosystems. These signals can have detrimental impacts not only on an organismal level, but also on community, population, and entire ecosystem levels, including humans.'

  17. Microcystin-RR exposure results in growth impairment by disrupting thyroid endocrine in zebrafish larvae.

    PubMed

    Xie, Liqiang; Yan, Wei; Li, Jing; Yu, Liqin; Wang, Jianghua; Li, Guangyu; Chen, Nan; Steinman, Alan D

    2015-07-01

    Recent studies have shown that cyanobacteria-derived microcystins (MCs) have the potential to disrupt endocrine systems. However, the effects of microcystin-RR (MC-RR) and their underlying mechanisms are poorly resolved in fish. In this study, MC-RR exposure through submersion caused serious developmental toxicity, such as growth delay and depressed heart rates in zebrafish larvae. We also detected decreased levels of thyroid hormones (THs), suggesting that MC-RR-triggered thyroid endocrine disruption might contribute to the growth impairment observed in developing zebrafish. To further our understanding of mechanisms of MC-RR-induced endocrine toxicity, quantitative real-time PCR (QPCR) analysis was performed on hypothalamic-pituitary-thyroid (HPT) axis related genes, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2), of developing zebrafish embryos exposed to 0, 0.3, 1.0 or 3.0mgL(-1) MC-RR until 96h post-fertilization. Our results showed that transcription pattern of HPT axis related genes were greatly changed by MC-RR exposure, except TG gene. Furthermore, western blot was used to validate the results of gene expression. The results showed protein synthesis of TG was not affected, while that of NIS was significantly up-regulated, which are in accordance with gene expression. The overall results indicated that exposure to MC-RR can induce developmental toxicity, which might be associated with thyroid endocrine disruption in developing zebrafish larvae.

  18. Analysis of Endocrine Disrupting Pesticides by Capillary GC with Mass Spectrometric Detection

    PubMed Central

    Matisová, Eva; Hrouzková, Svetlana

    2012-01-01

    Endocrine disrupting chemicals, among them many pesticides, alter the normal functioning of the endocrine system of both wildlife and humans at very low concentration levels. Therefore, the importance of method development for their analysis in food and the environment is increasing. This also covers contributions in the field of ultra-trace analysis of multicomponent mixtures of organic pollutants in complex matrices. With this fact conventional capillary gas chromatography (CGC) and fast CGC with mass spectrometric detection (MS) has acquired a real importance in the analysis of endocrine disrupting pesticide (EDP) residues. This paper provides an overview of GC methods, including sample preparation steps, for analysis of EDPs in a variety of matrices at ultra-trace concentration levels. Emphasis is put on separation method, mode of MS detection and ionization and obtained limits of detection and quantification. Analysis time is one of the most important aspects that should be considered in the choice of analytical methods for routine analysis. Therefore, the benefits of developed fast GC methods are important. PMID:23202677

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

    PubMed Central

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

    2016-01-01

    The extent of our knowledge on the number of chemical compounds related to anthropogenic activities that can cause damage to the environment and to organisms is increasing. Endocrine disrupting chemicals (EDCs) are one group of potentially hazardous substances that include natural and synthetic chemicals and have the ability to mimic endogenous hormones, interfering with their biosynthesis, metabolism, and normal functions. Adverse effects associated with EDC exposure have been documented in aquatic biota and there is widespread interest in the characterization and understanding of their modes of action. Fish are considered one of the primary risk organisms for EDCs. Zebrafish (Danio rerio) are increasingly used as an animal model to study the effects of endocrine disruptors, due to their advantages compared to other model organisms. One approach to assess the toxicity of a compound is to identify those patterns of gene expression found in a tissue or organ exposed to particular classes of chemicals, through new technologies in genomics (toxicogenomics), such as microarrays or whole-genome sequencing. Application of these technologies permit the quantitative analysis of thousands of gene expression changes simultaneously in a single experiment and offer the opportunity to use transcript profiling as a tool to predict toxic outcomes of exposure to particular compounds. The application of toxicogenomic tools for identification of chemicals with endocrine disrupting capacity using the zebrafish model system is reviewed. PMID:28217008

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

    PubMed

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

    2016-12-01

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

  1. Endocrine-disrupting chemicals and obesity development in humans: a review.

    PubMed

    Tang-Péronard, J L; Andersen, H R; Jensen, T K; Heitmann, B L

    2011-08-01

    This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

  2. A path forward in the debate over health impacts of endocrine disrupting chemicals.

    PubMed

    Zoeller, R Thomas; Bergman, Åke; Becher, Georg; Bjerregaard, Poul; Bornman, Riana; Brandt, Ingvar; Iguchi, Taisen; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Skakkebaek, Niels E; Toppari, Jorma; Vandenberg, Laura N

    2014-12-22

    Several recent publications reflect debate on the issue of "endocrine disrupting chemicals" (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as "endocrine disrupting chemical", "adverse effects", and "endocrine system". The second is focused on elements of hormone action including "potency", "endpoints", "timing", "dose" and "thresholds". The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate.

  3. Vitellogenin and zona radiata proteins as biomarkers of endocrine disruption in peregrine falcon (Falco peregrinus).

    PubMed

    Jiménez, Begoña; Mori, Gabriele; Concejero, Miguel A; Merino, Rubén; Casini, Silvia; Fossi, María Cristina

    2007-04-01

    The aim of this study was to test a specific method for the detection of Vitellogenin (Vtg) and Zona Radiata Proteins (Zrp) in plasma from peregrine falcon (Falco peregrinus) as specific biomarkers for the evaluation of the effects of endocrine disruptors. The method was assayed with different peregrine falcon individuals (including mature and immature birds of both sexes) from a Spanish population being studied in terms of their contamination with organochlorine compounds with endocrine disrupting properties. This study shows that mouse anti bird Vtg monoclonal antibody ND3C3 (Biosense) seems to be the most specific antibody in binding plasmatic lipoproteins in peregrine falcon when compared to other anti Vtg antibodies. Rabbit anti salmon Zrp polyclonal antibodies O146 (Biosense) show cross-reactivity with Zrp in the samples studied. These preliminary results confirm the applicability of both of these diagnostic tools assayed (induction of Vtg and Zrp) in detecting exposure to Endocrine Disrupting Chemicals (EDCs) in this species. The increase of Vtg and Zrp detected in male specimens suggest a potential hazard to EDCs in the peregrine falcon which represents a species still affected by organochlorine compounds, and in particular those with estrogenic activity.

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

    PubMed

    Zawatski, William; Lee, Mary M

    2013-01-01

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

  5. Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish.

    PubMed

    Kanungo, Jyotshna; Cuevas, Elvis; Guo, Xiaoqing; Lopez, Aida G; Ramirez-Lee, Manuel A; Trickler, William; Paule, Merle G; Ali, Syed F

    2012-09-27

    Nicotine, a drug of abuse, has been reported to have many adverse effects on the developing nervous system. In rodents, chronic nicotine exposure inhibits estrogen-mediated neuroprotection against cerebral ischemia in females suggesting that nicotine could disrupt endocrine targets. Zebrafish have been used as a model system for examining mechanisms underlying nicotinic effects on neuronal development. Here, using zebrafish embryos, we demonstrate that nicotine alters the expression of the validated endocrine disruption (ED) biomarkers, vitellogenin (vtg 1 and vtg 2) and cytochrome p450 aromatase (cyp19a1a and cyp19a1b) at the transcriptional level. Increased expression of three of these molecular markers (vtg 1, vtg 2 and cyp19a1b) in response to 17β-estradiol (E2) was more pronounced in 48hpf (hours post-fertilization) embryos than in the 24hpf embryos. While 24hpf embryos were non-responsive in this regard to 25μM nicotine, a similar exposure of the 48hpf embryos for 24h significantly down-regulated the expression of all four ED biomarker genes indicating that nicotine's anti-estrogenic effects are detectable in the 48hpf zebrafish embryos. These results provide direct molecular evidence that nicotine is an endocrine disruptor in zebrafish.

  6. Endocrine disruption of cadmium in rats using the OECD enhanced TG 407 test system.

    PubMed

    Wang, Heng Juan; Liu, Zhao Ping; Jia, Xu Dong; Chen, Hao; Tan, Yan Jun

    2014-12-01

    To evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline. Sprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected. Cd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney. Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  7. Determination and occurrence of organic micropollutants in reverse osmosis treatment for advanced water reuse.

    PubMed

    Gomez, Veronica; Majamaa, Katariina; Pocurull, Eva; Borrull, Francesc

    2012-01-01

    The growing demand on water resources has increased the interest in wastewater reclamation for multiple end-use applications such as indirect and direct potable reuse. In these applications, the removal of organic micropollutants is of a greater concern than in conventional wastewater treatment. This article presents a collection of data of trace organic micropollutants in an urban wastewater treatment plant (WWTP) in North East Spain using reverse osmosis (RO) membrane treatment. The RO rejection values of the organic molecules studied with a wide range of solute size and hydrophobicity were determined. Several chromatographic methods monitoring different endocrine disrupting chemicals (EDCs), pharmaceuticals and personal care products (PPCPs) were used. Results indicated that secondary effluents from this Spanish WWTP contained most of the studied organic compounds indicating incomplete removal of organics in the conventional treatment of the plant. However, the rejection of most micropollutants was high for all three RO membrane types (low energy, high rejection, fouling resistant) tested. It was observed that some selected micropollutants were less efficiently removed (e.g. the small and polar and the more hydrophobic) and the molecular weight and membrane material influenced removal efficiencies.

  8. Traumatic brain injury and neuro-endocrine disruption: medical and psychosocial rehabilitation.

    PubMed

    Webb, Nadia E; Little, Brittany; Loupee-Wilson, Stephanie; Power, Elizabeth M

    2014-01-01

    Traumatic Brain Injury (TBI) initiates a cascade of neuromodulatory damage that blurs the distinctions between physical and psychological medicine. Monitoring endocrine function through labs is not part of the medical care algorithm for treatment of TBI, but the clinical symptoms are easily misidentified as they include: depression, fatigue, poor concentration, irritability and a decline in overall cognitive functioning. The reciprocal flow of change between neuroendocrine health and psychosocial health is well established within the field of neuroscience, social psychology, endocrinology and behavioral neurology, but has not translated into patient care. This paper outlines common neuroendocrine disruptions secondary to TBI and their clinical implications for treating mental health professionals. Wider adoption of the consensus guidelines on the detection and monitoring of endocrine abnormalities post-TBI may diminish the severity of functional impairment and improve quality of life.

  9. Neuropeptides and enzymes are targets for the action of endocrine disrupting chemicals in the vertebrate brain.

    PubMed

    Panzica, G C; Bo, E; Martini, M A; Miceli, D; Mura, E; Viglietti-Panzica, C; Gotti, S

    2011-01-01

    Endocrine-disrupting chemicals (EDC) are molecules that interfere with endocrine signaling pathways and produce adverse consequences on animal and human physiology, such as infertility or behavioral alterations. Some EDC act through binding to androgen or/and estrogen receptors primarily operating through a genomic mechanism regulating gene expression. This mechanism of action may induce profound developmental adverse effects, and the major targets of the EDC action are the gene products, i.e., mRNAs inducing the synthesis of various peptidic molecules, which include neuropeptides and enzymes related to neurotransmitters syntheses. Available immunohistochemical data on some of the systems that are affected by EDC in lower and higher vertebrates are detailed in this review.

  10. Regulatory Decisions on Endocrine Disrupting Chemicals Should be Based on the Principles of Endocrinology

    PubMed Central

    Vandenberg, Laura N.; Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Myers, John Peterson; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

    2013-01-01

    For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose-response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialogue on their impact on risk assessment. PMID:23411111

  11. Endocrine disrupters, microRNAs, and primordial germ cells: a dangerous cocktail.

    PubMed

    Brieño-Enríquez, Miguel Angel; Larriba, Eduardo; Del Mazo, Jesús

    2016-09-15

    Endocrine-disrupting chemicals (EDCs) are environmental pollutants that may change the homeostasis of the endocrine system, altering the differentiation of germ cells with consequences for reproduction. In mammals, germ cell differentiation begins with primordial germ cells (PGCs) during embryogenesis. Primordial germ cell development and gametogenesis are genetically regulated processes, in which the posttranscriptional gene regulation could be mediated by small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Here, we review the deleterious effects of exposure during fetal life to EDCs mediated by deregulation of ncRNAs, and specifically miRNAs on PGC differentiation. Moreover, the environmental stress induced by exposure to some EDCs during the embryonic window of development could trigger reproductive dysfunctions transgenerationally transmitted by epigenetic mechanisms with the involvement of miRNAs expressed in germ line cells. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology.

    PubMed

    Vandenberg, Laura N; Colborn, Theo; Hayes, Tyrone B; Heindel, Jerrold J; Jacobs, David R; Lee, Duk-Hee; Myers, John Peterson; Shioda, Toshi; Soto, Ana M; vom Saal, Frederick S; Welshons, Wade V; Zoeller, R Thomas

    2013-07-01

    For years, scientists from various disciplines have studied the effects of endocrine disrupting chemicals (EDCs) on the health and wellbeing of humans and wildlife. Some studies have specifically focused on the effects of low doses, i.e. those in the range that are thought to be safe for humans and/or animals. Others have focused on the existence of non-monotonic dose-response curves. These concepts challenge the way that chemical risk assessment is performed for EDCs. Continued discussions have clarified exactly what controversies and challenges remain. We address several of these issues, including why the study and regulation of EDCs should incorporate endocrine principles; what level of consensus there is for low dose effects; challenges to our understanding of non-monotonicity; and whether EDCs have been demonstrated to produce adverse effects. This discussion should result in a better understanding of these issues, and allow for additional dialog on their impact on risk assessment.

  13. Consequences of endocrine disrupting chemicals on reproductive endocrine function in birds: establishing reliable end points of exposure.

    PubMed

    Ottinger, M A; Quinn, M J; Lavoie, E; Abdelnabi, M A; Thompson, N; Hazelton, J L; Wu, J M; Beavers, J; Jaber, M

    2005-08-01

    It has been difficult to establish reliable indices of exposure to endocrine disrupting chemicals (EDCs) appropriate for a variety of avian species because of a vast array of reproductive strategies. Data from mammals, reptiles and fish provide insight on likely mechanisms of action for EDCs. However, many of the effects of EDCs are weaker than the actions of the native hormones, making it difficult to assess adverse effects in domestic and wild birds. It is clear that differential sensitivity to EDCs exists across species, due to the timing and mode of exposure, compound toxicity and age of the individual. Our studies on EDCs are conducted in the quail model system, with focus on reproductive endocrine, neuroendocrine and behavioral responses. Studies have included EDC exposure, either by egg injection or via diet. Results from egg injection studies showed the following: (1) estradiol administered by embryonic day 12 demasculinized male sexual behavior, altered hypothalamic neurotransmitters and reduced hen day production and fertility in a dose dependent fashion, (2) methoxychlor (MXC) or vinclozolin impaired male sexual behavior in adult quail and (3) DDE exposure impaired reproductive and immune related end points. Two-generation studies were conducted on Japanese and northern bobwhite quail with dietary methoxychlor (MXC) exposure (0, 5 and 10 ppm) beginning in adults (P1), continuing in their offspring (F1), with F2 offspring raised on control diet. MXC exposure impaired male sexual behavior, hypothalamic catecholamines and plasma steroid hormones. Moreover, MXC exposure had reproductive consequences observable at both the lower and higher doses of MXC in F1 and F2 generations. These data demonstrate that embryonic EDC exposure interferes with sexual differentiation of neural systems that direct reproduction.

  14. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals.

    PubMed

    Sanderson, J Thomas

    2006-11-01

    Various chemicals found in the human and wildlife environments have the potential to disrupt endocrine functions in exposed organisms. Increasingly, the enzymes involved in the steroid biosynthesis pathway are being recognized as important targets for the actions of various endocrine-disrupting chemicals. Interferences with steroid biosynthesis may result in impaired reproduction, alterations in (sexual) differentiation, growth, and development and the development of certain cancers. Steroid hormone synthesis is controlled by the activity of several highly substrate-selective cytochrome P450 enzymes and a number of steroid dehydrogenases and reductases. Particularly aromatase (CYP19), the enzyme that converts androgens to estrogens, has been the subject of studies into the mechanisms by which chemicals interfere with sex steroid hormone homeostasis and function, often related to (de)feminization and (de)masculinazation processes. Studies in vivo and in vitro have focussed on ovarian and testicular function, with less attention given to other steroidogenic organs, such as the adrenal cortex. This review aims to provide a comprehensive overview of the state of knowledge regarding the mechanisms by which chemicals interfere with the function of steroidogenic enzymes in various tissues and organisms. The endocrine toxicities and mechanisms of action related to steroidogenesis of a number of classes of drugs and environmental contaminants are discussed. In addition, several potential in vitro bioassays are reviewed for their usefulness as screening tools for the detection of chemicals that can interfere with steroidogenesis. Analysis of the currently scattered state of knowledge indicates that still relatively little is known about the underlying mechanisms of interference of chemicals with steroidogenesis and their potential toxicity in steroidogenic tissues, neither in humans nor in wildlife. Considerably more detailed and systematic research in this area of

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

    Brown, James S.

    2009-01-01

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

  17. An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

    SciTech Connect

    Frizzell, Caroline; Ndossi, Doreen; Kalayou, Shewit; Eriksen, Gunnar S.; Verhaegen, Steven; Sørlie, Morten; Elliott, Christopher T.; Ropstad, Erik; Connolly, Lisa

    2013-08-15

    Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene expression.

  18. Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders

    PubMed Central

    Le Magueresse-Battistoni, Brigitte; Labaronne, Emmanuel; Vidal, Hubert; Naville, Danielle

    2017-01-01

    Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules. PMID:28588754

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

    SciTech Connect

    Taxvig, Camilla Olesen, Pelle Thonning; Nellemann, Christine

    2011-02-01

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

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

    PubMed

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

    2011-02-01

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

  1. Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters.

    PubMed

    Isling, Louise Krag; Boberg, Julie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Axelstad, Marta; Christiansen, Sofie; Vinggaard, Anne Marie; Taxvig, Camilla; Kortenkamp, Andreas; Hass, Ulla

    2014-01-01

    This study examined late-life effects of perinatal exposure of rats to a mixture of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, u.v.-filters, bisphenol A, parabens, and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.

  2. 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.

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

    PubMed

    Khalil, Naila; Chen, Aimin; Lee, Miryoung

    2014-12-01

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

  4. An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

    USGS Publications Warehouse

    Iwanowicz, L.R.; Blazer, V.S.

    2011-01-01

    Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

  5. Bisphenol A and phthalate endocrine disruption of parental and social behaviors

    PubMed Central

    Rosenfeld, Cheryl S.

    2015-01-01

    Perinatal exposure to endocrine disrupting chemicals (EDCs) can induce promiscuous neurobehavioral disturbances. Bisphenol A and phthalates are two widely prevalent and persistent EDCs reported to lead to such effects. Parental and social behaviors are especially vulnerable to endocrine disruption, as these traits are programmed by the organizational-activational effects of testosterone and estrogen. Exposure to BPA and other EDCs disrupts normal maternal care provided by rodents and non-human primates, such as nursing, time she spends hunched over and in the nest, and grooming her pups. Paternal care may also be affected by BPA. No long-term study has linked perinatal exposure to BPA or other EDC and later parental behavioral deficits in humans. The fact that the same brain regions and neural hormone substrates govern parental behaviors in animal models and humans suggests that this suite of behaviors may also be vulnerable in the latter. Social behaviors, such as communication, mate choice, pair bonding, social inquisitiveness and recognition, play behavior, social grooming, copulation, and aggression, are compromised in animal models exposed to BPA, phthalates, and other EDCs. Early contact to these chemicals is also correlated with maladaptive social behaviors in children. These behavioral disturbances may originate by altering the fetal or adult gonadal production of testosterone or estrogen, expression of ESR1, ESR2, and AR in the brain regions governing these behaviors, neuropeptide/protein hormone (oxytocin, vasopressin, and prolactin) and their cognate neural receptors, and/or through epimutations. Robust evidence exists for all of these EDC-induced changes. Concern also exists for transgenerational persistence of such neurobehavioral disruptions. In sum, evidence for social and parental deficits induced by BPA, phthalates, and related chemicals is strongly mounting, and such effects may ultimately compromise the overall social fitness of populations to

  6. Endocrine disruption in Sphoeroides testudineus tissues and sediments highlights contamination in a northeastern Brazilian estuary.

    PubMed

    Pimentel, Marcionília Fernandes; Damasceno, Évila Pinheiro; Jimenez, Paula Christine; Araújo, Pedro Filipe Ribeiro; Bezerra, Marcielly Freitas; de Morais, Pollyana Cristina Vasconcelos; Cavalcante, Rivelino Martins; Loureiro, Susana; Lotufo, Letícia Veras Costa

    2016-05-01

    In recent decades, considerable attention has been devoted to endocrine disruptor chemicals (EDC) and studies on fish feminization have increased throughout the years as a key signal for aquatic environmental contamination. The input of domestic sewage into water reservoirs is common in South American countries, especially in cities that experienced rapid population growths and unplanned urbanization. This study aimed at characterizing morphofunctional parameters of the tropical fish Sphoeroides testudineus and investigating the potential occurrence and effects of endocrine disruptors in the Pacoti River (Ceará, Brazil), often considered a reference site. After collection from the field, fish were measure/weighted and desiccated for gender identification (males, females, and undifferentiated), gonadal histology, and vitellogenin expression. From the biometric analysis, undifferentiated fish showed lower weight and length than female and male fish, although no differences in the condition index were observed. The gonadal weight of undifferentiated fish was significantly lower than those of females and males. Although this pattern was observed, gonadosomatic index (GSI) showed a different pattern, with differences being observed just between males and the other two groups (females and undifferentiated). Vitellogenin (VTG) expression was detected in many mature male and undifferentiated fish, indicating endocrine disruption. In addition, several EDCs (estrone, 17α-estradiol, 17β-estradiol, 17α-ethinylestradiol, diethylstilbestrol, and estriol) were identified and quantified in sediments from the sampling site. These results were unexpected and indicative that the Pacoti River is impaired by estrogenic contamination.

  7. EDCs DataBank: 3D-Structure database of endocrine disrupting chemicals.

    PubMed

    Montes-Grajales, Diana; Olivero-Verbel, Jesus

    2015-01-02

    Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system, frequently found in everyday products and epidemiologically associated with several diseases. The purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of information from different databases and text mining tools, useful for almost any kind of research regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors, through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several formats. This database is freely available at http://edcs.unicartagena.edu.co.

  8. Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

    SciTech Connect

    Kucka, Marek; Pogrmic-Majkic, Kristina; Fa, Svetlana; Stojilkovic, Stanko S.; Kovacevic, Radmila

    2012-11-15

    Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. -- Highlights: ► Atrazine stimulates cAMP accumulation in pituitary and Leydig cells. ► Atrazine also stimulates PRL and androgens secretion. ► Stimulatory effects of atrazine were abolished in cells with IBMX-inhibited PDEs. ► Atrazine specificity toward c

  9. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    PubMed Central

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-01-01

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings. PMID:24637910

  10. Thyroid endocrine system disruption by pentachlorophenol: an in vitro and in vivo assay.

    PubMed

    Guo, Yongyong; Zhou, Bingsheng

    2013-10-15

    The present study aimed to evaluate the disruption caused to the thyroid endocrine system by pentachlorophenol (PCP) using in vitro and in vivo assays. In the in vitro assay, rat pituitary GH3 cells were exposed to 0, 0.1, 0.3, and 1.0 μM PCP. PCP exposure significantly downregulated basal and triiodothyronine (T3)-induced Dio 1 transcription, indicating the antagonistic activity of PCP in vitro. In the in vivo assay, zebrafish embryos were exposed to 0, 1, 3, and 10 μg/L of PCP until 14 days post-fertilization. PCP exposure resulted in decreased thyroxine (T4) levels, but elevated contents of whole-body T3. PCP exposure significantly upregulated the mRNA expression of genes along hypothalamic-pituitary-thyroid (HPT) axis, including those encoding thyroid-stimulating hormone, sodium/iodide symporter, thyroglobulin, Dio 1 and Dio 2, alpha and beta thyroid hormone receptor, and uridinediphosphate-glucuronosyl-transferase. PCP exposure did not influence the transcription of the transthyretin (TTR) gene. The results indicate that PCP potentially disrupts the thyroid endocrine system both in vitro and in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2012-01-01

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

  12. Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals

    PubMed Central

    Vrijheid, M; Armstrong, B; Dolk, H; van Tongeren, M; Botting, B

    2003-01-01

    Background: Reported rises in the prevalence of hypospadias and other abnormalities of the male reproductive system may be a result of exposure to endocrine disrupting chemicals. Aims: To analyse the relation between risk of hypospadias and maternal occupation, particularly with regard to exposure to potential endocrine disrupting chemicals (EDCs). Methods: Data (1980–96) from the National Congenital Anomaly System (NCAS) were used to analyse the proportion of all congenital anomaly cases (n = 35 962) which were notified with hypospadias (n = 3471) by occupational codes (348 individual job titles) and by categories of exposure to potential EDCs from a job exposure matrix. Results: Five individual occupations (of 348) showed nominally statistically significant excesses, none of which had possible or probable exposure to potential EDCs. Odds ratios for "possible" or "probable" compared to "unlikely" exposure to potential EDCs did not show statistically significant increases in any of the EDC categories after adjustment for social class of the mother and father, nor was there evidence of an upward trend in risk with likelihood of exposure. In the 1992–96 time period odds ratios were increased for hairdressers (the largest group exposed to potential EDCs) and for probable exposure to phthalates (of which hairdressers form the largest group) before social class adjustment. Conclusions: There was little evidence for a relation between risk of hypospadias and maternal occupation or occupational exposure to potential EDCs, but as the exposure classification was necessarily crude, these findings should be interpreted with caution. PMID:12883014

  13. To Cull or Not To Cull? Considerations for Studies of Endocrine-Disrupting Chemicals

    PubMed Central

    Vandenberg, Laura N.

    2016-01-01

    The power of animal models is derived from the ability to control experimental variables so that observed effects may be unequivocally attributed to the factor that was changed. One variable that is difficult to control in animal experiments is the number and composition of offspring in a litter. To account for this variability, artificial equalization of the number of offspring in a litter (culling) is often used. The rationale for culling, however, has always been controversial. The Developmental Origins of Health and Disease concept provides a new context to evaluate the pros and cons of culling in laboratory animal studies, especially in the context of endocrine-disrupting chemicals. Emerging evidence indicates that culling, especially of large litters, can drastically change the feeding status of a pup, which can result in compensatory growth with long-term consequences for the animal, including increased risk of cardio-metabolic diseases. Similarly, culling of litters to intentionally bias sex ratios can alter the animal's behavior and physiology, with effects observed on a wide range of outcomes. Thus, in an attempt to control for variability in developmental rates, culling introduces an uncontrolled or confounding variable, which itself may affect a broad spectrum of health-related consequences. Variabilities in culling protocols could be responsible for differences in responses to endocrine-disrupting chemicals reported across studies. Because litter sex composition and size are vectors that can influence both prenatal and postnatal growth, they are essential considerations for the interpretation of results from laboratory animal studies. PMID:27175970

  14. Parental exposure to microcystin-LR induced thyroid endocrine disruption in zebrafish offspring, a transgenerational toxicity.

    PubMed

    Cheng, Houcheng; Yan, Wei; Wu, Qin; Liu, Chunsheng; Gong, Xiuying; Hung, Tien-Chieh; Li, Guangyu

    2017-11-01

    Microcystin-LR is the most poisonous and commonly encountered hepatotoxin produced by cyanobacteria in an aquatic ecosystem, and it may cause thyroid dysfunction in fish. The present study aimed to reveal the effects of transgenerational toxicity of MCLR on the thyroid endocrine system under sub-chronic exposure conditions. Adult zebrafish (F0) were exposed to environmentally relevant concentrations (1, 5 and 25 μg/L) of MCLR for 45 days. The produced F1 embryos were then tested without further MCLR treatment. In the F0 generation, exposure to 25 μg/L MCLR reduced thyroxine (T4) but not 3, 5, 3'-triiodothyronine (T3) levels in females, while the T4 and T3 levels were unchanged in males. After parental exposure to MCLR, we observed a decreased hatching and growth retardation correlated with reduced thyroid hormone levels in the F1 offspring. The gene transcription and protein expression along the hypothalamic-pituitary-thyroid axis were detected to further investigate the possible mechanisms of MCLR-induced thyroid disruption. Our results indicated MCLR could disturb the thyroid endocrine system under environmentally relevant concentrations and the disrupting effects could be remarkably transmitted to its F1 offspring. We regard these adverse effects as a parental transgenerational toxicity of MCLR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Multi-class of endocrine disrupting compounds in aquaculture ecosystems and health impacts in exposed biota.

    PubMed

    Ismail, Nur Afifah Hanun; Wee, Sze Yee; Aris, Ahmad Zaharin

    2017-09-08

    Fishes are a major protein food source for humans, with a high economic value in the aquaculture industry. Because endocrine disrupting compounds (EDCs) have been introduced into aquatic ecosystems, the exposure of humans and animals that depend on aquatic foods, especially fishes, should be seriously considered. EDCs are emerging pollutants causing global concern because they can disrupt the endocrine system in aquatic organisms, mammals, and humans. These pollutants have been released into the environment through many sources, e.g., wastewater treatment plants, terrestrial run-off (industrial activities, pharmaceuticals, and household waste), and precipitation. The use of pharmaceuticals, pesticides, and fertilizers for maintaining and increasing fish health and growth also contributes to EDC pollution in the water body. Human and animal exposure to EDCs occurs via ingestion of contaminated matrices, especially aquatic foodstuffs. This paper aims to review human EDC exposure via fish consumption. In respect to the trace concentration of EDCs in fish, types of instrument and clean-up method are of great concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Application of ecotoxicogenomics for studying endocrine disruption in vertebrates and invertebrates.

    PubMed

    Iguchi, Taisen; Watanabe, Hajime; Katsu, Yoshinao

    2006-04-01

    Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans. Developing organisms are particularly sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in both reproductive and nonreproductive organs, including persistent molecular alterations. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, need to be identified for investigators to understand the molecular basis of estrogenic activity during embryonic development. For investigators to understand molecular mechanisms of toxicity in various species, toxicogenomics/ecotoxicogenomics, defined as the integration of genomics (transcriptomics, proteomics, metabolomics) into toxicology and ecotoxicology, need to be established as powerful tools for research. As the initial step toward using genomics to examine endocrine-disrupting chemicals, estrogen receptors and other steroid hormone receptors have been cloned in various species, including reptiles, amphibians, and fish, and alterations in the expression of these genes in response to chemicals were investigated. We are identifying estrogen-responsive genes in mouse reproductive tracts using cDNA microarrays and trying to establish microarray systems in the American alligator, roach, medaka, and water fleas (Daphnia magna). It is too early to define common estrogen-responsive genes in various animal species; however, toxicogenomics and ectotoxicogenomics provide powerful tools to help us understand the molecular mechanism of chemical toxicities in various animal species.

  17. Thyroid endocrine disruption in zebrafish larvae following exposure to hexaconazole and tebuconazole.

    PubMed

    Yu, Liang; Chen, Mengli; Liu, Yihua; Gui, Wenjun; Zhu, Guonian

    2013-08-15

    The widely used triazole fungicides have the potential to disrupt endocrine system, but little is known of such effects or underlying mechanisms of hexaconazole (HEX) and tebuconazole (TEB) in fish. In the present study, zebrafish (Danio rerio) embryos were exposed to various concentrations of HEX (0.625, 1.25 and 2.5 mg/L) and TEB (1, 2 and 4 mg/L) from fertilization to 120 h post-fertilization (hpf). The whole body content of thyroid hormone and transcription of genes in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. The results showed that thyroxine (T4) levels were significantly decreased, while triiodothyronine (T3) concentrations were significantly increased after exposure to HEX and TEB, indicating thyroid endocrine disruption. Exposure to HEX significantly induced the transcription of all the measured genes (i.e., corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSHβ), sodium/iodide symporter (NIS), transthyretin (TTR), uridine diphosphate glucuronosyltransferase (UGT1ab), thyronine deiodinase (Dio1 and Dio2), thyroid hormone receptors (TRα and TRβ) in the HPT axis, but did not affect the transcription of thyroglobulin (TG). However, TEB exposure resulted in the upregulation of all the measured genes, excepting that TG, Dio1and TRα had not changed significantly. The overall results indicated that exposure to HEX and TEB could alter thyroid hormone levels as well as gene transcription in the HPT axis in zebrafish larvae.

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

    PubMed Central

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

    2014-01-01

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

  19. Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    PubMed Central

    Zoeller, R. Thomas; Hass, Ulla; Kortenkamp, Andreas; Grandjean, Philippe; Myers, John Peterson; DiGangi, Joseph; Bellanger, Martine; Hauser, Russ; Legler, Juliette; Skakkebaek, Niels E.; Heindel, Jerrold J.

    2015-01-01

    Context: Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. Objective: The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU). Design: A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data. Results: Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or $209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs. Conclusions: EDC exposures in the EU are likely to contribute substantially to disease and

  20. Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union.

    PubMed

    Trasande, Leonardo; Zoeller, R Thomas; Hass, Ulla; Kortenkamp, Andreas; Grandjean, Philippe; Myers, John Peterson; DiGangi, Joseph; Bellanger, Martine; Hauser, Russ; Legler, Juliette; Skakkebaek, Niels E; Heindel, Jerrold J

    2015-04-01

    Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU). A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data. Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or $209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs. EDC exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in

  1. Atrazine Acts as an Endocrine Disrupter by Inhibiting cAMP-specific Phosphodiesterase-4

    PubMed Central

    Kucka, Marek; Pogrmic-Majkic, Kristina; Fa, Svetlana; Stojilkovic, Stanko S.; Kovacevic, Radmila

    2014-01-01

    Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. PMID:23022511

  2. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers

    PubMed Central

    Sheikh, Ishfaq A.; Turki, Rola F.; Abuzenadah, Adel M.; Damanhouri, Ghazi A.; Beg, Mohd A.

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15–31 amino acid residues of SHBG and a commonality of 55–95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates. PMID:26963243

  3. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    PubMed

    Sheikh, Ishfaq A; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

  4. Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats

    PubMed Central

    Zhang, Zhaobin; Shi, Jiachen; Jiao, Zhihao; Shao, Bing

    2016-01-01

    Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth. PMID:27149376

  5. Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro.

    PubMed

    Albert, O; Desdoits-Lethimonier, C; Lesné, L; Legrand, A; Guillé, F; Bensalah, K; Dejucq-Rainsford, N; Jégou, B

    2013-07-01

    only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. Our studies were performed in vitro. We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.

  6. Analysis of Endocrine Disruption in Southern California Coastal Fish Using an Aquatic Multispecies Microarray

    PubMed Central

    Baker, Michael E.; Ruggeri, Barbara; Sprague, L. James; Eckhardt-Ludka, Colleen; Lapira, Jennifer; Wick, Ivan; Soverchia, Laura; Ubaldi, Massimo; Polzonetti-Magni, Alberta Maria; Vidal-Dorsch, Doris; Bay, Steven; Gully, Joseph R.; Reyes, Jesus A.; Kelley, Kevin M.; Schlenk, Daniel; Breen, Ellen C.; Šášik, Roman; Hardiman, Gary

    2009-01-01

    Background Endocrine disruptors include plasticizers, pesticides, detergents, and pharmaceuticals. Turbot and other flatfish are used to characterize the presence of chemicals in the marine environment. Unfortunately, there are relatively few genes of turbot and other flatfish in GenBank, which limits the use of molecular tools such as microarrays and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to study disruption of endocrine responses in sentinel fish captured by regulatory agencies. Objectives We fabricated a multigene cross-species microarray as a diagnostic tool to screen the effects of environmental chemicals in fish, for which there is minimal genomic information. The array included genes that are involved in the actions of adrenal and sex steroids, thyroid hormone, and xenobiotic responses. This microarray will provide a sensitive tool for screening for the presence of chemicals with adverse effects on endocrine responses in coastal fish species. Methods We used a custom multispecies microarray to study gene expression in wild hornyhead turbot (Pleuronichthys verticalis) collected from polluted and clean coastal waters and in laboratory male zebrafish (Danio rerio) after exposure to estradiol and 4-nonylphenol. We measured gene-specific expression in turbot liver by qRT-PCR and correlated it to microarray data. Results Microarray and qRT-PCR analyses of livers from turbot collected from polluted areas revealed altered gene expression profiles compared with those from nonaffected areas. Conclusions The agreement between the array data and qRT-PCR analyses validates this multispecies microarray. The microarray measurement of gene expression in zebrafish, which are phylogenetically distant from turbot, indicates that this multispecies microarray will be useful for measuring endocrine responses in other fish. PMID:19270792

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

    PubMed

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

    2016-11-01

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

  8. [Endocrine disruption agents: environment, health, public policies, and the precautionary principle].

    PubMed

    Vandelac, L

    2000-01-01

    The already substantial body of evidence and growing web of suspicions as to the scale and severity of the cascade effects of endocrine disrupters (related to persistent organic pollutants or POPs) on the health of ecosystems and humans have sparked such concern that in June 1998, representatives of 94 countries meeting in Montreal under the aegis of UNEP signed a draft international agreement to phase out the most harmful POPs. Related to particular persistent organic pollutants--toxic semi-volatile and persistent chemical compounds now found everywhere in the environment, such as BPCs, organochlorine pesticides, dioxins and furans, that build up in the bodies of organisms that consume other contaminated organisms along the food chain--endocrine disrupters are strongly suspected of affecting the health of animals and adversely impacting the health, fertility and even intellectual faculties of humans. For example, very low-level exposure to some POPs is associated with some hormone-dependent cancers, damage to the central and peripheral nervous systems, impaired immune system function, reproductive disorders and developmental disruptions in newborns and infants, who can be affected in utero or through breast-feeding. Considering the extreme complexity of the scientific and socio-economic effects of POP-related endocrine disrupters, there are those who, advocate a wait-and-see approach, claiming that there is not enough formal scientific proof. There are others who use the available evidence to advance the research, press for bans on incriminated substances and look for global, integrated and viable alternatives. And there are other still who, with careless disregard for the Precautionary Principle, are quite prepared to talk about the perverse effects of POPs in order to justify the increased use of artificial means of reproduction or the replacement of chemical pesticides by pest-resistant genetically modified organisms (GMOs), thereby opening the door to

  9. Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis

    PubMed Central

    Trasande, L.; Zoeller, R. T.; Hass, U.; Kortenkamp, A.; Grandjean, P.; Myers, J. P.; DiGangi, J.; Hunt, P. M.; Rudel, R.; Sathyanarayana, S.; Bellanger, M.; Hauser, R.; Legler, J.; Skakkebaek, N. E.; Heindel, J. J.

    2017-01-01

    SUMMARY A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs. PMID:27003928

  10. Exposure to butachlor causes thyroid endocrine disruption and promotion of metamorphosis in Xenopus laevis.

    PubMed

    Li, Shuying; Li, Meng; Wang, Qiangwei; Gui, Wenjun; Zhu, Guonian

    2016-06-01

    Butachlor is extensively applied in rice paddy ecosystem in china, and has been widespread contaminant in the aquatic environment. Here, Xenopus laevis was used for the evaluation of teratogenesis developmental toxicity, and disruption of thyroid system when exposure to different concentrations of butachlor by window phase exposure. Acute toxicity investigation shown that 96 h-LC50 value of butachlor was 1.424 mg L(-1) and 0.962 mg L(-1) for tadpoles (starting from stages 46/47) and embryos (starting from stages 8/9), respectively. Exposure to butachlor caused malformation, including abnormal eye, pericardial edema, enlarged proctodaeum and bent tail. Window phase exposure test indicated that butachlor significantly promote the contents of whole-body thyroid hormones (THs, T3 and T4) at higher levels, indicating thyroid endocrine disruption. At 7 days, exposure to butachlor up-regulated the mRNA expression of genes involved in THs synthesis and metabolism (tshα, tg, tpo and dio1) and THs receptors (trα and trβ). At 14 days, up-regulation of the mRNA expression of genes related to THs synthesis and metabolism (tshα, tshβ, tg, tpo, dio1, dio2 and ttr) and THs receptors (trβ) were also observed after the exposure to butachlor. At 21 days, butachlor up-regulated the mRNA expression of tshα, tg, tpo genes and down-regulated the mRNA expression of tshβ, tg, dio1, ttr and trα genes. These results showed that butachlor could change the mRNA expression of genes involved in the HPT axis and increase whole-body thyroid hormones levels of X. laevis tadpoles in a dose- and time-dependent manner, causing thyroid endocrine disruption and developmental toxicity.

  11. Impact of endocrine-disrupting chemicals on neural development and the onset of neurological disorders.

    PubMed

    Kajta, Małgorzata; Wójtowicz, Anna K

    2013-01-01

    Even though high doses of organic pollutants are toxic, relatively low concentrations have been reported to cause long-term alterations in functioning of individual organisms, populations and even next generations. Among these pollutants are dioxins, polychlorinated biphenyls, pesticides, brominated flame retardants, plasticizers (bisphenol A, nonylphenol, and phthalates) as well as personal care products and drugs. In addition to toxic effects, they are able to interfere with hormone receptors, hormone synthesis or hormone conversion. Because these chemicals alter hormone-dependent processes and disrupt functioning of the endocrine glands, they have been classified as endocrine-disrupting chemicals (EDCs). Because certain EDCs are able to alter neural transmission and the formation of neural networks, the term neural-disrupting chemicals has been introduced, thus implicating EDCs in the etiology of neurological disorders. Recently, public concern has been focused on the effects of EDCs on brain function, concomitantly with an increase in neuropsychiatric disorders, including autism, attention deficit and hyperactivity disorder as well as learning disabilities and aggressiveness. Several lines of evidence suggest that exposure to EDCs is associated with depression and could result in neural degeneration. EDCs act via several classes of receptors with the best documented mechanisms being reported for nuclear steroid and xenobiotic receptors. Low doses of EDCs have been postulated to cause incomplete methylation of specific gene regions in the young brain and to impair neural development and brain functions across generations. Efforts are needed to develop systematic epidemiological studies and to investigate the mechanisms of action of EDCs in order to fully understand their effects on wildlife and humans.

  12. Neonatal Exposure to Endocrine Disrupting Chemicals Impairs Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice.

    PubMed

    Bhaskar, Rakesh; Mishra, Ashish K; Mohanty, Banalata

    2017-02-16

    Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In this study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29, and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various end-points studied. Brain weight was significantly decreased in the mixture-exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture-exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture-exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture-exposed group offspring. Testosterone level was significantly decreased only at PND 29, but corticosterone level was increased at both PND 29 and PND 63 in mixture-exposed offspring. T-maze task performance revealed significantly increased time duration and reduced path efficiency in mixture-exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization.

  13. AB159. Endocrine disrupting chemicals: toxicological risk assessment in vivo and in vitro models

    PubMed Central

    Thuy, Vo Thi Bich; Nguyen Binh, Le Thi; Phuong Oanh, Kim Thi; Van Hai, Nong

    2015-01-01

    In several studies, scientists asserted that many of endocrine disruptors (EDs), which have been involved in developmental, reproductive, neural, immunological, and other problems in wildlife and laboratory animals. Some environmental EDs, such as di-(2-ethylhexyl) phthalate (DEHP), flutamide (Flu), parabens, are used in many products in life and environment. However, the adverse effects caused by EDs can be temporary or permanent and the mechanism(s) through which these chemicals elicit their effects on biological systems of human and animal health is not clearly understood. The specific aim of this study is to evaluate endocrine disrupting chemicals-induced impact on the male or female reproductive system. An attempt is also made to elucidate the impact of these EDs in an in vitro model, i.e., GH3 rat pituitary cell line. A great deal of work has been carried out on the toxicity of phthalate, Flu, parabens in vivo and in vitro models. In brief, studies have been indicated that long-term and short-term exposure to various endocrine disrupting compounds (i.e., DEHP, Flu, parabens) during development stage (i.e., gestation, neonatal, immature, peripubertal) were done to find alternative dysfunctions later in animal life. The development and function of male or female reproductive tract showed many abnormalities, e.g., menstrual cycle irregularities; impaired fertility, endometriosis, and polycystic ovarian syndrome in female or morphological and functional gonadal dysfunction, e.g., infertility and decreased libido, congenital malformations (altered embryonic and fetal intrauterine development) and testicular dysgenesis syndrome in male. In addition, the differential gene expression patterns by microarray analysis following EDs exposure were found, particularly in steroid hormone synthesis, androgen and/or estrogen synthesis, and sex determination-related gene. On the other hand, studies revealed that parabens, a weak estrogenic chemical, exerted their actions on

  14. 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

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

    SciTech Connect

    McLachlan, John A.

    2000-06-01

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

  16. Endocrine disrupters in the aquatic environment: the Austrian approach--ARCEM.

    PubMed

    Bursch, W; Fuerhacker, M; Gemeiner, M; Grillitsch, B; Jungbauer, A; Kreuzinger, N; Moestl, E; Scharf, S; Schmid, E; Skutan, S; Walter, I

    2004-01-01

    A consortium of Austrian scientists (ARCEM) carried out a multidisciplinary environmental study on Austrian surface and ground waters including chemical monitoring, bioindication, risk assessment and risk management for selected endocrine disrupters: 17beta-estradiol, estriol, estrone, 17alpha-ethinylestradiol, 4-nonylphenol, 4-nonylphenol ethoxylates (4-NP1EO, 4-NP2EO) and their degradation products, ocytlphenol, ocytlphenol ethoxylates (OP1EO, OP2EO) as well as bisphenol A. To obtain data representative for Austria, a material flow analysis served to select relevant compounds and water samples were collected monthly over one year at those sites routinely used in Austrian water quality control. The following results were obtained and conclusions drawn: 1. Chemical monitoring: As compared to other countries, relatively low levels of pollution with endocrine disrupters were detected. 2. Bioindication: In the surface waters under study, male fish showed significant signs of feminization and demasculinization (increased production of the egg-yolk protein and histological changes of the gonads. 3. Risk assessment: For humans, exposure via either drinking water abstraction (ground water) or fish consumption was considered. The exposure levels of the compounds under study were below those considered to result in human health risks. Likewise, for bisphenol A and octylphenols, there was no indication for risk posed upon the aquatic environment (fish). However, nonylphenol or 17alpha-ethinylestradiol exposure along with results of bioindication (2) suggest a borderline estrogenic activity in a considerable number of surface waters. Consequently the emissions of these substances into the surface waters affected have to be reduced. 4. Risk management: Waste water treatment experiments revealed a positive correlation between the removal rate of endocrine disrupters from the waste water and the sludge retention time in the treatment plants. These substances are removed to a

  17. Fifteen years after "Wingspread"- Environmental Endocrine Disrupters and human and wildlife health: Where we are today and where we need to go.

    EPA Science Inventory

    In 1991 a group of expert scientists at a Wingspread work session on endocrine disrupting chemicals (EDCs) concluded that "Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and hum...

  18. Fifteen years after "Wingspread"- Environmental Endocrine Disrupters and human and wildlife health: Where we are today and where we need to go.

    EPA Science Inventory

    In 1991 a group of expert scientists at a Wingspread work session on endocrine disrupting chemicals (EDCs) concluded that "Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and hum...

  19. Simultaneous determination of 76 micropollutants in water samples by headspace solid phase microextraction and gas chromatography-mass spectrometry.

    PubMed

    Martínez, C; Ramírez, N; Gómez, V; Pocurull, E; Borrull, F

    2013-11-15

    This study focuses on the development of an analytical method based on headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) for the simultaneous determination of 76 micropollutants in water samples. The selected micropollutants include volatile organic compounds (VOCs) (e.g. chlorobenzenes, chloroalkanes), endocrine disrupting compounds (EDCs) (e.g. bisphenol A and tributyl phosphate), odour compounds (e.g. limonene, phenol), fragrance allergens (e.g. geraniol, eugenol) and some pesticides (e.g. heptachlor, terbutryn). The experimental conditions affecting their extraction, such as the type of fibre, temperature and time of extraction, sample volume and ionic strength of the samples were optimized using HS-SPME. The method showed good linear range, reproducibility between days, repeatability and low detection limits (at ng L(-1) levels). The validated method has been applied to determine the target organic micropollutants in aqueous samples from different experimental research units of surface water, sea water, waste water and those effluents of advance membrane treatments. The optimized method showed good performance in the different types of samples studied. The analysis revealed the presence of several micropollutants at concentrations between 20 and 5000 μg L(-1), such as ethylbenzene, o-xylene, p-isopropilbenzene, D-limonene, citral and isoeugenol, due to the fact that these species are commonly used in domestic and industrial applications.

  20. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

    PubMed Central

    Welshons, Wade V; Thayer, Kristina A; Judy, Barbara M; Taylor, Julia A; Curran, Edward M; vom Saal, Frederick S

    2003-01-01

    Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted. PMID:12826473

  1. Naturally-induced endocrine disruption by the parasite Ligula intestinalis (Cestoda) in roach (Rutilus rutilus).

    PubMed

    Trubiroha, Achim; Kroupova, Hana; Wuertz, Sven; Frank, Sabrina N; Sures, Bernd; Kloas, Werner

    2010-04-01

    Fish represent the most frequently used vertebrate class for the investigation of endocrine disruption (ED) in wildlife. However, field studies are complicated by exposure scenarios involving a variety of anthropogenic and natural influences interfering with the endocrine system. One natural aspect rarely considered in ecotoxicological studies is how parasites modulate host physiology. Therefore, investigations were carried out to characterise the impacts of the parasitic tapeworm Ligula intestinalis on plasma sex steroid levels and expression of key genes associated with the reproduction in roach (Rutilus rutilus), a sentinel species for wildlife ED research. Parasitisation by L. intestinalis suppressed gonadal development in both genders of roach and analysis of plasma sex steroids revealed substantially lower levels of 17beta-oestradiol (E2) and 11-ketotestosterone (11-KT) in infected females as well as E2, 11-KT, and testosterone in infected males. Consistently, in both, infected females and males, expression of the oestrogen dependent genes such as vitellogenin and brain-type aromatase in liver and brain was reduced. Furthermore, parasitisation differentially modulated mRNA expression of the oestrogen and androgen receptors in brain and liver. Most prominently, liver expression of oestrogen receptor 1 was reduced in infected females but not in males, whereas expression of oestrogen receptor 2a was up-regulated in both genders. Further, insulin-like growth factor 1 mRNA in the liver was increased in infected females but not in males. Despite severe impacts on plasma sex steroids and pituitary gonadotropin expression, brain mRNA levels of gonadotropin-releasing hormone (GnRH) precursors encoding GnRH2 and GnRH3 were not affected by L. intestinalis-infection. In summary, the present results provide basic knowledge of the endocrine system in L. intestinalis-infected roach and clearly demonstrate that parasites can cause ED in fish.

  2. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats.

    PubMed

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie; Pedersen, Anne Stilling; Mortensen, Mette Sidsel; Jørgensen, Jennifer Solgaard; Vinggaard, Anne Marie; Hass, Ulla

    2015-07-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined. Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.

  3. Epigenetic effects of endocrine-disrupting chemicals on female reproduction: an ovarian perspective.

    PubMed

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2010-10-01

    The link between in utero and neonatal exposure to environmental toxicants, such as endocrine-disrupting chemicals (EDCs) and adult female reproductive disorders is well established in both epidemiological and animal studies. Recent studies examining the epigenetic mechanisms involved in mediating the effects of EDCs on female reproduction are gathering momentum. In this review, we describe the developmental processes that are susceptible to EDC exposures in female reproductive system, with a special emphasis on the ovary. We discuss studies with select EDCs that have been shown to have physiological and correlated epigenetic effects in the ovary, neuroendocrine system, and uterus. Importantly, EDCs that can directly target the ovary can alter epigenetic mechanisms in the oocyte, leading to transgenerational epigenetic effects. The potential mechanisms involved in such effects are also discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Are the mediterraneantop predators exposed to toxicological risk due to endocrine disrupters?

    PubMed

    Fossi, M C; Casini, S; Marsili, L; Ausili, A; di Sciara, G N

    2001-12-01

    Man-made endocrine disrupting chemicals (EDCs) range across all continents and oceans; some geographic areas are potentially more threatened than others: one of these is the Mediterranean Sea. This basin has limited exchange of water with the Atlantic Ocean and is surrounded by some of the most heavily populated and industrialized countries in the world. Accordingly, levels of some xenobiotics are much higher here than in other seas and oceans. In this research the unexplored hypothesis that Mediterranean top predator species (such as large pelagic fish and marine mammals) are potentially at risk due to EDCs is investigated. Here we illustrate the development of sensitive biomarkers (Vitellogenin, Zona Radiata proteins) for evaluation of toxicological risk in top marine predators (Xiphias gladius, Thunnus thynnus thynnus), and nonlethal techniques, such as nondestructive biomarkers (BPMO activities in skin biopsy), for the hazard assessment of threatened species exposed to EDCs, such as marine mammals (Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis, and Balaenoptera physalus).

  5. Endocrine-disrupting actions of PCBs on brain development and social and reproductive behaviors

    PubMed Central

    Bell, Margaret R

    2014-01-01

    Polychlorinated biphenyls are among the most well-studied endocrine-disrupting chemicals (EDCs) for their neurobehavioral effects, especially neurodevelopment and cognitive performance. In addition, past research has demonstrated effects of PCBs on circulating hormones and associated changes in reproductive behaviors. This article will focus on recent advances that have been made in characterizing developmental PCB effects on reproductive function, broader social and affective behaviors, and the neuroendocrine mechanisms behind such changes. In general, PCBs seem to inhibit reproductive function by suppressing multiple aspects of the associated hypothalamic circuitry. Additionally, PCBs may also reduce motivation for social behaviors and induce depressive-like symptoms via overall reductions in dopaminergic and glutamatergic functions in the limbic system. However, more work with human-relevant exposure paradigms is needed to fully support these conclusions. PMID:25310366

  6. Epigenetic effects of endocrine-disrupting chemicals on female reproduction: An ovarian perspective

    PubMed Central

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2010-01-01

    The link between in utero and neonatal exposure to environmental toxicants, such as endocrine-disrupting chemicals (EDCs) and adult female reproductive disorders is well established in both epidemiological and animal studies. Recent studies examining the epigenetic mechanisms involved in mediating the effects of EDCs on female reproduction are gathering momentum. In this review, we describe the developmental processes that are susceptible to EDC exposures in female reproductive system, with a special emphasis on the ovary. We discuss studies with select EDCs that have been shown to have physiological and correlated epigenetic effects in the ovary, neuroendocrine system, and uterus. Importantly, EDCs that can directly target the ovary can alter epigenetic mechanisms in the oocyte, leading to transgenerational epigenetic effects. The potential mechanisms involved in such effects are also discussed. PMID:20609371

  7. Transcriptional analysis of endocrine disruption using zebrafish and massively parallel sequencing

    PubMed Central

    Baker, Michael E.; Hardiman, Gary

    2014-01-01

    Endocrine disrupting chemicals (EDCs) including plasticizers, pesticides, detergents and pharmaceuticals, affect a variety of hormone-regulated physiological pathways in humans and wildlife. Many EDCs are lipophilic molecules and bind to hydrophobic pockets in steroid receptors, such as the estrogen receptor and androgen receptor, which are important in vertebrate reproduction and development. Indeed, health effects attributed to EDCs include reproductive dysfunction (e.g., reduced fertility, reproductive tract abnormalities and skewed male/female sex ratios in fish), early puberty, various cancers and obesity. A major concern is the effects of exposure to low concentrations of endocrine disruptors in utero and post partum, which may increase the incidence of cancer and diabetes in adults. EDCs affect transcription of hundreds and even thousands of genes, which has created the need for new tools to monitor the global effects of EDCs. The emergence of massive parallel sequencing for investigating gene transcription provides a sensitive tool for monitoring the effects of EDCs on humans and other vertebrates as well as elucidating the mechanism of action of EDCs. Zebrafish conserve many developmental pathways found in humans, which makes zebrafish a valuable model system for studying EDCs especially on early organ development because their embryos are translucent. In this article we review recent advances in massive parallel sequencing approaches with a focus on zebrafish. We make the case that zebrafish exposed to EDCs at different stages of development, can provide important insights on EDC effects on human health. PMID:24850832

  8. Frontiers in endocrine disruption: Impacts of organotin on the hypothalamus-pituitary-thyroid axis.

    PubMed

    Santos-Silva, Ana Paula; Andrade, Marcelle Novaes; Pereira-Rodrigues, Paula; Paiva-Melo, Francisca Diana; Soares, Paula; Graceli, Jones Bernardes; Dias, Glaecir Roseni Mundstock; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires; Miranda-Alves, Leandro

    2017-07-31

    Endocrine disruptors (EDs), chemical substances widely used in industry and ubiquitously distributed in the environment, are able to interfere with the synthesis, release, transport, metabolism, receptor binding, action, or elimination of endogenous hormones. EDs affect homeostasis mainly by acting on nuclear and nonnuclear steroid receptors but also on serotonin, dopamine, norepinephrine and orphan receptors in addition to thyroid hormone receptors. Tributyltin (TBT), an ED widely used as a pesticide and biocide in antifouling paints, has well-documented actions that include inhibiting aromatase and affecting the nuclear receptors PPARγ and RXR. TBT exposure in humans and experimental models has been shown to mainly affect reproductive function and adipocyte differentiation. Since thyroid hormones play a fundamental role in regulating the basal metabolic rate and energy homeostasis, it is crucial to clarify the effects of TBT on the hypothalamus-pituitary-thyroid axis. Therefore, we review herein the main effects of TBT on important metabolic pathways, with emphasis on disruption of the thyroid axis that could contribute to the development of endocrine and metabolic disorders, such as insulin resistance and obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

    PubMed

    Dogan, Selen; Simsek, Tayup

    2016-07-01

    The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Removal of endocrine disrupting chemicals (EDCs) using low pressure reverse osmosis membrane (LPROM).

    PubMed

    Razak, A R A; Ujang, Z; Ozaki, H

    2007-01-01

    Endocrine disrupting chemicals (EDCs) are the focus of current environmental issues, as they can cause adverse health effects to animals and human, subsequent to endocrine function. The objective of this study was to remove a specific compound of EDCs (i.e. pentachlorophenol, C(6)OCL(5)Na, molecular weight of 288 g/mol) using low pressure reverse osmosis membrane (LPROM). A cross flow module of LPROM was used to observe the effects of operating parameters, i.e. pH, operating pressure and temperature. The design of the experiment was based on MINITAB(TM) software, and the analysis of results was conducted by factorial analysis. It was found that the rejection of pentachlorophenol was higher than 80% at a recovery rate of 60 to 70%. The rejection was subjected to increase with the increase of pH. The flux was observed to be increased with the increase of operating pressure and temperature. This study also investigated the interaction effects between operating parameters involved.

  11. Sex reversal assessments reveal different vulnerability to endocrine disruption between deeply diverged anuran lineages

    PubMed Central

    Tamschick, Stephanie; Rozenblut-Kościsty, Beata; Ogielska, Maria; Lehmann, Andreas; Lymberakis, Petros; Hoffmann, Frauke; Lutz, Ilka; Kloas, Werner; Stöck, Matthias

    2016-01-01

    Multiple anthropogenic stressors cause worldwide amphibian declines. Among several poorly investigated causes is global pollution of aquatic ecosystems with endocrine disrupting compounds (EDCs). These substances interfere with the endocrine system and can affect the sexual development of vertebrates including amphibians. We test the susceptibility to an environmentally relevant contraceptive, the artificial estrogen 17α-ethinylestradiol (EE2), simultaneously in three deeply divergent systematic anuran families, a model-species, Xenopus laevis (Pipidae), and two non-models, Hyla arborea (Hylidae) and Bufo viridis (Bufonidae). Our new approach combines synchronized tadpole exposure to three EE2-concentrations (50, 500, 5,000 ng/L) in a flow-through-system and pioneers genetic and histological sexing of metamorphs in non-model anurans for EDC-studies. This novel methodology reveals striking quantitative differences in genetic-male-to-phenotypic-female sex reversal in non-model vs. model species. Our findings qualify molecular sexing in EDC-analyses as requirement to identify sex reversals and state-of-the-art approaches as mandatory to detect species-specific vulnerabilities to EDCs in amphibians. PMID:27029458

  12. Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system.

    PubMed

    Sidorkiewicz, Iwona; Zaręba, Kamil; Wołczyński, Sławomir; Czerniecki, Jan

    2017-07-01

    Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can cause disturbances in the endocrine system and have multiple harmful effects on health by targeting different organs and systems in the human body. Mass industrial production and widespread use of EDCs have resulted in worldwide contamination. Accumulating evidence suggest that human exposure to EDCs is related to the impairment of male reproductive function and can interrupt other hormonally regulated metabolic processes, particularly if exposure occurs during early development. Investigation of studies absent in previous reviews and meta-analysis of adverse effects of EDCs on functioning of the male reproductive system is the core of this work. Four main modes of action of EDCs on male fertility have been summarized in this review. First, studies describing estrogen- pathway disturbing chemicals are investigated. Second, androgen-signaling pathway alterations and influence on androgen sensitive tissues are examined. Third, evaluation of steroidogenesis dysfunction is discussed by focusing on the steroid hormone biosynthesis pathway, which is targeted by EDCs. Last, the reportedly destructive role of reactive oxygen species (ROS) on sperm function is discussed. Spermatogenesis is a remarkably complex process, hence multiple studies point out various dysfunctions depending on the development state at which the exposure occurred. Collected data show the need to account for critical windows of exposure such as fetal, perinatal and pubertal periods as well as effects of mixtures of several compounds in future research.

  13. Toxicological characteristics of endocrine-disrupting chemicals: developmental toxicity, carcinogenicity, and mutagenicity.

    PubMed

    Choi, Seul Min; Yoo, Sun Dong; Lee, Byung Mu

    2004-01-01

    It is generally accepted that endocrine-disrupting chemicals (EDCs) play a role in a variety of adverse health effects in an intact organism or its progeny as a consequence of changes in the endocrine system. Primary toxic effects of EDCs were reported to be related to infertility, reduction in sperm count, and teratogenicity, but other important toxic effects of EDCs such as carcinogenicity and mutagenicity have also been demonstrated. The aim of the present study was to systematically analyze the toxicological characteristics of EDCs in pesticides, industrial chemicals, and metals. A comprehensive literature survey on the 48 EDCs classified by the Centers for Disease Control and Prevention (CDC) was conducted using a number of databases which included Medline, Toxline, and Toxnet. The survey results revealed that toxicological characteristics of EDCs were shown to produce developmental toxicity (81%), carcinogenicity (79%, when positive in at least one animal species; 48%, when classified based on IARC evaluation), mutagenicity (79%), immunotoxicity (52%), and neurotoxicity (50%). Regarding the hormone-modulating effects of the 48 EDCs, estrogenic effects were the most predominant in pesticides, while effects on thyroid hormone were found for heavy metals. EDCs showing estrogen-modulating effects were closely related to carcinogenicity or mutagenicity with a high degree of sensitivity. Systematic information on the toxicological characteristics of the EDCs will be useful for future research directions on EDCs, the development of new screening methods, legal regulation, and for investigations of their mechanism of action.

  14. QSAR modeling and prediction of the endocrine-disrupting potencies of brominated flame retardants.

    PubMed

    Papa, Ester; Kovarich, Simona; Gramatica, Paola

    2010-05-17

    In the European Union REACH regulation, the chemicals with particularly harmful behaviors, such as endocrine disruptors (EDs), are subject to authorization, and the identification of safer alternatives to these chemicals is required. In this context, the use of quantitative structure-activity relationships (QSAR) becomes particularly useful to fill the data gap due to the very small number of experimental data available to characterize the environmental and toxicological profiles of new and emerging pollutants with ED behavior such as brominated flame retardants (BFRs). In this study, different QSAR models were developed on different responses of endocrine disruption measured for several BFRs. The multiple linear regression approach was applied to a variety of theoretical molecular descriptors, and the best models, which were identified from all of the possible combinations of the structural variables, were internally validated for their performance using the leave-one-out (Q(LOO)(2) = 73-91%) procedure and scrambling of the responses. External validation was provided, when possible, by splitting the data sets in training and test sets (range of Q(EXT)(2) = 76-90%), which confirmed the predictive ability of the proposed equations. These models, which were developed according to the principles defined by the Organization for Economic Co-operation and Development to improve the regulatory acceptance of QSARs, represent a simple tool for the screening and characterization of BFRs.

  15. In Silico Analysis of the Conservation of Human Toxicity and Endocrine Disruption Targets in Aquatic Species

    PubMed Central

    2015-01-01

    Pharmaceuticals and industrial chemicals, both in the environment and in research settings, commonly interact with aquatic vertebrates. Due to their short life-cycles and the traits that can be generalized to other organisms, fish and amphibians are attractive models for the evaluation of toxicity caused by endocrine disrupting chemicals (EDCs) and adverse drug reactions. EDCs, such as pharmaceuticals or plasticizers, alter the normal function of the endocrine system and pose a significant hazard to human health and the environment. The selection of suitable animal models for toxicity testing is often reliant on high sequence identity between the human proteins and their animal orthologs. Herein, we compare in silico the ligand-binding sites of 28 human “side-effect” targets to their corresponding orthologs in Danio rerio, Pimephales promelas, Takifugu rubripes, Xenopus laevis, and Xenopus tropicalis, as well as subpockets involved in protein interactions with specific chemicals. We found that the ligand-binding pockets had much higher conservation than the full proteins, while the peroxisome proliferator-activated receptor γ and corticotropin-releasing factor receptor 1 were notable exceptions. Furthermore, we demonstrated that the conservation of subpockets may vary dramatically. Finally, we identified the aquatic model(s) with the highest binding site similarity, compared to the corresponding human toxicity target. PMID:24392850

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

    PubMed

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

    2009-10-30

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

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

    PubMed

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

    2014-09-12

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

  18. In silico analysis of the conservation of human toxicity and endocrine disruption targets in aquatic species.

    PubMed

    McRobb, Fiona M; Sahagún, Virginia; Kufareva, Irina; Abagyan, Ruben

    2014-01-01

    Pharmaceuticals and industrial chemicals, both in the environment and in research settings, commonly interact with aquatic vertebrates. Due to their short life-cycles and the traits that can be generalized to other organisms, fish and amphibians are attractive models for the evaluation of toxicity caused by endocrine disrupting chemicals (EDCs) and adverse drug reactions. EDCs, such as pharmaceuticals or plasticizers, alter the normal function of the endocrine system and pose a significant hazard to human health and the environment. The selection of suitable animal models for toxicity testing is often reliant on high sequence identity between the human proteins and their animal orthologs. Herein, we compare in silico the ligand-binding sites of 28 human "side-effect" targets to their corresponding orthologs in Danio rerio, Pimephales promelas, Takifugu rubripes, Xenopus laevis, and Xenopus tropicalis, as well as subpockets involved in protein interactions with specific chemicals. We found that the ligand-binding pockets had much higher conservation than the full proteins, while the peroxisome proliferator-activated receptor γ and corticotropin-releasing factor receptor 1 were notable exceptions. Furthermore, we demonstrated that the conservation of subpockets may vary dramatically. Finally, we identified the aquatic model(s) with the highest binding site similarity, compared to the corresponding human toxicity target.

  19. Endocrine disrupting chemical emissions from combustion sources: diesel particulate emissions and domestic waste open burn emissions

    NASA Astrophysics Data System (ADS)

    Sidhu, Sukh; Gullett, Brian; Striebich, Richard; Klosterman, Joy; Contreras, Jesse; DeVito, Michael

    Emissions of endocrine disrupting chemicals (EDCs) from combustion sources are poorly characterized due to the large number of compounds present in the emissions, the complexity of the analytical separations required, and the uncertainty regarding identification of chemicals with endocrine effects. In this work, multidimensional gas chromatographic-mass spectrometry (MDGC-MS) was used to characterize emissions from both controlled (diesel engine) and uncontrolled (open burning of domestic waste) combustion sources. The results of this study suggest that, by using MDGC-MS, one can resolve a much greater percentage of the chromatogram and identify about 84% of these resolved compounds. This increase in resolution helped to identify and quantify various classes of polycyclic aromatic hydrocarbons (PAHs) in the combustion emissions that had not been identified previously. Significant emissions (when compared to industrial sources) of known EDCs, dioctyl phthalate (over ˜2,500,000 kg year -1) and bisphenol A (over ˜75,000 kg year -1) were estimated from uncontrolled domestic waste burning. Emissions of several suspected EDCs (oxygenated PAHs) were observed in both diesel soot and the uncontrolled domestic waste burn samples. The emission rates of known and suspected EDCs estimated in this study suggest that combustion emissions need to be characterized for EDCs to further assess its importance as a source of EDC exposure.

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

    PubMed Central

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

    2014-01-01

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

  1. Early Life Exposure to Ractopamine Causes Endocrine-Disrupting Effects in Japanese Medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Wang, Sisi; Lin, Xia; Tan, Hana; Fu, Zhengwei

    2016-02-01

    β-Agonists, which are used as human pharmaceuticals or feed additives, have been detected in aquatic environments. β-Agonists have also been proposed for use in aquaculture. However, there are limited data available regarding the adverse effects of β-agonists in aquatic organisms. In this study, ractopamine was selected as the representative β-agonist, and medaka embryos were exposed at concentrations ranging from 5 to 625 μg/L for 44 days. In contrast to what has been found in mammals, ractopamine caused no growth response in medaka. However, the transcriptional changes of genes related to the hypothalamic-pituitary-gonadal (HPG) axis, especially in females, suggested that β-agonists may have the potential to disrupt the endocrine system. Moreover, genes involved in anti-oxidative activity or detoxification were affected in a gender-specific manner. These findings, particularly the effects on the endocrine system of fish, will advance our understanding of the ecotoxicity of β-agonists.

  2. Sex reversal assessments reveal different vulnerability to endocrine disruption between deeply diverged anuran lineages.

    PubMed

    Tamschick, Stephanie; Rozenblut-Kościsty, Beata; Ogielska, Maria; Lehmann, Andreas; Lymberakis, Petros; Hoffmann, Frauke; Lutz, Ilka; Kloas, Werner; Stöck, Matthias

    2016-03-31

    Multiple anthropogenic stressors cause worldwide amphibian declines. Among several poorly investigated causes is global pollution of aquatic ecosystems with endocrine disrupting compounds (EDCs). These substances interfere with the endocrine system and can affect the sexual development of vertebrates including amphibians. We test the susceptibility to an environmentally relevant contraceptive, the artificial estrogen 17α-ethinylestradiol (EE2), simultaneously in three deeply divergent systematic anuran families, a model-species, Xenopus laevis (Pipidae), and two non-models, Hyla arborea (Hylidae) and Bufo viridis (Bufonidae). Our new approach combines synchronized tadpole exposure to three EE2-concentrations (50, 500, 5,000 ng/L) in a flow-through-system and pioneers genetic and histological sexing of metamorphs in non-model anurans for EDC-studies. This novel methodology reveals striking quantitative differences in genetic-male-to-phenotypic-female sex reversal in non-model vs. model species. Our findings qualify molecular sexing in EDC-analyses as requirement to identify sex reversals and state-of-the-art approaches as mandatory to detect species-specific vulnerabilities to EDCs in amphibians.

  3. Small is useful in endocrine disrupter assessment--four key recommendations for aquatic invertebrate research.

    PubMed

    Hutchinson, Thomas H

    2007-02-01

    As we enter the 21st "biocentury", with issues such as biodiversity and biotechnology growing in public profile, it is important to reflect on the immense ecological, medical and economic importance of invertebrates. Efforts to understand the diverse biology of invertebrates come from many directions, including Nobel Prize winning developmental biology, research to control insects that threaten human health and food supplies, aquaculture opportunities and also within ecotoxicology. In the latter context, this special journal volume highlights the importance of addressing endocrine disruption in aquatic invertebrates, from molecular and cellular biomarkers to population-relevant adverse effects. The contributors to this special volume have provided an excellent assessment of both the fundamental endocrinology and applied ecotoxicology of many aquatic invertebrate groups. On the premise that reproductive success is ultimately the vital population parameter, this chapter gives a personal view of key gaps in knowledge in invertebrate reproductive and developmental endocrinology and ecotoxicology. Based on current knowledge, there are four key issues that need to be prioritised within aquatic ecotoxicology: (1) a wider assessment of the reproductive status of invertebrates in both freshwater and coastal ecosystems; (2) prioritisation of laboratory studies in OECD and other regulatory test organisms, including basic endocrinology and ADME (absorption, distribution, metabolism and excretion) research; (3) development and validation of mechanistic biomarkers that can be used as "signposts" to help prioritise species and chronic test endpoint selection, and help link data from laboratory and field studies; and (4) develop a comparative invertebrate toxicology database utilising the prioritised reference chemicals from the EDIETA workshop, encompassing the diverse modes-of-action pertinent to endocrine disrupter testing in both aquatic arthropod and non

  4. Waterborne exposure to triadimefon causes thyroid endocrine disruption and developmental delay in Xenopus laevis tadpoles.

    PubMed

    Li, Meng; Li, Shuying; Yao, Tingting; Zhao, Renjie; Wang, Qiangwei; Zhu, Guonian

    2016-08-01

    Triadimefon (TDF) is a triazole-derivative fungicide that is detectable in the environment and target agricultural products, prompting concern over its risk to wildlife and human health. In our study, Nieuwkoop & Faber stage 51 Xenopus laevis tadpoles were exposed to different nominal concentrations TDF (0, 0.112, and 1.12mg/L) for 21 days while the tadpoles were undergoing pre-morphological development. Developmental condition, bioaccumulation and thyroid hormone levels, and mRNA expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDF caused a reduction in developmental rates on pre-metamorphosis of X. laevis. TDF exposure significantly decreased thyroid hormone (T4 and T3) concentrations, indicating thyroid endocrine disruption. The downregulation of thyroglobulin and upregulation of genes related to thyroid hormone metabolism (ugt1ab) might be responsible for the decreased thyroid hormone concentrations. Treatment with TDF also significantly increased mRNA expression of genes involved in thyroid-stimulating hormone as a compensatory mechanism response to decreased thyroid hormone concentrations. Gene expression and in silico ligand docking studies were combined to study the interaction between TDF and thyroid hormone receptor. Results showed that TDF could consequently affect the HPT axis signaling pathway. In addition, bioconcentration of TDF was observed in tadpoles, indicating the bioactivity of this compound. Taken together, the results suggest that TDF alters the HPT axis-related genes and changes thyroid hormone contents in X. laevis tadpoles, thus causing thyroid endocrine disruption and consequently delaying thyroid hormones-dependent metamorphic development.

  5. Endocrine disruption mechanism of o,p'-DDT in mature male tilapia (Oreochromis niloticus)

    SciTech Connect

    Leanos-Castaneda, Olga . E-mail: olgalidia09@yahoo.com; Kraak, Glen van der; Rodriguez-Canul, Rossanna; Gold, G.

    2007-06-01

    The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER.

  6. Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio.

    PubMed

    Jurewicz, Joanna; Radwan, Michał; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Wielgomas, Bartosz; Ligocka, Danuta; Brzeźnicki, Sławomir; Hanke, Wojciech

    2016-06-01

    In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats.

    PubMed

    Axelstad, Marta; Christiansen, Sofie; Boberg, Julie; Scholze, Martin; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Kortenkamp, Andreas; Hass, Ulla

    2014-01-01

    Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures, and the dose levels reflecting 100, 200, and 450 times this exposure were tested. The compounds were also grouped according to their estrogenicity or anti-androgenicity, and their joint effects were tested at two different doses, with each group reflecting 200 or 450 times human exposure. In addition, a single paracetamol dose was tested (350 mg/kg per day). All exposures and a vehicle were administered by oral gavage to time-mated Wistar dams rats throughout gestation and lactation, and their offspring were assessed for reproductive effects at birth and in prepuberty. The mixture doses, which included the anti-androgenic compounds, affected the male offspring by causing decreased anogenital distance, increased nipple retention (NR), and reduced ventral prostate weights, at both medium and high doses. In addition, the weights of the levator ani/bulbocavernosus muscle (LABC) were decreased at the high dose of anti-androgen mixture. No effects were seen after exposure to the estrogenic chemicals alone, whereas males exposed solely to paracetamol showed decreased LABC weights and increased NR. Thus adverse reproductive effects were observed at mixtures reflecting 200 times high-end human exposure, which is relatively close to the safety margin covered by the regulatory uncertainty factor of 100. This suggests that highly exposed human population groups may not be sufficiently protected against mixtures of endocrine-disrupting chemicals.

  8. Effects of endocrine disrupting chemicals from leather industry effluents on male reproductive system.

    PubMed

    Kumar, Vikas; Majumdar, Chandrajeetbalo; Roy, Partha

    2008-09-01

    The leather tanning industry is characterized by the production of different kinds of effluents, generated in each step of leather processing. These effluents have various chemical compounds which may cause toxicity and endocrine disruption and are thus known as endocrine disrupting chemicals (EDC). This study was aimed to examine the androgenic potential of leather industry effluents collected from northern region of India. Hershberger assay data showed a significant increase (p<0.05) in the weight and structure of sex accessory tissues of castrated rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change (p<0.05) in the expression patterns of the major steroidogenic enzymes in adrenal and testes namely, cytochrome P450scc, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydorgenase in castrated and intact rats. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile demonstrated a dose dependent increase in testicular and adrenal testosterone productions in intact and castrated rats, respectively. This was further supported by decreased level of gonadotrophic hormones (LH and FSH) in treated groups of animals. Further, the effluent treatment resulted in the development of hyperplasia in seminiferous tubules of testes in treated rats as evident from histopathological studies and about two-fold increases in daily sperm production. On analysis of water samples using GC-MS, it was found to contain various aromatic compounds (nonylphenol, hexaclrobenzene and several azo dyes) some of which independently demonstrated similar effects as shown by water samples. Our data suggests that the effluents from leather industry have potential EDC demonstrating androgenic activities.

  9. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

    PubMed

    Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

    2017-04-01

    Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China.

    PubMed

    Law, Alice Yu Sheung; Wei, Xi; Zhang, Xiaowei; Mak, Nak Ki; Cheung, Kwai Chung; Wong, Ming Hung; Giesy, John Paul; Wong, Chris Kong Chu

    2012-01-01

    Endocrine disrupting chemicals (EDCs) consist of a diverse group of industrial chemicals and pharmacological agents. The use of instrumental analyses as the first screening tool might not be cost-effective to identify the existence of enormous numbers of chemical contaminants in environments. Also, knowledge of the concentration of individual residues is difficult to use to evaluate biological impacts of contaminants to wildlife and humans. The primary objective of the present study was to develop and to test the feasibility of using a battery of exposure biomarkers for the rapid-screening of various endocrine disrupting activities present in food. The measurement of the EDC-elicited activities involved various (i) receptor-mediated responses, including androgenic, estrogenic, dioxin-like, glucocorticoid-like, progesterone-like, peroxisome proliferator-like and retinoid-like as well as (ii) the non-receptor mediated responses through modulation of cellular reactive oxygen species (ROS) and ATP content. Samples of both local and imported pork, beef and chicken as well as freshwater and seawater fishes were collected. Extracts of different foods exhibited various dioxin-like and "hormonal" activities. Fish and chicken skin were found to be the major source of exogenous "hormonal" and dioxin-like substances in diets. Extracts of beef and pork contained lesser potencies of hormonally-active agents. Our data suggest that the proposed EDC-screening platform may be useful in a risk assessment for the routine monitoring of EDCs in foods. Continuous monitoring and research is warranted to assess the physiological consequences of the consumption.

  11. Commercial processed food may have endocrine-disrupting potential: soy-based ingredients making the difference.

    PubMed

    Omoruyi, Iyekhoetin Matthew; Kabiersch, Grit; Pohjanvirta, Raimo

    2013-01-01

    Processed and packaged food items as well as ready-to-eat snacks are neglected and poorly characterised sources of human exposure to endocrine-disrupting chemicals (EDCs). In this study we investigated the presence of xenoestrogens in commercially processed and packaged Finnish foods, arising from substances deliberately added or inadvertently contaminating the food, substances formed as a result of food processing, or substances leaching from food packaging materials. Samples were obtained in three separate batches of equivalent products from both a supermarket and a local representative of a global chain of hamburger restaurants and extracted by a solid-phase extraction method. Their endocrine-disrupting potential was determined by yeast bioluminescent assay, using two recombinant yeast strains Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc. In this test system, the majority of samples (both foodstuffs and wrappers) analysed proved negative. However, all batches of industrially prepared hamburgers (but not those obtained from a hamburger restaurant) as well as pepper salami significantly induced luciferase activity in the BMAEREluc/ERα yeast strain indicating the presence of xenoestrogens, with estradiol equivalents of these products ranging from 0.2 to 443 pg g(-1). All three products contained soy-based ingredients, which apparently accounted for, or at least contributed to, their high estrogenic activity, since no signal in the assay was observed with extracts of the packaging material, while two different soy sauces tested yielded an intense signal (28 and 54 pg ml(-1) estradiol-equivalent). These findings imply that by and large chemicals arising in the processing or packaging of foodstuffs in Finland constitute an insignificant source of xenoestrogens to consumers. However, soy-derived ingredients in certain food items might render the entire products highly estrogenic. The estrogenic activity of soy is attributed to isoflavones whose

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

    USGS Publications Warehouse

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

    2014-01-01

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

  13. Spatial distribution and quantification of endocrine-disrupting chemicals in Sado River estuary, Portugal.

    PubMed

    Ribeiro, Cláudia; Pardal, Miguel Angelo; Tiritan, Maria Elizabeth; Rocha, Eduardo; Margalho, Rui Miguel; Rocha, Maria João

    2009-12-01

    The important Portuguese Sado River estuary has never been investigated for the presence of potentially endocrine-disrupting chemicals (EDCs), such as natural estrogens (estradiol, estrone), pharmaceutical estrogens (17alpha-ethynylestradiol), phytoestrogens (daidzein, genistein and biochanin A), or industrial chemicals (4-octylphenol, 4-nonylphenol, and bisphenol A). Thus, the main objective of this study was to evaluate their presence at 13 sampling points distributed between both the industrial and the natural reserve areas of the estuary, zones 1 and 2, respectively. For that, water samples collected in summer and winter were processed by solid phase extraction and analyzed by high-performance liquid chromatography with photodiode array detection and gas chromatography-mass spectroscopy. Results showed that estrone, ethynylestradiol, all the aforementioned phytoestrogens as well as bisphenol A and 4-octylphenol were found in zone 1. In zone 2, neither estrogens nor 4-OP were found. However, in the same zone, daidzein (500 ng/L) and genistein (320 ng/L) attained their highest levels in summer, whereas biochanin A peaked in winter (170 ng/L). Furthermore, bisphenol A was also found in some areas of zone 2, but showed similar concentrations in both surveys (about 220 ng/L). This study demonstrated that the Sado River estuary had low EDCs levels, suggesting that the Sado's high hydrodynamic activity may be involved in the dilution of local pollution. It was suggested that at the current levels of concentrations, all assayed EDCs are unlikely to individually cause endocrine disruption in local animals. However, under a continuous exposure scenario, an additive and/or synergistic action of the estrogenic chemicals load can not be excluded, and so, continuous monitoring is advisable.

  14. Endocrine disruption mechanism of o,p'-DDT in mature male tilapia (Oreochromis niloticus).

    PubMed

    Leaños-Castañeda, Olga; van der Kraak, Glen; Rodríguez-Canul, Rossanna; Gold, G

    2007-06-01

    The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER.

  15. Parental transfer of polybrominated diphenyl ethers (PBDEs) and thyroid endocrine disruption in zebrafish.

    PubMed

    Yu, Liqin; Lam, James C W; Guo, Yongyong; Wu, Rudolf S S; Lam, Paul K S; Zhou, Bingsheng

    2011-12-15

    Polybrominated diphenyl ethers (PBDEs) have the potential to disrupt the thyroid endocrine system. The objective of the present study was to characterize the disrupting effects of long-term exposure on the thyroid endocrine system in adult fish and their progeny following parental exposure to PBDEs. Zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations (1, 3, and 10 μg/L) of the PBDE mixture DE-71 for 5 months until sexual maturation. In the F0 generation, exposure to DE-71 significantly increased plasma thyroxine (T4) but not 3,5,3'-triiodothyronine (T3) in females. This increased T4 was accompanied by decreased mRNA levels of corticotropin-releasing hormone (CRH) and thyrotropin β-subunit (TSHβ) in the brain. The F1 generation was further examined with or without continued DE-71 treatment conditions. Exposure to DE-71 in the F0 fish caused significant increases in T4 and T3 levels in the F1 larvae and modified gene expressions in the hypothalamic-pituitary-thyroid axis (HPT axis) under both conditions. Decreased hatching and inhibition of growth in the F1 offspring were observed in the condition without DE-71 treatment. Continued DE-71 treatment in the F1 embryos/larvae resulted in further decreased hatching, and increased malformation rates compared with those without DE-71 exposure. Analysis of F1 eggs indicated that parental exposure to DE-71 could result in a transfer of PBDEs and thyroid hormones (THs) to their offspring. For the first time, we demonstrated that parental exposure to low concentrations of PBDEs could affect THs in the offspring and the transgenerational PBDE-induced toxicity in subsequent nonexposed generations.

  16. Endocrine-Disrupting Effects of Pesticides through Interference with Human Glucocorticoid Receptor.

    PubMed

    Zhang, Jianyun; Zhang, Jing; Liu, Rui; Gan, Jay; Liu, Jing; Liu, Weiping

    2016-01-05

    Many pesticides have been identified as endocrine-disrupting chemicals (EDCs) due to their ability to bind sex-steroid hormone receptors. However, little attention has been paid to the ability of pesticides to interfere with other steroid hormone receptors such as glucocorticoid receptor (GR) that plays a critical role in metabolic, endocrine, immune, and nervous systems. In this study, the glucocorticoidic and antiglucocorticoidic effects of 34 pesticides on human GR were investigated using luciferase reporter gene assay. Surprisingly, none of the test chemicals showed GR agonistic activity, but 12 chemicals exhibited apparent antagonistic effects. Bifenthrin, λ-cyhalothrin, cypermethrin, resmethrin, o,p'-DDT, p,p'-DDT, methoxychlor, ethiofencarb, and tolylfluanid showed remarkable GR antagonistic properties with RIC20 values lower than 10(-6) M. The disruption of glucocorticoid-responsive genes in H4IIE and J774A.1 cells was further evaluated on these 12 GR antagonists. In H4IIEcells, four organochlorine insecticides, bifenthrin, and 3-PBA decreased cortisol-induced PEPCK gene expression, while o,p'-DDT and methoxychlor inhibited cortisol-stimulated Arg and TAT gene expression. Cypermethrin and tolyfluanid attenuated cortisol-induced TAT expression. In J774A.1 cells, λ-cyhalothrin, resmethrin, 3-PBA, o,p'-DDT, p,p'-DDT, p,p'-DDE, methoxychlor- and tolylfluanid-reduced cortisol-stimulated GILZ expression. Furthermore, molecular docking simulation indicated that different interactions may stabilize the binding between molecules and GR. Our findings suggest that comprehensive screening and evaluation of GR antagonists and agonists should be considered to better understand the health and ecological risks of man-made chemicals such as pesticides.

  17. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    SciTech Connect

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blueher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  18. Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement.

    PubMed

    Solecki, Roland; Kortenkamp, Andreas; Bergman, Åke; Chahoud, Ibrahim; Degen, Gisela H; Dietrich, Daniel; Greim, Helmut; Håkansson, Helen; Hass, Ulla; Husoy, Trine; Jacobs, Miriam; Jobling, Susan; Mantovani, Alberto; Marx-Stoelting, Philip; Piersma, Aldert; Ritz, Vera; Slama, Remy; Stahlmann, Ralf; van den Berg, Martin; Zoeller, R Thomas; Boobis, Alan R

    2017-02-01

    Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria.

  19. Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment.

    PubMed

    Patisaul, Heather B; Roberts, Simon C; Mabrey, Natalie; McCaffrey, Katherine A; Gear, Robin B; Braun, Joe; Belcher, Scott M; Stapleton, Heather M

    2013-02-01

    Firemaster® 550 (FM 550), a fire-retardant mixture used in foam-based products, was recently identified as a common contaminant in household dust. The chemical structures of its principle components suggest they have endocrine disrupting activity, but nothing is known about their physiological effects at environmentally relevant exposure levels. The goal of this exploratory study was to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550 in rats exposed to 100 or 1000 µg/day across gestation and lactation. FM 550 components accumulated in tissues of exposed dams and offspring and induced phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects included increased serum thyroxine levels and reduced hepatic carboxylesterease activity in dams, and advanced female puberty, weight gain, male cardiac hypertrophy, and altered exploratory behaviors in offspring. Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels. © 2012 Wiley Periodicals, Inc.

  20. Accumulation and Endocrine Disrupting Effects of the Flame Retardant Mixture Firemaster® 550 in Rats: An Exploratory Assessment

    PubMed Central

    Patisaul, Heather B.; Roberts, Simon C.; Mabrey, Natalie; McCaffrey, Katherine A.; Gear, Robin B.; Braun, Joe; Belcher, Scott M.; Stapleton, Heather M.

    2013-01-01

    Firemaster® 550 (FM 550), a fire-retardant mixture used in foam-based products, was recently identified as a common contaminant in household dust. The chemical structures of its principle components suggest they have endocrine disrupting activity, but nothing is known about their physiological effects at environmentally relevant exposure levels. The goal of this exploratory study was to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550 in rats exposed to 100 or 1000 μg/day across gestation and lactation. FM 550 components accumulated in tissues of exposed dams and offspring and induced phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects included increased serum thyroxine levels and reduced hepatic carboxylesterease activity in dams, and advanced female puberty, weight gain, male cardiac hypertrophy, and altered exploratory behaviors in offspring. Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels. PMID:23139171

  1. Endocrine Disrupting Chemicals in Fish: Developing Exposure Indicators and Predictive Models of Effects Based on Mechanism of Action

    EPA Science Inventory

    In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of endocrine-disrupting chemicals (EDCs) on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a syste...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  4. A PERSPECTIVE ON THE RISK ASSESSMENT PROCESS FOR ENDOCRINE-DISRUPTIVE EFFECTS ON WILDLIFE AND HUMAN HEALTH

    EPA Science Inventory

    The topic of endocrine disrupting chemicals (EDCs) presents significant issues to the risk assessment process. . . We have a working definition of an EDC, that provides a starting point for considering what chemicals are of concern. We also have an understanding of the important ...

  5. Low dose mixture effects of endocrine disrupters and their implications for regulatory thresholds in chemical risk assessment.

    PubMed

    Kortenkamp, Andreas

    2014-12-01

    Today's chemical exposures are characterised by a widely spread blanket of contamination composed of myriads of chemicals, many of them endocrine disrupters, all at rather low levels. With their focus on considering single chemicals one by one, the approaches used by regulatory bodies worldwide for safety assessments of chemicals cannot keep up with these pollution patterns. A substantial challenge lies in the assessment of combination effects from large numbers of endocrine disrupters and other chemicals, all at low doses. We retrace the development of experimental and conceptual approaches required for assessing low dose mixtures, with an emphasis on work with endocrine disrupting chemicals. We find that nearly 20 years of research has produced good evidence for combination effects at levels around experimental thresholds. One obstacle in deciding on the relevance of this evidence is incomplete information about the range of endocrine-disrupting chemicals that make up combined exposures. These knowledge gaps need to be closed urgently, as is currently discussed under the heading of exposome research.

  6. Endocrine Disrupting Chemicals in Fish: Developing Exposure Indicators and Predictive Models of Effects Based on Mechanism of Action

    EPA Science Inventory

    In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of endocrine-disrupting chemicals (EDCs) on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a syste...

  7. SPECIES DIFFERENCES IN ANDROGEN AND ESTROGEN RECEPTOR STRUCTURE AND FUNCTION AMONG VERTEBRATES AND INVERTEBRATES: INTERSPECIES EXTRAPOLATIONS REGARDING ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Species Differences in Androgen and Estrogen Receptor Structure and Function Among Vertebrates and Invertebrates: Interspecies Extrapolations regarding Endocrine Disrupting Chemicals
    VS Wilson1, GT Ankley2, M Gooding 1,3, PD Reynolds 1,4, NC Noriega 1, M Cardon 1, P Hartig1,...

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

    EPA Science Inventory

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

  9. ASSESSMENT OF A FATHEAD MINNOW REPRODUCTION ASSAY FOR IDENTIFYING ENDOCRINE-DISRUPTING CHEMICALS WITH DIVERSE MODES OF ACTION

    EPA Science Inventory

    The US EPA has developed a short-term reproduction test with the fathead minnow to identify potential endocrine disrupting chemicals (EDCs). The assay is initiated by collecting baseline spawning data from reproductively-active adult fathead minnows for 21 d, followed by a 21 d e...

  10. SPECIES DIFFERENCES IN ANDROGEN AND ESTROGEN RECEPTOR STRUCTURE AND FUNCTION AMONG VERTEBRATES AND INVERTEBRATES: INTERSPECIES EXTRAPOLATIONS REGARDING ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Species Differences in Androgen and Estrogen Receptor Structure and Function Among Vertebrates and Invertebrates: Interspecies Extrapolations regarding Endocrine Disrupting Chemicals
    VS Wilson1, GT Ankley2, M Gooding 1,3, PD Reynolds 1,4, NC Noriega 1, M Cardon 1, P Hartig1,...

  11. A PERSPECTIVE ON THE RISK ASSESSMENT PROCESS FOR ENDOCRINE-DISRUPTIVE EFFECTS ON WILDLIFE AND HUMAN HEALTH

    EPA Science Inventory

    The topic of endocrine disrupting chemicals (EDCs) presents significant issues to the risk assessment process. . . We have a working definition of an EDC, that provides a starting point for considering what chemicals are of concern. We also have an understanding of the important ...

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

    EPA Science Inventory

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

  13. A computational approach predicting CYP450 metabolism and estrogenic activity of an endocrine disrupting compound (PCB-30).

    PubMed

    Harris, Jason B; Eldridge, Melanie L; Sayler, Gary; Menn, Fu-Min; Layton, Alice C; Baudry, Jerome

    2014-07-01

    Endocrine disrupting chemicals influence growth and development through interactions with the hormone system, often through binding to hormone receptors such as the estrogen receptor. Computational methods can predict endocrine disrupting chemical activity of unmodified compounds, but approaches predicting activity following metabolism are lacking. The present study uses a well-known environmental contaminant, PCB-30 (2,4,6-trichlorobiphenyl), as a prototype endocrine disrupting chemical and integrates predictive (computational) and experimental methods to determine its metabolic transformation by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) into estrogenic byproducts. Computational predictions suggest that hydroxylation of PCB-30 occurs at the 3- or 4-phenol positions and leads to metabolites that bind more strongly than the parent molecule to the human estrogen receptor alpha (hER-α). Gas chromatography-mass spectrometry experiments confirmed that the primary metabolite for CYP3A4 and CYP2D6 is 4-hydroxy-PCB-30, and the secondary metabolite is 3-hydroxy-PCB-30. Cell-based bioassays (bioluminescent yeast expressing hER-α) confirmed that hydroxylated metabolites are more estrogenic than PCB-30. These experimental results support the applied model's ability to predict the metabolic and estrogenic fate of PCB-30, which could be used to identify other endocrine disrupting chemicals involved in similar pathways. © 2014 SETAC.

  14. Endocrine-disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence.

    PubMed

    Petro, Evi M L; Leroy, Jo L M R; Covaci, Adrian; Fransen, Erik; De Neubourg, Diane; Dirtu, Alin C; De Pauw, Ingrid; Bols, Peter E J

    2012-04-01

    Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called 'endocrine-disrupting chemicals' (EDCs) or 'endocrine disruptors', can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum. Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination. Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even

  15. Developmental exposure to endocrine disrupting chemicals alters the epigenome: Identification of reprogrammed targets

    PubMed Central

    Prusinski, Lauren; Al-Hendy, Ayman; Yang, Qiwei

    2016-01-01

    Endocrine disruptions induced by environmental toxicants have placed an immense burden on society to properly diagnose, treat and attempt to alleviate symptoms and disease. Environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life - a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical and cellular events. Humans may encounter endocrine disrupting chemicals (EDCs) daily and during all stages of life, from conception and fetal development through adulthood and senescence. Though puberty and perimenopausal periods may be affected by endocrine disruption due to hormonal effects, prenatal and early postnatal windows are most critical for proper development due to rapid changes in system growth. Developmental reprogramming is shown to be caused by alterations in the epigenome. Development is the time when epigenetic programs are ‘installed’ on the genome by ‘writers’, such as histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), which add methyl groups to lysine and arginine residues on histone tails and to CpG sites in DNA, respectively. A number of environmental compounds, referred to as estrogenic endocrine disruptors (EEDs), are able to bind to estrogen receptors (ERs) and interfere with the normal cellular development in target tissues including the prostate and uterus. These EEDs, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease. Due to the lack of fully understanding the underlying mechanisms of how environmental toxicants and their level of exposure affect the human genome, it can be challenging to create clear

  16. The US federal framework for research on endocrine disrupters and an analysis of research programs supported during fiscal year 1996

    USGS Publications Warehouse

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

    1998-01-01

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

  17. Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

    PubMed Central

    Braun, Joseph M.

    2017-01-01

    Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

  18. Polybrominated Diphenyl Ethers Induce Developmental Neurotoxicity in a Human in Vitro Model: Evidence for Endocrine Disruption

    PubMed Central

    Schreiber, Timm; Gassmann, Kathrin; Götz, Christine; Hübenthal, Ulrike; Moors, Michaela; Krause, Guido; Merk, Hans F.; Nguyen, Ngoc-Ha; Scanlan, Thomas S.; Abel, Josef; Rose, Christine R.; Fritsche, Ellen

    2010-01-01

    Background Polybrominated diphenyl ethers (PBDEs) are persistent and bioaccumulative flame retardants, which are found in rising concentrations in human tissues. They are of concern for human health because animal studies have shown that they possess the potential to be developmentally neurotoxic. Objective Because there is little knowledge of the effects of PBDEs on human brain cells, we investigated their toxic potential for human neural development in vitro. Moreover, we studied the involvement of thyroid hormone (TH) disruption in the effects caused by PBDEs. Methods We used the two PBDE congeners BDE-47 and BDE-99 (0.1–10 μM), which are most prominent in human tissues. As a model of neural development, we employed primary fetal human neural progenitor cells (hNPCs), which are cultured as neurospheres and mimic basic processes of brain development in vitro: proliferation, migration, and differentiation. Results PBDEs do not disturb hNPC proliferation but decrease migration distance of hNPCs. Moreover, they cause a reduction of differentiation into neurons and oligodendrocytes. Simultaneous exposure with the TH receptor (THR) agonist triiodothyronine rescues these effects on migration and differentiation, whereas the THR antagonist NH-3 does not exert an additive effect. Conclusion PBDEs disturb development of hNPCs in vitro via endocrine disruption of cellular TH signaling at concentrations that might be of relevance for human exposure. PMID:20368126

  19. Bridging epidemiology and model organisms to increase understanding of endocrine disrupting chemicals and human health effects.

    PubMed

    Woodruff, Tracey J

    2011-10-01

    Concerning temporal trends in human reproductive health has prompted concern about the role of environmentally mediated risk factors. The population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products, subsequently multiple chemicals are found human populations around the globe. Recent reviews find that endocrine disrupting chemicals (EDCs) can adversely affect reproductive and developmental health. However, there are still many knowledge gaps. This paper reviews some of the key scientific concepts relevant to integrating information from human epidemiologic and model organisms to understand the relationship between EDC exposure and adverse human health effects. Additionally, areas of new insights which influence the interpretation of the science are briefly reviewed, including: enhanced understanding of toxicity pathways; importance of timing of exposure; contribution of multiple chemical exposures; and low dose effects. Two cases are presented, thyroid disrupting chemicals and anti-androgens chemicals, which illustrate how our knowledge of the relationship between EDCs and adverse human health effects is strengthened and data gaps reduced when we integrate findings from animal and human studies.

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

    PubMed

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

    2005-01-01

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

  1. Studying the effects of genistein on gene expression of fish embryos as an alternative testing approach for endocrine disruption.

    PubMed

    Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Muth-Köhne, Elke; Giesy, John P; Hecker, Markus; Fenske, Martina

    2013-01-01

    Assessment of endocrine disruption currently relies on testing strategies involving adult vertebrates. In order to minimize the use of animal tests according to the 3Rs principle of replacement, reduction and refinement, we propose a transcriptomics and fish embryo based approach as an alternative to identify and analyze an estrogenic activity of environmental chemicals. For this purpose, the suitability of 48 h and 7 days post-fertilization zebrafish and medaka embryos to test for estrogenic disruption was evaluated. The embryos were exposed to the phytoestrogen genistein and subsequently analyzed by microarrays and quantitative real-time PCR. The functional analysis showed that the genes affected related to multiple metabolic and signaling pathways in the early fish embryo, which reflect the known components of genistein's mode of actions, like apoptosis, estrogenic response, hox gene expression and steroid hormone synthesis. Moreover, the transcriptomic data also suggested a thyroidal mode of action and disruption of the nervous system development. The parallel testing of two fish species provided complementary data on the effects of genistein at gene expression level and facilitated the separation of common from species-dependent effects. Overall, the study demonstrated that combining fish embryo testing with transcriptomics can deliver abundant information about the mechanistic effects of endocrine disrupting chemicals, rendering this strategy a promising alternative approach to test for endocrine disruption in a whole organism in-vitro scale system. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Generation of fluorescent zebrafish to study endocrine disruption and potential crosstalk between thyroid hormone and corticosteroids.

    PubMed

    Terrien, Xavier; Fini, Jean-Baptiste; Demeneix, Barbara A; Schramm, Karl-Werner; Prunet, Patrick

    2011-09-01

    Several environmental chemicals disrupt thyroid function, a key regulator of normal development involved in many physiological processes in fish. We studied the effects of such chemicals in vivo using transient transgenic zebrafish (Danio rerio), expressing Green Fluorescent Protein (GFP) under the control of a TH/bZIP promoter from Xenopus laevis. Exposure to thyroid hormone (T3) at 10(-8)M increased GFP fluorescence in F0 embryos and larvae. Transient transgenic embryos were exposed to a T3 signaling agonist (TRIAC) or antagonists (NH(3) or NaClO(4)), or to the endocrine disruptor Bisphenol A (BPA). When tested alone, TRIAC increased fluorescence, confirming the specificity of our model. Exposure to NH(3) or NaClO(4) decreased fluorescence, reflecting inhibition of thyroid function. When tested alone, BPA did not modify fluorescence, but when tested with T3, it significantly reduced T3-induced fluorescence, suggesting disruption of the thyroid function by BPA. The expression of genes involved in the TH axis (TR-alpha, TR-beta, TSH) and the corticoid axis (GR and MR) was followed by q-PCR after T3 or BPA exposure (24 or 48h) and at different developmental stages (0, 1, or 5 days post-fertilization). Expression of TR-alpha, TR-beta, and TSH genes increased after 48h T3 exposure in 1-day-old larvae. When tested alone, BPA only slightly affected gene expression. When applied with T3, BPA decreased expression of all candidate genes in 1-day-old embryos compared to the T3 treated group, in agreement with data obtained with the TH/bZIP-eGFP zebrafish model. Finally, we show that T3 exposure leads to up-regulation of MR and GR genes. This study provides a new rapid diagnostic tool for characterizing the disrupting effects of toxicants on thyroid function and suggests possible crosstalk between the TR and Corticoid Signaling system.

  3. Towards an internationally harmonized test method for reproductive and developmental effects of endocrine disrupters in marine copepods.

    PubMed

    Kusk, K Ole; Wollenberger, Leah

    2007-02-01

    New and updated methods to detect and characterize endocrine disrupting chemicals (EDCs) are urgently needed for the purpose of environmental risk assessment since these substances are often not detected using existing chronic toxicity tests. Numerous reports on the effects of EDCs on crustacean development and reproduction have been published and the development of life-cycle tests with crustaceans has been prioritized within the OECD work program for endocrine disrupter testing and assessment. As a result, Sweden, and Denmark initiated a proposal for development of a full life-cycle test with marine copepods (Acartia tonsa, Nitocra spinipes, Tisbe battagliai, and Amphiascus tenuiremis). The present paper gives an overview on the endocrine system of crustaceans with special emphasis on development and reproduction, which are targets for endocrine disruption, and reviews available methods for detecting effects on development and reproduction in calanoid and harpacticoid copepods. A draft OECD guideline Copepod Development and Reproduction Test has been developed, and a pre-validation of this draft guideline was completed in 2005. An updated draft guideline, taking into account the results of the pre-validation, is now under validation in an international ring-test, which is running till the end of 2006.

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

    PubMed

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

    2017-07-01

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

  5. Generation and characterization of gsuα:EGFP transgenic zebrafish for evaluating endocrine-disrupting effects

    SciTech Connect

    Cheng, Xiaoxia; Chen, Xiaowen; Jin, Xia; He, Jiangyan; Yin, Zhan

    2014-07-01

    The glycoprotein subunit α (gsuα) gene encodes the shared α subunit of the three pituitary heterodimeric glycoprotein hormones: follicle-stimulating hormone β (Fshβ), luteinizing hormone β (Lhβ) and thyroid stimulating hormone β (Tshβ). In our current study, we identified and characterized the promoter region of zebrafish gsuα and generated a stable gsuα:EGFP transgenic line, which recapitulated the endogenous gsuα expression in the early developing pituitary gland. A relatively conserved regulatory element set is presented in the promoter regions of zebrafish and three other known mammalian gsuα promoters. Our results also demonstrated that the expression patterns of the gsuα:EGFP transgene were all identical to those expression patterns of the endogenous gsuα expression in the pituitary tissue when our transgenic fish were treated with various endocrine chemicals, including forskolin (FSK), SP600125, trichostatin A (TSA), KClO{sub 4}, dexamethasone (Dex), β-estradiol and progesterone. Thus, this gsuα:EGFP transgenic fish reporter line provides another valuable tool for investigating the lineage development of gsuα-expressing gonadotrophins and the coordinated regulation of various glycoprotein hormone subunit genes. These reporter fish can serve as a novel platform to perform screenings of endocrine-disrupting chemicals (EDCs) in vivo as well. - Highlights: • Identification of the promoter of zebrafish glycoprotein subunit α (gsuα) gene • Generation of stable transmission gsuα:EGFP transgenic zebrafish reporter • Demonstration of the recapitulation of the gsuα:EGFP and endogenous gsuα expression • Suggestion of the gsuα:EGFP transgenic zebrafish as a novel platform for EDC study.

  6. Endocrine-disrupting effects of cattle feedlot effluent on an aquatic sentinel species, the fathead minnow.

    PubMed

    Orlando, Edward F; Kolok, Alan S; Binzcik, Gerry A; Gates, Jennifer L; Horton, Megan K; Lambright, Christy S; Gray, L Earl; Soto, Ana M; Guillette, Louis J

    2004-03-01

    Over the last decade, research has examined the endocrine-disrupting action of various environmental pollutants, including hormones, pharmaceuticals, and surfactants, in sewage treatment plant effluent. Responding to the growth of concentrated animal feeding operations (CAFOs) and the pollutants present in their wastewater (e.g., nutrients, pharmaceuticals, and hormones), the U.S. Environmental Protection Agency developed a new rule that tightens the regulation of CAFOs. In this study, we collected wild fathead minnows (Pimephales promelas) exposed to feedlot effluent (FLE) and observed significant alterations in their reproductive biology. Male fish were demasculinized (having lower testicular testosterone synthesis, altered head morphometrics, and smaller testis size). Defeminization of females, as evidenced by a decreased estrogen:androgen ratio of in vitro steroid hormone synthesis, was also documented. We did not observe characteristics in either male or female fish indicative of exposure to environmental estrogens. Using cells transfected with the human androgen receptor, we detected potent androgenic responses from the FLE. Taken together, our morphologic, endocrinologic, and in vitro gene activation assay data suggest two hypotheses: a) there are potent androgenic substance(s) in the FLE, and/or b) there is a complex mixture of androgenic and estrogenic substances that alter the hypothalamic-pituitary-gonadal axis, inhibiting the release of gonadotropin-releasing hormone or gonadotropins. This is the first study demonstrating that the endocrine and reproductive systems of wild fish can be adversely affected by FLE. Future studies are needed to further investigate the effects of agricultural runoff and to identify the biologically active agents, whether natural or pharmaceutical in origin.

  7. Investigation of potential endocrine disrupting effects of mosquito larvicidal Bacillus thuringiensis israelensis (Bti) formulations.

    PubMed

    Maletz, Sibylle; Wollenweber, Marc; Kubiak, Katharina; Müller, Annett; Schmitz, Stefan; Maier, Dieter; Hecker, Markus; Hollert, Henner

    2015-12-01

    Bti is successfully used as a biological control agent for mosquito control. It has proven to be ecological friendly, and thus, is used in ecologically sensitive habitats. Recent investigations of groundwater in Germany have detected estrogenic activity in five consecutive groundwater wells in a region where Bti is applied. Therefore, it was suspected that this compound can act as an environmental xenoestrogen. In the present study, five Bti formulations as well as the active ingredient, VectoBac® TP (TP), were investigated regarding their estrogenic activity using the LYES and ER CALUX® assays. Furthermore, their steroidogenesis disruption properties were studied using the H295R Steroidogenesis Assay. Additionally, field samples from a Bti application area as well as samples from an artificial pond were examined. Three of the Bti formulations and the active ingredient TP showed significant estrogenic activity in the LYES (up to 52 ng·l(-1) estradiol equivalents (EEQ) in the 18-fold concentration) and/or the ER CALUX® (up to 1 ng·EEQ·l(-1) in the 18-fold concentration). In the H295R significant but weak effects with no dose-response-relationship on the production of estradiol, and 21-hydroxyprogesterone (WDG) as well as testosterone (TP) by H295R cells could be observed. The field samples as well as the samples from the artificial pond showed no significant increase of estrogenic activity after application of TP or WDG in the ER CALUX®. With the exception of the controlled laboratory experiments with direct application of Bti to the utilized in vitro test systems the present study did not reveal any significant effects of Bti on endocrine functions that would indicate that the application of Bti could cause adverse endocrine effects to organisms in aquatic ecosystems. Instead, our results support previous studies that the use of Bti products against mosquitos would be safe even for sensitive habitats such as conservation areas. Copyright © 2015 Elsevier B

  8. 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.

  9. Regenerative response and endocrine disrupters in crinoid echinoderms: an old experimental model, a new ecotoxicological test.

    PubMed

    Candia Carnevali, M D

    2005-01-01

    The regenerative phenomena that reproduce developmental processes in adult organisms and are regulated by endocrine and neurohumoral mechanisms can provide new sensitive tests for monitoring the effects of exposure to anthropogenic chemicals such as endocrine disrupter (ED) contaminants. These pollutants in fact can be bioaccumulated by the organisms, causing dysfunctions in steroid hormone production/metabolism and activities and inducing dramatic effects on reproductive competence, development and growth in many animals, man included. Current research is exploring the effects of exposure to different classes of compounds well known for their ED activity, such as polychlorinated biphenyls (PCBs), nonylphenols and organotins, on regenerative potential of echinoderms, a relatively unexplored and promising applied approach which offers the unique chance to study physiological developmental processes in adult animals. The selected test species is the crinoid Antedon mediterranea, which represents a valuable experimental model for investigation into the regenerative process from the macroscopic to the molecular level. The present study employs an integrated approach which combines exposure experiments, chemical analysis and biological analysis utilizing classical methods of light (LM) and electron (TEM and SEM) microscopy and immunocytochemistry. The experiments were carried out on experimentally induced arm regenerations in controlled conditions with exposure concentrations comparable to those of moderately polluted coastal zones in order to reproduce common conditions of exposure to environmental contaminants. The results of the exposure tests were analysed in terms of effects at the whole organism, at the tissue and cellular level, and possible sites of action of EDs. Our results show that prolonged exposure to these compounds significantly affects the regenerative mechanisms by inducing appreciable anomalies in terms of regeneration times, overall growth, general

  10. Characterization of endocrine-disruption and clinical manifestations in large-mouth bass from Florida lakes

    SciTech Connect

    Gross, D.A.; Gross, T.S.; Johnson, B.; Folmar, L.

    1995-12-31

    Previous efforts from this laboratory have documented altered endocrine function and sexual differentiation for alligators and turtles from Lake Apopka in Central Florida. This lake has been exposed to a variety of contaminants which are potentially endocrine-disrupting. Therefore, a survey of large mouth bass populations was conducted on several lakes in North Central Florida to examine reproductive and clinical health. Large-mouth bass were collected from lakes Apopka, Griffin, Jessup and Woodruff. Approximately 24 fish (12 males and 12 females) were collected from each lake during the spawning (March--April) and non-reproductive (July--August) seasons. Plasma samples were collected for analysis of estrogen, testosterone and 11-keto-testosterone concentrations. Gonadal and liver tissues were collected for histological analysis. General blood chemistry analyses and parasite surveys were also conducted to estimate general health. Additionally, fillet samples were collected and analyzed for pesticide levels. Fish from Lake Apopka had unusual concentrations of estrogen and 11-keto-testosterone in plasma when compared to bass from Lakes Woodruff, Jessup and Griffin. Parasites loads were significantly higher for bass from lake Apopka than from the other lakes. Male bass on Apopka had depressed concentrations of 11-keto-testosterone, skewing the E/T ratios upward while female bass had higher concentrations of estrogens than females from the other lakes, again resulting in skewed E/T ratios. These skewed E/T ratios are similar to those observed for alligators on the same lake and raise the possibility that they are caused by contaminants. However, contaminant levels in fillets did not differ significantly between lakes. These studies indicate potentially altered reproductive and immunological function for large-mouth bass living in a contaminated lake.

  11. Simultaneous profiling of 17 steroid hormones for the evaluation of endocrine-disrupting chemicals in H295R cells.

    PubMed

    Jumhawan, Udi; Yamashita, Toshiyuki; Ishida, Kazuya; Fukusaki, Eiichiro; Bamba, Takeshi

    2017-01-01

    There is urgent need to develop a new protocol for the evaluation of chemical substances to potentially interact with the endocrine system and induce numerous pathological issues. The recently validated in vitro screening assay is limited on monitoring two steroid hormones. Methodology & results: The H295R model cell was exposed to seven endocrine disrupting chemicals (EDCs). The levels of 17 steroid hormones in cell extracts were subsequently determined by a quantitative targeted GC/MS/MS method. Through wide coverage, this system managed to capture the effects of exposure to increasing EDCs concentrations in the entire steroidogenic pathways. The developed approach could be beneficial for the mechanistic investigation of EDCs.

  12. Bioavailability of endocrine disrupting chemicals (EDCs): Liposome-water partitioning and lipid membrane permeation

    NASA Astrophysics Data System (ADS)

    Kwon, Jung-Hwan

    The bioavailability of endocrine disrupting chemicals (EDCs) is a function of a number of parameters including the ability of the chemical to partition into organic tissue and reach receptor sites within an organism. In this dissertation, equilibrium partition coefficients between water and lipid membrane vesicles and artificial lipid membrane permeability were investigated for evaluating bioavailability of aqueous pollutants. Structurally diverse endocrine disrupting chemicals were chosen as model compounds for partitioning experiments and simple hydrophobic organic chemicals were used for the evaluation of a parallel artificial membrane device developed to mimic bioconcentration rates in fish. Hydrophobic interactions represented by octanol/water partition coefficients (KOWs) were not appropriate for estimating lipid membrane/water partition coefficients (Klipws) for the selected EDCs having a relatively large molar liquid volume (MLV) and containing polar functional groups. Correlations that include MLV and polar surface area (PSA) reduce the predicted value of log K lipw, suggesting that lipid membranes are less favorable than 1-octanol for a hydrophobic solute because of the changes in membrane fluidity and the amount of cholesterol in the lipid bilayers. These results suggested that KOW alone has limited potential for estimating K lipw, and MLV or PSA may be used as additional descriptors for developing quantitative structure-activity relationships (QSARs). The poor correlations between KOW and Klipw observed in this research may be due to the highly organized structure of lipid bilayers. Measured thermodynamic constants demonstrated that the entropy contribution becomes more dominant for more organized liposomes having saturated lipid tails. This implies that entropy-driven partitioning process makes Klipw different from KOW especially for more saturated lipid bilayer membranes. In the parallel artificial membrane system developed, a membrane filter

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

    PubMed

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

    2006-06-01

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

  14. ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

    EPA Science Inventory

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

  15. ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

    EPA Science Inventory

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

  16. Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors

    PubMed Central

    2013-01-01

    The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. PMID:23981490

  17. Science and policy on endocrine disrupters must not be mixed: a reply to a "common sense" intervention by toxicology journal editors.

    PubMed

    Bergman, Åke; Andersson, Anna-Maria; Becher, Georg; van den Berg, Martin; Blumberg, Bruce; Bjerregaard, Poul; Bornehag, Carl-Gustaf; Bornman, Riana; Brandt, Ingvar; Brian, Jayne V; Casey, Stephanie C; Fowler, Paul A; Frouin, Heloise; Giudice, Linda C; Iguchi, Taisen; Hass, Ulla; Jobling, Susan; Juul, Anders; Kidd, Karen A; Kortenkamp, Andreas; Lind, Monica; Martin, Olwenn V; Muir, Derek; Ochieng, Roseline; Olea, Nicolas; Norrgren, Leif; Ropstad, Erik; Ross, Peter S; Rudén, Christina; Scheringer, Martin; Skakkebaek, Niels Erik; Söder, Olle; Sonnenschein, Carlos; Soto, Ana; Swan, Shanna; Toppari, Jorma; Tyler, Charles R; Vandenberg, Laura N; Vinggaard, Anne Marie; Wiberg, Karin; Zoeller, R Thomas

    2013-08-27

    The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.

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

    PubMed

    Brander, Susanne M; Connon, Richard E; He, Guochun; Hobbs, James A; Smalling, Kelly L; Teh, Swee J; White, J Wilson; Werner, Inge; Denison, Michael S; Cherr, Gary N

    2013-01-01

    Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i

  19. Effects of copper on growth, metamorphosis and endocrine disruption of Bufo gargarizans larvae.

    PubMed

    Wang, Chao; Liang, Gang; Chai, Lihong; Wang, Hongyuan

    2016-01-01

    Chinese toad (Bufo gargarizans) tadpoles were exposed to copper (1, 6.4, 32 and 64μgL(-1) copper) from the beginning of larval period through completion of metamorphosis. We examined the effects of chronic copper exposure on mortality, growth, time to metamorphosis, tail resorption time, body size at the metamorphic climax (Gs 42) and completion of metamorphosis (Gs 46) and thyroid gland histology. In addition, type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. Our result showed that 6.4-64μgL(-1) copper concentration increased the mortality and inhibited the growth of B. gargarizans tadpoles. In addition, significant reduction in size at Gs 42 and a time delay to Gs 42 were observed at 6.4-64μgL(-1) copper treatments. Moreover, histological examinations have clearly revealed that 64μgL(-1) copper caused follicular cell hyperplasia in thyroid gland. According to real-time PCR results, exposure to 32 and 64μgL(-1) copper significantly up-regulated mRNA expression of Dio3, but down-regulated mRNA expression of TRα and TRβ mRNA level. We concluded that copper delayed amphibian metamorphosis through changing mRNA expression of Dio3, TRα and TRβ, which suggests that copper might have the endocrine-disrupting effect. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Manufacturing doubt about endocrine disrupter science--A rebuttal of industry-sponsored critical comments on the UNEP/WHO report "State of the Science of Endocrine Disrupting Chemicals 2012".

    PubMed

    Bergman, Åke; Becher, Georg; Blumberg, Bruce; Bjerregaard, Poul; Bornman, Riana; Brandt, Ingvar; Casey, Stephanie C; Frouin, Heloise; Giudice, Linda C; Heindel, Jerrold J; Iguchi, Taisen; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Lind, P Monica; Muir, Derek; Ochieng, Roseline; Ropstad, Erik; Ross, Peter S; Skakkebaek, Niels Erik; Toppari, Jorma; Vandenberg, Laura N; Woodruff, Tracey J; Zoeller, R Thomas

    2015-12-01

    We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford-Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity.

  1. Sustainable biodegradation of phenolic endocrine-disrupting chemicals by Phragmites australis-rhizosphere bacteria association.

    PubMed

    Toyama, T; Ojima, T; Tanaka, Y; Mori, K; Morikawa, M

    2013-01-01

    The efficacy of two rhizobacteria (Sphingobium fuliginis TIK1 and Sphingobium sp. IT4) of Phragmites australis for the sustainable treatment of water polluted with phenolic endocrine-disrupting chemicals (EDCs) was investigated. Strains TIK1 and IT4 have recently been isolated from Phragmites rhizosphere and shown to degrade various 4-alkylphenols-TIK1 via phenolic ring hydroxylation and meta-cleavage and IT4 via ipso-hydroxylation. The two strains also degraded bisphenol A (BPA), bisphenol B, bisphenol E, bisphenol F, bisphenol P and bisphenol S (BPS). Thus, strains TIK1 and IT4 have wide degradation spectra for phenolic EDCs. The two strains utilized Phragmites root extracts as a sole carbon source and sustainably colonized Phragmites roots, where they degraded phenolic EDCs. In sequencing batch reactor experiments using Phragmites in association with TIK1 or IT4, both associations repeatedly removed phenolic EDCs from polluted secondary effluent water (BPA, BPS, 4-tert-butylphenol, 4-tert-octylphenol and 4-nonylphenol) from polluted secondary effluent water. The results suggest that hydroponic systems using Phragmites-TIK and Phragmites-IT4 associations would be useful for sustainable treatment of polluted waters containing various phenolic EDCs.

  2. Endocrine Disrupting Chemicals and the Developmental Programming of Adipogenesis and Obesity

    PubMed Central

    Janesick, Amanda; Blumberg, Bruce

    2016-01-01

    Obesity and related disorders are a burgeoning public health epidemic, particularly in the U.S. Currently 34% of the U.S. population is clinically obese (BMI > 30) and 68% are overweight (BMI > 25), more than double the worldwide average and 10-fold higher than Japan and South Korea. Obesity occurs when energy intake exceeds energy expenditure; however, individuals vary widely in their propensity to gain weight and accrue fat mass, even at identical levels of excess caloric input. Clinical, epidemiological, and biological studies show that obesity is largely programmed during early life, including the intrauterine period. The environmental obesogen hypothesis holds that prenatal or early life exposure to certain endocrine disrupting chemicals can predispose exposed individuals to increased fat mass and obesity. Obesogen exposure can alter the epigenome of multipotent stromal stem cells, biasing them toward the adipocyte lineage at the expense of bone. Hence, humans exposed to obesogens during early life might have an altered stem cell compartment, which is preprogrammed toward an adipogenic fate. This results in a higher steady state number of adipocytes and potentially a lifelong struggle to maintain a healthy weight, which can be exacerbated by societal influences that promote poor diet and inadequate exercise. This review focuses on the developmental origins of the adipocyte, the relationship between adipocyte number and obesity, and how obesogenic chemicals may interfere with the highly efficient homeostatic mechanisms regulating adipocyte number and energy balance. PMID:21425440

  3. Extent of endocrine disruption in fish of western and Alaskan National Parks

    USGS Publications Warehouse

    Schreck, Carl B.; Kent, Michael

    2013-01-01

    In 2008 2009, 998 fish were collected from 43 water bodies across 11 western Alaskan national parks and analyzed for reproductive abnormalities. Exposure to estrogenic substances such as pesticides can induce abnormalities like intersex. Results suggest there is a greater propensity for male intersex fish collected from parks located in the Rocky Mountains, and specifically in Rocky Mountain NP. Individual male intersex fish were also identified at Lassen Volcanic, Yosemite, and WrangellSt. Elias NPs. The preliminary finding of female intersex was determined to be a false positive. The overall goal of this project was to assess the general health of fish from eleven western national parks to infer whether health impacts may be linked to contaminant health thresholds for animal andor human health. This was accomplished by evaluating the presence of intersex fish with eggs developing in male gonads or sperm developing in female gonads using histology. In addition, endocrine disrupting compounds and other contaminants were quantified in select specimens. General histologic appearance of the gonadal tissue and spleen were observed to assess health.

  4. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

    SciTech Connect

    Liu, Yanzhen; Mei, Chenfang; Liu, Hao; Wang, Hongsheng; Zeng, Guoqu; Lin, Jianhui; Xu, Meiying

    2014-09-05

    Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.

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

    SciTech Connect

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

    2009-03-01

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

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

    PubMed

    Schwindt, Adam R

    2015-08-01

    The effects of endocrine disrupting compounds (EDCs) on aquatic wildlife are increasingly being recognized for their complexity. Investigators have detected alterations at multiple levels of biological organization in offspring exposed to EDCs through the blood or germ line of the parents, suggesting that generational consequences of EDCs are evident. Exposure to EDCs through the parents is concerning because if the resulting phenotype of the offspring is heritable and affects fitness, then evolutionary consequences may be evident. This review summarizes the evidence for transgenerational effects of EDCs in aquatic wildlife and illustrates cases where alterations appear to be transmitted maternally, paternally, or parentally. The literature indicates that EDC exposure to the parents induces developmental, physiological, endocrinological, and behavioral changes as well as increased mortality of offspring raised in clean environments. What is lacking, however, is a clear demonstration of heritable transgenerational effects in aquatic wildlife. Therefore, it is not known if the parental effects are the result of developmental or phenotypic plasticity or if the altered phenotypes are durably passed to subsequent generations. Epigenetic changes to gene regulation are discussed as a possible mechanism responsible for EDC induced parental effects. Additional research is needed to evaluate if heritable effects of EDCs are evident in aquatic wildlife, as has been demonstrated for terrestrial mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals

    PubMed Central

    Beronius, Anna; Vandenberg, Laura N.

    2016-01-01

    The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs. PMID:26847432

  8. Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

    PubMed

    Xin, Frances; Susiarjo, Martha; Bartolomei, Marisa S

    2015-07-01

    Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of an individual. Moreover, recent studies have revealed that early life perturbations can affect the health of subsequent generations. Hypothesized mechanisms of multi- and transgenerational inheritance of abnormal developmental phenotypes include epigenetic misregulation in germ cells. In this review, we will focus on the available data demonstrating the ability of endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, and parabens, to alter epigenetic marks in rodents and humans. These epigenetic marks include DNA methylation, histone post-translational modifications, and non-coding RNAs. We also review the current evidence for multi- and transgenerational inheritance of abnormal developmental changes in the offspring following EDC exposure. Based on published results, we conclude that EDC exposure can alter the mouse and human epigenome, with variable tissue susceptibilities. Although increasing data suggest that exposure to EDCs is linked to transgenerational inheritance of reproductive, metabolic, or neurological phenotypes, more studies are needed to validate these observations and to elucidate further whether these developmental changes are directly associated with the relevant epigenetic alterations.

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

    PubMed

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

    2013-01-01

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

  10. Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption.

    PubMed

    Nardi, Jessica; Moras, Patricia Bonamigo; Koeppe, Carina; Dallegrave, Eliane; Leal, Mirna Bainy; Rossato-Grando, Luciana Grazziotin

    2017-02-01

    Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control.

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

    USGS Publications Warehouse

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

    2015-01-01

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

  12. Analysis and occurrence of typical endocrine-disrupting chemicals in three sewage treatment plants.

    PubMed

    Wang, L Y; Zhang, X H; Tam, N F Y

    2010-01-01

    Seven typical endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), 4-tert-octylphenol (OP), estrone (E1), estradiol (E2), 17α-estradiol (17α-E2), estriol (E3) and 17α-ethinylestradiol (EE2) in wastewater, were simultaneously determined with gas chromatography-mass spectrometry (GC-MS). Samples, including influents, effluents and wastewater of different unit processes, were taken seasonally from three different sewage treatment plants. The result showed that BPA and EE2 were the two main types of EDCs in all the samples. The average concentration of BPA were in the range of 268.1-2,588.5 ng l⁻¹ in influents and 34.0-3,099.6 ng l⁻¹ in effluents, while EE2 ranging from 133.1 to 403.2 ng l⁻¹ and from 35.3 to 269.1 ng l⁻¹, respectively. Seasonal change of EDCs levels in effluents was obvious between wet season and dry season. Besides, BPA and E3 could be effectively removed by the biological treatment processes (oxidation ditch and A²/O) with the unit removal of 64-91% and 63-100% for each compound, while other five EDCs had moderate or low removal rates. The study also proved that physical treatment processes, including screening, primary sedimentation and pure aeration, had no or little effect on EDCs removal.

  13. [Endocrine disruption: a challenge in research, public health and clinical practice].

    PubMed

    Fudvoye, J; Franssen, D; Naveau, E; Pinson, A; Gerard, A; Bourguignon, J-P; Parent, A S

    2014-01-01

    Epidemiological and experimental data highlight the fetal and early postnatal life as critical periods for the effects of endocrine disrupting chemicals (EDCs), since exposure to EDCs during these periods can predispose to disease later in life. EDCs' effects include disorders of the reproductive system throughout life (abnormalities of sexual differentiation, infertility or subfertility and some neoplasia) and disorders of energy balance (obesity and metabolic syndrome). They could also influence the development of the cerebral cortex. However, the demonstration of the involvement of a single EDC remains difficult in human since we are virtually exposed to a mixture of several ubiquitous EDCs which are variably persistent in the environment and the body and have lifelong consequences. Moreover, since their dose-response relationship can be non-monotonic, setting a threshold dose for EDCs effects has become meaningless. Pregnant women, newborns and young children appear to be mostly at risk. However, the role of the physician remains difficult and raises several questions: how can we formulate justified, applicable and updated recommendations that are not counterproductive or alarmist...in a society that has to take the necessary steps to regulate production and protect the population?

  14. QSAR classification models for the prediction of endocrine disrupting activity of brominated flame retardants.

    PubMed

    Kovarich, Simona; Papa, Ester; Gramatica, Paola

    2011-06-15

    The identification of potential endocrine disrupting (ED) chemicals is an important task for the scientific community due to their diffusion in the environment; the production and use of such compounds will be strictly regulated through the authorization process of the REACH regulation. To overcome the problem of insufficient experimental data, the quantitative structure-activity relationship (QSAR) approach is applied to predict the ED activity of new chemicals. In the present study QSAR classification models are developed, according to the OECD principles, to predict the ED potency for a class of emerging ubiquitary pollutants, viz. brominated flame retardants (BFRs). Different endpoints related to ED activity (i.e. aryl hydrocarbon receptor agonism and antagonism, estrogen receptor agonism and antagonism, androgen and progesterone receptor antagonism, T4-TTR competition, E2SULT inhibition) are modeled using the k-NN classification method. The best models are selected by maximizing the sensitivity and external predictive ability. We propose simple QSARs (based on few descriptors) characterized by internal stability, good predictive power and with a verified applicability domain. These models are simple tools that are applicable to screen BFRs in relation to their ED activity, and also to design safer alternatives, in agreement with the requirements of REACH regulation at the authorization step. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. [Investigation of endocrine disrupting chemicals in a drinking water work located in Songhua River basin].

    PubMed

    Shao, Xiao-Ling; Ma, Jun; Wen, Gang

    2008-10-01

    Solid phase extraction-high performance liquid chromatography was used for simultaneously determination of 13 endocrine disrupting chemicals (EDCs) in water samples taken from each treatment unit of a drinking water treatment plant located in Songhua River basin. Results show that steroid estrogens exist in all water samples except for tap water, varying at a level of 4-44 ng x L(-1). Four of phthalate acid esters (PAEs), bisphenol A (BPA) and 3 alkylphenols (APs) are detected almost in all samples with concentration ranging from 2 to 163 760 ng x L(-1). The most abundant EDCs are di-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP). Results also demonstrate that the coagulation-sedimentation process plays a dominant role in the removal of EDCs in the plant with an average removal efficiency of 63%, though the contents of few EDCs in its effluent are higher than those in the influent. Processes of sand filtration and chlorination are unstable, and only several of EDCs investigated are removed partially. In addition, the concentrations of most EDCs left in the effluent of the plant are increased after pipe delivering. It verifies that EDCs in drinking water partly come from the release of pipe material for water delivering besides the contaminated source water.

  16. Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

    PubMed Central

    Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

    2016-01-01

    Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

  17. Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

    PubMed Central

    Xin, Frances; Susiarjo, Martha; Bartolomei, Marisa S.

    2015-01-01

    Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of an individual. Moreover, recent studies have revealed that early life perturbations can affect the health of subsequent generations. Hypothesized mechanisms of multi- and transgenerational inheritance of abnormal developmental phenotypes include epigenetic misregulation in germ cells. In this review, we will focus on the available data demonstrating the ability of endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, and parabens, to alter epigenetic marks in rodents and humans. These epigenetic marks include DNA methylation, histone post-translational modifications, and non-coding RNAs. We also review the current evidence for multi- and transgenerational inheritance of abnormal developmental changes in the offspring following EDC exposure. Based on published results, we conclude that EDC exposure can alter the mouse and human epigenome, with variable tissue susceptibilities. Although increasing data suggest that exposure to EDCs is linked to transgenerational inheritance of reproductive, metabolic, or neurological phenotypes, more studies are needed to validate these observations and to elucidate further whether these developmental changes are directly associated with the relevant epigenetic alterations. PMID:26026600

  18. Dimorphic placental stress: A repercussion of interaction between endocrine disrupting chemicals (EDCs) and fetal sex.

    PubMed

    Sood, Surbhi; Shekhar, Sudhanshu; Santosh, Winkins

    2017-02-01

    Placental homeostasis is critical for fetal development as it determines the health of mother and fetus during pregnancy and in later life. Interestingly even the fetus, in a sexually dimorphic manner, influences the pedantic growth and development of placenta. Although placenta is thought to act as a protective barrier against chemical exposures, certain endocrine disrupting chemicals (EDCs) that are circulating in mother's blood tend to cross placenta. These EDCs have been reported to cause changes in expression levels of certain genes, immunogenic factors and non-coding RNAs such as micro RNA (miRNA) and long non-coding RNA (lncRNA) leading to placental stress. We hypothesize that these changes in placenta occur in a sexually dimorphic manner as a result of interaction between EDC exposure and fetal sex. Therefore, we propose that the ability of placenta to respond and buffer EDC exposure depends on fetal sex and, hence the EDC associated disease susceptibility of one sex differs from the other.

  19. Semivolatile endocrine-disrupting compounds in paired indoor and outdoor air in two northern California communities.

    PubMed

    Rudel, Ruthann A; Dodson, Robin E; Perovich, Laura J; Morello-Frosch, Rachel; Camann, David E; Zuniga, Michelle M; Yau, Alice Y; Just, Allan C; Brody, Julia Green

    2010-09-01

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

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

    PubMed

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

    2008-04-01

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

  1. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation†

    PubMed Central

    Jensen, G.E.; Niemelä, J.R.; Wedebye, E.B.; Nikolov, N.G.

    2008-01-01

    A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure–activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption. PMID:19061080

  2. DJ-1, a target protein for an endocrine disrupter, participates in the fertilization in mice.

    PubMed

    Okada, Masahiko; Matsumoto, Ken-ichi; Niki, Takeshi; Taira, Takahiro; Iguchi-Ariga, Sanae M M; Ariga, Hiroyoshi

    2002-07-01

    DJ-1 was first identified as an activated ras-dependent oncogene product and was later also found to be an infertility-related protein affected by sperm toxicants such as ornidazole (OR) and epichlorohydrin. These findings suggest that DJ-1 has functions in both somatic cells and sperm. In this study, to determine the relationship between DJ-1 and an endocrine disrupter and to determine the functions of DJ-1 in sperm, in vitro fertilization experiments were carried out using eggs and sperm extracted from mice that had or had not been treated with OR. We found that the amount of DJ-1 in sperm and the efficiency of fertilization decreased with the increasing dose of OR to which the mice were exposed. The addition of an anti-mouse DJ-1 serum to sperm solution before the in vitro fertilization reaction with eggs resulted in a decrease in the efficiency of fertilization to about one-third of that when pre-immune serum was added to sperm solution, indicating that DJ-1 participates in the fertilization.

  3. Neonicotinoids act like endocrine disrupting chemicals in newly-emerged bees and winter bees.

    PubMed

    Baines, Danica; Wilton, Emily; Pawluk, Abbe; de Gorter, Michael; Chomistek, Nora

    2017-09-08

    Accumulating evidence suggests that neonicotinoids may have long-term adverse effects on bee health, yet our understanding of how this could occur is incomplete. Pesticides can act as endocrine disrupting chemicals (EDCs) in animals providing characteristic multiphasic dose-response curves and non-lethal endpoints in toxicity studies. However, it is not known if neonicotinoids act as EDCs in bees. To address this issue, we performed oral acute and chronic toxicity studies including concentrations recorded in nectar and pollen, applying acetamiprid, clothianidin, imidacloprid, and thiamethoxam to bumble bees, honey bees and leafcutter bees, the three most common bee species managed for pollination. In acute toxicity studies, late-onset symptoms, such as ataxia, were recorded as non-lethal endpoints for all three bee species. Clothianidin and thiamethoxam produced biphasic dose-response curves for all three bee species. Clothianidin and thiamethoxam were extremely toxic to winter worker honey bees prior to brood production in spring, making this the most sensitive bee stage identified to date. Chronic exposure to field-realistic levels of neonicotinoids reduced bee survival and caused significant late-onset symptoms for all three bee species. Given these findings, neonicotinoid risk should be reevaluated to address the EDC-like behavior and the sensitivity of winter worker honey bees.

  4. Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water.

    PubMed

    Benotti, Mark J; Trenholm, Rebecca A; Vanderford, Brett J; Holady, Janie C; Stanford, Benjamin D; Snyder, Shane A

    2009-02-01

    The drinking water for more than 28 million people was screened for a diverse group of pharmaceuticals, potential endocrine disrupting compounds (EDCs), and other unregulated organic contaminants. Source water, finished drinking water, and distribution system (tap) water from 19 U.S. water utilities was analyzed for 51 compounds between 2006 and 2007. The 11 most frequently detected compounds were atenolol, atrazine, carbamazepine, estrone, gemfibrozil, meprobamate, naproxen, phenytoin, sulfamethoxazole, TCEP, and trimethoprim. Median concentrations of these compounds were less than 10 ng/L, except for sulfamethoxazole in source water (12 ng/L), TCEP in source water (120 ng/L), and atrazine in source, finished, and distribution system water (32, 49, and 49 ng/L). Atrazine was detected in source waters far removed from agricultural application where wastewater was the only known source of organic contaminants. The occurrence of compounds in finished drinking water was controlled by the type of chemical oxidation (ozone or chlorine) used at each plant. At one drinking water treatment plant, summed monthly concentrations of the detected analytes in source and finished water are reported. Atenolol, atrazine, DEET, estrone, meprobamate, and trimethoprim can serve as indicator compounds representing potential contamination from other pharmaceuticals and EDCs and can gauge the efficacy of treatment processes.

  5. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows.

    PubMed

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-13

    Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

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

    PubMed

    Solé, Alba; Matamoros, Víctor

    2016-12-01

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

  7. Enzymatic degradation of endocrine-disrupting chemicals in aquatic plants and relations to biological Fenton reaction.

    PubMed

    Reis, A R; Sakakibara, Y

    2012-01-01

    In order to evaluate the removal performance of trace phenolic endocrine-disrupting chemicals (EDCs) by aquatic plants, batch and continuous experiments were conducted using floating and submerged plants. The EDCs used in this study were bisphenol A, 2,4-dichlorophenol, 4-tert-octylphenol, pentachlorophenol, and nonylphenol. The feed concentration of each EDC was set at 100 μg/L. Continuous experiments showed that every EDC except pentachlorophenol was efficiently removed by different aquatic plants through the following reaction, catalyzed by peroxidases: EDCs+H(2)O(2)→Products+H(2)O(2). Peroxidases were able to remove phenolic EDCs in the presence of H(2)O(2) over a wide pH range (from 3 to 9). Histochemical localization of peroxidases showed that they were located in every part of the root cells, while highly concentrated zones were observed in the epidermis and in the vascular tissues. Although pentachlorophenol was not removed in the continuous treatment, it was rapidly removed by different aquatic plants when Fe(2+) was added, and this removal occurred simultaneously with the consumption of endogenous H(2)O(2). These results demonstrated the occurrence of a biological Fenton reaction and the importance of H(2)O(2) as a key endogenous substance in the treatment of EDCs and refractory toxic pollutants.

  8. Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals

    PubMed Central

    Kortenkamp, Andreas

    2007-01-01

    In the last 10 years, good evidence has become available to show that the combined effects of endocrine disruptors (EDs) belonging to the same category (e.g., estrogenic, antiandrogenic, or thyroid-disrupting agents) can be predicted by using dose addition. This is true for a variety of end points representing a wide range of organizational levels and biological complexity. Combinations of EDs are able to produce significant effect, even when each chemical is present at low doses that individually do not induce observable effects. However, comparatively little is known about mixtures composed of chemicals from different classes of EDs. Nevertheless, I argue that the accumulated evidence seriously undermines continuation with the customary chemical-by-chemical approach to risk assessment for EDs. Instead, we should seriously consider group-wise regulation of classes of EDs. Great care should be taken to define such classes by using suitable similarity criteria. Criteria should focus on common effects, rather than common mechanisms. In this review I also highlight research needs and identify the lack of information about exposure scenarios as a knowledge gap that seriously hampers progress with ED risk assessment. Future research should focus on investigating the effects of combinations of EDs from different categories, with considerable emphasis on elucidating mechanisms. This strategy may lead to better-defined criteria for grouping EDs for regulatory purposes. Also, steps should be taken to develop dedicated mixtures exposure assessment for EDs. PMID:18174957

  9. Small fish models for identifying and assessing the effects of endocrine-disrupting chemicals.

    PubMed

    Ankley, Gerald T; Johnson, Rodney D

    2004-01-01

    Endocrine-disrupting chemicals (EDCs), particularly those that affect the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates, have become a focus of regulatory screening and testing throughout the world. Small fish species, principally the fathead minnow (Pimephales promelas), Japanese medaka (Oryzias latipes), and zebrafish (Danio rerio), are used as model organisms for several of these testing programs. Fish are appropriate models for testing EDCs, not only from the perspective of existing ecological impacts, but also in terms of species extrapolation. Specifically, there is a significant degree of conservation of basic aspects of the HPG axis across vertebrates, which provides a technically robust basis for using results from fish tests to predict likely modes/mechanisms of action of potential EDCs in other vertebrates. Different experimental designs/endpoints for partial- and full-life cycle tests with fish that enable a consideration of a broad range of EDCs are described. Examples of results with specific chemicals in tests with the fathead minnow, medaka, and zebrafish are presented and discussed in terms of sensitivity and specificity for different classes of EDCs.

  10. Extranuclear-initiated estrogenic actions of endocrine disrupting chemicals: Is there toxicology beyond paracelsus?

    PubMed

    Nadal, Angel; Fuentes, Esther; Ripoll, Cristina; Villar-Pazos, Sabrina; Castellano-Muñoz, Manuel; Soriano, Sergi; Martinez-Pinna, Juan; Quesada, Ivan; Alonso-Magdalena, Paloma

    2017-01-31

    Endocrine Disrupting Chemicals (EDCs), including bisphenol-A (BPA) do not act as traditional toxic chemicals inducing massive cell damage or death in an unspecific manner. EDCs can work upon binding to hormone receptors, acting as agonists, antagonists or modulators. Bisphenol-A displays estrogenic activity and, for many years it has been classified as a weak estrogen, based on the classic transcriptional action of estrogen receptors serving as transcription factors. However, during the last two decades our knowledge about estrogen signaling has advanced considerably. It is now accepted that estrogen receptors ERα and ERβ activate signaling pathways outside the nucleus which may or may not involve transcription. In addition, a new membrane estrogen receptor, GPER, has been proposed. Pharmacological and molecular evidence, along with results obtained in genetically modified mice, demonstrated that BPA, and its substitute BPS, are potent estrogens acting at nanomolar concentrations via extranuclear ERα, ERβ, and GPER. The different signaling pathways activated by BPA and BPS explain the well-known estrogenic effects of low doses of EDCs as well as non-monotonic dose-response relationships. These signaling pathways may help to explain the actions of EDCs with estrogenic activity in the etiology of different pathologies, including type-2 diabetes and obesity.

  11. Endocrine disrupting compounds in drinking water supply system and human health risk implication.

    PubMed

    Wee, Sze Yee; Aris, Ahmad Zaharin

    2017-09-01

    To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Neuroendocrine and behavioral effects of embryonic exposure to endocrine disrupting chemicals in birds.

    PubMed

    Ottinger, Mary Ann; Lavoie, Emma; Thompson, Nichola; Barton, Ashley; Whitehouse, Kasen; Barton, Meredith; Abdelnabi, Mahmoud; Quinn, Micha