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Sample records for endocrine disruption health

  1. Endocrine-Disrupting Chemicals and Reproductive Health.

    PubMed

    Zlatnik, Marya G

    2016-07-01

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

  2. Endocrine-Disrupting Chemicals and Reproductive Health.

    PubMed

    Zlatnik, Marya G

    2016-07-01

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

  3. 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

  4. Endocrine disrupting chemicals: effects on human male reproductive health.

    PubMed

    Murray, T J; Lea, R G; Abramovich, D R; Haites, N E; Fowler, P A

    2001-04-01

    There is now considerable evidence that male reproductive function is declining in human and wildlife populations. This is coincident with the increasing use and prevalence of man-made chemicals in the environment over the last fifty years. Certain chemicals have subsequently been shown to disturb the developing fetal endocrine system of laboratory animals in utero. In these experiments, treatment caused similar male reproductive problems in offspring as those already observed in wildlife and human populations. In addition, both the human DES data and rodent studies have shown that there are specific windows of gestation when the developing fetal gonad is highly sensitive to small endocrine changes. Animal in vivo and human in vitro studies have identified EDC sensitive genes. Consequently, hypotheses are being generated concerning mechanism of action e.g. disturbed testicular apoptosis and altered hepatic biotransformation of steroids. While animal studies provide us with valuable insights into the range of effects that can be attributed to in utero EDC exposure, varying maternal doses employed by different research groups make relation of the results to human observations difficult. The EDC concentration representative of fetal exposure levels is uncertain. Confounding factors include: (a) the vast number of chemicals termed EDCs, (b) the ability of chemicals to bioaccumulate in body lipid, (c) the metabolism of body lipid during pregnancy releasing the mothers lifetime EDC legacy into circulation and (d) the poorly understood kinetics of EDC transfer across the placenta. Thus, the level of fetal exposure can only be crudely estimated at present. This highlights the need for large animal models of EDC in utero exposure where the partitioning of EDCs between the mother and fetus and transfer across the placenta can be studied in detail. Despite considerable effort the mechanisms by which these endocrine disrupting chemicals exert their effects are still largely

  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. 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

  7. Endocrine disrupting chemicals

    PubMed Central

    Yeung, Bonnie HY; Wan, Hin T; Law, Alice YS

    2011-01-01

    In the past 200 years, an enormous number of synthetic chemicals with diverse structural features have been produced for industrial, medical and domestic purposes. These chemicals, originally thought to have little or no biological toxicity, are widely used in our daily lives as well as are commonly present in foods. It was not until the first World Wildlife Federation Wingspread Conference held in 1994 were concerns about the endocrine disrupting (ED) effects of these chemicals articulated. The potential hazardous effects of endocrine disrupting chemicals (EDCs) on human health and ecological well-being are one of the global concerns that affect the health and propagation of human beings. Considerable numbers of studies indicated that endocrine disruption is linked to “the developmental basis of adult disease,” highlighting the significant effects of EDC exposure on a developing organism, leading to the propensity of an individual to develop a disease or dysfunction in later life. In this review, we intend to provide environmental, epidemiological and experimental data to associate pollutant exposure with reproductive disorders, in particular on the development and function of the male reproductive system. Possible effects of pollutant exposure on the processes of embryonic development, like sex determination and masculinization are described. In addition, the effects of pollutant exposure on hypothalamus-pituitary-gonadal axis, testicular signaling, steroidogenesis and spermatogenesis are also discussed. PMID:22319671

  8. Endocrine disrupters as obesogens.

    PubMed

    Grün, Felix; Blumberg, Bruce

    2009-05-25

    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.

  9. 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...

  10. [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

  11. 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

  12. 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

  13. 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

    2014-01-01

    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. PMID:25533907

  14. Endocrine disrupting chemicals and endometriosis.

    PubMed

    Smarr, Melissa M; Kannan, Kurunthachalam; Buck Louis, Germaine M

    2016-09-15

    Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women's fertility, somatic health, and overall quality of life. Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease. We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques. Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates. To address the equivocal findings for various EDCs, future research directions for filling data gaps include [1] use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities; [2] the collection of various biologic media, including target tissues for quantifying exposures; [3] study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders; and [4] novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis. PMID:27424048

  15. 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.

  16. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

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

  17. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  18. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals. PMID:26465197

  19. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    USGS Publications Warehouse

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  20. REMOVAL OF ENDOCRINE DISRUPTING CHEMICALS USING DRINKING WATER TREATMENT PROCESSES

    EPA Science Inventory

    A group of chemicals, known as endocrine disrupting chemicals (EDCs), has been identified as having the potential to cause adverse health effect in humans and wildlife. Among this group DDT, DDE, PCBs, endosulfan, methoxychlor, diethylphthalate, diethylhexylphalate, and bisphenol...

  1. 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

  2. Sunscreens: are they beneficial for health? An overview of endocrine disrupting properties of UV-filters.

    PubMed

    Krause, M; Klit, A; Blomberg Jensen, M; Søeborg, T; Frederiksen, H; Schlumpf, M; Lichtensteiger, W; Skakkebaek, N E; Drzewiecki, K T

    2012-06-01

    Today, topical application of sunscreens, containing ultraviolet-filters (UV-filters), is preferred protection against adverse effects of ultraviolet radiation. Evidently, use of sunscreens is effective in prevention of sunburns in various models. However, evidence for their protective effects against melanoma skin cancer is less conclusive. Three important observations prompted us to review the animal data and human studies on possible side effects of selected chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV-filters is increasing worldwide; (2) the incidence of the malignant disorder for which sunscreens should protect, malignant melanoma, is rapidly increasing and (3) an increasing number of experimental studies indicating that several UV-filters might have endocrine disruptive effects. The selected UV-filters we review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4-aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated potential side effects of UV-filters, although human exposure is high as UV-filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters, BP-3, has been found in 96% of urine samples in the US and several UV-filters in 85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure to UV-filters contribute to possible adverse effects on the developing organs of foetuses and children. PMID:22612478

  3. 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

  4. 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...

  5. 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

  6. Endocrine disrupters: a human risk?

    PubMed

    Waring, R H; Harris, R M

    2005-12-01

    Endocrine disrupters (EDs) alter normal hormonal regulation and may be naturally occurring or environmental contaminants. Classically, EDs act genomically, with agonistic or antagonistic effects on steroid receptors and may alter reproductive function and/or cause feminisation by binding to oestrogen or androgen receptors; their binding to the thyroid receptor may dysregulate the neuroendocrine system. Recently, it has been shown that EDs can also act by non-genomic mechanisms, altering steroid synthesis (inhibition of cytochrome P450 isoforms) or steroid metabolism. The alkylphenol and phthalate plasticisers inhibit the inactivation of oestrogens by sulphation (via SULT 1A1 and 1E1 isoforms) and so cause a rise in levels of the free active endogenous oestrogens. A range of ED effects have been shown in mammals, fish, birds, reptiles, amphibia and aquatic invertebrates but it is not yet clear whether these processes also occur in human beings. It is evident that EDs, as well as altering reproduction, can cause changes in neurosteroid levels and so have the potential to affect immune function, behaviour and memory. This may be of long-term concern since traces of EDs such as plasticisers, brominated fire retardants, sunscreen agents and cosmetic ingredients are widely distributed in the environment and in human biofluids. PMID:16271281

  7. 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 ...

  8. 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 ...

  9. 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...

  10. 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

  11. Fifteen Years after “Wingspread”—Environmental Endocrine Disrupters and Human and Wildlife Health: Where We are Today and Where We Need to Go

    PubMed Central

    Hotchkiss, Andrew K.; Rider, Cynthia V.; Blystone, Chad R.; Wilson, Vickie S.; Hartig, Phillip C.; Ankley, Gerald T.; Foster, Paul M.; Gray, Clark L.; Gray, L. Earl

    2008-01-01

    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 humans. Endocrine disruption can be profound because of the crucial role hormones play in controlling development.” Since that time, there have been numerous documented examples of adverse effects of EDCs in invertebrates, fish, wildlife, domestic animals, and humans. Hormonal systems can be disrupted by numerous different anthropogenic chemicals including antiandrogens, androgens, estrogens, AhR agonists, inhibitors of steroid hormone synthesis, antithyroid substances, and retinoid agonists. In addition, pathways and targets for endocrine disruption extend beyond the traditional estrogen/androgen/thyroid receptor–mediated reproductive and developmental systems. For example, scientists have expressed concern about the potential role of EDCs in increasing trends in early puberty in girls, obesity and type II diabetes in the United States and other populations. New concerns include complex endocrine alterations induced by mixtures of chemicals, an issue broadened due to the growing awareness that EDCs present in the environment include a variety of potent human and veterinary pharmaceutical products, personal care products, nutraceuticals and phytosterols. In this review we (1) address what have we learned about the effects of EDCs on fish, wildlife, and human health, (2) discuss representative animal studies on (anti)androgens, estrogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin–like chemicals, and (3) evaluate regulatory proposals being considered for screening and testing these chemicals. PMID:18281716

  12. 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.

  13. Regulation of endocrine-disrupting chemicals: critical overview and deficiencies in toxicology and risk assessment for human health.

    PubMed

    Harvey, Philip W; Everett, David J

    2006-03-01

    Regulation of endocrine-disrupting chemicals is reviewed in terms of hazard assessment (regulatory toxicology) and risk assessment. The current range of regulatory general toxicology protocols can detect endocrine toxicity, but specific endocrine toxicology tests are required to confirm mechanisms (e.g. oestrogenic, anti-androgenic). Strategies for validating new endocrine toxicology protocols and approaches to data assessment are discussed, and deficiencies in regulatory toxicology testing (e.g. lack of adrenocortical function assessment) identified. Recent evidence of a role of prolactin in human breast cancer also highlights deficiencies in regulatory evaluation. Actual human exposure to chemicals and the high-exposure example of chemicals in body-care cosmetics is reviewed with reference to evidence that common ingredients (e.g. parabens, cyclosiloxanes) are oestrogenic. The hypothesis and epidemiology concerning chemical exposure from body-care cosmetics (moisturizers, lotions, sun screens, deodorants) and breast cancer in women is reviewed, applying Bradford-Hill criteria for association and causality, and research requirements are identified.

  14. 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

  15. Endocrine disrupters and human health: could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women?

    PubMed

    Harvey, Philip W; Darbre, Philippa

    2004-01-01

    In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of: data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application

  16. 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...

  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. 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. 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.

  20. Endocrine-disrupting chemicals use distinct mechanisms of action to modulate endocrine system function.

    PubMed

    Henley, Derek V; Korach, Kenneth S

    2006-06-01

    The term endocrine-disrupting chemicals is used to define a structurally diverse class of synthetic and natural compounds that possess the ability to alter various components of the endocrine system and potentially induce adverse health effects in exposed individuals and populations. Research on these compounds has revealed that they use a variety of both nuclear receptor-mediated and non-receptor-mediated mechanisms to modulate different components of the endocrine system. This review will describe in vitro and in vivo studies that highlight the spectrum of unique mechanisms of action and biological effects of four endocrine-disrupting chemicals--diethylstilbestrol, genistein, di(n-butyl)phthalate, and methoxyacetic acid--to illustrate the diverse and complex nature of this class of compounds.

  1. 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. PMID:26414233

  2. 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.

  3. 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

  4. 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.

  5. Human health and endocrine disruption: a simple multicriteria framework for the qualitative assessment of end point specific risks in a context of scientific uncertainty.

    PubMed

    Martin, Olwenn V; Lester, John N; Voulvoulis, Nikolaos; Boobis, Alan R

    2007-08-01

    Endocrine disruption remains one of the most controversial contemporary environmental issues. While the desired level of protection is ultimately a societal choice, endocrine toxicity could result in a wide spectrum of adverse health effects. Although the application of the causal framework of weight-of-evidence approaches to complex toxicological issues has incited much interest, no international criteria or guidance have yet been developed. In this context, the evidence on end point-specific risks to human health contained in the International Program on Chemical Safety Global assessment of the State-of-Science on Endocrine Disruptors report was updated and assessed qualitatively using three simple criteria relevant to the practical application of the precautionary principle (PP): incidence trends, association, and consequence. The current degree of knowledge was then ranked according to ignorance, uncertainty, and risk. The main sources of scientific uncertainty in relation to incidence trends were associated with the evolution of diagnostic criteria or diagnostic tests, while genetic susceptibility is often proposed as an explanation for the wide geographic variations in the incidence of some diseases. Such genetic polymorphisms are also offered as a potential explanation for some of the inconsistent findings or lack of clear dose-response gradients described under the association criterion. The methodology yielded a relative paucity of data addressing directly the impact for adverse human health effect from both individual and public health perspectives. Results are discussed within the context of the application of the PP. Within a participatory context, this simple framework could provide a useful decision-making tool to both communicate scientific uncertainty to the wider public and manage uncertain risks.

  6. 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

  7. 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

  8. Fungal laccases degradation of endocrine disrupting compounds.

    PubMed

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

    2014-01-01

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

  9. 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

  10. 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.

  11. [Impact of endocrine disrupting chemicals on semen quality].

    PubMed

    Zhu, Qian-xi; Huang, Yu-feng

    2011-10-01

    Endocrine disrupting chemicals (EDCs) are natural or man-made agents that interfere in some way with human or animal normal endocrine function, and even influence the endocrine function of their offspring. There are many kinds of EDCs, which are widely present in soil, water, and even food. This review elaborates the impact of EDCs on human and animal semen quality from the viewpoint of epidemiology and biology by focusing on pesticides, plasticizers and detergents. PMID:22049803

  12. 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

  13. 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...

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

    EPA Science Inventory

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

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

    PubMed

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

    2003-08-01

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

  16. 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

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

    PubMed

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

    2015-07-01

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

  18. 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...

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

    PubMed

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

    2016-04-01

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

  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. Hormone Health Network

    MedlinePlus

    ... Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types of ... Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types of ...

  2. Courage for simplification and imperfection in the 21st century assessment of "Endocrine disruption".

    PubMed

    Dietrich, Daniel R

    2010-01-01

    "Endocrine disruption" is a public and political buzzword that has and is still receiving high media attention. Based on the latter, numerous tiered testing strategies have evolved that should ensure that humans will not run a health risk due to the voluntary or involuntary exposure to endocrine active compounds (EAS). An analysis of the currently available knowledge on EAS mediated endocrine disruption in humans demonstrates that there are very few EAS that causally induce endocrine disruptive effects. Conversely, the association EAS exposure with increased risk or incidences of endocrine disruptive effects in humans are difficult to reconcile with the results from animal studies. Consequently, the analysis of the traditional and historically grown tiered approach in EAS testing, often at very high doses or concentrations, demonstrates that the likelihood of detecting EAS with true potential for endocrine disruption in humans is very low, primarily due to inherent differences between the surrogate species and the human, and will provide for a high number of false-positives commensurate with low efficiency, high cost, and often violently disputed interpretations of what the data would mean for human risk assessment. It is thus proposed that EAS testing for putative endocrine disruption in humans and qualitative and quantitative evaluation for risk assessment purposes should be entirely focused on human data, and derived from a combination of in silico and in vitro systems, PBPK modeling, metabonomic or genomic profiling of human tissue, realistic human EAS exposure, dose-effect principles and adverse effect scenarios, human patient or exposure cohort datasets, etc. Animals models should be used only where specific pathways in endocrine physiology and thus development and reproduction is nearly identical to the situation in the human, thereby guaranteeing that causal exposure and effect relationships in the animals can be extrapolated to the human.

  3. 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

  4. 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, ...

  5. 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...

  6. 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.

  7. 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. PMID:26136137

  8. 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. PMID:26063868

  9. 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. PMID:27285165

  10. 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

  11. 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

  12. 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

  13. Low Testosterone and Men's Health

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  14. 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

  15. 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

  16. 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.

  17. Prediction of the endocrine disruption profile of pesticides.

    PubMed

    Devillers, J; Bro, E; Millot, F

    2015-01-01

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

  18. 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

    2016-01-01

    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

  19. Recent Advances on Endocrine Disrupting Effects of UV Filters

    PubMed Central

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

    2016-01-01

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

  20. 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.

  1. 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...

  2. 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...

  3. 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...

  4. 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. ...

  5. 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.

  6. Thyroid effects of endocrine disrupting chemicals.

    PubMed

    Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

    2012-05-22

    In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties. PMID:21939731

  7. 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...

  8. Alcohol-induced disruption of endocrine signaling.

    PubMed

    Ronis, Martin J J; Wands, Jack R; Badger, Thomas M; de la Monte, Suzanne M; Lang, Charles H; Calissendorff, Jan

    2007-08-01

    This article contains the proceedings of a symposium at the 2006 ISBRA meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of long-term ethanol consumption on liver injury and repair, by Jack R. Wands; (2) Alcohol-induced insulin resistance in liver: potential roles in regulation of ADH expression, ethanol clearance, and alcoholic liver disease, by Thomas M. Badger; (3) Chronic gestational exposure to ethanol causes brain insulin and insulin-like growth factor resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 signaling in muscle: a mechanism underlying alcoholic myopathy, by Charles H. Lang; (5) The role of reduced plasma estradiol and impaired estrogen signaling in alcohol-induced bone loss, by Martin J. Ronis; and (6) Short-term influence of alcohol on appetite-regulating hormones in man, by Jan Calissendorff.

  9. 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

  10. Environmental factors affecting pregnancy: endocrine disrupters, nutrients and metabolic pathways.

    PubMed

    Bazer, Fuller W; Wu, Guoyao; Johnson, Gregory A; Wang, Xiaoqiu

    2014-12-01

    Uterine adenogenesis, a unique post-natal event in mammals, is vulnerable to endocrine disruption by estrogens and progestins resulting in infertility or reduced prolificacy. The absence of uterine glands results in insufficient transport of nutrients into the uterine lumen to support conceptus development. Arginine, a component of histotroph, is substrate for production of nitric oxide, polyamines and agmatine and, with secreted phosphoprotein 1, it affects cytoskeletal organization of trophectoderm. Arginine is critical for development of the conceptus, pregnancy recognition signaling, implantation and placentation. Conceptuses of ungulates and cetaceans convert glucose to fructose which is metabolized via multiple pathways to support growth and development. However, high fructose corn syrup in soft drinks and foods may increase risks for metabolic disorders and increase insulin resistance in adults. Understanding endocrine disrupters and dietary substances, and novel pathways for nutrient metabolism during pregnancy can improve survival and growth, and prevent chronic metabolic diseases in offspring. PMID:25224489

  11. Possible endocrine disrupting effects of parabens and their metabolites.

    PubMed

    Boberg, Julie; Taxvig, Camilla; Christiansen, Sofie; Hass, Ulla

    2010-09-01

    Parabens are preservatives used in a wide range of cosmetic products, including products for children, and some are permitted in foods. However, there is concern for endocrine disrupting effects. This paper critically discusses the conclusions of recent reviews and original research papers and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites, little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when comparing worst-case exposure to NOAELs from experimental studies in rats and mice.

  12. 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

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

    PubMed

    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

  14. CONTAMINANT-INDUCED ENDOCRINE DISRUPTION IN WILDLIFE

    EPA Science Inventory

    Environmental contaminants have posed a threat to the health of wildlife since the onset of the industrial age. Over the last four decades, much concern has focused on the lethal, carcinogenic and/or extreme teratogenic manifestations of environmental pollution. During the last d...

  15. CHILDREN'S EXPOSURES TO ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    EPA is committed to protecting children's health by identifying, assessing, and reducing the risks from chemicals present in the air they breathe, food they eat, water they drink, and surfaces they touch. The Agency is committed to understanding the extent of children's exposure...

  16. 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

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

    PubMed

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

    2014-01-01

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

  18. 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,...

  19. Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben.

    PubMed

    Boberg, J; Axelstad, M; Svingen, T; Mandrup, K; Christiansen, S; Vinggaard, A M; Hass, U

    2016-07-01

    Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben. PMID:27122241

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

    PubMed

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

    2014-01-01

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

  1. 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.

  2. 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. PMID:26825073

  3. 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

  4. 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...

  5. Direct action of endocrine disrupting chemicals on human sperm.

    PubMed

    Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L; Alvarez, Luis; Brenker, Christoph; Rehfeld, Anders; Frederiksen, Hanne; Wäschle, Benjamin; Kaupp, U Benjamin; Balbach, Melanie; Wachten, Dagmar; Skakkebaek, Niels E; Almstrup, Kristian; Strünker, Timo

    2014-07-01

    Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca(2+) increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate Ca(2+) levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization. PMID:24820036

  6. Direct action of endocrine disrupting chemicals on human sperm

    PubMed Central

    Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L; Alvarez, Luis; Brenker, Christoph; Rehfeld, Anders; Frederiksen, Hanne; Wäschle, Benjamin; Kaupp, U Benjamin; Balbach, Melanie; Wachten, Dagmar; Skakkebaek, Niels E; Almstrup, Kristian; Strünker, Timo

    2014-01-01

    Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca2+ increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate Ca2+ levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization. PMID:24820036

  7. What Is Women's Endocrine Health?

    MedlinePlus

    ... healthy lifestyle and harness the power to prevent endocrine disorders, the Power of Prevention. Childhood Childhood is a ... frequent at this time. Learning how to prevent endocrine disorders during this age is pivotal. Young Women At ...

  8. Methods for the Determination of Endocrine-Disrupting Phthalate Esters.

    PubMed

    Qureshi, Munawar Saeed; Yusoff, Abdull Rahim bin Mohd; Wirzal, Mohd Dzul Hakim; Sirajuddin; Barek, Jiri; Afridi, Hassan Imran; Üstündag, Zafer

    2016-01-01

    Phthalates are endocrine disruptors frequently occurring in the general and industrial environment and in many industrial products. Moreover, they are also suspected of being carcinogenic, teratogenic, and mutagenic, and they show diverse toxicity profiles depending on their structures. The European Union and the United States Environmental Protection Agency (US EPA) have included many phthalates in the list of priority substances with potential endocrine-disrupting action. They are: dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBP), diethylhexyl phthalate (DEHP), di-iso-nonyl phthalate (DINP), di-iso-decyl phthalate (DIDP), di-n-decyl phthalate (DnDP), and dioctyl phthalate (DOP). There is an ever-increasing demand for new analytical methods suitable for monitoring different phthalates in various environmental, biological, and other matrices. Separation and spectrometric methods are most frequently used. However, modern electroanalytical methods can also play a useful role in this field because of their high sensitivity, reasonable selectivity, easy automation, and miniaturization, and especially low investment and running costs, which makes them suitable for large-scale monitoring. Therefore, this review outlines possibilities and limitations of various analytical methods for determination of endocrine-disruptor phthalate esters in various matrices, including somewhat neglected electroanalytical methods.

  9. Methods for the Determination of Endocrine-Disrupting Phthalate Esters.

    PubMed

    Qureshi, Munawar Saeed; Yusoff, Abdull Rahim bin Mohd; Wirzal, Mohd Dzul Hakim; Sirajuddin; Barek, Jiri; Afridi, Hassan Imran; Üstündag, Zafer

    2016-01-01

    Phthalates are endocrine disruptors frequently occurring in the general and industrial environment and in many industrial products. Moreover, they are also suspected of being carcinogenic, teratogenic, and mutagenic, and they show diverse toxicity profiles depending on their structures. The European Union and the United States Environmental Protection Agency (US EPA) have included many phthalates in the list of priority substances with potential endocrine-disrupting action. They are: dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBP), diethylhexyl phthalate (DEHP), di-iso-nonyl phthalate (DINP), di-iso-decyl phthalate (DIDP), di-n-decyl phthalate (DnDP), and dioctyl phthalate (DOP). There is an ever-increasing demand for new analytical methods suitable for monitoring different phthalates in various environmental, biological, and other matrices. Separation and spectrometric methods are most frequently used. However, modern electroanalytical methods can also play a useful role in this field because of their high sensitivity, reasonable selectivity, easy automation, and miniaturization, and especially low investment and running costs, which makes them suitable for large-scale monitoring. Therefore, this review outlines possibilities and limitations of various analytical methods for determination of endocrine-disruptor phthalate esters in various matrices, including somewhat neglected electroanalytical methods. PMID:25831046

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties.

    PubMed

    Marx-Stoelting, P; Niemann, L; Ritz, V; Ulbrich, B; Gall, A; Hirsch-Ernst, K I; Pfeil, R; Solecki, R

    2014-12-01

    Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation

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

    PubMed

    Husain, Qayyum; Qayyum, Shariq

    2013-09-01

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

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

    PubMed

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

    2016-01-01

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

  18. 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.

  19. Endocrine disrupter--estradiol--in Chesapeake Bay tributaries.

    PubMed

    Dorabawila, Nelum; Gupta, Gian

    2005-04-11

    Exogenous chemicals that interfere with natural hormonal functions are considered endocrine disrupting chemicals (EDCs). Estradiol (17beta-estradiol or E2) is the most potent of all xenoestrogens. Induction of vitellogenin (VTG) production in male fish occurs at E2 concentrations as low as 1 ng l-1. E2 reaches aquatic systems mainly through sewage and animal waste disposal. Surface water samples from ponds, rivers (Wicomico, Manokin and Pocomoke), sewage treatment plants (STPs), and coastal bays (Assawoman, Monie, Chincoteague, and Tangier Sound-Chesapeake Bay) on the Eastern Shore of Maryland were analyzed for E2 using enzyme linked immuno-sorbent assay (ELISA). E2 concentrations in river waters varied between 1.9 and 6.0 ng l-1. Highest E2 concentrations in river waters were observed immediately downstream of STPs. E2 concentrations in all the coastal bays tested were 2.3-3.2 ng l-1. PMID:15811666

  20. 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

  1. 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.

  2. Endocrine disrupting chemicals as potential risk factor for estrogen-dependent cancers.

    PubMed

    Rutkowska, Aleksandra Z; Szybiak, Aleksandra; Serkies, Krystyna; Rachoń, Dominik

    2016-08-01

    Civilization, industrialization, and urbanization create an environment where humans are continuously exposed to endocrine disrupting chemicals (EDCs). Some of breast cancers and endometrial cancer, which are the most common female malignant neoplasms, are estrogen-dependent tumors. Prolonged exposure to estrogens or substances with estrogenic properties may be a risk factor for their development. This paper aimed to discuss the potential adverse effect of EDCs on human health, including the role of EDCs in hormone-dependent carcinogenesis. A review of literature regarding the sources of environmental exposure to EDCs and molecular mechanisms of their action was performed. We analyzed the possible mechanisms of how these substances alter the function of the endocrine system, resulting in adverse health effects. Hundreds of substances with endocrine disrupting potential have been identified in our environment. There is accumulating evidence linking exposure to EDCs with the development of mammary and endometrial cancer. By interacting with steroid receptors, EDCs can impact the cellular processes potentially leading to carcinogenesis. There are also data showing the effect of EDCs on immune dysfunction. During lifespan, people are usually exposed to a mixture of various EDCs, which complicates the assessment of individual substances or compounds implicated in cancer development. As the prevalence of hormone-dependent tumors among women continues to increase, their successful prevention is of human benefit. Institutions representing medicine, science, industry, and governments should develop joint strategies to decrease exposure to EDC, and thus to reduce the risk of hormonedependent tumors in women. PMID:27509913

  3. 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 ...

  4. 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. PMID:22239237

  5. 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

  6. 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.

  7. 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. PMID:26118430

  8. 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

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

    PubMed

    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

    2016-07-01

    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.

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

    PubMed

    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

    2016-07-01

    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

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

    PubMed

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

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility". PMID:26825071

  12. 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

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

    PubMed Central

    Engel, Stephanie M.; Wolff, Mary S.

    2014-01-01

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

  14. Thyroid endocrine disruption and external body morphology of Zebrafish.

    PubMed

    Sharma, Prakash; Grabowski, Timothy B; Patiño, Reynaldo

    2016-01-15

    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, 0.15mM)], combination of MZ (0.15mM) and thyroxine (T4, 2nM), T4 (2nM), or control (reconstituted water) treatments until 33dpf and subsequently maintained in reconstituted water until 45dpf. Samples were taken at 33 and 45dpf 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 45dpf. 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 45dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45dpf 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 45dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45dpf. 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. PMID:26723187

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Determination of selected endocrine disrupting chemicals in Lake Van, Turkey.

    PubMed

    Oğuz, Ahmet R; Kankaya, Ertuğrul

    2013-09-01

    In the present study, we investigated the distribution of 17β-estradiol (E2), 17α-ethynylestradiol (EE2), alkylphenol ethoxylates (APEs) and organochlorine pesticides (DDE/DDT) in water and sediment samples in the Eastern Anatolia of Turkey, Lake Van, which is the largest soda lake in the world. The procedure consisted of solid phase extraction performed with OASIS HLB cartridges followed by non-competitive enzyme-linked immunosorbent assays (ELISA). The endocrine disrupting compounds E2, EE2, and DDT/DDE were detected in most of the lake samples with mean concentrations of 0.996 ± 0.304, 0.050 ± 0.022, and 0.749 ± 0.658 ng/L in water, respectively. Mean concentrations of E2, EE2 and DDT/DDE in sediment were 0.098 ± 0.053, 0.091 ± 0.072, and 1.281 ± 0.754 ng/g, respectively. APEs were not measured in the sediment samples. The EDCs levels in surface water and sediment samples were lower than that of other countries. The EDCs were also found in effluent and influent municipal sewage samples. Van city municipal wastewater treatment plant has no removal efficiency for EDCs. PMID:23771312

  20. 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

  1. 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...

  2. 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...

  3. 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.

  4. 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 ...

  5. 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...

  6. 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...

  7. Intersex in the clam Scrobicularia plana: a sign of endocrine disruption in estuaries?

    PubMed

    Chesman, B S; Langston, W J

    2006-09-22

    The phenomenon of endocrine disruption is currently a source of growing concern. Feminization of male fish in UK rivers has been shown to occur extensively and has been linked with exposure to endocrine-disrupting compounds present in the environment. Much less is known of the extent and scale of endocrine disruption in estuarine and marine ecosystems, particularly in invertebrates. We present evidence that intersex, in the form of ovotestis, is occurring in the common estuarine bivalve Scrobicularia plana, which is considered to be inherently gonochoristic. We report varying degrees in the severity of ovotestis in male S. plana, and have adopted and developed a grading method to assess the extent of this intersex condition. These findings indicate that S. plana offers potential for widespread screening and investigation of endocrine disruption, helping to focus remediatory strategy.

  8. Intersex in the clam Scrobicularia plana: a sign of endocrine disruption in estuaries?

    PubMed Central

    Chesman, B.S; Langston, W.J

    2006-01-01

    The phenomenon of endocrine disruption is currently a source of growing concern. Feminization of male fish in UK rivers has been shown to occur extensively and has been linked with exposure to endocrine-disrupting compounds present in the environment. Much less is known of the extent and scale of endocrine disruption in estuarine and marine ecosystems, particularly in invertebrates. We present evidence that intersex, in the form of ovotestis, is occurring in the common estuarine bivalve Scrobicularia plana, which is considered to be inherently gonochoristic. We report varying degrees in the severity of ovotestis in male S. plana, and have adopted and developed a grading method to assess the extent of this intersex condition. These findings indicate that S. plana offers potential for widespread screening and investigation of endocrine disruption, helping to focus remediatory strategy. PMID:17148420

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

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

    PubMed

    Suvorov, Alexander; Vandenberg, Laura N

    2016-07-01

    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.

  15. Effect of endocrine disrupters on photosystem II energy fluxes of green algae and cyanobacteria.

    PubMed

    Perron, Marie-Claude; Juneau, Philippe

    2011-05-01

    Among the numerous toxics found in the aquatic environment, endocrine disrupters can interfere with the normal functioning of the endocrine system of several organisms, leading to important consequences. Even if algae and cyanobacteria are non-target organisms without endocrine system, our goals were to verify if endocrine disrupters can affect photosynthetic activity and how energy flows through photosystem II (PSII) were altered. To reach these objectives, we exposed, for 15 min, two green algae (Chlamydomonas reinhardtii strain CC125, Pseudokirchneriella subcapitata strain CPCC37) and a toxic and a non-toxic strain of Microcystis aeruginosa (CPCC299 and CPCC632 respectively) to 4-octylphenol, 4-nonylphenol and β-estradiol at concentrations ranging from 0.1 to 5 μg/mL. We have shown for the first time that endocrine disrupters may have drastic effects on PSII energy fluxes. Furthermore, we showed that various species have different sensitivity to endocrine disrupters. P. subcapitata was tolerant to each endocrine disrupter tested, while flows of energy through PSII were affected similarly, but at different extent, for the other species. Cyanobacterial PSII energy fluxes were more affected than green algae, suggesting that the prokaryotic characteristics of these organisms are responsible of their high sensitivity.

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

    PubMed

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

    2007-06-01

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

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

    PubMed

    2013-01-01

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

  18. 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

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

    PubMed

    Zawatski, William; Lee, Mary M

    2013-01-01

    Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health. In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females, this review will focus on the small number of studies performed in males that report an association of polychlorinated biphenyls with earlier sexual maturity rating and confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal onset and progression in boys. Recent studies have also demonstrated that EDC exposure may affect pubertal testosterone production without having a noticeable effect on sexual maturity rating. A limitation to understand the effects of EDCs in humans is the potential for confounding due to the long temporal lag from early-life exposures to adult outcomes. The complex interplay of multiple environmental exposures over time also complicates the interpretation of human studies. These studies have identified critical windows of vulnerability during development when exposures to EDCs alter critical pathways and affect postnatal reproductive health. Contemporaneous exposures can also disrupt the hypothalamic-pituitary-gonadal axis. This paper will review the normal process of puberty in males and summarize human data that suggest potential perturbations in pubertal onset and tempo with early-life exposures to EDCs. PMID:23709001

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

    PubMed

    2013-01-01

    Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that interfere with endogenous endocrine action. The frequent use of chemicals with endocrine active properties in household products and contamination of soil, water, and food sources by persistent chemical pollutants result in ubiquitous exposures. Wildlife observations and animal toxicological studies reveal adverse effects of EDCs on reproductive health.In humans, a growing number of epidemiological studies report an association with altered pubertal timing and progression. While these data are primarily reported in females,this review will focus on the small number of studies performed in males that report an association of polychlorinated biphenyls with earlier sexual maturity rating and confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal onset and progression in boys. Recent studies have also demonstrated that EDC exposure may affect pubertal testosterone production without having a noticeable effect on sexual maturity rating.A limitation to understand the effects of EDCs in humans is the potential for confounding due to the long temporal lag from early-life exposures to adult outcomes. The complex interplay of multiple environmental exposures over time also complicates the interpretation of human studies. These studies have identified critical windows of vulnerability during development when exposures to EDCs alter critical pathways and affect postnatal reproductive health. Contemporaneous exposures can also disrupt the hypothalamic-pituitary-gonadal axis. This paper will review the normal process of puberty in males and summarize human data that suggest potential perturbations in pubertal onset and tempo with early-life exposures to EDCs. PMID:23977686

  1. 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.

  2. 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

  3. Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures.

    PubMed

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

    2014-03-14

    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.

  4. 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.

  5. Alterations in development of reproductive and endocrine systems of wildlife populations exposed to endocrine-disrupting contaminants.

    PubMed

    Guillette, L J; Gunderson, M P

    2001-12-01

    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 tissues. Documented disruptions or alterations in reproductive activity, morphology or physiology in wildlife populations have been correlated with contaminant-induced modifications in endocrine system functioning. Alterations of the endocrine system are complex, and not limited to a particular organ or molecular mechanism. For instance, contaminants have been shown to (1) act as hormone receptor agonists or antagonists, (2) alter hormone production at its endocrine source, (3) alter the release of stimulatory or inhibitory hormones from the pituitary or hypothalamus, (4) alter hepatic enzymatic biotransformation of hormones, and (5) alter the concentration or functioning of serum-binding proteins, altering free hormone concentrations in the serum. This review focuses on two of these alterations, altered hormone synthesis and hepatic biotransformation, as a number of recent studies indicate that these actions are important components of endocrine disruption in developing organisms. The possible role of contaminants in altering sex determination mechanisms is also examined.

  6. The TSCA Interagency Testing Committee (ITC) proposed strategy for identifying and coordinating U.S. government data needs for endocrine-disrupting chemicals

    SciTech Connect

    Walker, J.D.

    1995-12-31

    The ITC`s Endocrine-Disrupting Chemicals Subcommittee will implement a proposed strategy for identifying and coordinating the US government ecological and health effects data needs for endocrine-disrupting chemicals, These include chemicals with potential to cause reproductive, developmental, immunological, neurologic or other biological effects by adversely affecting endocrine tissues, hormones or receptors in fish, wildlife or humans. To meet these needs, the Subcommittee will consider three options. First, the information collecting authority of the Toxic Substances Control Act (TSCA) will be considered as a cost-effective mechanism to rapidly (within 60 days) obtain unpublished health and ecological effects studies related to reproductive effects and endocrine-disrupting activity. Second, the chemical testing authority of TSCA will be considered as a method to request that the manufacturers of endocrine-disrupting chemicals conduct tests that are amenable to standardization. Third, consideration will be given to coordinating standardized testing with testing related to research and to using the results of this research to develop standardized methods for assessing the effects of endocrine-disrupting chemicals. The Subcommittee will focus on 16 alkylphenol and alkylphenol ethoxylates with 1989 production or importation volumes greater than 1 million pounds that were identified using the Substructure based Computerized Chemical Selection Expert System (SuCCSES). The ITC`s proposed strategy will be discussed.

  7. 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

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

    PubMed

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

    2016-01-01

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

  9. 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...

  10. 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.

  11. 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. ...

  12. ISSUES IN ENDOCRINE DISRUPTION: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY

    EPA Science Inventory

    Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

  13. 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...

  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. 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

  16. 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

  17. Transcriptional analysis of endocrine disruption using zebrafish and massively parallel sequencing.

    PubMed

    Baker, Michael E; Hardiman, Gary

    2014-06-01

    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

  18. 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

  19. 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.'

  20. Disruption of Parenting Behaviors in California Mice, a Monogamous Rodent Species, by Endocrine Disrupting Chemicals

    PubMed Central

    Johnson, Sarah A.; Javurek, Angela B.; Painter, Michele S.; Peritore, Michael P.; Ellersieck, Mark R.; Roberts, R. Michael; Rosenfeld, Cheryl S.

    2015-01-01

    The nature and extent of care received by an infant can affect social, emotional and cognitive development, features that endure into adulthood. Here we employed the monogamous, California mouse (Peromyscus californicus), a species, like the human, where both parents invest in offspring care, to determine whether early exposure to endocrine disrupting chemicals (EDC: bisphenol A, BPA; ethinyl estradiol, EE) of one or both parents altered their behaviors towards their pups. Females exposed to either compound spent less time nursing, grooming and being associated with their pups than controls, although there was little consequence on their weight gain. Care of pups by males was less affected by exposure to BPA and EE, but control, non-exposed females appeared able to “sense” a male partner previously exposed to either compound and, as a consequence, reduced their own parental investment in offspring from such pairings. The data emphasize the potential vulnerability of pups born to parents that had been exposed during their own early development to EDC, and that effects on the male, although subtle, also have consequences on overall parental care due to lack of full acceptance of the male by the female partner. PMID:26039462

  1. 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.

  2. Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures

    PubMed Central

    Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

    2015-01-01

    Background Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. Objectives We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. Methods We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. Discussion In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. Conclusions We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs. Citation Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC. 2016. Endocrine-disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures. Environ Health Perspect 124:256–264; http://dx.doi.org/10.1289/ehp.1409535 PMID:26311476

  3. 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. PMID:26748264

  4. 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.

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

    SciTech Connect

    McLachlan, John A.

    2000-06-01

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

  6. 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...

  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. 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.

  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. PMID:27241264

  10. 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.

  11. 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. PMID:23823564

  12. 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.

  13. 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.

  14. Endocrine-Disrupting Effects of Pesticides through Interference with Human Glucocorticoid Receptor.

    PubMed

    Zhang, Jianyun; Zhang, Jing; Liu, Rui; Gan, Jay; Liu, Jing; Liu, Weiping

    2016-01-01

    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.

  15. 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

  16. 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

  17. Endocrine-Disrupting Effects of Pesticides through Interference with Human Glucocorticoid Receptor.

    PubMed

    Zhang, Jianyun; Zhang, Jing; Liu, Rui; Gan, Jay; Liu, Jing; Liu, Weiping

    2016-01-01

    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. PMID:26647222

  18. 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.

  19. Polyamide 6/chitosan nanofibers as support for the immobilization of Trametes versicolor laccase for the elimination of endocrine disrupting chemicals.

    PubMed

    Maryšková, Milena; Ardao, Inés; García-González, Carlos A; Martinová, Lenka; Rotková, Jana; Ševců, Alena

    2016-07-01

    In recent years, there has been an increase in efforts to improve wastewater treatment as the concentration of dangerous pollutants, such as endocrine disrupting chemicals, in wastewater increases. These compounds, which mimic the effect of hormones, have a negative impact on human health and are not easily removed from water. One way to effectively eliminate these pollutants is to use enzymatically activated materials. In this study, we report on the use of laccase from the white rot fungus Trametes versicolor immobilized onto polyamide 6/chitosan (PA6/CHIT) nanofibers modified using two different spacers (bovine serum albumin and hexamethylenediamine). We then tested the ability of the PA6/CHIT-laccase biocatalysts to eliminate a mixture containing 50μM of two endocrine disrupting chemicals: bisphenol A and 17α-ethinylestradiol. The PA6/CHIT nanofiber matrix used in this study not only proved to be a suitable carrier for immobilized and modified laccase but was also efficient in the removal of a mixture of endocrine disrupting chemicals in three treatment cycles.

  20. Endocrine-disrupting chemicals and oil and natural gas operations: Potential environmental contamination and recommendations to assess complex environmental mixtures

    USGS Publications Warehouse

    Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

    2015-01-01

    Background: Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. While these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals used throughout the process, including many known or suspected endocrine-disrupting chemicals.Objectives: We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and anti-hormonal activities for chemicals used.Methods: We discuss the literature on 1) surface and ground water contamination by oil and gas extraction operations, and 2) potential human exposure, particularly in context of the total hormonal and anti-hormonal activities present in surface and ground water from natural and anthropogenic sources, with initial analytical results and critical knowledge gaps discussed.Discussion: In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures.Conclusions: We describe a need for an endocrine-centric component for overall health assessments and provide supporting information that using this may help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

  1. Endocrine Disrupting Chemicals Research Program of the U.S. Environmental Protection Agency: Summary of a Peer-Review Report

    PubMed Central

    Harding, Anna K.; Daston, George P.; Boyd, Glen R.; Lucier, George W.; Safe, Stephen H.; Stewart, Juarine; Tillitt, Donald E.; Van Der Kraak, Glen

    2006-01-01

    At the request of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, a subcommittee of the Board of Scientific Counselors Executive Committee conducted an independent and open peer review of the Endocrine Disrupting Chemicals Research Program (EDC Research Program) of the U.S. EPA. The subcommittee was charged with reviewing the design, relevance, progress, scientific leadership, and resources of the program. The subcommittee found that the long-term goals and science questions in the EDC Program are appropriate and represent an understandable and solid framework for setting research priorities, representing a combination of problem-driven and core research. Long-term goal (LTG) 1, dealing with the underlying science surrounding endocrine disruptors, provides a solid scientific foundation for conducting risk assessments and making risk management decisions. LTG 2, dealing with defining the extent of the impact of endocrine-disrupting chemicals (EDCs), has shown greater progress on ecologic effects of EDCs compared with that on human health effects. LTG 3, which involves support of the Endocrine Disruptor Screening and Testing Program of the U.S. EPA, has two mammalian tests already through a validation program and soon available for use. Despite good progress, we recommend that the U.S. EPA a) strengthen their expertise in wildlife toxicology, b) expedite validation of the Endocrine Disruptors Screening and Testing Advisory Committee tests, c) continue dependable funding for the EDC Research Program, d) take a leadership role in the application of “omics” technologies to address many of the science questions critical for evaluating environmental and human health effects of EDCs, and e) continue to sponsor multidisciplinary intramural research and interagency collaborations. PMID:16882539

  2. Endocrine disrupting chemicals research program of the U.S. Environmental Protection Agency: summary of a peer-review report.

    PubMed

    Harding, Anna K; Daston, George P; Boyd, Glen R; Lucier, George W; Safe, Stephen H; Stewart, Juarine; Tillitt, Donald E; Van Der Kraak, Glen

    2006-08-01

    At the request of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, a subcommittee of the Board of Scientific Counselors Executive Committee conducted an independent and open peer review of the Endocrine Disrupting Chemicals Research Program (EDC Research Program) of the U.S. EPA. The subcommittee was charged with reviewing the design, relevance, progress, scientific leadership, and resources of the program. The subcommittee found that the long-term goals and science questions in the EDC Program are appropriate and represent an understandable and solid framework for setting research priorities, representing a combination of problem-driven and core research. Long-term goal (LTG) 1, dealing with the underlying science surrounding endocrine disruptors, provides a solid scientific foundation for conducting risk assessments and making risk management decisions. LTG 2, dealing with defining the extent of the impact of endocrine-disrupting chemicals (EDCs), has shown greater progress on ecologic effects of EDCs compared with that on human health effects. LTG 3, which involves support of the Endocrine Disruptor Screening and Testing Program of the U.S. EPA, has two mammalian tests already through a validation program and soon available for use. Despite good progress, we recommend that the U.S. EPA a) strengthen their expertise in wildlife toxicology, b) expedite validation of the Endocrine Disruptors Screening and Testing Advisory Committee tests, c) continue dependable funding for the EDC Research Program, d) take a leadership role in the application of "omics" technologies to address many of the science questions critical for evaluating environmental and human health effects of EDCs, and e) continue to sponsor multidisciplinary intramural research and interagency collaborations.

  3. Endocrine disrupting chemicals research program of the U.S. Environmental Protection Agency: summary of a peer-review report

    USGS Publications Warehouse

    Harding, Anna K.; Daston, George P.; Boyd, Glen R.; Lucier, George W.; Safe, Stephen H.; Stewart, Juarine; Tillitt, Donald E.; Van Der Kraak, Glen

    2006-01-01

    At the request of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, a subcommittee of the Board of Scientific Counselors Executive Committee conducted an independent and open peer review of the Endocrine Disrupting Chemicals Research Program (EDC Research Program) of the U.S. EPA. The subcommittee was charged with reviewing the design, relevance, progress, scientific leadership, and resources of the program. The subcommittee found that the long-term goals and science questions in the EDC Program are appropriate and represent an understandable and solid framework for setting research priorities, representing a combination of problem-driven and core research. Long-term goal (LTG) 1, dealing with the underlying science surrounding endocrine disruptors, provides a solid scientific foundation for conducting risk assessments and making risk management decisions. LTG 2, dealing with defining the extent of the impact of endocrine-disrupting chemicals (EDCs), has shown greater progress on ecologic effects of EDCs compared with that on human health effects. LTG 3, which involves support of the Endocrine Disruptor Screening and Testing Program of the U.S. EPA, has two mammalian tests already through a validation program and soon available for use. Despite good progress, we recommend that the U.S. EPA a) strengthen their expertise in wildlife toxicology, b) expedite validation of the Endocrine Disruptors Screening and Testing Advisory Committee tests, c) continue dependable funding for the EDC Research Program, d) take a leadership role in the application of “omics” technologies to address many of the science questions critical for evaluating environmental and human health effects of EDCs, and e) continue to sponsor multidisciplinary intramural research and interagency collaborations.

  4. Detection of an endocrine disrupter biomarker, vitellogenin, in largemouth bass serum using AlGaN/GaN high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Chu, Byung Hwan; Chang, C. Y.; Kroll, Kevin; Denslow, Nancy; Wang, Yu-Lin; Pearton, S. J.; Dabiran, A. M.; Wowchak, A. M.; Cui, B.; Chow, P. P.; Ren, Fan

    2010-01-01

    Endocrine disrupters are known to have negative effects on the environment and human health. Real time detection of vitellogenin, an endocrine disrupter biomarker, was demonstrated using AlGaN/GaN high electron mobility transistors (HEMTs). Anti-vitellogenin antibodies were chemically anchored to the gold-coated gate area of the HEMT and immobilized with thioglycolic acid. The potential difference that occurs from the vitellogenin antigen-antibody interaction-induced caused a drain current change in the HEMT. The HEMT sensor was tested for vitellogenin detection both in phosphate buffer saline and largemouth bass serum.

  5. 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 ...

  6. 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...

  7. 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...

  8. 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...

  9. 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 ...

  10. 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,...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

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

    PubMed

    Cajthaml, Tomáš

    2015-12-01

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

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

    PubMed

    Cajthaml, Tomáš

    2015-12-01

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

  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. 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 ...

  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. 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...

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

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

    PubMed Central

    2010-01-01

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

  11. Endocrine-disrupting activity of chemicals in diesel exhaust and diesel exhaust particles.

    PubMed

    Takeda, Ken; Tsukue, Naomi; Yoshida, Seiichi

    2004-01-01

    Diesel exhaust (DE) is known as the main cause of air pollution. DE is a complex mixture of particulate and vapor-phase compounds. The soluble organic fraction of the particulate materials in DE contains thousands of compounds including a variety of polycyclic aromatic hydrocarbons and heavy metals. To clarify the endocrine-disrupting activities of DE, we have reviewed the reports about the effects of DE on the reproductive and brain-nervous systems, and the endocrine-disrupting action of diesel exhaust particles (DEP). In utero exposure to low levels (0.1 mg DEP/m3) of DE from day 2 postcoitum (p.c.) until day 13 p.c. reduced the expression level of Ad4BP/SF-1 mRNA and thereby might affect the development of gonads. Low levels of DE also reduced the expression of several genes known to play key roles in gonadal development, including an enzyme necessary for testosterone synthesis. Mature male rats exposed to DE during the fetal period showed an irreversible decrease in daily sperm production due to an insufficient number of Sertoli cells. DE exposure during the fetal period influenced the brain tissue in newborn mice. In the 3 mg DEP/m3 exposure group at 10 weeks of age, a significant reduction in performance was observed in the passive avoidance learning test in both male and female mice. In addition, the fetal exposure of mice to DE affected the emotional behaviors associated with the serotonergic and dopaminergic systems in the mouse brain. In toluidine blue-stained specimens from the DE-exposed group, edema around the vessels where fluorescent granular perithelial (FGP) cells exist and degenerated granules within the FGP cytoplasm were observed; similar findings were obtained by electron microscopic examination. DEP contain many substances that stimulate Ah receptors, such as the polycyclic aromatic hydrocarbon containing benzo[a]pyrene. DEP also contain substances with estrogenic, antiestrogenic and antiandrogenic activities. The neutral substance fraction of

  12. 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

  13. Targeted toxicological testing to investigate the role of endocrine disrupters in puberty disorders.

    PubMed

    Maranghi, Francesca; Mantovani, Alberto

    2012-06-01

    Puberty is a process regulated by the endocrine system which physiological onset is poorly understood. Factors potentially leading to the disruption of this system may seriously affect the reproductive function development. Altered puberty onset can be an unspecific consequence of general toxicity in juvenile rodents; however, several toxicological studies indicate potential effects of specific substances on puberty development. In particular, the exposure to endocrine disrupters (ED) showing (anti)estrogenic, (anti)androgenic activity or interaction with hypothalamic-pituitary-gonadal (HPG) axis is considered biologically plausible and deserving attention. Risk assessment agencies call for data on children effects for their specific vulnerability or specific exposure situations. On the other hand, no international effort is foreseen to develop robust tools for characterizing chemical hazards in the immature organisms. For some chemicals the available data might be sufficient to trigger precautionary measures but a sound risk analysis needs an interdisciplinary integration between human medicine and experimental toxicology.

  14. Advancing Research on Endocrine Disrupting Chemicals in Breast Cancer: Expert Panel Recommendations

    PubMed Central

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

    2015-01-01

    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 over 85,000 endocrine disrupting chemicals are 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. PMID:25549947

  15. 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. PMID:24085605

  16. 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.

  17. 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.

  18. Embryonic exposure to butachlor in zebrafish (Danio rerio): endocrine disruption, developmental toxicity and immunotoxicity.

    PubMed

    Tu, Wenqing; Niu, Lili; Liu, Weiping; Xu, Chao

    2013-03-01

    Butachlor is a chloroacetanilide herbicide widely employed in weeding important crops. Recently, the study of the possible toxic effects of butachlor in non-target organisms has increased substantially. However, the endocrine disruption, developmental toxicity and immunotoxicity effects of butachlor in fish have not been fully investigated in previous studies. In the present study, zebrafish embryos were exposed to a range of butachlor concentrations from 4 to 20 μM to evaluate the embryonic toxicity of butachlor until 84 hours postfertilization (hpf). The results demonstrated that butachlor was highly toxic to zebrafish embryos, hindering the hatching process, resulting in a series of malformations and followed by mortality. The malformations observed included pericardial edema (PE) and yolk sac edema (YSE), which showed concentration-dependent responses. The analysis of endocrine gene transcription indicated that butachlor significantly induced the expression of the estrogen-responsive gene Vtg1 but had no effect on the expression of the ERα gene. The innate immune system appeared to be another possible target of butachlor. At 72 hpf, butachlor significantly up-regulated the innate immune system-related genes, including IL-1β, CC-chem, CXCL-C1c and IL-8. These data suggest that butachlor causes developmental toxicity, endocrine disruption and immune toxicity in the zebrafish embryo. Bidirectional interactions between the endocrine system and the immune system might be present, and further studies are needed to determine these possible pathways.

  19. Embryonic exposure to butachlor in zebrafish (Danio rerio): endocrine disruption, developmental toxicity and immunotoxicity.

    PubMed

    Tu, Wenqing; Niu, Lili; Liu, Weiping; Xu, Chao

    2013-03-01

    Butachlor is a chloroacetanilide herbicide widely employed in weeding important crops. Recently, the study of the possible toxic effects of butachlor in non-target organisms has increased substantially. However, the endocrine disruption, developmental toxicity and immunotoxicity effects of butachlor in fish have not been fully investigated in previous studies. In the present study, zebrafish embryos were exposed to a range of butachlor concentrations from 4 to 20 μM to evaluate the embryonic toxicity of butachlor until 84 hours postfertilization (hpf). The results demonstrated that butachlor was highly toxic to zebrafish embryos, hindering the hatching process, resulting in a series of malformations and followed by mortality. The malformations observed included pericardial edema (PE) and yolk sac edema (YSE), which showed concentration-dependent responses. The analysis of endocrine gene transcription indicated that butachlor significantly induced the expression of the estrogen-responsive gene Vtg1 but had no effect on the expression of the ERα gene. The innate immune system appeared to be another possible target of butachlor. At 72 hpf, butachlor significantly up-regulated the innate immune system-related genes, including IL-1β, CC-chem, CXCL-C1c and IL-8. These data suggest that butachlor causes developmental toxicity, endocrine disruption and immune toxicity in the zebrafish embryo. Bidirectional interactions between the endocrine system and the immune system might be present, and further studies are needed to determine these possible pathways. PMID:23294635

  20. 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.

  1. Causes of endocrine disrupting potencies in surface water in East China.

    PubMed

    Shi, Wei; Deng, Dongyang; Wang, Yuting; Hu, Guanjiu; Guo, Jing; Zhang, Xiaowei; Wang, Xinru; Giesy, John P; Yu, Hongxia; Wang, Ziheng

    2016-02-01

    Surface water is essential for human health and ecological diversity, but some endocrine disrupting chemicals are detectable. Both thyroid receptor (TR) and androgen receptor (AR) agonistic/antagonistic potencies in grade II surface water in East China were investigated using reporter gene assays. While none of the water exhibited agonistic potency, significant AR and TR antagonistic potencies were detectable. TR antagonistic equivalents (TR-AntEQ) and AR antagonistic equivalents (AR-AntEQ) ranged from 3.6 to 76.1 μg dibutyl phthalate/L and from 2.3 to 242.6 μg flutamide/L, respectively. The TR and AR antagonistic potencies in the Yangtze River watershed were highlighted, with equivalents greater than the lowest observable effect concentration (LOEC) of dibutyl phthalate and flutamide, respectively. Phthalate esters (PAEs) being the most abundant explained most of the TR antagonistic potency, contributing more than 65% of the TR-AntEQ and diisobutyl phthalate (DiBP) was the major contributor. In most surface waters studied, PAEs contributed little of the AR-AntEQ, but the frequently detected octylphenol, nonylphenol and benzo[a]pyrene might be responsible. PMID:26495828

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

    PubMed Central

    Kerdivel, Gwenneg; Habauzit, Denis; Pakdel, Farzad

    2013-01-01

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

  3. 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

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

    PubMed

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

    2013-01-01

    The occurrence of 14 endocrine disrupting compounds (EDCs), pharmaceuticals and personal care products (PPCPs) in influents, effluents and sludge from five wastewater treatment plants (WWTPs) in southern California was studied in winter and summer. All 14 compounds were detected in influent samples from the five WWTPs except for estrone. Paracetamol, naproxen and ibuprofen were the dominant compounds, with mean concentrations of 41.7, 35.7 and 22.3 μg/L, respectively. The treatment removal efficiency for most compounds was more than 90% and concentrations in the effluents were relatively low. Seasonal variation of the compounds' concentration in the wastewater was significant: the total concentration of each compound in the wastewater was higher in winter than in summer, which is attributed to more human consumption of pharmaceuticals during winter and faster degradation of the compounds in summer. The highest concentrations of triclosan and octylphenol were detected in sewage sludge, with mean concentrations of 1505 and 1179 ng/g, respectively. Risk quotients (RQs), expressed as the ratios of environmental concentrations and the predicted no-effect concentrations (PNEC), were less than unity for all the compounds except for estrone in the effluents, indicating no immediate ecological risk is expected. However, RQs were higher than unity for 2 EDCs (estrone and octylphenol) and carbamazepine in sludge samples, indicating a significant ecotoxicological risk to human health. Therefore, appropriate treatment of sewage sludge is required before its application. PMID:23178835

  5. Late Lessons from Early Warnings: Toward Realism and Precaution with Endocrine-Disrupting Substances

    PubMed Central

    Gee, David

    2006-01-01

    The histories of selected public and environmental hazards, from the first scientifically based early warnings about potential harm to the subsequent precautionary and preventive measures, have been reviewed by the European Environment Agency. This article relates the “late lessons” from these early warnings to the current debates on the application of the precautionary principle to the hazards posed by endocrine-disrupting substances (EDSs). Here, I summarize some of the definitional and interpretative issues that arise. These issues include the contingent nature of knowledge; the definitions of precaution, prevention, risk, uncertainty, and ignorance; the use of differential levels of proof; and the nature and main direction of the methodological and cultural biases within the environmental health sciences. It is argued that scientific methods need to reflect better the realities of multicausality, mixtures, timing of dose, and system dynamics, which characterize the exposures and impacts of EDSs. This improved science could provide a more robust basis for the wider and wise use of the precautionary principle in the assessment and management of the threats posed by EDSs. The evaluation of such scientific evidence requires assessments that also account for multicausal reality. Two of the often used, and sometimes misused, Bradford Hill “criteria,” consistency and temporality, are critically reviewed in light of multicausality, thereby illustrating the need to review all of the criteria in light of 40 years of progress in science and policymaking. PMID:16818262

  6. The non-genomic effects of endocrine-disrupting chemicals on mammalian sperm.

    PubMed

    Tavares, R S; Escada-Rebelo, S; Correia, M; Mota, P C; Ramalho-Santos, J

    2016-01-01

    Exposure to toxicants present in the environment, especially the so-called endocrine-disrupting chemicals (EDCs), has been associated with decreased sperm quality and increased anomalies in male reproductive organs over the past decades. Both human and animal populations are continuously exposed to ubiquitous synthetic and natural-occurring EDCs through diet, dermal contact and/or inhalation, therefore potentially compromising male reproductive health. Although the effects of EDC are likely induced via multiple genomic-based pathways, their non-genomic effects may also be relevant. Furthermore, spermatozoa are transcriptionally inactive cells that can come in direct contact with EDCs in reproductive fluids and secretions and are therefore a good model to address non-genomic effects. This review thus focuses on the non-genomic effects of several important EDCs relevant to mammalian exposure. Notably, EDCs were found to interfere with pre-existing pathways inducing a panoply of deleterious effects to sperm function that included altered intracellular Ca(2) (+) oscillations, induction of oxidative stress, mitochondrial dysfunction, increased DNA damage and decreased sperm motility and viability, among others, potentially jeopardizing male fertility. Although many studies have used non-environmentally relevant concentrations of only one compound for mechanistic studies, it is important to remember that mammals are not exposed to one, but rather to a multitude of environmental EDCs, and synergistic effects may occur. Furthermore, some effects have been detected with single compounds at environmentally relevant concentrations.

  7. 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

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

    PubMed

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

    2013-12-16

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

  9. 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.

  10. 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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Endocrine-disrupting effects and reproductive toxicity of low dose MCLR on male frogs (Rana nigromaculata) in vivo.

    PubMed

    Jia, Xiuying; Cai, Chenchen; Wang, Jia; Gao, Nana; Zhang, Hangjun

    2014-10-01

    Toxic cyanobacterial blooms are potential global threats to aquatic ecosystems and human health. The World Health Organization has set a provisional guideline limit of 1 μg/L microcystin-LR (MCLR) in freshwater. However, MCLR concentrations in several water bodies have exceeded this level. Despite this recommended human safety standard, MCLR-induced endocrine-disrupting effects and reproductive toxicity on male frog (Rana nigromaculata) were demonstrated in this study. Results showed that sperm motility and sperm count were significantly and negatively correlated with exposure time and concentration. By contrast, abnormal sperm rate was positively correlated with both parameters. Ultrastructural observation results revealed abnormal sperm morphologies, vacuoles in spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. These results indicated that MCLR could induce toxic effects on the reproductive system of frogs, significantly decrease testosterone content, and rapidly increase estradiol content. Prolonged exposure and increased concentration enhanced the relative expression levels of P450 aromatase and steroidogenic factor 1; thus, endocrine function in frogs was disrupted. This study is the first to demonstrate in vivo MCLR toxicity in the reproductive system of male R. nigromaculata. This study provided a scientific basis of the global decline in amphibian populations.

  13. Endocrine disrupting chemicals (EDCs) and female cancer: Informing the patients.

    PubMed

    Rachoń, Dominik

    2015-12-01

    Breast and uterine cancer are the most frequent female gender related neoplasms whose growth is mostly estrogen dependent. Therefore, any EDC exhibiting estrogenic effects may increase the risk of these two malignancies. This review focuses on the potential role of EDCs with estrogenic potential on the risk of breast and uterine neoplasms but also points to the possible role of the exposure to EDCs in the pathogenesis of ovarian and cervical cancer. It also underlines the necessity of informing the public about the presence of EDCs in common consumer products, their detrimental health effects and methods of reducing the exposure risk.

  14. Environmental signaling: a biological context for endocrine disruption.

    PubMed Central

    Cheek, A O; Vonier, P M; Oberdörster, E; Burow, B C; McLachlan, J A

    1998-01-01

    Endogenous and exogenous chemical signals have evolved as a means for organisms to respond to physical or biological stimuli in the environment. Sensitivity to these signals can make organisms vulnerable to inadvertent signals from xenobiotics. In this review we discuss how various chemicals can interact with steroid-like signaling pathways, especially estrogen. Numerous compounds have estrogenic activity, including steroids, phytoestrogens, and synthetic chemicals. We compare bioavailability, metabolism, interaction with receptors, and interaction with cell-signaling pathways among these three structurally diverse groups in order to understand how these chemicals influence physiological responses. Based on their mechanisms of action, chemical steroid mimics could plausibly be associated with recent adverse health trends in humans and animals. PMID:9539003

  15. Endocrine disruption in white ibises (Eudocimus albus) caused by exposure to environmentally relevant levels of methylmercury.

    PubMed

    Jayasena, Nilmini; Frederick, Peter C; Larkin, Iskande L V

    2011-10-01

    Methylmercury is a globally distributed pollutant and upper trophic level aquatic fauna are at particularly high risk of exposure. Although methylmercury is known to have a number of neurological and developmental effects, relatively little is known about effects on endocrine disruption and reproduction in aquatic fauna, particularly in response to chronic exposure at low concentrations. We experimentally exposed captive white ibises for 3.5 years (2005-2008) to dietary methylmercury at three environmentally relevant concentrations (0.05, 0.1 and 0.3 ppm wet weight in diet). We measured fecal concentrations of estradiol and testosterone metabolites in two consecutive breeding seasons (2007 and 2008). When effects were controlled for stage of breeding, this resulted in altered estradiol and testosterone concentrations in adult breeders of both sexes. Changes in endocrine expression were not consistent over both years, and a clear dose-response relationship was not always present. Endocrine changes were, however, associated at all dose levels with changes in reproductive behavior, reduced reproductive success and altered mate choice in males. Male-male pairing and altered courtship behavior in males were related both to dose treatment and, in 2008, to a demasculinized pattern of endocrine expression. Changes in hormone concentrations of dosed homosexually paired males, when present, were in the same direction but at a higher magnitude than those in heterosexual dosed males. Dosed homosexual males showed decreased testosterone during nest-building and elevated testosterone during incubation when compared with their dosed heterosexual counterparts during the 2008 breeding season. In the same year, exposed males had elevated estradiol during courtship, but had decreased estradiol during other stages in comparison with controls. Dosed females generally showed decreased estradiol and testosterone concentrations compared to controls, albeit not with a clear dose

  16. 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. PMID:25897773

  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. 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.'

  19. Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2-ethylhexyl) phthalate (MEHP).

    PubMed

    Zhai, Wenhui; Huang, Zhigang; Chen, Li; Feng, Cong; Li, Bei; Li, Tanshi

    2014-01-01

    Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L) from 2 h post-fertilization (hpf) to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab) might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8) and thyroid hormone synthesis (TSHβ, NIS and TG). However, the genes encoding proteins involved in TH transport (transthyretin, TTR) was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity. PMID:24658602

  20. Analysis of endocrine disrupting pesticides by capillary GC with mass spectrometric detection.

    PubMed

    Matisová, Eva; Hrouzková, Svetlana

    2012-09-01

    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.

  1. Waterborne exposure to bisphenol F causes thyroid endocrine disruption in zebrafish larvae.

    PubMed

    Huang, Guo-min; Tian, Xiao-feng; Fang, Xue-dong; Ji, Fu-jian

    2016-03-01

    While bisphenol F (BPF) has been frequently detected in various environmental compartments, limited information is available on its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 0.2, 2, 20, and 200 μg/L of BPF from 2 h post-fertilization (hpf) to 144 hpf. The whole-body content of thyroid hormones, thyroid-stimulating hormone (TSH), and transcription of genes belonging to the hypothalamic-pituitary-thyroid (HPT) axis were investigated. BPF exposure resulted in alterations of both T3 and T4 contents, increased the ratios of T3/T4, demonstrating thyroid endocrine disruption. Moreover, TSH content was significantly induced in a concentration-dependent manner after exposure to BPF. The increased gene transcription of dio2 might assist to degrade increased T3 contents. Treatment with BPF also significantly increased transcription of genes involved in thyroid hormone regulation (crh) and synthesis (nis and tg) as a compensatory mechanism for the decrease of T4 contents. However, the gene encoding protein involved in TH transport (ttr) was transcriptionally significantly down-regulated after exposure to BPF. Taken together, these results suggest that BPF alters the transcription of genes involved in the HPT axis as well as changes whole-body contents of thyroid hormones and TSH in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system.

  2. 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

  3. Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease.

    PubMed

    Kopras, Elizabeth; Potluri, Veena; Bermudez, Mei-Ling; Williams, Karin; Belcher, Scott; Kasper, Susan

    2014-04-01

    Development and fate of the stem cell are regulated by extrinsic signals from the environment. Endocrine-disrupting chemicals which perturb hormonal signaling in utero and during early childhood may cause deregulation of multiple developmental processes, ranging from breakdown of stem cell niche architecture, developmental reprograming and altered stem cell fate to impaired organ and gonad development and sexual differentiation. Therefore, study of the environmental effects on stem cell integrity and normal development is a new and emerging focus for developmental biologists and cell toxicologists. When combined with new human and mouse stem cell-based models, stem cell differentiation dynamics can be studied in more biologically relevant ways. In this study, we review the current status of our understanding of the molecular mechanisms by which endocrine disruptors alter embryonic stem cell and adult stem/progenitor cell fate, organ development, cancer stem cell activity, and tumorigenesis.

  4. 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. PMID:27521771

  5. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens.

    PubMed

    Boberg, Julie; Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Hadrup, Niels; Berthelsen, Line; Elleby, Anders; Kiersgaard, Maria; Vinggaard, Anne Marie; Hass, Ulla; Nellemann, Christine

    2013-09-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based.

  6. Environmental exposure to organophosphate pesticides: assessment of endocrine disruption and hepatotoxicity in pregnant women.

    PubMed

    Cecchi, A; Rovedatti, M G; Sabino, G; Magnarelli, G G

    2012-06-01

    In utero exposure is the first point of contact with environmental xenobiotics that may affect the maternal-placental-fetal balance. Considering that maternal pathophysiological changes affect intrauterine development, this pilot study was conducted to address how environmental exposure to organophosphate pesticides (OPs) during pregnancy may contribute to maternal endocrine disruption and disturbed hepatic function. A prospective study was carried out with pregnant women (n=97) living in a rural area of the Rio Negro province where OPs are intensively applied throughout 6 months of the year. Blood samples were obtained and biomarkers of OPs exposure (cholinesterases and β-glucuronidase), cortisol (CT) and progesterone (PG) levels, as well as glycemia, were determined. Parameters of liver injury were assayed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT); liver function was assayed by measuring albumin. Biomonitoring carried out during the pre-spraying period (PreS) and spraying period (SP) showed that the population studied was exposed to OPs, proven by the fact that plasma (PCh) and erythrocyte cholinesterase (AChE) decreased very significantly (p<0.01) during SP. CT values increased very significantly (p<0.01) in the first trimester of pregnancy during SP with respect to PreS. Individual values above the upper limit of the CT and PG reference range were found both in PreS and SP. This finding could be associated with changes in hormone metabolism pathways produced by OPs exposure. During the second trimester of pregnancy there were increases in ALT values and the AST/ALT ratio in SP, suggesting subclinical hepatotoxicity. In SP, glycemia was unchanged while albuminemia increased. Although anthropometric newborn parameters and pregnancy alterations were within normal values for the general population, the increase in CT in the maternal compartment may lead to impaired newborn health later in life.

  7. Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

    PubMed Central

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

    2012-01-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  8. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.

    PubMed

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

    2012-06-01

    For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

  9. A GLOBAL PERSPECTIVE ON ENDOCRINE DISRUPTION, WITH COMMENTS ON THE US EXPERIENCE

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. The International Programme on Chemical Safety (IPCS) of the World Health Organization has recently reviewed the curren...

  10. 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.

  11. 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.

  12. 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.

  13. Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network.

    PubMed

    Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian

    2016-10-01

    The adverse outcome pathway (AOP) framework could be helpful for chemical risk assessment and mechanistic research. The aim of the present study was to unravel the mechanism of chlordecone-induced endocrine disruption by illustrating the main molecular initiating event (MIE)/perturbations responsible for the observed effects. In silico simulations were performed to predict the MIE(s), and the results pointed to agonistic interaction with estrogen receptors (ERα, ERβ), androgen receptor (AR), cytochrome P450 (CYP19A) by chlordecone. In vivo endocrine disruptions were evaluated in rare minnow (Gobiocypris rarus) exposed to 0.01, 0.1, 1 and 10 μg L(-1) chlordecone from 2 h post-fertilization until sexually mature. In the females, increases of vitellogenin (vtg) mRNA levels in liver and gonad, plasma estradiol (E2), testosterone (T) and E2/T, and renalsomatic index confirmed the role of agonism of ER and CYP19A as MIEs, but the decreased gonadosomatic index, degenerated ovaries as well as the feed-forward response pointed to other potential but important MIEs and corresponding AOPs. In the males, increased E2/T ratio, increased testis vtg mRNA levels and occurrence of intersex confirmed the roles of agonism of ERα and CYP19A as main MIEs in chlordecone-induced endocrine disruptions. Our results also fetches out the limit of AOPs in predicting the adverse outcomes and explaining the mechanism of chemicals at present, thus reflected a critical need for expanding AOPs and AOP network before using it in chemical risk assessment. PMID:27448318

  14. 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.

  15. 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.

  16. 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

  17. Assessment of the endocrine-disrupting effects of short-chain chlorinated paraffins in in vitro models.

    PubMed

    Zhang, Quan; Wang, Jinghua; Zhu, Jianqiang; Liu, Jing; Zhang, Jianyun; Zhao, Meirong

    2016-09-01

    Short-chain chlorinated paraffins (SCCPs), which are candidate persistent organic pollutants (POPs) according to the Stockholm Convention, are of great concern because of their persistent bioaccumulation, long-range transport and potential adverse health effects. However, data on the endocrine-disrupting effects of SCCPs remain scarce. In this study, we first adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of three SCCPs (C10-40.40%, C10-66.10% and C11-43.20%) via receptor mediated and non-receptor mediated pathway. The dual-luciferase reporter gene assay revealed that all test chemicals significantly induced estrogenic effects, which were mediated by estrogen receptor α (ERα), in the following order: C11-43.20%>C10-66.10%>C10-40.40%. Notably, C10-40.40% and C10-66.10% also demonstrated remarkable anti-estrogenic activities. Only C11-43.20% showed glucocorticoid receptor-mediated (GR) antagonistic activity, with a RIC20 value of 2.6×10(-8)mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor β (TRβ). Meanwhile, all test SCCPs stimulated the secretion of 17β-estradiol (E2). Both C10-66.10% and C11-43.20% increased the production of cortisol at a high level in H295R cell lines. In order to explore the possible mechanism underlying the endocrine-disrupting effects of SCCPs through the non-receptor pathway, the mRNA levels of 9 steroidogenic genes were measured by real-time polymerase chain reaction (RT-PCR). StAR, 17βHSD, CYP11A1, CYP11B1, CYP19 and CYP21 were upregulated in a concentration-dependent manner by all chemicals. The data provided here emphasized that comprehensive assessments of the health and ecological risks of emerging contaminants, such as SCCPs, are of great concern and should be investigated further. PMID:27208783

  18. Reprint of "In silico methods in the discovery of endocrine disrupting chemicals".

    PubMed

    Vuorinen, Anna; Odermatt, Alex; Schuster, Daniela

    2015-09-01

    The prevalence of sex hormone-dependent cancers, reproductive problems, obesity, and cardiovascular complications has risen especially in the Western world. It has been suggested, that the exposure to various endocrine disrupting chemicals (EDCs) contributes to the development and progression of these diseases. EDCs can interfere with various proteins: nuclear steroid hormone receptors, such as estrogen-, androgen-, glucocorticoid- and mineralocorticoid receptors (ER, AR, GR, MR), and enzymes that are involved in steroid hormone synthesis and metabolism, for example hydroxysteroid dehydrogenases (HSDs). Numerous chemicals are known as endocrine disruptors. However, the mechanism of action for most of these EDCs is still unknown. It is exhaustive and time consuming to test in vitro all chemicals - potential EDCs - used in industry, agriculture or as food preservatives against their effects on the endocrine system. Computational methods, such as virtual screening, quantitative structure activity relationships and docking, are already well recognized and used in drug development. The same methods could also aid the research on EDCs. So far, the computational methods in the search of EDCs have been retrospective. There are, however, some prospective studies reporting the use of in silico methods: five studies reporting the identification of previously unknown 17β-HSD3 inhibitors, MR agonists, and ER antagonists/agonists. This review provides an overview of case studies and in silico methods that are used in the search of EDCs. This article is part of a Special Issue entitled 'CSR 2013'.

  19. Reprint of "In silico methods in the discovery of endocrine disrupting chemicals".

    PubMed

    Vuorinen, Anna; Odermatt, Alex; Schuster, Daniela

    2015-09-01

    The prevalence of sex hormone-dependent cancers, reproductive problems, obesity, and cardiovascular complications has risen especially in the Western world. It has been suggested, that the exposure to various endocrine disrupting chemicals (EDCs) contributes to the development and progression of these diseases. EDCs can interfere with various proteins: nuclear steroid hormone receptors, such as estrogen-, androgen-, glucocorticoid- and mineralocorticoid receptors (ER, AR, GR, MR), and enzymes that are involved in steroid hormone synthesis and metabolism, for example hydroxysteroid dehydrogenases (HSDs). Numerous chemicals are known as endocrine disruptors. However, the mechanism of action for most of these EDCs is still unknown. It is exhaustive and time consuming to test in vitro all chemicals - potential EDCs - used in industry, agriculture or as food preservatives against their effects on the endocrine system. Computational methods, such as virtual screening, quantitative structure activity relationships and docking, are already well recognized and used in drug development. The same methods could also aid the research on EDCs. So far, the computational methods in the search of EDCs have been retrospective. There are, however, some prospective studies reporting the use of in silico methods: five studies reporting the identification of previously unknown 17β-HSD3 inhibitors, MR agonists, and ER antagonists/agonists. This review provides an overview of case studies and in silico methods that are used in the search of EDCs. This article is part of a Special Issue entitled 'CSR 2013'. PMID:26291836

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

    PubMed

    Montes-Grajales, Diana; Olivero-Verbel, Jesus

    2015-01-01

    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.

  1. Neuroendocrine impacts of endocrine-disrupting chemicals in birds: life stage and species sensitivities.

    PubMed

    Ottinger, Mary Ann; Dean, Karen M

    2011-01-01

    Assessing potential risk associated with exposure to endocrine-disrupting chemicals (EDC) has been difficult due to species specific variation in vulnerability and to both short- and long-term effects produced by EDC. In precocial birds, embryonic exposure to EDC impacts sexual differentiation of neuroendocrine systems and behavior. Often, detectable nonlethal effects of EDC diminish as the organism matures such that the chronic impact of EDC may appear relatively innocuous by the time an individual is sexually mature. In addition, studies have not addressed lifetime effects of EDC exposure on birds. Consequently, it is difficult to assess chronic effects of nonlethal exposure on the fitness of an individual and whether there is a potential risk to a wild population. Assessing behavioral and neuroendocrine consequences of exposure is complicated by individual and species variation in sensitivity as well as exposure to complex mixtures. Our studies are designed to examine effects of individual EDC administered to the embryo as well as in a multigenerational dietary study in which birds received low doses of the pesticide methoxychlor (MXC). The influence of dietary MXC exposure was also compared between Japanese quail and northern bobwhite quail. The effects of dietary exposures to 0.5, 5, or 10 ppm that are relatively environmentally low were determined. The selection of these doses was to mimic levels that might be encountered in the field and higher doses that might potentially reveal effects of exposure at relatively low exposures. These doses were also based on the regulations by the U.S. Environmental Protection Agency that mandate a limit 0.04 ppm MXC in drinking water, with a limit of no more than 0.05 ppm in water that children drink. Further there is a limit of 1-100 ppm for crops and other food for human and livestock consumption; bottled water has a 0.1 ppm limit for MXC content. Our data are discussed in the context of applicability of toxicological

  2. 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

  3. 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.

  4. 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. PMID:24001430

  5. 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. PMID:23685399

  6. Impact of endocrine-disrupting chemicals on reproductive function in zebrafish (Danio rerio).

    PubMed

    Huang, Y; Wang, X L; Zhang, J W; Wu, K S

    2015-02-01

    The prevalence of endocrine-disrupting chemicals (EDCs) in the aquatic environment has been associated with the wide detection of alterations in the development and physiology of vertebrates. Zebrafish, as a model species, has been extensively used in toxicological research. In this review, we focus on recent published evidence of the harmful effects of EDCs on reproductive function in zebrafish, including skewed sex ratio, immature gonads, diminished sexual behaviour, decreased sperm count, reduced spawning and fertilization. These impairments mostly result from disruption to sex-steroid hormones induced by endocrine disruptors. We also discuss other effects of exposure to EDCs. In EDC exposure research, despite incomplete assessments of altered gonad histopathology and sexual behaviour, these present potential effective biomarkers or pathways for evaluating the reproductive function in zebrafish on EDC exposure. To date, the pernicious effects of some EDCs on the reproductive performance in laboratory zebrafish are well understood; however, similar alterations remain for further determination in wild-type fish and more kinds of EDCs. More studies should be performed under established scientific regulatory criteria to investigate the impact of EDCs on reproduction in zebrafish. Moreover, further research is required to explain the definite mechanism of sexual differentiation, which helps in understanding the shift of sexual phenotype with EDC exposure. PMID:25529055

  7. Application of Ecotoxicogenomics for Studying Endocrine Disruption in Vertebrates and Invertebrates

    PubMed Central

    Iguchi, Taisen; Watanabe, Hajime; Katsu, Yoshinao

    2006-01-01

    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. PMID:16818254

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

    PubMed

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

    2015-03-01

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

  9. 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.

  10. 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

  11. Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals.

    PubMed

    Kjærstad, Mia B; Taxvig, Camilla; Nellemann, Christine; Vinggaard, Anne Marie; Andersen, Helle R

    2010-12-01

    Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole~miconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17β-estradiol (miconazole>econazole~ketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole∼tebuconazole>propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity.

  12. 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

  13. Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae.

    PubMed

    Chen, Qi; Yu, Liqin; Yang, Lihua; Zhou, Bingsheng

    2012-04-01

    Polybrominated diphenyl ethers (PBDEs) have the potential to disturb the thyroid endocrine system, but little is known of such effects or underlying mechanisms of BDE-209 in fish. In the present study, bioconcentration and metabolism of BDE-209 were investigated in zebrafish embryos exposed at concentrations of 0, 0.08, 0.38 and 1.92 mg/L in water until 14 days post-fertilization (dpf). Chemical analysis revealed that BDE-209 was accumulated in zebrafish larvae, while also metabolic products were detected, including octa- and nona-BDEs, with nona-BDEs being predominant. The exposure resulted in alterations of both triiodothyronine (T3) and thyroxine (T4) levels, indicating thyroid endocrine disruption. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (CRH) and thyroid-stimulating hormone (TSHβ) were transcriptionally significantly up-regulated. Genes involved in thyroid development (Pax8 and Nkx2.1) and synthesis (sodium/iodide symporter, NIS, thyroglobulin, TG) were also transcriptionally up-regulated. Up-regulation of mRNA for thyronine deiodinase (Dio1 and Dio2) and thyroid hormone receptors (TRα and TRβ) was also observed. However, the genes encoding proteins involved in TH transport (transthyretin, TTR) and metabolism (uridinediphosphate-glucuronosyl-transferase, UGT1ab) were transcriptionally significantly down-regulated. Furthermore, protein synthesis of TG was significantly up-regulated, while that of TTR was significantly reduced. These results suggest that the hypothalamic-pituitary-thyroid axis can be evaluated to determine thyroid endocrine disruption by BDE-209 in developing zebrafish larvae. PMID:22307006

  14. Endocrine disruption effects of p,p'-DDE on juvenile zebrafish.

    PubMed

    Monteiro, Marta Sofia; Pavlaki, Maria; Faustino, Augusto; Rêma, Alexandra; Franchi, Mariana; Gediel, Letícia; Loureiro, Susana; Domingues, Inês; Rendón von Osten, Jaime; Mortágua Velho Maia Soares, Amadeu

    2015-03-01

    The persistent organic pollutant p,p'-DDE, the major metabolite of the insecticide DDT, has displayed evidence of endocrine disruption through the inhibition of androgen binding to androgen receptors in different species. Although p,p'-DDE was continuously detected in wild fish with abnormal gonad development such as intersex, little is known about its mode of action during gonad development in fish. To elucidate the potential endocrine effects of this pollutant in zebrafish (Danio rerio), juveniles (30 days post hatch) were exposed to p,p'-DDE during the critical window of sexual differentiation. Fish were exposed to sublethal concentrations ranging from 0.01 to 20 µg l(-1) over 14 days and were maintained in control water for an additional 4 months. As core endpoints, the vitellogenin (vtg) concentration was measured at the end of exposure, and sex ratio and the gonadosomatic index were assessed 4 months after the end of exposure. An increase in vtg production in whole body homogenate was observed in fish exposed to 0.2 and 2.0 µg l(-1) p,p'-DDE. No significant differences were displayed in morphological parameters such as the gonadosomatic index of males and females or sex ratio. However, exposed females presented histopathological changes that include the reduction of the number of mature oocytes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption in zebrafish exposed during gonad differentiation of juvenile specimens. Furthermore, vtg induction by p,p'-DDE in juvenile zebrafish arises as a predictive marker for adverse effects of this DDT metabolite on the ovarian function of female zebrafish. PMID:24832558

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

    PubMed

    Feng, Yixing; Zhang, Pin; 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

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

    PubMed Central

    Rotroff, Daniel M.; Dix, David J.; Houck, Keith A.; Knudsen, Thomas B.; Martin, Matthew T.; McLaurin, Keith W.; Reif, David M.; Crofton, Kevin M.; Singh, Amar V.; Xia, Menghang; Huang, Ruili

    2012-01-01

    Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S). Objective: In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays. Method: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance. Results: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data. Conclusions: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays. PMID:23052129

  17. 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

  18. 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.

  19. 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.

  20. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    PubMed

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. PMID:26057477

  1. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    PubMed

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.

  2. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site.

    PubMed

    Kassotis, Christopher D; Iwanowicz, Luke R; Akob, Denise M; Cozzarelli, Isabelle M; Mumford, Adam C; Orem, William H; Nagel, Susan C

    2016-07-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby. PMID:27073166

  3. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    USGS Publications Warehouse

    Kassotis, Christopher D.; Iwanowicz, Luke; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam; Orem, William H.; Nagel, Susan C.

    2016-01-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

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

    PubMed

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

    2009-01-01

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

  5. Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine-Disrupting Substances in the European Union

    PubMed Central

    Slama, Rémy; Bourguignon, Jean-Pierre; Demeneix, Barbara; Ivell, Richard; Panzica, Giancarlo; Kortenkamp, Andreas; Zoeller, R. Thomas

    2016-01-01

    , Kortenkamp A, Zoeller RT. 2016. Scientific issues relevant to setting regulatory criteria to identify endocrine disrupting substances in the European Union. Environ Health Perspect 124:1497–1503; http://dx.doi.org/10.1289/EHP217 PMID:27108591

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

    PubMed Central

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

    2013-01-01

    Endocrine-disruptor compounds (EDCs) can mimic natural hormones and produce adverse effects in the endocrine functions by interacting with estrogen receptors. EDCs include both natural and synthetic chemicals, such as hormones, personal care products, surfactants, and flame retardants, among others. EDCs are characterised by their ubiquitous presence at trace-level concentrations and their wide diversity. Since the discovery of the adverse effects of these pollutants on wildlife and human health, analytical methods have been developed for their qualitative and quantitative determination. In particular, mass-based analytical methods show excellent sensitivity and precision for their quantification. This paper reviews recently published analytical methodologies for the sample preparation and for the determination of these compounds in different environmental and biological matrices by liquid chromatography coupled with mass spectrometry. The various sample preparation techniques are compared and discussed. In addition, recent developments and advances in this field are presented. PMID:23738329

  7. 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

  8. 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.

  9. 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

  10. Intersex in Scrobicularia plana: transcriptomic analysis reveals novel genes involved in endocrine disruption.

    PubMed

    Ciocan, Corina M; Cubero-Leon, Elena; Peck, Mika R; Langston, William J; Pope, Nick; Minier, Christophe; Rotchell, Jeanette M

    2012-12-01

    Intersex, the appearance of female characteristics in male gonads, has been identified in a wide range of aquatic species worldwide, yet the underpinning molecular etiology remains uncharacterized. The presence of intersex has been shown to be a widespread phenomenon in bivalve, S. plana, populations from the southwest coast of the U.K., as well as inducible in an experimental exposure regime using endocrine disrupting compounds (EDCs). Herein, we use the suppressive subtractive hybridization approach to isolate differentially expressed transcripts in S. plana males exhibiting intersex. Transcripts involved in cell signaling, cell cycle control, energy production/metabolism, microtubule assembly, and sperm physiology are all highlighted as differentially expressed in intersex male clams. These provide both an insight into the molecular mechanisms of action involved in the development of intersex, as well as facilitating potential molecular-level "early warning" biomarkers of the condition.

  11. Developmental Toxicity of Endocrine Disrupters Bisphenol A and Vinclozolin in a Terrestrial Isopod

    PubMed Central

    van Gestel, C. A. M.; Soares, A. M. V. M.

    2010-01-01

    Studies of the effects of endocrine-disrupting compounds (EDCs) on invertebrates are still largely underrepresented. This work aims to fill this gap by assessing the effects of bisphenol A (BPA) and vinclozolin (Vz) on the terrestrial isopod Porcellio scaber (common rough woodlouse). Male adult and sexually undifferentiated juvenile woodlice were exposed to the toxicants. Effects on molting regime and growth were investigated independently for males and female woodlice after sexual differentiation. Both chemicals elicited developmental toxicity to P. scaber by causing overall decreased growth. Nevertheless, BPA induced molting, whereas Vz delayed it. Although the LC50 values for juvenile and adult survival were fairly similar, juvenile woodlice showed an increased chronic sensitivity to both chemicals, and female woodlice were most the sensitive to BPA. We recommend the use of adults, juveniles, female, and male woodlice, as well as a large range of toxicant concentrations, to provide valuable information regarding differential dose responses, effects, and threshold values for EDCs. PMID:20148245

  12. Development of an in vitro Ovary Culture System to Evaluate Endocrine Disruption in Wood Frog Tadpoles.

    PubMed

    Vu, Maria; Navarro-Martín, Laia; Gutierrez-Villagomez, Juan Manuel; Trudeau, Vance L

    2015-01-01

    Gonad-mesonephros complexes from wood frog (Lithobates sylvaticus) tadpoles were incubated in vitro for 1 wk to examine direct effects of naphthenic acids (NA) and 17α-ethinylestradiol (EE2) on ovarian differentiation. Histological images reveal successful preservation of gonadal integrity where cultured oocytes exhibited no significant differences in diameters and areas compared to uncultured conditions. Ovaries exposed to 10 μg/L 17α-EE2 contained oocytes with significantly advanced atresia and diminished areas and diameters, indicating a degree of ovarian regression. A significant reduction in oocyte area was observed in ovaries exposed to 3 mg/L of a commercial extract of petroleum-derived NA. This novel approach has applications for screening direct effects of endocrine-disrupting chemicals on gonadal function in tadpoles. PMID:26383587

  13. Generation and characterization of gsuα:EGFP transgenic zebrafish for evaluating endocrine-disrupting effects.

    PubMed

    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), KClO4, 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

    2016-01-01

    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

  18. Generation and characterization of gsuα:EGFP transgenic zebrafish for evaluating endocrine-disrupting effects.

    PubMed

    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), KClO4, 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. PMID:24747804

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

    PubMed

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

    2009-12-15

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

  20. Histopathology as a tool for the evaluation of endocrine disruption in zebrafish (Danio rerio).

    PubMed

    van der Ven, Leo T M; Wester, Piet W; Vos, Jeff G

    2003-04-01

    The importance of histology as a tool in the evaluation of endocrine disruption in fish depends on the choice and interpretation of appropriate endpoints, as is illustrated by the analysis of the effects of exposure to the estrogen 17beta-estradiol (E2) and the nonaromatizable androgen 17-methyldihydrotestosterone (MDHT). The E2 led to the disappearance of vitellogenic oocytes in the ovary and an increased area of relatively large, eosinophilic cells in the testis, which were identified as spermatogonia under high-power magnification; this was a relative increase, as was shown by histomorphometry, because of a decreased size of spermatogenic cysts and a relative decrease of spermatocyte cysts. The E2 also induced an accumulation of acidophilic fluid in vessels and interstitial spaces, confirmed by immunohistochemistry as vitellogenin, and basophilia in the liver also associated with the production of vitellogenin. The MDHT induced activation of Sertoli cells in the testis and a decreased presence of vitellogenic oocytes and a reduced growth of previtellogenic oocytes in the ovary. These observations indicate the advantages of examining multiple organ systems on whole-body sections and the application of adequate magnifications. Inclusion of additional techniques such as morphometry and immunohistochemistry is valuable to further uncover insidious effects of endocrine disruptors. PMID:12685728

  1. 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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2009-10-30

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

  4. Removal of endocrine-disrupting chemicals in activated sludge treatment works.

    PubMed

    Johnson, A C; Sumpter, J P

    2001-12-15

    The release of endocrine-disrupting chemicals into the aquatic environment has raised the awareness of the central role played by sewage treatment in lowland water quality. This review focuses on the activated sludge process, which is commonly used to treat sewage in large towns and cities and which successfully removes the bulk of the organic compounds that enter the works. However, not all compounds are completely broken down or converted to biomass. For example, the estrogenic alkylphenols and steroid estrogens found in effluent are the breakdown products of incomplete breakdown of their respective parent compounds. Batch microcosm studies have indicated that estrone, ethinylestradiol, and alkylphenols will not be completely eliminated in activated sludge over typical treatment times. Field data suggest that the activated sludge treatment process can consistently remove over 85% of estradiol, estriol, and ethinylestradiol. The removal performance for estrone appears to be less and is more variable. Because of its relatively high hydrophobicity, the accumulation of alkylphenol in sludge has been observed. Although it has not been examined, accumulation of ethinylestradiol in sludge is a possibility due to its recalcitrance and hydrophobicity. A comparison between the concentrations of some of the major endocrine-active chemicals in effluents and their biological potencies has been made, to direct attention to the chemicals of most concern. While water purification techniques such as UV or activated charcoal could significantly remove these microorganic contaminants, the high costs involved suggest that research into the potential for treatment optimization should receive more attention. PMID:11775141

  5. Health Disparities in Endocrine Disorders: Biological, Clinical, and Nonclinical Factors—An Endocrine Society Scientific Statement

    PubMed Central

    Brown, Arleen; Cauley, Jane A.; Chin, Marshall H.; Gary-Webb, Tiffany L.; Kim, Catherine; Sosa, Julie Ann; Sumner, Anne E.; Anton, Blair

    2012-01-01

    Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs. Participants in Development of Scientific Statement: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U.S. population-based studies. Search strategies combining Medical Subject Headings terms and keyword terms and phrases defined two concepts: 1) racial, ethnic, and sex differences including specific populations; and 2) the specific endocrine disorder or condition. The search identified systematic reviews, meta-analyses, large cohort and population-based studies, and original studies focusing on the prevalence and determinants of disparities in endocrine disorders. Consensus Process: The writing group focused on population differences in the highly prevalent endocrine diseases of type 2 diabetes mellitus and related conditions (prediabetes and diabetic complications), gestational diabetes, metabolic syndrome with a focus on obesity and dyslipidemia, thyroid disorders, osteoporosis, and vitamin D deficiency. Authors reviewed and synthesized evidence in their areas of expertise. The final statement incorporated responses to several levels of review: 1) comments of the SSTF and the

  6. 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.

  7. 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.

  8. 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. PMID:22039834

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

    PubMed

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

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. PMID:24713117

  10. 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.

  11. 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.

  12. Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides.

    PubMed

    Jacobsen, Pernille Rosenskjold; Axelstad, Marta; Boberg, Julie; Isling, Louise Krag; Christiansen, Sofie; Mandrup, Karen Riiber; Berthelsen, Line Olrik; Vinggaard, Anne Marie; Hass, Ulla

    2012-09-01

    There is growing concern of permanent damage to the endocrine and nervous systems after developmental exposure to endocrine disrupting chemicals. In this study the permanent reproductive and neurobehavioral effects of combined exposure to five endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, were examined. Pregnant and lactating rat dams were dosed with a mixture of the five pesticides at three different doses, or with the individual pesticides at one of two doses. Adverse effects were observed in young and adult male offspring from the group exposed to the highest dose of the mixture. These included reduced prostate and epididymis weights, increased testes weights, altered prostate histopathology, increased density of mammary glands, reduced sperm counts, and decreased spatial learning. As no significant effects were seen following single compound exposure at the doses included in the highest mixture dose, these results indicate cumulative adverse effects of the pesticide mixture. PMID:22677472

  13. 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.

  14. 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

  15. 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...

  16. 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...

  17. 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,...

  18. 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...

  19. 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...

  20. Accumulation of di(2-ethylhexyl) phthalate causes endocrine-disruptive effects in marine medaka (Oryzias melastigma) embryos.

    PubMed

    Ye, Ting; Kang, Mei; Huang, Qiansheng; Fang, Chao; Chen, Yajie; Liu, Liangpo; Dong, Sijun

    2016-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is extensively distributed in marine environments. However, limited research on the toxicological and molecular effects of DEHP on marine organisms has been conducted. Our study investigated the accumulation, elimination, and endocrine-disruptive effects of DEHP on embryonic marine medaka (Oryzias melastigma). The medaka embryos were continuously exposed to DEHP (0.01, 0.1, and 1 mg/L) or 17β-estradiol (E2, 0.01 mg/L) until hatching, and the newly hatched larvae were then transferred to clean sea water for 12 days of depuration. DEHP and E2 appeared to have no significant effects on the mortality and hatching rates of medaka embryos, but E2 exposure significantly delayed the hatching. Significantly higher DEHP embryonic burdens were detected in the group treated with higher DEHP (0.1 and 1 mg/L) at 10 dpf (days post fertilization). The recovered larvae showed an elimination tendency of DEHP during the recovery period. DEHP had no significant effects on the transcriptional responses of endocrine-disrupting biomarker genes in the 3-dpf embryos. Treatment with 0.1 and 1 mg/L DEHP elicited a significant induction of transcriptional responses of ER, PPAR, and the CYP19 genes in a concentration-dependent manner at 10 dpf, indicating endocrine disruption may be due to bioaccumulation of DEHP. With the elimination of DEHP during the depuration period, all of the effects on these genes showed no significant effects. However, 0.1 mg/L E2 significantly affected the expression of ER, PPAR, and the CYP19 genes in the exposed embryos at both 3 and 10 dpf and recovered larvae. Therefore, these results demonstrate that accumulation of DEHP caused endocrine disruption in medaka embryos and that recovery in clean sea water may weaken the endocrine-disrupting effects. PMID:25066029

  1. 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. PMID:26587739

  2. 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.

  3. 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.

    PubMed

    Stoker, T E; Parks, L G; Gray, L E; Cooper, R L

    2000-03-01

    Puberty in mammalian species is a period of rapid interactive endocrine and morphological changes. Therefore, it is not surprising that exposure to a variety of pharmaceutical and environmental compounds has been shown to dramatically alter pubertal development. This concern was recognized by the Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) that acknowledged the need for the development and standardization of a protocol for the assessment of the impact of endocrine-disrupting compounds (EDC) in the pubertal male and recommended inclusion of an assay of this type as an alternative test in the EDSTAC tier one screen (EPA, 98). The pubertal male protocol was designed to detect alterations of pubertal development, thyroid function, and hypothalamic-pituitary-gonadal (HPG) system peripubertal maturation. In this protocol, intact 23-day-old weanling male rats are exposed to the test substance for 30 days during which pubertal indices are measured. After necropsy, reproductive and thyroid tissues are weighed and evaluated histologically and serum taken for hormone analysis. The purpose of this review was to examine the available literature on pubertal development in the male rat and evaluate the efficacy of the proposed protocol for identifying endocrine-disrupting chemicals. The existing data indicate that this assessment of puberty in the male rat is a simple and effective method to detect the EDC activity of pesticides and toxic substances.

  4. TRIENNIAL REPRODUCTION SYMPOSIUM: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A.

    PubMed

    Vom Saal, F S

    2016-07-01

    During critical periods in fetal life, there is an increased vulnerability to perturbations in endocrine function due to environmental factors. Small shifts in concentrations of hormones that regulate the differentiation of organs, such as estradiol and testosterone, can have permanent effects on morphology, enzymatic activity, and hormone receptors in tissues as well as neurobehavioral effects. These changes can lead to effects throughout life, including impacting the risk for various diseases (referred to as the Developmental Origins of Adult Health and Disease hypothesis). The intrauterine position phenomenon concerns the consequence for fetuses of randomly implanting next to embryos of the same or opposite sex. An intrauterine position next to males vs. females results in small differences in serum testosterone and estradiol during fetal life that are associated with marked effects on life history (such as lifetime fecundity) in both males and females born in litters (mice, rats, gerbils, rabbits, and swine) as well as human twins. Research with mice subsequently demonstrated that a very small experimental change in fetal serum estradiol levels altered organogenesis and caused permanent changes in organ function. Taken together, these findings led to the hypothesis that environmental chemicals that mimic or antagonize hormone action (e.g., endocrine disrupting chemicals) could also be causing harm at very low exposures (the "low dose" hypothesis) within the range of exposure of humans, domesticated animals, and wildlife. There is now extensive evidence from experimental laboratory animals, sheep, and humans that fetal exposure to very low (presumably safe) doses of the endocrine disrupting chemical bisphenol A (BPA), which exhibits estrogenic activity, can cause permanent changes that can increase the risk of a wide array of diseases. The reasons that federal regulatory agencies are ignoring the massive literature showing adverse effects of BPA and other

  5. Thyroid disrupting chemicals in plastic additives and thyroid health.

    PubMed

    Andra, Syam S; Makris, Konstantinos C

    2012-01-01

    The globally escalating thyroid nodule incidence rates may be only partially ascribed to better diagnostics, allowing for the assessment of environmental risk factors on thyroid disease. Endocrine disruptors or thyroid-disrupting chemicals (TDC) like bisphenol A, phthalates, and polybrominated diphenyl ethers are widely used as plastic additives in consumer products. This comprehensive review studied the magnitude and uncertainty of TDC exposures and their effects on thyroid hormones for sensitive subpopulation groups like pregnant women, infants, and children. Our findings qualitatively suggest the mixed, significant (α = 0.05) TDC associations with natural thyroid hormones (positive or negative sign). Future studies should undertake systematic meta-analyses to elucidate pooled TDC effect estimates on thyroid health indicators and outcomes. PMID:22690712

  6. First evidence of endocrine disruption in feral carp from the Ebro River.

    PubMed

    Lavado, Ramón; Thibaut, Rémi; Raldúa, Demetrio; Martín, Rebeca; Porte, Cinta

    2004-04-15

    Feral carps (Cyprinus carpio) were collected in spring 2001 from five sites along the lower course of Ebro River (Spain) with the aim of investigating the existence of endocrine-disrupting effects. Several findings (low gonadosomatic index (GSI), plasmatic vitellogenin (VTG), depressed levels of testosterone, and histological alterations in gonads) detected in male carps downstream of Zaragoza's sewage treatment plant (STP) strongly suggest that the concentration of sewage effluent in the area is a major causal factor leading to the detected estrogenic effects. Important alterations (viz. delayed maturation in females, indications of arrested spermatogenesis in males) were detected in carps from Flix, a heavily industrialized area. Low ovarian P-450 aromatase and reduced glucuronidation of testosterone and estradiol in males were observed in Zaragoza and Canal Imperial de Aragón-an agricultural area-which suggest decreased estrogen synthesis, and possibly, reduced sex hormone excretion in those organisms. These results were related to some in vitro assays aimed to assess the interference of model compounds (atrazin, vinclozolin, diuron, pp'-DDE, dicofol, triphenyltin, nonylphenol, and fenarimol) with the glucuronidation of testosterone and estradiol by liver microsomal fractions. The fungicide fenarimol (10-20 microM) and nonylphenol (50 microM) were found to significantly inhibit (20%) both activities at relatively low doses. Overall, this work provides the first evidence of the existence of significant alterations of the endocrine system of carps from the medium-low course of the Ebro River and demonstrates the ability of several chemicals to modulate the inactivation of endogenous steroids.

  7. Endocrine disruption by di-(2-ethylhexyl)-phthalate in Chinese rare minnow (Gobiocypris rarus).

    PubMed

    Wang, Xiaofang; Yang, Yuanjin; Zhang, Liping; Ma, Yanbo; Han, Jian; Yang, Lihua; Zhou, Bingsheng

    2013-08-01

    Great concern has been raised over the potential impact of environmental contaminants on fish populations that inhabit the Three Gorge Reservoir. The present study investigated the endocrine-disrupting effects of di-(2-ethylhexyl)-phthalate (DEHP) on the Chinese rare minnow (Gobiocypris rarus), an endemic fish distributed in upstream waters in the Yangtze River. Adult rare minnow were exposed to environmentally relevant concentrations of DEHP (0 µg/L, 3.6 µg/L, 12.8 µg/L, 39.4 µg/L, and 117.6 µg/L) for a 21-d period. Then, concentrations of sex hormones in the plasma and relative transcription of various associated genes were measured in the hypothalamic-pituitary-gonadal (HPG) axis and liver of the fish. Exposure to DEHP resulted in greater circulating concentrations of testosterone (T) and lower concentrations of estradiol (E2), which were accompanied by upregulation of Cyp17 mRNA and downregulation of Cyp19a mRNA in the gonads of females. In males, increases of T and E2 levels were consistent with upregulation of Cyp17 and Cyp19a in the gonads. Furthermore, the T/E2 ratio was increased in females but reduced in males. A significant increase in the levels of hepatic vitellogenin (VTG) gene transcription was observed in both females and males. The present study showed that waterborne exposure to DEHP altered plasma sex hormone levels and modulated gene transcription profiles of associated genes in the HPG axis and liver, occurring mostly at higher concentrations (>39.4 µg/L), which suggests that environmental concentration of DEHP (5.4 µg/L) alone might not disturb the endocrine system of the rare minnow in the TGR.

  8. 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.

  9. 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. PMID:26254073

  10. 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.

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

    PubMed

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

    2007-10-15

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

  12. Detection and evaluation of endocrine-disruption activity in water samples from Portuguese rivers.

    PubMed

    Quirós, Laia; Céspedes, Raquel; Lacorte, Sílvia; Viana, Paula; Raldúa, Demetrio; Barceló, Damià; Piña, Benjamin

    2005-02-01

    Water samples (n = 183) from Portuguese rivers were tested for the presence of endocrine disruptors using the recombinant yeast assay (RYA) combined with chemical identification of compounds having endocrine-disruption properties by liquid chromatography coupled to mass spectrometry. Ten selected locations were sampled monthly for a period of 20 months, from April 2001 to December 2002. More than 90% of samples showed either no detectable or low levels of estrogenicity (<0.1 ng/L of estradiol equivalents). The remaining samples (17 in total, 9.3%) showed estrogenicity values ranging from 0.1 to 1.7 ng/L of estradiol equivalents; only two samples showed values greater than 1 ng/L of estradiol equivalents. Most highly estrogenic samples (13 of 17 samples) originated in five sampling sites clustered in two zones near Porto and Lisbon. Chemical analysis detected alkylphenolic compounds (octyl- and nonylphenol plus nonylphenol ethoxylates) in all samples, albeit at concentrations less than 1 microg/L for each compound in 80% of samples. Total analyte concentration exceeded 10 microg/L in only 10 samples, with all but one of those originating from only two sampling sites. In these two locations, a good correlation was observed between the concentrations of octylphenol, nonylphenol, and to a lesser extent, bisphenol A in the samples and their estrogenicity values as calculated by RYA. We conclude that estrogenic activity can be explained by alkylphenol contamination in only these sites; for the remainder, we propose that pesticides and urban waste may be the main factors responsible for estrogenic contamination. PMID:15719999

  13. Municipal landfill leachate-induced testicular oxidative damage is associated with biometal accumulation and endocrine disruption in rats.

    PubMed

    Adedara, Isaac A; Awogbindin, Ifeoluwa O; Adesina, Adebayo A; Oyebiyi, Oluwatosin O; Lawal, Tajudeen A; Farombi, Ebenezer O

    2015-01-01

    Improper management of hazardous wastes adversely impacts the environment and the public health. The present study was aimed at investigating the influence of Olushosun municipal landfill leachate (OMLL) from Ojota in the Lagos State of Nigeria on testicular function by assessing the plasma concentrations of reproductive hormones, testicular biometal levels, and antioxidant levels as well as observing the histological alterations in testes and epididymides of rats after exposure to 0, 12.5, and 25% OMLL in drinking water for 7 days. Exposure to OMLL significantly decreased the daily fluid intake, but it resulted in testicular biometal accumulation as follows: lead > cadmium > nickel > iron > copper. Acute exposure to OMLL induced oxidative stress and increased the activities of marker enzymes of testicular function but markedly decreased the circulatory concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, thyroid-stimulating hormone, triiodothyronine, and thyroxine. Testicular and epididymal degeneration with significant decrease in sperm quality and quantity were observed in OMLL-exposed rats. Collectively, the data presented herein indicate that exposure to OMLL-induced testicular dysfunction associated with biometal accumulation and endocrine disruption in rats. If the effects can be extrapolated to humans, OMLL may present significant health implications for individuals exposed to OMLL-contaminated substances. PMID:25179371

  14. Municipal landfill leachate-induced testicular oxidative damage is associated with biometal accumulation and endocrine disruption in rats.

    PubMed

    Adedara, Isaac A; Awogbindin, Ifeoluwa O; Adesina, Adebayo A; Oyebiyi, Oluwatosin O; Lawal, Tajudeen A; Farombi, Ebenezer O

    2015-01-01

    Improper management of hazardous wastes adversely impacts the environment and the public health. The present study was aimed at investigating the influence of Olushosun municipal landfill leachate (OMLL) from Ojota in the Lagos State of Nigeria on testicular function by assessing the plasma concentrations of reproductive hormones, testicular biometal levels, and antioxidant levels as well as observing the histological alterations in testes and epididymides of rats after exposure to 0, 12.5, and 25% OMLL in drinking water for 7 days. Exposure to OMLL significantly decreased the daily fluid intake, but it resulted in testicular biometal accumulation as follows: lead > cadmium > nickel > iron > copper. Acute exposure to OMLL induced oxidative stress and increased the activities of marker enzymes of testicular function but markedly decreased the circulatory concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, thyroid-stimulating hormone, triiodothyronine, and thyroxine. Testicular and epididymal degeneration with significant decrease in sperm quality and quantity were observed in OMLL-exposed rats. Collectively, the data presented herein indicate that exposure to OMLL-induced testicular dysfunction associated with biometal accumulation and endocrine disruption in rats. If the effects can be extrapolated to humans, OMLL may present significant health implications for individuals exposed to OMLL-contaminated substances.

  15. Occupation and occupational exposure to endocrine disrupting chemicals in male breast cancer: a case-control study in Europe

    PubMed Central

    Villeneuve, Sara; Cyr, Diane; Lynge, Elsebeth; Orsi, Laurent; Sabroe, Svend; Merletti, Franco; Gorini, Giuseppe; Morales-Suarez-Varela, Maria; Ahrens, Wolfgang; Baumgardt-Elms, Cornelia; Kaerlev, Linda; Eriksson, Mikael; Hardell, Lennart; Févotte, Joëlle; Guénel, Pascal

    2010-01-01

    Objectives Male breast cancer is a rare disease of largely unknown etiology. Besides genetic or hormone-related risk factors, a large number of environmental chemicals are suspected to play a role in breast cancer. The identification of occupations or occupational exposures associated with an increased incidence of breast cancer in men may help to identify mammary carcinogens in the environment. Methods Occupational risk factors of male breast cancer were investigated in a multi-centre case-control study conducted in 8 European countries, including 104 cases and 1901 controls. Lifetime work history was obtained during in-person interviews. Occupational exposures to endocrine disrupting chemicals (alkylphenolic compounds, phthalates, PCBs and dioxins) were assessed on a case-by-case basis from expert judgment. Results Male breast cancer incidence was more particularly increased in motor vehicle mechanics (OR=2.1, CI 1.0–4.4) with a dose-effect relationship with duration employment. It was also increased in paper makers and painters, and in workers in forestry and logging, health and social work, and manufacture of furniture. The odds ratio for exposure to alkylphenolic compounds above median was 3.8 (CI 1.5–9.5). This association persisted after adjustment for occupational exposures to other environmental estrogens. Conclusion These findings suggest that some environmental chemicals are possible mammary carcinogens. Gasoline, organic petroleum solvents or PAH can be suspected from the consistent elevated risk of male breast cancer observed in motor vehicle mechanics. Endocrine disruptors such as alkylphenolic compounds may play a role in breast cancer. PMID:20798010

  16. An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays.

    PubMed

    Kalayou, Shewit; Ndossi, Doreen; Frizzell, Caroline; Groseth, Per Kristian; Connolly, Lisa; Sørlie, Morten; Verhaegen, Steven; Ropstad, Erik

    2015-03-01

    Evidence that some of the fungal metabolites present in food and feed may act as potential endocrine disruptors is increasing. Enniatin B (ENN B) is among the emerging Fusarium mycotoxins known to contaminate cereals. In this study, the H295R and neonatal porcine Leydig cell (LC) models, and reporter gene assays (RGAs) have been used to investigate the endocrine disrupting activity of ENN B. Aspects of cell viability, cell cycle distribution, hormone production as well as the expression of key steroidogenic genes were assessed using the H295R cell model. Cell viability and hormone production levels were determined in the LC model, while cell viability and steroid hormone nuclear receptor transcriptional activity were measured using the RGAs. ENN B (0.01-100μM) was cytotoxic in the H295R and LC models used; following 48h incubation with 100μM. Flow cytometry analysis showed that ENN B exposure (0.1-25μM) led to an increased proportion of cells in the S phase at higher ENN B doses (>10μM) while cells at G0/G1 phase were reduced. At the receptor level, ENN B (0.00156-15.6μM) did not appear to induce any specific (ant) agonistic responses in reporter gene assays (RGAs), however cell viability was affected at 15.6μM. Measurement of hormone levels in H295R cells revealed that the production of progesterone, testosterone and cortisol in exposed cells were reduced, but the level of estradiol was not significantly affected. There was a general reduction of estradiol and testosterone levels in exposed LC. Only the highest dose (100μM) used had a significant effect, suggesting the observed inhibitory effect is more likely associated with the cytotoxic effect observed at this dose. Gene transcription analysis in H295R cells showed that twelve of the sixteen genes were significantly modulated (p<0.05) by ENN B (10μM) compared to the control. Genes HMGR, StAR, CYP11A, 3βHSD2 and CYP17 were downregulated, whereas the expression of CYP1A1, NR0B1, MC2R, CYP21, CYP11B1, CYP

  17. 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

  18. 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 ...

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

    PubMed

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

    2013-02-01

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

  20. 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.

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

    PubMed

    Brander, Susanne M; Connon, Richard E; He, Guochun; Hobbs, James A; Smalling, Kelly L; Teh, Swee J; White, J Wilson; Werner, Inge; Denison, Michael S; Cherr, Gary N

    2013-01-01

    Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i

  2. Risk Evaluation of Endocrine-Disrupting Chemicals: Effects of Developmental Exposure to Low Doses of Bisphenol A on Behavior and Physiology in Mice (Mus musculus).

    PubMed

    Gioiosa, Laura; Palanza, Paola; Parmigiani, Stefano; 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

  3. 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. PMID:26239693

  4. Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis

    PubMed Central

    Birks, Laura; Casas, Maribel; Garcia, Ana M.; Alexander, Jan; Barros, Henrique; Bergström, Anna; Bonde, Jens Peter; Burdorf, Alex; Costet, Nathalie; Danileviciute, Asta; Eggesbø, Merete; Fernández, Mariana F.; González-Galarzo, M. Carmen; Hanke, Wojciech; Jaddoe, Vincent; Kogevinas, Manolis; Kull, Inger; Lertxundi, Aitana; Melaki, Vasiliki; Andersen, Anne-Marie Nybo; Olea, Nicolás; Polanska, Kinga; Rusconi, Franca; Santa-Marina, Loreto; Santos, Ana Cristina; Vrijkotte, Tanja; Zugna, Daniela; Nieuwenhuijsen, Mark; Cordier, Sylvaine; Vrijheid, Martine

    2016-01-01

    , Hanke W, Jaddoe V, Kogevinas M, Kull I, Lertxundi A, Melaki V, Andersen AM, Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785–1793; http://dx.doi.org/10.1289/EHP208 PMID:27152464

  5. Exposure to Endocrine-Disrupting Chemicals during Pregnancy and Weight at 7 Years of Age: A Multi-pollutant Approach

    PubMed Central

    Agay-Shay, Keren; Martinez, David; Valvi, Damaskini; Garcia-Esteban, Raquel; Basagaña, Xavier; Robinson, Oliver; Casas, Maribel; Sunyer, Jordi

    2015-01-01

    Background Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce weight gain and obesity in children, but the obesogenic effects of mixtures have not been studied. Objective We evaluated the associations between pre- and perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years of age. Methods In pregnant women enrolled in a Spanish birth cohort study between 2004 and 2006, we measured the concentrations of 10 phthalate metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470 children at 7 years, body mass index (BMI) z-scores were calculated, and overweight was defined as BMI > 85th percentile. We estimated associations with EDCs in single-pollutant models and applied principal-component analysis (PCA) on the 27 pollutant concentrations. Results In single-pollutant models, HCB (hexachlorobenzene), βHCH (β-hexachlorocyclohexane), and polychlorinated biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z-scores; and HCB, βHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene) with overweight risk. PCA generated four factors that accounted for 43.4% of the total variance. The organochlorine factor was positively associated with BMI z-scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19, 5.63), and these associations were robust to adjustment for other EDCs. Exposure in the second tertile of the phthalate factor was inversely associated with overweight. Conclusions Prenatal exposure to organochlorines was positively associated with overweight at age 7 years in our study population. Other EDCs exposures did not confound this association. Citation Agay-Shay K, Martinez D, Valvi D, Garcia-Esteban R, Basagaña X, Robinson O, Casas M, Sunyer J, Vrijheid M. 2015. Exposure to endocrine-disrupting

  6. Bioinspired production of magnetic laccase-biotitania particles for the removal of endocrine disrupting chemicals.

    PubMed

    Ardao, Inés; Magnin, Delphine; Agathos, Spiros N

    2015-10-01

    Microbial laccases are powerful enzymes capable of degrading lignin and other recalcitrant compounds including endocrine disrupting chemicals (EDCs). Efficient EDC removal on an industrial scale requires robust, stable, easy to handle and cost-effective immobilized biocatalysts. In this direction, magnetic biocatalysts are attractive due to their easy separation through an external magnetic field. Recently, a bioinspired immobilization technique that mimics the natural biomineralization reactions in diatoms has emerged as a fast and versatile tool for generating robust, cheap, and highly stable (nano) biocatalysts. In this work, bioinspired formation of a biotitania matrix is triggered on the surface of magnetic particles in the presence of laccase in order to produce laccase-biotitania (lac-bioTiO2 ) biocatalysts suitable for environmental applications using a novel, fast and versatile enzyme entrapment technique. Highly active lac-bioTiO2 particles have been produced and the effect of different parameters (enzyme loading, titania precursor concentration, pH, duration of the biotitania formation, and laccase adsorption steps) on the apparent activity yield of these biocatalysts were evaluated, the concentration of the titania precursor being the most influential. The lac-bioTiO2 particles were able to catalyze the removal of bisphenol A, 17α-ethinylestradiol and diclofenac in a mixture of six model EDCs and retained 90% of activity after five reaction cycles and 60% after 10 cycles. PMID:26058804

  7. Distribution and risk assessment of suspected endocrine-disrupting pesticides in creek water of Mumbai, India.

    PubMed

    Singare, Pravin U

    2016-01-15

    The present study deals with the investigation of existing pollution levels and potential ecological risk assessment of endocrine-disrupting organochlorine and organophosphorous pesticide residues in the Vasai Creek water near Mumbai. The average concentration of α- and β-endosulfan (137.75 ng·L(-1)) exceeds the chronic criteria level of α- and β-endosulfan (6.5 ng·L(-1)) set by US EPA for freshwater aquatic organisms. The concentration levels of aldrin (75.31 ng·L(-1)), dieldrin (71.19 ng·L(-1)) and endrin (76.60 ng·L(-1)) was found to exceed the respective criteria levels of <0.13, 65.1, and 61 ng·L(-1) as set by US EPA for protection of freshwater aquatic organisms. In addition, the level of chlorpyrifos (208.77 ng·L(-1)) exceeds the recommended concentration value of <35 ng·L(-1) set by Ministry of Environment of British Colombia. The results of our study give an indication of probable ecotoxicological risk to the marine breeding organisms of creek. PMID:26652143

  8. 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.

  9. 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.

  10. Endocrine disrupting chemicals targeting estrogen receptor signaling: Identification and mechanisms of action

    PubMed Central

    Shanle, Erin K.; Xu, Wei

    2011-01-01

    Many endocrine disrupting chemicals (EDCs) adversely impact estrogen signaling by interacting with two estrogen receptors (ERs): ERα and ERβ. Though the receptors have similar ligand binding and DNA binding domains, ERα and ERβ have some unique properties in terms of ligand selectivity and target gene regulation. EDCs that target ER signaling can modify genomic and non-genomic ER activity through direct interactions with ERs, indirectly through transcription factors like the aryl hydrocarbon receptor (AhR), or through modulation of metabolic enzymes that are critical for normal estrogen synthesis and metabolism. Many EDCs act through multiple mechanisms as exemplified by chemicals that bind both AhR and ER, such as 3-methylcholanthrene. Other EDCs that target ER signaling include phytoestrogens, bisphenolics, and organochlorine pesticides and many alter normal ER signaling through multiple mechanisms. EDCs can also display tissue-selective ER agonist and antagonist activities similar to selective estrogen receptor modulators (SERMs) designed for pharmaceutical use. Thus, biological effects of EDCs need to be carefully interpreted because EDCs can act through complex tissue-selective modulation of ERs and other signaling pathways in vivo. Current requirements by the U.S. Environmental Protection Agency require some in vitro and cell-based assays to identify EDCs that target ER signaling through direct and metabolic mechanisms. Additional assays may be useful screens for identifying EDCs that act through alternative mechanisms prior to further in vivo study. PMID:21053929

  11. 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. PMID:23925178

  12. 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.

  13. 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.

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

    PubMed

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

    2015-02-01

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

  15. 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.

  16. Thyroid hormone signaling in the Xenopus laevis embryo is functional and susceptible to endocrine disruption.

    PubMed

    Fini, J B; Le Mével, S; Palmier, K; Darras, V M; Punzon, I; Richardson, S J; Clerget-Froidevaux, M S; Demeneix, B A

    2012-10-01

    Thyroid hormone (TH) is essential for vertebrate brain development. Most research on TH and neuronal development focuses on late development, mainly the perinatal period in mammals. However, in human infants neuromotor development correlates best with maternal TH levels in the first trimester of pregnancy, suggesting that TH signaling could affect early brain development. Studying TH signaling in early embryogenesis in mammals is experimentally challenging. In contrast, free-living embryos, such as Xenopus laevis, permit physiological experimentation independent of maternal factors. We detailed key elements of TH signaling: ligands, receptors (TR), and deiodinases during early X. laevis development, before embryonic thyroid gland formation. Dynamic profiles for all components were found. Between developmental stages 37 and 41 (~48 h after hatching, coincident with a phase of continuing neurogenesis) significant increases in T(3) levels as well as in mRNA encoding deiodinases and TR occurred. Exposure of embryos at this developmental stage for 24 h to either a TH antagonist, NH-3, or to tetrabromobisphenol A, a flame retardant and known TH disruptor, differentially modulated the expression of a number of TH target genes implicated in neural stem cell function or neural differentiation. Moreover, 24-h exposure to either NH-3 or tetrabromobisphenol A diminished cell proliferation in the brain. Thus, these data show first, that TH signaling exerts regulatory roles in early X. laevis neurogenesis and second, that this period represents a potential window for endocrine disruption. PMID:22968643

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

    USGS Publications Warehouse

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

    2015-01-01

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

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

    PubMed

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

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs)-naproxen and carbamazepine and one endocrine disrupting compound (EDC)-nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. PMID:19350922

  19. Phenolic endocrine-disrupting chemicals and intersex in wild crucian carp from Hun River, China.

    PubMed

    Zheng, Binghui; Liu, Ruizhi; Liu, Yue; Jin, Fen; An, Lihui

    2015-02-01

    This study investigated the concentrations of phenolic endocrine-disrupting chemicals (EDCs) and the incidence of ovo-testis (intersex) in wild crucian carp (Carassius carassius) sampled from the Hun River. As expected, nonylphenols (NP) and bisphenol A (BPA) were detected in all samples, and octylphenols (OP) were found in most samples. NP concentrations ranged from 1290 ± 584 to 3111 ± 2071 ng g(-1) wet weight (ww) in July and from 1132 ± 644 to 1556 ± 587 ng g(-1) ww in November; OP ranged from 6 ± 7 to 46 ± 38 ng g(-1) ww in July and from no detection to 22 ± 16 ng g(-1) ww in November; and BPA ranged from 4 ± 9 to 41 ± 24 ng g(-1) ww in July and from 6 ± 5 to 59 ± 24 ng g(-1) ww in November. Moreover, the concentrations of these compounds were higher in fish found down-stream of the sewage treatment plant (STP), and the lowest concentrations were found in fish up-stream of the STP. Concentrations of these EDCs in muscles might be correlated with the prevalence of intersex traits in wild fish, suggesting that these compounds contribute, at least in part, to the occurrence of intersex morphology. Thus, phenolic EDCs discharged from the STP pose a risk to the aquatic ecosystem in the Hun River. PMID:25465957

  20. Occurrence and fate of endocrine disrupting chemicals in ASP based sewage treatment plant in Hardwar.

    PubMed

    Saini, Gita; Pant, Shalini; Alam, Tanveer; Kazmi, A A

    2016-01-01

    The occurrence of emerging contaminants such as endocrine disrupting chemicals (EDCs) in our water resources is of prime concern. With this context, fate and seasonal variation of six EDCs (testosterone, T; progesterone, P; diethyl phthalate, DEP; dibutyl phthalate, DBP; propyl-paraben, PP and butyl-paraben, BP) were assessed throughout the year, i.e. in rainy, winter, spring and summer seasons in the raw, treated wastewater and activated sludge in an activated sludge process (ASP) based sewage treatment plant (STP) located in Haridwar, India. Qualitative and quantitative measurements were performed by gas chromatography-mass spectrometry (GC-MS) analysis. Results indicate that in summer, the examined STP could effectively remove 82.9% of T, 86.4% of P, 95.5% of DEP, 92.4% of DBP, 91.5% of PP, and 89.9% of BP from the wastewater. Among the EDCs considered, higher removal efficiencies were achieved for phthalates in the summer season. GC-MS analysis showed that a small fraction of EDCs was sorbed on the solid fraction of activated sludge. Scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transformation infrared spectroscopy analysis were also performed to investigate the occurrence of EDCs in biomass samples. Results of this study also demonstrated that removal efficiency, assessed in terms of physicochemical and microbiological parameters, was maximum in summer and reached minimum in rainy season. PMID:27642823

  1. Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes

    NASA Astrophysics Data System (ADS)

    Lv, Xuemin; Xiao, Sanhua; Zhang, Gang; Jiang, Pu; Tang, Fei

    2016-03-01

    This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46–12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens.

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  3. Distribution and estrogenic potential of endocrine disrupting chemicals (EDCs) in estuarine sediments from Mumbai, India.

    PubMed

    Tiwari, M; Sahu, S K; Pandit, G G

    2016-09-01

    Endocrine disrupting chemicals (EDCs) are responsible for inappropriate development and they alter the hormonal and homeostatic systems of organism. Phthalates (PAEs), bisphenol A (BPA) and other EDCs were monitored in surface sediments at different stations across Thane Creek, India. Analysis of PAEs was carried out using GC-MS technique, while BPA and other EDCs were analyzing on UPLC-PDA instrument. Di-n-butyl phthalate (DBP) had the highest concentration among all fourteen analyzed phthalates ranges between 0.13 and 0.4 mg kg(-1); and was detectable in all sediment samples. Strong correlation (r = 0.95, p < 0.01) was observed between total organic carbon (TOC, %) and total PAEs. BPA was also detected in all samples; average BPA concentration varies from 16.3 to 35.79 μg kg(-1) with mean value 25.15 μg kg(-1) dry weight of sediment. Synthetic EDCs such as 4-para-nonylphenol (NP) and 4-tert-octylphenol (OP) were also analyzed; and their average concentrations were founds to be 356.5 and 176 μg kg(-1), respectively. Estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) were the main contributors to the overall estradiol equivalent concentration (EEQs) in sediment, their average total percentage contributions is more than 90 %. PMID:27316650

  4. Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes.

    PubMed

    Lv, Xuemin; Xiao, Sanhua; Zhang, Gang; Jiang, Pu; Tang, Fei

    2016-01-01

    This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46-12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens. PMID:26953121

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

    PubMed

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

    2016-01-15

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

  6. Ecological risk of estrogenic endocrine disrupting chemicals in sewage plant effluent and reclaimed water.

    PubMed

    Sun, Yan; Huang, Huang; Sun, Ying; Wang, Chao; Shi, Xiao-Lei; Hu, Hong-Ying; Kameya, Takashi; Fujie, Koichi

    2013-09-01

    The long-term ecological risk of micropollutants, especially endocrine disrupting chemicals (EDCs) has threatened reclaimed water quality. In this study, estrogenic activity and ecological risk of eight typical estrogenic EDCs in effluents from sewage plants were evaluated. The estrogenic activity analysis showed that steroidal estrogens had the highest estrogenic activity (ranged from 10(-1) to 10(3) ng-E2/L), phenolic compounds showed weaker estrogenic activity (mainly ranged from 10(-3) to 10 ng-E2/L), and phthalate esters were negligible. The ecological risk of the estrogenic EDCs which was characterized by risk quotient ranged from 10(-4) to 10(3), with an order in descending: steroids estrogens, phenolic compounds and phthalate esters. The eight estrogenic EDCs were scored and sorted based on the comparison of the estrogenic activity and the ecological risk, suggesting that 17α-ethynylestradiol (EE2), estrone (E1) and estradiol (E2) should be the priority EDCs to control in municipal sewage plants. PMID:23735815

  7. 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. PMID:23850766

  8. Oxidation mechanism and overall removal rates of endocrine disrupting chemicals by aquatic plants.

    PubMed

    Reis, A R; Tabei, K; Sakakibara, Y

    2014-01-30

    The purpose of this study was to evaluate experimentally and theoretically the oxidation mechanisms and overall removal rates of phenolic endocrine disrupting chemicals (EDCs) by aquatic plants. EDCs used in this study were bisphenol-A (BPA), 2,4-dichlorophenol (2,4-DCP), 4-tert-octylphenol (4-t-OP), and pentachlorophenol (PCP). Referring to reported detection levels in aquatic environments and contaminated sites, the feed concentration of each EDC was set from 1 to 100μg/L. Experimental results showed that, except for PCP, phenolic EDCs were stably and concurrently removed by different types of aquatic plants over 70 days in long-term continuous treatments. Primal enzymes responsible for oxidation of BPA, 2,4-DCP, and 4-t-OP were peroxidases (POs). Moreover, enzymatic removal rates of BPA, 2,4-DCP, and 4-t-OP by POs were more than 2 orders of magnitude larger than those by aquatic plants. Assuming that overall removal rates of EDCs are controlled by mass transfer rates onto liquid films on the surface of aquatic plants, an electrochemical method based on the limiting current theory was developed to measure the mass transfer rates of EDCs. Because of extremely large removal rates of EDCs by POs, observed removal rates by aquatic plants were in reasonably good agreement with calculated results by a mathematical model developed based on an assumption that mass transfer limitation is a rate-limiting step.

  9. Occurrence and removal of phenolic endocrine disrupting chemicals in the water treatment processes

    PubMed Central

    Lv, Xuemin; Xiao, Sanhua; Zhang, Gang; Jiang, Pu; Tang, Fei

    2016-01-01

    This paper evaluated the occurrence and removal efficiency of four selected phenolic endocrine disrupting chemicals (bisphenol A (BPA), octylphenol (OP), nonylphenol (NP) and diethylstilbestrol (DES)) in two drinking waterworks in Jiangsu province which take source water from Taihu Lake. The recombined yeast estrogen screen (YES) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were applied to assess the estrogenicity and detect the estrogens in the samples. The estrogen equivalents (EEQs) ranged from nd (not detected) to 2.96 ng/L, and the estrogenic activities decreased along the processes. Among the 32 samples, DES prevailed in all samples, with concentrations ranging 1.46–12.0 ng/L, BPA, OP and NP were partially detected, with concentrations ranging from nd to 17.73 ng/L, nd to 0.49 ng/L and nd to 3.27 ng/L, respectively. DES was found to be the main contributor to the estrogenicity (99.06%), followed by NP (0.62%), OP (0.23%) and BPA (0.09%). From the observation of treatment efficiency, the advanced treatment processes presented much higher removal ratio in reducing DES, the biodegradation played an important role in removing BPA, ozonation and pre-oxidation showed an effective removal on all the four estrogens; while the conventional ones can also reduce all the four estrogens. PMID:26953121

  10. 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.

  11. 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

  12. Malathion exposure induces the endocrine disruption and growth retardation in the catfish, Clarias batrachus (Linn.).

    PubMed

    Lal, Bechan; Sarang, Mukesh Kumar; Kumar, Pankaj

    2013-01-15

    Many hormones are known for their role in the regulation of metabolic activities and somatic growth in fishes. The present study deals with the effects of malathion (an organophosphorous pesticide) on the levels of metabolic hormones that are responsible for promotion of somatic and ovarian growth of the freshwater catfish, Clarias batrachus. Malathion treatment for thirty days drastically reduced the food intake and body weight of fish. These fish also exhibited a great avoidance to food. Exposure of catfish to malathion reduced the levels of thyroxine (T(4)), triiodothyronine (T(3)), growth hormone (GH), insulin like growth factor-I (IGF-I), testosterone (T) and estradiol-17β (E(2)) in a dose dependent manner during all the studied reproductive phases, in general, except that malathion increased the level of GH during the quiescence phase. Significant reduction in muscle and hepatic protein content also occurred in the malathion-treated fish. Malathion exposure induced lipolysis too in the liver and muscle. The results thus support that malathion treatment disrupts the endocrine functions and the olfactory sensation responsible for food intake and gustatory feeding behavior, which ultimately leads to retardation of fish growth. PMID:23174696

  13. Photodegradation of estrogenic endocrine disrupting steroidal hormones in aqueous systems: Progress and future challenges.

    PubMed

    Sornalingam, Kireesan; McDonagh, Andrew; Zhou, John L

    2016-04-15

    This article reviews different photodegradation technologies used for the removal of four endocrine disrupting chemicals (EDCs): estrone (E1), 17β-estradiol (E2), estriol (E3) and 17α-ethinylestradiol (EE2). The degradation efficiency is greater under UV than visible light; and increases with light intensity up to when mass transfer becomes the rate limiting step. Substantial rates are observed in the environmentally relevant range of pH7-8, though higher rates are obtained for pH above the pKa (~10.4) of the EDCs. The effects of dissolved organic matter (DOM) on EDC photodegradation are complex with both positive and negative impacts being reported. TiO2 remains the best catalyst due to its superior activity, chemical and photo stability, cheap commercial availability, capacity to function at ambient conditions and low toxicity. The optimum TiO2 loading is 0.05-1gl(-1), while higher loadings have negative impact on EDC removal. The suspended catalysts prove to be more efficient in photocatalysis compared to the immobilised catalysts, while the latter are considered more suitable for commercial scale applications. Photodegradation mostly follows 1st or pseudo 1st order kinetics. Photodegradation typically eradicates or moderates estrogenic activity, though some intermediates are found to exhibit higher estrogenicity than the parent EDCs; the persistence of estrogenic activity is mainly attributed to the presence of the phenolic moiety in intermediates. PMID:26815298

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

    PubMed

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

    2013-01-15

    The concentrations of nine emerging contaminants, including pharmaceutically active compounds (PhACs) (ibuprofen, IBF; naproxen, NPX; diclofenac, DCF; ketoprofen, KFN) and endocrine disrupting chemicals (triclosan, TCS; bisphenol, BPA; nonylphenol, NP; nonylphenol monoethoxylate, NP1EO; nonylphenol diethoxylate, NP2EO), were determined in wastewater and sludge samples of two wastewater treatment plants (WWTPs) in Greece. Average concentrations in raw and treated wastewater ranged from 0.39 (KFN) to 12.52 μg L(-1) (NP) and from 80%) during anaerobic digestion, whereas removal of EDCs was lower, ranging up to 55% for NP1EO. PMID:23257325

  15. Bioinspired production of magnetic laccase-biotitania particles for the removal of endocrine disrupting chemicals.

    PubMed

    Ardao, Inés; Magnin, Delphine; Agathos, Spiros N

    2015-10-01

    Microbial laccases are powerful enzymes capable of degrading lignin and other recalcitrant compounds including endocrine disrupting chemicals (EDCs). Efficient EDC removal on an industrial scale requires robust, stable, easy to handle and cost-effective immobilized biocatalysts. In this direction, magnetic biocatalysts are attractive due to their easy separation through an external magnetic field. Recently, a bioinspired immobilization technique that mimics the natural biomineralization reactions in diatoms has emerged as a fast and versatile tool for generating robust, cheap, and highly stable (nano) biocatalysts. In this work, bioinspired formation of a biotitania matrix is triggered on the surface of magnetic particles in the presence of laccase in order to produce laccase-biotitania (lac-bioTiO2 ) biocatalysts suitable for environmental applications using a novel, fast and versatile enzyme entrapment technique. Highly active lac-bioTiO2 particles have been produced and the effect of different parameters (enzyme loading, titania precursor concentration, pH, duration of the biotitania formation, and laccase adsorption steps) on the apparent activity yield of these biocatalysts were evaluated, the concentration of the titania precursor being the most influential. The lac-bioTiO2 particles were able to catalyze the removal of bisphenol A, 17α-ethinylestradiol and diclofenac in a mixture of six model EDCs and retained 90% of activity after five reaction cycles and 60% after 10 cycles.

  16. Determination of nineteen 4-alkylphenol endocrine disrupters in Geneva municipal sewage wastewater.

    PubMed

    Espejo, Ramon; Valter, Karel; Simona, Marco; Janin, Yves; Arrizabalaga, Phillipe

    2002-11-01

    A method for the determination of 18 isomeric 4-nonylphenols and 4-tert.-octylphenol in wastewater using GC-MS and LC-MS has been developed. This procedure has been applied to the determination of the free allylphenols and the analysis of these substances in the form of 4-alkylphenol polyethoxylates, their various hydrosoluble metabolites and other hydrosoluble 4-alkylphenol containing degradation products ("bonded" alkylphenols) after their cleavage with hydroiodic acid. In the environment, the final degradation products of 4-alkylphenol polyethoxylates and their metabolites are the long-chain free 4-alkylphenols, which are responsible of endocrine disruption in various animal species. The average concentration of free alkylphenols in the wastewater of the sewage plant in Aïre, Geneva (Switzerland) ranges from 1.0 to 6.8 microg/l (average 2.5 microg/l). The concentration of "bonded" 4-alkylphenols can reach about 0.66 mg/l. The precision of the method and its accuracy are satisfactory with recovery rates for the free 4-alkylphenols and "bonded" 4-nonylphenols ranging from 74 to 79% and 80 to 87%, respectively. The relative standard deviation is lower than 6% for all analyzed compounds. The detection limits are in the range of 0.4 to 6 ng/l (typically 2 ng/l) and quantification limits are between 2 to 22 ng/l (typically 10 ng/l) for all individual isomeric alkylphenols. PMID:12462626

  17. Interpretation of fish biomarker data for identification, classification, risk assessment and testing of endocrine disrupting chemicals.

    PubMed

    Dang, ZhiChao

    2016-01-01

    Chemical induced changes in fish biomarkers vitellogenin (VTG), secondary sex characteristics (SSC), and sex ratio indicate modes/mechanisms of action (MOAs) of EAS (estrogen, androgen and steroidogenesis) pathways. These biomarkers could be used for defining MOAs and the causal link between MOAs and adverse effects in fish for the identification of endocrine disrupting chemicals (EDCs). This paper compiled data sets of 150 chemicals for VTG, 57 chemicals for SSC and 38 chemicals for sex ratio in fathead minnow, medaka and zebrafish. It showed 1) changes in fish biomarkers can indicate the MOAs as anticipated; 2) in addition to EAS pathways, chemicals with non-EAS pathways induced changes in fish biomarkers; 3) responses of fish biomarkers did not always follow the anticipated patterns of EAS pathways. These responses may result from the interaction of chemical-induced multiple MOAs and confounding factors like fish diet, infection, culture conditions, general toxicity and stress response. The complex response of fish biomarkers to a chemical of interest requires EDC testing at multiple biological levels. Interpretation of fish biomarker data should be combined with relevant information at different biological levels, which is critical for defining chemical specific MOAs. The utility of fish biomarker data for identification, classification, PBT assessment, risk assessment, and testing of EDCs in the regulatory context was discussed. This paper emphasizes the importance of fish biomarker data in the regulatory context, a weight of evidence approach for the interpretation of fish biomarker data and the need for defining levels of evidence for the identification of EDCs.

  18. Endocrine-disrupting chemicals in the Pearl River Delta and coastal environment: sources, transfer, and implications.

    PubMed

    Xu, Weihai; Yan, Wen; Huang, Weixia; Miao, Li; Zhong, Lifeng

    2014-12-01

    A study was conducted to investigate the occurrence and behavior of six endocrine-disrupting chemicals (EDCs) in sewage, river water, and seawater from the Pearl River Delta (PRD). The six EDCs under study were 4-nonylphenol (NP), bisphenol A (BPA), 17α-ethynylestradiol (EE2), estrone (E2), 17β-estradiol (E2), and estriol (E3). These EDCs, predominated by BPA, were found in high levels in the influents and the effluents of sewage treatment plants in the area. The relatively high concentrations (0.23-625 ng/L) of the EDCs detected in the receiving river water suggested that the untreated sewage discharge was a major contributor. The EDCs detected in eight outlets of the Pear River and the Pear River Estuary were in the ranges of 1.2-234 and 0.2-178 ng/L, respectively. The estrogen equivalents in the aquatic environments under study ranged from 0.08 to 4.5 ng/L, with E1 and EE2 being the two predominant contributors. As the fluxes of the EDCs from the PRD region to the nearby ocean are over 500 tons each year, the results of this study point to the potential that Pearl River is a significant source of the EDCs to the local environment there.

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

    PubMed Central

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

    2015-01-01

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

  20. Endocrine-Disrupting Chemicals and Climate Change: A Worst-Case Combination for Arctic Marine Mammals and Seabirds?

    PubMed Central

    Jenssen, Bjørn Munro

    2006-01-01

    The effects of global change on biodiversity and ecosystem functioning encompass multiple complex dynamic processes. Climate change and exposure to endocrine-disrupting chemicals (EDCs) are currently regarded as two of the most serious anthropogenic threats to biodiversity and ecosystems. We should, therefore, be especially concerned about the possible effects of EDCs on the ability of Arctic marine mammals and seabirds to adapt to environmental alterations caused by climate change. Relationships between various organochlorine compounds, necessary such as polychlorinated biphenyls, dichlorophenyldichloroethylene, hexachlorobenzene, and oxychlordane, and hormones in Arctic mammals and seabirds imply that these chemicals pose a threat to endocrine systems of these animals. The most pronounced relationships have been reported with the thyroid hormone system, but effects are also seen in sex steroid hormones and cortisol. Even though behavioral and morphological effects of persistent organic pollutants are consistent with endocrine disruption, no direct evidence exists for such relationships. Because different endocrine systems are important for enabling animals to respond adequately to environmental stress, EDCs may interfere with adaptations to increased stress situations. Such interacting effects are likely related to adaptive responses regulated by the thyroid, sex steroid, and glucocorticosteroid systems. PMID:16818250

  1. Endocrine-disrupting chemicals and climate change: A worst-case combination for arctic marine mammals and seabirds?

    PubMed

    Jenssen, Bjørn Munro

    2006-04-01

    The effects of global change on biodiversity and ecosystem functioning encompass multiple complex dynamic processes. Climate change and exposure to endocrine-disrupting chemicals (EDCs) are currently regarded as two of the most serious anthropogenic threats to biodiversity and ecosystems. We should, therefore, be especially concerned about the possible effects of EDCs on the ability of Arctic marine mammals and seabirds to adapt to environmental alterations caused by climate change. Relationships between various organochlorine compounds, necessary such as polychlorinated biphenyls, dichlorophenyldichloroethylene, hexachlorobenzene, and oxychlordane, and hormones in Arctic mammals and seabirds imply that these chemicals pose a threat to endocrine systems of these animals. The most pronounced relationships have been reported with the thyroid hormone system, but effects are also seen in sex steroid hormones and cortisol. Even though behavioral and morphological effects of persistent organic pollutants are consistent with endocrine disruption, no direct evidence exists for such relationships. Because different endocrine systems are important for enabling animals to respond adequately to environmental stress, EDCs may interfere with adaptations to increased stress situations. Such interacting effects are likely related to adaptive responses regulated by the thyroid, sex steroid, and glucocorticosteroid systems.

  2. The impact of endocrine-disrupting chemicals on oxidative stress and innate immune response in zebrafish embryos.

    PubMed

    Xu, Hai; Yang, Ming; Qiu, Wenhui; Pan, Chenyuan; Wu, Minghong

    2013-08-01

    Bisphenol A (BPA) and nonylphenol (NP) are well known endocrine-disrupting chemicals (EDCs) ubiquitous in the aquatic environment and are an ecotoxicological risk for the health of aquatic organisms. Limited attention has been given to the immunotoxicity of these chemicals. The present study revealed a concentration-dependent increase of reactive oxygen species content and an induced expression of redox-sensitive transcription factors in zebrafish embryos after exposure to various concentrations of BPA, NP, and BPA/NP mixture for 4 h to 168 h postfertilization. Transcription of genes related to the immune response, including IFNγ, IL1β, IL10, Mx, TNFα, CC-chemokine, and CXCL-clc, were significantly up-regulated on exposure to EDCs. A significant induction of concentrations of proinflammatory mediator, nitric oxide, accompanied by an increase in the activity of nitric oxide synthase (NOS) and an upregulation of inducible NOS gene expression, was detected in zebrafish embryos on exposures to EDCs. To elucidate the potential mechanisms by which BPA and NP activate the innate immune response, expression profiles of genes related to the Toll-like receptors (TLRs) signaling pathway were examined. Expressions of TLR3, TRIF, MyD88, SARM, IRAK4, and TRAF6 were altered on exposure to EDCs. The authors' results demonstrate that exposure to BPA and NP significantly affects the expression of genes related to immune response in zebrafish embryos following oxidative stress. PMID:23606268

  3. Epigenetic Regulation of Non-Lymphoid Cells by Bisphenol A, a Model Endocrine Disrupter: Potential Implications for Immunoregulation

    PubMed Central

    Khan, Deena; Ahmed, S. Ansar

    2015-01-01

    Endocrine disrupting chemicals (EDC) abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical, and consumer product industries. Many of the EDCs such as Bisphenol A (BPA) have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth, and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation, and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight the BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system. PMID:26097467

  4. Exposure to Endocrine Disrupters and Nuclear Receptor Gene Expression in Infertile and Fertile Women from Different Italian Areas

    PubMed Central

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

    2014-01-01

    Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERα, ERβ, AR, AhR, PPARγ, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARγ. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health. PMID:25268510

  5. Endocrine disrupting effects of domestic wastewater on reproduction, sexual behavior, and gene expression in the brackish medaka Oryzias melastigma.

    PubMed

    Chen, Te-Hao; Chou, Shi-Ming; Tang, Cheng-Hao; Chen, Chia-Yang; Meng, Pei-Jie; Ko, Fung-Chi; Cheng, Jing-O

    2016-05-01

    The objective of this study was to investigate the endocrine disrupting effects of domestic wastewater on fish using the brackish medaka Oryzias melastigma as the animal model. Estuarine water samples were collected from Sihchong Creek and Baoli Creek estuaries, Taiwan, in March of 2012 to assess the whole effluent toxicity (WET) of domestic wastewater produced by the local residents and tourists. Chemical analysis detected various pharmaceuticals and personal care products (PPCPs) in the field water samples. Some of these PPCPs are endocrine disrupting chemicals. In the laboratory-based bioassay, breeding pairs were exposed to the water samples (Sihchong, Baoli, and control) for 21 days. Cumulative number of eggs spawned was significantly higher in the Sihchong group. While fish swimming activity was not affected, sexual behavior of the male fish was significantly induced in both Sihchong and Baoli groups. Male and female gonad histology was not affected. Expression level of biomarker genes CYP1A1, HSP70, and VTG was significantly induced in the Sihchong group. This study indicates that the mixture of contaminants contained in the estuarine water may cause endocrine disrupting effects in fish.

  6. The presence of morphologically intermediate papilla syndrome in United Kingdom populations of sand goby (Pomatoschistus spp): endocrine disruption?

    PubMed

    Kirby, Mark F; Bignell, John; Brown, Elaine; Craft, John A; Davies, Ian; Dyer, Robert A; Feist, Steven W; Jones, Gary; Matthiessen, Peter; Megginson, Colin; Robertson, Fiona E; Robinson, Craig

    2003-02-01

    The sand goby (Pomatoschistus spp.) is a small estuarine fish. Its abundance, life history, and sedentary nature lead to its adoption as a key species in the U.K. Endocrine Disruption in the Marine Environment (EDMAR) Program. This study investigated the presence of classic markers of estrogenic exposure by determining vitellogenin (VTG) and zona radiata protein (ZRP) mRNA levels and ovotestis in estuarine-caught male gobies and investigated morphological changes in the urogenital papilla (UGP). Laboratory exposures to estrogens were also conducted to ascertain the responses of these markers. Wild-caught male fish showed no evidence of ovotestis, VTG, or ZRP mRNA induction. Laboratory exposures suggested that sensitivity of the goby to VTG/ ZRP mRNA induction was similar to flounder. The UGP inspection of wild-caught specimens revealed evidence of feminization of male papillae, a condition denoted as morphologically intermediate papilla syndrome (MIPS). Morphologically intermediate papilla syndrome was more prevalent at estrogenically contaminated sites. Juvenile goby experimentally exposed to 17beta-estradiol for 11 to 32 weeks exhibited signs of the MIPS condition, showing that it was inducible by estrogenic exposure and could therefore be a form of estrogenic endocrine disruption. The estuaries where the MIPS condition was most prevalent (>50% at certain sites) were the Tees, Mersey, and Clyde. The potential of the MIPS condition to significantly interfere with reproductive performance is discussed as well as its use as a monitoring tool for endocrine disruption in the estuarine environment.

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

    EPA Science Inventory

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

  8. A Comparison of RIA and LC-MS/MS Methods to Quantify Steroids in Rat Serum and Urine Following Exposure to an Endocrine Disrupting Chemical

    EPA Science Inventory

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

  9. Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine systems in humans: A review.

    PubMed

    Sun, Hong-Jie; Xiang, Ping; Luo, Jun; Hong, Huachang; Lin, Hongjun; Li, Hong-Bo; Ma, Lena Q

    2016-10-01

    Due to its toxicity as a carcinogen and wide distribution in the environment, arsenic (As) exposure in humans is of public concern globally. Many studies have manifested that As exposure induces cancers besides pathological effects in humans. Animal studies showed that chronic As exposure induces serious neurological effects. Based on recent studies, researchers proposed that As, including arsenate (AsV) and arsenite (AsIII), is also an endocrine disruptor. This review discusses the mechanisms of As toxicity on three endocrine systems including gonadal, adrenal and thyroid endocrine systems. Arsenic methylation and oxidative stress are responsible for As-induced disorders of endocrine systems, however, strong binding of AsIII to thiols also play an important role. Some studies showed AsV toxicity on endocrine systems, but mechanistic investigation is lacking. Research is needed to look into their toxicity mechanisms to help cure the illnesses caused by As-induced endocrine system disorders.

  10. Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine systems in humans: A review.

    PubMed

    Sun, Hong-Jie; Xiang, Ping; Luo, Jun; Hong, Huachang; Lin, Hongjun; Li, Hong-Bo; Ma, Lena Q

    2016-10-01

    Due to its toxicity as a carcinogen and wide distribution in the environment, arsenic (As) exposure in humans is of public concern globally. Many studies have manifested that As exposure induces cancers besides pathological effects in humans. Animal studies showed that chronic As exposure induces serious neurological effects. Based on recent studies, researchers proposed that As, including arsenate (AsV) and arsenite (AsIII), is also an endocrine disruptor. This review discusses the mechanisms of As toxicity on three endocrine systems including gonadal, adrenal and thyroid endocrine systems. Arsenic methylation and oxidative stress are responsible for As-induced disorders of endocrine systems, however, strong binding of AsIII to thiols also play an important role. Some studies showed AsV toxicity on endocrine systems, but mechanistic investigation is lacking. Research is needed to look into their toxicity mechanisms to help cure the illnesses caused by As-induced endocrine system disorders. PMID:27502899

  11. Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.

    PubMed

    Zoeller, R Thomas; Vandenberg, Laura N

    2015-01-01

    The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose-response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts' knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions. PMID:25971795

  12. Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals.

    PubMed

    Felton, Rachel G; Steiner, Cynthia C; Durrant, Barbara S; Keisler, Duane H; Milnes, Matthew R; Tubbs, Christopher W

    2015-12-01

    Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species.

  13. Effect of wastewater treatment facility closure on endocrine disrupting chemicals in a Coastal Plain stream

    USGS Publications Warehouse

    Bradley, Paul M.; Journey, Celeste A.; Clark, Jimmy M.

    2016-01-01

    Wastewater treatment facility (WWTF) closures are rare environmental remediation events; offering unique insight into contaminant persistence, long-term wastewater impacts, and ecosystem recovery processes. The U.S. Geological Survey assessed the fate of select endocrine disrupting chemicals (EDC) in surface water and streambed sediment one year before and one year after closure of a long-term WWTF located within the Spirit Creek watershed at Fort Gordon, Georgia. Sample sites included a WWTF-effluent control located upstream from the outfall, three downstream effluent-impacted sites located between the outfall and Spirit Lake, and one downstream from the lake's outfall. Prior to closure, the 2.2-km stream segment downstream from the WWTF outfall was characterized by EDC concentrations significantly higher (α = 0.05) than at the control site; indicating substantial downstream transport and limited in-stream attenuation of EDC, including pharmaceuticals, estrogens, alkylphenol ethoxylate (APE) metabolites, and organophosphate flame retardants (OPFR). Wastewater-derived pharmaceutical, APE metabolites, and OPFR compounds were also detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon under effluent discharge conditions. After the WWTF closure, no significant differences in concentrations or numbers of detected EDC compounds were observed between control and downstream locations. The results indicated EDC pseudo-persistence under preclosure, continuous supply conditions, with rapid attenuation following WWTF closure. Low concentrations of EDC at the control site throughout the study and comparable concentrations in downstream locations after WWTF closure indicated additional, continuing, upstream contaminant sources within the Spirit Creek watershed. 

  14. Potential endocrine disrupting organic chemicals in treated municipal wastewater and river water

    USGS Publications Warehouse

    Barber, L.B.; Brown, G.K.; Zaugg, S.D.

    2000-01-01

    Select endocrine disrupting organic chemicals were measured in treated wastewater from Chicago, IL, Minneapolis/St. Paul, MN, Detroit, MI, and Milwaukee, WI, and in the Des Plaines, Illinois, and Minnesota Rivers during the fall of 1997 and the spring of 1998. Emphasis was given to alkylphenolpolyethoxylate (APEO) derived compounds, although 17-??-estradiol, bisphenol A, caffeine, total organic carbon, ethylenediaminetetraacetic acid (EDTA), and other compounds also were measured. Contaminants were isolated by continuous liquid-liquid extraction (CLLE) with methylene chloride and analyzed by gas chromatography/mass spectrometry in full scan and selected ion monitoring modes. The extracts were derivatized to form the methyl esters of alkylphenolethoxycarboxylates (APEC), and EDTA was isolated by evaporation and derivatized to form the tetrapropyl ester. The mass spectra of nonylphenol (NP) and octylphenol (OP) compounds are complex and show variations among the different ethoxylate and carboxylate homologs, reflecting variations in the ethylene oxide chain length. Recoveries for target compounds and surrogate standards ranged from 20-130%, with relative standard deviations of 9.9-53%. Detection limits for the various compounds ranged from 0.06-0.35 ??g/L. Analysis of the wastewater effluents detected a number of compounds including NP, NPEO, OP, OPEO, NPEC, caffeine, and EDTA at concentrations ranging from <1-439 ??g/L, with EDTA and NPEC being most abundant. There was variability in compound distributions and concentrations between the various sewage treatment plants, indicating differences in treatment type and influent composition. Several wastewater-derived compounds were detected in the river samples, with EDTA and NPEC persisting for considerable distance downstream from wastewater discharges, and NP and NPEO being attenuated more rapidly.

  15. Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption.

    PubMed

    Chen, Lili; Jiang, Xiaolong; Feng, Haiwei; Shi, Hongjuan; Sun, Lina; Tao, Wenjing; Xi, Qingping; Wang, Deshou

    2016-03-01

    Estrogen, which is synthesized earlier in females than androgen in males, is critical for sex determination in non-mammalian vertebrates. However, it remains unknown that what would happen to the gonadal phenotype if estrogen and androgen were administrated simultaneously. In this study, XY and XX tilapia fry were treated with the same dose of 17α-methyltestosterone (MT) and 17β-estradiol (E2) alone and in combination from 0 to 30 days after hatching. Treatment of XY fish with E2 resulted in male to female sex reversal, while treatment of XX fish with MT resulted in female to male sex reversal. In contrast, simultaneous treatment of XX and XY fish with MT and E2 resulted in female, but with cyp11b2 and cyp19a1a co-expressed in the ovary. Serum 11-ketotestosteron level of the MT and E2 simultaneously treated XX and XY female was similar to that of the XY control, while serum E2 level of these two groups was similar to that of the XX control. Transcriptomic cluster analysis revealed that the MT and E2 treated XX and XY gonads clustered into the same branch with the XX control. However a small fraction of genes, which showed disordered expression, may be associated with stress response. These results demonstrated that estrogen could maintain the female phenotype of XX fish and feminize XY fish even in the presence of androgen. Simultaneous treatment with estrogen and androgen up-regulated the endogenous estrogen and androgen synthesis, and resulted in disordered gene expression and endocrine disruption in tilapia. PMID:26759274

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2016-03-01

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

  18. Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male mice.

    PubMed

    Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Miao, Wenyu; Lin, Xiaojian; Wang, Linggang; Fu, Zhengwei

    2015-07-01

    Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and household pests in China. At present, the commercial BF is a mixed compound containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis-BF. In the present study, the two individual cis-BF enantiomers were separated by a preparative supercritical fluid chromatography. Then, four week-old adolescent male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed that the transcription status of some genes involved in cholesterol synthesis and transport as well as testosterone (T) synthesis in the testes were influenced by cis-BF enantiomers. Especially, we observed that the transcription status of key genes on the pathway of T synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P45017α)) were selectively altered in the testis of mice when treated with 1S-cis-BF, suggesting that it is the possible reason to explain why the lower serum T concentration in 1S-cis-BF treated group. Taken together, it concluded that both of the cis-BF enantiomers have the endocrine disruption activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during the puberty. The data was helpful to understand the toxicity of cis-BF in mammals under enantiomeric level.

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

    PubMed

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

    2013-12-15

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

  20. Vitellogenin gene characterization and expression of Asian paddle crabs ( Charybdis japonica) following endocrine disrupting chemicals

    NASA Astrophysics Data System (ADS)

    Park, Kiyun; Kwak, Tae-Soo; Kwak, Ihn-Sil

    2014-06-01

    Vitellogenin (VTG), the yolk-precursor lipoprotein, has been widely recognized as a biomarker for the detection of estrogenic activity in water-borne chemical pollutants. The Asian paddle crab, Charybdis japonica, is a potential bio-indicator for monitoring marine environments. The aim of this study was to identify the possibility of using C. japonica VTG as biomarkers of stress caused by endocrine disrupting chemicals (EDCs). We characterized a partial sequence of the VTG cDNA in the C. japonica crab and evaluated the crab's mRNA expression profiles following exposure to different concentrations of bisphenol A (BPA) and 4-nonylphenol (NP) for 24 or 96 h. The sequence homology of C. japonica VTG is over 93% in nucleotide and over 98% in amino acid with the corresponding gene of other crabs. Phylogenetic analysis revealed that the C. japonica VTG is an ortholog of other species of lobster and shrimp. Tissue distribution analysis of the C. japonica VTG mRNA revealed that the expression of VTG mRNA was highest in the ovary of females and hepatopancreas. The expression of the C. japonica VTG gene in various BPA or NP concentrations during shorter and longer times was assessed. The expression of VTG transcripts was significantly increased in the C. japonica crab exposed to BPA and NP at different concentrations for 24 h. The mRNA expression of the VTG gene was significantly induced in concentration- and time-dependent manners after BPA or NP exposures for 96 h. These results indicate that crab C. japonica VTG could be used as a potential biomarker of EDCs in marine environment monitoring.

  1. Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption.

    PubMed

    Chen, Lili; Jiang, Xiaolong; Feng, Haiwei; Shi, Hongjuan; Sun, Lina; Tao, Wenjing; Xi, Qingping; Wang, Deshou

    2016-03-01

    Estrogen, which is synthesized earlier in females than androgen in males, is critical for sex determination in non-mammalian vertebrates. However, it remains unknown that what would happen to the gonadal phenotype if estrogen and androgen were administrated simultaneously. In this study, XY and XX tilapia fry were treated with the same dose of 17α-methyltestosterone (MT) and 17β-estradiol (E2) alone and in combination from 0 to 30 days after hatching. Treatment of XY fish with E2 resulted in male to female sex reversal, while treatment of XX fish with MT resulted in female to male sex reversal. In contrast, simultaneous treatment of XX and XY fish with MT and E2 resulted in female, but with cyp11b2 and cyp19a1a co-expressed in the ovary. Serum 11-ketotestosteron level of the MT and E2 simultaneously treated XX and XY female was similar to that of the XY control, while serum E2 level of these two groups was similar to that of the XX control. Transcriptomic cluster analysis revealed that the MT and E2 treated XX and XY gonads clustered into the same branch with the XX control. However a small fraction of genes, which showed disordered expression, may be associated with stress response. These results demonstrated that estrogen could maintain the female phenotype of XX fish and feminize XY fish even in the presence of androgen. Simultaneous treatment with estrogen and androgen up-regulated the endogenous estrogen and androgen synthesis, and resulted in disordered gene expression and endocrine disruption in tilapia.

  2. Interpretation of fish biomarker data for identification, classification, risk assessment and testing of endocrine disrupting chemicals.

    PubMed

    Dang, ZhiChao

    2016-01-01

    Chemical induced changes in fish biomarkers vitellogenin (VTG), secondary sex characteristics (SSC), and sex ratio indicate modes/mechanisms of action (MOAs) of EAS (estrogen, androgen and steroidogenesis) pathways. These biomarkers could be used for defining MOAs and the causal link between MOAs and adverse effects in fish for the identification of endocrine disrupting chemicals (EDCs). This paper compiled data sets of 150 chemicals for VTG, 57 chemicals for SSC and 38 chemicals for sex ratio in fathead minnow, medaka and zebrafish. It showed 1) changes in fish biomarkers can indicate the MOAs as anticipated; 2) in addition to EAS pathways, chemicals with non-EAS pathways induced changes in fish biomarkers; 3) responses of fish biomarkers did not always follow the anticipated patterns of EAS pathways. These responses may result from the interaction of chemical-induced multiple MOAs and confounding factors like fish diet, infection, culture conditions, general toxicity and stress response. The complex response of fish biomarkers to a chemical of interest requires EDC testing at multiple biological levels. Interpretation of fish biomarker data should be combined with relevant information at different biological levels, which is critical for defining chemical specific MOAs. The utility of fish biomarker data for identification, classification, PBT assessment, risk assessment, and testing of EDCs in the regulatory context was discussed. This paper emphasizes the importance of fish biomarker data in the regulatory context, a weight of evidence approach for the interpretation of fish biomarker data and the need for defining levels of evidence for the identification of EDCs. PMID:27155823

  3. Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination

    SciTech Connect

    Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric . E-mail: criigen@unicaen.fr

    2007-07-15

    Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 {mu}M (except for TBTO and DES, 10 {mu}M threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 {mu}M, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment.

  4. Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment.

    PubMed

    Fent, Karl

    2015-11-01

    In aquatic ecosystems, progesterone (P4) and synthetic progestins (gestagens) originate from excretion by humans and livestock. Synthetic progestins are used for contraception and as P4 for medical treatments as well. Despite significant use, their ecotoxicological implications are poorly understood. Only about 50% of the progestins in use have been analyzed for their environmental occurrence and effects in aquatic organisms. Here we critically summarize concentrations and effects of progestins in aquatic systems. P4 and progestins were mostly detected when analyzed for, and they occurred in the low ng/L range in wastewater and surface water. In animal farm waste and runoff, they reached up to several μg/L. P4 and synthetic progestins act through progesterone receptors but they also interact with other steroid hormone receptors. They act on the hypothalamus-pituitary-gonad axis, lead to oocyte maturation in female and sperm motility in male fish. Additionally, other pathways are affected as well, including the circadian rhythm. Effects of P4, mifepristone and eleven synthetic progestins have been studied in fish and a few compounds in frogs and mussels. Environmental risks may be associated with P4, dydrogesterone and medroxyprogesterone acetate, where transcriptional effects were found at highest environmental levels. Reproductive effects occurred at higher levels. However, norethindrone, levonorgestrel and norgestrel compromised reproduction at environmental (ng/L) concentrations. Thus, some of the progestins are very active endocrine disrupters. This review summarizes the current state of the art and highlights risks for fish. Further research is needed into environmental concentrations and effects of non-investigated progestins, unexplored modes of action, and the activity of mixtures of progestins and other steroids to fully assess their environmental risks. PMID:26276056

  5. Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals.

    PubMed

    Felton, Rachel G; Steiner, Cynthia C; Durrant, Barbara S; Keisler, Duane H; Milnes, Matthew R; Tubbs, Christopher W

    2015-12-01

    Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species. PMID:26372180

  6. A transcriptomics-based biological framework for studying mechanisms of endocrine disruption in small fish species.

    PubMed

    Wang, Rong-Lin; Bencic, David; Villeneuve, Daniel L; Ankley, Gerald T; Lazorchak, Jim; Edwards, Stephen

    2010-07-01

    This study sought to construct a transcriptomics-based framework of signal transduction pathways, transcriptional regulatory networks, and the hypothalamic-pituitary gonadal (HPG) axis in zebrafish (Danio rerio) to facilitate formulation of specific, testable hypotheses regarding the mechanisms of endocrine disruption in fish. For the analyses involved, we used data from a total of more than 300 microarrays representing 58 conditions, which encompassed 4 tissue types from zebrafish of both genders exposed for 1 of 3 durations to 10 different test chemicals (17alpha-ethynyl estradiol, fadrozole, 17beta-trenbolone, fipronil, prochloraz, flutamide, muscimol, ketoconazole, trilostane, and vinclozolin). Differentially expressed genes were identified by one class t-tests for each condition, and those with false discovery rates of less than 40% and treatment/control ratios > or =1.3-fold were mapped to orthologous human, mouse, and rat pathways by Ingenuity Pathway Analysis to look for overrepresentation of known biological pathways. To complement the analysis of known biological pathways, the genes regulated by approximately 1800 transcription factors were inferred using the ARACNE mutual information-based algorithm. The resulting gene sets for all transcriptional factors, along with a group of compiled HPG-axis genes and approximately 130 publicly available biological pathways, were analyzed for their responses to the 58 treatment conditions by Gene Set Enrichment Analysis (GSEA) and its variant, Extended-GSEA. The biological pathways and transcription factors associated with multiple distinct treatments showed substantial interactions among the HPG-axis, TGF-beta, p53, and several of their cross-talking partners. These candidate networks/pathways have a variety of profound impacts on such cellular functions as stress response, cell cycle, and apoptosis.

  7. Carbendazim has the potential to induce oxidative stress, apoptosis, immunotoxicity and endocrine disruption during zebrafish larvae development.

    PubMed

    Jiang, Jinhua; Wu, Shenggan; Wang, Yanhua; An, Xuehua; Cai, Leiming; Zhao, Xueping; Wu, Changxing

    2015-10-01

    Increasing evidence have suggested deleterious effects of carbendazim on reproduction, apoptosis, immunotoxicity and endocrine disruption in mice and rats, however, the developmental toxicity of carbendazim to aquatic organisms remains obscure. In the present study, we utilized zebrafish as an environmental monitoring model to characterize the effects of carbendazim on expression of genes related to oxidative stress, apoptosis, immunotoxicity and endocrine disruption during larval development. Different trends in gene expression were observed upon exposing the larvae to 4, 20, 100, and 500 μg/L carbendazim for 4 and 8d. The mRNA levels of catalase, glutathione peroxidase and manganese superoxide dismutase (CAT, GPX, and Mn/SOD) were up-regulated after exposure to different concentrations of carbendazim for 4 or 8d. The up-regulation of p53, Apaf1, Cas8 and the down-regulation of Bcl2, Mdm2, Cas3 in the apoptosis pathway, as well as the increased expression of cytokines and chemokines, including CXCL-C1C, CCL1, IL-1b, IFN, IL-8, and TNFα, suggested carbendazim might trigger apoptosis and immune response during zebrafish larval development. In addition, the alteration of mRNA expression of VTG, ERα, ERβ1, ERβ2, TRα, TRβ, Dio1, and Dio2 indicated the potential of carbendazim to induce endocrine disruption in zebrafish larvae. These data suggested that carbendazim could simultaneously induce multiple responses during zebrafish larval development, and bidirectional interactions among oxidative stress, apoptosis pathway, immune and endocrine systems might be present. PMID:26055223

  8. Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters.

    PubMed

    Kharlyngdoh, Joubert Banjop; Pradhan, Ajay; Asnake, Solomon; Walstad, Anders; Ivarsson, Per; Olsson, Per-Erik

    2015-01-01

    Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5α-reductases and β-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE

  9. Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters.

    PubMed

    Kharlyngdoh, Joubert Banjop; Pradhan, Ajay; Asnake, Solomon; Walstad, Anders; Ivarsson, Per; Olsson, Per-Erik

    2015-01-01

    Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5α-reductases and β-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE

  10. Developmental endpoints of chronic exposure to suspected endocrine-disrupting chemicals on benthic and hyporheic freshwater copepods.

    PubMed

    Di Marzio, W D; Castaldo, D; Di Lorenzo, T; Di Cioccio, A; Sáenz, M E; Galassi, D M P

    2013-10-01

    The aims of this study were: (i) to assess if carbamate pesticides and ammonium, widely detected in European freshwater bodies, can be considered ecologically relevant endocrine-disrupting chemicals (EDCs) for benthic and interstitial freshwater copepods; and (ii) to evaluate the potential of copepods as sentinels for monitoring ecosystem health. In order to achieve these objectives, four species belonging to the harpacticoid copepod genus Bryocamptus, namely B. (E.) echinatus, B. (R.) zschokkei, B. (R.) pygmaeus and B. (B.) minutus, were subjected to chronic exposures to Aldicarb and ammonium. A significant deviation from the developmental time of unexposed control cultures was observed for all the species in test cultures. Aldicarb caused an increase in generation time over 80% in both B. minutus and B. zschokkei, but less than 35% in B. pygmaeus and B. echinatus. Ammonium increased generation time over 33% in B. minutus, and 14, 12 and 3.5% for B. pygmaeus, B. zschokkei and B. echinatus, respectively. On the basis of these results it can be concluded that chronic exposure to carbamate pesticides and ammonium alters the post-naupliar development of the test-species and propose their potential role as EDCs, leaving open the basis to search what are the mechanism underlying. A prolonged developmental time would probably produce a detrimental effect on population attributes, such as age structure and population size. These deviations from a pristine population condition may be considered suitable biological indicators of ecosystem stress, particularly useful to compare polluted to unpolluted reference sites. Due to their dominance in both benthic and interstitial habitats, and their sensitivity as test organisms, freshwater benthic and hyporheic copepods can fully be used as sentinel species for assessing health condition of aquatic ecosystems as required by world-wide water legislation. PMID:23890366

  11. In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia.

    PubMed

    Shannon, Maeve; Rehfeld, Anders; Frizzell, Caroline; Livingstone, Christina; McGonagle, Caoimhe; Skakkebaek, Niels E; Wielogórska, Ewa; Connolly, Lisa

    2016-05-15

    The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor. PMID:26965840

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

    EPA Science Inventory

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

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

  15. Parental occupational exposure to endocrine disrupting chemicals and male genital malformations: A study in the danish national birth cohort study

    PubMed Central

    2011-01-01

    Background Sex hormones closely regulate development of the male genital organs during fetal life. The hypothesis that xenobiotics may disrupt endogenous hormonal signalling has received considerable scientific attention, but human evidence is scarce. Objectives We analyse occurrence of hypospadias and cryptorchidism according to maternal and paternal occupational exposure to possible endocrine disrupting chemicals. Methods We conducted a follow-up study of 45,341 male singleton deliveries in the Danish National Birth Cohort during 1997-2009. Information on work during pregnancy was obtained by telephone interviews around gestational week 16. Parents' job titles were classified according to DISCO-88. A job exposure matrix for endocrine disrupting chemicals (EDCs) was implemented to assess occupational exposures. The Medical Birth and National Hospital Register provided data on congenital anomalies diagnosed at birth or during follow-up, which ended in 2009. Crude and adjusted hazard ratios (HR) were obtained from Cox regression models. Results Among all pregnancies, 6.3% were classified as possibly or probably exposed to EDCs. The most prevalent occupations conferring possible exposure were cleaners, laboratory technicians, hairdressers and agricultural workers (58% of all potentially exposed). The final cumulative incidence of cryptorchidism in boys was 2.2% (1002 cases), and of hypospadias 0.6% (262 cases). The occurrence of hypospadias increased when mothers were probably [HRa = 1.8 (95% CI 1.0-2.6)] or possibly exposed to one or more EDCs [HRa = 2.6 (95% CI 1.8-3.4). Possible paternal exposure to heavy metals increased the risk of hypospadias [HRa 2.2 (95% CI: 1.0-3.4)] and cryptorchidism [HRa 1.9 (95% CI: 1.1-2.7)]. None of the exposure groups reached statistical significance. Conclusion The study provides some but limited evidence that occupational exposure to possible endocrine disrupting chemicals during pregnancy increases the risk of hypospadias. PMID

  16. Developmental toxicity and endocrine disruption of naphthenic acids on the early life stage of zebrafish (Danio rerio).

    PubMed

    Wang, Jie; Cao, Xiaofeng; Huang, Yi; Tang, Xiaoyan

    2015-12-01

    Oil sands process-affected water (OSPW) has been reported to exhibit adverse effects on the environment and wildlife. Although the compounds responsible are unknown, naphthenic acids (NAs) have been considered to be implicated. The current study was designed to investigate whether NAs might cause developmental toxicity and endocrine disruption on the early life stage of zebrafish (Danio rerio). The success of embryo hatch was inhibited by 2.5 mg l(-1) oil sands NAs (OS-NAs) exposure, and both OSPW NAs and commercial NAs (C-NAs) exposure resulted in a variety of developmental lesions in the fish larvae, such as yolk sac edema, pericardial edema and spinal malformation. The transcription of genes involved cytochrome P450 aromatase (CYP19a and CYP19b), estrogen receptors (ERα, ERβ1 and ERβ2), and vitellogenin (VTG) was analyzed to evaluate the endocrine disrupting effects of NAs. Significant up-regulated gene expressions of CYP19b, ERα and VTG were observed in both OS-NAs and C-NAs groups, which indicated the deleteriously estrogenic potential of NAs. These results confirmed that NAs derived from crude petroleum could negatively impact the development and endocrine function of zebrafish, and be primarily responsible for the toxicity of OSPW.

  17. Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle.

    PubMed

    Dickerson, Sarah M; Gore, Andrea C

    2007-06-01

    Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with the normal function of an organism's endocrine system. Many EDCs are resistant to biodegradation, due to their structural stability, and persist in the environment. The focus of this review is on natural and artificial EDCs that act through estrogenic mechanisms to affect reproductive neuroendocrine systems. This endocrine axis comprises the hypothalamic gonadotropin-releasing hormone (GnRH), pituitary gonadotropins, and gonadal steroid hormones, including estrogens. Although it is not surprising that EDCs that mimic or antagonize estrogen receptors may exert actions upon reproductive targets, the mechanisms for these effects are complex and involve all three levels of the hypothalamic-pituitary-gonadal (HPG) system. Nevertheless, considerable evidence links exposure to estrogenic environmental EDCs with neuroendocrine reproductive deficits in wildlife and in humans. The effects of an EDC are variable across the life cycle of an animal, and are particularly potent when exposure occurs during fetal and early postnatal development. As a consequence, abnormal sexual differentiation, disrupted reproductive function, or inappropriate sexual behavior may be detected later in life. This review will cover the effects of two representative classes of estrogenic EDCs, phytoestrogens and polychlorinated biphenyls (PCBs), on neuroendocrine reproductive function, from molecules to behavior, across the vertebrate life cycle. Finally, we identify the gaps of knowledge in this field and suggest future directions for study.

  18. Assessment of endocrine-disrupting chemicals attenuation in a coastal plain stream prior to wastewater treatment plant closure

    USGS Publications Warehouse

    Bradley, Paul M.; Journey, Celeste A.

    2014-01-01

    The U.S. Geological Survey is conducting a combined pre/post-closure assessment at a long-term wastewater treatment plant (WWTP) site at Fort Gordon near Augusta, Georgia. Here, we assess select endocrine-active chemicals and benthic macroinvertebrate community structure prior to closure of the WWTP. Substantial downstream transport and limited instream attenuation of endocrine-disrupting chemicals (EDCs) was observed in Spirit Creek over a 2.2-km stream segment downstream of the WWTP outfall. A modest decline (less than 20% in all cases) in surface water detections was observed with increasing distance downstream of the WWTP and attributed to partitioning to the sediment. Estrogens detected in surface water in this study included estrone (E1), 17β-estradiol (E2), and estriol (E3). The 5 ng/l and higher mean estrogen concentrations observed in downstream locations indicated that the potential for endocrine disruption was substantial. Concentrations of alkylphenol ethoxylate (APE) metabolite EDCs also remained statistically elevated above levels observed at the upstream control site. Wastewater-derived pharmaceutical and APE metabolites were detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon. The results indicate substantial EDC occurrence, downstream transport, and persistence under continuous supply conditions and provide a baseline for a rare evaluation of ecosystem response to WWTP closure.

  19. Developmental toxicity and endocrine disruption of naphthenic acids on the early life stage of zebrafish (Danio rerio).

    PubMed

    Wang, Jie; Cao, Xiaofeng; Huang, Yi; Tang, Xiaoyan

    2015-12-01

    Oil sands process-affected water (OSPW) has been reported to exhibit adverse effects on the environment and wildlife. Although the compounds responsible are unknown, naphthenic acids (NAs) have been considered to be implicated. The current study was designed to investigate whether NAs might cause developmental toxicity and endocrine disruption on the early life stage of zebrafish (Danio rerio). The success of embryo hatch was inhibited by 2.5 mg l(-1) oil sands NAs (OS-NAs) exposure, and both OSPW NAs and commercial NAs (C-NAs) exposure resulted in a variety of developmental lesions in the fish larvae, such as yolk sac edema, pericardial edema and spinal malformation. The transcription of genes involved cytochrome P450 aromatase (CYP19a and CYP19b), estrogen receptors (ERα, ERβ1 and ERβ2), and vitellogenin (VTG) was analyzed to evaluate the endocrine disrupting effects of NAs. Significant up-regulated gene expressions of CYP19b, ERα and VTG were observed in both OS-NAs and C-NAs groups, which indicated the deleteriously estrogenic potential of NAs. These results confirmed that NAs derived from crude petroleum could negatively impact the development and endocrine function of zebrafish, and be primarily responsible for the toxicity of OSPW. PMID:25995127

  20. Estrogenic endocrine-disrupting chemicals modulate the production of inflammatory mediators and cell viability of lipopolysaccharide-stimulated macrophages.

    PubMed

    Kim, Hyun Gyung; Yeon, Seung-min; Kim, Kyong Hoon; Kim, Heejoong; Park, Jong-Il; Kang, Hyun-Jin; Cha, Eun Ji; Park, Hee-Deung; Kang, Hyo Jung; Park, Tae Won; Jeon, Young-Ho; Park, Young In; Chang, Kyu-Tae; Jung, Yong Woo

    2015-04-01

    Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-α-ethynylestradiol, 17-β-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages.

  1. Dietary exposure to endocrine disrupting chemicals in metropolitan population from China: a risk assessment based on probabilistic approach.

    PubMed

    He, Dongliang; Ye, Xiaolei; Xiao, Yonghua; Zhao, Nana; Long, Jia; Zhang, Piwei; Fan, Ying; Ding, Shibin; Jin, Xin; Tian, Chong; Xu, Shunqing; Ying, Chenjiang

    2015-11-01

    The intake of contaminated foods is an important exposure pathway for endocrine disrupting chemicals (EDCs). However, data on the occurrence of EDCs in foodstuffs are sporadic and the resultant risk of co-exposure is rarely concerned. In this study, 450 food samples representing 7 food categories (mainly raw and fresh food), collected from three geographic cities in China, were analyzed for eight EDCs using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Besides estrone (E1), other EDCs including diethylstilbestrol (DES), nonylphenol (NP), bisphenol A (BPA), octylphenol (OP), 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3) were ubiquitous in food. Dose-dependent relationships were found between NP and EE2 (r=0.196, p<0.05), BPA (r=0.391, p<0.05). Moreover, there existed a correspondencebetween EDCs congener and food category. Based on the obtained database of EDCs concentration combined with local food consumption, dietary EDCs exposure was estimated using the Monte Carlo Risk Assessment (MCRA) system. The 50th and 95th percentile exposure of any EDCs isomer were far below the tolerable daily intake (TDI) value identically. However, the sum of 17β-estradiol equivalents (∑EEQs) exposure in population was considerably larger than the value of exposure to E2, which implied the underlying resultant risk of multiple EDCs in food should be concern. In conclusion, co-exposure via food consumption should be considered rather than individual EDCs during health risk evaluation. PMID:26025473

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

    PubMed

    Cwiek-Ludwicka, Kazimiera; Ludwicki, Jan K

    2014-01-01

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

  3. Behaviour of estrogenic endocrine-disrupting chemicals in permeable carbonate sands.

    PubMed

    Shepherd, Benjamin O; Erler, Dirk V; Tait, Douglas R; van Zwieten, Lukas; Kimber, Stephen; Eyre, Bradley D

    2015-08-01

    The remediation of four estrogenic endocrine-disrupting compounds (EDCs), estrone (E1), estradiol (E2), ethinylestradiol (EE2) and estriol (E3), was measured in saturated and unsaturated carbonate sand-filled columns dosed with wastewater from a sewage treatment plant. The estrogen equivalency (EEQ) of inlet wastewater was 1.2 ng L(-1) and was remediated to an EEQ of 0.5 ng L(-1) through the unsaturated carbonate sand-filled columns. The high surface area of carbonate sand and associated high microbial activity may have assisted the degradation of these estrogens. The fully saturated sand columns showed an increase in total estrogenic potency with an EEQ of 2.4 ng L(-1), which was double that of the inlet wastewater. There was a significant difference (P < 0.05) in total estrogenic potency between aerobic and anaerobic columns. The breakdown of conjugated estrogens to estrogenic EDCs formed under long residence time and reducing conditions may have been responsible for the increase in the fully saturated columns. This may also be explained by the desorption of previously sorbed estrogenic EDCs. The effect of additional filter materials, such as basalt sediment and coconut fibre, on estrogenic EDC reduction was also tested. None of these amendments provided improvements in estrogen remediation relative to the unamended unsaturated carbonate sand columns. Aerobic carbonate sand filters have good potential to be used as on-site wastewater treatment systems for the reduction of estrogenic EDCs. However, the use of fully saturated sand filters, which are used to promote denitrification, and the loss of nitrogen as N2 were shown to cause an increase in EEQ. The potential for the accumulation of estrogenic EDCs under anaerobic conditions needs to be considered when designing on-site sand filtration systems required to reduce nitrogen. Furthermore, the accumulation of estrogens under anaerobic conditions such as under soil absorption systems or leachate fields has the

  4. Pesticide mixtures, endocrine disruption, and amphibian declines: are we underestimating the impact?

    PubMed

    Hayes, Tyrone B; Case, Paola; Chui, Sarah; Chung, Duc; Haeffele, Cathryn; Haston, Kelly; Lee, Melissa; Mai, Vien Phoung; Marjuoa, Youssra; Parker, John; Tsui, Mable

    2006-04-01

    Amphibian populations are declining globally at an alarming rate. Pesticides are among a number of proposed causes for these declines. Although a sizable database examining effects of pesticides on amphibians exists, the vast majority of these studies focus on toxicological effects (lethality, external malformations, etc.) at relatively high doses (parts per million). Very few studies focus on effects such as endocrine disruption at low concentrations. Further, most studies examine exposures to single chemicals only. The present study examined nine pesticides (four herbicides, two fungicides, and three insecticides) used on cornfields in the midwestern United States. Effects of each pesticide alone (0.1 ppb) or in combination were examined. In addition, we also examined atrazine and S-metolachlor combined (0.1 or 10 ppb each) and the commercial formulation Bicep II Magnum, which contains both of these herbicides. These two pesticides were examined in combination because they are persistent throughout the year in the wild. We examined larval growth and development, sex differentiation, and immune function in leopard frogs (Rana pipiens). In a follow-up study, we also examined the effects of the nine-compound mixture on plasma corticosterone levels in male African clawed frogs (Xenopus laevis). Although some of the pesticides individually inhibited larval growth and development, the pesticide mixtures had much greater effects. Larval growth and development were retarded, but most significantly, pesticide mixtures negated or reversed the typically positive correlation between time to metamorphosis and size at metamorphosis observed in controls: exposed larvae that took longer to metamorphose were smaller than their counterparts that metamorphosed earlier. The nine-pesticide mixture also induced damage to the thymus, resulting in immunosuppression and contraction of flavobacterial meningitis. The study in X. laevis revealed that these adverse effects may be due to an

  5. Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    PubMed Central

    Legler, Juliette; Fletcher, Tony; Govarts, Eva; Porta, Miquel; Blumberg, Bruce; Heindel, Jerrold J.

    2015-01-01

    Context: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. Results: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555–5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6–86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200–56 400) with associated costs of €835 million (sensitivity analysis: €835 million–16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion

  6. Behaviour of estrogenic endocrine-disrupting chemicals in permeable carbonate sands.

    PubMed

    Shepherd, Benjamin O; Erler, Dirk V; Tait, Douglas R; van Zwieten, Lukas; Kimber, Stephen; Eyre, Bradley D

    2015-08-01

    The remediation of four estrogenic endocrine-disrupting compounds (EDCs), estrone (E1), estradiol (E2), ethinylestradiol (EE2) and estriol (E3), was measured in saturated and unsaturated carbonate sand-filled columns dosed with wastewater from a sewage treatment plant. The estrogen equivalency (EEQ) of inlet wastewater was 1.2 ng L(-1) and was remediated to an EEQ of 0.5 ng L(-1) through the unsaturated carbonate sand-filled columns. The high surface area of carbonate sand and associated high microbial activity may have assisted the degradation of these estrogens. The fully saturated sand columns showed an increase in total estrogenic potency with an EEQ of 2.4 ng L(-1), which was double that of the inlet wastewater. There was a significant difference (P < 0.05) in total estrogenic potency between aerobic and anaerobic columns. The breakdown of conjugated estrogens to estrogenic EDCs formed under long residence time and reducing conditions may have been responsible for the increase in the fully saturated columns. This may also be explained by the desorption of previously sorbed estrogenic EDCs. The effect of additional filter materials, such as basalt sediment and coconut fibre, on estrogenic EDC reduction was also tested. None of these amendments provided improvements in estrogen remediation relative to the unamended unsaturated carbonate sand columns. Aerobic carbonate sand filters have good potential to be used as on-site wastewater treatment systems for the reduction of estrogenic EDCs. However, the use of fully saturated sand filters, which are used to promote denitrification, and the loss of nitrogen as N2 were shown to cause an increase in EEQ. The potential for the accumulation of estrogenic EDCs under anaerobic conditions needs to be considered when designing on-site sand filtration systems required to reduce nitrogen. Furthermore, the accumulation of estrogens under anaerobic conditions such as under soil absorption systems or leachate fields has the

  7. HORMONAL PROCESSES IN DECAPOD CRUSTACEAN LARVAE AS BIOMARKERS OF ENDOCRINE DISRUPTING CHEMICALS IN THE MARINE ENVIRONMENT

    EPA Science Inventory

    Knowledge of endocrine control of the complex larval developmental processes in insects (metamorphosis) has led to the introduction of insect hormones and their analogues as insecticides known as insect growth regulators (IGRs) with the largest group being juvenile hormone analog...

  8. EVALUATION OF TRICLOSAN AS A POTENTIAL ENDOCRINE DISRUPTING CHEMICAL (POSTER SESSION)

    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. ...

  9. Screening breeding sites of the common toad (Bufo bufo) in England and Wales for evidence of endocrine disrupting activity.

    PubMed

    Pickford, Daniel B; Jones, Alexandra; Velez-Pelez, Alejandra; Orton, Frances; Iguchi, Taisen; Mitsui, Naoko; Tooi, Osamu

    2015-07-01

    Anuran amphibians are often present in agricultural landscapes and may therefore be exposed to chemicals in surface waters used for breeding. We used passive accumulation devices (SPMD and POCIS) to sample contaminants from nine breeding sites of the Common toad (Bufo bufo) across England and Wales, measuring endocrine activity of the extracts in a recombinant yeast androgen screen (YAS) and yeast estrogen screen (YES) and an in vitro vitellogenin induction screen in primary culture of Xenopus laevis hepatocytes. We also assessed hatching, growth, survival, and development in caged larvae in situ, and sampled metamorphs for gonadal histopathology. None of the SPMD extracts exhibited estrogen receptor or androgen receptor agonist activity, while POCIS extracts from two sites in west-central England exhibited concentration-dependent androgenic activity in the YAS. Three sites exhibited significant estrogenic activity in both the YES and the Xenopus hepatocyte. Hatching rates varied widely among sites, but there was no consistent correlation between hatching rate and intensity of agricultural activity, predicted concentrations of agrochemicals, or endocrine activity measured in YES/YAS assays. While a small number of intersex individuals were observed, their incidence could not be associated with predicted pesticide exposure or endocrine activitity measured in the in vitro screens. There were no significant differences in sex ratio, as determined by gonadal histomorphology among the study sites, and no significant correlation was observed between proportion of males and predicted exposure to agrochemicals. However, a negative correlation did become apparent in later sampling periods between proportion of males and estrogenic activity of the POCIS sample, as measured in the YES. Our results suggest that larval and adult amphibians may be exposed to endocrine disrupting chemicals in breeding ponds, albeit at low concentrations, and that chemical contaminants other than

  10. Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians--screening for estrogen, androgen and thyroid hormone disruption.

    PubMed

    Scholz, S; Renner, P; Belanger, S E; Busquet, F; Davi, R; Demeneix, B A; Denny, J S; Léonard, M; McMaster, M E; Villeneuve, D L; Embry, M R

    2013-01-01

    Endocrine disruption is considered a highly relevant hazard for environmental risk assessment of chemicals, plant protection products, biocides and pharmaceuticals. Therefore, screening tests with a focus on interference with estrogen, androgen, and thyroid hormone pathways in fish and amphibians have been developed. However, they use a large number of animals and short-term alternatives to animal tests would be advantageous. Therefore, the status of alternative assays for endocrine disruption in fish and frogs was assessed by a detailed literature analysis. The aim was to (i) determine the strengths and limitations of alternative assays and (ii) present conclusions regarding chemical specificity, sensitivity, and correlation with in vivo data. Data from 1995 to present were collected related to the detection/testing of estrogen-, androgen-, and thyroid-active chemicals in the following test systems: cell lines, primary cells, fish/frog embryos, yeast and cell-free systems. The review shows that the majority of alternative assays measure effects directly mediated by receptor binding or resulting from interference with hormone synthesis. Other mechanisms were rarely analysed. A database was established and used for a quantitative and comparative analysis. For example, a high correlation was observed between cell-free ligand binding and cell-based reporter cell assays, between fish and frog estrogenic data and between fish embryo tests and in vivo reproductive effects. It was concluded that there is a need for a more systematic study of the predictive capacity of alternative tests and ways to reduce inter- and intra-assay variability.

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

    EPA Science Inventory

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

  12. Probing the binding of an endocrine disrupting compound-Bisphenol F to human serum albumin: Insights into the interactions of harmful chemicals with functional biomacromolecules

    NASA Astrophysics Data System (ADS)

    Pan, Fang; Xu, Tianci; Yang, Lijun; Jiang, Xiaoqing; Zhang, Lei

    2014-11-01

    Bisphenol F (BPF) as an endocrine disrupting compounds (EDCs) pollutant in the environment poses a great threat to human health. To evaluate the toxicity of BPF at the protein level, the effects of BPF on human serum albumin (HSA) were investigated at three temperatures 283, 298, and 308 K by multiple spectroscopic techniques. The experimental results showed that BPF effectively quenched the intrinsic fluorescence of HSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and the binding subdomain were measured, and indicated that BPF could spontaneously bind with HSA on subdomain IIA through H-bond and van der Waals interactions. Furthermore, the conformation of HSA was demonstrably changed in the presence of BPF. The work provides accurate and full basic data for clarifying the binding mechanisms of BPF with HSA in vivo and is helpful for understanding its effect on protein function during its transportation and distribution in blood.

  13. Occurrence and risk assessment of pharmaceuticals and personal care products and endocrine disrupting chemicals in reclaimed water and receiving groundwater in China.

    PubMed

    Li, Zhen; Xiang, Xi; Li, Miao; Ma, Yeping; Wang, Jihua; Liu, Xiang

    2015-09-01

    Groundwater recharge using reclaimed water is considered a promising method to alleviate groundwater depletion. However, pollutants in reclaimed water could be recharged into groundwater during this process, thereby posing a risk to groundwater and human health. In this study, 12 cities in northern China were selected for reclaimed water and groundwater sampling. Analysis of the samples revealed the presence of nine pharmaceutical and personal care products (PPCPs) and five endocrine disrupting compounds (EDCs). In reclaimed water, all the PPCPs and EDCs were found, with sulpiride (SP) and estriol (E3) being most frequently detected. In groundwater samples, only ketoprofen (KP), mefenamic acid (MA), nalidixic acid (NA) and SP were detected among PPCPs, while bisphenol-A (BPA) was dominant among the target EDCs. The risk quotients (RQs) of all target PPCPs and EDCs except 17α-ethinyl estradiol (EE2) and E3 were below 1 in groundwater samples, indicating that EE2 and E3 deserve priority preferential treatment before recharging.

  14. Vitellogenin expression in wild cyprinid Petroleuciscus esfahani as a biomarker of endocrine disruption along the Zayandeh Roud River, Iran.

    PubMed

    Gilannejad, Neda; Dorafshan, Salar; Heyrati, Fatemeh Paykan; Soofiani, Nasrollah Mahboobi; Asadollah, Saeid; Martos-Sitcha, Juan Antonio; Prat, Francisco; Yúfera, Manuel; Martínez-Rodríguez, Gonzalo

    2016-02-01

    Aquatic environments are the ultimate sink for most of anthropogenic pollutants. The Zayandeh Roud River is the most important river in the central Iranian Plateau, supplying water to a large population. In order to determine the potential occurrence and in vivo effects of Endocrine Disrupting Chemicals (EDCs) with estrogenic or anti-androgenic properties we analyzed the wild populations of an extensively distributed endemic fish species, Petroleuciscus esfahani. For this purpose, specimens were caught from two sites upstream and two sites downstream of the expected major anthropogenic pollution sources. P. esfahani full-length cDNAs for vitellogenin (vtg), with 4177 base pairs (bp) encoding a 1339 amino acids (aa), and for β-actin (actb), with 1776 bp encoding a 375 aa, were amplified and cloned. Hepatic vtg mRNA expression levels were measured by quantitative real-time PCR. Condition factor, gonadosomatic index and sex ratio were calculated and compared with vtg expression. Gonad histology was performed to study the possible presence of intersex condition. Detection of vtg transcripts in male individuals from the two downstream sampling sites supports the hypothesis of exposure to EDCs in these regions. Higher vtg expression in male individuals, together with reduced gonad size and condition factor, in specimens from the site located downstream of the major steel mill plant suggest a major endocrine disruption in this area.

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

    PubMed

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

    2016-01-01

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

  16. Vitellogenin expression in wild cyprinid Petroleuciscus esfahani as a biomarker of endocrine disruption along the Zayandeh Roud River, Iran.

    PubMed

    Gilannejad, Neda; Dorafshan, Salar; Heyrati, Fatemeh Paykan; Soofiani, Nasrollah Mahboobi; Asadollah, Saeid; Martos-Sitcha, Juan Antonio; Prat, Francisco; Yúfera, Manuel; Martínez-Rodríguez, Gonzalo

    2016-02-01

    Aquatic environments are the ultimate sink for most of anthropogenic pollutants. The Zayandeh Roud River is the most important river in the central Iranian Plateau, supplying water to a large population. In order to determine the potential occurrence and in vivo effects of Endocrine Disrupting Chemicals (EDCs) with estrogenic or anti-androgenic properties we analyzed the wild populations of an extensively distributed endemic fish species, Petroleuciscus esfahani. For this purpose, specimens were caught from two sites upstream and two sites downstream of the expected major anthropogenic pollution sources. P. esfahani full-length cDNAs for vitellogenin (vtg), with 4177 base pairs (bp) encoding a 1339 amino acids (aa), and for β-actin (actb), with 1776 bp encoding a 375 aa, were amplified and cloned. Hepatic vtg mRNA expression levels were measured by quantitative real-time PCR. Condition factor, gonadosomatic index and sex ratio were calculated and compared with vtg expression. Gonad histology was performed to study the possible presence of intersex condition. Detection of vtg transcripts in male individuals from the two downstream sampling sites supports the hypothesis of exposure to EDCs in these regions. Higher vtg expression in male individuals, together with reduced gonad size and condition factor, in specimens from the site located downstream of the major steel mill plant suggest a major endocrine disruption in this area. PMID:26479453

  17. Endocrine disrupting, haematological and biochemical effects of polybrominated diphenyl ethers in a terrestrial songbird, the European starling (Sturnus vulgaris).

    PubMed

    Van den Steen, Evi; Eens, Marcel; Geens, Ann; Covaci, Adrian; Darras, Veerle M; Pinxten, Rianne

    2010-11-15

    We exposed female European starlings (Sturnus vulgaris) during a 6month period to environmentally relevant concentrations of a pentabromodiphenyl ether (Penta-BDE) mixture (about 1740μg/kg body weight) through subcutaneous implants, and examined endocrine disruptive, haematological and biochemical effects. To investigate endocrine disrupting effects of PBDEs, testosterone, estradiol and thyroid hormones (T(3) and T(4)) were measured in the plasma. We found no significant differences between the control and exposed groups for any of the hormones. However, 14days after implantation, T(3) concentrations tended to be lower in the exposed group compared to the control group. For albumin, our results suggest that short term exposure of PBDEs may result in a negative effect on albumin, while the opposite was observed on a longer term (6months after implantation). However, from the statistical analysis, effects on albumin disappeared when excluding females that laid eggs. These results demonstrate that observed effects during the breeding season should be interpreted carefully when the breeding status of females is unknown. There were no significant differences found between the control and exposed groups for the other biochemical parameters (total protein, uric acid, cholesterol, aspartate transaminase, total antioxidative capacity, high-density lipoproteins and creatine kinase) and haematological parameters (amount of red blood cells, haemoglobin concentration, haematocrit, mean corpuscular volume and mean corpuscular haemoglobin). All together, our results suggest that European starlings, similar to other passerine species, may be less sensitive to the effects of organohalogenated pollutants, such as PBDEs, than other bird species. PMID:20888617

  18. Impedance Biosensing to detect food allergens, endocrine disrupting chemicals, and food pathogens

    NASA Astrophysics Data System (ADS)

    Radhakrishnan, Rajeswaran

    Electrochemical impedance biosensors can be viewed as an AC electroanalytical method for the analyte detection in the fields of biomedicine, environmental monitoring, and food and agriculture, amongst others. The most common format for AC impedance biosensing involves surface immobilization of an antibody, receptor protein, DNA strand, or other species capable of bio-recognition, and AC impedance detection of the binding event. Technological application of AC impedance biosensors has been hindered by several obstacles, including the more complex circuitry required for AC relative to DC electrochemistry, chemical and physical interference arising from non-specific adsorption, and the stability and reproducibility of protein immobilization. One focus of these PhD studies is on methods to reduce or compensate for non-specific adsorption, including sample dilution, site blocking with BSA, and the use of control electrodes onto which reference antibodies are immobilized. Examples that will be presented include impedance detection of food pathogens, such as Listeria monocytogenes, using a mouse monoclonal antibody immobilized onto an Au electrode. This yields detection limits of 5 CFU/ml and 4 CFU/ml for ideal solutions and filtered tomato extract, respectively. Control experiments with an Au electrode onto which a mouse monoclonal antibody to GAPDH is immobilized demonstrate that non-specific adsorption is insignificant for the system and methodology studied here. Control experiments with Salmonella enterica demonstrate no cross-reactivity to this food pathogen. In addition, Detection of two endocrine-disrupting chemicals (EDC), norfluoxetine and BDE-47, is reported here by impedance biosensing, with a detection limit of 8.5 and 1.3 ng/ml for norfluoxetine and BDE-47, respectively. Additional research has focused on alternative substrates and linker chemistries for protein immobilization, including the use of degenerate (highly doped) Si and bidendate thiol monolayer

  19. Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnaea stagnalis Exposed to Different Endocrine Disrupting Chemicals

    PubMed Central

    Giusti, Arnaud; Leprince, Pierre; Mazzucchelli, Gabriel; Thomé, Jean-Pierre; Lagadic, Laurent; Ducrot, Virginie; Joaquim-Justo, Célia

    2013-01-01

    Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant

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

    PubMed

    Manickum, T; John, W

    2014-01-15

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

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

    PubMed

    Manickum, T; John, W

    2014-01-15

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

  2. SIGNIFICANCE OF EXPERIMENTAL STUDIES FOR ASSESSING ADVERSE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS

    EPA Science Inventory

    The U.S. Environmental Protection Agency (US EPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce andr...

  3. INTERLABORATORY STUDY ON THE USE OF STEROID HORMONES IN EXAMINING ENDOCRINE DISRUPTION.

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among ...

  4. AN INTERLABORATORY STUDY ON THE USE OF STEROID HORMONES IN EVALUATING ENDOCRINE DISRUPTION

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among a...

  5. AN INTERLABORATORY STUDY ON THE USE OF STERIOD HORMONES IN EXAMINING ENDOCRINE DISRUPTION.

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among a...

  6. Nigerian bonny light crude oil induces endocrine disruption in male rats.

    PubMed

    Adedara, Isaac A; Ebokaiwe, Azubike P; Mathur, Premendu P; Farombi, Ebenezer O

    2014-04-01

    Exposure to Nigerian bonny light crude oil (BLCO) in the southern part of Nigeria has been reported to be associated with reproductive toxicity, but there is paucity of information on its interference with steroidogenesis. This study investigated the influence of BLCO on testicular steroidogenesis and plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Adult male Wistar rats were orally treated with BLCO dissolved in corn oil at 0, 200 and 800 mg/kg for 7 days. Immunoblot analysis revealed that BLCO exposure suppressed steroid acute regulatory protein and androgen-binding protein expression with concomitant decrease in 3β-hydroxysteroid dehydrogenase (HSD) and 17β-hydroxysteroid dehydrogenase activities. BLCO exposure significantly decreased plasma concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin and intratesticular testosterone, but elevated thyrotropin, triiodothyronine and thyroxine above the control values. The data presented herein indicate that undue exposure to BLCO has an inhibitory effect on testicular steroidogenesis. The underlying mechanisms for BLCO-induced testicular dysfunction may involve its disruptive effect on the brain-pituitary-testicular axis. These observations highlight the potential risk to public health for a population where, unfortunately, oil spillages occur freq