Science.gov

Sample records for potential endocrine disrupting

  1. 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. ...

  2. 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

  3. 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...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  6. 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

  7. 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

    2016-01-01

    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

  8. 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

  9. 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

  10. 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

  11. 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...

  12. 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...

  13. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

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

  14. Endocrine Effects of Circadian Disruption.

    PubMed

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

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems. PMID:26208951

  15. 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.

  16. 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. ...

  17. 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

  18. 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

  19. 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.

  20. 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

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

    PubMed

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

    2010-12-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17β-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use. PMID:20970168

  2. 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.

  3. 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.

    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.

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. Direct photodegradation of androstenedione and testosterone in natural sunlight: inhibition by dissolved organic matter and reduction of endocrine disrupting potential.

    PubMed

    Young, Robert B; Latch, Douglas E; Mawhinney, Douglas B; Nguyen, Thanh-Hoa; Davis, Jasmine C C; Borch, Thomas

    2013-08-01

    In surface waters, two of the most commonly observed androgenic steroid hormones are androstenedione (AD) and testosterone (T). This study compares the photodegradation of dilute (<10 μg L(-1)) aqueous solutions of AD and T in natural sunlight, and evaluates the endocrine-disrupting potential of the resulting solutions. This study also examines the effect of dissolved organic matter (DOM) on AD photodegradation. During spring and summer at Henderson, NV, USA (latitude 36.04°N), AD and T underwent direct photodegradation, with half-lives ranging from 3.7 to 10.8 h. In three model DOM solutions, AD's half-life increased by 11% to 35%. Using screening factors to eliminate DOM's inner filter effect, quantum yield calculations suggested that light screening was primarily responsible for AD's increased half-life, and that physical quenching further inhibited AD's photodegradation in two out of three DOM solutions. In vitro androgenic activity of the AD and T solutions decreased approximately as fast as AD and T were removed, suggesting that solar photodegradation reduces the risk of endocrine disruption in surface waters impacted by AD or T, subject to continuing inputs. Reduced in vitro androgenic activity appears to be related to steroid ring cleavage and the formation of highly oxidized photoproducts. PMID:23796267

  9. 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

  10. 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...

  11. 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...

  12. The challenge posed by endocrine-disrupting chemicals.

    PubMed Central

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

    1997-01-01

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

  13. Aerobic biodegradation potential of endocrine disrupting chemicals in surface-water sediment at Rocky Mountains National Park, USA

    USGS Publications Warehouse

    Bradley, Paul M.; Battaglin, William A.; Iwanowicz, Luke; Clark, Jimmy M.; Journey, Celeste A.

    2016-01-01

    Endocrine disrupting chemicals (EDC) in surface water and bed sediment threaten the structure and function of aquatic ecosystems. In natural, remote, and protected surface-water environments where contaminant releases are sporadic, contaminant biodegradation is a fundamental driver of exposure concentration, timing, duration, and, thus, EDC ecological risk. Anthropogenic contaminants, including known and suspected EDC, were detected in surface water and sediment collected from 2 streams and 2 lakes in Rocky Mountains National Park (ROMO). The potential for aerobic EDC biodegradation was assessed in collected sediments using 6 14C-radiolabeled model compounds. Aerobic microbial mineralization of natural (estrone and 17β-estradiol) and synthetic (17α-ethinylestradiol) estrogen was significant at all sites. ROMO bed sediment microbial communities also effectively degraded the xenoestrogens, bisphenol-A and 4-nonylphenol. The same sediment samples exhibited little potential for aerobic biodegradation of triclocarban, however, illustrating the need to assess a wider range of contaminant compounds. The current results support recent concerns over the widespread environmental occurrence of carbanalide antibacterials, like triclocarban and triclosan, and suggest that backcountry use of products containing these compounds should be discouraged.

  14. Aerobic biodegradation potential of endocrine-disrupting chemicals in surface-water sediment at Rocky Mountain National Park, USA.

    PubMed

    Bradley, Paul M; Battaglin, William A; Iwanowicz, Luke R; Clark, Jimmy M; Journey, Celeste A

    2016-05-01

    Endocrine-disrupting chemicals (EDCs) in surface water and bed sediment threaten the structure and function of aquatic ecosystems. In natural, remote, and protected surface-water environments where contaminant releases are sporadic, contaminant biodegradation is a fundamental driver of exposure concentration, timing, duration, and, thus, EDC ecological risk. Anthropogenic contaminants, including known and suspected EDCs, were detected in surface water and sediment collected from 2 streams and 2 lakes in Rocky Mountain National Park (Colorado, USA). The potential for aerobic EDC biodegradation was assessed in collected sediments using 6 (14) C-radiolabeled model compounds. Aerobic microbial mineralization of natural (estrone and 17β-estradiol) and synthetic (17α-ethinylestradiol) estrogen was significant at all sites. Bed sediment microbial communities in Rocky Mountain National Park also effectively degraded the xenoestrogens bisphenol-A and 4-nonylphenol. The same sediment samples exhibited little potential for aerobic biodegradation of triclocarban, however, illustrating the need to assess a wider range of contaminant compounds. The present study's results support recent concerns over the widespread environmental occurrence of carbanalide antibacterials, like triclocarban and triclosan, and suggest that backcountry use of products containing these compounds should be discouraged. Environ Toxicol Chem 2016;35:1087-1096. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. PMID:26588039

  15. 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

  16. 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...

  17. 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 ...

  18. 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

  19. Estuarine and coastal zone marine pollution by the nonionic alkylphenol ethoxylates endocrine disrupters: is there a potential ecotoxicological problem?

    PubMed

    Zoller, Uri

    2006-02-01

    The nonionic biodegradation-resistant ("hard") alkylphenol ethoxylate (APEO) surfactants and their degradation products are known endocrine disrupting chemicals (EDCs). We report here the findings concerning the APEOs concentrations and homologic distribution profiles in Israel's estuarine and coastal zone seawater to serve as a case study. The concentrations in sewage-containing rivers, estuaries and 50-60-m offshore sea (Mediterranean) water were found to be 12.5-75.1, 4.2-25.0 and 0.9-2.6 microg/L, respectively. The corresponding homologic distribution profiles were found to be within the range of 1-10% each, somewhat skewing, as expected, towards the more toxic shorter-chain ethoxylates. Egg production by zebrafish, exposed to 75, 25 and 10 microg/L of a typical industrial APEOs was reduced up to 89.6%, 84.7% and 76.9%, respectively, between the 8th and 28th days of exposure. Apparently, there is a potential APEOs-related ecotoxicological health risk problem. PMID:16225920

  20. 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

    and DPTE are potent AR antagonists and the alterations in LAT gene transcription suggest that these compounds can affect neuronal functions and should be considered as potential neurotoxic and endocrine disrupting compounds. PMID:25454221

  1. Emerging endocrine disrupters: perfluoroalkylated substances.

    PubMed

    Jensen, Allan Astrup; Leffers, Henrik

    2008-04-01

    In recent years, polyfluorinated chemicals (PFCs) have increasingly been used as surfactants in various industry- and consumer products, because of their unique properties as repellents of dirt, water and oils. The most well-known PFCs are perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their derivatives belonging to the group of perfluoroalkylated substances. The PFCs are very persistent in the environment, and some of them have been discovered as global pollutants of air, water, soil and wildlife and even found in remote polar areas. Bioaccumulation occurs also in humans, and everybody in our society has traces of these PFCs in their blood and internal organs such as the liver, kidneys, spleen, gall bladder and testes. In the blood, PFOS and PFOA are bound to serum proteins. The acute toxicity of the polyfluorinated substances is moderate but some substances can induce peroxisome proliferation in rat livers and may change the fluidity of cell membranes. Some of these PFCs, such as PFOS and PFOA, are potential developmental toxicants and are suspected endocrine disruptors with effects on sex hormone levels resulting in lower testosterone levels and higher oestradiol level. Other PFCs have oestrogenic effects in cell cultures. The industrial production of PFOS and its derivatives stopped in 2000, and the European Union has banned most uses from the summer of 2008. However, hundreds of related chemicals: homologues with shorter or longer alkyl chain, PFOA and telomers, which potentially may degrade to perfluoroalkanoic (carboxylic) acids, are not regulated. PMID:18315716

  2. 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

  3. 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...

  4. Endocrine Disrupting Chemicals and Disease Susceptibility

    PubMed Central

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

    2011-01-01

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

  5. 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. ...

  6. 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

  7. 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

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

    PubMed

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

    2013-01-01

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

  9. 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

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

    EPA Science Inventory

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

  11. Pretilachlor has the potential to induce endocrine disruption, oxidative stress, apoptosis and immunotoxicity during zebrafish embryo development.

    PubMed

    Jiang, Jinhua; Chen, Yanhong; Yu, Ruixian; Zhao, Xueping; Wang, Qiang; Cai, Leiming

    2016-03-01

    The objectives of the present study were to investigate the toxic effects of pretilachlor on zebrafish during its embryo development. The results demonstrated that the transcription of genes involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis was increased after exposure to 50, 100, 200μg/L pretilachlor for 96h, the aromatase activity, vitellogenin (VTG) and thyroid hormones T3 and T4 levels in zebrafish were also up-regulated simultaneously. Pretilachlor exposure induced a noticeable increase in ROS level, increased the transcription and level of antioxidant proteins (e.g., CAT, SOD and GPX). Moreover, the up-regulation of P53, Mdm2, Bbc3 expression and Caspase3 and Caspase9 activities in the apoptosis pathway suggested pretilachlor might trigger cell apoptosis in zebrafish. In addition, the transcription of CXCL-C1C, IL-1β and IL-8 related to the innate immunity was down-regulated after pretilachlor exposure. These data suggested that pretilachlor could simultaneously induce endocrine disruption, apoptosis, oxidative stress and immunotoxicity during zebrafish embryo development. PMID:26851375

  12. 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

  13. 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

  14. 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

  15. 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

  16. The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells.

    PubMed

    Asnake, Solomon; Pradhan, Ajay; Kharlyngdoh, Joubert Banjop; Modig, Carina; Olsson, Per-Erik

    2015-12-01

    Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, allyl-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropyl-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyl-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR. In silico modeling studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the chicken AR ligand-binding pocket. In vitro transfection assays revealed that all three brominated compounds acted as chicken AR antagonists, inhibiting testosterone induced AR activation. In addition, qRT-PCR studies confirmed that they act as AR antagonists and demonstrated that they also alter gene expression patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE, TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken. PMID:26318274

  17. 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

  18. ENVIRONMENTAL ANALYSIS OF ENDOCRINE DISRUPTING EFFECTS FROM HYDROCARBON CONTAMINANTS IN THE ECOSYSTEM

    EPA Science Inventory

    The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disrupters. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals an...

  19. Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.

    PubMed

    Uchida, Masaya; Ishibashi, Hiroshi; Yamamoto, Ryoko; Koyanagi, Akiko; Kusano, Teruhiko; Tominaga, Nobuaki; Ishibashi, Yasuhiro; Arizono, Koji

    2015-09-01

    Although several previous studies have demonstrated the presence of equine estrogens in the aquatic environment, limited data are currently available on the endocrine-disrupting potentials in fish and the risks they pose to aquatic organisms. To investigate the interactions of major equine estrogens equilin (Eq) and equilenin (Eqn), as well as their metabolites 17α-dihydroequilin, 17β-dihydroequilin, 17α-dihydroequilenin and 17β-dihydroequilenin, with the estrogen receptor α (ERα) of medaka (Oryzias latipes), a three-dimensional model of the ligand-binding domain (LBD) of ERα was built in silico, and docking simulations were performed. The docking simulation analysis indicated that the interaction of 17β-dihydroequilenin with the ERα LBD is the most potent, followed by those of 17α-dihydroequilin and 17β-dihydroequilin, whereas those of Eq and Eqn were least potent. We further analyzed gene expression profiles in the livers of male medaka exposed to Eq and Eqn. A DNA microarray representing 6000 genes revealed that 24-h exposure to Eq and Eqn (100 ng/L) upregulated the expression of 6 and 34 genes in the livers of males, respectively. Genes upregulated by Eq included the estrogenic biomarker genes vitellogenins and choriogenins, suggesting the estrogenic potential of Eq. In contrast, Eqn exposure upregulated several cancer-related genes, such as mediator complex subunit 16 and RAS oncogene family members, suggesting a carcinogenic potential for Eqn. These results suggest that equine estrogens may have not only endocrine-disrupting potentials via the ERα signaling pathway but also carcinogenic potency in male medaka. PMID:25611945

  20. 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

  1. Distribution and seasonal variation of estrogenic endocrine disrupting compounds, N-nitrosodimethylamine, and N-nitrosodimethylamine formation potential in the Huangpu River, China.

    PubMed

    Zhang, Ai; Li, Yongmei; Chen, Ling

    2014-05-01

    Detection of estrogenic endocrine disrupting compounds (EDCs) and N-nitrosodimethylamine (NDMA) in drinking water has led to rising concerns. There are, however, a paucity of studies on the distribution and seasonal variation of NDMA and NDMA formation potential (NDMA-FP) in natural waters, especially in China. For EDCs, limited studies have investigated the distribution and seasonal variation of estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), technical-nonylphenols (t-NP), and bisphenol A (BPA) in Shanghai. In this study, water samples were collected from 11 sampling sites along the Huangpu River in 2012. The distribution and seasonal variation of EDCs, NDMA, and NDMA-FP were investigated. The results showed that all of the 11 sampling sites were contaminated by the target compounds. Compared with E2 and EE2, higher E1 and E3 concentrations were usually detected in the Huangpu River. The values of 17β-estradiol equivalents (EEQ) suggest a high possibility of endocrine effects on exposed organisms in the Huangpu River. NDMA-FP and t-NP were the dominant contaminants among the eight target compounds. The detection rates of the target compounds and their concentrations were both higher in dry seasons than in wet seasons. Higher concentrations of target compounds were observed in urban sampling sites near drainage outlets, and also in suburban sampling sites where intensive livestock farming and farmlands were located. PMID:25079632

  2. Exploring potential contributors to endocrine disrupting activities in Taiwan's surface waters using yeast assays and chemical analysis.

    PubMed

    Chou, Pei-Hsin; Lin, Yi-Ling; Liu, Tong-Cun; Chen, Kuang-Yu

    2015-11-01

    Surface waters serve as sinks for anthropogenic contaminants, including naturally occurring hormones and a variety of synthetic endocrine active substances. To investigate the presence of endocrine active contaminants in the aquatic environment in Taiwan, river water and suspended solids were analyzed by yeast assays to examine the distribution of estrogenic, androgenic, and aryl hydrocarbon receptor agonist activities. The results showed that dry-season river samples exhibited strong estrogenic and aryl hydrocarbon receptor agonist activities, but no androgenic activity was detected. Owing to the ubiquitous detection of estrogenic activities in Taiwan's surface waters, samples were further subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for quantification of selected estrogenic compounds. LC-MS/MS results indicated that natural estrogens, such as estrone and 17β-estradiol were often the most contributing compounds for the bioassay-derived estrogenic activities due to their strong estrogenic potencies and high detection frequencies, whereas high concentrations of bisphenol A and nonylphenol also posed a threat to the aquatic ecosystems in Taiwan. Water samples eliciting strong estrogenic activities were further fractionated using high performance liquid chromatography, and significant estrogenic activities were detected in fractions containing estrone, 17β-estradiol, 17α-ethynylestradiol, and bisphenol A. Also, the presence of unidentified estrogenic compounds was found in few river water samples. Further identification of unknown endocrine active substances is necessary to better protect the aquatic environment in Taiwan. PMID:26295540

  3. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    PubMed

    Nashev, Lyubomir G; Schuster, Daniela; Laggner, Christian; Sodha, Seloni; Langer, Thierry; Wolber, Gerhard; Odermatt, Alex

    2010-04-15

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), which catalyzes the last step of testosterone synthesis in testicular Leydig cells and plays an essential role during male sexual development. Among other chemicals, benzophenone (BP) UV-filters were predicted as potential 17beta-HSD3 inhibitors. Biological analyses revealed (2,4-dihydroxyphenyl)-phenylmethanone (also known as benzophenone-1, BP-1) as an inhibitor of human 17beta-HSD3 (IC(50) 1.05microM). BP-1 also efficiently blocked conversion of androstenedione to testosterone by mouse and rat 17beta-HSD3 in whole-organ enzyme assays. Moreover, BP-1 antagonized the testosterone-dependent activation of androgen receptors (IC(50) 5.7microM), suggesting synergistic anti-androgenic effects of BP-1 by preventing testosterone formation and blocking receptor activation. In addition, analyses of several commonly used UV-filters on estrogen- and androgen-metabolizing 17beta-HSD enzymes revealed 3-benzylidene camphor (3-BC) and 4-methylbenzylidene camphor (4-MBC) as low micromolar 17beta-HSD2 inhibitors. In conclusion, screening of virtual chemical structure libraries can facilitate the identification of compounds interfering with hormone action. The potential disruption of 17beta-HSD enzyme function by the UV-filters BP-1, 3-BC and 4-MBC requires further investigation and should be considered for safety assessment of these chemicals. PMID:20005209

  4. 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...

  5. Potential toxicological hazard due to endocrine-disrupting chemicals on Mediterranean top predators: State of art, gender differences and methodological tools

    SciTech Connect

    Fossi, M.C. . E-mail: fossi@unisi.it; Casini, S.; Marsili, L.

    2007-05-15

    Man-made endocrine-disrupting chemicals (EDCs) range across all continents and oceans. Some geographic areas are potentially more threatened than others: one of these is the Mediterranean Sea. Levels of some xenobiotics are much higher here than in other seas and oceans. In this paper we review the final results of a project supported by the Italian Ministry of the Environment, in which the hypothesis that Mediterranean top predator species (such as large pelagic fish and marine mammals) are potentially at risk due to EDCs was investigated. We illustrate the need to develop and apply sensitive methodological tools, such as biomarkers (Vitellogenin, Zona Radiata proteins and CYP1A activities) for evaluation of toxicological risk in large pelagic fish top predators (Swordfish (Xiphias gladius), Bluefin Tuna (Thunnus thynnus thynnus)) and nondestructive biomarkers (CYP1A activities and fibroblast cell culture in skin biopsy), for the hazard assessment of threatened marine mammals species (Striped Dolphin, (Stenella coeruleoalba), Bottlenose Dolphin (Tursiops truncatus), Common Dolphin (Delphinus delphis) and Fin Whale (Balaenoptera physalus))exposed to EDCs. Differential gender susceptibility to EDCs is also explored both in large pelagic fish and in cetaceans. In cetaceans, male specimens showed higher cytochrome P450 induction (BPMO in skyn biopsies, CYP2B in fibroblasts cell cultures) by xenobiotics with respect to females.

  6. Reconnaissance of 17 beta-estradiol, 11-ketotestosterone, vitellogenin, and gonad histopathology in common carp of United States streams; potential for contaminant-induced endocrine disruption

    USGS Publications Warehouse

    Goodbred, Steven L.; Gilliom, Robert J.; Gross, Timothy S.; Denslow, Nancy P.; Bryant, Wade B.; Schoeb, Trenton R.

    1997-01-01

    A reconnaissance of sex steroid hormones and other biomarkers in common carp was used to assess whether endocrine disruption may be occurring in fish in United States streams, to evaluate relations between endocrine disruption and contaminant levels, and to determine requirements for further studies. 17?-estradiol, 11-ketotestosterone, vitellogenin, and gonadal histopathology were measured in adult carp (usually 10--15 for each sex) at 25 sites (647 fish), representing a wide range of environmental settings typical of major regions of the nation. Fish were collected during August--December 1994, a period of gonadal maturation after spawning. Contaminants evaluated were organochlorine pesticides and polychlorinated biphenyls in tissue; phthalates, phenols, and polycyclic aromatic hydrocarbons in bed sediment; and dissolved pesticides in water. Mean site concentrations of steroid hormones spanned two orders of magnitude for both sexes. No significant regional differences in steroid hormones were detected for males, but females from the Northern and Southern Midcontinent were significantly different from other regions of the country in one or both hormones. Within all regions there were significant differences between sites in one or both hormones for both sexes. Most correlation coefficients between biomarkers and contaminants were negative. Contaminants that had significant (a=0.05) correlations with biomarkers were organochlorine pesticides, phenols, and dissolved pesticides. The strongest pattern common to both males and females was a negative correlation between the hormone ratio (E2/11-KT) and dissolved pesticides. The significant site-to-site differences in biomarkers, and the presence of significant correlations between biomarkers and contaminants, are evidence that fish in some streams may be experiencing endocrine disruption. Improved information is needed to evaluate whether endocrine disruption is actually occurring and if there are reproductive effects on

  7. A plea for risk assessment of endocrine disrupting chemicals.

    PubMed

    Testai, Emanuela; Galli, Corrado L; Dekant, Wolfgang; Marinovich, Marina; Piersma, Aldert H; Sharpe, Richard M

    2013-12-01

    Some recent EU Regulations have focused on the potential risks posed by the presence of endocrine disrupters (ED) into the environment. However there are conflicting opinions on how to assess the risk from exposure to these molecules that can reversibly modulate hormonal activity, endocrine active substances (EAS) rather than causing irreversible damage (ED). The present paper attempts to discuss that perturbation of normal endocrine homeostasis in itself may not be an adverse effect, since the endocrine system is naturally dynamic and responsive to various stimuli as part of its normal function and it is modulated according to the characteristic trend of the dose-response curve. EDs should be evaluated using a weight-of-evidence (WoE) approach. If a chemical meets the criteria to be defined as an ED in experimental animals, the relevance of observed effects to the human then needs to be addressed. Hazard-based risk management is therefore not justified since does not meet the criteria for a sound scientifically based assessment. PMID:23939142

  8. 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

  9. 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. PMID:25666658

  10. 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...

  11. 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 ...

  12. 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...

  13. 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

  14. 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

  15. Stereoselectivity and the potential endocrine disrupting activity of di-(2-ethylhexyl)phthalate (DEHP) against human progesterone receptor: a computational perspective.

    PubMed

    Sheikh, Ishfaq Ahmad

    2016-05-01

    Di-(2-ethylhexyl)phthalate (DEHP) is a phthalate plasticizer and is one of the very common endocrine-disrupting chemicals (EDCs) contaminating our ecosystem. It is used for imparting flexibility to plastics and frequently used in personal and industrial products. Clinical and experimental studies have indicated that exposure to DEHP is associated with developmental abnormalities of the reproductive system particularly of male neonates, endometriosis and miscarriage in women, low sperm counts and lower sperm motility and DNA integrity in men, and placental problems with higher rates of low birth weight, premature birth, and fetal loss in laboratory animals. Binding of DEHP to progesterone receptor (PR) represents a potential mechanism of interference in the reproductive functions. DEHP is a chiralmolecule and is available commercially as a racemic mixture of RR, SS and RS stereoisomers. The ability of individual stereoisomers of DEHP to interfere with the reproductive functions of humans and animals is not known and molecular interactions of DEHP stereoisomers with PR are not available. In the present study, in silico approaches were adopted for molecular simulation studies of the three stereoisomers of DEHP with PR. The study suggested that all three stereoisomers of DEHP have the potential to compete with the normal substrate binding of PR. However, the binding of DEHP to PR was stereoselective with RR stereoisomer of DEHP having the best binding characteristics compared with SS, and RS stereoisomers. It has been suggested that stereoselectivity may be employed for improving the safety of the commercial compounds using pure stereoisomers instead of racemic mixtures. PMID:26879776

  16. Endocrine-Disrupting Potential of Bisphenol A, Bisphenol A Dimethacrylate, 4-n-Nonylphenol, and 4-n-Octylphenol in Vitro: New Data and a Brief Review

    PubMed Central

    Bonefeld-Jørgensen, Eva C.; Long, Manhai; Hofmeister, Marlene V.; Vinggaard, Anne Marie

    2007-01-01

    Background An array of environmental compounds is known to possess endocrine disruption (ED) potentials. Bisphenol A (BPA) and bisphenol A dimethacrylate (BPA-DM) are monomers used to a high extent in the plastic industry and as dental sealants. Alkylphenols such as 4-n-nonylphenol (nNP) and 4-n-octylphenol (nOP) are widely used as surfactants. Objectives We investigated the effect in vitro of these four compounds on four key cell mechanisms including transactivation of a) the human estrogen receptor (ER), b) the human androgen receptor (AR), c) the aryl hydrocarbon receptor (AhR), and d) aromatase activity. Results All four compounds inhibited aromatase activity and were agonists and antagonists of ER and AR, respectively. nNP increased AhR activity concentration-dependently and further increased the 2,3,7,8-tetrachlorodibenzo-p-dioxin AhR action. nOP caused dual responses with a weak increased and a decreased AhR activity at lower (10−8 M) and higher concentrations (10−5–10−4 M), respectively. AhR activity was inhibited with BPA (10−5–10−4 M) and weakly increased with BPA-DM (10−5 M), respectively. nNP showed the highest relative potency (REP) compared with the respective controls in the ER, AhR, and aromatase assays, whereas similar REP was observed for the four chemicals in the AR assay. Conclusion Our in vitro data clearly indicate that the four industrial compounds have ED potentials and that the effects can be mediated via several cellular pathways, including the two sex steroid hormone receptors (ER and AR), aromatase activity converting testosterone to estrogen, and AhR; AhR is involved in syntheses of steroids and metabolism of steroids and xenobiotic compounds. PMID:18174953

  17. 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

  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. 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.

  20. 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

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

    PubMed Central

    Schantz, S L; Widholm, J J

    2001-01-01

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

  2. 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, ...

  3. 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...

  4. 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

  5. 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.

  6. 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

  7. 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.'

  8. 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.

  9. Diverse animal models to examine potential role(s) and mechanism of endocrine disrupting chemicals on the tumor progression and prevention: Do they have tumorigenic or anti-tumorigenic property?

    PubMed Central

    Park, Min-Ah; Hwang, Kyung-A

    2011-01-01

    Acting as hormone mimics or antagonists in the interaction with hormone receptors, endocrine disrupting chemicals (EDCs) have the potentials of disturbing the endocrine system in sex steroid hormone-controlled organs and tissues. These effects may lead to the disruption of major regulatory mechanisms, the onset of developmental disorders, and carcinogenesis. Especially, among diverse EDCs, xenoestrogens such as bisphenol A, dioxins, and di(2-ethylhexyl)phthalate, have been shown to activate estrogen receptors (ERs) and to modulate cellular functions induced by ERs. Furthermore, they appear to be closely related with carcinogenicity in estrogen-dependant cancers, including breast, ovary, and prostate cancers. In in vivo animal models, prenatal exposure to xenoestrogens changed the development of the mouse reproductive organs and increased the susceptibility to further carcinogenic exposure and tumor occurence in adults. Unlike EDCs, which are chemically synthesized, several phytoestrogens such as genistein and resveratrol showed chemopreventive effects on specific cancers by contending with ER binding and regulating normal ER action in target tissues of mice. These results support the notion that a diet containing high levels of phytoestrogens can have protective effects on estrogen-related diseases. In spite of the diverse evidences of EDCs and phytoestrogens on causation and prevention of estrogen-dependant cancers provided in this article, there are still disputable questions about the dose-response effect of EDCs or chemopreventive potentials of phytoestrogens. As a wide range of EDCs including phytoestrogens have been remarkably increasing in the environment with the rapid growth in our industrial society and more closely affecting human and wildlife, the potential risks of EDCs in endocrine disruption and carcinogenesis are important issues and needed to be verified in detail. PMID:22232634

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. BIOMARKERS OF ENDOCRINE DISRUPTION AT THE MRNA LEVEL

    EPA Science Inventory

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

  15. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS: JOURNAL ARTICLE

    EPA Science Inventory

    NRMRL-CIN-1600 Sayles*, G.D. Environmental Engineering and Endocrine Disrupting Chemicals. ASCE Journal of Environmental Engineering (Arnold, R.G. (Ed.), Reston, VA: American Society of Civil Engineers) 128 (1):1-2 (2002). EPA/600/J- 02/001. ...

  16. Endocrine disruption: fact or urban legend?

    PubMed

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

    2013-12-16

    Endocrine disruptors (EDs) are substances that cause adverse health effects via endocrine-mediated mechanisms in an intact organism or its progeny or (sub) populations. Purported EDCs in personal care products include 4-MBC (UV filter) or parabens that showed oestrogenic activity in screening tests, although regulatory toxicity studies showed no adverse effects on reproductive endpoints. Hormonal potency is the key issue of the safety of EDCs. Oestrogen-based drugs, e.g. the contraceptive pill or the synthetic oestrogen DES, possess potencies up to 7 orders of magnitude higher than those of PCP ingredients; yet, in utero exposure to these drugs did not adversely affect fertility or sexual organ development of offspring unless exposed to extreme doses. Additive effects of EDs are unlikely due to the multitude of mechanisms how substances may produce a hormone-like activity; even after uptake of different substances with a similar mode of action, the possibility of additive effects is reduced by different absorption, metabolism and kinetics. This is supported by a number of studies on mixtures of chemical EDCs. Overall, despite of 20 years of research a human health risk from exposure to low concentrations of exogenous chemical substances with weak hormone-like activities remains an unproven and unlikely hypothesis. PMID:24177261

  17. 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

  18. 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

  19. 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

  20. 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

  1. Endocrine-disrupting compounds in reclaimed water and residential ponds and exposure potential for dislodgeable residues in turf irrigated with reclaimed water.

    PubMed

    Sidhu, Harmanpreet S; Wilson, Patrick C; O'Connor, George A

    2015-07-01

    Endocrine-disrupting chemicals (EDCs) occur in reclaimed water (RW), which may serve as an exposure source for humans. The presence of EDCs in RW used to irrigate turf and in nearby water-retention ponds was determined. In addition, the total dislodgeable mass of each EDC was determined after irrigation (using RW) to simulate exposure of a 3-year-child playing in turf grass recently irrigated with RW. Five EDCs (estrone, 17β-estradiol, 17α-ethynylestradiol, bisphenol A, and 4-n-nonylphenol) were quantified in 28 samples of RWs (wastewater-treatment plant effluents) and 88 samples from residential surface water-retention ponds. St. Augustine variety of turf grass was irrigated with spiked RW to study dislodgement of the five EDCs overtime using a drag-sled method. Grass clippings were analyzed to relate masses of EDC on grass with masses dislodged. EDCs were detected in both RW and ponds at ng/L concentrations. Maximum EDC masses were dislodged immediately after irrigation. Dislodged masses of estrone and 17β-estradiol are two separate EDCs, 17β-estradiol and 17α-ethynylestradiol decreased rapidly and were lower than detection limits 4 h after application. Dislodged bisphenol-A and nonylphenol decreased more slowly but were not detected 6 h after application. Avoiding contact with recently irrigated turf grass should decrease the risks of exposure to these EDCs. PMID:25758534

  2. Investigations of potential endocrine disruption and sexual dimorphism in nestling tree swallows (Tachycineta bicolor) with a range of PCB body burdens

    USGS Publications Warehouse

    Yorks, A.L.; Rattner, B.A.; Melancon, M.J.; Bakst, M.R.

    1998-01-01

    Polychlorinated biphenyls (PCBs) elicit endocrine disruptive effects in many species, including birds. Tree swallows (Tachycineta bicolor) were studied at eight sites, located in Maryland, Pennsylvania, and New York, with a range of PCB contamination to determine effects on gender and gonadal development of nestling offipring. Blood samples were collected from nestlings and genetic sex was determined by polymerase chain reaction amplification of sex chromatin in nucleated red blood cells. Gonads were excised and fixed for subsequent gross and histologic examination. PCB analyses of twelve-day old nestlings indicated that residue concentrations varied considerably among the eight sites. Of the 145 nestlings examined anatomically, the phenotypic sex ratio was 53% female and 47% male. No intersexes were observed. Histological observations revealed some variation such as numbers of spermatogonia and stages of follicular development among individuals. Genotypic evaluation of the 145 nestlings revealed complete concordance with phenotypic observations. Although there were significant differences in PCB exposure among study sites, there was no evidence of abnormal gonadal development or anatomical gender alteration in nestling Tree swallows.

  3. 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

  4. 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

  5. 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...

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

    EPA Science Inventory

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

  7. Chemical communication threatened by endocrine-disrupting chemicals.

    PubMed Central

    Fox, Jennifer E

    2004-01-01

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

  8. 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

  9. 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

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

    PubMed Central

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

    2005-01-01

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

  11. 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

  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. 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

  14. 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

  15. 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

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

    PubMed Central

    Barrett, Emily S.; Sobolewski, Marissa

    2014-01-01

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

  17. 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

  18. 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

  19. 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

  20. Effect of chronic exposure to two components of Tritan copolyester on Daphnia magna, Moina macrocopa, and Oryzias latipes, and potential mechanisms of endocrine disruption using H295R cells.

    PubMed

    Jang, Sol; Ji, Kyunghee

    2015-11-01

    Tritan copolyester is a novel plastic form from Eastman Company utilizing three main monomers, 1,4-cyclohexanedimethanol (CHDM), dimethyl terephthalate (DMT), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol. Despite Tritan has been widely applied for plastic bottles, the effects of long-term exposure to these compounds have seldom been investigated. We investigated chronic effects and endocrine disruption potential of CHDM and terephthalic acid (TPA), main mammalian metabolite formed from DMT, using crustacean Daphnia magna and Moina macrocopa, and freshwater fish (Oryzias latipes). The effects on sex hormone balance and the associated mechanisms were also investigated by use of H295R cells. In chronic toxicity test, D. magna showed significant decrease in reproduction (number of young per female) after exposure to 10 mg/L TPA. In early life stage exposure using O. latipes, significant decrease of juvenile survival and weight were observed in fish exposed to 10 mg/L and ≥1 mg/L CHDM, respectively. Expressions of vtg2 mRNA in fish exposed to CHDM and those of cyp19b, star, cyp17, and cyp19a mRNAs in fish exposed to TPA were significantly up-regulated. The results of H295R cell assay also showed that both chemicals at high concentrations could alter sex hormone production in steroidogenic pathway. The effective concentrations of the tested compounds were several orders of magnitude greater than the concentrations can be detected in ambient waters. Further in vivo and in vitro studies will be needed to investigate the effect of co-polymer on endocrine disruption. PMID:26289545

  1. 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.

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

    PubMed Central

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

    2004-01-01

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

  3. Molasses as a possible cause of an "endocrine disruptive syndrome" in calves.

    PubMed

    Masgoret, M S; Botha, C J; Myburgh, J G; Naudé, T W; Prozesky, L; Naidoo, V; Van Wyk, J H; Pool, E J; Swan, G E

    2009-06-01

    During the mid 1990s a potentially serious, chronic syndrome was reported in well-managed beef and dairy herds from unrelated parts of South Africa. Farmers reported that it manifested as various combinations of decreased production, decreased weaning masses, apparent immune breakdown in previously immunocompetent animals, increased reproductive disorders, various mineral imbalances in non-deficient areas and goitre, noticeable as enlarged thyroid glands. The farmers associated this syndrome with certain batches of sugar cane molasses and molasses-based products. The syndrome was reminiscent of an "endocrine disruptive syndrome". The objective of this study was to evaluate the suspected endocrine disruptive effect of molasses included in cattle feed. Using existing in vitro assays, four batches of molasses syrup were screened for possible inclusion in a calf feeding trial. Two batches were selected for the trial. Thirty-two, 4- to 6-week-old, weaned Holstein bull calves were included in the single phase, three treatment, parallel design experiment. In two of the groups of calves, two different batches of molasses were included in their rations respectively. The control group was fed a ration to which no molasses was added, but which was balanced for energy and mineral content. The mass gain of the calves was recorded over the 6-month study period. The calves were clinically examined every week and clinical pathology parameters, immune responses and endocrine effects were regularly evaluated. Even though endocrine disrupting effects were detected with the in vitro screening assays, these could not be reproduced in the calves in the experiment. The two batches of molasses utilized in the calf feeding trial did not induce major differences in any of the parameters measured, with the exception of a lower mass gain in one of the molasses-fed groups (Group 1), which tended towards significance. The results of the study indicate that the two batches of molasses had no

  4. 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

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

    PubMed

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

    2016-06-01

    The herbicide acetochlor is widely used and detected in the environment and biota, and has been suspected to disrupt the thyroid endocrine system, but underlying mechanisms have not yet been clarified. In the present study, zebrafish larvae (7 days post-fertilization) were exposed to a series concentration of acetochlor (0, 1, 3, 10, 30, 100 and 300 µg l(-1) ) within a 14-day window until 21 days post-fertilization. Thyroid hormones and mRNA expression profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. Exposure to the positive control, 3,5,3'-triiodothyronine (T3 ), altered the mRNA expression, suggesting that the HPT axis in the critical window of zebrafish responded to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. The mRNA expressions of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tpo) were upregulated significantly with acetochlor treatment, which might be responsible for the increased thyroxine concentrations. The downregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) and transport (ttr) in zebrafish larvae exposed to acetochlor might further explain the increased thyroxine levels and decreased T3 levels. The mRNA expression of the thyroid hormone receptor (trα) was also upregulated upon acetochlor exposure. Results suggested that acetochlor altered mRNA expression of the HPT axis-related genes and changed the whole body thyroid hormone levels in zebrafish larvae. It demonstrated that acetochlor could cause endocrine disruption of the thyroid system by simulating the biological activity of T3 . Copyright © 2015 John Wiley & Sons, Ltd. PMID:26397822

  6. Endocrine Disruption of Brain Sexual Differentiation by Developmental PCB Exposure

    PubMed Central

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Patisaul, Heather B.; Woller, Michael J.

    2011-01-01

    In mammals, sexual differentiation of the hypothalamus occurs during prenatal and early postnatal development due in large part to sex differences in hormones. These early organizational processes are critically important for the attainment and maintenance of adult reproductive functions. We tested the hypothesis that perinatal exposure to polychlorinated biphenyls (PCBs) that disrupt hormonal pathways would perturb reproductive maturation and the sexually dimorphic development of neuroendocrine systems in the preoptic area (POA). Pregnant Sprague-Dawley rats were injected on gestational d 16 and 18 with vehicle (dimethylsulfoxide), Aroclor 1221 (A1221, an estrogenic PCB mix), a reconstituted PCB mixture representing those highest in human body burden (PCBs 138, 153, 180), or estradiol benzoate, an estrogenic control. Male and female pups were monitored for somatic and reproductive development. In adulthood, some rats were perfused and used for immunohistochemistry of estrogen receptor α, kisspeptin, and coexpression of Fos in GnRH neurons. Other rats were used to obtain fresh-frozen POA dissections for use in a PCR-based 48-gene expression array. Pubertal onset was advanced and estrous cyclicity irregular in endocrine-disrupted females. Furthermore, sexual differentiation of female neuroendocrine systems was masculinized/defeminized. Specifically, in the adult female anteroventral periventricular nucleus, estrogen receptor α-cell numbers and kisspeptin fiber density were significantly decreased, as was GnRH-Fos coexpression. PCR analysis identified androgen receptor, IGF-I, N-methyl-d-aspartate receptor subunit NR2b, and TGFβ1 mRNAs as significantly down-regulated in endocrine-disrupted female POAs. These data suggest that developmental PCBs profoundly impair the sexual differentiation of the female hypothalamus. PMID:21190954

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

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

    EPA Science Inventory

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

  13. Human testicular insulin-like factor 3 and endocrine disrupters.

    PubMed

    Bay, Katrine; Anand-Ivell, Ravinder

    2014-01-01

    The hormone insulin-like factor 3 (INSL3) is produced by testicular Leydig cells. Production of INSL3 is dependent on the state of Leydig cell differentiation and is stimulated by the long-term trophic effects of luteinizing hormone. INSL3 is, along with the other major Leydig cell hormone testosterone, essential for testicular descent, which in humans should be completed before birth. The incidence of cryptorchidism (incomplete descent of the testis) may have increased in some developed countries during recent decades. Experimental studies have shown that maternal exposure to endocrine-disrupting chemicals (EDCs), such as phthalates, can result in cryptorchidism among male offspring and that INSL3 production, like steroidogenesis, is susceptible to phthalate exposure. Inhibition of these hormones may occur via a general phthalate-induced impairment of Leydig cell development and maturation. Recent studies have also addressed the sensitivity of human Leydig cells to EDCs, though with varied conclusions. PMID:24388196

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

    PubMed Central

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

    2012-01-01

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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Exposure to endocrine disrupting compounds via the food chain: Is packaging a relevant source?

    PubMed

    Muncke, Jane

    2009-08-01

    Contamination of foodstuffs by environmental pollutants (e.g. dioxins, metals) receives much attention. Until recently, food packaging as a source of xenobiotics, especially those with endocrine disrupting properties, has received little awareness despite its ubiquitous use. This article reviews the regulations and use of endocrine disrupting compounds (EDCs) in food packaging and discusses their presence within the context of new toxicology paradigms. I focused on substances known to be legally used in food packaging that have been shown to exhibit endocrine disruptive effects in biological systems. I compiled a list of 50 known or potential EDCs used in food contact materials and examined data of EDCs leaching from packaging into food, with a focus on nonylphenol. I included recent advances in toxicology: mixture effects, the developmental origins of adult disease hypothesis, low-dose effects, and epigenetics. I especially considered the case of bisphenol A. The core hypothesis of this review is that chemicals leaching from packaging into food contribute to human EDCs exposure and might lead to chronic disease in light of the current knowledge. Food contact materials are a major source of food contaminants. Many migrating compounds, possibly with endocrine disruptive properties, remain unidentified. There is a need for information on identity/quantity of chemicals leaching into food, human exposure, and long-term impact on health. Especially EDCs in food packaging are of concern. Even at low concentrations, chronic exposure to EDCs is toxicologically relevant. Concerns increase when humans are exposed to mixtures of similar acting EDCs and/or during sensitive windows of development. In particular, non-intentionally added substances (NIAS) migrating from food contact materials need toxicological characterization; the overall migrate of the finished packaging could be evaluated for biological effects using bioassays. The widespread legal use of EDCs in food

  20. 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

  1. 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

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

    EPA Science Inventory

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

  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. Problems in testing and risk assessment of endocrine disrupting chemicals with regard to developmental toxicology.

    PubMed

    Mantovani, A; Stazi, A V; Macrì, C; Maranghi, F; Ricciardi, C

    1999-10-01

    Endocrine disrupting chemicals (EDCs) may affect mammalian development either indirectly (by impairing implantation, placental development, lactation, etc.) or directly, altering the maturation of target tissues. Current regulatory tests for reproductive/developmental toxicity should be carefully evaluated with regard to risk assessment of EDCs, considering hazard identification (are relevant endpoints being assessed?) and dose-response assessment (are sensitive NOEL/dose-response curves being provided?). Many in vitro and in vivo assays for sex steroid disruption are available; provided that the metabolic capacities of the assays are defined, they could be integrated in a sensitive battery for early detection of steroid-disrupting potentials. The screening battery should address further regulatory in vivo tests (e.g. what specific parameters have to be investigated). As regards dose-response, qualitative differences may be observed between lower and higher exposures, showing primary hormone-related effects and frank embryotoxicity, respectively. Other problems concern (a) the identification of critical developmental windows, according to hormone concentrations and/or receptor levels in the developing target tissues; (b) the potential for interactions between chemicals with common mechanism/target (e.g. xenoestrogens); (c) most important, besides sex steroids more attention should be given to other mechanisms of endocrine disruption, e.g., thyroid effects, which can be highly relevant to prenatal and postnatal development. PMID:10467724

  5. Vitellogenin-like gene expression in freshwater amphipod Gammarus fossarum (Koch, 1835): functional characterization in females and potential for use as an endocrine disruption biomarker in males.

    PubMed

    Xuereb, Benoît; Bezin, Laurent; Chaumot, Arnaud; Budzinski, Hélène; Augagneur, Sylvie; Tutundjian, Renaud; Garric, Jeanne; Geffard, Olivier

    2011-08-01

    The induction of vitellogenin (Vtg) synthesis is widely accepted as a biomarker of estrogenic exposure in male and juvenile fish. Vtg synthesis has emerged as an interesting endpoint to assess endocrine disruptor (ED) effects in crustaceans. However, studies reporting induction of Vtg in male crustaceans are lacking. This study investigated the expression of the Vtg gene in a freshwater amphipod, Gammarus fossarum, using calibrated real-time reverse transcription polymerase chain reaction (real-time RT PCR). First, we described the basal pattern of expression in healthy male and female organisms at different reproductive moult stages, in order to validate the function of this gene. Females expressed from 200 to 700 times more Vtg transcripts than males, depending on the female reproductive stage. Females displayed significant elevation of Vtg mRNA levels at the end of the inter-moult phase and at the beginning of the pre-moult phase. Second, male gammarids were exposed to the estrogenic compound nonylphenol (NP) (0.05, 0.5, 5 and 50 μg L(-1)) and to the anti-androgen cyproterone (1, 10, 100 and 1000 μg L(-1)) for 2, 4, 8 and 16 days. Both chemicals altered the pattern of interindividual variability of Vtg gene expression in males with strong induction in some individuals. Finally, the impact of urban wastewater treatment plants (WWTP) on male Vtg gene expression was assessed in organisms transplanted in the field during in situ bioassay campaigns in three different watersheds. Induction of the Vtg mRNA level was observed in males transplanted downstream from WWTP effluent discharge in two of the three study sites. PMID:21701845

  6. 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...

  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. 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

  9. 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

  10. 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...

  11. 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...

  12. 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.

  13. 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

  14. 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

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

    PubMed

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

    2016-08-01

    Nonylphenol is in the focus of worldwide endocrine-disrupter research and accounted for as a priority hazardous substance of the Water Framework Directive of the European Union. Technical nonylphenol consists of a very complex mixture of isomers and enantiomers. As estrogenic effect and degradation behavior in environmental processes of single nonylphenols are heavily dependent on the structure of the nonyl side chain, it is absolutely necessary to consider the nonylphenol problem from an isomer and enantiomer-specific viewpoint. In this study, an enantiomer-specific separation of eight defined synthesized nonylphenol isomers by five different special chiral cyclodextrin columns was performed underivatized and after methylation, silylation, and acylation. This work demonstrates that three columns out of the investigated five show an excellent separation behavior for the studied different nonylphenol isomers and can be used for the enantiomer-specific determination of nonylphenols in food, other biological matrices, and environmental samples in the future. Graphical abstract Enantiomeric pair of 4-NP170 (4-[1-ethyl-1,3,3-trimethylbutyl]phenol). PMID:27236316

  16. 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

  17. 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

  18. 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.

  19. 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...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  4. 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...

  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. 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. PMID:21439565

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

    PubMed

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

    2012-02-21

    The urban-water cycle modifies natural stream hydrology, and domestic and commercial activities increase the burden of endocrine-disrupting chemicals, such as steroidal hormones and 4-nonylphenol, that can disrupt endocrine system function in aquatic organisms. This paper presents a series of integrated chemical and biological investigations into the occurrence, fate, and effects of endocrine-disrupting chemicals in the City of Boulder Colorado's WWTF and Boulder Creek, the receiving stream. Results are presented showing the effects of a full-scale upgrade of the WWTF (that treats 0.6 m(3) s(-1) of sewage) from a trickling filter/solids contact process to an activated sludge process on the removal of endocrine-disrupting compounds and other contaminants (including nutrients, boron, bismuth, gadolinium, and ethylenediaminetetraacetic acid) through each major treatment unit. Corresponding impacts of pre- and postupgrade effluent chemistry on fish reproductive end points were evaluated using on-site, continuous-flow experiments, in which male fathead minnows (Pimephales promelas) were exposed for 28 days to upstream Boulder Creek water and WWTF effluent under controlled conditions. The upgrade of the WWTF resulted in improved removal efficiency for many endocrine-disrupting chemicals, particularly 17β-estradiol and estrone, and fish exposed to the postupgrade effluent indicated reduction in endocrine disruption relative to preupgrade conditions. PMID:22300164

  8. 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

  9. 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.

  10. 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

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

    SciTech Connect

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

    1993-10-01

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

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

    PubMed

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

    2016-05-01

    In recent decades, considerable attention has been devoted to endocrine disruptor chemicals (EDC) and studies on fish feminization have increased throughout the years as a key signal for aquatic environmental contamination. The input of domestic sewage into water reservoirs is common in South American countries, especially in cities that experienced rapid population growths and unplanned urbanization. This study aimed at characterizing morphofunctional parameters of the tropical fish Sphoeroides testudineus and investigating the potential occurrence and effects of endocrine disruptors in the Pacoti River (Ceará, Brazil), often considered a reference site. After collection from the field, fish were measure/weighted and desiccated for gender identification (males, females, and undifferentiated), gonadal histology, and vitellogenin expression. From the biometric analysis, undifferentiated fish showed lower weight and length than female and male fish, although no differences in the condition index were observed. The gonadal weight of undifferentiated fish was significantly lower than those of females and males. Although this pattern was observed, gonadosomatic index (GSI) showed a different pattern, with differences being observed just between males and the other two groups (females and undifferentiated). Vitellogenin (VTG) expression was detected in many mature male and undifferentiated fish, indicating endocrine disruption. In addition, several EDCs (estrone, 17α-estradiol, 17β-estradiol, 17α-ethinylestradiol, diethylstilbestrol, and estriol) were identified and quantified in sediments from the sampling site. These results were unexpected and indicative that the Pacoti River is impaired by estrogenic contamination. PMID:27094055

  13. 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. PMID:25451822

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Zebrafish (Danio rerio) as a model organism for investigating endocrine disruption.

    PubMed

    Segner, Helmut

    2009-03-01

    Endocrine-disrupting compounds (EDCs) are widespread in the aquatic environment and can cause alterations in development, physiological homeostasis and health of vertebrates. Zebrafish, Danio rerio, has been suggested as a model species to identify targets as well as modes of EDC action. In fact, zebrafish has been found useful in EDC screening, in EDC effects assessment and in studying targets and mechanisms of EDC action. Since many of the environmental EDCs interfere with the sex steroid system of vertebrates, most EDC studies with zebrafish addressed disruption of sexual differentiation and reproduction. However, other targets of EDCs action must not be overlooked. For using a species as a toxicological model, a good knowledge of the biological traits of this species is a pre-requisite for the rational design of test protocols and endpoints as well as for the interpretation and extrapolation of the toxicological findings. Due to the genomic resources available for zebrafish and the long experience with zebrafish in toxicity testing, it is easily possible to establish molecular endpoints for EDC effects assessment. Additionally, the zebrafish model offers a number of technical advantages including ease and cost of maintenance, rapid development, high fecundity, optical transparency of embryos supporting phenotypic screening, existence of many mutant strains, or amenability for both forward and reverse genetics. To date, the zebrafish has been mainly used to identify molecular targets of EDC action and to determine effect thresholds, while the potential of this model species to study immediate and delayed physiological consequences of molecular interactions has been instrumentalized only partly. One factor that may limit the exploitation of this potential is the still rather fragmentary knowledge of basic biological and endocrine traits of zebrafish. Information on species-specific features in endocrine processes and biological properties, however, need to be

  20. 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

  1. 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...

  2. 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

  3. Challenges and future directions to evaluating the association between prenatal exposure to endocrine disrupting chemicals and childhood obesity

    PubMed Central

    Romano, Megan E.; Savitz, David A.; Braun, Joseph M.

    2014-01-01

    Obesity is an increasing public health threat worldwide. However, there has been insufficient research addressing the obesogenic potential of prenatal exposure to environmental endocrine disrupting chemicals, largely due to complexities in the design, analysis, and interpretation of such studies. This review describes relevant biological mechanisms, addresses current challenges for investigators, presents potential strategies for overcoming them, and identifies areas where further development is required to improve future research. Special considerations for exposure assessment, outcome heterogeneity, and complex confounding structures are described. PMID:25328860

  4. 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

  5. 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

  6. 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

  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. 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, ...

  9. 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

  10. 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

  11. 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

  12. Are the mediterraneantop predators exposed to toxicological risk due to endocrine disrupters?

    PubMed

    Fossi, M C; Casini, S; Marsili, L; Ausili, A; di Sciara, G N

    2001-12-01

    Man-made endocrine disrupting chemicals (EDCs) range across all continents and oceans; some geographic areas are potentially more threatened than others: one of these is the Mediterranean Sea. This basin has limited exchange of water with the Atlantic Ocean and is surrounded by some of the most heavily populated and industrialized countries in the world. Accordingly, levels of some xenobiotics are much higher here than in other seas and oceans. In this research the unexplored hypothesis that Mediterranean top predator species (such as large pelagic fish and marine mammals) are potentially at risk due to EDCs is investigated. Here we illustrate the development of sensitive biomarkers (Vitellogenin, Zona Radiata proteins) for evaluation of toxicological risk in top marine predators (Xiphias gladius, Thunnus thynnus thynnus), and nonlethal techniques, such as nondestructive biomarkers (BPMO activities in skin biopsy), for the hazard assessment of threatened species exposed to EDCs, such as marine mammals (Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis, and Balaenoptera physalus). PMID:11795396

  13. [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

  14. 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

  15. 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.

  16. 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

  17. THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS ON GULF PIPEFISH

    EPA Science Inventory

    Pipefish exposed to endocrine disruptors, such as EE2, are expected to have lower reproductive success, resulting in a decrease in recruitment in exposed populations. Egg viability also is expected to be lowest in the paired mating of an exposed male and female, compared to...

  18. 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.

  19. 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 ...

  20. 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...

  1. Reproductive failure and endocrine disruption by organohalogens in fish-eating birds.

    PubMed

    Bosveld, Albertus T C; van den Berg, Martin

    2002-12-27

    Effects of organohalogens in fish-eating birds in the field have been monitored largely by studying reproductive outcome in contaminated populations or, at the individual level, by studying the sexual behaviour, egg production, or embryonal and postnatal development and survival. Endocrine disruption has been suggested as a mechanism, but proven cause-effect relationships between specific compounds and endocrine disruption with subsequent reduced reproductive outcome in fish-eating birds are scarce. The effects of organochlorines on hormone metabolism and circulating steroid levels are reviewed and discussed in relation to observed reproductive failures in the field. PMID:12505302

  2. 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

  3. 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. PMID:23110442

  4. 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.

  5. Endocrine disruption mechanism of o,p'-DDT in mature male tilapia (Oreochromis niloticus)

    SciTech Connect

    Leanos-Castaneda, Olga . E-mail: olgalidia09@yahoo.com; Kraak, Glen van der; Rodriguez-Canul, Rossanna; Gold, G.

    2007-06-01

    The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER.

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

    EPA Science Inventory

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

  7. 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. PMID:26395355

  8. 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

  9. 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

  10. 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

  11. Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio.

    PubMed

    Jurewicz, Joanna; Radwan, Michał; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Wielgomas, Bartosz; Ligocka, Danuta; Brzeźnicki, Sławomir; Hanke, Wojciech

    2016-06-01

    In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations. PMID:27031570

  12. 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

  13. 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.

  14. 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.

  15. Developmental effects of dioxins and related endocrine disrupting chemicals.

    PubMed

    Birnbaum, L S

    1995-12-01

    Alteration of hormones has long been known to affect development. TCDD and related PHAHs modulate the levels of many hormonal systems. Dioxins cause a spectrum of morphological and functional developmental deficits. Fetotoxicity, thymic atrophy, and structural malformations are often noted. Delayed genitourinary tract effects have been observed, and recent studies reported behavioral effects. Highly exposed human offspring have exhibited developmental problems as well. Recently, hormonal and neurological abnormalities have been reported in infants from the general population. The complex alteration of multiple endocrine systems is likely associated with the spectrum of adverse developmental effects caused by dioxin and related compounds. PMID:8597137

  16. 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...

  17. 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 ...

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

    EPA Science Inventory

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

  19. [Exposure to endocrine disrupting chemicals and children's health: problems in epidemiological studies].

    PubMed

    Kishi, Reiko; Sata, Fumihiro; Saijo, Yasuaki; Kurahashi, Norie; Kato, Shizue; Nakajima, Sonomi; Sasaki, Seiko

    2006-01-01

    Most endocrine disrupting chemicals are characterized by their properties to induce marked phenotypic changes in offspring such as congenital anomalies and neurodevelopmental dysfunctions. Although an increase in the prevalence of hypospadias or cryptorchidism has been reported in various countries, improvement in diagnostic techniques and more attention to the features of the diseases have also been emphasized. Although there have been a few reports that hypospadias or cryptorchidism had been associated with diethylstilbestrol (DES), pesticides and so on, the associations between these diseases and endocrine disrupting chemicals remain unclear. Recently, the association between maternal metabolic polymorphism or paternal smoking during pregnancy and these diseases has been reported. There are also variable clinical features in children's neurobehavioral development, and thyroid and immune functions in relation to exposure to endocrine disrupting chemicals such as polychlorinated biphenyls (PCBs) and dioxins. Only a few Dutch studies have suggested that perinatal exposure to background level of PCB/dioxin confers immunity to allergy development. Genetic susceptibility to environmental endocrine disrupting chemicals may be related to adverse pregnancy outcomes. It is suggested that well-designed epidemiological studies such as prospective cohort studies should be performed to elucidate this association. PMID:16506651

  20. 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,...

  1. 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...

  2. 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...

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

    EPA Science Inventory

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

  4. 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 ...

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

    EPA Science Inventory

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

  6. 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...

  7. 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...

  8. 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...

  9. 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 ...

  10. 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...

  11. 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...

  12. Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin

    PubMed Central

    Nordeen, Steven K.; Bona, Betty J.; Jones, David N.; Lambert, James R.; Jackson, Twila A.

    2013-01-01

    Dietary plant flavonoids have been proposed to contribute to cancer prevention, neuroprotection, and cardiovascular health through their anti-oxidant, anti-inflammatory, pro-apoptotic, and antiproliferative activities. As a consequence, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks. We show that two flavonoids, luteolin and quercetin, are promiscuous endocrine disruptors. These flavonoids display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model. Concurrently, luteolin possesses potent estrogen agonist activity while quercetin is considerably less effective. These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy, plant-rich diet. PMID:23836117

  13. 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. PMID:25378272

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

    USGS Publications Warehouse

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

    2015-01-01

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

  15. Endocrine disrupting compounds: can they target the immune system of fish?

    PubMed

    Casanova-Nakayama, Ayako; Wenger, Michael; Burki, Richard; Eppler, Elisabeth; Krasnov, Aleksei; Segner, Helmut

    2011-01-01

    Endocrine disruption, in particular disruption by estrogen-active compounds, has been identified as an important ecotoxicological hazard in the aquatic environment. Research on the impact of endocrine disrupting compounds (EDCs) on wildlife has focused on disturbances of the reproductive system. However, there is increasing evidence that EDCs affect a variety of physiological systems other than the reproductive system. Here, we discuss if EDCs may be able to affect the immune system of fish, as this would have direct implications for individual fitness and population growth. Evidence suggesting an immunomodulatory role of estrogens in fish comes from the following findings: (a) estrogen receptors are expressed in piscine immune organs, (b) immune gene expression is modulated by estrogen exposure, and (c) pathogen susceptibility of fish increases under estrogen exposure. PMID:21683417

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. EADB: An Estrogenic Activity Database for Assessing Potential Endocrine Activity

    EPA Science Inventory

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many ...

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

    SciTech Connect

    McLachlan, John A.

    2000-09-14

    The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites.

  2. Hypothesis-driven weight of evidence analysis to determine potential endocrine activity of MTBE.

    PubMed

    de Peyster, Ann; Mihaich, Ellen

    2014-08-01

    Endocrine-related endpoints in animals have been reported to respond to high doses of methyl tertiary-butyl ether (MTBE), however, a systematic and transparent evaluation of endocrine potential has not been published. Resolving whether MTBE exhibits endocrine activity is important given regulatory and public interest in endocrine disrupting substances and their potential for causing adverse effects in humans or wildlife. A weight-of-evidence (WoE) analysis was conducted, focusing on hypotheses related to the potential for MTBE to interact with estrogen, androgen, and thyroid pathways, and steroidogenesis. To reach scientifically justified conclusions based on the totality of evidence, this WoE procedure involved a semi-quantitative relevance weighting of each endpoint for each hypothesis and systematic consideration of each endpoint in various study designs. This procedure maximized use of an extensive body of relevant and reliable literature on MTBE with evidence supporting or opposing a given mode of action hypothesis. Evaluating the strength and consistency of observations from many MTBE studies also provided a way to assess whether high doses used in experiments with MTBE confound identification of direct endocrine system responses. Based on results of studies using mammalian and fish models and in vitro screening assays, this WoE assessment reveals that MTBE lacks direct endocrine activity. PMID:24813373

  3. 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

  4. 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

  5. Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water.

    PubMed

    Benotti, Mark J; Trenholm, Rebecca A; Vanderford, Brett J; Holady, Janie C; Stanford, Benjamin D; Snyder, Shane A

    2009-02-01

    The drinking water for more than 28 million people was screened for a diverse group of pharmaceuticals, potential endocrine disrupting compounds (EDCs), and other unregulated organic contaminants. Source water, finished drinking water, and distribution system (tap) water from 19 U.S. water utilities was analyzed for 51 compounds between 2006 and 2007. The 11 most frequently detected compounds were atenolol, atrazine, carbamazepine, estrone, gemfibrozil, meprobamate, naproxen, phenytoin, sulfamethoxazole, TCEP, and trimethoprim. Median concentrations of these compounds were less than 10 ng/L, except for sulfamethoxazole in source water (12 ng/L), TCEP in source water (120 ng/L), and atrazine in source, finished, and distribution system water (32, 49, and 49 ng/L). Atrazine was detected in source waters far removed from agricultural application where wastewater was the only known source of organic contaminants. The occurrence of compounds in finished drinking water was controlled by the type of chemical oxidation (ozone or chlorine) used at each plant. At one drinking water treatment plant, summed monthly concentrations of the detected analytes in source and finished water are reported. Atenolol, atrazine, DEET, estrone, meprobamate, and trimethoprim can serve as indicator compounds representing potential contamination from other pharmaceuticals and EDCs and can gauge the efficacy of treatment processes. PMID:19244989

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

    PubMed Central

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

    1995-01-01

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

  7. 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

  8. Endocrine disruption and ovarian morphometric responses in rats following exposure to tetradifon.

    PubMed

    Badraoui, Riadh; Abdelmoula, Nouha B; Feki, Nozha; Ben Nasr, Hmed; Rebai, Tarek

    2010-04-01

    We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17beta-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17beta-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat. PMID:19800343

  9. 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. PMID:25549947

  10. 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