Endocrine disrupting chemicals and disease susceptibility.

PubMed

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

2011-11-01

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

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

PubMed Central

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

2012-01-01

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

SMALL FISH MODELS FOR IDENTIFYING AND ASSESSING THE EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Endocrine-disrupting chemicals (EDCs), in particular those which affect the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates, have become a focus of regulatory screening and testing throughout the world. Small fish species, principally the fathead minnow (Pimephales prom...

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

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...

Recent Advances on Endocrine Disrupting Effects of UV Filters.

PubMed

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

2016-08-03

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

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

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...

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

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

First characterization of the endocrine-disrupting potential of indoor gaseous and particulate contamination: comparison with urban outdoor air (France).

PubMed

Oziol, Lucie; Alliot, Fabrice; Botton, Jérémie; Bimbot, Maya; Huteau, Viviane; Levi, Yves; Chevreuil, Marc

2017-01-01

The composition of endocrine-disrupting compounds (EDCs) in the ambient air of indoor environments has already been described, but little is known about the inherent endocrine-disrupting potential of indoor air contamination. We therefore aimed to study the distribution of bioactive EDCs in the gaseous and particulate phases of indoor air using a cellular bioassay approach that integrates the interaction effects between chemicals. Organic air extracts, both gaseous and particulate, were taken from three indoor locations (office, apartment, and children's day care) in France and sampled in two different seasons in order to study their interference with the signaling of estrogen, androgen, and thyroid receptors. The experiments were also conducted on aerial extracts from an outdoor site (urban center). We found that gaseous and/or particulate extracts from all locations displayed estrogenicity, anti-androgenicity, and thyroidicity. Overall, indoor air extracts had a higher endocrine-disrupting potential compared to outdoor ones, especially during winter and in the day care. The biological activities were predominant for the gaseous extracts and tended to increase for the particulate extracts in cool conditions. In conclusion, our data confirmed the presence of bioactive EDCs in a gaseous state and highlighted their indoor origin and concentration, especially in the cold season.

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

PubMed Central

Patisaul, Heather B.

2017-01-01

A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is ‘synthetic’ v. what is ‘natural,’ shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour. PMID:27389644

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

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. ...

Identification of endocrine disrupting chemicals acting on human aromatase.

PubMed

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

2018-01-01

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

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

PubMed Central

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

2017-01-01

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

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

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

EPA Pesticide Factsheets

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

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...

[Perspectives on endocrine disruption].

PubMed

Olea, N; Fernández, M F; Araque, P; Olea-Serrano, F

2002-01-01

Two decades ago, reports of alterations in the reproductive function of some wild animal species and clear evidence of human and animal exposure to chemical substances with hormonal activity agonist and antagonist generated what is known now as the hypothesis of endocrine disruption. This is an emerging environmental health problem that has challenged some of the paradigms on which the control and regulation of the use of chemical compounds is based. The need to include in routine toxicology tests new research objectives that specifically refer to the development and growth of species and to the homeostasis and functionality of hormonal systems, has served to complicate both the evaluation of new compounds and the re-evaluation of existing ones. The repercussions on regulation and international trade have not taken long to be felt. On both sides of the Atlantic, screening systems for endocrine disrupters have been designed and established, and research programmes have been launched to characterise and quantify adverse effects on human and animal health and to develop preventive measures.

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.

2016-01-01

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.

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

PubMed

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

2016-03-01

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. 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. 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. 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. 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.

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

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

PubMed

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

2014-12-22

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

Endocrine disruption, parasites and pollutants in wild freshwater fish.

PubMed

Jobling, S; Tyler, C R

2003-01-01

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

Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

USGS Publications Warehouse

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie K.; Schwarz, Tamar; Meador, James P.

2018-01-01

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated—interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

PubMed

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ron; Guiney, Patrick D; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

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...

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...

Species-specific considerations in using the fish embryo test as an alternative to identify endocrine disruption.

PubMed

Schiller, Viktoria; Zhang, Xiaowei; Hecker, Markus; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

2014-10-01

A number of regulations have been implemented that aim to control the release of potentially adverse endocrine disrupters into the aquatic environment based on evidence from laboratory studies. Currently, such studies rely on testing approaches with adult fish because reliable alternatives have not been validated so far. Fish embryo tests have been proposed as such an alternative, and here we compared two species (medaka and zebrafish) to determine their suitability for the assessment of substances with estrogenic and anti-androgenic activity. Changes in gene expression (in here the phrase gene expression is used synonymously to gene transcription, although it is acknowledged that gene expression is additionally regulated, e.g., by translation and protein stability) patterns between the two species were compared in short term embryo exposure tests (medaka: 7-day post fertilization [dpf]; zebrafish: 48 and 96h post fertilization [hpf]) by using relative quantitative real-time RT-PCR. The tested genes were related to the hypothalamic-gonadal-axis and early steroidogenesis. Test chemicals included 17α-ethinylestradiol and flutamide as estrogenic and anti-androgenic reference compounds, respectively, as well as five additional substances with endocrine activities, namely bisphenol A, genistein, prochloraz, linuron and propanil. Estrogenic responses were comparable in 7-dpf medaka and 48/96-hpf zebrafish embryos and included transcriptional upregulation of aromatase b, vitellogenin 1 as well as steroidogenic genes, suggesting that both species reliably detected exposure to estrogenic compounds. However, anti-androgenic responses differed between the two species, with each species providing specific information concerning the mechanism of anti-androgenic disruption in fish embryos. Although small but significant changes in the expression of selected genes was observed in 48-hpf zebrafish embryos, exposure prolonged to 96hpf was necessary to obtain a response indicative

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 ...

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

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...

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

PubMed Central

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

2015-01-01

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

New insights into the endocrine disrupting effects of brominated flame retardants.

PubMed

Legler, Juliette

2008-09-01

The objective of this review is to provide an overview of recent studies demonstrating the endocrine disrupting (ED) effects of brominated flame retardants (BFRs), while highlighting interesting data presented at the recent international BFR workshop in Amsterdam in April, 2007. A review written in 2002 was used as a starting point and about 60 publications published since 2003 were reviewed. New insights into the in vivo effects of BFRs on thyroid hormone, estrogen and androgen pathways in both mammalian and non-mammalian models are provided, and novel (in vitro) findings on the mechanisms underlying ED effects are highlighted. Special attention is also given to reports on neurotoxicological effects at relatively low doses of BFRs, although an endocrine-related mechanism is disputable. Convincing evidence has been published showing that BFRs and importantly, BFR metabolites, have the potential to disrupt endocrine systems at multiple target sites. While some studies suggest a wide margin of safety between effect concentrations in rodent models and levels encountered in humans and the environment, other studies demonstrate that exposure to low doses relevant for humans and wildlife at critical time points in development can result in profound effects on both endocrine pathways and (neuro)development.

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.

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. ...

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

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

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

PubMed Central

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

2016-01-01

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

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.

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.

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...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.more » 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

Consensus models to predict endocrine disruption for all ...

EPA Pesticide Factsheets

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

Characterization of endocrine disruption potentials of coastal sediments of Taean, Korea employing H295R and MVLN assays-Reconnaissance at 5years after Hebei Spirit oil spill.

PubMed

Liu, Xiaoshan; Jung, Dawoon; Zhou, Kairu; Lee, Sangwoo; Noh, Kiwan; Khim, Jong Seong; Giesy, John P; Yim, Un Hyuk; Shim, Won Joon; Choi, Kyungho

2018-02-01

Endocrine disrupting potentials were assessed for sediment samples collected near Hebei Spirit oil spill (HSOS) site, between December 2007 and January 2012. For comparison, major crude oil (CO) of HSOS, or its weathered form were assessed. Both raw extracts (REs) and their fractionated samples were tested using H295R and MVLNluc bioassays. In H295R cells, REs of crude and weathered oil (WO), and nine of 14 sediments significantly increased E2 levels, which were correlated with the concentrations of PAHs. Steroidogenic disruption potentials of the sediments generally decreased over time. Among silica fractions of all REs, aromatic hydrocarbons (F2) and polar compounds (F3) caused greater E2 levels. While, in MVLN cell bioassay, only three of 14 sediment REs showed estrogen receptor binding potencies, and no temporal trend was observed. In conclusion, oil spill can cause endocrine disruption in the affected ecosystem through steroidogenic alteration for years, and such potencies attenuate over time. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-10-01

to setting regulatory criteria to identify endocrine disrupting substances in the European Union. Environ Health Perspect 124:1497-1503; http://dx.doi.org/10.1289/EHP217.

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

PubMed Central

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

2016-01-01

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

Endocrine Disrupting Chemicals Mediated through Binding Androgen Receptor Are Associated with Diabetes Mellitus

PubMed Central

Sakkiah, Sugunadevi; Wang, Tony; Zou, Wen; Wang, Yuping; Pan, Bohu; Tong, Weida; Hong, Huixiao

2017-01-01

Endocrine disrupting chemicals (EDCs) can mimic natural hormone to interact with receptors in the endocrine system and thus disrupt the functions of the endocrine system, raising concerns on the public health. In addition to disruption of the endocrine system, some EDCs have been found associated with many diseases such as breast cancer, prostate cancer, infertility, asthma, stroke, Alzheimer’s disease, obesity, and diabetes mellitus. EDCs that binding androgen receptor have been reported associated with diabetes mellitus in in vitro, animal, and clinical studies. In this review, we summarize the structural basis and interactions between androgen receptor and EDCs as well as the associations of various types of diabetes mellitus with the EDCs mediated through androgen receptor binding. We also discuss the perspective research for further understanding the impact and mechanisms of EDCs on the risk of diabetes mellitus. PMID:29295509

Bird populations as sentinels of endocrine disrupting chemicals.

PubMed

Carere, Claudio; Costantini, David; Sorace, Alberto; Santucci, Daniela; Alleva, Enrico

2010-01-01

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

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 ...

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

PubMed Central

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

2015-01-01

Breast cancer incidence continues to increase in the US and Europe, a reflection of the growing influence of environment factors that interact with personal genetics. The US Environmental Protection Agency estimates that over 85,000 endocrine disrupting chemicals are among the common daily exposures that could affect the risk of disease. The daunting tasks of identifying, characterizing, and elucidating the mechanisms of endocrine disrupting chemicals in breast cancer need to be addressed to produce a comprehensive model that will facilitate preventive strategies and public policy. An expert panel met to describe and bring attention to needs linking common environmental exposures, critical windows of exposure, and optimal times of assessment in investigating breast cancer risk. The group included investigators with extensive experience in the use of rodent models and in leading population studies and produced a set of recommendations for effective approaches to gaining insights into the environmental origins of breast cancer across the lifespan. PMID:25549947

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frizzell, Caroline; Ndossi, Doreen; Sokoine University of Agriculture, Morogoro

2013-08-15

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

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

PubMed Central

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

2016-01-01

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

Levels of endocrine disrupting compounds in South China Sea.

PubMed

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

2014-08-30

The occurrence of estrogens in the aquatic environment has become a major concern worldwide because of their strong endocrine disrupting potency. In this study, concentrations of four estrogenic compounds, estrone (E1), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), estriol (E3) were determined with liquid chromatography-tandem mass spectrometry analyses in surface water from South China Sea, and distributions and potential risks of their estrogenic activity were assessed. The estrogenic compounds E1, E2 and E3 were detected in most of the samples, with their concentrations up to 11.16, 3.71 and 21.63 ng L(-1). However, EE2 was only detected in 3 samples. Causality analysis, EEQ values from chemical analysis identified E2 as the main responsible compounds. Based on the EEQ values in the surface water, high estrogenic risks were in the coastal water, and low estrogenic risks in the open sea. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

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. ...

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...

Commercial processed food may have endocrine-disrupting potential: soy-based ingredients making the difference.

PubMed

Omoruyi, Iyekhoetin Matthew; Kabiersch, Grit; Pohjanvirta, Raimo

2013-01-01

Processed and packaged food items as well as ready-to-eat snacks are neglected and poorly characterised sources of human exposure to endocrine-disrupting chemicals (EDCs). In this study we investigated the presence of xenoestrogens in commercially processed and packaged Finnish foods, arising from substances deliberately added or inadvertently contaminating the food, substances formed as a result of food processing, or substances leaching from food packaging materials. Samples were obtained in three separate batches of equivalent products from both a supermarket and a local representative of a global chain of hamburger restaurants and extracted by a solid-phase extraction method. Their endocrine-disrupting potential was determined by yeast bioluminescent assay, using two recombinant yeast strains Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc. In this test system, the majority of samples (both foodstuffs and wrappers) analysed proved negative. However, all batches of industrially prepared hamburgers (but not those obtained from a hamburger restaurant) as well as pepper salami significantly induced luciferase activity in the BMAEREluc/ERα yeast strain indicating the presence of xenoestrogens, with estradiol equivalents of these products ranging from 0.2 to 443 pg g(-1). All three products contained soy-based ingredients, which apparently accounted for, or at least contributed to, their high estrogenic activity, since no signal in the assay was observed with extracts of the packaging material, while two different soy sauces tested yielded an intense signal (28 and 54 pg ml(-1) estradiol-equivalent). These findings imply that by and large chemicals arising in the processing or packaging of foodstuffs in Finland constitute an insignificant source of xenoestrogens to consumers. However, soy-derived ingredients in certain food items might render the entire products highly estrogenic. The estrogenic activity of soy is attributed to isoflavones whose

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

PubMed

Dogan, Selen; Simsek, Tayup

2016-07-01

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

Annamalai, Jayshree; Namasivayam, Vasudevan

2015-03-01

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

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...

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

PubMed Central

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

2014-01-01

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

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...

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

USGS Publications Warehouse

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

2011-01-01

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

The Effects of Nanomaterials as Endocrine Disruptors

PubMed Central

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

2013-01-01

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

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

Determination of endocrine-disrupting chemicals in human milk by dispersive liquid-liquid microextraction.

PubMed

Vela-Soria, Fernando; Jiménez-Díaz, Inmaculada; Díaz, Caridad; Pérez, José; Iribarne-Durán, Luz María; Serrano-López, Laura; Arrebola, Juan Pedro; Fernández, Mariana Fátima; Olea, Nicolás

2016-09-01

Human populations are widely exposed to numerous so-called endocrine-disrupting chemicals, exogenous compounds able to interfere with the endocrine system. This exposure has been associated with several health disorders. New analytical procedures are needed for biomonitoring these xenobiotics in human matrices. A quick and inexpensive methodological procedure, based on sample treatment by dispersive liquid-liquid microextraction, is proposed for the determination of bisphenols, parabens and benzophenones in samples. LOQs ranged from 0.4 to 0.7 ng ml(-1) and RSDs from 4.3 to 14.8%. This methodology was satisfactorily applied in the simultaneous determination of a wide range of endocrine-disrupting chemicals in human milk samples and is suitable for application in biomonitoring studies.

Endocrine-disrupting chemicals in aquatic environment: what are the risks for fish gametes?

PubMed

Carnevali, Oliana; Santangeli, Stefania; Forner-Piquer, Isabel; Basili, Danilo; Maradonna, Francesca

2018-06-11

Over the past 25 years, extensive research in vertebrate species has identified several genomic pathways altered by exposures to anthropogenic chemicals with hormone-like activity mediated by their interaction with nuclear receptors. In addition, many pollutants have been shown to interfere with non-genomic (non-classical) pathways, but this mechanism of endocrine disruption is still poorly understood. Recently, the number of publications describing the effects of Endocrine disrupting chemicals (EDCs) on fish reproduction, focusing on the deregulation of the hypothalamus-pituitary-gonadal axis as well as on gamete quality, significantly increased. Depending on their ability to mimic endogenous hormones, the may differently affect male or female reproductive physiology. Inhibition of gametogenesis, development of intersex gonads, alteration of the gonadosomatic index, and decreased fertility rate have been largely documented. In males, alterations of sperm density, motility, and fertility have been observed in several wild species. Similar detrimental effects were described in females, including negative outcomes on oocyte growth and maturation plus the occurrence of apoptotic/autophagic processes. These pathways may affect gamete viability considered as one of the major indicators of reproductive endocrine disruption. Pollutants act also at DNA level producing DNA mutations and changes in epigenetic pathways inducing specific mechanisms of toxicity and/or aberrant cellular responses that may affect subsequent generation(s) through the germline. In conclusion, this review summarizes the effects caused by EDC exposure on fish reproduction, focusing on gametogenesis, giving a general overview of the different aspects dealing with this issue, from morphological alteration, deregulation of steroidogenesis, hormonal synthesis, and occurrence of epigenetic process.

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...

Possible endocrine disrupting effects of parabens and their metabolites.

PubMed

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

2010-09-01

Parabens are preservatives used in a wide range of cosmetic products, including products for children, and some are permitted in foods. However, there is concern for endocrine disrupting effects. This paper critically discusses the conclusions of recent reviews and original research papers and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites, little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when comparing worst-case exposure to NOAELs from experimental studies in rats and mice. Copyright 2010 Elsevier Inc. All rights reserved.

Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

PubMed

Pinson, Anneline; Franssen, Delphine; Gérard, Arlette; Parent, Anne-Simone; Bourguignon, Jean-Pierre

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the "altered function(s) of the endocrine system". Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

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...

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rapid, portable detection of endocrine disrupting chemicals through ligand-nuclear hormone receptor interactions.

PubMed

Hunt, J Porter; Schinn, Song-Min; Jones, Matthew D; Bundy, Bradley C

2017-12-04

Endocrine disrupting chemicals (EDC) are structurally diverse compounds that can interact with nuclear hormone receptors, posing significant risk to human and ecological health. Unfortunately, many conventional biosensors have been too structure-specific, labor-intensive or laboratory-oriented to detect broad ranges of EDC effectively. Recently, several technological advances are providing more rapid, portable, and affordable detection of endocrine-disrupting activity through ligand-nuclear hormone receptor interactions. Here, we overview these recent advances applied to EDC biosensors - including cell lyophilization, cell immobilization, cell-free systems, smartphone-based signal detection, and improved competitive binding assays.

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...

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

PubMed

Vandenberg, Laura N; Ågerstrand, Marlene; Beronius, Anna; Beausoleil, Claire; Bergman, Åke; Bero, Lisa A; Bornehag, Carl-Gustaf; Boyer, C Scott; Cooper, Glinda S; Cotgreave, Ian; Gee, David; Grandjean, Philippe; Guyton, Kathryn Z; Hass, Ulla; Heindel, Jerrold J; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Macleod, Malcolm R; Martin, Olwenn V; Norinder, Ulf; Scheringer, Martin; Thayer, Kristina A; Toppari, Jorma; Whaley, Paul; Woodruff, Tracey J; Rudén, Christina

2016-07-14

The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This

Determination of acidic pharmaceuticals and potential endocrine disrupting compounds in wastewaters and spring waters by selective elution and analysis by gas chromatography-mass spectrometry.

PubMed

Gibson, Richard; Becerril-Bravo, Elías; Silva-Castro, Vanessa; Jiménez, Blanca

2007-10-26

Although the trend in development of analytical methods for emerging contaminants is towards reduced sample preparation and increased detector selectivity, there are still benefits from removal of matrix material during sample preparation. This paper describes a simple method for acidic pharmaceuticals and a range of potential endocrine disrupting compounds in untreated wastewaters and spring waters. It is based on separation of the two classes during elution from the extraction cartridge with final analysis by gas chromatography-mass spectrometry. 3,4-D was used as the recovery standard for the acids while 4-n-nonylphenol and [2H4]estrone were used for the endocrine disrupters; mean recoveries varied between 89% and 111%. The method was also extensively validated by fortification with the target compounds. Recoveries of acids were from 68% to 97% with relative standard deviations generally less than 10% and recoveries of endocrine disrupters were 68-109% with relative standard deviations less than 20%. Detection limits varied from 0.005 to 1 ng/L in spring water, and from 0.5 to 100 ng/L in untreated wastewater. Concentrations of the analytes in the wastewater ranged from 0.018 to 22.4 microg/L. Values were comparable to reported data, although concentrations were generally relatively high, probably because of a lack of treatment. Triclosan, phthalates, estrone, 17beta-estradiol, ibuprofen, and naproxen were present in the spring water from aquifers recharged indirectly with this wastewater after its use for irrigation; concentrations ranged from 0.01 to 25.0 ng/L. The much lower concentrations compared to wastewater indicate effective removal processes on passage through the soil and subsoil.

Peer-reviewed and unbiased research, rather than ‘sound science’, should be used to evaluate endocrine-disrupting chemicals

PubMed Central

Trasande, Leonardo; Vandenberg, Laura N; Bourguignon, Jean-Pierre; Myers, John Peterson; Slama, Remy; Saal, Frederick vom; Zoeller, Robert Thomas

2017-01-01

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, ‘manufactured doubt’ continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. ‘Good laboratory practice’ (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than ‘sound science’, should be used to evaluate endocrine-disrupting chemicals. PMID:27417427

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

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

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 ...

Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.

PubMed

Trasande, Leonardo; Vandenberg, Laura N; Bourguignon, Jean-Pierre; Myers, John Peterson; Slama, Remy; Vom Saal, Frederick; Zoeller, Robert Thomas

2016-11-01

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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...

Effect of Endocrine Disruptor Pesticides: A Review

PubMed Central

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

2011-01-01

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

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.

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

PubMed

Guo, Yongyong; Zhou, Bingsheng

2013-10-15

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

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

Measurement of endocrine disrupting and asthma-associated chemicals in hair products used by Black women.

PubMed

Helm, Jessica S; Nishioka, Marcia; Brody, Julia Green; Rudel, Ruthann A; Dodson, Robin E

2018-08-01

Personal care products are a source of exposure to endocrine disrupting and asthma-associated chemicals. Because use of hair products differs by race/ethnicity, these products may contribute to exposure and disease disparities. This preliminary study investigates the endocrine disrupting and asthma-associated chemical content of hair products used by U.S. Black women. We used gas chromatography/mass spectrometry (GC/MS) to test 18 hair products in 6 categories used by Black women: hot oil treatment, anti-frizz/polish, leave-in conditioner, root stimulator, hair lotion, and relaxer. We tested for 66 chemicals belonging to 10 chemical classes: ultraviolet (UV) filters, cyclosiloxanes, glycol ethers, fragrances, alkylphenols, ethanolamines, antimicrobials, bisphenol A, phthalates, and parabens. The hair products tested contained 45 endocrine disrupting or asthma-associated chemicals, including every targeted chemical class. We found cyclosiloxanes, parabens, and the fragrance marker diethyl phthalate (DEP) at the highest levels, and DEP most frequently. Root stimulators, hair lotions, and relaxers frequently contained nonylphenols, parabens, and fragrances; anti-frizz products contained cyclosiloxanes. Hair relaxers for children contained five chemicals regulated by California's Proposition 65 or prohibited by EU cosmetics regulation. Targeted chemicals were generally not listed on the product label. Hair products used by Black women and children contained multiple chemicals associated with endocrine disruption and asthma. The prevalence of parabens and DEP is consistent with higher levels of these compounds in biomonitoring samples from Black women compared with White women. These results indicate the need for more information about the contribution of consumer products to exposure disparities. A precautionary approach would reduce the use of endocrine disrupting chemicals in personal care products and improve labeling so women can select products consistent with

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 ...

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

PubMed

Montes-Grajales, Diana; Olivero-Verbel, Jesus

2015-01-02

Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system, frequently found in everyday products and epidemiologically associated with several diseases. The purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of information from different databases and text mining tools, useful for almost any kind of research regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors, through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several formats. This database is freely available at http://edcs.unicartagena.edu.co. Copyright © 2014. Published by Elsevier Ireland Ltd.

Studying the effects of genistein on gene expression of fish embryos as an alternative testing approach for endocrine disruption.

PubMed

Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Muth-Köhne, Elke; Giesy, John P; Hecker, Markus; Fenske, Martina

2013-01-01

Assessment of endocrine disruption currently relies on testing strategies involving adult vertebrates. In order to minimize the use of animal tests according to the 3Rs principle of replacement, reduction and refinement, we propose a transcriptomics and fish embryo based approach as an alternative to identify and analyze an estrogenic activity of environmental chemicals. For this purpose, the suitability of 48 h and 7 days post-fertilization zebrafish and medaka embryos to test for estrogenic disruption was evaluated. The embryos were exposed to the phytoestrogen genistein and subsequently analyzed by microarrays and quantitative real-time PCR. The functional analysis showed that the genes affected related to multiple metabolic and signaling pathways in the early fish embryo, which reflect the known components of genistein's mode of actions, like apoptosis, estrogenic response, hox gene expression and steroid hormone synthesis. Moreover, the transcriptomic data also suggested a thyroidal mode of action and disruption of the nervous system development. The parallel testing of two fish species provided complementary data on the effects of genistein at gene expression level and facilitated the separation of common from species-dependent effects. Overall, the study demonstrated that combining fish embryo testing with transcriptomics can deliver abundant information about the mechanistic effects of endocrine disrupting chemicals, rendering this strategy a promising alternative approach to test for endocrine disruption in a whole organism in-vitro scale system. Copyright © 2012 Elsevier Inc. All rights reserved.

A Multi-Receptor and Multi-Species Assay for Potential Endocrine Disruptor Targets (SLAS meeting)

EPA Science Inventory

Screening methods for detecting potential endocrine disrupting chemicals rely chiefly on transactivation assays targeting nuclear receptors such as the estrogen (ER) and androgen receptors (AR). These assays are predominately human-based; yet environmental exposure can affect div...

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

PubMed

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

2016-07-01

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs. © 2016 American Society of Andrology and European Academy of Andrology.

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,...

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...

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

PubMed Central

Matisová, Eva; Hrouzková, Svetlana

2012-01-01

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

Health risk assessment procedures for endocrine disrupting compounds within different regulatory frameworks in the European Union.

PubMed

Beronius, Anna; Rudén, Christina; Hanberg, Annika; Håkansson, Helen

2009-11-01

In this study we have investigated how different regulatory frameworks in Europe cope with identification and risk assessment of endocrine disrupting compounds (EDCs). Four regulatory groups were selected for the investigation: existing industrial chemicals, environmental pollutants in food, pharmaceuticals and plant protection products. The legislation and guidelines for each of these groups were scrutinized and compared in detail. In addition, one recent European risk assessment document each for three identified EDCs, i.e. bisphenol A, dioxins and vinclozolin, were reviewed and compared. We found that the requirements for toxicity testing and availability and scope of risk assessment guidelines varied between the four regulatory frameworks. Also, the general principles regarding the human relevance of the mode of action identified in animal tests differed in the different risk assessments. In conclusion, there is little conformity in the risk assessment processes between these groups of chemicals. Because of the complicated nature of endocrine disruption, test methods, principles and criteria for data interpretation traditionally used might not be directly applicable to EDCs and further development of a transparent and reliable risk assessment process for this type of substances is needed.

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.

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...

In silico methods in the discovery of endocrine disrupting chemicals.

PubMed

Vuorinen, Anna; Odermatt, Alex; Schuster, Daniela

2013-09-01

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

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...

Using short-term bioassays to evaluate the endocrine disrupting capacity of the pesticides linuron and fenoxycarb.

PubMed

Spirhanzlova, Petra; De Groef, Bert; Nicholson, Freda E; Grommen, Sylvia V H; Marras, Giulia; Sébillot, Anthony; Demeneix, Barbara A; Pallud-Mothré, Sophie; Lemkine, Gregory F; Tindall, Andrew J; Du Pasquier, David

2017-10-01

Several short-term whole-organism bioassays based on transgenic aquatic models are now under validation by the OECD (Organization for Economic Co-operation and Development) to become standardized test guidelines for the evaluation of the endocrine activity of substances. Evaluation of the endocrine disrupting capacity of pesticides will be a domain of applicability of these future reference tests. The herbicide linuron and the insecticide fenoxycarb are two chemicals commonly used in agricultural practices. While numerous studies indicate that linuron is likely to be an endocrine disruptor, there is little information available on the effect of fenoxycarb on vertebrate endocrine systems. Using whole-organism bioassays based on transgenic Xenopus laevis tadpoles and medaka fry we assessed the potential of fenoxycarb and linuron to disrupt thyroid, androgen and estrogen signaling. In addition we used in silico approach to simulate the affinity of these two pesticides to human hormone receptors. Linuron elicited thyroid hormone-like activity in tadpoles at all concentrations tested and, showed an anti-estrogenic activity in medaka at concentrations 2.5mg/L and higher. Our experiments suggest that, in addition to its previously established anti-androgenic action, linuron exhibits thyroid hormone-like responses, as well as acting at the estrogen receptor level to inhibit estrogen signaling. Fenoxycarb on the other hand, did not cause any changes in thyroid, androgen or estrogen signaling at the concentrations tested. Copyright © 2017 Elsevier Inc. All rights reserved.

A NEW HIGH RESOLUTION MASS SPECTROMETRY TECHNIQUE FOR IDENTIFYING PHARMACEUTICALS AND POTENTIAL ENDOCRINE DISRUPTORS IN DRINKING WATER SOURCES

EPA Science Inventory

A New High Resolution Mass Spectrometry Technique for Identifying Pharmaceuticals and Potential Endocrine Disruptors in Drinking Water Sources

Andrew H. Grange and G. Wayne Sovocool U.S.EPA, ORD, NERL, ESD, ECB, P.O. Box 93478, Las Vegas, NV 891933478

Mass spectra...

Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids.

PubMed

Strajhar, Petra; Tonoli, David; Jeanneret, Fabienne; Imhof, Raphaella M; Malagnino, Vanessa; Patt, Melanie; Kratschmar, Denise V; Boccard, Julien; Rudaz, Serge; Odermatt, Alex

2017-04-15

The validated OECD test guideline 456 based on human adrenal H295R cells promotes measurement of testosterone and estradiol production as read-out to identify potential endocrine disrupting chemicals. This study aimed to establish optimal conditions for using H295R cells to detect chemicals interfering with the production of key adrenal steroids. H295R cells' supernatants were characterized by liquid chromatography-mass spectrometry (LC-MS)-based steroid profiling, and the influence of experimental conditions including time and serum content was assessed. Steroid profiles were determined before and after incubation with reference compounds and chemicals to be tested for potential disruption of adrenal steroidogenesis. The H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amounts of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48h incubation. Thus, inclusion of positive and negative controls and a steroid profile of the complete medium prior to the experiment (t=0h) was necessary to characterize H295R cells' steroid production and indicate alterations caused by exposure to chemicals. Among the tested chemicals, octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the positive control torcetrapib. Gene expression analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression, although less pronounced than torcetrapib. Further experiments need to assess the toxicological relevance of octyl methoxycinnamate- and acetyl tributylcitrate-induced corticosteroid production. In conclusion, the extended profiling and appropriate controls allow detecting chemicals that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chemicals for further investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2008-01-01

In 1991, a group of expert scientists at a Wingspread work session on endocrine-disrupting chemicals (EDCs) concluded that “Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and humans. Endocrine disruption can be profound because of the crucial role hormones play in controlling development.” Since that time, there have been numerous documented examples of adverse effects of EDCs in invertebrates, fish, wildlife, domestic animals, and humans. Hormonal systems can be disrupted by numerous different anthropogenic chemicals including antiandrogens, androgens, estrogens, AhR agonists, inhibitors of steroid hormone synthesis, antithyroid substances, and retinoid agonists. In addition, pathways and targets for endocrine disruption extend beyond the traditional estrogen/androgen/thyroid receptor–mediated reproductive and developmental systems. For example, scientists have expressed concern about the potential role of EDCs in increasing trends in early puberty in girls, obesity and type II diabetes in the United States and other populations. New concerns include complex endocrine alterations induced by mixtures of chemicals, an issue broadened due to the growing awareness that EDCs present in the environment include a variety of potent human and veterinary pharmaceutical products, personal care products, nutraceuticals and phytosterols. In this review we (1) address what have we learned about the effects of EDCs on fish, wildlife, and human health, (2) discuss representative animal studies on (anti)androgens, estrogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin–like chemicals, and (3) evaluate regulatory proposals being considered for screening and testing these chemicals. PMID:18281716

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...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taxvig, Camilla, E-mail: camta@food.dtu.dk; 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 endogenousmore » 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.« less

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

PubMed

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

2011-02-01

Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-02-01

The French Agency for Food, Environmental and Occupational Health and Safety (Anses) hosted a two-day workshop on Endocrine Disruptors: Exposure and Potential Impact on Consumers Health, bringing together participants from international organizations, academia, research institutes and from German, Swedish, Danish and French governmental agencies. The main objective of the workshop was to share knowledge and experiences on endocrine disruptors (ED) exposure and potential impact on consumers' health, to identify current risk assessment practices and knowledge gaps and issue recommendations on research needs and future collaboration. The following topics were reviewed: (1) Definition of ED, (2) endpoints to be considered for Risk assessment (RA) of ED, (3) non-monotonic dose response curves, (4) studies to be considered for RA (regulatory versus academic studies), (5) point of departure and uncertainty factors, (6) exposure assessment, (7) regulatory issues related to ED. The opinions expressed during this workshop reflect day-to-day experiences from scientists, regulators, researchers, and others from many different countries in the fields of risk assessment, and were regarded by the attendees as an important basis for further discussions. Accordingly, the participants underlined the need for more exchange in the future to share experiences and improve the methodology related to risk assessment for endocrine disrupters. Copyright © 2012 Elsevier Inc. All rights reserved.

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 R.; 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.

Environmental epigenetics: a role in endocrine disease?

PubMed

Fleisch, Abby F; Wright, Robert O; Baccarelli, Andrea A

2012-10-01

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes.

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

EPA Science Inventory

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

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

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...

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

PubMed

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

2016-01-05

Many pesticides have been identified as endocrine-disrupting chemicals (EDCs) due to their ability to bind sex-steroid hormone receptors. However, little attention has been paid to the ability of pesticides to interfere with other steroid hormone receptors such as glucocorticoid receptor (GR) that plays a critical role in metabolic, endocrine, immune, and nervous systems. In this study, the glucocorticoidic and antiglucocorticoidic effects of 34 pesticides on human GR were investigated using luciferase reporter gene assay. Surprisingly, none of the test chemicals showed GR agonistic activity, but 12 chemicals exhibited apparent antagonistic effects. Bifenthrin, λ-cyhalothrin, cypermethrin, resmethrin, o,p'-DDT, p,p'-DDT, methoxychlor, ethiofencarb, and tolylfluanid showed remarkable GR antagonistic properties with RIC20 values lower than 10(-6) M. The disruption of glucocorticoid-responsive genes in H4IIE and J774A.1 cells was further evaluated on these 12 GR antagonists. In H4IIEcells, four organochlorine insecticides, bifenthrin, and 3-PBA decreased cortisol-induced PEPCK gene expression, while o,p'-DDT and methoxychlor inhibited cortisol-stimulated Arg and TAT gene expression. Cypermethrin and tolyfluanid attenuated cortisol-induced TAT expression. In J774A.1 cells, λ-cyhalothrin, resmethrin, 3-PBA, o,p'-DDT, p,p'-DDT, p,p'-DDE, methoxychlor- and tolylfluanid-reduced cortisol-stimulated GILZ expression. Furthermore, molecular docking simulation indicated that different interactions may stabilize the binding between molecules and GR. Our findings suggest that comprehensive screening and evaluation of GR antagonists and agonists should be considered to better understand the health and ecological risks of man-made chemicals such as pesticides.

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.

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

Effects of endocrine disrupting chemicals from leather industry effluents on male reproductive system.

PubMed

Kumar, Vikas; Majumdar, Chandrajeetbalo; Roy, Partha

2008-09-01

The leather tanning industry is characterized by the production of different kinds of effluents, generated in each step of leather processing. These effluents have various chemical compounds which may cause toxicity and endocrine disruption and are thus known as endocrine disrupting chemicals (EDC). This study was aimed to examine the androgenic potential of leather industry effluents collected from northern region of India. Hershberger assay data showed a significant increase (p<0.05) in the weight and structure of sex accessory tissues of castrated rats. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated a significant change (p<0.05) in the expression patterns of the major steroidogenic enzymes in adrenal and testes namely, cytochrome P450scc, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydorgenase in castrated and intact rats. This was further supported by increased enzymatic activities measured in vitro spectrophotometrically. Serum hormone profile demonstrated a dose dependent increase in testicular and adrenal testosterone productions in intact and castrated rats, respectively. This was further supported by decreased level of gonadotrophic hormones (LH and FSH) in treated groups of animals. Further, the effluent treatment resulted in the development of hyperplasia in seminiferous tubules of testes in treated rats as evident from histopathological studies and about two-fold increases in daily sperm production. On analysis of water samples using GC-MS, it was found to contain various aromatic compounds (nonylphenol, hexaclrobenzene and several azo dyes) some of which independently demonstrated similar effects as shown by water samples. Our data suggests that the effluents from leather industry have potential EDC demonstrating androgenic activities.

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

PubMed

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

2018-02-01

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

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...

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

PubMed

Perharič, Lucija; Fatur, Tanja; Drofenik, Jernej

2016-06-01

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

Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

PubMed Central

Braun, Joseph M.

2017-01-01

Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

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...

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...

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...

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

EPA Pesticide Factsheets

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

Simultaneous profiling of 17 steroid hormones for the evaluation of endocrine-disrupting chemicals in H295R cells.

PubMed

Jumhawan, Udi; Yamashita, Toshiyuki; Ishida, Kazuya; Fukusaki, Eiichiro; Bamba, Takeshi

2017-01-01

There is urgent need to develop a new protocol for the evaluation of chemical substances to potentially interact with the endocrine system and induce numerous pathological issues. The recently validated in vitro screening assay is limited on monitoring two steroid hormones. Methodology & results: The H295R model cell was exposed to seven endocrine disrupting chemicals (EDCs). The levels of 17 steroid hormones in cell extracts were subsequently determined by a quantitative targeted GC/MS/MS method. Through wide coverage, this system managed to capture the effects of exposure to increasing EDCs concentrations in the entire steroidogenic pathways. The developed approach could be beneficial for the mechanistic investigation of EDCs.

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...

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...

Fifteen years after "Wingspread"- Environmental Endocrine Disrupters and human and wildlife health: Where we are today and where we need to go.

EPA Science Inventory

In 1991 a group of expert scientists at a Wingspread work session on endocrine disrupting chemicals (EDCs) concluded that "Many compounds introduced into the environment by human activity are capable of disrupting the endocrine system of animals, including fish, wildlife, and hum...

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 ...

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...

Evaluation of an In Vitro Multi-Receptor and Multi-Species Assay for Potential Endocrine Disruptor Targets (SOT)

EPA Science Inventory

Receptor sequence conservation across species may be a key factor determining susceptibility to potential endocrine disrupting chemicals. Computational approaches that compare receptor sequence similarities (e.g. SeqAPASS; https://seqapass.epa.gov/seqapass/) have been proposed to...

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 ...

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

PubMed

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

2009-01-01

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

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. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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...

Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health.

PubMed

Tapia-Orozco, Natalia; Santiago-Toledo, Gerardo; Barrón, Valeria; Espinosa-García, Ana María; García-García, José Antonio; García-Arrazola, Roeb

2017-04-01

Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

USGS Publications Warehouse

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

2012-01-01

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

Research on Endocrine Disruptors

EPA Pesticide Factsheets

EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Are Endocrine Disrupting Compounds a Health Risk in Drinking Water?

PubMed Central

Falconer, Ian R.

2006-01-01

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

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

PubMed

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

2016-11-01

Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

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

EPA Science Inventory

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

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...

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

PubMed

Vuorinen, Anna; Odermatt, Alex; Schuster, Daniela

2015-09-01

The prevalence of sex hormone-dependent cancers, reproductive problems, obesity, and cardiovascular complications has risen especially in the Western world. It has been suggested, that the exposure to various endocrine disrupting chemicals (EDCs) contributes to the development and progression of these diseases. EDCs can interfere with various proteins: nuclear steroid hormone receptors, such as estrogen-, androgen-, glucocorticoid- and mineralocorticoid receptors (ER, AR, GR, MR), and enzymes that are involved in steroid hormone synthesis and metabolism, for example hydroxysteroid dehydrogenases (HSDs). Numerous chemicals are known as endocrine disruptors. However, the mechanism of action for most of these EDCs is still unknown. It is exhaustive and time consuming to test in vitro all chemicals - potential EDCs - used in industry, agriculture or as food preservatives against their effects on the endocrine system. Computational methods, such as virtual screening, quantitative structure activity relationships and docking, are already well recognized and used in drug development. The same methods could also aid the research on EDCs. So far, the computational methods in the search of EDCs have been retrospective. There are, however, some prospective studies reporting the use of in silico methods: five studies reporting the identification of previously unknown 17β-HSD3 inhibitors, MR agonists, and ER antagonists/agonists. This review provides an overview of case studies and in silico methods that are used in the search of EDCs. This article is part of a Special Issue entitled 'CSR 2013'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors

PubMed Central

2013-01-01

The “common sense” intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. PMID:23981490

Test driving ToxCast: endocrine profiling for1858 chemicals included in phase II

EPA Science Inventory

Introduction: Identifying chemicals to test for potential endocrine disruption beyond those already implicated in the peer-reviewed literature is a challenge. This review is intended to help by summarizing findings from the Environmental Protection Agency’s (EPA) ToxCast™ high th...

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. 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.

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

PubMed

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

2016-09-01

Short-chain chlorinated paraffins (SCCPs), which are candidate persistent organic pollutants (POPs) according to the Stockholm Convention, are of great concern because of their persistent bioaccumulation, long-range transport and potential adverse health effects. However, data on the endocrine-disrupting effects of SCCPs remain scarce. In this study, we first adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of three SCCPs (C10-40.40%, C10-66.10% and C11-43.20%) via receptor mediated and non-receptor mediated pathway. The dual-luciferase reporter gene assay revealed that all test chemicals significantly induced estrogenic effects, which were mediated by estrogen receptor α (ERα), in the following order: C11-43.20%>C10-66.10%>C10-40.40%. Notably, C10-40.40% and C10-66.10% also demonstrated remarkable anti-estrogenic activities. Only C11-43.20% showed glucocorticoid receptor-mediated (GR) antagonistic activity, with a RIC20 value of 2.6×10(-8)mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor β (TRβ). Meanwhile, all test SCCPs stimulated the secretion of 17β-estradiol (E2). Both C10-66.10% and C11-43.20% increased the production of cortisol at a high level in H295R cell lines. In order to explore the possible mechanism underlying the endocrine-disrupting effects of SCCPs through the non-receptor pathway, the mRNA levels of 9 steroidogenic genes were measured by real-time polymerase chain reaction (RT-PCR). StAR, 17βHSD, CYP11A1, CYP11B1, CYP19 and CYP21 were upregulated in a concentration-dependent manner by all chemicals. The data provided here emphasized that comprehensive assessments of the health and ecological risks of emerging contaminants, such as SCCPs, are of great concern and should be investigated further. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

2015-01-01

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

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

USGS Publications Warehouse

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

2015-01-01

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

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. © 2014 SETAC.

Assessment of endocrine disruption potential of essential oils of culinary herbs and spices involving glucocorticoid, androgen and vitamin D receptors.

PubMed

Bartoňková, Iveta; Dvořák, Zdeněk

2018-04-25

Essential oils (EOs) of culinary herbs and spices are consumed on a daily basis. They are multicomponent mixtures of compounds with already demonstrated biological activities. Taking into account regular dietary intake and the chemical composition of EOs, they may be considered as candidates for endocrine-disrupting entities. Therefore, we examined the effects of 31 EOs of culinary herbs and spices on transcriptional activities of glucocorticoid receptor (GR), androgen receptor (AR) and vitamin D receptor (VDR). Using reporter gene assays in stably transfected cell lines, weak anti-androgen and anti-glucocorticoid activity was observed for EO of vanilla and nutmeg, respectively. Moderate augmentation of calcitriol-dependent VDR activity was caused by EOs of ginger, thyme, coriander and lemongrass. Mixed anti-glucocorticoid and VDR-stimulatory activities were displayed by EOs of turmeric, oregano, dill, caraway, verveine and spearmint. The remaining 19 EOs were inactive against all receptors under investigation. Analyses of GR, AR and VDR target genes by means of RT-PCR confirmed the VDR-stimulatory effects, but could not confirm the anti-glucocorticoid and anti-androgen effects of EOs. In conclusion, although we observed minor effects of several EOs on transcriptional activities of GR, AR and VDR, the toxicological significance of these effects is very low. Hence, 31 EOs of culinary herbs and spices may be considered safe, in terms of endocrine disruption involving receptors GR, AR and VDR.

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...

A critical review of histopathological findings associated with endocrine and non-endocrine hepatic toxicity in fish models.

PubMed

Wolf, Jeffrey C; Wheeler, James R

2018-04-01

Although frequently examined as a target organ for non-endocrine toxicity, histopathological evaluation of the liver is becoming a routine component of endocrine disruption studies that utilize various fish species as test subjects. However, the interpretation of microscopic liver findings can be challenging, especially when attempting to distinguish adverse changes associated with endocrine disrupting substances from those caused by systemic or direct hepatic toxicity. The purpose of this project was to conduct a critical assessment of the available peer-reviewed and grey literature concerning the histopathologic effects of reproductive endocrine active substances (EAS) and non-endocrine acting substances in the livers of fish models, and to determine if liver histopathology can be used to reliably distinguish endocrine from non-endocrine etiologies. The results of this review suggest that few compound-specific histopathologic liver effects have been identified, among which are estrogen agonist-induced increases in hepatocyte basophilia and proteinaceous intravascular fluid in adult male teleosts, and potentially, decreased hepatocyte basophilia in female fish exposed to substances that possess androgenic, anti-estrogenic, or aromatase inhibitory activity. This review also used published standardized methodology to assess the credibility of the histopathology data in each of the 117 articles that reported liver effects of treatment, and consequently it was determined that in only 37% of those papers were the data considered either highly credible or credible. The outcome of this work highlights the value of histopathologic liver evaluation as an investigative tool for EAS studies, and provides information that may have implications for EAS hazard assessment. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

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

USGS Publications Warehouse

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

2015-01-01

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

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

PubMed

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

2015-12-01

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

Do endocrine disruptors cause hypospadias?

PubMed Central

Botta, Sisir; Cunha, Gerald R.

2014-01-01

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

Bisphenol A in the aquatic environment and its endocrine-disruptive effects on aquatic organisms.

PubMed

Kang, Jeong-Hun; Asai, Daisuke; Aasi, Daisuke; Katayama, Yoshiki

2007-01-01

Bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane], which is mainly used in the production of epoxy resins and polycarbonate plastics, is a known endocrine disruptor and is acutely toxic to aquatic organisms. Due to intensified usage of these products, exposure of organisms to BPA via several routes, such as the environment and food, has increased. The aquatic environment is an important area for the study of BPA. This report reviews the literature concerning contamination routes and degradation of BPA in the aquatic environment and its endocrine-disruptive effects on aquatic organisms.

Weight of evidence approaches for the identification of endocrine disrupting properties of chemicals: Review and recommendations for EU regulatory application.

PubMed

Gross, Melanie; Green, Richard M; Weltje, Lennart; Wheeler, James R

2017-12-01

A Weight-of-evidence (WoE) evaluation should be applied in assessing all the available data for the identification of endocrine disrupting (ED) properties of chemicals. The European Commission draft acts specifying criteria under the biocidal products and plant protection products regulations require that WoE is implemented for the assessment of such products. However, only some general considerations and principles of how a WoE should be conducted are provided. This paper reviews WoE approaches to distil key recommendations specifically for the evaluation of potential ED properties of chemicals. In a manner, which is consistent with existing, published WoE frameworks, the WoE evaluation of ED properties can be divided into four phases: 1) Definition of causal questions and data gathering and selection, 2) Review of individual studies, 3) Data integration and evaluation, and 4) Drawing conclusions based on inferences. Recommendations are made on how to conduct each phase robustly and transparently to help guide the WoE evaluation of potential endocrine disrupting properties of chemicals within a European regulatory context. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

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

A review on endocrine disruptors and their possible impacts on human health.

PubMed

Kabir, Eva Rahman; Rahman, Monica Sharfin; Rahman, Imon

2015-07-01

Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible. Copyright © 2015 Elsevier B.V. All rights reserved.

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 ...

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.

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...

Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

EPA Science Inventory

Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). These assays can be sensitive ...

Evaluation of Endocrine Disrupting Compounds Migration in Household Food Containers under Domestic Use Conditions.

PubMed

Sáiz, Jorge; Gómara, Belén

2017-08-09

Plasticizers and plastic monomers are commonly used in packaging. Most of them act as endocrine disrupters and are susceptible to migrate from the packaging to the food. We evaluated the migration of endocrine disrupting compounds from three different household food containers to four food simulants under different domestic treatments and for different periods of time, with the aim of reproducing real domestic conditions. The results showed that the migration to the simulants increased with the storage time, up to more than 50 times in certain cases. The heating power seemed to increase the migration processes (up to more than 30 times), and reusing containers produced an increase or decrease of the concentrations depending on the container type and the simulant. The concentrations found were lower than other concentrations reported (always less than 4000 pg/mL, down to less than 20 pg/mL), which might be a consequence of the domestic conditions used.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kucka, Marek; Pogrmic-Majkic, Kristina; Fa, Svetlana

2012-11-15

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

Effects of endocrine-disrupting contaminants on amphibian oogenesis: methoxychlor inhibits progesterone-induced maturation of Xenopus laevis oocytes in vitro.

PubMed Central

Pickford, D B; Morris, I D

1999-01-01

There is currently little evidence of pollution-induced endocrine dysfunction in amphibia, in spite of widespread concern over global declines in this ecologically diverse group. Data regarding the potential effects of endocrine-disrupting contaminants (EDCs) on reproductive function in amphibia are particularly lacking. We hypothesized that estrogenic EDCs may disrupt progesterone-induced oocyte maturation in the adult amphibian ovary, and tested this with an in vitro germinal vesicle breakdown assay using defolliculated oocytes from the African clawed frog, Xenopus laevis. While a variety of natural and synthetic estrogens and xenoestrogens were inactive in this system, the proestrogenic pesticide methoxychlor was a surprisingly potent inhibitor of progesterone-induced oocyte maturation (median inhibitive concentration, 72 nM). This inhibitory activity was specific to methoxychlor, rather than to its estrogenic contaminants or metabolites, and was not antagonized by the estrogen receptor antagonist ICI 182,780, suggesting that this activity is not estrogenic per se. The inhibitory activity of methoxychlor was dose dependent, reversible, and early acting. However, washout was unable to reverse the effect of short methoxychlor exposure, and methoxychlor did not competitively displace [3H]progesterone from a specific binding site in the oocyte plasma membrane. Therefore, methoxychlor may exert its action not directly at the site of progesterone action, but downstream on early events in maturational signaling, although the precise mechanism of action is unclear. The activity of methoxychlor in this system indicates that xenobiotics may exert endocrine-disrupting effects through interference with progestin-regulated processes and through mechanisms other than receptor antagonism. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:10090707

Reproductive Impacts of Endocrine-Disrupting Chemicals on Wildlife Species: Implications for Conservation of Endangered Species.

PubMed

Tubbs, Christopher W; McDonough, Caitlin E

2018-02-15

Wildlife have proven valuable to our understanding of the potential effects of endocrine-disrupting chemicals (EDCs) on human health by contributing considerably to our understanding of the mechanisms and consequences of EDC exposure. But the threats EDCs present to populations of wildlife species themselves are significant, particularly for endangered species whose existence is vulnerable to any reproductive perturbation. However, few studies address the threats EDCs pose to endangered species owing to challenges associated with their study. Here, we highlight those barriers and review the available literature concerning EDC effects on endangered species. Drawing from other investigations into nonthreatened wildlife species, we highlight opportunities for new approaches to advance our understanding and potentially mitigate the effects of EDCs on endangered species to enhance their fertility.

QSAR PRIORITIZATION OF CHEMICAL INVENTORIES FOR ENDOCRINE DISRUPTOR TESTING

EPA Science Inventory

Binding affinity between chemicals and the estrogen receptor (ER) serves as an indicator of the potential to cause endocrine disruption through this receptor-mediated endocrine pathway. Estimating ER binding affinity is, therefore, one strategic approach to reducing the costs of ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLachlan, J.

1998-06-01

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

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...

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 ...

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 ...

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

Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

PubMed Central

Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

2014-01-01

Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK

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

PubMed

McLachlan, J A

2016-07-01

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

Endocrine disrupting chemicals and growth of children.

PubMed

Botton, Jérémie; Kadawathagedara, Manik; de Lauzon-Guillain, Blandine

2017-06-01

According to the "environmental obesogen hypothesis", early-life (including in utero) exposure to endocrine disrupting chemicals (EDCs) may disturb the mechanisms involved in adipogenesis or energy storage, and thus may increase the susceptibility to overweight and obesity. Animal models have shown that exposure to several of these chemicals could induce adipogenesis and mechanisms have been described. Epidemiological studies are crucial to know whether this effect could also be observed in humans. We aimed at summarizing the literature in epidemiology on the relationship between EDCs exposure and child's growth. Overall, epidemiological studies suggest that pre- and/or early postnatal exposure to some EDCs may increase the risk of overweight or obesity during childhood. In that review, we present some limitations of these studies, mainly in exposure assessment, that currently prevent to conclude about causality. Recent advances in epidemiology should bring further knowledge. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

PubMed

Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

2017-04-01

Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

ECETOC Florence workshop on risk assessment of endocrine substances, including the potency concept.

PubMed

Fegert, Ivana

2013-12-16

The European regulation on plant protection products (1107/2009) and the Biocidal Products Regulation (EC Regulation 528/2012) only support the marketing and use of chemicals if they do not cause endocrine disruption in humans or wildlife species. Also, substances with endocrine properties are subject to authorization under the European regulation on the registration, evaluation, authorization and restriction of chemicals (REACH; 1907/2006). Therefore, the regulatory consequences of identifying a substance as an endocrine disrupting chemical are severe. In contrast to that, basic scientific criteria, necessary to define endocrine disrupting properties, are not described in any of these legislative documents. Thus, the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) established a task force to provide scientific criteria for the identification and assessment of chemicals with endocrine disrupting properties that may be used within the context of these three legislative texts (ECETOC, 2009a). In 2009, ECETOC introduced a scientific framework as a possible concept for identifying endocrine disrupting properties within a regulatory context (ECETOC, 2009b; Bars et al., 2011a,b). The proposed scientific criteria integrated, in a weight of evidence approach, information from regulatory (eco)toxicity studies and mechanistic/screening studies by combining evidence for adverse effects detected in apical whole-organism studies with an understanding of the mode of action (MoA) of endocrine toxicity. However, since not all chemicals with endocrine disrupting properties are of equal hazard, an adequate concept should also be able to differentiate between chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes). For this purpose, the task force refined this part of their concept. Following an investigation of the key factors at a second workshop of invited regulatory, academic and industry scientists, the

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

EPA Science Inventory

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

Investigation of potential endocrine disrupting effects of mosquito larvicidal Bacillus thuringiensis israelensis (Bti) formulations.

PubMed

Maletz, Sibylle; Wollenweber, Marc; Kubiak, Katharina; Müller, Annett; Schmitz, Stefan; Maier, Dieter; Hecker, Markus; Hollert, Henner

2015-12-01

Bti is successfully used as a biological control agent for mosquito control. It has proven to be ecological friendly, and thus, is used in ecologically sensitive habitats. Recent investigations of groundwater in Germany have detected estrogenic activity in five consecutive groundwater wells in a region where Bti is applied. Therefore, it was suspected that this compound can act as an environmental xenoestrogen. In the present study, five Bti formulations as well as the active ingredient, VectoBac® TP (TP), were investigated regarding their estrogenic activity using the LYES and ER CALUX® assays. Furthermore, their steroidogenesis disruption properties were studied using the H295R Steroidogenesis Assay. Additionally, field samples from a Bti application area as well as samples from an artificial pond were examined. Three of the Bti formulations and the active ingredient TP showed significant estrogenic activity in the LYES (up to 52 ng·l(-1) estradiol equivalents (EEQ) in the 18-fold concentration) and/or the ER CALUX® (up to 1 ng·EEQ·l(-1) in the 18-fold concentration). In the H295R significant but weak effects with no dose-response-relationship on the production of estradiol, and 21-hydroxyprogesterone (WDG) as well as testosterone (TP) by H295R cells could be observed. The field samples as well as the samples from the artificial pond showed no significant increase of estrogenic activity after application of TP or WDG in the ER CALUX®. With the exception of the controlled laboratory experiments with direct application of Bti to the utilized in vitro test systems the present study did not reveal any significant effects of Bti on endocrine functions that would indicate that the application of Bti could cause adverse endocrine effects to organisms in aquatic ecosystems. Instead, our results support previous studies that the use of Bti products against mosquitos would be safe even for sensitive habitats such as conservation areas. Copyright © 2015 Elsevier B

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.

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

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.

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

PubMed

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

2016-07-01

In recent years, there has been an increase in efforts to improve wastewater treatment as the concentration of dangerous pollutants, such as endocrine disrupting chemicals, in wastewater increases. These compounds, which mimic the effect of hormones, have a negative impact on human health and are not easily removed from water. One way to effectively eliminate these pollutants is to use enzymatically activated materials. In this study, we report on the use of laccase from the white rot fungus Trametes versicolor immobilized onto polyamide 6/chitosan (PA6/CHIT) nanofibers modified using two different spacers (bovine serum albumin and hexamethylenediamine). We then tested the ability of the PA6/CHIT-laccase biocatalysts to eliminate a mixture containing 50μM of two endocrine disrupting chemicals: bisphenol A and 17α-ethinylestradiol. The PA6/CHIT nanofiber matrix used in this study not only proved to be a suitable carrier for immobilized and modified laccase but was also efficient in the removal of a mixture of endocrine disrupting chemicals in three treatment cycles. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-01

The objective of this study was to investigate the endocrine disrupting effects of domestic wastewater on fish using the brackish medaka Oryzias melastigma as the animal model. Estuarine water samples were collected from Sihchong Creek and Baoli Creek estuaries, Taiwan, in March of 2012 to assess the whole effluent toxicity (WET) of domestic wastewater produced by the local residents and tourists. Chemical analysis detected various pharmaceuticals and personal care products (PPCPs) in the field water samples. Some of these PPCPs are endocrine disrupting chemicals. In the laboratory-based bioassay, breeding pairs were exposed to the water samples (Sihchong, Baoli, and control) for 21 days. Cumulative number of eggs spawned was significantly higher in the Sihchong group. While fish swimming activity was not affected, sexual behavior of the male fish was significantly induced in both Sihchong and Baoli groups. Male and female gonad histology was not affected. Expression level of biomarker genes CYP1A1, HSP70, and VTG was significantly induced in the Sihchong group. This study indicates that the mixture of contaminants contained in the estuarine water may cause endocrine disrupting effects in fish. Copyright © 2016 Elsevier Ltd. All rights reserved.

ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS

EPA Science Inventory

Endocrine Active Substances and Dose-Response for Individuals and Populations
Hugh A. Barton

Abstract for IUPAC-SCOPE article

Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

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

EPA Science Inventory

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

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

PubMed

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

2014-01-01

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

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

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...

Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting Chemicals and Mycotoxins through Stable Isotope Techniques.

PubMed

Owino, Victor O; Cornelius, Carolin; Loechl, Cornelia U

2018-03-23

Multiple drivers of the double burden of malnutrition (DBM) include a rapid shift from predominantly plant-based diets to energy-dense foods based on meats, milk, animal fats and vegetable oils. The shift to overweight and obesity is driven by increased exposure to mass media, urbanization, technological advances in food processing, rising income and increased population density associated with increased access to cheap foods. At the same time, undernutrition persists mainly due to food insecurity and lack of access to safe water, sanitation and adequate health care. All known nutrition interventions result in only one third reduction in stunting. Little consideration has been given to hazardous exposure to endocrine disrupting chemicals (EDCs) and microbial toxins as major components of the malnutrition-causal framework. These hazards include microbial toxins, for example, mycotoxins, and environmental pollutants such as persistent organic pollutants (POPs), some of which are known to disrupt the endocrine system. These hazards sit at the cross road of undernutrition and overweight and obesity since the exposure cuts across the critical window of opportunity (the first 1000 days). In this review, we update on the role of food and environmental contaminants, especially EDCs and aflatoxins, in child growth and on the implications for metabolic dysfunction and disease risk in later life, and discuss potential applications of nuclear and isotopic techniques to elucidate the underlying biological mechanisms, outcome indicators, as well as occurrence levels.

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.

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

PubMed

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

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

Development of QSAR models for predicting the binding affinity of endocrine disrupting chemicals to eight fish estrogen receptor.

PubMed

He, Junyi; Peng, Tao; Yang, Xianhai; Liu, Huihui

2018-02-01

Endocrine disrupting effect has become a central point of concern, and various biological mechanisms involve in the disruption of endocrine system. Recently, we have explored the mechanism of disrupting hormonal transport protein, through the binding affinity of sex hormone-binding globulin in different fish species. This study, serving as a companion article, focused on the mechanism of activating/inhibiting hormone receptor, by investigating the binding interaction of chemicals with the estrogen receptor (ER) of different fish species. We collected the relative binding affinity (RBA) of chemicals with 17β-estradiol binding to the ER of eight fish species. With this parameter as the endpoints, quantitative structure-activity relationship (QSAR) models were established using DRAGON descriptors. Statistical results indicated that the developed models had satisfactory goodness of fit, robustness and predictive ability. The Euclidean distance and Williams plot verified that these models had wide application domains, which covered a large number of structurally diverse chemicals. Based on the screened descriptors, we proposed an appropriate mechanism interpretation for the binding potency. Additionally, even though the same chemical had different affinities for ER from different fish species, the affinity of ER exhibited a high correlation for fish species within the same Order (i.e., Salmoniformes, Cypriniformes, Perciformes), which consistent with that in our previous study. Hence, when performing the endocrine disrupting effect assessment, the species diversity should be taken into account, but maybe the fish species in the same Order can be grouped together. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of 3-nitro-1,2,4-triazol-5-one as a potential endocrine disrupting chemical in rats using the Hershberger and uterotrophic bioassays.

PubMed

Quinn, M J; Bannon, D I; Jackovitz, A M; Hanna, T L; Shiflett, A A; Johnson, M S

2014-01-01

The explosive 3-nitro-1,2,4-triazol-5-one (NTO) is an insensitive formulation developed to replace high energetics that are susceptible to accidental detonation from heat, shock, and impact. Although studies have shown NTO to be nontoxic at acute exposures, recent subacute and subchronic tests have demonstrated effects on testes and subsequent sperm production in rats. This study assessed endocrine disruption as a potential mechanism for these reproductive effects via the Hershberger and uterotrophic bioassays. These assays are 2 of the US Environmental Protection Agency's tier 1 in vivo screens for the Endocrine Disruptor Screening Program that measure differences in androgen- and estrogen-sensitive tissue weights in castrated and ovariectomized rats. The gonadectomized rats were orally exposed to NTO in a corn oil vehicle at doses of 250, 500, or 1000 mg/kg body weight (bw)/d for 10 and 3 days for the Hershberger and uterotrophic assays, respectively, according to standard protocols. Male rats also received testosterone (0.2 mg/kg/d, subcutaneous) and antiandrogenic flutamide (3mg/kg/d, oral) as negative and positive controls, and females received 17 α-ethynyl estradiol (0.3 µg/d, subcutaneous) as positive controls. 3-Nitro-1,2,4-triazol-5-one caused neither a decrease in androgen-sensitive male reproductive selected tissue (seminal vesicles with fluid/without fluid, glans penis, Cowper gland, ventral prostrate, and levator ani-bulbocavernosus) weights nor a change in uterine weights. The results of this study provide no evidence to suggest that NTO acts like an estrogenic or antiandrogenic endocrine disruptor in rats at these doses. © The Author(s) 2014.

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.

Comparison of UV photolysis, nanofiltration, and their combination to remove hormones from a drinking water source and reduce endocrine disrupting activity.

PubMed

Sanches, Sandra; Rodrigues, Alexandre; Cardoso, Vitor V; Benoliel, Maria J; Crespo, João G; Pereira, Vanessa J

2016-06-01

A sequential water treatment combining low pressure ultraviolet direct photolysis with nanofiltration was evaluated to remove hormones from water, reduce endocrine disrupting activity, and overcome the drawbacks associated with the individual processes (production of a nanofiltration-concentrated retentate and formation of toxic by-products). 17β-Estradiol, 17α-ethinylestradiol, estrone, estriol, and progesterone were spiked into a real water sample collected after the sedimentation process of a drinking water treatment plant. Even though the nanofiltration process alone showed similar results to the combined treatment in terms of the water quality produced, the combined treatment offered advantage in terms of the load of the retentate and decrease in the endocrine-disrupting activity of the samples. Moreover, the photolysis by-products produced, with higher endocrine disrupting activity than the parent compounds, were effectively retained by the membrane. The combination of direct LP/UV photolysis with nanofiltration is promising for a drinking water utility that needs to cope with sudden punctual discharges or deterioration of the water quality and wants to decrease the levels of chemicals in the nanofiltration retentate.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

PubMed Central

Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

2017-01-01

BACKGROUND More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four

Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

PubMed Central

Heger, Nicholas E; Hall, Susan J; Sandrof, Moses A; McDonnell, Elizabeth V; Hensley, Janan B; McDowell, Erin N; Martin, Kayla A; Gaido, Kevin W; Johnson, Kamin J

2012-01-01

Background: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. Objectives: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. Methods: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. Results: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. Conclusions: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. PMID:22511013

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

PubMed

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

2017-12-01

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

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

EPA Science Inventory

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

Where do we go from here: Challenges and the future of endocrine disrupting compound screening and testing

EPA Science Inventory

ABSTRACTWorldwide concern about the impacts of endocrine disrupting compounds on both human and environmental health has led to implementation of multiple screening and testing programs. In most cases these programs have focused on impacts to the estrogen, androgen and thyroid h...

Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

PubMed

Kumar, A Kiran; Reddy, M Venkateswar; Chandrasekhar, K; Srikanth, S; Mohan, S Venkata

2012-01-01

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fossi, M.C.; Casini, S.; Marsili, L.

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,more » 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.« less

TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

EPA Science Inventory

This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

Endocrine disruption in aquatic systems: up-scaling research to address ecological consequences.

PubMed

Windsor, Fredric M; Ormerod, Steve J; Tyler, Charles R

2018-02-01

Endocrine-disrupting chemicals (EDCs) can alter biological function in organisms at environmentally relevant concentrations and are a significant threat to aquatic biodiversity, but there is little understanding of exposure consequences for populations, communities and ecosystems. The pervasive nature of EDCs within aquatic environments and their multiple sub-lethal effects make assessments of their impact especially important but also highly challenging. Herein, we review the data on EDC effects in aquatic systems focusing on studies assessing populations and ecosystems, and including how biotic and abiotic processes may affect, and be affected by, responses to EDCs. Recent research indicates a significant influence of behavioural responses (e.g. enhancing feeding rates), transgenerational effects and trophic cascades in the ecological consequences of EDC exposure. In addition, interactions between EDCs and other chemical, physical and biological factors generate uncertainty in our understanding of the ecological effects of EDCs within aquatic ecosystems. We illustrate how effect thresholds for EDCs generated from individual-based experimental bioassays of the types commonly applied using chemical test guidelines [e.g. Organisation for Economic Co-operation and Development (OECD)] may not necessarily reflect the hazards associated with endocrine disruption. We argue that improved risk assessment for EDCs in aquatic ecosystems urgently requires more ecologically oriented research as well as field-based assessments at population-, community- and food-web levels. © 2017 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

Mobilization of endocrine-disrupting chemicals and estrogenic activity in simulated rainfall runoff from land-applied biosolids.

PubMed

Giudice, Ben D; Young, Thomas M

2011-10-01

Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine-disrupting compounds, heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the endocrine-disrupting compounds bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of 16 metals; and estrogenic activity via the estrogen receptor-mediated chemical activated luciferase gene expression (ER-CALUX) bioassay. Triclocarban (2.3-17.3 ng/L), triclosan (<51-309 ng/L), and octylphenol (<4.9-203 ng/L) were commonly detected. Chromium (2.0-22 µg/L), Co (2.5-10 µg/L), Ni (28-235 µg/L), Cu (14-110 µg/L), As (1.2-2.7 µg/L), and Se (0.29-12 µg/L) were quantifiable over background levels. Triclosan, Ni, and Cu were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below the maximum allowable regulatory limits. The ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, although unknown contributors or matrix effects were also found. Copyright © 2011 SETAC.

Occurrence, fate, and ecosystem implications of endocrine active compounds in select rivers of Minnesota

NASA Astrophysics Data System (ADS)

Writer, J.; Keefe, S.; Barber, L. B.; Brown, G.; Schoenfuss, H.; Kiesling, R.; Gray, J. L.

2009-12-01

Select endocrine active compounds (EACs) were measured in four rivers in southern Minnesota. Additionally, caged and wild fish were assessed for indication of endocrine disruption using plasma vitellogenin and histopathology. Low concentrations of EACs were identified in all rivers, as was elevated plasma vitellogenin in caged and wild fish, indicating potential endocrine disruption. To evaluate the persistence of these compounds in small rivers, a tracer study was performed on one of the rivers (Redwood River) using Lagrangian sampling coupled with hydrologic modeling incorporating transient storage. Mass exchange (transient storage, sorption) and degradation were approximated as pseudo first order processes, and in-stream removal rates were then computed by comparing conservative tracer concentrations to organic compound concentrations. Production of estrone and 4-nonylphenol in the studied reach as a result of biochemical transformation from their parent compounds (17β-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17β-estradiol and nonylphenol to undergo a 50% reduction in concentration was >2 km and >10 km, respectively. These results indicate that EACs are transported several kilometers downstream from discharge sources and therefore have the potential of adversely impacting the lotic ecosystem over these distances.

Endocrine disruptive effects of chemicals eluted from nitrile-butadiene rubber gloves using reporter gene assay systems.

PubMed

Satoh, Kanako; Nonaka, Ryouichi; Ohyama, Ken-ichi; Nagai, Fumiko; Ogata, Akio; Iida, Mitsuru

2008-03-01

Disposable gloves made of nitrile-butadiene rubber (NBR) are used for contact with foodstuffs rather than polyvinyl chloride gloves containing di(2-ethylhexyl)phthalate (DEHP), because endocrine-disruptive effects are suspected for phthalate diesters including DEHP. However, 4,4'-butylidenebis(6-t-butyl-m-cresol) (BBBC), 2,4-di-t-butylphenol, and 2,2,4-trimetyl-1,3-pentanediol diisobutyrate can be eluted from NBR gloves, and possibly also detected in food. In this study, we examined the endocrine-disrupting effects of these chemicals via androgen receptor (AR) and estrogen receptor (ER)-mediated pathways using stably transfected reporter gene cell lines expressing AR (AR-EcoScreen system) and ER (MVLN cells), respectively. We also examined the binding activities of these chemicals to AR and ER. The IC50 value of BBBC for antagonistic androgen was in the range of 10(-6)M. The strength of inhibition was about 5 times that of a known androgen antagonist, 1,1'-(2,2-dichloroethylidene)bis[4-chlorobenzene] (p,p'-DDE), and similar to that of bisphenol A. The IC50 value of BBBC for antagonistic estrogen was in the range of 10(-6)M. These results suggest that BBBC and its structural homologue, 4,4'-thiobis(6-t-butyl-m-cresol) are androgen and estrogen antagonists. It is therefore necessary to study these chemicals in vivo, and clarify their effect on the endocrine system.

Proteomic analysis of the reproductive organs of the hermaphroditic gastropod Lymnaea stagnalis exposed to different endocrine disrupting chemicals.

PubMed

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

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

In vitro profiling of toxicity and endocrine disrupting effects of bisphenol analogues by employing MCF-7 cells and two-hybrid yeast bioassay.

PubMed

Lei, Bingli; Xu, Jie; Peng, Wei; Wen, Yu; Zeng, Xiangying; Yu, Zhiqiang; Wang, Yipei; Chen, Tian

2017-01-01

The potentially adverse health implications of bisphenol A (BPA) have led to increasing use of alternative bisphenols (BPs). However, little is known about the toxicity of alternative BPs. In this study, the cytotoxicity, genotoxicity, intracellular ROS formation, and Ca 2+ fluctuation effects of BPs on MCF-7 cells were evaluated. At the same time, the estrogenic and thyroidal hormone effect potentials of six BPs were also evaluated using two-hybrid yeast bioassay. The results showed that most BPs at 0.01-1 μM significantly increased cell viability in MCF-7 cells and at higher exposure concentrations of 25-100 μM, they caused a significant decrease of cell viability. At the same time, these BPs also at 25-100 μM significantly increased LDH release of MCF-7 cells. In addition, several BPs at 10-50 μM resulted in a significantly concentration-depended increase in DNA-damaging effect on MCF-7 cells and elevated ROS production. Most BPs at 0.0001-10 μM significantly increased intracellular Ca 2+ level. These results showed that bisphenol AF (BPAF) and thiodiphenol (TDP) exerted cell biological effect, estrogenic, and thyroidal effect potentials greater than those of BPA. The cytotoxicity and endocrine disrupting effects of other BPs are similar to or slightly lower than those of BPA. Therefore, as potential alternatives to BPA, endocrine disrupting effects and potential health harm of alternative BPs to human can also not be ignored. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 278-289, 2017. © 2016 Wiley Periodicals, Inc.

Intergenerational effects of endocrine-disrupting compounds: a review of the Michigan polybrominated biphenyl registry.

PubMed

Curtis, Sarah W; Conneely, Karen N; Marder, Mary E; Terrell, Metrecia L; Marcus, Michele; Smith, Alicia K

2018-06-11

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

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

PubMed

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

2016-02-01

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

Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

PubMed

Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

2018-05-01

Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental alterations and endocrine-disruptive responses in farmed Nile crocodiles (Crocodylus niloticus) exposed to contaminants from the Crocodile River, South Africa.

PubMed

Arukwe, Augustine; Myburgh, Jan; Langberg, Håkon A; Adeogun, Aina O; Braa, Idunn Godal; Moeder, Monika; Schlenk, Daniel; Crago, Jordan Paul; Regoli, Francesco; Botha, Christo

2016-04-01

In the present study, the developmental (including fertility) and endocrine-disruptive effects in relation to chemical burden in male and female Nile crocodiles (Crocodylus niloticus), from a commercial crocodile farm in the Brits district, South Africa, exposed to various anthropogenic aquatic contaminants from the natural environment was investigated. Hepatic transcript levels for vitellogenin (Vtg), zona pellucida (ZP) and ERα (also in gonads) were analyzed using real-time PCR. Plasma estradiol-17β (E2), testosterone (T) and 11-ketotestosterone (11-KT) were analyzed using enzyme immunoassay. Gonadal aromatase and hepatic testosterone metabolism (6β-hydroxylase (6β-OHase)) were analyzed using biochemical methods. Overall, there is high and abnormal number (%) of infertile and banded eggs during the studied reproductive seasons, showing up to 57 and 34% of infertile eggs in the 2009/2010 and 2013/2014 seasons, respectively. In addition, the percentage of banded eggs ranged between 10 and 19% during the period of 2009-2014 seasons. While hepatic ERα, Vtg, ZP mRNA and testosterone 6β-OHase, were equally expressed in female and male crocodiles, gonadal ERα mRNA and aromatase activity were significantly higher in females compared to male crocodiles. On the other hand, plasma T and 11-KT levels were significantly higher in males, compared to female crocodiles. Principal component analysis (PCA) produced significant grouping that revealed correlative relationships between reproductive/endocrine-disruptive variables and liver contaminant burden, that further relates to measured contaminants in the natural environment. The overall results suggest that these captive pre-slaughter farm crocodiles exhibited responses to anthropogenic aquatic contaminants with potentially relevant consequences on key reproductive and endocrine pathways and these responses may be established as relevant species endocrine disruptor biomarkers of exposure and effects in this threatened

Effects of elevated glucocorticoids on reproduction and development: relevance to endocrine disruptor screening.

PubMed

Witorsch, Raphael J

2016-01-01

This article reviews the influence of the hypothalamo-pituitary-adrenocortical (HPA) axis on mammalian male and female reproduction and development of offspring and its potential impact on the identification of endocrine disruptive chemicals by in vivo assays. In the adult male rat and baboon, stress suppresses testosterone secretion via a direct inhibitory effect of elevated glucocorticoids on Leydig cells. In adult female sheep, stress disrupts reproductive function via multi-stage mechanisms involving glucocorticoid-mediated suppression of LH secretion, LH action on the ovary and the action of estradiol on its target cells (e.g., uterus). While physiological concentrations of endogenous glucocorticoids are supportive of fetal development, excessive glucocorticoids in utero (i.e., maternal stress) adversely affect mammalian offspring by "programing" abnormalities that are primarily manifest postpartum. The influence of stress on reproduction and development can also be mediated by 11β-hydroxysteroid dehydrogenase (HSD), a bi-directional oxidative:reductive pathway, which governs the balance between biologically active (reduced) endogenous glucocorticoid and inactive (oxidized) metabolites. This pathway is mediated primarily by two isozymes, 11β - HSD1 (reductase) and 11β-HSD2 (oxidase) which act both in an intracrine (intracellular) and endocrine (systemic) fashion. The 11β-HSD pathway appears to play a variety of physiological roles in mammalian reproduction and development and is a target for selected xenobiotics. The effects of the HPA axis on mammalian reproduction and development are potential confounders for in vivo bioassays in rodents employed to identify endocrine disruptive chemicals. Accordingly, consideration of the impact of the HPA axis should be incorporated into the design of bioassays for evaluating endocrine disruptors.

Plasma biomarkers in juvenile marine fish provide evidence for endocrine modulation potential of organotin compounds.

PubMed

Min, Byung Hwa; Kim, Bo-Mi; Kim, Moonkoo; Kang, Jung-Hoon; Jung, Jee-Hyun; Rhee, Jae-Sung

2018-08-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used to control marine fouling. Here, we show that organotin stimulation reduces the hormone levels in the plasma of two economically important aquaculture fish. Blood plasma samples were collected from juvenile red seabream and black rockfish exposed to environmentally realistic concentrations of TBT and TPT for 14 days. The levels of two plasma biomarkers, namely the yolk protein precursor vitellogenin (VTG) and the sex steroid 17β-estradiol (E2), were measured to determine the endocrine disrupting potential of the organotin compounds. Both organotin compounds were dose-dependently accumulated in the blood of two fish. Exposure to waterborne TBT and TBT significantly decreased the plasma VTG levels in both the juvenile fish in a dose-dependent manner. In contrast, the treatment with E2, a well-known VTG inducer, significantly increased the plasma VTG levels in both the fish. In addition, the mRNA levels of vtg were also downregulated in the liver tissues of both the fish at 100 and/or 1000 ng L -1 of TBT or TPT exposure. The plasma E2 titers were significantly suppressed at 100 and/or 1000 ng L -1 of TBT or TPT exposure for 14 days compared to their titer in the control. Since estrogen directly regulates vtg gene expression and VTG synthesis, our results reveal the endocrine disrupting potential of organotin compounds, and subsequently the endocrine modulation at early stage of fish can trigger further fluctuations in sexual differentiation, maturation, sex ration or egg production. In addition, the results demonstrate their effects on non-target organisms, particularly on animals reared in aquaculture and fisheries. Copyright © 2018 Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

2006-01-01

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

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

PubMed

Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

2016-12-01

More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95

Extent of endocrine disruption in fish of western and Alaskan National Parks

USGS Publications Warehouse

Schreck, Carl B.; Kent, Michael

2013-01-01

In 2008 2009, 998 fish were collected from 43 water bodies across 11 western Alaskan national parks and analyzed for reproductive abnormalities. Exposure to estrogenic substances such as pesticides can induce abnormalities like intersex. Results suggest there is a greater propensity for male intersex fish collected from parks located in the Rocky Mountains, and specifically in Rocky Mountain NP. Individual male intersex fish were also identified at Lassen Volcanic, Yosemite, and WrangellSt. Elias NPs. The preliminary finding of female intersex was determined to be a false positive. The overall goal of this project was to assess the general health of fish from eleven western national parks to infer whether health impacts may be linked to contaminant health thresholds for animal andor human health. This was accomplished by evaluating the presence of intersex fish with eggs developing in male gonads or sperm developing in female gonads using histology. In addition, endocrine disrupting compounds and other contaminants were quantified in select specimens. General histologic appearance of the gonadal tissue and spleen were observed to assess health.

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

PubMed

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

2010-09-01

Growing attention has been recently paid to safety of food and drinking water, making necessary the adoption of policies for water sources protection and the development of sensitive and rapid analytical methods to identify micropollutants. Endocrine-disrupting compounds (EDCs) have emerged as a major issue as they alter the functioning of the endocrine system. Since ingestion of EDCs via food is considered the major exposure route, there is a growing interest in understanding EDC fate during drinking water treatment and in monitoring potential contamination of surface waters and groundwaters. In this work, a fast liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the determination of 4-n-nonylphenol (NP), bisphenol A (BPA), estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) in drinking waters. In the literature analytical articles seldom provide details regarding fragmentation pathways. In this paper spectra of the five EDCs in negative ESI were interpreted with the support of accurate mass spectra acquired by a quadrupole time-of-flight instrument; fragmentation pathways were also proposed. The chromatographic separation of EDCs was optimized on a Pinnacle DB Biphenylic column with a water-acetonitrile gradient. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode using bisphenol A-d(16) (BPA-d(16)) as internal standard; calibration curves showed good correlation coefficients (0.9989-0.9997). All figures of merit of the method were satisfactory; limits of detection were in the range 0.2-0.4 ng/ml. The method was applied to the determination of the analytes in waters sampled by polar organic chemical integrative samplers in a drinking water treatment plant. Rather low concentration of BPA, NP and E1 were measured in the inlet, while none of the considered EDCs was detected in the outlet. 2010 John Wiley & Sons, Ltd.

Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement.

PubMed

Solecki, Roland; Kortenkamp, Andreas; Bergman, Åke; Chahoud, Ibrahim; Degen, Gisela H; Dietrich, Daniel; Greim, Helmut; Håkansson, Helen; Hass, Ulla; Husoy, Trine; Jacobs, Miriam; Jobling, Susan; Mantovani, Alberto; Marx-Stoelting, Philip; Piersma, Aldert; Ritz, Vera; Slama, Remy; Stahlmann, Ralf; van den Berg, Martin; Zoeller, R Thomas; Boobis, Alan R

2017-02-01

Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria.

Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biemann, Ronald, E-mail: ronald.biemann@medizin.uni-halle.de; Navarrete Santos, Anne; Navarrete Santos, Alexander

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,more » 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.« less

Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products

PubMed Central

Nishioka, Marcia; Standley, Laurel J.; Perovich, Laura J.; Brody, Julia Green; Rudel, Ruthann A.

2012-01-01

Background: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. Objectives: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. Methods: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. Results: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Conclusions: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in

In vitro endocrine disruption and TCDD-like effects of three novel brominated flame retardants: TBPH, TBB, & TBCO.

PubMed

Saunders, David M V; Higley, Eric B; Hecker, Markus; Mankidy, Rishikesh; Giesy, John P

2013-11-25

The novel brominated flame retardants (NBFRs), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), Bis(2-ethylhexyl)-2,3,4,5-tetrabromophtalate (TBPH), and 1,2,5,6-tetrabromocyclooctane (TBCO) are components of flame retardant mixtures including Firemaster 550 and Saytex BC-48. Despite the detection of these NBFRs in environmental and biotic matrices, studies regarding their toxicological effects are poorly represented in the literature. The present study examined endocrine disruption by these three NBFRs using the yeast YES/YAS reporter assay and the mammalian H295R steroidogenesis assay. Activation of the aryl hydrocarbon receptor (AhR) was also assessed using the H4IIE reporter assay. The NBFRs produced no TCDD-like effects in the H4IIE assay or agonistic effects in the YES/YAS assays. TBB produced a maximal antiestrogenic effect of 62% at 0.5mgL(-1) in the YES assay while TBPH and TBCO produced maximal antiandrogenic effects of 74% and 59% at 300mgL(-1) and 1500mgL(-1), respectively, in the YAS assay. Significant effects were also observed in the H295R assay. At 0.05mgL(-1), 15mgL(-1), and 15mgL(-1) TBB, TBPH, and TBCO exposures, respectively resulted in a 2.8-fold, 5.4-fold, and 3.3-fold increase in concentrations of E2. This is one of the first studies to demonstrate the in vitro endocrine disrupting potentials of TBB, TBPH, and TBCO. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

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

PubMed

Suvorov, Alexander; Vandenberg, Laura N

2016-07-01

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

Are In Vitro Methods for the Detection of Endocrine Potentials in the Aquatic Environment Predictive for In Vivo Effects? Outcomes of the Projects SchussenAktiv and SchussenAktivplus in the Lake Constance Area, Germany

PubMed Central

Henneberg, Anja; Bender, Katrin; Blaha, Ludek; Giebner, Sabrina; Kuch, Bertram; Köhler, Heinz-R.; Maier, Diana; Oehlmann, Jörg; Richter, Doreen; Scheurer, Marco; Schulte-Oehlmann, Ulrike; Sieratowicz, Agnes; Ziebart, Simone; Triebskorn, Rita

2014-01-01

Many studies about endocrine pollution in the aquatic environment reveal changes in the reproduction system of biota. We analysed endocrine activities in two rivers in Southern Germany using three approaches: (1) chemical analyses, (2) in vitro bioassays, and (3) in vivo investigations in fish and snails. Chemical analyses were based on gas chromatography coupled with mass spectrometry. For in vitro analyses of endocrine potentials in water, sediment, and waste water samples, we used the E-screen assay (human breast cancer cells MCF-7) and reporter gene assays (human cell line HeLa-9903 and MDA-kb2). In addition, we performed reproduction tests with the freshwater mudsnail Potamopyrgus antipodarum to analyse water and sediment samples. We exposed juvenile brown trout (Salmo trutta f. fario) to water downstream of a wastewater outfall (Schussen River) or to water from a reference site (Argen River) to investigate the vitellogenin production. Furthermore, two feral fish species, chub (Leuciscus cephalus) and spirlin (Alburnoides bipunctatus), were caught in both rivers to determine their gonadal maturity and the gonadosomatic index. Chemical analyses provided only little information about endocrine active substances, whereas the in vitro assays revealed endocrine potentials in most of the samples. In addition to endocrine potentials, we also observed toxic potentials (E-screen/reproduction test) in waste water samples, which could interfere with and camouflage endocrine effects. The results of our in vivo tests were mostly in line with the results of the in vitro assays and revealed a consistent reproduction-disrupting (reproduction tests) and an occasional endocrine action (vitellogenin levels) in both investigated rivers, with more pronounced effects for the Schussen river (e.g. a lower gonadosomatic index). We were able to show that biological in vitro assays for endocrine potentials in natural stream water reasonably reflect reproduction and endocrine disruption

Sleep and the Endocrine System.

PubMed

Morgan, Dionne; Tsai, Sheila C

2016-03-01

In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep and the endocrine system.

PubMed

Morgan, Dionne; Tsai, Sheila C

2015-07-01

In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Endocrine Aspects of Environmental “Obesogen” Pollutants

PubMed Central

Nappi, Francesca; Barrea, Luigi; Di Somma, Carolina; Savanelli, Maria Cristina; Muscogiuri, Giovanna; Orio, Francesco; Savastano, Silvia

2016-01-01

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called “obesogenic environment”. Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity. PMID:27483295

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).

Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

PubMed Central

Magnusson, Ulf; Persson, Sara

2015-01-01

Contents The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man-made endocrine disruptors. PMID:26382024

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

PubMed

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

2015-04-01

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

Brominated flame retardants as possible endocrine disrupters.

PubMed

Darnerud, P O

2008-04-01

Brominated flame retardants (BFR) are endocrine disrupters in experimental systems, both in vitro and in vivo. Although BFR effects on thyroid hormones are well confirmed, studies of effects on oestrogen/androgen systems are fewer but today growing in numbers. The effects of BFR on other hormone systems are still unknown. Hormonal effect levels in animals start from ca 1 mg/kg b.w., but there are exceptions: effects on spermatogenesis, suggesting hormonal causes, have been observed at a low dose (60 microg/kg b.w.) of a polybrominated diphenyl ether (PBDE) congener, BDE-99. It could be concluded that hormonal effects are of importance in risk assessment, and in some cases where effects are seen at low levels safety margins may be insufficient. One additional uncertainty is the lack of reliable human data that could be used to support animal BFR observations. In spite of the recent regulation of PBDE production, levels of both PBDE and of other BFR groups are still present in environmental samples. Thus, we have to deal with the possible effects of human BFR exposure for times to come. In order to reduce BFR exposure, the routes of exposure should be carefully examined and ways to reduce levels in major exposure routes considered.

Occurrence and effects of endocrine-disrupting chemicals in the St. Croix River

USGS Publications Warehouse

Elliott, Sarah M.; Lee, Kathy E.

2016-01-01

The St. Croix River is one of the last undisturbed, large floodplain rivers in the upper Mississippi River System. The Saint Croix National Scenic Riverway encompasses 255 river miles from the St. Croix Flowage and Namekagon River to the confluence of the St. Croix River with the Mississippi River at Prescott, Wisconsin. The Wild and Scenic Rivers Act of 1968 includes protection of the “outstandingly remarkable values” of the St. Croix and Namekagon rivers, which are included in the first eight designated wild and scenic rivers. The National Park Service (NPS) supports efforts to ensure these high-quality waters are not degraded by endocrine-disrupting or pharmaceutically active chemicals.

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

PubMed

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

PubMed Central

Midic, Uros; Vincent, Kailey A.; VandeVoort, Catherine A; Latham, Keith E.

2016-01-01

Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. PMID:27614199

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells.

PubMed

Midic, Uros; Vincent, Kailey A; VandeVoort, Catherine A; Latham, Keith E

2016-10-01

Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-06-01

Butachlor is extensively applied in rice paddy ecosystem in china, and has been widespread contaminant in the aquatic environment. Here, Xenopus laevis was used for the evaluation of teratogenesis developmental toxicity, and disruption of thyroid system when exposure to different concentrations of butachlor by window phase exposure. Acute toxicity investigation shown that 96 h-LC50 value of butachlor was 1.424 mg L(-1) and 0.962 mg L(-1) for tadpoles (starting from stages 46/47) and embryos (starting from stages 8/9), respectively. Exposure to butachlor caused malformation, including abnormal eye, pericardial edema, enlarged proctodaeum and bent tail. Window phase exposure test indicated that butachlor significantly promote the contents of whole-body thyroid hormones (THs, T3 and T4) at higher levels, indicating thyroid endocrine disruption. At 7 days, exposure to butachlor up-regulated the mRNA expression of genes involved in THs synthesis and metabolism (tshα, tg, tpo and dio1) and THs receptors (trα and trβ). At 14 days, up-regulation of the mRNA expression of genes related to THs synthesis and metabolism (tshα, tshβ, tg, tpo, dio1, dio2 and ttr) and THs receptors (trβ) were also observed after the exposure to butachlor. At 21 days, butachlor up-regulated the mRNA expression of tshα, tg, tpo genes and down-regulated the mRNA expression of tshβ, tg, dio1, ttr and trα genes. These results showed that butachlor could change the mRNA expression of genes involved in the HPT axis and increase whole-body thyroid hormones levels of X. laevis tadpoles in a dose- and time-dependent manner, causing thyroid endocrine disruption and developmental toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occurrence of steroid estrogens, endocrine-disrupting phenols, and acid pharmaceutical residues in urban riverine water of the Pearl River Delta, South China.

PubMed

Peng, Xianzhi; Yu, Yiyi; Tang, Caiming; Tan, Jianhua; Huang, Qiuxin; Wang, Zhendi

2008-07-01

A scoping study was conducted to investigate the residues of nineteen pharmaceuticals and personal care products (PPCPs), including 4 natural and 3 synthetic steroid estrogens, 7 endocrine-disrupting phenols, and 5 acid pharmaceuticals in three urban streams and the Major Pearl River at Guangzhou, a megapolis in the Pearl River Delta, South China. Estrone was detected in >60% water samples with a maximum concentration of 65 ng L(-1). Endocrine-disrupting phenols (nonylphenol, bisphenol A, triclosan, 2-phenylphenol, methyparaben, and propylparaben) were found to be widely present at rather high concentrations in the urban riverine water of Guangzhou. Salicylic acid, clofibric acid and ibuprofen were detected in most water samples with maximum concentrations of 2098, 248 and 1417 ng L(-1) respectively, whereas naproxen was less frequently detected and also at lower concentration. Both the detection frequencies and median concentrations of the PPCPs appeared higher during the low-flow season than during the high-flow season. The seasonal difference in PPCPs occurrence was probably attributed to the dilution effect caused by the rainfall. PPCPs in the urban riverine water of Guangzhou originated mainly from random discharge and/or leakage of municipal wastewater. PPCPs contamination in the Major Pearl River may be of a potential environmental issue, especially during the low-flow season.

Paracetamol causes endocrine disruption and hepatotoxicity in male fish Rhamdia quelen after subchronic exposure.

PubMed

Guiloski, Izonete Cristina; Ribas, João Luiz Coelho; Piancini, Laercio Dante Stein; Dagostim, Ana Carolina; Cirio, Silvana Maris; Fávaro, Luis Fernando; Boschen, Suelen Lúcio; Cestari, Marta Margarete; da Cunha, Cláudio; Silva de Assis, Helena Cristina

2017-07-01

Paracetamol is one of the most widely sold non-prescription drugs. This study aimed to evaluate the effects of the paracetamol on reproductive, biochemical, genetic, histopathological and hematogical biomarkers by waterborne exposure. Male fish of Rhamdia quelen were exposed to environmental concentrations of paracetamol (0, 0.25, 2.5μg/L) in a semi-static bioassay for 21days. Hemoglobin and hematocrit were reduced upon exposure to 0.25μg/L of paracetamol. Leukocytes and thrombocytes increased after paracetamol exposure. Paracetamol reduced testosterone levels in all exposed groups and increased estradiol levels at higher concentration. Serotonin and dopamine levels increased at exposure to 0.25μg/L. Paracetamol also caused protein carbonyls and increased SOD activity in fish exposed to 2.5μg/L and in addition led to an inhibition of EROD and GST activities in both concentrations. Hepatic genotoxicity occurred at the 0.25μg/L concentration. Hepatic tissues of exposed fish showed mild blood congestion and leucocytes infiltration. The results showed that paracetamol disrupted the hypothalamic-pituitary-gonadal axis, changed hematological parameters and caused hepatotoxicity in Rhamdia quelen. The findings suggest that this drug merits attention relative to its potential endocrine disrupter effect and hepatotoxicity, even at concentrations found in the aquatic environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system.

PubMed

Sidorkiewicz, Iwona; Zaręba, Kamil; Wołczyński, Sławomir; Czerniecki, Jan

2017-07-01

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can cause disturbances in the endocrine system and have multiple harmful effects on health by targeting different organs and systems in the human body. Mass industrial production and widespread use of EDCs have resulted in worldwide contamination. Accumulating evidence suggest that human exposure to EDCs is related to the impairment of male reproductive function and can interrupt other hormonally regulated metabolic processes, particularly if exposure occurs during early development. Investigation of studies absent in previous reviews and meta-analysis of adverse effects of EDCs on functioning of the male reproductive system is the core of this work. Four main modes of action of EDCs on male fertility have been summarized in this review. First, studies describing estrogen- pathway disturbing chemicals are investigated. Second, androgen-signaling pathway alterations and influence on androgen sensitive tissues are examined. Third, evaluation of steroidogenesis dysfunction is discussed by focusing on the steroid hormone biosynthesis pathway, which is targeted by EDCs. Last, the reportedly destructive role of reactive oxygen species (ROS) on sperm function is discussed. Spermatogenesis is a remarkably complex process, hence multiple studies point out various dysfunctions depending on the development state at which the exposure occurred. Collected data show the need to account for critical windows of exposure such as fetal, perinatal and pubertal periods as well as effects of mixtures of several compounds in future research.

Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum.

PubMed

Page, Robert B; Monaghan, James R; Samuels, Amy K; Smith, Jeramiah J; Beachy, Christopher K; Voss, S Randal

2007-02-01

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals

PubMed Central

Beronius, Anna; Vandenberg, Laura N.

2016-01-01

The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs. PMID:26847432

Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals.

PubMed

Beronius, Anna; Vandenberg, Laura N

2015-12-01

The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs.

Endocrine control of epigenetic mechanisms in male reproduction.

PubMed

Ankolkar, Mandar; Balasinor, N H

2016-01-01

Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders. Investigations of the female in cases of poor reproductive outcome have been the main strategy towards diagnosis. However, despite the male partner contributing half of his genome to the progeny, thorough investigations in the male have been ignored. Environmental pollutants are all pervading and are encountered in our day-to-day life. Many of these pollutants have potential to disrupt the endocrine system. Here, we discuss how the male gametes (spermatozoa) are susceptible to a myriad of epigenetic insults inflicted by exposure to endocrine disruptors and how important is the contribution of the epigenetic marks of the spermatozoa in healthy reproduction. We advocate that sperm epigenetics should be considered as a significant contributor to reproductive health and should be researched further and be subsequently included in routine diagnostic workup in cases of poor reproductive outcome.

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, ...

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

PubMed Central

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

2013-01-01

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

The evaluation of endocrine disrupting effects of tert-butylphenols towards estrogenic receptor α, androgen receptor and thyroid hormone receptor β and aquatic toxicities towards freshwater organisms.

PubMed

Wang, Jiaying; Wang, Jingpeng; Liu, Jinsong; Li, Jianzhi; Zhou, Lihong; Zhang, Huanxin; Sun, Jianteng; Zhuang, Shulin

2018-05-09

The phenolic compounds have posed public concern for potential threats to human health and ecosystem. Tert-butylphenols (TBPs), as one group of emerging contaminants, showed potential endocrine disrupting effects and aquatic toxicities. In the present study, we detected concentrations of 2,4-DTBP ranging from <0.001 to 0.057 μg/L (detection limit: 0.001 μg/L) in drinking water source from the Qiantang River in East China in April 2016. The endocrine disrupting effects of 2-TBP, 2,4-DTBP and 2,6-DTBP toward human estrogen receptor α (ERα), androgen receptor (AR) and thyroid hormone receptor β (TRβ) were evaluated using human recombinant two-hybrid yeast bioassay. Their aquatic toxicities were investigated with indicator organisms including Photobacterium phosphoreum, Vibrio fischeri and freshwater green alga Chlamydomonas reinhardtii. 2-TBP and 2,4-DTBP exhibited moderate antagonistic effects toward human ERα and AR in a concentration-dependent manner. 2-TBP significantly inhibited the light emission of P. phosphoreum. 2-TBP, 2,4-DTBP and 2,6-DTBP significantly inhibited the growth of C. reinhardtii and reduced the chlorophyll content. Our results suggest the potential adverse effects of TBPs on human health and aquatic organisms. The data will facilitate further risk assessment of TBPs and related contaminants. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-07-01

Do mild analgesics affect the endocrine system of the human adult testis? Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin

Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain.

PubMed

Rebuli, Meghan E; Patisaul, Heather B

2016-06-01

Brain sex differences are found in nearly every region of the brain and fundamental to sexually dimorphic behaviors as well as disorders of the brain and behavior. These differences are organized during gestation and early adolescence and detectable prior to puberty. Endocrine disrupting compounds (EDCs) interfere with hormone action and are thus prenatal exposure is hypothesized to disrupt the formation of sex differences, and contribute to the increased prevalence of pediatric neuropsychiatric disorders that present with a sex bias. Available evidence for the ability of EDCs to impact the emergence of brain sex differences in the rodent brain was reviewed here, with a focus on effects detected at or before puberty. The peer-reviewed literature was searched using PubMed, and all relevant papers published by January 31, 2015 were incorporated. Endpoints of interest included molecular cellular and neuroanatomical effects. Studies on behavioral endpoints were not included because numerous reviews of that literature are available. The hypothalamus was found to be particularly affected by estrogenic EDCs in a sex, time, and exposure dependent manner. The hippocampus also appears vulnerable to endocrine disruption by BPA and PCBs although there is little evidence from the pre-pubertal literature to make any conclusions about sex-specific effects. Gestational EDC exposure can alter fetal neurogenesis and gene expression throughout the brain including the cortex and cerebellum. The available literature primarily focuses on a few, well characterized EDCs, but little data is available for emerging contaminants. The developmental EDC exposure literature demonstrates evidence of altered neurodevelopment as early as fetal life, with sex specific effects observed throughout the brain even before puberty. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of endocrine-disruption and clinical manifestations in large-mouth bass from Florida lakes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, D.A.; Gross, T.S.; Johnson, B.

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,more » 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.« less

Contaminant impacts to the endocrine system in largemouth bass in northeast U.S. rivers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S.B.; Sorenson, S.K.

1995-12-31

The National Biological Service (NBS) in cooperation with the USGS-National Water Quality Assessment (NAWQA) program conducted a reconnaissance investigation of potential disruption of the endocrine system in carp and largemouth bass (LMB) from streams and rivers across the US. Chemical analysis of sediment and fish tissue, from agricultural and industrial sites in NAWQA study units, indicated the potential for impacts to the endocrine system of fish. Collections of 39 male and 28 female LMB were made in fall 1994 from contaminated and reference sites in three major river systems in the Northeast US (Potomac, Hudson, and Connecticut rivers). Additional fishmore » collections will be made at these same sites in Spring 1995. Blood and gonadal tissue samples will give a triad of bioindicators (17B-estradiol/11-ketotestosterone ratios, vitellogenin, and gonad histopathology) of potential endocrine disruption. Chemical residue for tissue will also be made from selected LMB to compare with the bioindicators. Comparisons of contaminated sites and reference site indicated a significantly lower E/T ratio in female LMB from two contaminated sites (Housatonic River in the Connecticut River system and the Anacostia River in the Potomac River system). Additionally, significantly higher E/T ratios in male LMB were found from each of the three river systems. These E/T ratios indicate that endocrine disruption is both estrogenic to male LMB (feminization) and potentially androgenic to the female LMB (masculinization).« less

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

PubMed

Vom Saal, F S

2016-07-01

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

Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells.

PubMed

Pérez-Albaladejo, Elisabet; Fernandes, Denise; Lacorte, Silvia; Porte, Cinta

2017-02-01

Plasticizers are suspected to be toxic and/or to modulate or disrupt the endocrine system of humans and to cross the placental barrier, being embryonic and fetal development a particularly vulnerable period. This work investigates the comparative toxicity and ability to interfere with the synthesis of steroids and to generate reactive oxygen species (ROS) of a selected number of plasticizers, including bisphenol A (BPA), nonyl- (NP) and octylphenol (OP), benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), di(2-ethylhexyl)phthalate (DEHP) and dimethyl phthalate (DMP), in the human placenta JEG-3 cells. Moreover, the bioavailability of chemicals in culture medium has been investigated. After 24h exposure, OP and NP showed the highest cytotoxicity (EC 50 : 36-40μM) followed by BPA (138-219μM), whereas no significant toxicity was observed for phthalates. Notwithstanding, BBP and DBP significantly decreased P450 aromatase activity (experimental IC 50 : 14-15μM), while NP and OP (20μM) increased the activity. Overall, this study evidences the differential toxicity and ability to modulate placental aromatase activity of some of the compounds nowadays used as plasticizers, and highlights the need of an accurate determination of the bioavailability of chemicals to improve the sensitivity of in-vitro tests. Copyright © 2016 Elsevier B.V. All rights reserved.

SPECIES DIFFERENCES IN ANDROGEN AND ESTROGEN RECEPTOR STRUCTURE AND FUNCTION AMONG VERTEBRATES AND INVERTEBRATES: INTERSPECIES EXTRAPOLATIONS REGARDING ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Species Differences in Androgen and Estrogen Receptor Structure and Function Among Vertebrates and Invertebrates: Interspecies Extrapolations regarding Endocrine Disrupting Chemicals
VS Wilson1, GT Ankley2, M Gooding 1,3, PD Reynolds 1,4, NC Noriega 1, M Cardon 1, P Hartig1,...

Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting Chemicals.

PubMed

Mimoto, Mizuho S; Nadal, Angel; Sargis, Robert M

2017-06-01

Environmental toxicants are increasingly implicated in the global decline in metabolic health. Focusing on diabetes, herein, the molecular and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair energy homeostasis are discussed. Emerging data implicate MDC perturbations in a variety of pathways as contributors to metabolic disease pathogenesis, with effects in diverse tissues regulating fuel utilization. Potentiation of traditional metabolic risk factors, such as caloric excess, and emerging threats to metabolism, such as disruptions in circadian rhythms, are important areas of current and future MDC research. Increasing evidence also implicates deleterious effects of MDCs on metabolic programming that occur during vulnerable developmental windows, such as in utero and early post-natal life as well as pregnancy. Recent insights into the mechanisms by which MDCs alter energy homeostasis will advance the field's ability to predict interactions with classical metabolic disease risk factors and empower studies utilizing targeted therapeutics to treat MDC-mediated diabetes.

Overview of air pollution and endocrine disorders

PubMed Central

Darbre, Philippa D

2018-01-01

Over recent years, many environmental pollutant chemicals have been shown to possess the ability to interfere in the functioning of the endocrine system and have been termed endocrine disrupting chemicals (EDCs). These compounds exist in air as volatile or semi-volatile compounds in the gas phase or attached to particulate matter. They include components of plastics (phthalates, bisphenol A), components of consumer goods (parabens, triclosan, alkylphenols, fragrance compounds, organobromine flame retardants, fluorosurfactants), industrial chemicals (polychlorinated biphenyls), products of combustion (polychlorinated dibenzodioxins/furans, polyaromatic hydrocarbons), pesticides, herbicides, and some metals. This review summarizes current knowledge concerning the sources of EDCs in air, measurements of levels of EDCs in air, and the potential for adverse effects of EDCs in air on human endocrine health. PMID:29872334

Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain.

PubMed

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

2014-01-01

Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further

Early Life Exposure to Endocrine-Disrupting Chemicals Causes Lifelong Molecular Reprogramming of the Hypothalamus and Premature Reproductive Aging

PubMed Central

Walker, Deena M.; Zama, Aparna M.; Armenti, AnnMarie E.; Uzumcu, Mehmet

2011-01-01

Gestational exposure to the estrogenic endocrine disruptor methoxychlor (MXC) disrupts the female reproductive system at the molecular, physiological, and behavioral levels in adulthood. The current study addressed whether perinatal exposure to endocrine disruptors reprograms expression of a suite of genes expressed in the hypothalamus that control reproductive function and related these molecular changes to premature reproductive aging. Fischer rats were exposed daily for 12 consecutive days to vehicle (dimethylsulfoxide), estradiol benzoate (EB) (1 mg/kg), and MXC (low dose, 20 μg/kg or high dose, 100 mg/kg), beginning on embryonic d 19 through postnatal d 7. The perinatally exposed females were aged to 16–17 months and monitored for reproductive senescence. After euthanasia, hypothalamic regions [preoptic area (POA) and medial basal hypothalamus] were dissected for real-time PCR of gene expression or pyrosequencing to assess DNA methylation of the Esr1 gene. Using a 48-gene PCR platform, two genes (Kiss1 and Esr1) were significantly different in the POA of endocrine-disrupting chemical-exposed rats compared with vehicle-exposed rats after Bonferroni correction. Fifteen POA genes were up-regulated by at least 50% in EB or high-dose MXC compared with vehicle. To understand the epigenetic basis of the increased Esr1 gene expression, we performed bisulfite conversion and pyrosequencing of the Esr1 promoter. EB-treated rats had significantly higher percentage of methylation at three CpG sites in the Esr1 promoter compared with control rats. Together with these molecular effects, perinatal MXC and EB altered estrous cyclicity and advanced reproductive senescence. Thus, early life exposure to endocrine disruptors has lifelong effects on neuroendocrine gene expression and DNA methylation, together with causing the advancement of reproductive senescence. PMID:22016562

An Assessment of the Effects of the Endocrine Disrupting Chemical 17ß-Trenbolone on Japanese Medaka Fish in a Multigenerational Exposure

EPA Science Inventory

Presently the research emphasis for endocrine disrupting chemicals has been on the development of short-term screening assays. However, assessing effect concentrations of the most sensitive developmental stages impacted in longer-term and multi-generation tests remains to be det...

DIFFERENCES IN THE STRUCTURE AND FUNCTION OF FATHEAD MINNOW AND HUMAN ERA: IMPLICATIONS FOR IN VITRO TESTING OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Mammalian receptors and assay systems are generally used for in vitro analysis of endocrine disrupting chemicals (EDC) with the assumption that minor differences in amino acid sequences among species do not translate into significant differences in receptor function. We have fou...

Nanotoxicity: a growing need for study in the endocrine system.

PubMed

Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

2013-05-27

Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals

PubMed Central

Rich, Alisa L.; Phipps, Laura M.; Tiwari, Sweta; Rudraraju, Hemanth; Dokpesi, Philip O.

2016-01-01

An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID:27660460

Vitellogenin levels and others biomarkers show evidences of endocrine disruption in fish species from Iguaçu River - Southern Brazil.

PubMed

Yamamoto, F Y; Garcia, J R E; Kupsco, A; Oliveira Ribeiro, C A

2017-11-01

The adverse effects of endocrine disrupting chemicals (EDCs) on aquatic wildlife and human health represent a current issue of high public concern. Even so, they are still poorly studied in aquatic environments of South America. The aim of the present study was to investigate the impact of EDCs in five cascading reservoirs from the Iguaçu River, evaluating reproductive endpoints in three native fish species (Astyanax bifasciatus, Chrenicicla iguassuensis and Geophagus brasiliensis). Additionally, a polyclonal antiserum anti-vitellogenin from G. brasiliensis and a capture ELISA assay were developed for detection of estrogenic or anti-estrogenic activities in male and female fish, respectively. Vitellogenin (VTG) levels in male fish from the Iguacu River was observed, as well as decreased levels of vitellogenin and estradiol in the plasma of female fish. These findings were associated with immature gonads and lower gonadosomatic index in G. brasiliensis adult females from the Foz do Areia (FA) Reservoir. Additionally, both endemic species (Astyanax bifasciatus and Chrenicicla iguassuensis) displayed immature gonads and histological changes, such as degeneration of germ cells, in other studied reservoirs. The current results suggest that these reproductive responses may be associated with the bioavailability of EDCs in the Iguaçu River. These impacts are likely related to chemicals released by human activities, especially from sewage and industrial sources and agricultural production, detected in previous studies. Overall, the FA reservoir was potentially the most affected by chemicals with endocrine properties, and further studies are necessary to identify and quantify these chemicals. Copyright © 2017. Published by Elsevier Ltd.

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

Biodegradation of Endocrine-Disrupting Chemicals and Residual Organic Pollutants of Pulp and Paper Mill Effluent by Biostimulation.

PubMed

Chandra, Ram; Sharma, Pooja; Yadav, Sangeeta; Tripathi, Sonam

2018-01-01

Effluent discharged from the pulp and paper industry contains various refractory and androgenic compounds, even after secondary treatment by activated processes. Detailed knowledge is not yet available regarding the properties of organic pollutants and methods for their bioremediation. This study focused on detecting residual organic pollutants of pulp and paper mill effluent after biological treatment and assessing their degradability by biostimulation. The major compounds identified in the effluent were 2,3,6-trimethylphenol, 2-methoxyphenol (guaiacol), 2,6-dimethoxyphenol (syringol), methoxycinnamic acid, pentadecane, octadecanoic acid, trimethylsilyl ester, cyclotetracosane, 5,8-dimethoxy-6-methyl-2,4-bis(phenylmethyl)napthalen-1-ol, and 1,2-benzendicarboxylic acid diisononyl ester. Most of these compounds are classified as endocrine-disrupting chemicals and environmental toxicants. Some compounds are lignin monomers that are metabolic products from secondary treatment of the discharged effluent. This indicated that the existing industrial process could not further degrade the effluent. Supplementation by carbon (glucose 1.0%) and nitrogen (peptone 0.5%) bio-stimulated the degradation process. The degraded sample after biostimulation showed either disappearance or generation of metabolic products under optimized conditions, i.e., a stirring rate of 150 rpm and temperature of 37 ± 1°C after 3 and 6 days of bacterial incubation. Isolated potential autochthonous bacteria were identified as Klebsiella pneumoniae IITRCP04 (KU715839), Enterobacter cloacae strain IITRCP11 (KU715840), Enterobacter cloacae IITRCP14 (KU715841), and Acinetobacter pittii strain IITRCP19 (KU715842). Lactic acid, benzoic acid, and vanillin, resulting from residual chlorolignin compounds, were generated as potential value-added products during the detoxification of effluent in the biostimulation process, supporting the commercial importance of this process.

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 ...

Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis.

PubMed

Attina, Teresa M; Hauser, Russ; Sathyanarayana, Sheela; Hunt, Patricia A; Bourguignon, Jean-Pierre; Myers, John Peterson; DiGangi, Joseph; Zoeller, R Thomas; Trasande, Leonardo

2016-12-01

Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (€1=$1·33). The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2·33% of GDP] vs $217 billion [1·28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12·6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental toxicology and risk assessment: Standardization of biomarkers for endocrine disruption and environmental assessment: Eighth volume. Special technical publication 1364

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henshel, D.S.; Black, M.C.; Harrass, M.C.

1999-07-01

This conference was held April 20--22, 1998 in Atlanta, Georgia. The purpose of this conference was to provide a multidisciplinary forum for exchange of state-of-the-art information on biological markers in toxicology and risk assessment, including endocrine disrupter screening assays. Attention is focused on the following: aquatic toxicology; behavioral toxicology; biochemical indicators; developmental indicators; endocrine indicators; biodegradation and fate of chemicals; quality assurance and quality control within laboratory and field studies; risk assessment and communication, and harmonization of standards development. Individual papers have been processed separately for inclusion in the appropriate data bases.

Exploitation of Trametes versicolor for bioremediation of endocrine disrupting chemicals in bioreactors

PubMed Central

Sannia, Giovanni; Raganati, Francesca; Olivieri, Giuseppe; Marzocchella, Antonio; Schlosser, Dietmar

2017-01-01

Endocrine disrupting chemicals (EDCs) are environmental contaminants causing increasing concerns due to their toxicity, persistence and ubiquity. In the present study, degradative capabilities of Trametes versicolor, Pleurotus ostreatus and Phanerochaete chrysosporium to act on five EDCs, which represent different classes of chemicals (phenols, parabens and phthalate) and were first applied as single compounds, were assessed. T. versicolor was selected due to its efficiency against target EDCs and its potentialities were exploited against a mixture of EDCs in a cost-effective bioremediation process. A fed-batch approach as well as a starvation strategy were applied in order to reduce the need for input of ‘fresh’ biomass, and avoid the requirement for external nutrients. The fungus was successfully operated in two different bioreactors over one week. Semi-batch cultures were carried out by daily adding a mixture of EDCs to the bioreactors in a total of five consecutive degradation cycles. T. versicolor was able to efficiently remove all compounds during each cycle converting up to 21 mg L-1 day-1 of the tested EDCs. The maintained ability of T. versicolor to remove EDCs without any additional nutrients represents the main outcome of this study, which enables to forecast its application in a water treatment process. PMID:28575092

Exploitation of Trametes versicolor for bioremediation of endocrine disrupting chemicals in bioreactors.

PubMed

Pezzella, Cinzia; Macellaro, Gemma; Sannia, Giovanni; Raganati, Francesca; Olivieri, Giuseppe; Marzocchella, Antonio; Schlosser, Dietmar; Piscitelli, Alessandra

2017-01-01

Endocrine disrupting chemicals (EDCs) are environmental contaminants causing increasing concerns due to their toxicity, persistence and ubiquity. In the present study, degradative capabilities of Trametes versicolor, Pleurotus ostreatus and Phanerochaete chrysosporium to act on five EDCs, which represent different classes of chemicals (phenols, parabens and phthalate) and were first applied as single compounds, were assessed. T. versicolor was selected due to its efficiency against target EDCs and its potentialities were exploited against a mixture of EDCs in a cost-effective bioremediation process. A fed-batch approach as well as a starvation strategy were applied in order to reduce the need for input of 'fresh' biomass, and avoid the requirement for external nutrients. The fungus was successfully operated in two different bioreactors over one week. Semi-batch cultures were carried out by daily adding a mixture of EDCs to the bioreactors in a total of five consecutive degradation cycles. T. versicolor was able to efficiently remove all compounds during each cycle converting up to 21 mg L-1 day-1 of the tested EDCs. The maintained ability of T. versicolor to remove EDCs without any additional nutrients represents the main outcome of this study, which enables to forecast its application in a water treatment process.

Effects on Biotransformation, Oxidative Stress, and Endocrine Disruption in Rainbow Trout (Oncorhynchus mykiss) Exposed to Hydraulic Fracturing Flowback and Produced Water.

PubMed

He, Yuhe; Folkerts, Erik J; Zhang, Yifeng; Martin, Jonathan W; Alessi, Daniel S; Goss, Greg G

2017-01-17

The effects of hydraulic fracturing (HF) flowback and produced water (HF-FPW), a complex saline mixture of injected HF fluids and deep formation water that return to the surface, was examined in rainbow trout (Oncorhynchus mykiss). Exposure to HF-FPWs resulted in significant induction of ethoxyresorufin-O-deethylase (EROD) activity in both liver and gill tissues. Increased lipid peroxidation via oxidative stress was also detected by thiobarbituric acid reactive substances (TBARS) assay. The mRNA expressions of a battery of genes related to biotransformation, oxidative stress, and endocrine disruption were also measured using quantitative real-time polymerase chain reaction (Q-RT-PCR). The increased expression of cyp1a (2.49 ± 0.28-fold), udpgt (2.01 ± 0.31-fold), sod (1.67 ± 0.09-fold), and gpx (1.58 ± 0.10-fold) in raw sample exposure group (7.5%) indicated elevated metabolic enzyme activity, likely through the aryl hydrocarbon receptor pathway, and generation of reactive oxygen species. In addition, the elevated vtg and era2 expression demonstrated endocrine disrupting potential exerted by HF-FPW in rainbow trout. The overall results suggested HF-FPW could cause significant adverse effects on fish, and the organic contents might play the major role in its toxicity. Future studies are needed to help fully determine the toxic mechanism(s) of HF-FPW on freshwater fish, and aid in establishing monitoring, treatment, and remediation protocols for HF-FPW.

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

PubMed

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

2018-05-01

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

Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

EPA Science Inventory

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

Use of nuclear receptor luciferase-based bioassays to detect endocrine active chemicals in a biosolids-biochar amended soil.

PubMed

Anderson, Carolyn G; Joshi, Geetika; Bair, Daniel A; Oriol, Charlotte; He, Guochun; Parikh, Sanjai J; Denison, Michael S; Scow, Kate M

2017-08-01

Biosolids are a potentially valuable source of carbon and nutrients for agricultural soils; however, potential unintended impacts on human health and the environment must be considered. Virtually all biosolids contain trace amounts endocrine-disrupting chemicals derived from human use of pharmaceuticals and personal care products (PPCPs). One potential way to reduce the bioavailability of PPCPs is to co-apply biosolids with biochar to soil, because biochar's chemical (e.g., aromaticity) and physical properties (e.g., surface area) give it a high affinity to bind many organic chemicals in the environment. We developed a soil-specific extraction method and utilized a luciferase-based bioassay (CALUX) to detect endocrine active chemicals in a biosolids-biochar co-amendment soil greenhouse study. Both biochar (walnut shell, 900 °C) and biosolids had positive impacts on carrot and lettuce biomass accumulation over our study period. However, the walnut shell biochar stimulated aryl hydrocarbon receptor activity, suggesting the presence of potential endocrine active chemicals in the biochar. Since the biochar rate tested (100 t ha -1 ) is above the average agronomic rate (10-20 t ha -1 ), endocrine effects would not be expected in most environmental applications. The effect of high temperature biochars on endocrine system pathways must be explored further, using both quantitative analytical tools to identify potential endocrine active chemicals and highly sensitive bioanalytical assays such as CALUX to measure the resulting biological activity of such compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Xiaoxia; University of Chinese Academy of Sciences, Beijing; Chen, Xiaowen

The glycoprotein subunit α (gsuα) gene encodes the shared α subunit of the three pituitary heterodimeric glycoprotein hormones: follicle-stimulating hormone β (Fshβ), luteinizing hormone β (Lhβ) and thyroid stimulating hormone β (Tshβ). In our current study, we identified and characterized the promoter region of zebrafish gsuα and generated a stable gsuα:EGFP transgenic line, which recapitulated the endogenous gsuα expression in the early developing pituitary gland. A relatively conserved regulatory element set is presented in the promoter regions of zebrafish and three other known mammalian gsuα promoters. Our results also demonstrated that the expression patterns of the gsuα:EGFP transgene were allmore » identical to those expression patterns of the endogenous gsuα expression in the pituitary tissue when our transgenic fish were treated with various endocrine chemicals, including forskolin (FSK), SP600125, trichostatin A (TSA), KClO{sub 4}, dexamethasone (Dex), β-estradiol and progesterone. Thus, this gsuα:EGFP transgenic fish reporter line provides another valuable tool for investigating the lineage development of gsuα-expressing gonadotrophins and the coordinated regulation of various glycoprotein hormone subunit genes. These reporter fish can serve as a novel platform to perform screenings of endocrine-disrupting chemicals (EDCs) in vivo as well. - Highlights: • Identification of the promoter of zebrafish glycoprotein subunit α (gsuα) gene • Generation of stable transmission gsuα:EGFP transgenic zebrafish reporter • Demonstration of the recapitulation of the gsuα:EGFP and endogenous gsuα expression • Suggestion of the gsuα:EGFP transgenic zebrafish as a novel platform for EDC study.« less

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

PubMed

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

2015-04-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-08-01

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

Parabens and their effects on the endocrine system.

PubMed

Nowak, Karolina; Ratajczak-Wrona, Wioletta; Górska, Maria; Jabłońska, Ewa

2018-03-27

Preservatives (ingredients which inhibit growth of microorganisms) are used to prolong shelf life of various foods, cosmetics, and pharmaceutical products. Parabens are one of the most popular preservatives used in the aforementioned products and is currently being used worldwide. Parabens are easily absorbed by the human body. Thus, it is important to discuss about their safety with respect to human physiology. In view of the current literature, which classifies parabens as a group of endocrine disrupting chemicals (EDCs), it seems that the precise assessment of their influence on the human endocrine system is particularly important. Disruption of the endocrine homoeostasis might lead to multidirectional implications causing disruption of fitness and functions of the body. Therefore, in this review article, we aimed to summarize the current literature on properties, occurrence, and metabolism of parabens as well as to present recent progress in knowledge about their influence on the human endocrine system. Copyright © 2018 Elsevier B.V. All rights reserved.

A review of the evidence for endocrine disrupting effects of current-use chemicals on wildlife populations.

PubMed

Matthiessen, Peter; Wheeler, James R; Weltje, Lennart

2018-03-01

This review critically examines the data on claimed endocrine-mediated adverse effects of chemicals on wildlife populations. It focuses on the effects of current-use chemicals, and compares their apparent scale and severity with those of legacy chemicals which have been withdrawn from sale or use, although they may still be present in the environment. The review concludes that the effects on wildlife of many legacy chemicals with endocrine activity are generally greater than those caused by current-use chemicals, with the exception of ethinylestradiol and other estrogens found in sewage effluents, which are causing widespread effects on fish populations. It is considered that current chemical testing regimes and risk assessment procedures, at least those to which pesticides and biocides are subjected, are in part responsible for this improvement. This is noteworthy as most ecotoxicological testing for regulatory purposes is currently focused on characterizing apical adverse effect endpoints rather than identifying the mechanism(s) responsible for any observed effects. Furthermore, a suite of internationally standardized ecotoxicity tests sensitive for potential endocrine-mediated effects is now in place, or under development, which should ensure further characterization of substances with these properties so that they can be adequately regulated.

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...

In Silico Identification and Pharmacological Evaluation of Novel Endocrine Disrupting Chemicals That Act via the Ligand-Binding Domain of the Estrogen Receptor α

PubMed Central

Kufareva, Irina; Abagyan, Ruben

2014-01-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM–3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. PMID:24928891

Altered Amphibian Secondary Sex Characteristics following Exposure to Model Endocrine Disruptors

EPA Science Inventory

The formation of the secondary sex characteristics, oviducts and nuptial pads, are under the control of steroid hormones in frogs and as such are potential targets for endocrine-disrupting compounds. Oviducts are large, convoluted tubules derived from the Mullerian ducts in whic...

Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer.

PubMed

Scsukova, Sona; Rollerova, Eva; Bujnakova Mlynarcikova, Alzbeta

2016-12-01

A growing body of evidence suggests that exposure to chemical substances designated as endocrine disrupting chemicals (EDCs) due to their ability to disturb endocrine (hormonal) activity in humans and animals, may contribute to problems with fertility, pregnancy, and other aspects of reproduction. The presence of EDCs has already been associated with reproductive malfunction in wildlife species, but it remains difficult to prove causal relationships between the presence of EDCs and specific reproductive problems in vivo, especially in females. On the other hand, the increasing number of experiments with laboratory animals and in vitro research indicate the ability of different EDCs to influence the normal function of female reproductive system, and even their association with cancer development or progression. Research shows that EDCs may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming. In this review article, we aim to point out a possible contribution of EDCs to the onset and development of female reproductive disorders and endocrine-related cancers with regard to the period of exposure to EDCs and affected endpoints (organs or processes). Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Effects of Exposure to the Endocrine-Disrupting Chemical Bisphenol A During Critical Windows of Murine Pituitary Development.

PubMed

Eckstrum, Kirsten S; Edwards, Whitney; Banerjee, Annesha; Wang, Wei; Flaws, Jodi A; Katzenellenbogen, John A; Kim, Sung Hoon; Raetzman, Lori T

2018-01-01

Critical windows of development are often more sensitive to endocrine disruption. The murine pituitary gland has two critical windows of development: embryonic gland establishment and neonatal hormone cell expansion. During embryonic development, one environmentally ubiquitous endocrine-disrupting chemical, bisphenol A (BPA), has been shown to alter pituitary development by increasing proliferation and gonadotrope number in females but not males. However, the effects of exposure during the neonatal period have not been examined. Therefore, we dosed pups from postnatal day (PND)0 to PND7 with 0.05, 0.5, and 50 μg/kg/d BPA, environmentally relevant doses, or 50 μg/kg/d estradiol (E2). Mice were collected after dosing at PND7 and at 5 weeks. Dosing mice neonatally with BPA caused sex-specific gene expression changes distinct from those observed with embryonic exposure. At PND7, pituitary Pit1 messenger RNA (mRNA) expression was decreased with BPA 0.05 and 0.5 μg/kg/d in males only. Expression of Pomc mRNA was decreased at 0.5 μg/kg/d BPA in males and at 0.5 and 50 μg/kg/d BPA in females. Similarly, E2 decreased Pomc mRNA in both males and females. However, no noticeable corresponding changes were found in protein expression. Both E2 and BPA suppressed Pomc mRNA in pituitary organ cultures; this repression appeared to be mediated by estrogen receptor-α and estrogen receptor-β in females and G protein-coupled estrogen receptor in males, as determined by estrogen receptor subtype-selective agonists. These data demonstrated that BPA exposure during neonatal pituitary development has unique sex-specific effects on gene expression and that Pomc repression in males and females can occur through different mechanisms. Copyright © 2018 Endocrine Society.

Endocrine Disrupting Chemicals and the Developmental Programming of Adipogenesis and Obesity

PubMed Central

Janesick, Amanda; Blumberg, Bruce

2016-01-01

Obesity and related disorders are a burgeoning public health epidemic, particularly in the U.S. Currently 34% of the U.S. population is clinically obese (BMI > 30) and 68% are overweight (BMI > 25), more than double the worldwide average and 10-fold higher than Japan and South Korea. Obesity occurs when energy intake exceeds energy expenditure; however, individuals vary widely in their propensity to gain weight and accrue fat mass, even at identical levels of excess caloric input. Clinical, epidemiological, and biological studies show that obesity is largely programmed during early life, including the intrauterine period. The environmental obesogen hypothesis holds that prenatal or early life exposure to certain endocrine disrupting chemicals can predispose exposed individuals to increased fat mass and obesity. Obesogen exposure can alter the epigenome of multipotent stromal stem cells, biasing them toward the adipocyte lineage at the expense of bone. Hence, humans exposed to obesogens during early life might have an altered stem cell compartment, which is preprogrammed toward an adipogenic fate. This results in a higher steady state number of adipocytes and potentially a lifelong struggle to maintain a healthy weight, which can be exacerbated by societal influences that promote poor diet and inadequate exercise. This review focuses on the developmental origins of the adipocyte, the relationship between adipocyte number and obesity, and how obesogenic chemicals may interfere with the highly efficient homeostatic mechanisms regulating adipocyte number and energy balance. PMID:21425440

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.

ENDOCRINE DISRUPTORS FROM COMBUSTION AND VEHICULAR EMISSIONS: IDENTIFICATION AND SOURCE NOMINATION

EPA Science Inventory

During the last decade, concerns have been raised regarding the possible harmful effects of exposure to certain chemicals that are capable of modulating or disrupting the function of the endocrine system. These chemicals, which are referred to as endocrine disrupting chemicals (E...

Occurrence of endocrine-disrupting and other wastewater compunds during water treatment with case studies from Lincoln, Nebraska and Berlin, Germany

USGS Publications Warehouse

Verstraeten, Ingrid M.; Heberer, T.; Vogel, J.R.; Speth, T.; Zuehlke, S.; Duennbier, U.

2003-01-01

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. Studies conducted during the last decade in Lincoln, Nebraska, and Berlin, Germany, indicate that removal of less polar compounds probably can be obtained through bank filtration, ground-water enrichment, and additional drinking-water and wastewater treatment processes. Polar compounds, such as atrazine and some metabolites, occur in drinking water obtained from contaminated surface water or ground water, but at concentrations generally lower than those occurring in wastewater and surface water. The results of the studies also suggest that concentrations of nonpolar estrogenic compounds decrease during drinking-water pretreatment processes such as bank filtration and ground-water enrichment.

High-Throughput Effect-Directed Analysis Using Downscaled in Vitro Reporter Gene Assays To Identify Endocrine Disruptors in Surface Water

PubMed Central

2018-01-01

Effect-directed analysis (EDA) is a commonly used approach for effect-based identification of endocrine disruptive chemicals in complex (environmental) mixtures. However, for routine toxicity assessment of, for example, water samples, current EDA approaches are considered time-consuming and laborious. We achieved faster EDA and identification by downscaling of sensitive cell-based hormone reporter gene assays and increasing fractionation resolution to allow testing of smaller fractions with reduced complexity. The high-resolution EDA approach is demonstrated by analysis of four environmental passive sampler extracts. Downscaling of the assays to a 384-well format allowed analysis of 64 fractions in triplicate (or 192 fractions without technical replicates) without affecting sensitivity compared to the standard 96-well format. Through a parallel exposure method, agonistic and antagonistic androgen and estrogen receptor activity could be measured in a single experiment following a single fractionation. From 16 selected candidate compounds, identified through nontargeted analysis, 13 could be confirmed chemically and 10 were found to be biologically active, of which the most potent nonsteroidal estrogens were identified as oxybenzone and piperine. The increased fractionation resolution and the higher throughput that downscaling provides allow for future application in routine high-resolution screening of large numbers of samples in order to accelerate identification of (emerging) endocrine disruptors. PMID:29547277

The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity.

PubMed

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

2012-05-06

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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

CGCampbell@lbl.gov

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

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

EPA Science Inventory

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

Endocrine disrupting alkylphenolic chemicals and other contaminants in wastewater treatment plant effluents, urban streams, and fish in the Great Lakes and Upper Mississippi River Regions

USGS Publications Warehouse

Barber, Larry B.; Loyo-Rosales, Jorge E.; Rice, Clifford P.; Minarik, Thomas A.; Oskouie, Ali K.

2015-01-01

Urban streams are an integral part of the municipal water cycle and provide a point of discharge for wastewater treatment plant (WWTP) effluents, allowing additional attenuation through dilution and transformation processes, as well as a conduit for transporting contaminants to downstream water supplies. Domestic and commercial activities dispose of wastes down-the-drain, resulting in wastewater containing complex chemical mixtures that are only partially removed during treatment. A key issue associated with WWTP effluent discharge into streams is the potential to cause endocrine disruption in fish. This study provides a long-term (1999-2009) evaluation of the occurrence of alkylphenolic endocrine disrupting chemicals (EDCs) and other contaminants discharged from WWTPs into streams in the Great Lakes and Upper Mississippi River Regions (Indiana, Illinois, Michigan, Minnesota, and Ohio). The Greater Metropolitan Chicago Area Waterways, Illinois, were evaluated to determine contaminant concentrations in the major WWTP effluents and receiving streams, and assess the behavior of EDCs from their sources within the sewer collection system, through the major treatment unit processes at a WWTP, to their persistence and transport in the receiving stream. Water samples were analyzed for alkylphenolic EDCs and other contaminants, including 4-nonylphenol (NP), 4-nonylphenolpolyethoxylates (NPEO), 4-nonylphenolethoxycarboxylic acids (NPEC), 4-tert-octylphenol (OP), 4-tert-octylphenolpolyethoxylates (OPEO), bisphenol A, triclosan, ethylenediaminetetraacetic acid (EDTA), and trace elements. All of the compounds were detected in all of the WWTP effluents, with EDTA and NPEC having the greatest concentrations. The compounds also were detected in the WWTP effluent dominated rivers. Multiple fish species were collected from river and lake sites and analyzed for NP, NPEO, NPEC, OP, and OPEO. Whole-body fish tissue analysis indicated widespread occurrence of alkylphenolic compounds

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... include the sex hormones (e.g., estrogen and androgen), the hypothalamic-pituitary-adrenal axis, the thyroid hormone, and the hormones involved in the feedback regulation of those components (e.g., gonadotropin releasing hormone and corticotropin). Changes in endocrine function can result in...

Behaviour of endocrine disrupting chemicals during the treatment of municipal sewage sludge.

PubMed

Ivashechkin, P; Corvini, P F X; Dohmann, M

2004-01-01

Agricultural application of municipal sewage sludge has been emotionally discussed in the last decades, because the latter contains endocrine disrupting chemicals (EDCs) and other organic micropollutants with unknown fate and risk potential. Bisphenol A (BPA) was chosen as a model substance to investigate the influence of sludge conditioning on the end-concentration of EDCs in sludge. Adsorption studies with radioactive-labelled BPA showed that more than 75% BPA in anaerobically digested sludge is bound to solids (log Kd = 2.09-2.30; log Koc = 2.72-3.11). Sludge conditioning with polymer or iron (III) chloride alone had no influence on the adsorption of BPA. After conditioning with iron (III) chloride and calcium hydroxide desorption of BPA took place. Apparently, it occurred due to the deprotonation of BPA (pKa= 10.3) as the pH-value reached 12.4 during the process. The same behaviour is expected for other phenolic EDCs with similar pKa (nonylphenol, 17beta-estradiol, estron, estriol, 17alpha-ethinylestradiol). This study shows high affinity of BPA to the anaerobically digested sludge and importance of conditioning in the elimination of EDCs during the sludge treatment. Addition of polymer is favourable in the case of sludge incineration. Conditioning with iron (III) chloride and calcium hydroxide shows advantages for the use of sludge as fertiliser.

Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.

PubMed Central

Zacharewski, T

1998-01-01

It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy. PMID:9599705

[Arterial hypertension secondary to endocrine disorders].

PubMed

Minder, Anna; Zulewski, Henryk

2015-06-01

Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

November 6, 2017, Virtual Meeting on the Charge Questions for the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) Meeting on Endocrine Disruption

EPA Pesticide Factsheets

This virtual FIFRA SAP meeting will be discus questions on Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways

Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting.

PubMed

Street, Maria Elisabeth; Angelini, Sabrina; Bernasconi, Sergio; Burgio, Ernesto; Cassio, Alessandra; Catellani, Cecilia; Cirillo, Francesca; Deodati, Annalisa; Fabbrizi, Enrica; Fanos, Vassilios; Gargano, Giancarlo; Grossi, Enzo; Iughetti, Lorenzo; Lazzeroni, Pietro; Mantovani, Alberto; Migliore, Lucia; Palanza, Paola; Panzica, Giancarlo; Papini, Anna Maria; Parmigiani, Stefano; Predieri, Barbara; Sartori, Chiara; Tridenti, Gabriele; Amarri, Sergio

2018-06-02

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals.

PubMed

Macejova, Dana; Toporova, L; Brtko, J

2016-07-01

Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

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

EPA Science Inventory

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

The Endocrine Disrupting Chemical Tolylfluanid Alters Adipocyte Metabolism via Glucocorticoid Receptor Activation

PubMed Central

Neel, Brian A.; Brady, Matthew J.

2013-01-01

Glucocorticoid signaling plays a critical role in regulating energy metabolism. Emerging data implicate environmental endocrine-disrupting chemicals as contributors to the obesity and diabetes epidemics. Previous studies have shown that the phenylsulfamide fungicide tolylfluanid (TF) augments glucocorticoid receptor (GR)-dependent luciferase expression in 3T3-L1 preadipocytes while modulating insulin action in primary murine and human adipocytes. Studies were performed to interrogate glucocorticoid signaling in primary adipocytes exposed to TF. TF mimicked the gene transcription profile of the murine glucocorticoid corticosterone (Cort). Cellular fractionation assays demonstrated that TF treatment promoted the activating serine phosphorylation of GR, augmenting its cytoplasmic-to-nuclear translocation as well as its enrichment at glucocorticoid response elements on the glucocorticoid-induced leucine zipper gene promoter. After acute treatment, Cort or TF promoted insulin receptor substrate-1 (IRS-1) gene and protein expression. Either treatment also enriched GR binding at an identified glucocorticoid response element in the IRS-1 gene. TF or Cort each increased insulin-stimulated lipogenesis, an effect resulting from increased lipogenic gene expression and enhanced insulin-stimulated dephosphorylation of acetyl-coenzyme A carboxylase. The augmentation of insulin-stimulated lipogenesis was mediated through a specific enhancement of Akt phosphorylation at T308. These findings support modulation of IRS-1 levels as a mechanism for glucocorticoid-mediated changes in insulin action in primary adipocytes. Albeit with less affinity than Cort, in silico analysis suggests that TF can interact with the ligand binding pocket of GR. Collectively, these studies identify TF as a structurally unique environmental glucocorticoid. Glucocorticoid signaling may thus represent a novel pathway by which environmental toxicants promote the development of metabolic diseases. PMID:23340252

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

PubMed Central

Preciados, Mark; Yoo, Changwon; Roy, Deodutta

2016-01-01

During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.

PubMed

Preciados, Mark; Yoo, Changwon; Roy, Deodutta

2016-12-13

During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of

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

PubMed

Takeda, Ken; Tsukue, Naomi; Yoshida, Seiichi

2004-01-01

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

Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts

EPA Science Inventory

Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts Katie B. Paul 1.2, Ruth Marfil-Vega 1 Marc A. Mills3, Steve 0. Simmons2, Vickie S. Wilson4, Kevin M. Crofton2 10ak Rid...

Conifer Diterpene Resin Acids Disrupt Juvenile Hormone-Mediated Endocrine Regulation in the Indian Meal Moth Plodia interpunctella.

PubMed

Oh, Hyun-Woo; Yun, Chan-Seok; Jeon, Jun Hyoung; Kim, Ji-Ae; Park, Doo-Sang; Ryu, Hyung Won; Oh, Sei-Ryang; Song, Hyuk-Hwan; Shin, Yunhee; Jung, Chan Sik; Shin, Sang Woon

2017-07-01

Diterpene resin acids (DRAs) are important components of oleoresin and greatly contribute to the defense strategies of conifers against herbivorous insects. In the present study, we determined that DRAs function as insect juvenile hormone (JH) antagonists that interfere with the juvenile hormone-mediated binding of the JH receptor Methoprene-tolerant (Met) and steroid receptor coactivator (SRC). Using a yeast two-hybrid system transformed with Met and SRC from the Indian meal moth Plodia interpunctella, we tested the interfering activity of 3704 plant extracts against JH III-mediated Met-SRC binding. Plant extracts from conifers, especially members of the Pinaceae, exhibited strong interfering activity, and four active interfering DRAs (7α-dehydroabietic acid, 7-oxodehydroabietic acid, dehydroabietic acid, and sandaracopimaric acid) were isolated from roots of the Japanese pine Pinus densiflora. The four isolated DRAs, along with abietic acid, disrupted the juvenile hormone-mediated binding of P. interpunctella Met and SRC, although only 7-oxodehydroabietic acid disrupted larval development. These results demonstrate that DRAs may play a defensive role against herbivorous insects via insect endocrine-disrupting activity.

Consensus models to predict endocrine disruption for all human-exposure chemicals (AAAS Annual Meeting)

EPA Science Inventory

Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been te...

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

PubMed

Hauser, Russ; Skakkebaek, Niels E; Hass, Ulla; Toppari, Jorma; Juul, Anders; Andersson, Anna Maria; Kortenkamp, Andreas; Heindel, Jerrold J; Trasande, Leonardo

2015-04-01

Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual

Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption.

PubMed

Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

2013-12-01

Exposure to environmental chemicals known as endocrine disruptors (EDs) is in many cases associated with an unpredictable hazard for wildlife and human health. The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable ED assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17α-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed

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

2010-09-01

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

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

PubMed

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

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

In silico identification and pharmacological evaluation of novel endocrine disrupting chemicals that act via the ligand-binding domain of the estrogen receptor α.

PubMed

McRobb, Fiona M; Kufareva, Irina; Abagyan, Ruben

2014-09-01

Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM-3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

CDNA CLONING OF FATHEAD MINNOW (PIMEPHALES PROMELAS) ESTROGEN AND ANDROGEN RECEPTORS FOR USE IN STEROID RECEPTOR EXTRAPOLATION STUDIES FOR ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

cDNA Cloning of Fathead minnow (Pimephales promelas) Estrogen and Androgen Receptors for Use in Steroid Receptor Extrapolation Studies for Endocrine Disrupting Chemicals.

Wilson, V.S.1,, Korte, J.2, Hartig P. 1, Ankley, G.T.2, Gray, L.E., Jr 1, , and Welch, J.E.1. 1U.S...

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.

Embryonic exposure to carbendazim induces the transcription of genes related to apoptosis, immunotoxicity and endocrine disruption in zebrafish (Danio rerio).

PubMed

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

2014-12-01

Carbendazim is one of the most widespread environmental contaminant that can cause major concern to human and animal reproductive system. To date, very few studies have been conducted on the toxic effect of carbendazim in the non-target organism zebrafish (Danio rerio). The study presented here aimed to assess how carbendazim triggers apoptosis, immunotoxicity and endocrine disruption pathways in zebrafish during its embryo development. Our results demonstrated that the expression patterns of many key genes involved in cell apoptosis pathway (e.g. P53, Mdm2, Bbc3 and Cas8) were significantly up-regulated upon the exposure to carbendazim at the concentration of 500 μg/L, while the Bcl2 and Cas3 were down-regulated at the same concentration, interestingly, the expression level of Ogg1 decreased at all the exposure concentrations. It was also observed that the mRNA levels of CXCL-C1C, CCL1, IL-1b and TNFα which were closely related to the innate immune system, were affected in newly hatched zebrafish after exposed to different concentrations of carbendazim. Moreover, the expression of genes that are involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis including VTG, ERα, ERβ2, Dio1, Dio2, Thraa and Thrb were all down-regulated significantly after the exposure to carbendazim. The expression levels of two cytochrome P450 aromatases CYP19a and CYP19b were increased significantly after 20 and 100 μg/L carbendazim exposure, respectively. Taken together, our results indicated that carbendazim had the potential to induce cell apoptosis and cause immune toxicity as well as endocrine disruption in zebrafish during the embryo developmental stage. The information presented here also help to elucidate the environmental risks caused by the carbendazim-induced toxicity in aquatic organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

IDENTIFYING ENDOCRINE DISRUPTORS BY HIGH-RESOLUTION MASS SPECTROMETRY

EPA Science Inventory

The EPA is currently interested in human and ecosystem exposure to endocrine disruptors (1)-compounds that interfere with endogenous hormone systems. Possible endocrine disruptors in the environment include certain pesticides, industrial by-products, and pharmaceuticals. Such c...

Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yanzhen; Mei, Chenfang; Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070

Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growthmore » factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.« less

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. Published by Elsevier Inc.

A Pathway Approach to Predicting Thyroid Hormone Disrupting Activity of Chemicals Using in vitro, ex vivo and in vivo Assays

EPA Science Inventory

The potential for commercial and industrial chemicals that may be released into the environment to have endocrine disrupting activity is of concern for human health and wildlife. Most initial endocrine disruptor research has focused on estrogen- or androgen-mediated pathways. In ...

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: a review of rodent and human data.

PubMed

Rasier, G; Toppari, J; Parent, A-S; Bourguignon, J-P

2006-07-25

Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

Circadian Clock Control of Endocrine Factors

PubMed Central

Gamble, Karen L.; Berry, Ryan; Frank, Stuart J.; Young, Martin E.

2015-01-01

Organisms experience dramatic fluctuations in demands/stresses over the course of the day. In order to maintain biological processes within physiologic boundaries, it is imperative that mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors undoubtedly play an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 period, but so too does responsiveness of target tissues to these signals/stimuli. Emerging evidence suggests that these daily oscillations do not occur solely in response to behavioral fluctuations associated with sleep/wake and feeding/fasting cycles, but are orchestrated in part by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks, through genetic and/or environmental means, appears to precipitate numerous common disorders, including cardiometabolic diseases and cancer. Collectively, these observations, which are reviewed within the current article, have led to suggestion that strategies designed to realign normal circadian rhythmicities hold a therapeutic potential for the treatment of various endocrine-related disorders. PMID:24863387

High-throughput in Vitro Data To Inform Prioritization of Ambient Water Monitoring and Testing for Endocrine Active Chemicals.

PubMed

Heiger-Bernays, Wendy J; Wegner, Susanna; Dix, David J

2018-01-16

The presence of industrial chemicals, consumer product chemicals, and pharmaceuticals is well documented in waters in the U.S. and globally. Most of these chemicals lack health-protective guidelines and many have been shown to have endocrine bioactivity. There is currently no systematic or national prioritization for monitoring waters for chemicals with endocrine disrupting activity. We propose ambient water bioactivity concentrations (AWBCs) generated from high throughput data as a health-based screen for endocrine bioactivity of chemicals in water. The U.S. EPA ToxCast program has screened over 1800 chemicals for estrogen receptor (ER) and androgen receptor (AR) pathway bioactivity. AWBCs are calculated for 110 ER and 212 AR bioactive chemicals using high throughput ToxCast data from in vitro screening assays and predictive pathway models, high-throughput toxicokinetic data, and data-driven assumptions about consumption of water. Chemical-specific AWBCs are compared with measured water concentrations in data sets from the greater Denver area, Minnesota lakes, and Oregon waters, demonstrating a framework for identifying endocrine bioactive chemicals. This approach can be used to screen potential cumulative endocrine activity in drinking water and to inform prioritization of future monitoring, chemical testing and pollution prevention efforts.

Endocrine Disrupting Chemical Induced "Pollution of Metabolic Pathways": A Case of Shifting Paradigms With Implications for Vascular Diseases.

PubMed

Janardhanan, Rajiv

2018-05-14

The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities. Both preclinical animal experiments, as well as epidemiological studies, have correlated EDC exposure with metabolic disorders such as metabolic syndrome, type 2 diabetes as well as cardiovascular health. Here we briefly review the statutory impact of EDCs on metabolic disruption as well as their impact on environmental health. Finally, difficulties pertaining to the categorization of EDC induced metabolic diseases as risk factors for global disease burden have been addressed taking into account the complexity of such interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Disruptive Civil Technologies: Six Technologies With Potential Impacts on US Interests Out to 2025

DTIC Science & Technology

2008-04-01

power (geopolitical, military, economic, or social cohesion). The six disruptive technologies were identified through a process carried out by...clustering, development of technology descriptors, screening, and prioritizing, analysts down-selected from 102 potentially disruptive technologies . They

Digestive enzymatic patterns as possible biomarkers of endocrine disruption in the red mullet (Mullus barbatus): A preliminary investigation.

PubMed

Caruso, Gabriella; De Pasquale, Francesca; Mita, Damiano Gustavo; Micale, Valeria

2016-04-15

During two seasonal trawl surveys (April and October, 2012), red mullet specimens were caught from two sites of the northern Sicilian coast (Western Mediterranean), characterized by different degrees of pollution, to assess whether their digestive enzymes could be cost-effective diagnostic tools for endocrine disruption. Pepsin, chymotrypsin, carboxypeptidases A and B, amylase and lipase were measured in the digestive tract of each fish. During both samplings, significant differences in the digestive enzymatic patterns of fish collected from the two sites were found. In April, pepsin and lipase contents were significantly lower in fish from the most impacted site than in those from the reference site. In October, the enzymatic patterns showed trends different from spring, with controversial results for carboxypeptidases A and B and amylase. Pepsin and lipase patterns suggest a detrimental effect played by organic pollutants and the use of these enzymes as possible biomarkers of exposure to endocrine disruptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Liying; Sedykh, Alexander; Tripathi, Ashutosh

2013-10-01

Identification of endocrine disrupting chemicals is one of the important goals of environmental chemical hazard screening. We report on the development of validated in silico predictors of chemicals likely to cause estrogen receptor (ER)-mediated endocrine disruption to facilitate their prioritization for future screening. A database of relative binding affinity of a large number of ERα and/or ERβ ligands was assembled (546 for ERα and 137 for ERβ). Both single-task learning (STL) and multi-task learning (MTL) continuous quantitative structure–activity relationship (QSAR) models were developed for predicting ligand binding affinity to ERα or ERβ. High predictive accuracy was achieved for ERα bindingmore » affinity (MTL R{sup 2} = 0.71, STL R{sup 2} = 0.73). For ERβ binding affinity, MTL models were significantly more predictive (R{sup 2} = 0.53, p < 0.05) than STL models. In addition, docking studies were performed on a set of ER agonists/antagonists (67 agonists and 39 antagonists for ERα, 48 agonists and 32 antagonists for ERβ, supplemented by putative decoys/non-binders) using the following ER structures (in complexes with respective ligands) retrieved from the Protein Data Bank: ERα agonist (PDB ID: 1L2I), ERα antagonist (PDB ID: 3DT3), ERβ agonist (PDB ID: 2NV7), and ERβ antagonist (PDB ID: 1L2J). We found that all four ER conformations discriminated their corresponding ligands from presumed non-binders. Finally, both QSAR models and ER structures were employed in parallel to virtually screen several large libraries of environmental chemicals to derive a ligand- and structure-based prioritized list of putative estrogenic compounds to be used for in vitro and in vivo experimental validation. - Highlights: • This is the largest curated dataset inclusive of ERα and β (the latter is unique). • New methodology that for the first time affords acceptable ERβ models. • A combination of QSAR and docking enables prediction of affinity and

Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

PubMed

Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

2008-05-01

Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination

Effects of multiwalled carbon nanotubes and triclocarban on several eukaryotic cell lines: elucidating cytotoxicity, endocrine disruption, and reactive oxygen species generation

NASA Astrophysics Data System (ADS)

Simon, Anne; Maletz, Sibylle X.; Hollert, Henner; Schäffer, Andreas; Maes, Hanna M.

2014-08-01

To date, only a few reports about studies on toxic effects of carbon nanotubes (CNT) are available, and their results are often controversial. Three different cell lines (rainbow trout liver cells (RTL-W1), human adrenocortical carcinoma cells (T47Dluc), and human adrenocarcinoma cells (H295R)) were exposed to multiwalled carbon nanotubes, the antimicrobial agent triclocarban (TCC) as well as the mixture of both substances in a concentration range of 3.13 to 50 mg CNT/L, 31.25 to 500 μg TCC/L, and 3.13 to 50 mg CNT/L + 1% TCC (percentage relative to carbon nanotubes concentration), respectively. Triclocarban is a high-production volume chemical that is widely used as an antimicrobial compound and is known for its toxicity, hydrophobicity, endocrine disruption, bioaccumulation potential, and environmental persistence. Carbon nanotubes are known to interact with hydrophobic organic compounds. Therefore, triclocarban was selected as a model substance to examine mixture toxicity in this study. The influence of multiwalled carbon nanotubes and triclocarban on various toxicological endpoints was specified: neither cytotoxicity nor endocrine disruption could be observed after exposure of the three cell lines to carbon nanotubes, but the nanomaterial caused intracellular generation of reactive oxygen species in all cell types. For TCC on the other hand, cell vitality of 80% could be observed at a concentration of 2.1 mg/L for treated RTL-W1 cells. A decrease of luciferase activity in the ER Calux assay at a triclocarban concentration of 125 μg/L and higher was observed. This effect was less pronounced when multiwalled carbon nanotubes were present in the medium. Taken together, these results demonstrate that multiwalled carbon nanotubes induce the production of reactive oxygen species in RTL-W1, T47Dluc, and H295R cells, reveal no cytotoxicity, and reduce the bioavailability and toxicity of the biocide triclocarban.

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

PubMed

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

2011-12-01

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

Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

PubMed Central

Gore, Andrea C.

2009-01-01

The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

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

ENDOCRINE DISRUPTORS: LESSONS LEARNED

EPA Science Inventory

For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates.

PubMed Central

Wynne-Edwards, K E

2001-01-01

Hormone disruption is a major, underappreciated component of the plant chemical arsenal, and the historical coevolution between hormone-disrupting plants and herbivores will have both increased the susceptibility of carnivores and diversified the sensitivities of herbivores to man-made endocrine disruptors. Here I review diverse evidence of the influence of plant secondary compounds on vertebrate reproduction, including human reproduction. Three of the testable hypotheses about the evolutionary responses of vertebrate herbivores to hormone-disrupting challenges from their diet are developed. Specifically, the hypotheses are that a) vertebrate herbivores will express steroid hormone receptors in the buccal cavity and/or the vomeronasal organ; b) absolute sex steroid concentrations will be lower in carnivores than in herbivores; and c) herbivore steroid receptors should be more diverse in their binding affinities than carnivore lineages. The argument developed in this review, if empirically validated by support for the specific hypotheses, suggests that a) carnivores will be more susceptible than herbivores to endocrine-disrupting compounds of anthropogenic origin entering their bodies, and b) diverse herbivore lineages will be variably susceptible to any given natural or synthetic contaminant. As screening methods for hormone-disrupting potential are compared and adopted, comparative endocrine physiology research is urgently needed to develop models that predict the broad applicability of those screening results in diverse vertebrate species. PMID:11401754

Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system

PubMed Central

Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Jepsen, Karl J

2018-01-01

Abstract Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals. PMID:29732168

Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system.

PubMed

Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Bartolomei, Marisa S; Jepsen, Karl J

2018-04-01

Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals.

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

PubMed Central

Gee, David

2006-01-01

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

Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union.

PubMed

Hunt, Patricia A; Sathyanarayana, Sheela; Fowler, Paul A; Trasande, Leonardo

2016-04-01

A growing body of evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to female reproductive disorders. To calculate the associated combined health care and economic costs attributable to specific EDC exposures within the European Union (EU). An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. Cost-of-illness estimation used multiple peer-reviewed sources. Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. The most robust EDC-related data for female reproductive disorders exist for 1) diphenyldichloroethene-attributable fibroids and 2) phthalate-attributable endometriosis in Europe. In both cases, the strength of epidemiological evidence was rated as low and the toxicological evidence as moderate, with an assigned probability of causation of 20%–39%. Across the EU, attributable cases were estimated to be 56 700 and 145 000 women, respectively, with total combined economic and health care costs potentially reaching €163 million and €1.25 billion. EDCs (diphenyldichloroethene and phthalates) may contribute substantially to the most common reproductive disorders in women, endometriosis and fibroids, costing nearly €1.5 billion annually. These estimates represent only EDCs for which there were sufficient epidemiologic studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.

QSAR classification models for the prediction of endocrine disrupting activity of brominated flame retardants.

PubMed

Kovarich, Simona; Papa, Ester; Gramatica, Paola

2011-06-15

The identification of potential endocrine disrupting (ED) chemicals is an important task for the scientific community due to their diffusion in the environment; the production and use of such compounds will be strictly regulated through the authorization process of the REACH regulation. To overcome the problem of insufficient experimental data, the quantitative structure-activity relationship (QSAR) approach is applied to predict the ED activity of new chemicals. In the present study QSAR classification models are developed, according to the OECD principles, to predict the ED potency for a class of emerging ubiquitary pollutants, viz. brominated flame retardants (BFRs). Different endpoints related to ED activity (i.e. aryl hydrocarbon receptor agonism and antagonism, estrogen receptor agonism and antagonism, androgen and progesterone receptor antagonism, T4-TTR competition, E2SULT inhibition) are modeled using the k-NN classification method. The best models are selected by maximizing the sensitivity and external predictive ability. We propose simple QSARs (based on few descriptors) characterized by internal stability, good predictive power and with a verified applicability domain. These models are simple tools that are applicable to screen BFRs in relation to their ED activity, and also to design safer alternatives, in agreement with the requirements of REACH regulation at the authorization step. Copyright © 2011 Elsevier B.V. All rights reserved.

Tissue explant coculture model of the hypothalamic-pituitary-gonadal-liver axis of the fathead minnow (Pimephales promelas) as a predictive tool for endocrine disruption.

PubMed

Johnston, Theresa K; Perkins, Edward; Ferguson, Duncan C; Cropek, Donald M

2016-10-01

Endocrine-disrupting compounds (EDCs) can impact the reproductive system by interfering with the hypothalamic-pituitary-gonadal (HPG) axis. Although in vitro testing methods have been developed to screen chemicals for endocrine disruption, extrapolation of in vitro responses to in vivo action shows inconsistent accuracy. The authors describe a tissue coculture of the fathead minnow (Pimephales promelas) HPG axis and liver (HPG-L) as a tissue explant model that mimics in vivo results. Brain (hypothalamus), pituitary, gonad, and liver tissue explants from adult fish were examined for function both individually and in coculture to determine combinations and conditions that could replicate in vivo behavior. Only cocultures had the ability to respond to an EDC, trenbolone, similarly to in vivo studies, based on estradiol, testosterone, and vitellogenin production trends, where lower exposure doses suppressed hormone production but higher doses increased production, resulting in distinctive U-shaped curves. These data suggest that a coculture system with all components of the HPG-L axis can be used as a link between in vitro and in vivo studies to predict endocrine system disruption in whole organisms. This tissue-based HPG-L system acts as a flexible deconstructed version of the in vivo system for better control and examination of the minute changes in system operation and response on EDC exposure with options to isolate, interrogate, and recombine desired components. Environ Toxicol Chem 2016;35:2530-2541. Published 2016 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. Published 2016 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.

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

PubMed Central

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

2010-01-01

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

Developmental toxicity of endocrine disrupters bisphenol A and vinclozolin in a terrestrial isopod.

PubMed

Lemos, M F L; van Gestel, C A M; Soares, A M V M

2010-08-01

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

ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

PubMed Central

Weiss, Bernard

2011-01-01

Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease

PubMed Central

2017-01-01

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants. PMID:28785583

Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae

PubMed Central

Zhang, Dan-hua; Zhou, En-xiang; Yang, Zhu-lin

2017-01-01

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption. PMID:28467477

Effects of copper on growth, metamorphosis and endocrine disruption of Bufo gargarizans larvae.

PubMed

Wang, Chao; Liang, Gang; Chai, Lihong; Wang, Hongyuan

2016-01-01

Chinese toad (Bufo gargarizans) tadpoles were exposed to copper (1, 6.4, 32 and 64μgL(-1) copper) from the beginning of larval period through completion of metamorphosis. We examined the effects of chronic copper exposure on mortality, growth, time to metamorphosis, tail resorption time, body size at the metamorphic climax (Gs 42) and completion of metamorphosis (Gs 46) and thyroid gland histology. In addition, type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. Our result showed that 6.4-64μgL(-1) copper concentration increased the mortality and inhibited the growth of B. gargarizans tadpoles. In addition, significant reduction in size at Gs 42 and a time delay to Gs 42 were observed at 6.4-64μgL(-1) copper treatments. Moreover, histological examinations have clearly revealed that 64μgL(-1) copper caused follicular cell hyperplasia in thyroid gland. According to real-time PCR results, exposure to 32 and 64μgL(-1) copper significantly up-regulated mRNA expression of Dio3, but down-regulated mRNA expression of TRα and TRβ mRNA level. We concluded that copper delayed amphibian metamorphosis through changing mRNA expression of Dio3, TRα and TRβ, which suggests that copper might have the endocrine-disrupting effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Update on the Mammalian Tier 1 Endocrine Disruptor Screening Protocols

EPA Science Inventory

The endocrine system provides a number of target sites that may be susceptible to disruption by environmental agents. In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system (http://w...

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

77 FR 12297 - Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening Program; Notice of Availability... chemicals to receive orders under the Endocrine Disruptor Screening Program by demonstrating the information... potential endocrine effects. Potentially affected entities identified by the North American Industrial...

The relative risk and its distribution of endocrine disrupting chemicals, pharmaceuticals and personal care products to freshwater organisms in the Bohai Rim, China.

PubMed

Zhang, Meng; Shi, Yajuan; Lu, Yonglong; Johnson, Andrew C; Sarvajayakesavalu, Suriyanarayanan; Liu, Zhaoyang; Su, Chao; Zhang, Yueqing; Juergens, Monika D; Jin, Xiaowei

2017-07-15

In this study, the risks to aquatic organisms posed by 12 commonly detected pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) that are extensively used in Bohai coastal region of China were examined. These were linear alkylbenzene sulfonate (LAS), nonylphenol (NP), diethylhexyl phthalate (DEHP), norfloxacin (NOR), sulfamethoxazole (SMX), erythromycin (ERY), bisphenol A (BPA), ofloxacin (OFL), carbamazepine (CBZ), naproxen (NPX), atenolol (ATL) and metoprolol (MET). Their relative risk was ranked based on the proximity between the medians of the reported effect concentrations and measured river or lake water concentrations. The surfactants (LAS) and endocrine disrupting chemicals NP (a breakdown product of the surfactant nonylphenol polyethoxylate) and DEHP (a plasticizer) were identified as posing the greatest risk from this range of chemicals. LAS had a hundred-fold higher risk than any of the pharmaceuticals. The highest risk ranked pharmaceuticals were all antibiotics. Zinc (Zn) and mercury (Hg) were added to the comparison as representative heavy metals. Zn posed a risk higher than all the organics. The risk posed by Hg was less than the surfactants but greater than the selected pharmaceuticals. Whereas LAS and DEHP could cause harmful effects to all the wildlife groups, NP and BPA posed the greatest risk to fish. Antibiotics showed the highest risk to algae. Spatial and temporal distributions of PPCPs and EDCs were conducted for risk identification, source analysis and seasonal change exploration. Municipal sewage effluent linked to urban areas was considered to be the major source of pharmaceuticals. With regard to seasonal influence the risk posed by LAS to the aquatic organisms was significantly affected by wet and dry seasonal change. The dilution effects were the common feature of LAS and ERY risks. The difference in LAS and ERY risk patterns along the rivers was mainly affected by the elimination process

Long-Term Effects of Environmental Endocrine Disruptors on Reproductive Physiology and Behavior

PubMed Central

Patisaul, Heather B.; Adewale, Heather B.

2009-01-01

It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs), either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates. PMID:19587848

CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

EPA Science Inventory

For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

The fate of pharmaceuticals and personal care products (PPCPs), endocrine disrupting contaminants (EDCs), metabolites and illicit drugs in a WWTW and environmental waters.

PubMed

Archer, Edward; Petrie, Bruce; Kasprzyk-Hordern, Barbara; Wolfaardt, Gideon M

2017-05-01

A large number of emerging contaminants (ECs) are known to persist in surface waters, and create pressure on wastewater treatment works (WWTW) for their effective removal. Although a large database for the levels of these pollutants in water systems exist globally, there is still a lack in the correlation of the levels of these pollutants with possible long-term adverse health effects in wildlife and humans, such as endocrine disruption. The current study detected a total of 55 ECs in WWTW influent surface water, 41 ECs in effluent, and 40 ECs in environmental waters located upstream and downstream of the plant. A list of ECs persisted through the WWTW process, with 28% of all detected ECs removed by less than 50%, and 18% of all ECs were removed by less than 25%. Negative mass balances of some pharmaceuticals and metabolites were observed within the WWTW, suggesting possible back-transformation of ECs during wastewater treatment. Three parental illicit drug compounds were detected within the influent of the WWTW, with concentrations ranging between 27.6 and 147.0 ng L -1 for cocaine, 35.6-120.6 ng L -1 for mephedrone, and 270.9-450.2 ng L -1 for methamphetamine. The related environmental risks are also discussed for some ECs, with particular reference to their ability to disrupt endocrine systems. The current study propose the potential of the pharmaceuticals carbamazepine, naproxen, diclofenac and ibuprofen to be regarded as priority ECs for environmental monitoring due to their regular detection and persistence in environmental waters and their possible contribution towards adverse health effects in humans and wildlife. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Joint acute and endocrine disruptive toxicities of malathion, cypermethrin and prochloraz to embryo-larval zebrafish, Danio rerio.

PubMed

Guo, Dongmei; Wang, Yanhua; Qian, Yongzhong; Chen, Chen; Jiao, Bining; Cai, Leiming; Wang, Qiang

2017-01-01

It remains a daunting challenge to determine ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) in environmental toxicology. In the present study, we investigated acute and endocrine disruptive toxicities of cypermethrin (CPM), malathion (MAL), prochloraz (PRO) and their binary mixtures of MAL + CPM and MAL + PRO to the early life stages of zebrafish. In the acute lethal toxicity test, three pesticides exhibited different levels of toxicity to zebrafish larvae, and the order of toxicity was as follows: CPM > PRO > MAL. The binary mixture of MAL + CPM displayed a synergistic effect on zebrafish larvae after exposure for 24, 48, 72 and 96 h. However, binary mixture of MAL + PRO showed an antagonistic effect. To evaluate the estrogenic effect, the expression of genes in the hypothalamic-pituitary-gonadal axis was assessed after zebrafish embryos were exposed to CPM, MAL, PRO and their binary mixtures from blastula stage (1 h post-fertilization, 1 hpf) to 14 dpf (14 d post-fertilization). Our data indicated that the transcription patterns of many key genes (vtg1, vtg2, era, erβ1, erβ2, cyp19a1a and cyp19a1b) were affected in hatched zebrafish after exposure to CPM, MAL and PRO. Moreover, following exposure to binary mixtures of 1000 μg/L MAL +4 μg/L CPM and 1000 μg/L MAL +900 μg/L PRO, the gene expressions were significantly changed compared with the individual pesticides. Our data provided a better understanding of bidirectional interactions of toxic response induced by these pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review.

PubMed

Lind, P Monica; Lind, Lars

2018-05-09

The purpose of this study was to review the epidemiological and experimental evidence linking background exposure to a selection of environmental endocrine-disrupting chemicals (EDCs) with diabetes and impaired glucose metabolism. The review summarises the literature on both cross-sectional and prospective studies in humans, as well as experimental in vivo and in vitro studies. The findings were subjected to evidence grading according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. We found >40 cross-sectional and seven prospective studies regarding EDCs and risk of diabetes. Taken together, there is moderate evidence for a relationship between exposure to dichlorodiphenyldichloroethylene (p,p'-DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane, and diabetes development. Regarding polychlorinated biphenyls (PCBs), it is likely that the rodent models used are not appropriate, and therefore the evidence is poorer than for p,p'-DDE. For other EDCs, such as bisphenol A, phthalates and perfluorinated chemicals, the evidence is scarce, since very few prospective studies exist. Brominated flame retardants do not seem to be associated with a disturbed glucose tolerance. Thus, evidence is accumulating that EDCs might be involved in diabetes development. Best evidence exists for p,p'-DDE. For other chemicals, both prospective studies and supporting animal data are still lacking.

Domain-Specific QSAR Models for Identifying Potential Estrogenic Activity of Phenols (FutureTox III)

EPA Science Inventory

Computational tools can be used for efficient evaluation of untested chemicals for their ability to disrupt the endocrine system. We have employed previously developed global QSAR models that were trained and validated on the ToxCast/Tox21 ER assay data for virtual screening of a...

Determination of free and conjugated forms of endocrine-disrupting chemicals in human biological fluids by GC-MS.

PubMed

Azzouz, Abdelmonaim; Rascón, Andrés J; Ballesteros, Evaristo

2016-06-01

Humans are exposed to hazardous substances including endocrine-disrupting chemicals (EDCs). These compounds have been associated with some diseases such as cancer and ascribed adverse effects on life-essential organs. The method, which allows the determination of both free and conjugated forms of EDCs, involves the liquid-liquid extraction from the sample with ethyl acetate, followed by its preconcentration and clean-up by SPE in a continuous system for the subsequent determination by GC-MS. The proposed method affords very low LODs and RSD. This allowed its successful application to the determination of EDCs in human urine, blood and breast milk. The most frequently founded were methylparaben, ethylparaben, bisphenol A and triclosan.

Effects of multiwalled carbon nanotubes and triclocarban on several eukaryotic cell lines: elucidating cytotoxicity, endocrine disruption, and reactive oxygen species generation

PubMed Central

2014-01-01

To date, only a few reports about studies on toxic effects of carbon nanotubes (CNT) are available, and their results are often controversial. Three different cell lines (rainbow trout liver cells (RTL-W1), human adrenocortical carcinoma cells (T47Dluc), and human adrenocarcinoma cells (H295R)) were exposed to multiwalled carbon nanotubes, the antimicrobial agent triclocarban (TCC) as well as the mixture of both substances in a concentration range of 3.13 to 50 mg CNT/L, 31.25 to 500 μg TCC/L, and 3.13 to 50 mg CNT/L + 1% TCC (percentage relative to carbon nanotubes concentration), respectively. Triclocarban is a high-production volume chemical that is widely used as an antimicrobial compound and is known for its toxicity, hydrophobicity, endocrine disruption, bioaccumulation potential, and environmental persistence. Carbon nanotubes are known to interact with hydrophobic organic compounds. Therefore, triclocarban was selected as a model substance to examine mixture toxicity in this study. The influence of multiwalled carbon nanotubes and triclocarban on various toxicological endpoints was specified: neither cytotoxicity nor endocrine disruption could be observed after exposure of the three cell lines to carbon nanotubes, but the nanomaterial caused intracellular generation of reactive oxygen species in all cell types. For TCC on the other hand, cell vitality of 80% could be observed at a concentration of 2.1 mg/L for treated RTL-W1 cells. A decrease of luciferase activity in the ER Calux assay at a triclocarban concentration of 125 μg/L and higher was observed. This effect was less pronounced when multiwalled carbon nanotubes were present in the medium. Taken together, these results demonstrate that multiwalled carbon nanotubes induce the production of reactive oxygen species in RTL-W1, T47Dluc, and H295R cells, reveal no cytotoxicity, and reduce the bioavailability and toxicity of the biocide triclocarban. PMID:25170332

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

PubMed

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

2013-01-01

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

Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays.

PubMed

Coady, Katherine K; Kan, H Lynn; Schisler, Melissa R; Gollapudi, B Bhaskar; Neal, Barbara; Williams, Amy; LeBaron, Matthew J

2014-08-01

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was evaluated in five in vitro screening assays to assess the potential for interaction with the androgen, estrogen and steroidogenesis pathways in the endocrine system. The assays were conducted to meet the requirements of the in vitro component of Tier 1 of the United States Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP), and included assays for estrogen receptor (ER) binding (rat uterine cytosol ER binding assay), ER-mediated transcriptional activation (HeLa-9903-ERα transactivation assay), androgen receptor (AR) binding (rat prostate cytosol AR binding assay), aromatase enzymatic activity inhibition (recombinant human CYP19 aromatase inhibition assay), and interference with steroidogenesis (H295R steroidogenesis assay). Results from these five assays demonstrated that 2,4-D does not have the potential to interact in vitro with the estrogen, androgen, or steroidogenesis pathways. These in vitro data are consistent with a corresponding lack of endocrine effects observed in apical in vivo animal studies, and thus provide important supporting data valuable in a comprehensive weight of evidence evaluation indicating a low potential of 2,4-D to interact with the endocrine system. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-07-01

Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby. Copyright © 2016 Elsevier B.V. All rights reserved.

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

USGS Publications Warehouse

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

2016-01-01

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

Use of sub-micron sized resin particles for removal of endocrine disrupting compounds and pharmaceuticals from water and wastewater.

PubMed

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

2017-01-01

Endocrine disrupting compounds (EDCs) and pharmaceuticals pose a challenge for water and wastewater treatment because they exist at very low concentrations in the presence of substances at much higher concentrations competing for adsorption sites. Sub-micron sized resin particles (approximately 300nm in diameter) (SMR) were tested to evaluate their potential as a treatment for EDCs including: 17-β estradiol (E2), 17-α ethinylestradiol (EE2), estrone (E1), bisphenol A (BPA), and diethylstilbestrol (DES) as well as 12 pharmaceuticals. SMR were able to remove 98% of spiked E2, 80% of EE2, 87% of BPA, and up to 97% of DES from water. For a 0.5ppm mixture of E2, EE2, E1, BPA and DES, the minimum removal was 24% (E2) and the maximum was 49% (DES). They were also able to remove the pharmaceuticals from deionized water and wastewater. Overall, SMR are a promising advanced treatment for removal of both EDCs and pharmaceuticals. Copyright © 2016. Published by Elsevier B.V.

76 FR 49473 - Petition to Maximize Practical Utility of List 1 Chemicals Screened Through EPA's Endocrine...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... Utility of List 1 Chemicals Screened Through EPA's Endocrine Disruptor Screening Program; Notice of... to the test orders issued under the Endocrine Disruptor Screening Program. DATES: Comments must be... testing of chemical substances for potential endocrine effects. Potentially affected entities, identified...

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

PubMed

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

2015-10-01

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

Endocrine Disruptors: A Potential Risk Factor for Gestational Diabetes Mellitus.

PubMed

Ehrlich, Shelley; Lambers, Donna; Baccarelli, Andrea; Khoury, Jane; Macaluso, Maurizio; Ho, Shuk-Mei

2016-11-01

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Increasing rates of people identifying as transgender presenting to Endocrine Services in the Wellington region.

PubMed

Delahunt, John W; Denison, Hayley J; Sim, Dalice A; Bullock, Jemima J; Krebs, Jeremy D

2018-01-19

Overseas clinics specialising in management of transgender people have noted a marked increase in the numbers of people requesting therapy in the last few years. No data has been presented for New Zealand. We therefore reviewed the number of transgender people seen in the Wellington Endocrine Service to assess if the pattern was similar and assess any potential problems for service delivery. Using hospital records, we reviewed the new appointments of people who were referred for advice on gender reassignment and seen in the Wellington Endocrine Service from 1990 to 2016. In total, 438 people who identified as transgender attended the clinic at least once in this period. There has been a progressive increase in number of people identifying as transgender presenting to the clinic, particularly since 2010. In addition to increasing overall numbers, there has been in particular increase in referrals for people under age 30, as well as an increasing proportion of people requesting female-to-male (FtM) therapy so that it is now approaching the number of people requesting male-to-female therapy (MtF). The pattern observed is comparable to changes reported overseas. These changes have practical consequences for the delivery of both secondary and primary level healthcare, requiring an increased focus on clinical coordination between the relevant medical services and their links to the primary services sector.

Elucidating the Links Between Endocrine Disruptors and Neurodevelopment

PubMed Central

Blawas, Ashley M.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.

2015-01-01

Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811

Introduction to the Endocrine System

MedlinePlus

... by downloading the Hormone Health Network's 3D Patient Education mobile app ! The endocrine system is a series of glands that produce and ... Network partners with other organizations to further patient education on hormone related issues. Network Sponsors The Hormone Health ... Disrupting Chemicals (EDCs) Steroid and Hormone ...

Effect-directed identification of endocrine disruptors in plastic baby teethers.

PubMed

Berger, Elisabeth; Potouridis, Theodoros; Haeger, Astrid; Püttmann, Wilhelm; Wagner, Martin

2015-11-01

Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved. Copyright © 2015 John Wiley & Sons, Ltd.

White rot fungi and advanced combined biotechnology with nanomaterials: promising tools for endocrine-disrupting compounds biotransformation.

PubMed

Huang, Danlian; Guo, Xueying; Peng, Zhiwei; Zeng, Guangming; Xu, Piao; Gong, Xiaomin; Deng, Rui; Xue, Wenjing; Wang, Rongzhong; Yi, Huan; Liu, Caihong

2018-08-01

Endocrine-disrupting compounds (EDCs) can interfere with endocrine systems and bio-accumulate through the food chain and even decrease biodiversity in contaminated areas. This review discusses a critical overview of recent research progress in the biotransformation of EDCs (including polychlorinated biphenyl and nonylphenol, and suspected EDCs such as heavy metals and sulfonamide antibiotics) by white rot fungi (WRF) based on techniques with an emphasis on summarizing and analyzing fungal molecular, metabolic and genetic mechanisms. Not only intracellular metabolism which seems to perform essential roles in the ability of WRF to transform EDCs, but also advanced applications are deeply discussed. This review mainly reveals the removal pathway of heavy metal and antibiotic pollutants because the single pollution almost did not exist in a real environment while the combined pollution has become more serious and close to people's life. The trends in WRF technology and its related advanced applications which use the combined technology, including biocatalysis of WRF and adsorption of nanomaterials, to degrade EDCs have also been introduced. Furthermore, challenges and future research needs EDCs biotransformation by WRF are also discussed. This research, referring to metabolic mechanisms and the combined technology of WRF with nanomaterials, undoubtedly contributes to the applications of biotechnology. This review will be of great benefit to an understanding of the trends in biotechnology for the removal of EDCs.

Epigenetic impacts of endocrine disruptors in the brain☆

PubMed Central

Walker, Deena M.; Gore, Andrea C.

2017-01-01

The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. PMID:27663243

A novel ICK mutation causes ciliary disruption and lethal endocrine-cerebro-osteodysplasia syndrome.

PubMed

Oud, Machteld M; Bonnard, Carine; Mans, Dorus A; Altunoglu, Umut; Tohari, Sumanty; Ng, Alvin Yu Jin; Eskin, Ascia; Lee, Hane; Rupar, C Anthony; de Wagenaar, Nathalie P; Wu, Ka Man; Lahiry, Piya; Pazour, Gregory J; Nelson, Stanley F; Hegele, Robert A; Roepman, Ronald; Kayserili, Hülya; Venkatesh, Byrappa; Siu, Victoria M; Reversade, Bruno; Arts, Heleen H

2016-01-01

Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) with polydactyly syndromes, and hydrolethalus syndrome. In this study, we present a novel homozygous ICK mutation in a fetus with ECO syndrome and compare the effect of this mutation with the previously reported ICK variant on ciliogenesis and cilium morphology. Through homozygosity mapping and whole-exome sequencing, we identified a second variant (c.358G > T; p.G120C) in ICK in a Turkish fetus presenting with ECO syndrome. In vitro studies of wild-type and mutant mRFP-ICK (p.G120C and p.R272Q) revealed that, in contrast to the wild-type protein that localizes along the ciliary axoneme and/or is present in the ciliary base, mutant proteins rather enrich in the ciliary tip. In addition, immunocytochemistry revealed a decreased number of cilia in ICK p.R272Q-affected cells. Through identification of a novel ICK mutation, we confirm that disruption of ICK causes ECO syndrome, which clinically overlaps with the spectrum of ciliopathies. Expression of ICK-mutated proteins result in an abnormal ciliary localization compared to wild-type protein. Primary fibroblasts derived from an individual with ECO syndrome display ciliogenesis defects. In aggregate, our findings are consistent with recent reports that show that ICK regulates ciliary biology in vitro and in mice, confirming that ECO syndrome is a severe ciliopathy.

Ecdysone receptor agonism leading to lethal molting disruption in arthropods: Review and adverse outcome pathway development

EPA Science Inventory

Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, s...

Surface molecular imprinting onto fluorescein-coated magnetic nanoparticlesvia reversible addition fragmentation chain transfer polymerization: A facile three-in-one system for recognition and separation of endocrine disrupting chemicals

NASA Astrophysics Data System (ADS)

Li, Ying; Dong, Cunku; Chu, Jia; Qi, Jingyao; Li, Xin

2011-01-01

In this study, we present a general protocol for the making of surface-imprinted magnetic fluorescence beads viareversible addition-fragmentation chain transfer polymerization. The resulting composites were characterized by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and energy dispersive spectroscopy. The as-synthesized beads exhibited homogeneous polymer films (thickness of about 5.7 nm), spherical shape, high fluorescence intensity and magnetic property (Magnetization (Ms) = 3.67 emu g-1). The hybrids bind the original template 17β-estradiol with an appreciable selectivity over structurally related compounds. In addition, the resulting hybrids performed without obvious deterioration after five repeated cycles. This study therefore demonstrates the potential of molecularly imprinted polymers for the recognition and separation of endocrine disrupting chemicals.In this study, we present a general protocol for the making of surface-imprinted magnetic fluorescence beads viareversible addition-fragmentation chain transfer polymerization. The resulting composites were characterized by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and energy dispersive spectroscopy. The as-synthesized beads exhibited homogeneous polymer films (thickness of about 5.7 nm), spherical shape, high fluorescence intensity and magnetic property (Magnetization (Ms) = 3.67 emu g-1). The hybrids bind the original template 17β-estradiol with an appreciable selectivity over structurally related compounds. In addition, the resulting hybrids performed without obvious deterioration after five repeated cycles. This study therefore demonstrates the potential of molecularly imprinted polymers for the recognition and separation of endocrine disrupting chemicals. Electronic

An Isomer-Specific Approach to Endocrine-Disrupting Nonylphenol in Infant Food.

PubMed

Günther, Klaus; Räcker, Torsten; Böhme, Roswitha

2017-02-15

Nonylphenols (NPs) are persistent endocrine disruptors that are priority hazardous substances of the European Union Water Framework Directive. Their presence in the environment has caused growing concern regarding their impact on human health. Recent studies have shown that nonylphenol is ubiquitous in commercially available foodstuffs and is also present in human blood. The isomer distribution of 4-nonylphenol was analyzed by gas chromatography - mass spectrometry in 44 samples of infant food. Our study shows that the distribution of nonylphenol isomers is dependent on the foodstuff analyzed. Although some isomer groups prevail, different distributions are frequent. Variations are even found in the same food group. Nonylphenol is a complex mixture of isomers, and the estrogenic potentials of each of these isomers are very different. Consequently, to determine the potential toxicological impact of NP in food, an isomer-specific approach is necessary.

An environmentally relevant endocrine-disrupting antiandrogen, vinclozolin, affects calling behavior of male Xenopus laevis.

PubMed

Hoffmann, Frauke; Kloas, Werner

2010-09-01

Vinclozolin (VIN) is an antiandrogenic model substance as well as a common fungicide that can affect the endocrine system of vertebrates. The objective of this study was to investigate how VIN affects mate calling behavior of South African clawed frogs (Xenopus laevis) and whether it is effective at environmentally relevant concentrations. Male X. laevis were injected with human chorionic gonadotropin (hCG) to stimulate their androgen-controlled mate calling behavior and were treated with VIN at concentrations of 10(-6), 10(-8) and 10(-10)M. VIN at 10(-6)M reduced calling activity. Furthermore, the vocalization composition of VIN-treated X. laevis was altered. The call types advertisement calls and chirping are uttered by reproductively active males, whereas the call types growling, ticking, and rasping indicate a sexually unaroused state of a male. VIN at any of the tested concentrations led to a decrease in utterance of calls, which indicate a sexually aroused state of the males, and an increase in relative proportions of calls, indicating a sexually unaroused state of the males. Additionally, the mean duration of clicks and the number of accentuated clicks during the advertisement calls decreased at all concentrations of VIN. No significant differences were observed in any other temporal or spectral calling parameters between the treatments. This study illustrates that exposure to the antiandrogen VIN might result in a reduced reproductive success by altering mate calling behavior of X. laevis. Moreover, it suggests that the behavioral parameters examined in this study can be used as sensitive biomarkers for detecting antiandrogenic endocrine disrupting compounds in amphibians. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

PubMed

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

2015-04-01

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

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

PubMed Central

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

2008-01-01

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

Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor-and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metamorphosis.

PubMed

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

2008-02-01

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

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

PubMed

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Cosmetics as endocrine disruptors: are they a health risk?

PubMed

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

2015-12-01

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

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

PubMed Central

2010-01-01

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

Prepubertal subchronic exposure to soy milk and glyphosate leads to endocrine disruption.

PubMed

Nardi, Jessica; Moras, Patricia Bonamigo; Koeppe, Carina; Dallegrave, Eliane; Leal, Mirna Bainy; Rossato-Grando, Luciana Grazziotin

2017-02-01

Lactose intolerance is characterized by low or inexistent levels of lactase, and the main treatment consists of dietary changes, especially replacing dairy milk by soy milk. Soy contains phytoestrogens, substances with known estrogenic activity, besides, glyphosate-based herbicides are extensively used in soy crops, being frequently a residue in soy beans, bringing to a concern regarding the consumption of soy-based products, especially for children in breastfeeding period with lactose intolerance. This study evaluated the pubertal toxicity of a soy milk rich feeding (supplemented or not with glyphosate, doses of 50 and 100 mg/kg) during prepubertal period in male rats. Endocrine disruption was observed through decrease in testosterone levels, decrease in Sertoli cell number and increase in the percentage of degenerated Sertoli and Leydig cells in animals receiving soy milk supplemented with glyphosate (both doses) and in animals treated only with soy milk. Animals treated with soy milk with glyphosate (both doses) showed decrease spermatids number and increase of epididymal tail mass compared to control, and decrease in the diameter of seminiferous tubules compared to soy milk control group. Animals receiving soy milk supplemented with 100 mg/kg glyphosate showed decrease in round spermatids and increase in abnormal sperm morphology, compared to control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine Profiling and Prioritization of Environmental Chemicals Using ToxCast Data

PubMed Central

Reif, David M.; Martin, Matthew T.; Tan, Shirlee W.; Houck, Keith A.; Judson, Richard S.; Richard, Ann M.; Knudsen, Thomas B.; Dix, David J.; Kavlock, Robert J.

2010-01-01

Background The prioritization of chemicals for toxicity testing is a primary goal of the U.S. Environmental Protection Agency (EPA) ToxCast™ program. Phase I of ToxCast used a battery of 467 in vitro, high-throughput screening assays to assess 309 environmental chemicals. One important mode of action leading to toxicity is endocrine disruption, and the U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) has been charged with screening pesticide chemicals and environmental contaminants for their potential to affect the endocrine systems of humans and wildlife. Objective The goal of this study was to develop a flexible method to facilitate the rational prioritization of chemicals for further evaluation and demonstrate its application as a candidate decision-support tool for EDSP. Methods Focusing on estrogen, androgen, and thyroid pathways, we defined putative endocrine profiles and derived a relative rank or score for the entire ToxCast library of 309 unique chemicals. Effects on other nuclear receptors and xenobiotic metabolizing enzymes were also considered, as were pertinent chemical descriptors and pathways relevant to endocrine-mediated signaling. Results Combining multiple data sources into an overall, weight-of-evidence Toxicological Priority Index (ToxPi) score for prioritizing further chemical testing resulted in more robust conclusions than any single data source taken alone. Conclusions Incorporating data from in vitro assays, chemical descriptors, and biological pathways in this prioritization schema provided a flexible, comprehensive visualization and ranking of each chemical’s potential endocrine activity. Importantly, ToxPi profiles provide a transparent visualization of the relative contribution of all information sources to an overall priority ranking. The method developed here is readily adaptable to diverse chemical prioritization tasks. PMID:20826373

Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption.

PubMed

Kugathas, Subramaniam; Audouze, Karine; Ermler, Sibylle; Orton, Frances; Rosivatz, Erika; Scholze, Martin; Kortenkamp, Andreas

2016-04-01

There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects. We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis. Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket. The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances-o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)-showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor. Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine-disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action. Kugathas S, Audouze K, Ermler S, Orton F, Rosivatz E

Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption

PubMed Central

Kugathas, Subramaniam; Audouze, Karine; Ermler, Sibylle; Orton, Frances; Rosivatz, Erika; Scholze, Martin; Kortenkamp, Andreas

2015-01-01

Background: There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects. Objectives: We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis. Methods: Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket. Results: The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances—o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)—showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor. Conclusions: Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine-disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action

The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buoso, Erica; Galasso, Marilisa; Ronfani, Melania

We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity andmore » protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.« less

Subchronic exposure to kalach 360 SL-induced endocrine disruption and ovary damage in female rats.

PubMed

Hamdaoui, Latifa; Naifar, Manel; Rahmouni, Fatma; Harrabi, Bahira; Ayadi, Fatma; Sahnoun, Zouheir; Rebai, Tarek

2018-02-01

Kalach 360 SL (KL), glyphosate (G) surfactant-based herbicides, is a systemic herbicide effective against weeds. It was applied in agriculture in Tunisia and throughout the world, which can represent a risk to non-target organisms. The aim of this study was to investigate the morphological and biochemical aspects of ovary injury after exposure to KL. Female Wistar rats were divided into three groups: group 1 was used as a control; group 2 orally received 0.07 ml of KL, (126 mg of G/kg) and group 3 orally received 0.175 ml of KL (315 mg of G/kg) each day for 60 days. The subchronic exposure of KL induces impaired folliculogenesis, ovary development, decreased oestrogen secretion, promoted oxidative stress and impairments of ovary histological aspects. Histological finding shows necrosis cell, vacuolisation of follicles, dissociated oocytes and granulosa cell, associated with several atretic follicles. We conclude that KL induces endocrine disruption and ovary damage in female rats.

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

PubMed Central

Cheung, Leonard Y. M.; Okano, Hideyuki

2016-01-01

The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. PMID:27616671

Evaluating Endocrine Disruption Activity of Deposits on Firefighting Gear Using a Sensitive and High Throughput Screening Method.

PubMed

Stevenson, Max; Alexander, Barbara; Baxter, C Stuart; Leung, Yuet-Kin

2015-12-01

Adverse health outcomes related to exposure to endocrine disrupting chemicals, including increased incidences of coronary heart disease, prostate and testicular cancers, and congenital disabilities, have been reported in firefighters or their offspring. We, therefore, measured the estrogenic and antiestrogenic activity of extracts of used firefighter gear to assess exposure to these agents. Extracts and known chemical contaminants were examined for estrogenicity and antiestrogenicity in yeast cells expressing the estrogen receptor. Most extracts of used gear and phthalate diesters detectable on this gear displayed strong antiestrogenic effects. Notably, new glove and hood extracts showed significant estrogenic activity. Overall, our data suggest that firefighters are exposed to both estrogenic and antiestrogenic agents, possibly phthalates that may lead to health risks observed in this occupation as a result of perturbation of hormone homeostasis.

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...

Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using lindane.

PubMed

Matsuura, Ikuo; Saitoh, Tetsuji; Tani, Einosuke; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru; Ikeda, Yasuo

2005-12-01

A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases

Development of a multiresidue method for the determination of endocrine disrupters in fish fillet using gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Munaretto, Juliana S; Ferronato, Giovana; Ribeiro, Lucila C; Martins, Manoel L; Adaime, Martha B; Zanella, Renato

2013-11-15

Endocrine Disrupter Compounds (EDCs) are responsible for alterations in the endocrine system functions. Aquatic organisms are able to accumulate EDCs residues, being the major source of contamination for top predators and human consumers. This study aimed to develop and validate a method for the determination of 40 EDCs in fish fillet using modified QuEChERS and Gas Chromatography coupled with Mass Spectrometry in tandem (GC-MS/MS). A factorial design was used to optimize the extraction procedure. Method validation presented recoveries from 70.1% to 120.0% with RSD<20% and method limit of detection ranged from 0.3 to 7.5 µg kg(-1), showing good accuracy and precision. This method was successfully applied to the analysis of fish fillet from different species and residues of bisphenol A, chlorpyrifos and bifenthrin were detected. The proposed method proved to be effective for the determination of EDCs in fish fillet at very low concentration levels. © 2013 Elsevier B.V. All rights reserved.

A Method for the Determination of Genetic Sex in the Fathead Minnow, Pimephales promelas, to Support Testing of Endocrine-active Chemicals

EPA Science Inventory

Fathead minnows are used as a model fish species for the characterization of the endocrine-disrupting potential of environmental contaminants. This research describes the development of a PCR method that can determine the genetic sex in this species. This method, when incorpora...

Transcriptomic, cellular and life-history responses of Daphnia magna chronically exposed to benzotriazoles: Endocrine-disrupting potential and molting effects

PubMed Central

Giraudo, Maeva; Douville, Mélanie; Cottin, Guillaume; Houde, Magali

2017-01-01

Benzotriazoles (BZTs) are ubiquitous aquatic contaminants used in a wide range of industrial and domestic applications from aircraft deicers to dishwasher tablets. Acute toxicity has been reported in aquatic organisms for some of the BZTs but their mode of action remains unknown. The objectives of this study were to evaluate the transcriptomic response of D. magna exposed to sublethal doses of 1H-benzotriazole (BTR), 5-methyl-1H-benzotriazole (5MeBTR) and 5-chloro-1H-benzotriazole (5ClBTR) using RNA-sequencing and quantitative real-time PCR. Cellular and life-history endpoints (survival, number of neonates, growth) were also investigated. Significant effects on the molting frequency were observed after 21-d exposure to 5MeBTR and 5ClBTR. No effects on molting frequency were observed for BTR but RNA-seq results indicated that this BZT induced the up-regulation of genes coding for cuticular proteins, which could have compensated the molting disruption. Molting in cladocerans is actively controlled by ecdysteroid hormones. Complementary short-term temporal analysis (4- and 8-d exposure) of the transcription of genes related to molting and hormone-mediated processes indicated that the three compounds had specific modes of action. BTR induced the transcription of genes involved in 20-hydroxyecdysone synthesis, which suggests pro-ecdysteroid properties. 5ClBTR exposure induced protein activity and transcriptional levels of chitinase enzymes, associated with an impact on ecdysteroid signaling pathways, which could explain the decrease in molt frequency. Finally, 5MeBTR seemed to increase molt frequency through epigenetic processes. Overall, results suggested that molting effects observed at the physiological level could be linked to endocrine regulation impacts of BZTs at the molecular level. PMID:28196088

Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabiting Northeast U.S. national wildlife refuge waters: A reconnaissance study.

PubMed

Iwanowicz, L R; Blazer, V S; Pinkney, A E; Guy, C P; Major, A M; Munney, K; Mierzykowski, S; Lingenfelser, S; Secord, A; Patnode, K; Kubiak, T J; Stern, C; Hahn, C M; Iwanowicz, D D; Walsh, H L; Sperry, A

2016-02-01

Intersex as the manifestation of testicular oocytes (TO) in male gonochoristic fishes has been used as an indicator of estrogenic exposure. Here we evaluated largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) form 19 National Wildlife Refuges (NWRs) in the Northeast U.S. inhabiting waters on or near NWR lands for evidence of estrogenic endocrine disruption. Waterbodies sampled included rivers, lakes, impoundments, ponds, and reservoirs. Here we focus on evidence of endocrine disruption in male bass evidenced by gonad histopathology including intersex or abnormal plasma vitellogenin (Vtg) concentrations. During the fall seasons of 2008-2010, we collected male smallmouth bass (n=118) from 12 sites and largemouth bass (n=173) from 27 sites. Intersex in male smallmouth bass was observed at all sites and ranged from 60% to 100%; in male largemouth bass the range was 0-100%. Estrogenicity, as measured using a bioluminescent yeast reporter, was detected above the probable no effects concentration (0.73ng/L) in ambient water samples from 79% of the NWR sites. Additionally, the presence of androgen receptor and glucocorticoid receptor ligands were noted as measured via novel nuclear receptor translocation assays. Mean plasma Vtg was elevated (>0.2mg/ml) in male smallmouth bass at four sites and in male largemouth bass at one site. This is the first reconnaissance survey of this scope conducted on US National Wildlife Refuges. The baseline data collected here provide a necessary benchmark for future monitoring and justify more comprehensive NWR-specific studies. Published by Elsevier Inc.

Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabiting Northeast U.S. National Wildlife Refuge waters: A reconnaissance study

USGS Publications Warehouse

Iwanowicz, Luke R.; Blazer, Vicki S.; Pinkney, A.E.; Guy, C.P.; Major, A.M.; Munney, K.; Mierzykowski, S.; Lingenfelser, S.; Secord, A.; Patnode, K.; Kubiak, T.J.; Stern, C.; Hahn, Cassidy M.; Iwanowicz, Deborah; Walsh, Heather L.; Sperry, Adam J.

2016-01-01

Intersex as the manifestation of testicular oocytes (TO) in male gonochoristic fishes has been used as an indicator of estrogenic exposure. Here we evaluated largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) form 19 National Wildlife Refuges (NWRs) in the Northeast U.S. inhabiting waters on or near NWR lands for evidence of estrogenic endocrine disruption. Waterbodies sampled included rivers, lakes, impoundments, ponds, and reservoirs. Here we focus on evidence of endocrine disruption in male bass evidenced by gonad histopathology including intersex or abnormal plasma vitellogenin (Vtg) concentrations. During the fall seasons of 2008–2010, we collected male smallmouth bass (n=118) from 12 sites and largemouth bass (n=173) from 27 sites. Intersex in male smallmouth bass was observed at all sites and ranged from 60% to 100%; in male largemouth bass the range was 0–100%. Estrogenicity, as measured using a bioluminescent yeast reporter, was detected above the probable no effects concentration (0.73 ng/L) in ambient water samples from 79% of the NWR sites. Additionally, the presence of androgen receptor and glucocorticoid receptor ligands were noted as measured via novel nuclear receptor translocation assays. Mean plasma Vtg was elevated (>0.2 mg/ml) in male smallmouth bass at four sites and in male largemouth bass at one site. This is the first reconnaissance survey of this scope conducted on US National Wildlife Refuges. The baseline data collected here provide a necessary benchmark for future monitoring and justify more comprehensive NWR-specific studies.

Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

PubMed

Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

2016-01-01

Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment

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

PubMed

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

2014-09-01

Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive. Copyright © 2014 Elsevier B.V. All rights reserved.

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

PubMed Central

Stel, Jente

2015-01-01

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans. PMID:26241072

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.

PubMed

Stel, Jente; Legler, Juliette

2015-10-01

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

TRAINING AND TECHNOLOGY TRANSFER OF ORD-DEVELOPED MOLECULAR BIOLOGY-BASED TOOLS: 1. ENDOCRINE DISRUPTING CHEMICAL FATHEAD MINNOW BIOASSAY; 2. MICROBIAL SOURCE TRACKING METHODS; 3. FIELD IDENTIFICATION OF GENETICALLY MODIFIED CROP PLANTS

EPA Science Inventory

Region 9 RSL and ORD/NERL scientists developed a course for the RSC (Regional Science Council)-sponsored training class on Molecular Biology Concepts. The training will take place as part of the technology transfer of a fish EDC (endocrine disrupting chemical) bioassay to the Reg...

Amphibian metamorphosis as a model for studying endocrine disruption on vertebrate development: effect of bisphenol A on thyroid hormone action.

PubMed

Heimeier, Rachel A; Shi, Yun-Bo

2010-09-01

Thyroid hormone (TH) is essential for proper development in vertebrates. TH deficiency during gestation and early postnatal development produces severe neurological, skeletal, metabolism and growth abnormalities. It is therefore important to consider environmental chemicals that may interfere with TH signaling. Exposure to environmental contaminants that disrupt TH action may underlie the increasing incidence of human developmental disorders worldwide. One contaminant of concern is the xenoestrogen bisphenol A (BPA), a chemical widely used to manufacture polycarbonate plastics and epoxy resins. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. As TH action at the cellular level is highly conserved across vertebrate species, amphibian metamorphosis serves as an important TH-dependent in vivo vertebrate model for studying potential contributions of BPA toward human developmental disorders. Using Xenopus laevis as a model, we and others have demonstrated the inhibitory effects of BPA exposure on metamorphosis. Genome-wide gene expression analysis revealed that surprisingly, BPA primarily targets the TH-signaling pathway essential for metamorphosis in Xenopus laevis. Given the importance of the genomic effects of TH during metamorphosis and the conservation in its regulation in higher vertebrates, these observations suggest that the effect of BPA in human embryogenesis is through the inhibition of the TH pathway and warrants further investigation. Our findings further argue for the critical need to use in vivo animal models coupled with systematic molecular analysis to determine the developmental effects of endocrine disrupting compounds. Published by Elsevier Inc.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System

PubMed Central

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed. PMID:29615977

Dermatologic manifestations of endocrine disorders

PubMed Central

Lause, Michael; Kamboj, Alisha

2017-01-01

The skin serves as a window for clinicians to understand, diagnose, and monitor endocrine disease. Dermatologic manifestations of endocrinopathies contribute significantly to an individual’s health and quality of life. In this review, we outline various disorders of the hypothalamic-pituitary axis, thyroid gland, pancreas, adrenal gland, and androgen axis as well as hereditary endocrine syndromes. In acromegaly, glycosaminoglycan deposition contributes to a thickening of skin and soft tissue, which manifests as coarsening and enlargement of facial and acral structures. Stimulation of the thyrotropin receptor in hyperthyroidism results in mesenchymal tissue proliferation and consequent pretibial myxedema; other associated cutaneous features include onycholysis, and hyperhidrosis. Individuals with hypothyroidism exhibit cold, dry skin and brittle hair as well as a jaundice-like appearance due to carotene excess. The cutaneous features of diabetes mellitus (DM), mediated to a large extent by hyperglycemia and hyperinsulinemia, include necrobiosis lipoidica diabeticorum (NLD), diabetic dermopathy, and acanthosis nigricans. Pediatric patients with Cushing’s syndrome almost invariably present with truncal obesity and growth retardation; disruption of collagen formation and the catabolic effects of hypercortisolism result in skin atrophy and purple abdominal striae. In patients with Addison’s disease, generalized hyperpigmentation, secondary to elevated levels of melanocyte-stimulating hormone (MSH), is most prominent in sun-exposed areas. Due to hyperandrogenism, individuals with polycystic ovarian syndrome (PCOS) often exhibit hirsutism, acne vulgaris, and androgenetic alopecia. In multiple endocrine neoplasia (MEN) syndromes, specific gene mutations may lead to angiofibromas, lichen amyloidosis, and ganglioneuromas. Disruptions of immune regulation result in autoimmune polyglandular syndromes (APS) and associated clinical features including chronic mucocutaneous

Effects of Alcohol on the Endocrine System

PubMed Central

Rachdaoui, Nadia; Sarkar, Dipak K.

2013-01-01

Synopsis The endocrine system ensures a proper communication between various organs of the body to maintain a constant internal environment. The endocrine system also plays an essential role in enabling the body to respond and appropriately cope with changes in the internal or external environments, such as respond to stress and injury. These functions of the endocrine system to maintain body homeostasis are aided by its communication with the nervous system, immune system and body’s circadian mechanism. Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. PMID:24011889

ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

EPA Science Inventory

Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

CUMULATIVE DEVELOPMENTAL EFFECTS OF ENDOCRINE DISRUPTERS: SYNERGY OR ADDITIVITY?

EPA Science Inventory

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

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

USGS Publications Warehouse

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

2016-01-01

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

Neuroendocrine Disruption: More than Hormones are Upset

PubMed Central

Waye, Andrew; Trudeau, Vance L.

2011-01-01

Only a small proportion of the published research on endocrine-disrupting chemicals (EDC) directly examined effects on neuroendocrine processes. There is an expanding body of evidence that anthropogenic chemicals exert effects on neuroendocrine systems and that these changes might impact peripheral organ systems and physiological processes. Neuroendocrine disruption extends the concept of endocrine disruption to include the full breadth of integrative physiology (i.e., more than hormones are upset). Pollutants may also disrupt numerous other neurochemical pathways to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. Several examples are presented in this review, from both vertebrates and invertebrates, illustrating that diverse environmental pollutants including pharmaceuticals, organochlorine pesticides, and industrial contaminants have the potential to disrupt neuroendocrine control mechanisms. While most investigations on EDC are carried out with vertebrate models, an attempt is also made to highlight the importance of research on invertebrate neuroendocrine disruption. The neurophysiology of many invertebrates is well described and many of their neurotransmitters are similar or identical to those in vertebrates; therefore, lessons learned from one group of organisms may help us understand potential adverse effects in others. This review argues for the adoption of systems biology and integrative physiology to address the effects of EDC. Effects of pulp and paper mill effluents on fish reproduction are a good example of where relatively narrow hypothesis testing strategies (e.g., whether or not pollutants are sex steroid mimics) have only partially solved a major problem in environmental biology. It is clear that a global, integrative physiological approach, including improved understanding of neuroendocrine control mechanisms, is warranted to fully understand the impacts of pulp and paper mill effluents

PROGRESS IN THE OECD WORK ON ENDOCRINE DISRUPTORS TESTING AND ASSESSMENT FOR ENVIRONMENTAL SPECIES

EPA Science Inventory

The OECD Special Activity on endocrine disruptors testing and assessment (EDTA) started in 1996 at the request of member countries and industry with the objective to develop test methods for the detection and characterization of endocrine disrupting chemicals. The purpose of the ...

Endocrine disrupting chemicals in New Orleans surface waters and Mississippi Sound sediments.

PubMed

Wang, Guangdi; Ma, Peng; Zhang, Qiang; Lewis, John; Lacey, Michelle; Furukawa, Yoko; O'Reilly, S E; Meaux, Shelley; McLachlan, John; Zhang, Shaoyuan

2012-05-01

Endocrine disrupting compounds (EDCs), represented by steroid hormones, organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and bisphenol A have been determined in four sediment cores from the Gulf of Mexico, from New Orleans surface water (Lake Pontchartrain and Mississippi River), and from the influent and effluent of a New Orleans municipal sewage treatment plant. During the five-month monitoring of selected EDCs in the Mississippi River (MR) and Lake Pontchartrain (LP) in 2008, 21 of 29 OCPs in MR and 17 of 29 OCPs in LP were detected; bisphenol A was detected in all of the samples. Steroid hormones (estrone, 17β-estradiol and 17α-ethinylestradiol) were detected occasionally. Total EDC (OCPs + PCBs + steroid hormones + bisphenol A) concentrations in the two surface water samples were found to vary from 148 to 1112 ng L(-1). Strong correlation of the distribution of total OCPs, total PCBs and total EDCs between solid and water phases was found in LP, while moderate or no correlation existed in MR. OCPs, PCBs, steroid hormones, and bisphenol A were all detected in the ocean sediments, and total EDCs were measured in the range of 77 to 1796 ng g(-1) dry sediment weight. The EDCs were also found in untreated and treated municipal sewage samples with a removal efficiency of 83% for OCPs but no removal efficiency for 17α-ethinylestradiol.

Association between Endocrine Disrupting Phenols in Colostrums and Maternal and Infant Health

PubMed Central

Yi, B.; Kim, C.; Park, M.; Han, Y.; Park, J. Y.; Yang, M.

2013-01-01

Bisphenol A (BPA) and alkylphenols (APs) are well-known endocrine disrupting chemicals (EDCs) which may threat the next generations' health. We performed biomonitoring of these phenols in colostrums to assess risk of the phenols in breast-fed neonates. Study subjects were the lactating mothers who delivered babies within 2 weeks (N = 325; 30.67 ± 3.45 years) and their neonates (N = 326; embryonic period, 39.1 ± 1.5 weeks). BPA, nonylphenol (NP), and octylphenol (OP) in colostrums were quantified with LC/MS/MS. Information for environmental exposure sources of the phenols was obtained by questionnaires. As results, median level of BPA in colostrums was 7.8 ng/mL, while most NP or OP was not detected. Regarding health risks of phenols, levels of total NP in colostrums were elevated among sick mothers with toxemia, thyroid disorders, gastritis, and so forth than health mothers (3.51 ± 4.98 versus 2.04 ± 3.71 ng/mL, P = 0.02). Dairy products intake and detergents use were positively correlated with total BPA levels (Ps < 0.05). In conclusion, we estimate most neonates who are exposed to BPA rather than NP or OP via colostrums and recommend continuous biomonitoring of the phenols to clarify their suspected health risk on neonates and pregnant or gestation mothers. PMID:23737772

The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis.

PubMed

Ball, Lonnele J; Palesh, Oxana; Kriegsfeld, Lance J

2016-10-01

Most physiological processes in the brain and body exhibit daily (circadian) rhythms coordinated by an endogenous master clock located in the suprachiasmatic nucleus of the hypothalamus that are essential for normal health and functioning. Exposure to sunlight during the day and darkness at night optimally entrains biological rhythms to promote homeostasis and human health. Unfortunately, a major consequence of the modern lifestyle is increased exposure to sun-free environments during the day and artificial lighting at night. Additionally, behavioral disruptions to circadian rhythms (ie, repeated transmeridian flights, night or rotating shift work, or sleep disturbances) have a profound influence on health and have been linked to a number of pathological conditions, including endocrine-dependent cancers. Specifically, night shift work has been identified as a significant risk factor for breast cancer in industrialized countries. Several mechanisms have been proposed by which shift work-induced circadian disruptions promote cancer. In this review, we examine the importance of the brain-body link through which circadian disruptions contribute to endocrine-dependent diseases, including breast carcinogenesis, by negatively impacting neuroendocrine and neuroimmune cells, and we consider preventive measures directed at maximizing circadian health.

The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis

PubMed Central

Ball, Lonnele J.; Palesh, Oxana

2016-01-01

Most physiological processes in the brain and body exhibit daily (circadian) rhythms coordinated by an endogenous master clock located in the suprachiasmatic nucleus of the hypothalamus that are essential for normal health and functioning. Exposure to sunlight during the day and darkness at night optimally entrains biological rhythms to promote homeostasis and human health. Unfortunately, a major consequence of the modern lifestyle is increased exposure to sun-free environments during the day and artificial lighting at night. Additionally, behavioral disruptions to circadian rhythms (ie, repeated transmeridian flights, night or rotating shift work, or sleep disturbances) have a profound influence on health and have been linked to a number of pathological conditions, including endocrine-dependent cancers. Specifically, night shift work has been identified as a significant risk factor for breast cancer in industrialized countries. Several mechanisms have been proposed by which shift work-induced circadian disruptions promote cancer. In this review, we examine the importance of the brain-body link through which circadian disruptions contribute to endocrine-dependent diseases, including breast carcinogenesis, by negatively impacting neuroendocrine and neuroimmune cells, and we consider preventive measures directed at maximizing circadian health. PMID:27712099

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, ...

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

PubMed Central

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

2015-01-01

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

Gene Expression Changes Related to Endocrine Function and Decline in Reproduction in Fathead Minnow (Pimephales promelas) after Dietary Methylmercury Exposure

PubMed Central

Klaper, Rebecca; Rees, Christopher B.; Drevnick, Paul; Weber, Daniel; Sandheinrich, Mark; Carvan, Michael J.

2006-01-01

Background Methylmercury (MeHg) is a known neurotoxic agent, but the mechanisms by which MeHg may act on reproductive pathways are relatively unknown. Several studies have indicated potential changes in hormone levels as well as declines in vertebrates with increasing dietary MeHg exposure. Objectives The purpose of this study was to identify alterations in gene expression associated with MeHg exposure, specifically those associated with previously observed changes in reproduction and reproductive biomarkers. Fathead minnows, Pimephales promelas, were fed one of three diets that were similar to documented concentrations of MeHg in the diets of wild invertivorous and piscivorous fish. We used a commercial macroarray in conjunction with quantitative polymerase chain reaction to examine gene expression in fish in relation to exposure to these environmentally relevant doses of MeHg. Results Expression of genes commonly associated with endocrine disruption was altered with Hg exposure. Specifically, we observed a marked up-regulation in vitellogenin mRNA in individual Hg-exposed males and a significant decline in vitellogenin gene expression in female fish with increasing Hg concentrations. Other genes identified by the macroarray experiment included those associated with egg fertilization and development, sugar metabolism, apoptosis, and electron transport. We also observed differences in expression patterns between male and female fish not related to genes specifically associated with reproduction, indicating a potential physiological difference in the reaction of males and females to MeHg. Conclusion Gene expression data may provide insight into the mechanisms by which MeHg affects reproduction in fish and indicate how MeHg differs in its effect from other heavy metals and endocrine-disrupting compounds. PMID:16966085

Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

PubMed Central

Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

2016-01-01

Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

Extranuclear-initiated estrogenic actions of endocrine disrupting chemicals: Is there toxicology beyond paracelsus?

PubMed

Nadal, Angel; Fuentes, Esther; Ripoll, Cristina; Villar-Pazos, Sabrina; Castellano-Muñoz, Manuel; Soriano, Sergi; Martinez-Pinna, Juan; Quesada, Ivan; Alonso-Magdalena, Paloma

2018-02-01

Endocrine Disrupting Chemicals (EDCs), including bisphenol-A (BPA) do not act as traditional toxic chemicals inducing massive cell damage or death in an unspecific manner. EDCs can work upon binding to hormone receptors, acting as agonists, antagonists or modulators. Bisphenol-A displays estrogenic activity and, for many years it has been classified as a weak estrogen, based on the classic transcriptional action of estrogen receptors serving as transcription factors. However, during the last two decades our knowledge about estrogen signaling has advanced considerably. It is now accepted that estrogen receptors ERα and ERβ activate signaling pathways outside the nucleus which may or may not involve transcription. In addition, a new membrane estrogen receptor, GPER, has been proposed. Pharmacological and molecular evidence, along with results obtained in genetically modified mice, demonstrated that BPA, and its substitute BPS, are potent estrogens acting at nanomolar concentrations via extranuclear ERα, ERβ, and GPER. The different signaling pathways activated by BPA and BPS explain the well-known estrogenic effects of low doses of EDCs as well as non-monotonic dose-response relationships. These signaling pathways may help to explain the actions of EDCs with estrogenic activity in the etiology of different pathologies, including type-2 diabetes and obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endocrine disrupting compounds in drinking water supply system and human health risk implication.

PubMed

Wee, Sze Yee; Aris, Ahmad Zaharin

2017-09-01

To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

The ability of white-rot fungi to degrade the endocrine-disrupting compound nonylphenol.

PubMed

Soares, Ana; Jonasson, Karin; Terrazas, Enrique; Guieysse, Benoit; Mattiasson, Bo

2005-03-01

Phanerochaete chrysosporium, Pleurotus ostreatus, Trametes versicolor and Bjerkandera sp. BOL13 were tested for their ability to degrade the endocrine-disrupting compound nonylphenol at an initial concentration of 100 mg l-1. The highest removals were achieved with T. versicolor and Bjerkandera sp. BOL13, which were able to degrade 97 mg l-1 and 99 mg l-1 of nonylphenol in 25 days of incubation, respectively. Nonylphenol removal was associated with the production of laccase by T. versicolor, but the levels of laccase, manganese peroxidase and lignin peroxidase produced by Bjerkandera sp. BOL13 were very low. At 14 degrees C, T. versicolor and Bjerkandera sp. BOL13 sustained the removal of 88 mg l-1 and 79 mg l-1 of nonylphenol, respectively. No pollutant removal was recorded at 4 degrees C, although both fungi could grow at this temperature in the absence of nonylphenol. A microtoxicity assay showed that the fungi produced compounds that were toxic to Vibrio fischerii; and thus a reduction in toxicity could not be correlated with nonylphenol metabolism. T. versicolor and Bjerkandera sp. BOL13 were capable of colonizing soil artificially contaminated with 430 mg kg-1 of nonylphenol. Only 1.3+/-0.1% of nonylphenol remained in the soil after 5 weeks of incubation.

Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis.

PubMed

Chen, Lianguo; Zhang, Weipeng; Ye, Rui; Hu, Chenyan; Wang, Qiangwei; Seemann, Frauke; Au, Doris W T; Zhou, Bingsheng; Giesy, John P; Qian, Pei-Yuan

2016-04-19

In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28 days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 μg/L), the active ingredient in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across diverse levels of biological organization to reveal the underlying mechanisms of its endocrine disruptive effects. Gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male HPGL axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. Overall, the present results elucidated the estrogenic mechanisms along HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive impairments of DCOIT at environmentally realistic concentrations highlights the need for more comprehensive investigations of its potential ecological risks.