Endocrine Disrupters A Scientific Perspective

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Endocrine-Disrupting Chemicals

Author : Andrea C. Gore
Publisher : Springer Science & Business Media
Page : 361 pages
File Size : 43,8 Mb
Release : 2007-06-08
Category : Medical
ISBN : 9781597451079

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Endocrine-Disrupting Chemicals by Andrea C. Gore Pdf

This book provides comprehensive coverage of the three most important themes in the field of Endocrine Disrupting Chemicals (EDC) research: the basic biology of EDCs, particularly their effects on reproductive systems; EDC effects on humans and wildlife, including biomedical considerations; and potential interventions and practical advice for dealing with the problem of EDCs.

Environmental Endocrine Disruptors

Author : A Crain,L J GuilletteJr
Publisher : CRC Press
Page : 355 pages
File Size : 55,7 Mb
Release : 2000-08-17
Category : Medical
ISBN : 1560325712

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Environmental Endocrine Disruptors by A Crain,L J GuilletteJr Pdf

Addresses many aspects of endocrine disruption by environmental encountered toxic substances. Initial chapters provide essential background information whilst later chapters address specific aspects of endocrine disrupting contaminants (EDC)

Endocrine Disruptors in the Environment

Author : Sushil K. Khetan
Publisher : John Wiley & Sons
Page : 410 pages
File Size : 52,8 Mb
Release : 2014-06-23
Category : Technology & Engineering
ISBN : 9781118852934

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Endocrine Disruptors in the Environment by Sushil K. Khetan Pdf

Endocrine Disruptors in the Environment A concise and engaging overview of endocrine disruption phenomena that brings complex concepts within the reach of non-specialists For most of the last decade, the science of endocrine disruption has evolved with more definitive evidence of its damaging potential to health and environment. This book lists the major environmental chemicals of concern and their mechanism of endocrine disruption including remedial measures for them. Divided into three parts, Endocrine Disruptors in the Environment begins with an overview of the endocrine system and endocrine disruptors, discussing their salient features and presenting a historical perspective of endocrine disruption phenomena. It then goes on to cover hormone- signaling mechanisms, followed by various broad classes of putative endocrine disruptors, before introducing readers to environmental epigenetic modifications. Part two of the book focuses on removal processes of various EDCs by biotic and abiotic transformation/degradation. The last section consists of four chapters embracing themes on finding solutions to environmental EDCs—including their detection, regulation, replacement, and remediation. Endocrine Disruptors in the Environment is the first book to detail the endocrine effects of several known environmental contaminants and their mechanism of endocrine disruption. Additionally, it: Covers both the chemistry and biology of endocrine disruption and compiles almost all the known endocrine disrupting environmental chemicals and their mechanisms of toxicity Addresses policy and regulatory issues relevant to EDCs including scientific uncertainty and precautionary policy Brings forth the use of Green Chemistry principles in avoiding endocrine disruption in the designing and screening for safer chemicals and remediation of the EDCs in aquatic environment Includes a useful glossary of technical terms, a list of acronyms, topical references, and a subject index Endocrine Disruptors in the Environment is an ideal book for environmental chemists and endocrine toxicologists, developmental biologists, endocrinologists, epidemiologists, environmental health scientists and advocates, and regulatory officials tasked with risk assessment in environment and health areas.

The Endocrine Disruptors

Author : Maria Marino
Publisher : Unknown
Page : 179 pages
File Size : 52,5 Mb
Release : 2007-01-01
Category : Endocrine disrupting chemicals
ISBN : 8178952831

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The Endocrine Disruptors by Maria Marino Pdf

In recent years, it has become evident that many chemicals present in the environment can mimic, antagonize or alter the physiological actions of endogenous hormones. These compounds have been termed endocrine disrupters (EDs) and defined as exogenous substances that cause adverse health effects in an intact organism or in its progeny, consequent to changes in endocrine function [1]. EDs, even when present in minute amounts (part per trillion), could interfere with the synthesis, secretion, transport, metabolism, binding, action, or elimination of natural hormones responsible for homeostasis maintenance, reproduction, and developmental processes [2]. Currently more than 100 chemicals have been identified as EDs. Within this heterogeneous group of molecules we find: (a) synthetic chemicals used in industry, agriculture, and consumer products; (b) synthetic chemicals used as pharmaceutical drugs; and (c) natural chemicals found in human and animal food. About half of these compounds are substituted with halogen groups, mostly chlorine and bromine, and include dioxins, polychlorinated biphenyls, organochlorine pesticides, methoxychlor, dieldrin, and hexachlorocyclohexane. EDs have long environmental half-life resulting in a continue increase of their global concentration in the environment and can be detected and may concentrate at great distances from where they are produced, used or released. EDs have very low water solubility and extremely high lipid solubility, leading to their bioaccumulation in adipose tissue. Exposure to EDs can occur from a number of different sources: humans and animals can be exposed involuntarily by drinking contaminated polluted water, breathing contaminated air, ingesting food, contacting contaminated soil or even in the workplace. Although endocrine disruption has only received high-profile attention for just over a decade [2], the phenomenon does have a longer historical background. In the early 1900s, pig farmers in the USA complained of fertility problems in swine herds fed on moldy grain [3], and concern was stimulated in the 1940s by reports of infertility in sheep grazing on certain clovers in Western Australia [4]. Over the following two decades, estrogenic actions were evidenced in birds [5] and in mammals [6] owing to the dissemination of the agrochemical orto-dichlorodiphenyltrichloroethane (DDT), at the same time masculinization of bivalves and gastropods[7], with concomitant declines in population, was found in the 1970s with the introduction of tributyltin into antifouling paints for the boats, while feminization of fishes was observed in UK rivers in the presence of estrogenic components in sewage effluent [8]. Also the occurrence of genital abnormalities in both male and female alligators in Lake Apopka (FL, USA) were observed as effect of a spill of the pesticide difocol in 1980. After these first observations the scientific community increased the awareness of the consequences of exposure to chemicals which can interfere with reproductive functions [9]. Endocrine disruption in wildlife is now acknowledged to be a widespread problem, much resulting from environmental pollution, and, in the case of aquatic forms of wildlife, from the continuous exposure to these chemicals in the water. Extrapolation of the results of these researches on wildlife resulted in concern that the same compounds could interfere with hormone action in humans. Handling hazardous substances and the risk of exposure to chemicals are a painful part of modern life, as technology and science progress. Moreover, exposure to chemicals present in foods, at home, and at work is an important risk factor for human health, especially since our scientific knowledge is still not sufficient to ensure proper prevention. Nowadays there is justifiable concern that endocrine disruption could be the underlying cause of increasing female and male reproductive problems, thus endocrine disruption is one of the topics receiving much attention throughout all sectors of the society, and the debate between pharmaceutical companies and public health organisms is increasing. Both parts will call for urgent need of more research. The scientific challenge for the future is to identify the relevant real-life sources of exposure of the human population to endocrine-disrupting compounds and to find the appropriate remediation actions. This can be done: (a) by assessing the impact on human health of long-term, low-dose exposure to such chemicals; (b) by understanding the synergistic effects of the copious number of chemicals to which humans and animals are exposed; (c) by defining the variety of underlying mechanisms at molecular, cellular and physiological level, (d) by exploiting new technologies addressed to the remediation of the environment polluted by the presence of EDs, and (e) by designing and developing new sensors or biosensors capable of determining their concentration in traces. The review presented in this book has been written under the sponsorship of the Interuniversitary Consortium National Institute of Biostructures and Biosystems (INBB) , constituted by 26 Public Italian Universities. INBB is stimulating the research on endocrine disruptors, by encouraging and coordinating joint research projects between its members and those of other Italian public scientific institutions. This book represents one of the results of the meeting The biological and clinical research on endocrine disruptors: current status and perspectives , held in Rome during 2005 from October 27 to 28 and organized by INBB and ISPESL (Istituto Superiore Prevenzione e Sicurezza del Lavoro). The first three chapters of this book review the EDs effects on natural population living in aquatic ecosystems where EDs, due to their lipophilicity, tend to concentrate in sediments and in food webs. The edible mussel Mytilus (Chapter 1), a marine bivalve that can accumulate large amounts of organic contaminants, represents a species of economical, ecological and public health-related interest. Amphibians (Chapter 2) are favourite models for studying various aspects of reproduction, development of the central nervous system and metamorphosis. Moreover, there is great concern about the EDs and the dramatic decline of wild amphibian populations. In Chapter 3 different species of fishes are considered as experimental models to analyze, by both genomic and proteomic approaches, the expression of key molecules involved in reproduction and in detoxification processes. The following two chapters focus on the EDs effects on thyroid functions and on the development of central mechanisms controlling reproduction. Wildlife observations in polluted areas clearly demonstrate a significant incidence of thyroid imbalance in several species. Several EDs are now known or suspected to be thyroid disruptors altering thyroid economy at multiple levels. These compounds may interfere with thyroid homeostasis through many mechanisms of action, at receptor level, in binding to transport proteins, in cellular uptake mechanisms or in modifying the metabolism of thyroid hormones. Chapter 4 offers a focus on endocrine disrupting activity of chemical compounds on thyroid function. The dimorphic control of reproductive functions depends on the ability of the central nervous system, particularly the hypothalamus, to respond properly to circulating reproductive hormones. This ability is acquired during a perinatal critical period, when the presence of different levels of sex steroid hormones in male and female fetuses/neonates induces a sex-specific morpho-functional development of the neuronal networks controlling reproduction. The perinatal stage is thus particularly sensitive to endogenous or exogenous substances that interfere with the activities of sex steroid hormones. Chapter 5 summarizes the current knowledge on the neuro-endocrine disrupting potential of the perinatal exposure to the major classes of EDs focusing the attention on animal studies aimed to identify the EDs action mechanisms and the resulting impairment of the reproductive behavior. Flavonoids are defined as naturally occurring molecules of plant origin, capable of acting as hormone mimetics or antagonists, but also as endocrine disruptors. Many of them have been marketed as dietary supplements or nutraceuticals with health claims, thus leading to significant increase in flavonoid consumption levels in the Western population. Even though several reports suggest for these compounds health-promoting effects in preventing age-related diseases such as atherosclerosis, hormone-dependent cancers, and osteoporosis, the mechanistic aspects of their activity have not been fully clarified and a wide consensus of the pros and cons of their use in humans has not been reached by the scientific community. Chapter 6 presents an overview of the state of the art of the knowledge on the molecular mechanisms underlying flavonoids estrogen-like activity. Feed additives represent a major issue for the safety of foods of animal origin, as they constitute the bulk of chemicals used in animal production. Feeds can also be a major vehicle for human dietary intake of persistent EDs (Chapter 7). Farm animals ingest these substances with food and drinking water and it is likely that the range of ingestion will increase in the future as growing amounts of sewage sludges are recycled onto agricultural land with an overall increase of environmental contamination exerting adverse effects on human health. Research on how the exposure to EDs affects human health in the work environment (Chapter 8) attracts increasing attention among international scientists. Certain workplaces pose particular problems as regards the potential risk connected to processes involving the use, manufacture and handling of these chemicals, and the type of job that puts workers at greatest risk of contact with them. Some EDCs represent occupational risk factors credibly capable of inducing hormone-dependent tumors. Occupational exposure to EDs is a highly complicated question: risk factors in the workplace must be identified; how they penetrate the body has to be established; confounding factors in everyday environments are numerous, and it is hard to make a definite diagnosis of their effects on human health. Owing to the harmful health effects of EDs, the attention of many scientists has been attracted towards the remediation of environment polluted by their presence and the design and development of sensors or biosensors capable of determining their concentration in traces. In Chapter 9 the experimental results concerning the enzymatic remediation of waters polluted by Bisphenol A (BPA), taken as a model of endocrine disruptors, is discussed in view of the potential application of the technology of non-isothermal bioreactors to the treatment of polluted waters. Also the functioning of a tyrosinase-based sensor able to measure the BPA concentration in traces is presented in the same chapter. These reviews emphasize that many environmental chemicals possess endocrine-disrupting properties, and that exposure to such chemicals can have adverse effects on health and reproduction even at very low concentrations. Great care should be used when attempting to apply these data to other species or real life situations. Indeed only a paucity of information is available on the metabolism and tissue distribution of these chemicals which may vary according to species physiology as well as to levels and duration of exposure. Furthermore, the possible interactions between single contaminants of the complex mixtures present in the environment may induce completely unpredictable effects, due to synergies or reciprocal inhibition effects, suggesting great caution in drawing conclusions. It is hoped that these reviews will serve to stimulate further research on EDs and human health. References 1.Report of the proceedings of the European workshop on the impact of endocrine disrupters on human health and wildlife. 1996, Weybridge, UK, report EUR17549 of the environment and climate change research programme of DGXII of the European commission. 2.Colborn T, vom Saal FS & Soto AM. Environ Health Perspectiv 1993, 101, 378 384. 3.McNutt SH, Purwin P & Murray C. J Amer Veterinary Medical Ass 1928, 73, 484. 4.Bennets H, Underwood EJ & Shier FL. Australian Veterinary Journal 1946, 22, 2 12. 5.Burlington H & Linderman VF. Proceedings of the Society for Experimental Biology and Medicine 1950, 74, 48 51. 6.Bitman J, Cecil HC, Harris SJ & Fries GF. Science 1968, 162, 371 372. 7.Matthiessen P. Pure and Applied Chemistry 2003, 75, 2197 2206. 8.Jobling S, Nolan M, Tyler CR et al. Environmental Science and Technology 1998, 32, 2498 2506. 9.Guillette Jr. LJ & Gunderson MP. Reproduction 2001, 122, 857 864.

Endocrine-Disrupting Chemicals

Author : Andrea C. Gore
Publisher : Humana
Page : 0 pages
File Size : 41,5 Mb
Release : 2010-11-09
Category : Medical
ISBN : 1617377953

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Endocrine-Disrupting Chemicals by Andrea C. Gore Pdf

This book provides comprehensive coverage of the three most important themes in the field of Endocrine Disrupting Chemicals (EDC) research: the basic biology of EDCs, particularly their effects on reproductive systems; EDC effects on humans and wildlife, including biomedical considerations; and potential interventions and practical advice for dealing with the problem of EDCs.

Endocrine Disrupters

Author : Polyxeni Nicolopoulou-Stamati,Luc Hens,Vyvyan C. Howard
Publisher : Springer Science & Business Media
Page : 385 pages
File Size : 41,8 Mb
Release : 2013-03-14
Category : Medical
ISBN : 9789401597692

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Endocrine Disrupters by Polyxeni Nicolopoulou-Stamati,Luc Hens,Vyvyan C. Howard Pdf

During recent decades, millions of tonnes of man-made chemicals have been produced and released into the environment, with very little safety testing. Many of these chemical substances have been found to interfere with the endocrine system and modulate its function. This book not only overviews the effects of endocrine/disrupting substances on human health, but also addresses the regulatory problems from the point of view of international organisations, including the WHO, the EU, and the European Chlorine Industry. This volume contains the proceedings of a workshop held at the International Hippocrates Foundation on Kos Island, Greece, in September 1999. The workshop was part of the activities of the ASPIS project, which aims at raising awareness of environmental health impacts among multidisciplinary groups. The contributions to this volume are the result of the interaction of participants at the workshop. As such, it addresses the issue of endocrine disrupters from many different points of view and allows the subject to be approached by a multidisciplinary readership, including: decision makers, medical doctors, environmental experts, post/and undergraduate students, lawyers, engineers, and journalists.

Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals

Author : National Academies of Sciences, Engineering, and Medicine,Division on Earth and Life Studies,Board on Environmental Studies and Toxicology,Committee on Endocrine-Related Low-Dose Toxicity
Publisher : National Academies Press
Page : 423 pages
File Size : 41,8 Mb
Release : 2017-08-14
Category : Science
ISBN : 9780309458627

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Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals by National Academies of Sciences, Engineering, and Medicine,Division on Earth and Life Studies,Board on Environmental Studies and Toxicology,Committee on Endocrine-Related Low-Dose Toxicity Pdf

To safeguard public health, the US Environmental Protection Agency (EPA) must keep abreast of new scientific information and emerging technologies so that it can apply them to regulatory decision-making. For decades the agency has dealt with questions about what animal-testing data to use to make predictions about human health hazards, how to perform dose-response extrapolations, how to identify and protect susceptible subpopulations, and how to address uncertainties. As alternatives to traditional toxicity testing have emerged, the agency has been faced with additional questions about how to incorporate data from such tests into its chemical assessments and whether such tests can replace some traditional testing methods. Endocrine active chemicals (EACs) have raised concerns that traditional toxicity-testing protocols might be inadequate to identify all potential hazards to human health because they have the ability to modulate normal hormone function, and small alterations in hormone concentrations, particularly during sensitive life stages, can have lasting and significant effects. To address concerns about potential human health effects from EACs at low doses, this report develops a strategy to evaluate the evidence for such low-dose effects.

Endocrine Disrupters

Author : Anonim
Publisher : Academic Press
Page : 485 pages
File Size : 54,9 Mb
Release : 2014-01-02
Category : Medical
ISBN : 9780128005859

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Endocrine Disrupters by Anonim Pdf

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Series provides up-to-date information on vitamin and hormone research spanning data from molecular biology to the clinic. A volume can focus on a single molecule or on a disease that is related to vitamins or hormones. A hormone is interpreted broadly so that related substances, such as transmitters, cytokines, growth factors and others can be reviewed. This volume focuses on endocrine disrupters. Expertise of the contributors Coverage of a vast array of subjects In depth current information at the molecular to the clinical levels Three-dimensional structures in color Elaborate signaling pathways

Multi-System Endocrine Disruption

Author : Jean-Pierre Bourguignon,Bernard Jégou,Bernard Kerdelhué,Jorma Toppari,Yves Christen
Publisher : Springer
Page : 176 pages
File Size : 53,9 Mb
Release : 2011-09-10
Category : Medical
ISBN : 3642227767

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Multi-System Endocrine Disruption by Jean-Pierre Bourguignon,Bernard Jégou,Bernard Kerdelhué,Jorma Toppari,Yves Christen Pdf

Endocrine disruption is an expanding field due to the numerous chemicals involved and, as evidenced more recently, the variety of homeostatic systems that they can alter throughout life. The gathering of experts from all over the world should help to identify health disorders that are possibly or likely related to exposure to endocrine disrupters. The research needs have been discussed as well as recommendations prioritizing target groups and following the precautionary principle.

Hormonally Active Agents in the Environment

Author : National Research Council,Commission on Life Sciences,Board on Environmental Studies and Toxicology,Committee on Hormonally Active Agents in the Environment
Publisher : National Academies Press
Page : 453 pages
File Size : 54,8 Mb
Release : 2000-02-03
Category : Science
ISBN : 9780309064194

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Hormonally Active Agents in the Environment by National Research Council,Commission on Life Sciences,Board on Environmental Studies and Toxicology,Committee on Hormonally Active Agents in the Environment Pdf

Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.

Endocrine Disruptors, Brain, and Behavior

Author : Heather B. Patisaul,Scott M. Belcher
Publisher : Oxford University Press
Page : 336 pages
File Size : 48,7 Mb
Release : 2017-04-10
Category : Psychology
ISBN : 9780190669034

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Endocrine Disruptors, Brain, and Behavior by Heather B. Patisaul,Scott M. Belcher Pdf

Our world and bodies are becoming increasingly polluted with chemicals capable of interfering with our hormones and thus, possibly, our present and future neural and mental health. As authors Heather Patisaul and Scott Belcher outline, there is a large lack of data and evidence in this causal relationship, which begs a need for further study to accelerate progress in the endocrinology and neuroendocrinology fields. Endocrine Disruptors, Brain, and Behavior focuses on if and how these chemicals, known as endocrine disrupting compounds (EDCs), affect the development and function of the brain and might be contributing to neural disorders rapidly rising in prevalence. The book provides an overall synthesis of the EDC field, including its historical roots, major hypotheses, key findings, and research gaps. The authors explain why even the concept of endocrine disruption is controversial in some circles, how differing definitions of endocrine disruption and what constitutes an "adverse" outcome on the brain shape public policy, and where the current capacity by different stakeholders (industry, academia, regulatory agencies) to evaluate chemicals for safety in a regulatory context begins and ends. The book concludes with suggestions for future research needs and a summary of emerging technology which might prove capable of more effectively evaluating existing and emerging chemicals for endocrine disrupting properties. As such, it provides the context for interdisciplinary and innovative input from a broad spectrum of fields, including those well-schooled in neuroscience, evolutionary biology, brain, behavior, sex differences, and neuroendocrinology.

Challenges in Endocrine Disruptor Toxicology and Risk Assessment

Author : Alexandra Fucic,Alberto Mantovani
Publisher : Royal Society of Chemistry
Page : 539 pages
File Size : 41,6 Mb
Release : 2020-12-08
Category : Science
ISBN : 9781788017411

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Challenges in Endocrine Disruptor Toxicology and Risk Assessment by Alexandra Fucic,Alberto Mantovani Pdf

Insight into the role of hormones, particularly estrogen and testosterone, in health and disease etiology - including interactions with other hormone pathways - has dramatically changed. Estrogen and androgen receptors, with their polymorphisms, are key molecules in all tissues and are involved in a number of homeostatic mechanisms but also pathological processes including carcinogenesis and the development of metabolic and neurological disorders such as diabetes and Alzheimer's disease. Endocrine disrupting chemicals (EDCs) can interfere with the endocrine (hormone) systems at certain dosages and play a key role in the pathology of disease. Most known EDCs are manmade and are therefore an increasing concern given the number commonly found in household products and the environment. This book will cover the mechanisms of EDC pathology across the spectrum of disease, as well as risk assessment and government and legal regulation to provide a holistic view of the current issues and cutting-edge research in the topic. With contributions from global leaders in the field, this book will be an ideal reference for toxicologists, endocrinologists and researchers interested in developmental biology, regulatory toxicology and the interface between environment and human health.

Toxic Bodies

Author : Nancy Langston
Publisher : Yale University Press
Page : 253 pages
File Size : 45,5 Mb
Release : 2010-03-02
Category : Science
ISBN : 9780300162998

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Toxic Bodies by Nancy Langston Pdf

In 1941 the Food and Drug Administration approved the use of diethylstilbestrol (DES), the first synthetic chemical to be marketed as an estrogen and one of the first to be identified as a hormone disruptor—a chemical that mimics hormones. Although researchers knew that DES caused cancer and disrupted sexual development, doctors prescribed it for millions of women, initially for menopause and then for miscarriage, while farmers gave cattle the hormone to promote rapid weight gain. Its residues, and those of other chemicals, in the American food supply are changing the internal ecosystems of human, livestock, and wildlife bodies in increasingly troubling ways. In this gripping exploration, Nancy Langston shows how these chemicals have penetrated into every aspect of our bodies and ecosystems, yet the U.S. government has largely failed to regulate them and has skillfully manipulated scientific uncertainty to delay regulation. Personally affected by endocrine disruptors, Langston argues that the FDA needs to institute proper regulation of these commonly produced synthetic chemicals.

Review of the Environmental Protection Agency's State-of-the-science Evaluation of Nonmonotonic Dose-response Relationships as They Apply to Endocrine Disruptors

Author : National Research Council (U.S.). Committee to Review EPA's State of the Science Paper on Nonmonotonic Dose Reponse,Board on Environmental Studies and Toxicology,Division on Earth and Life Studies,National Research Council
Publisher : Unknown
Page : 0 pages
File Size : 44,5 Mb
Release : 2014
Category : Medical
ISBN : 0309297540

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Review of the Environmental Protection Agency's State-of-the-science Evaluation of Nonmonotonic Dose-response Relationships as They Apply to Endocrine Disruptors by National Research Council (U.S.). Committee to Review EPA's State of the Science Paper on Nonmonotonic Dose Reponse,Board on Environmental Studies and Toxicology,Division on Earth and Life Studies,National Research Council Pdf

Potential health effects from chemicals that disrupt endocrine function pose an environmental health concern because of their ability to interfere with normal hormone function in human and wildlife populations. The endocrine system regulates biological processes throughout the body and is sensitive to small changes in hormone concentrations. Endocrine-disruptor research has focused primarily on chemicals that affect three hormone pathways that play important roles in reproduction and development - the estrogen, androgen, and thyroid hormone pathways. Some of this research has identified dose-response relationships that have nonmonotonic curves. Nonmonotonic dose-response curves (NMDRs) are of concern because they do not follow the usual assumption made in toxicology that as dose decreases the response also decreases. The existence of NMDRs has been a controversial topic for decades, and there has been considerable debate about their implications for how chemicals are tested and for how risks from such chemicals are assessed. Toxicity tests are designed to identify hazards and to characterize dose-response relationships, so tests are aimed at finding a (high) dose that elicits a response, and dose-response is explored by testing lower doses spaced to identify statistically a no- or lowest-observed-adverse-effect level. The concern for NMDRs is that such studies, as currently designed, might not detect the inflection of the dose-response curve if only a few doses are tested or if the change in inflection occurs below the range of doses tested. Another concern is that some NMDRs are found for biological effects that are not usually evaluated in toxicity tests. If current testing strategies are inadequate to account for NMDRs, changes to risk assessment practices might be necessary. To help address these issues, the U.S. Environmental Protection Agency (EPA) developed a draft State-of-the-Science Evaluation: Nonmonotonic Dose Responses as they Apply to Estrogen, Androgen, and Thyroid Pathways and EPA Testing and Assessment Procedures. EPA asked the National Research Council to conduct an independent review of this evaluation to ensure that it is scientifically sound and of high quality. Review of Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response as they Apply to Endocrine Disrupters evaluates whether EPA's evaluation presents a scientifically sound and high-quality analysis of the literature on NMDRs. This report reviews how well the EPA evaluation described how the assessment was performed, whether consistent methods and criteria were applied in the analysis of different evidence streams, and whether appropriate methods were applied to evaluating the evidence. The report makes recommendations to improve EPA's process and strengthen the evaluation.