Challenges In Endocrine Disruptor Toxicology And Risk Assessment

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.

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.

Updated with new and expanded chapters, Endocrine Disruption and Human Health, Second Edition provides an introduction to what endocrine disruptors are, the issues surrounding them, the source of these chemicals in the ecosystem and the mechanisms of action and assay systems. Contributions by specialists are included to discuss the varying effects of endocrine disruption on human health, and procedures for risk assessment of endocrine disruptors, and current approaches to their regulation are also covered. With new material on topics such as low-term, low dose mixtures, windows of susceptibility, epigenetics, EDCs effect on the gut microbiome, EDCs in from polluted air and oral exposures, green chemistry, and nanotechnology, the new edition of Endocrine Disruption and Human Health is a valuable and informative text for academic and clinical researchers and other health professionals approaching endocrine disruption and its effects on human health for the first time, graduate students, and advanced undergraduate students. Provides readers with access to a range of information from the basic mechanisms and assays through to cutting-edge research investigating concerns for human health Presents a comprehensive, translational look at all aspects of endocrine disruption and its effects on human health Offers guidance on the risk assessment of endocrine disruptors and current relevant regulatory considerations Newly added content on topics like low-term, low dose mixtures, windows of susceptibility to EDCs, EDCs effect on the gut microbiome, green chemistry, and nanotechnology

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.

Discussions regarding regulation of endocrine disruptors (EDs) and combination effects are ongoing in Europe. Among the central topics of discussion are establishment of criteria for identification of EDs, whether there is a threshold for endocrine disrupting effects and how EDs should be handled within relevant EU regulations. In addition, a roadmap for further EU work regarding combination effects has been presented, but more detailed discussions are needed regarding scientific issues and regulatory intervention. Possible Member State initiatives to provide input to these EU processes were discussed in a Nordic workshop held in Oslo in November 2013. This report describes the workshop presentations, initiatives and thoughts from each of the Nordic countries, the plenary discussions, and the main workshop outcomes.

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.

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.