Endocrine Disruptors in the Environment E-Book

Sushil K. Khetan

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 698

Veröffentlichungsjahr: 2014

Beschreibung

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.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

Foreword

Preface

Acknowledgements

Acronyms

Glossary

Chapter 1: Environmental Endocrine Disruptors

1.1 Introduction

1.2 Salient Aspects about Endocrine Disruption

1.3 Historical Perspective of Endocrine Disruption

1.4 Scope and Layout of this Book

1.5 Conclusion

References

Part I : Mechanisms of Hormonal Action and Putative Endocrine Disruptors

Chapter 2: Mechanisms of Endocrine System Function

2.1 Introduction

2.2 Hormonal Axes

2.3 Hormonal Cell Signaling

2.4 Sex Steroids

2.5 Thyroid Hormones

2.6 Conclusions and Future Prospects

References

Chapter 3: Environmental Chemicals Targeting Estrogen Signaling Pathways

3.1 Introduction

3.2 Steroidal Estrogens

3.3 Nonsteroidal Estrogenic Chemicals

3.4 Metalloestrogens

3.5 Conclusion and Future Prospects

References

Chapter 4: Anti-Androgenic Chemicals

4.1 Introduction

4.2 Testosterone Synthesis Inhibitors

4.3 Androgen Receptor (AR) Antagonists

4.4 AR Antagonists and Fetal Testosterone Synthesis Inhibitors

4.5 Comparative Anti-Androgenic Effects of Pesticides to Androgen Agonist DHT

4.6 Conclusions and Future Prospects

References

Chapter 5: Thyroid-Disrupting Chemicals

5.1 Introduction

5.2 Thyroid Synthesis Inhibition by Interference in Iodide Uptake

5.3 TH Transport Disruptors and Estrogen Sulfotransferases Inhibitors

5.4 Thyroid Hormone Level Disruptors

5.5 Selective Thyroid Hormone Antagonists

5.6 Conclusions and Future Prospects

References

Chapter 6: Activators of PPAR, RXR, AR, and Steroidogenic Factor 1

6.1 Introduction

6.2 Peroxisome Proliferator-Activated Receptor (PPAR) Agonists

6.3 Aryl Hydrocarbon Receptor (AR) Agonists

6.4 Steroidogenesis Modulator (Aromatase Expression Inducer)

6.5 Conclusions and Future Prospects

References

Chapter 7: Effects of EDC Mixtures

7.1 Introduction

7.2 Combined Effect of Exposure to Multiple Chemicals

7.3 Mixture Effects of Estrogenic Chemicals

7.4 Mixture Effects of Estrogens and Anti-Estrogens

7.5 Mixture Effects of Anti-Androgens

7.6 Mixture Effects of Thyroid Disrupting Chemicals

7.7 Mixture Effects of Chemicals Acting via AhR

7.8 Conclusions and Future Prospects

References

Chapter 8: Environmentally Induced Epigenetic Modifications and Transgenerational Effects

8.1 Introduction

8.2 Regulatory Epigenetic Modifications

8.3 Epigenetic Dysregulation Effects of Endocrine Disruption

8.4 Environmental Epigenetic Effects of Heavy Metals Exposure

8.5 Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations

8.6 Transgenerational Actions of EDCs Mixture on Reproductive Disease

8.7 Conclusions and Future Prospects

References

Part II : Removal Mechanisms of EDC Through Biotic and Abiotic Processes

Chapter 9: Biodegradations and Biotransformations of Selected Examples of EDCs

9.1 Introduction

9.2 Natural and Synthetic Steroidal Estrogens

9.3 Alkylphenols

9.4 Phthalates

9.5 Insecticides

9.6 Fungicides

9.7 Herbicides

9.8 Polychlorinated Biphenyls (PCBs)

9.10 Triclosan

9.11 Conclusions and Future Prospects

References

Chapter 10: Abiotic Degradations/Transformations of EDCs Through Oxidation Processes

10.1 Introduction

10.2 Natural and Synthetic Estrogens

10.3 Bisphenol A

10.4 4-Octylphenol and 4-Nonylphenol

10.5 Parabens

10.6 Phthalates – Photocatalytic Degradation

10.7 Linuron

10.8 Atrazine

10.9 Polybrominated Diphenyl Ether (PBDE) Flame Retardants

10.10 Triclosan

10.11 PFOA and PFOS

10.12 Conclusions

References

Part III : Screening and Testing for Potential EDC, Implications for Water Quality Sustainability, Policy and Regulatory Issues, and Green Chemistry Principles in the Design of Safe Chemicals and Remediation of EDC

Chapter 11: Screening and Testing Programs for EDCs

11.1 Introduction

11.2 Endocrine Disruptor Screening Program (EDSP)

11.3 Assays for the Detection of Chemicals that alter the Estrogen Signaling Pathway

11.4 Assays for the Detection of Chemicals that alter the Androgenic Signaling Pathway

11.5 Assays for the Detection of Chemicals that alter the Hpt Axis

11.6 The USEPA's EDSP21 Work Plan

11.7 Conclusions and Future Prospects

References

Chapter 12: Trace Contaminants: Implications for Water Quality Sustainability

12.1 Introduction

12.2 Trace Contaminants Sources in Water

12.3 Wastewater Reclamation Processes

12.4 Indirect Water Reuse Systems

12.5 Leaching of Contaminants in Water – the Case of Bottled Water

12.6 Water Quality Sustainability and Health Effects

12.7 Toxicological Implications

12.8 Regulatory Structures to Maintain Water Quality

12.9 Conclusions and Future Prospects

References

Chapter 13: Policy and Regulatory Considerations for EDCs

13.1 Introduction

13.2 Regulating Paradigm Shift in Conventional Toxicology

13.3 Policy Options for EDC Regulation

13.4 Controversy on Regulatory Framework for EDCs

13.5 Conclusions and Future Prospects

References

Chapter 14: Green Chemistry Principles in the Designing and Screening for Safe Chemicals and Remediation of EDCs

14.1 Introduction

14.2 Benign by Design Chemicals

14.3 Chemical Endocrine Disruption Screening Protocol

14.4 Green Oxidative Remediation of EDCs

14.5 Conclusions and Future Prospects

References

Index

End User License Agreement

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Guide

Cover

Table of Contents

Preface

Part I : Mechanisms of Hormonal Action and Putative Endocrine Disruptors

Chapter 1: Environmental Endocrine Disruptors

List of Illustrations

Figure 1.1

Figure 1.2

Figure 1.3

Figure 1.4

Figure 1.5

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 2.6

Figure 2.7

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List of Tables

Table 1.1

Table 2.1

Table 3.1

Table 3.2

Table 3.3

Table 3.4

Table 3.5

Table 3.6

Table 4.1

Table 7.1

Table 11.1

Table 11.2

Table 14.1

Endocrine Disruptors in the Environment

Sushil K. Khetan

Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Khetan, Sushil K.

Endocrine disruptors in the environment / Sushil K. Khetan.

pages cm

Includes bibliographical references and index.

ISBN 978-1-118-85293-4 (cloth)

1. Endocrine-disrupting chemicals–Environmental aspects. 2. Endocrine-disrupting chemicals–Toxicity testing. 3. Endocrine toxicology. I. Title.

RA1224.2.K48 2014

614.5′94–dc23

2013047840

Foreword

Why should people concern themselves with endocrine disruptors (EDs)? And why should scientists, and especially green chemists, rank endocrine disruption as the single most important problem space for their work in reducing/eliminating chemical hazards? These are key questions that Dr. Sushil Khetan seeks to answer through the scholarly journey he undertakes in this bravely and conscientiously constructed book entitled Endocrine Disruptors in the Environment.

I write “bravely” because Endocrine Disruptors in the Environment integrates aspects of physiology, biology, genetics, epigenetics, endocrinology, toxicology, ecotoxicology, public policy, and green chemistry into a concise and coherent picture of the challenges that endocrine disruption poses. Dr. Khetan was trained as an organic chemist, and spent much of his working career in the pesticides industry at the interfaces of chemistry with biology and toxicology. Thereafter, he joined the Institute for Green Science (IGS) of Carnegie Mellon University and spent many years working to help advance this emerging field. Green science has as its core goals the challenges of helping to conceive, articulate, and build the scientific dimension of a sustainable civilization. Dr. Khetan has a keen sense for what is of great importance to the positive advancement of science, especially chemistry. He enthusiastically adopted the IGS insight that to be effective in the pursuit of sustainability, green chemists have to find ways to understand endocrine disruption well enough to be able to avoid EDs by design in the commercialized products and processes of the future. One of Dr. Khetan's great accomplishments in these years was to read and interpret for the IGS the literature on pharmaceuticals in the environment. His efforts resulted the Chemical Reviews article, “Human Pharmaceuticals in the Aquatic Environment: A Challenge to Green Chemistry,” which we coauthored in 2007. Many pharmaceuticals are developmental disruptors and are ecotoxic at environmentally relevant concentrations, typically in wastewater from low parts per billion and to even as low as subparts per trillion, consistent with the endocrine system being targeted. Dr. Khetan's work helped to underpin the IGS development of technologies based on TAML activator/hydrogen peroxide oxidation catalysis that possess high technical, environmental, and cost performances for degrading excreted and adventitious pharmaceuticals in wastewater before the water is released to the environment.

Over the last several years, Dr. Khetan has thrown himself heart and soul into writing Endocrine Disruptors in the Environment as a way of finding answers to the following questions which involve us all and which have tectonic significance to whether or not the chemical enterprise can become a positive force in the pursuit of a sustainable civilization:

What can each of us do to build a safer world upon becoming aware that everyday commercial chemicals are disrupting the hormonal control of cellular development and signaling to change the way life develops and evolves?

What should those scientists who are designing the technologies of the future do in light of the mountain of evidence which prescribes that the ever-expanding adverse effects of low doses of EDs are potentially ruinous of any meaningful quest for a sustainable future?

What must society do given that some EDs are high production volume chemicals that are integral to myriad products and processes across the material fabric of our civilization but result in the endemic exposure of living things to both individual EDs and mixtures of EDs?

How can scientists resolve the obvious dilemmas with certain existing EDs that society would wish to keep for valuable benefits – where and how through the full lifecycles can these EDs be intercepted so that the benefits can be maintained while the collateral adverse effects are avoided? Some chemicals have been designed and/or deployed to take advantage of endocrine disruption properties; the steroid components of the birth control pill are examples in point.

Why have I posed these questions in such dramatic terms? To me, the scientific case is indisputable that endocrine disruption turns the whole meaning of chemicals to the advancement of our civilization on its head. In the light of endocrine disruption, nothing in the chemical enterprise can ever look quite the same. The very idea that infinitesimal traces of commercial chemicals could be altering the way life develops and evolves is shocking. The chemicals we use in food, in agriculture, in our homes, in personal cares products, in pharmaceuticals, in fact across the entire landscape of our highly chemical civilization were never meant to disrupt development. But now we understand that some of them clearly do as an almost inescapable consequence of the way the endocrine system works to control cellular development and signaling. So every chemical has to be reexamined to see whether our appreciation of it is upside down – to learn whether short-term benefits are accompanied by longer-term penalties which society absolutely must avoid. And we must know whether new chemicals have uncontrollable endocrine disruption properties. An Everest of scientific information now has the potential to require the chemical industry to re-evaluate, reposition, and even abandon lucrative products as a prerequisite for a sustainable future. This reality further highlights Dr. Khetan's courage in writing this book.

The above underlying questions are of immediate relevance to anyone who wants our civilization to last. Dr. Khetan skillfully describes how the questions are being approached by researchers and their supporters who have led in developing our understanding of EDs, by government officials who evaluate and regulate against toxic chemicals, by commentators and advocates who raise public awareness about chemical hazards, by corporation owners and stockholders who have the power to insist that chemical producing and/or using companies chart courses away from endocrine disruptors, by corporate executives who hold the responsibility for developing practical company policies and dynamics that do not expand but instead reduce public and environmental exposures to EDs, by researchers who are responsible for learning how to avoid EDs, and by educators who are responsible for teaching future generations about the dangers of EDs. In fact, everyone at some level shares the responsibility for ensuring that the chemical sector of our civilization finds a new path forward that frees living things from ED exposures.

Dr. Khetan's highly informative book can be of assistance to anyone who is working to advance the economy while protecting the future from endocrine disruption. Its publication comes at a time when government officials and informed members of the public are scrutinizing EDs' adverse effects on wildlife and people with growing conviction that regulatory control is unavoidable. At the same time, segments of the chemical industry and its trade associations are lobbying to convince the powers that be that chemicals are safe once they have passed the classical toxicological screening we have relied on for decades. This screening does not adequately recognize the peculiarities of how the endocrine system works by using small concentrations of hormones to control the fate of cellular development. Unfortunately, even at low doses, EDs disrupt these hormone signals that are exquisitely programmed by healthy organisms in both time and space. Dr. Khetan's combining of the science with the policy issues and remediation efforts rounds out his treatise to deliver a multidisciplinary, cross-sectoral, and trans-cultural domain as is required for understanding and coping with endocrine disruption to advance sustainability. Dr. Khetan also makes a special attempt to show how positive paths forward are deriving from green chemistry.

In conclusion, in writing Endocrine Disruptors in the Environment, Dr. Khetan has embarked on a courageous exercise to scan the broad literature of endocrine disruption and to explore whether he, in his own person, can provide an example of the challenging journey that the science of chemistry and the chemical enterprise must undertake. What has resulted is a treasure trove of well-organized information covering the things that readers would want to know about endocrine disruption but did not know how or whom to ask. Ultimately, this is an immensely positive book because, as we are learning about EDs and how to identify them, we are also learning about how to avoid them by design and even to how to eliminate some of them after they have been used for beneficial purposes, but before collateral negative effects can be manifested. And, it is my fervent hope that the fruits of Dr. Khetan's labor of interest and conviction will advance the ability of chemists to build a chemical world that is free of endocrine disruption.

Terrence J. Collins

Teresa Heinz Professor of Green Chemistry and Director

Institute for Green Science

Carnegie Mellon University

Pittsburgh, PA

Preface

The last two decades have seen an increase in the number of reports on organic chemicals that pollute the aquatic environment and in turn our drinking water supplies. Aquatic ecosystems are especially susceptible to exposure to compounds with endocrine-disrupting activity, because a great variety of substances exhibiting such activity are eventually introduced into the surface waters. Environmental contaminants called endocrine disruptors (EDs), a diverse group of chemicals and heavy metals, are now widely reported to affect the reproductive and developmental health of animals, experimental as well as wild, and are considered to be the developmental basis of many diseases, including obesity in humans. These chemicals mimic the function of various hormones and induce an imbalance in the natural hormonal milieu. Plasticizers, such as phthalates, that can block the functioning of male sex hormones, and basic chemicals for plastics, such as bisphenol A, that act like female hormones have been found in the blood and urine of most people in the United States.

Traditional toxicology testing has largely missed endocrine disruption in the first place and overlooked chemicals that could penetrate the womb environment and interfere with the development of the embryo and fetus. The idea that the dose makes the poison is overly simplistic. The latest research results clearly demonstrate that biology is affected by low doses of chemicals, often within the range of general population exposure, and reveals the sensitivity of the developing individual to the slightest chemical perturbation during development. It has been demonstrated that exposure to a biologically active chemical within the range in which free hormones operate can have an effect. And exposure to the chemical leads to an entirely different suite of effects that change during progressive stages of development than when the same chemical is administered in high doses after an individual has fully developed. These studies have also confirmed that endocrine effects are time specific, chemical and/or hormone specific, and also dose related.

The very idea that some man-made chemicals are the cause of unintended physiological and environmental effects is worrisome. Chemists often primarily see the beneficial and useful aspects of synthetic substances. And as scientists, they may be skeptical about claims that specific synthetic chemicals cause harm. This has led to the introduction of consumer products that unintentionally contain harmful chemicals such as EDs, and to the subsequent replacement of these products. One reason is that most chemists have no training in basic toxicology or an understanding of the science around endocrine-disrupting substances. Therefore, it is crucial that they have access to this science in order to understand the basis of the problem in a language they can absorb and thus enable them to offer viable solution(s). There are many areas where scientists can effectively contribute. For example, some of the most severe examples of endocrine disruption in fish have been found adjacent to sewage treatment plants and near the discharge of effluents from pulp and paper mills. The participation of scientists from interrelated disciplines will yield solutions to various problems arising out of environmental sources of endocrine disruption. Some of the areas include looking at life-cycle effects of chemicals introduced in new products, finding safe substitutes of problematic chemicals, designing of safer chemicals, employing green catalytic processes for remediation of endocrine-disrupting contaminants, and providing inputs to policy and regulatory issues of chemicals.

While specialists in different scientific disciplines such as endocrinology, toxicology, molecular and developmental biology, physiology, and others have peered into the subject, focusing on human health endpoints in the literature in the last decade, there is a distinct lack of a holistic view due to the difficulty in comprehension of this interdisciplinary area. One of the prime objectives of this book is to fill this gap by synthesizing current knowledge relevant to endocrine disruption and reviewing well-studied environmental contaminants. Endocrine toxicology science requires expertise in environmental chemistry, green chemistry, and toxicology including ecotoxicology, endocrinology, developmental biology, epidemiology, and risk assessment. Of course, no one discipline can cover all of these areas, so progress in endocrine disruption science will require collaborations across disciplinary boundaries. Therefore, I hope that this book would be of interest to professionals in these disciplines working or participating in research across the boundary of their specific discipline. It is also my hope that this book would interest scientists in academia and the chemical industry, regulators, as well as environmentalists and policy makers.

Endocrine disruption, which is considered an esoteric science topic, much like global warming was a decade earlier, has lately become mainstream headline news in the media. There were great many skeptics in the linkage of global warming to the generation of CO2 from anthropogenic sources then, but few can deny this linkage today (with atmospheric CO2 concentrations reaching 400 ppm versus norm of 275 ppm level) and it is now too late to avoid the negative impacts of climate change, resulting in a steadily warming climate, melting glaciers and the Arctic Sea, and rapidly spreading droughts. Analogously, for most of the last decade, the science of endocrine disruption has evolved with more definitive evidences of its damaging potential to health and environment. Endocrine disruption can have devastating population-level effects with a potential to change human gender ratio, early puberty, reproductive disruption, infertility, abortions, and life-threatening diseases such as breast cancer in women, prostate cancer in men, and thyroid cancer. Increasingly, science is able to provide the mechanistic basis of multigenerational deleterious effects of low levels exposure to endocrine disruptors.

As in the case of global warming, there is a section of society that has adopted the precautionary approach and moved towards things such as organic foods, avoiding plastic bottles for infant feeding, and so on. Nonetheless, there remains a vast gap in knowledge and awareness of the risks. A February 2013 United Nations report declared EDs a “global threat” to wildlife and humans, particularly infants and children, with close to 800 chemicals known or suspected to disrupt hormone function, but thousands in use that have never been tested. Therefore, it has become imperative to involve a large swath of scientific community to urgently work toward the prevention and cure of its effects. Exposure to EDCs and their effects on human and wildlife health is a global problem that will require global solutions. There is also a need to stimulate new adaptive approaches that break down institutional and traditional scientific barriers and foster collaboration and stimulate interdisciplinary and multidisciplinary team science. I hope that this book would help to contribute toward these goals. For updates on the book contents, please visit www.sushilkhetan.com.

Acknowledgements

I am grateful to many of my colleagues in academia and industry who have made useful suggestions for improving this book as a reference source. My special thanks are to Prof. Terry Collins, who inspired me to review the subject from a chemical perspective and graciously wrote the foreword for this book. I especially recognize Dr. Anurag Khetan, Dr. Rick Stahlhut, and Dr. Naseer Ali for offering their critical comments and useful suggestions during various stages of the planning, researching, and writing of this book.

Finally, I would like to acknowledge the constant support of my wife, Manju, who endured countless hours of working on the manuscript. Without her forbearance and understanding, this venture could never have been accomplished.

Sushil K. Khetan