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Endocrine Disruptors in the Environment

ISBN: 978-1-118-89115-5
408 pages
May 2014
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Description

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.

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Table of Contents

Foreword xiv

Preface xviii

Acronyms xxi

Glossary xxvi

1 Environmental Endocrine Disruptors 1

1.1 Introduction, 1

1.1.1 The Endocrine System, 1

1.1.2 Endocrine Disrupting Chemicals (EDCs), 3

1.1.3 Sources of EDCs in the Environment, 4

1.1.4 Deleterious Effects of EDCs on Wildlife and on Humans, 6

1.1.5 Endocrine Disruption Endpoints, 6

1.2 Salient Aspects about Endocrine Disruption, 7

1.2.1 Low-Dose Effects and Nonmonotonic Dose Responses, 7

1.2.2 Exposures during Periods of Heightened Susceptibility in Critical Life Stages, 9

1.2.3 Delayed Dysfunction, 11

1.2.4 Importance of Mixtures, 11

1.2.5 Transgenerational, Epigenetic Effects, 12

1.3 Historical Perspective of Endocrine Disruption, 12

1.4 Scope and Layout of this Book, 19

1.5 Conclusion, 20

References, 21

PART I MECHANISMS OF HORMONAL ACTION AND PUTATIVE ENDOCRINE DISRUPTORS 27

2 Mechanisms of Endocrine System Function 29

2.1 Introduction, 29

2.2 Hormonal Axes, 29

2.2.1 Hypothalamus–Pituitary–Gonad (HPG) Axis, 31

2.2.2 The Hypothalamic–Pituitary–Thyroid (HPT) Axis, 33

2.2.3 The Hypothalamic–Pituitary–Adrenal (HPA) Axis, 34

2.3 Hormonal Cell Signaling, 35

2.3.1 Receptors and Hormone Action, 35

2.3.2 Genomic Signaling Pathway, 36

2.3.3 Rapid-Response Pathway (Nongenomic Signaling), 38

2.3.4 Receptor Agonists, Partial Agonists, and Antagonists, 40

2.4 Sex Steroids, 41

2.4.1 Physiologic Estrogens, 41

2.4.2 Androgens, 43

2.5 Thyroid Hormones, 45

2.6 Conclusions and Future Prospects, 46

References, 47

3 Environmental Chemicals Targeting Estrogen Signaling Pathways 51

3.1 Introduction, 51

3.1.1 Gonadal Estrogen Function Disruptors, 52

3.2 Steroidal Estrogens, 54

3.2.1 Physiologic Estrogens, 55

3.2.2 17α-Ethinylestradiol (EE2), 55

3.2.3 Phytoestrogens, 57

3.2.4 Mycoestrogen – Zearalenone (ZEN), 59

3.3 Nonsteroidal Estrogenic Chemicals, 60

3.3.1 Diethylstilbestrol (DES), 60

3.3.2 Organochlorine Insecticides, 62

3.3.3 Polychlorinated Biphenyls (PCBs), 65

3.3.4 Alkyphenols, 65

3.3.5 Parabens (Hydroxy Benzoates), 73

3.3.6 Sun Screens (Chemical UV Filters), 74

3.4 Metalloestrogens, 75

3.4.1 Cadmium (Cd), 76

3.4.2 Lead (Pb), 76

3.4.3 Mercury (Hg), 77

3.4.4 Arsenic (As), 77

3.5 Conclusion and Future Prospects, 78

References, 78

4 Anti-Androgenic Chemicals 91

4.1 Introduction, 91

4.2 Testosterone Synthesis Inhibitors, 92

4.2.1 Phthalates, 92

4.3 Androgen Receptor (AR) Antagonists, 96

4.3.1 Organochlorine (OC) Pesticides, 96

4.3.2 Organophosphorus (OP) Insecticides, 98

4.3.3 Bisphenol A (BPA), 99

4.3.4 Polybrominated Diphenyl Ethers (PBDEs), 99

4.3.5 Vinclozolin (VZ), 100

4.3.6 Procymidone, 101

4.4 AR Antagonists and Fetal Testosterone Synthesis Inhibitors, 102

4.4.1 Prochloraz, 102

4.4.2 Linuron, 103

4.5 Comparative Anti-Androgenic Effects of Pesticides to Androgen Agonist DHT, 103

4.6 Conclusions and Future Prospects, 103

References, 104

5 Thyroid-Disrupting Chemicals 111

5.1 Introduction, 111

5.2 Thyroid Synthesis Inhibition by Interference in Iodide Uptake, 113

5.2.1 Perchlorate, 113

5.3 TH Transport Disruptors and Estrogen Sulfotransferases Inhibitors, 114

5.3.1 Polychlorinated Biphenyls (PCBs), 114

5.3.2 Triclosan, 116

5.4 Thyroid Hormone Level Disruptors, 117

5.4.1 Polybrominated Diphenyl Ethers (PBDEs), 117

5.5 Selective Thyroid Hormone Antagonists, 119

5.5.1 Bisphenols, 119

5.5.2 Perfluoroalkyl Acids (PFAAs), 120

5.5.3 Phthalates, 120

5.6 Conclusions and Future Prospects, 121

References, 121

6 Activators of PPAR, RXR, AhR, and Steroidogenic Factor 1 126

6.1 Introduction, 126

6.2 Peroxisome Proliferator-Activated Receptor (PPAR) Agonists, 127

6.2.1 Organotin Antifoulant Biocides, 128

6.2.2 Perfluoroalkyl Compounds (PFCs), 130

6.2.3 Phthalates, 132

6.3 Aryl Hydrocarbon Receptor (AhR) Agonists, 133

6.3.1 Polychlorinated-Dibenzodioxins (PCDDs) and -Dibenzofurans (PCDFs), 133

6.3.2 Coplanar Polychlorinated Biphenyls, 135

6.3.3 Substituted Urea and Anilide Herbicides, 135

6.4 Steroidogenesis Modulator (Aromatase Expression Inducer), 136

6.4.1 Atrazine, 136

6.5 Conclusions and Future Prospects, 138

References, 139

7 Effects of EDC Mixtures 146

7.1 Introduction, 146

7.2 Combined Effect of Exposure to Multiple Chemicals, 146

7.3 Mixture Effects of Estrogenic Chemicals, 148

7.4 Mixture Effects of Estrogens and Anti-Estrogens, 151

7.5 Mixture Effects of Anti-Androgens, 152

7.5.1 Anti-Androgens with Common Mechanism of Action, 152

7.5.2 Anti-Androgens with Different Modes of Action, 154

7.5.3 Chronic Exposure of Low Dose Mixture of Anti-Androgens Versus Acute Exposure to High Dose Individual Compounds, 156

7.6 Mixture Effects of Thyroid Disrupting Chemicals, 157

7.7 Mixture Effects of Chemicals Acting via AhR, 158

7.8 Conclusions and Future Prospects, 158

References, 161

8 Environmentally Induced Epigenetic Modifications and Transgenerational Effects 166

8.1 Introduction, 166

8.2 Regulatory Epigenetic Modifications, 168

8.2.1 Methylation of Cytosine Residues in the DNA and Impact on Gene Expression (Transcriptional Silencing), 168

8.2.2 Remodeling of Chromatin Structure through Post-Translational Modifications of Histone Tails
(Determinants of Accessibility), 170

8.2.3 Regulation of Gene Expression by Noncoding RNAs, 173

8.2.4 DNA Demethylation, 174

8.2.5 Assays for Epigenetic Modification, 175

8.3 Epigenetic Dysregulation Effects of Endocrine Disruption, 176

8.3.1 Bisphenol A (BPA): A Case Study, 177

8.3.2 DEHP, 179

8.4 Environmental Epigenetic Effects of Heavy Metals Exposure, 179

8.4.1 Cadmium, 180

8.4.2 Arsenic, 180

8.4.3 Nickel, 180

8.4.4 Lead, 181

8.5 Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations, 181

8.5.1 DES, 182

8.5.2 Vinclozolin, 183

8.5.3 Methoxychlor, 185

8.5.4 BPA, 185

8.5.5 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 185

8.6 Transgenerational Actions of EDCs Mixture on Reproductive Disease, 186

8.7 Conclusions and Future Prospects, 187

References, 188

PART II REMOVAL MECHANISMS OF EDCs THROUGH BIOTIC AND ABIOTIC PROCESSES 195

9 Biodegradations and Biotransformations of Selected Examples of EDCs 197

9.1 Introduction, 197

9.2 Natural and Synthetic Steroidal Estrogens, 199

9.2.1 17β-Estradiol and Estrone, 199

9.2.2 17α-Ethynylestradiol, 202

9.3 Alkylphenols, 205

9.3.1 4-n-Nonylphenol (4-NP1), 205

9.3.2 4-tert-Nonylphenol Isomer 4-(1-Ethyl-1,4-Eimethylpentyl) Phenol (NP112), 208

9.3.3 4-tert-Nonylphenol Isomer 4-[1-Ethyl-1,3-Dimethylpentyl] Phenol (4-NP111), 210

9.3.4 4-n- and 4-tert-Octylphenols, 212

9.3.5 Bisphenol A, 214

9.4 Phthalates, 220

9.4.1 Di-n-butyl Phthalate (DBP), 221

9.4.2 n-Butyl Benzyl Phthalate (BBP), 222

9.4.3 Di-(2-ethylhexyl) Phthalate (DEHP), 223

9.4.4 Di-n-octyl Phthalate (DOP), 226

9.5 Insecticides, 226

9.5.1 Methoxychlor, 226

9.6 Fungicides, 228

9.6.1 Vinclozolin, 228

9.6.2 Procymidone, 231

9.6.3 Prochloraz, 232

9.7 Herbicides, 232

9.7.1 Linuron, 232

9.7.2 Atrazine, 233

9.8 Polychlorinated Biphenyls (PCBs), 236

9.9 Polybrominated Diphenyl Ethers (PBDEs), 238

9.9.1 2,2′,4,4′-Tetrabromodiphenyl Ether (BDE-47), 238

9.9.2 2,2′,4,4′,5-Penta-bromodiphenyl Ether (BDE-99), 243

9.9.3 3,3′,4,4′,5,5′,6,6′-Decabromodiphenyl Ether (BDE-209), 243

9.10 Triclosan, 245

9.11 Conclusions and Future Prospects, 245

References, 246

10 Abiotic Degradations/Transformations of EDCs Through Oxidation Processes 254

10.1 Introduction, 254

10.2 Natural and Synthetic Estrogens, 256

10.2.1 17β-Estradiol (E2) and Estrone (E1), 256

10.2.2 17α-Ethinylestradiol (EE2), 260

10.3 Bisphenol A, 260

10.3.1 Chlorination with HOCl, 263

10.3.2 Catalytic Oxidation with H2O2, 263

10.3.3 Oxidation with KMnO4, 266

10.3.4 Oxidation with MnO2, 267

10.3.5 Treatment with Zero-Valent Aluminum, 267

10.3.6 Ozonation, 267

10.3.7 Fenton Reaction, 270

10.3.8 Photolytic and Photocatalytic Degradation, 272

10.4 4-Octylphenol and 4-Nonylphenol, 272

10.4.1 Chlorination, 272

10.4.2 Ozonation, 274

10.4.3 Photocatalytic Degradation, 274

10.5 Parabens, 274

10.5.1 Ozonation, 276

10.5.2 Photocatalytic Degradation, 276

10.6 Phthalates – Photocatalytic Degradation, 276

10.6.1 Dibutyl Phthalate (DBP), 277

10.6.2 n-Butyl Benzylphthalate, 277

10.6.3 Di(2-Ethylhexyl)phthalate (DEHP), 279

10.7 Linuron, 279

10.7.1 Treatment with O3, UV, and UV/O3, 279

10.8 Atrazine, 281

10.8.1 Fenton Reaction, 281

10.8.2 Reaction with Ozone, Ozone/H2O2, and Ozone/OH Radicals, 282

10.8.3 Treatment with δ-MnO2, 282

10.8.4 Reductive Dechlorination, 282

10.8.5 Photocatalytic Degradation, 282

10.9 Polybrominated Diphenyl Ether (PBDE) Flame Retardants, 282

10.9.1 Photochemical Degradation, 282

10.9.2 TiO2-Mediated Photocatalytic Debromination, 284

10.9.3 Zero-Valent Iron Reductive Debromination, 285

10.10 Triclosan, 285

10.10.1 Clorination with HOCl, 285

10.10.2 Oxidation with KMnO4/MnO2, 286

10.10.3 Ozonation, 286

10.10.4 Photochemical Transformation, 286

10.11 PFOA and PFOS, 289

10.11.1 Modified Fenton Reaction, 289

10.11.2 Sonochemical Degradation, 289

10.11.3 Photocatalytic Reaction, 289

10.12 Conclusions, 289

References, 290

PART III SCREENING AND TESTING FOR POTENTIAL EDCs, IMPLICATIONS FOR WATER QUALITY SUSTAINABILITY, POLICY AND REGULATORY ISSUES, AND GREEN CHEMISTRY PRINCIPLES IN THE DESIGN OF SAFE CHEMICALS AND REMEDIATION OF EDCs 297

11 Screening and Testing Programs for EDCs 299

11.1 Introduction, 299

11.2 Endocrine Disruptor Screening Program (EDSP), 300

11.2.1 EDSP Tier 1, 301

11.2.2 EDSP Tier 2, 302

11.3 Assays for the Detection of Chemicals that Alter the Estrogen Signaling Pathway, 304

11.3.1 The ER Binding Assay (USEPA OPPTS 890.1250), 304

11.3.2 ERα Transcriptional Activation Assay (USEPA OPPTS 890.1300; OECD 455), 304

11.3.3 Aromatase Assay (USEPA OPPTS 890.1200), 306

11.3.4 In vivo Uterotrophic Bioassay in Rodents (USEPA OPPTS 890.1600; OECD 440), 307

11.3.5 Pubertal Female Rat Assay (USEPA OPPTS 890.1450), 308

11.3.6 Twenty-One-Day Fish Reproduction Assay (USEPA OPPTS 890.1350; OECD 229), 308

11.4 Assays for the Detection of Chemicals that Alter the Androgenic Signaling Pathway, 308

11.4.1 AR Binding Assay (Rat Prostate Cytosol) (USEPA OPPTS 890.1150), 309

11.4.2 H295R Steroidogenesis Assay (USEPA OPPTS 890.1550), 309

11.4.3 Hershberger Bioassay in Rats for Androgenicity (USEPA OCSPP 890.1400; OECD 441), 309

11.4.4 Pubertal Male Rat Assay (USEPA OPPTS 890.1500), 310

11.4.5 Strengths and Limitations of Assays for Interference with Androgen Action, 310

11.5 Assays for the Detection of Chemicals that Alter the HPT Axis, 311

11.5.1 Amphibian Metamorphosis Assay (OPPTS 890.1100), 311

11.5.2 Strengths and Limitations of Thyroid Disrupting Chemical Assays, 311

11.6 The USEPA’s EDSP21 Work Plan, 312

11.6.1 The USEPA ToxCast Program, 313

11.6.2 Tox21 HTS Programs, 314

11.7 Conclusions and Future Prospects, 316

References, 317

12 Trace Contaminants: Implications forWater Quality Sustainability 320

12.1 Introduction, 320

12.2 Trace Contaminants Sources in Water, 321

12.3 Wastewater Reclamation Processes, 323

12.3.1 Primary Treatment: Sedimentation/Coagulation, 323

12.3.2 Secondary Treatment: Removal by Physical Methods or Biological Process, 324

12.3.3 Tertiary Treatment: Redox Processes, 325

12.4 Indirect Water Reuse Systems, 326

12.4.1 Removal of Trace Contaminants for Potable Water Reuse Applications, 326

12.5 Leaching of Contaminants in Water – the Case of Bottled Water, 327

12.6 Water Quality Sustainability and Health Effects, 328

12.7 Toxicological Implications, 329

12.8 Regulatory Structures to Maintain Water Quality, 330

12.9 Conclusions and Future Prospects, 331

References, 333

13 Policy and Regulatory Considerations for EDCs 339

13.1 Introduction, 339

13.2 Regulating Paradigm Shift in Conventional Toxicology, 340

13.2.1 Downward Movement of Safe Thresholds, 341

13.2.2 Nonmonotonic Low-Dose Effects (Nonthreshold substances), 341

13.2.3 Sensitivity of Development Periods, 342

13.2.4 Cumulative Exposures to Multiple EDCs (Exposures can be Additive), 342

13.2.5 Long Latency Between Exposure and Effect (Delayed Effects), 343

13.3 Policy Options for EDC Regulation, 344

13.3.1 Scientific Uncertainty and Precautionary Policy, 344

13.3.2 Shifting the Burden of Proving Safe Products, 345

13.3.3 Need to Broaden the Risk Assessment, 346

13.3.4 Cutting-Edge Bioassays Showing Developmental Endpoints, 346

13.4 Controversy on Regulatory Framework for EDCs, 348

13.4.1 Diversity of Viewpoints of the Risk Assessors and the Endocrine Scientists, 348

13.4.2 A Debate on EU Regulatory Framework for EDCs, 350

13.5 Conclusions and Future Prospects, 351

References, 353

14 Green Chemistry Principles in the Designing and Screening for Safe Chemicals and Remediation of EDCs 357

14.1 Introduction, 357

14.2 Benign by Design Chemicals, 358

14.3 Chemical Endocrine Disruption Screening Protocol, 361

14.3.1 Tiered Protocol for Endocrine Disruption, 361

14.4 Green Oxidative Remediation of EDCs, 363

14.4.1 Catalytic Oxidation Processes, 364

14.5 Conclusions and Future Prospects, 366

References, 368

Index 371

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Author Information

SUSHIL K. KHETAN, PhD, a research chemist at the Institute for Green Science in Carnegie Mellon University, has been working at the confluence of environmental and green chemistry. Earlier he worked in the agrochemicals industry and published two books on environmentally-friendly pest control technologies. He has consulted globally for several international organizations.

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Reviews

“This book is a great resource for those wanting an overview of this grand collaborative enterprise, or for those preparing the next generation for investigating, problem-solving, and managing our bio-chemical future, giving us a chance to balance modern living with safety.”  (Endocrine Disruptors, 1 October 2014)

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