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.
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
