Description
Book SynopsisOffers an overview of endocrine disruption phenomena. This book lists the major environmental chemicals of concern and their mechanism of endocrine disruption including remedial measures for them. It also focuses on removal processes of various EDCs by biotic and abiotic transformation/degradation.
Trade Review“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)
Table of ContentsForeword 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 for Water 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
