Chapter
Chapter 1 Environmental Endocrine Disruptors
1.1.1 The Endocrine System
1.1.2 Endocrine Disrupting Chemicals (EDCs)
1.1.3 Sources of EDCs in the Environment
1.1.4 Deleterious Effects of EDCs on Wildlife and on Humans
1.1.5 Endocrine Disruption Endpoints
1.2 Salient Aspects about Endocrine Disruption
1.2.1 Low-Dose Effects and Nonmonotonic Dose Responses
1.2.2 Exposures during Periods of Heightened Susceptibility in Critical Life Stages
1.2.3 Delayed Dysfunction
1.2.4 Importance of Mixtures
1.2.5 Transgenerational, Epigenetic Effects
1.3 Historical Perspective of Endocrine Disruption
1.4 Scope and Layout of this Book
Part I Mechanisms of Hormonal Action and Putative Endocrine Disruptors
Chapter 2 Mechanisms of Endocrine System Function
2.2.1 Hypothalamus-Pituitary-Gonad (HPG) Axis
2.2.2 The Hypothalamic-Pituitary-Thyroid (HPT) Axis
2.2.3 The Hypothalamic-Pituitary-Adrenal (HPA) Axis
2.3 Hormonal Cell Signaling
2.3.1 Receptors and Hormone Action
2.3.2 Genomic Signaling Pathway
2.3.3 Rapid-Response Pathway (Nongenomic Signaling)
2.3.4 Receptor Agonists, Partial Agonists, and Antagonists
2.4.1 Physiologic Estrogens
2.6 Conclusions and Future Prospects
Chapter 3 Environmental Chemicals Targeting Estrogen Signaling Pathways
3.1.1 Gonadal Estrogen Function Disruptors
3.2.1 Physiologic Estrogens
3.2.2 17alpha-Ethinylestradiol (EE2)
3.2.4 Mycoestrogen-Zearalenone (ZEN)
3.3 Nonsteroidal Estrogenic Chemicals
3.3.1 Diethylstilbestrol (DES)
3.3.2 Organochlorine Insecticides
3.3.3 Polychlorinated Biphenyls (PCBs)
3.3.5 Parabens (Hydroxy Benzoates)
3.3.6 Sun Screens (Chemical UV Filters)
3.5 Conclusion and Future Prospects
Chapter 4 Anti-Androgenic Chemicals
4.2 Testosterone Synthesis Inhibitors
4.3 Androgen Receptor (AR) Antagonists
4.3.1 Organochlorine (OC) Pesticides
4.3.2 Organophosphorus (OP) Insecticides
4.3.4 Polybrominated Diphenyl Ethers (PBDEs)
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
Chapter 5 Thyroid-Disrupting Chemicals
5.2 Thyroid Synthesis Inhibition by Interference in Iodide Uptake
5.3 TH Transport Disruptors and Estrogen Sulfotransferases Inhibitors
5.3.1 Polychlorinated Biphenyls (PCBs)
5.4 Thyroid Hormone Level Disruptors
5.4.1 Polybrominated Diphenyl Ethers (PBDEs)
5.5 Selective Thyroid Hormone Antagonists
5.5.2 Perfluoroalkyl Acids (PFAAs)
5.6 Conclusions and Future Prospects
Chapter 6 Activators of PPAR, RXR, AhR, and Steroidogenic Factor 1
6.2 Peroxisome Proliferator-Activated Receptor (PPAR) Agonists
6.2.1 Organotin Antifoulant Biocides
6.2.2 Perfluoroalkyl Compounds (PFCs)
6.3 Aryl Hydrocarbon Receptor (AhR) Agonists
6.3.1 Polychlorinated-Dibenzodioxins (PCDDs) and -Dibenzofurans (PCDFs)
6.3.2 Coplanar Polychlorinated Biphenyls
6.3.3 Substituted Urea and Anilide Herbicides
6.4 Steroidogenesis Modulator (Aromatase Expression Inducer)
6.5 Conclusions and Future Prospects
Chapter 7 Effects of EDC Mixtures
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
7.5.1 Anti-Androgens with Common Mechanism of Action
7.5.2 Anti-Androgens with Different Modes of Action
7.5.3 Chronic Exposure of Low Dose Mixture of Anti-Androgens Versus Acute Exposure to High Dose Individual Compounds
7.6 Mixture Effects of Thyroid Disrupting Chemicals
7.7 Mixture Effects of Chemicals Acting via AhR
7.8 Conclusions and Future Prospects
Chapter 8 Environmentally Induced Epigenetic Modifications and Transgenerational Effects
8.2 Regulatory Epigenetic Modifications
8.2.1 Methylation of Cytosine Residues in the DNA and Impact on Gene Expression (Transcriptional Silencing)
8.2.2 Remodeling of Chromatin Structure through Post-Translational Modifications of Histone Tails (Determinants of Accessibility)
8.2.3 Regulation of Gene Expression by Noncoding RNAs
8.2.5 Assays for Epigenetic Modification
8.3 Epigenetic Dysregulation Effects of Endocrine Disruption
8.3.1 Bisphenol A (BPA): A Case Study
8.4 Environmental Epigenetic Effects of Heavy Metals Exposure
8.5 Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations
8.5.5 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
8.6 Transgenerational Actions of EDCs Mixture on Reproductive Disease
8.7 Conclusions and Future Prospects
Part II Removal Mechanisms of EDC through Biotic and Abiotic Processes
Chapter 9 Biodegradations and Biotransformations of Selected Examples of EDCs
9.2 Natural and Synthetic Steroidal Estrogens
9.2.1 17beta-Estradiol and Estrone
9.2.2 17alpha-Ethynylestradiol
9.3.1 4-n-Nonylphenol (4-NP1)
9.3.2 4-tert-Nonylphenol Isomer 4-(1-Ethyl-1,4-Eimethylpentyl) Phenol (NP112)
9.3.3 4-tert-Nonylphenol Isomer 4-[1-Ethyl-1,3-Dimethylpentyl] Phenol (4-NP111)
9.3.4 4-n- and 4-tert-Octylphenols
9.4.1 Di-n-butyl Phthalate (DBP)
9.4.2 n-Butyl Benzyl Phthalate (BBP)
9.4.3 Di-(2-ethylhexyl) Phthalate (DEHP)
9.4.4 Di-n-octyl Phthalate (DOP)
9.8 Polychlorinated Biphenyls (PCBs)
9.9 Polybrominated Diphenyl Ethers (PBDEs)
9.9.1 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47)
9.9.2 2,2',4,4',5-Penta-bromodiphenyl Ether (BDE-99)
9.9.3 3,3',4,4',5,5',6,6'-Decabromodiphenyl Ether (BDE-209)
9.11 Conclusions and Future Prospects
Chapter 10 Abiotic Degradations/Transformations of EDCs Through Oxidation Processes
10.2 Natural and Synthetic Estrogens
10.2.1 17beta-Estradiol (E2) and Estrone (E1)
10.2.2 17alpha-Ethinylestradiol (EE2)
10.3.1 Chlorination with HOCl
10.3.2 Catalytic Oxidation with H2O2
10.3.3 Oxidation with KMnO4
10.3.4 Oxidation with MnO2
10.3.5 Treatment with Zero-Valent Aluminum
10.3.8 Photolytic and Photocatalytic Degradation
10.4 4-Octylphenol and 4-Nonylphenol
10.4.3 Photocatalytic Degradation
10.5.2 Photocatalytic Degradation
10.6 Phthalates-Photocatalytic Degradation
10.6.1 Dibutyl Phthalate (DBP)
10.6.2 n-Butyl Benzylphthalate
10.6.3 Di(2-Ethylhexyl)phthalate (DEHP)
10.7.1 Treatment with O3, UV, and UV/O3
10.8.2 Reaction with Ozone, Ozone/H2O2, and Ozone/OH Radicals
10.8.3 Treatment with delta-MnO2
10.8.4 Reductive Dechlorination
10.8.5 Photocatalytic Degradation
10.9 Polybrominated Diphenyl Ether (PBDE) Flame Retardants
10.9.1 Photochemical Degradation
10.9.2 TiO2-Mediated Photocatalytic Debromination
10.9.3 Zero-Valent Iron Reductive Debromination
10.10.1 Clorination with HOCl
10.10.2 Oxidation with KMnO4/MnO2
10.10.4 Photochemical Transformation
10.11.1 Modified Fenton Reaction
10.11.2 Sonochemical Degradation
10.11.3 Photocatalytic Reaction
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
11.2 Endocrine Disruptor Screening Program (EDSP)
11.3 Assays for the Detection of Chemicals that Alter the Estrogen Signaling Pathway
11.3.1 The ER Binding Assay (USEPA OPPTS 890.1250)
11.3.2 ERalpha Transcriptional Activation Assay (USEPA OPPTS 890.1300; OECD 455)
11.3.3 Aromatase Assay (USEPA OPPTS 890.1200)
11.3.4 In vivo Uterotrophic Bioassay in Rodents (USEPA OPPTS 890.1600; OECD 440)
11.3.5 Pubertal Female Rat Assay (USEPA OPPTS 890.1450)
11.3.6 Twenty-One-Day Fish Reproduction Assay (USEPA OPPTS 890.1350; OECD 229)
11.4 Assays for the Detection of Chemicals that Alter the Androgenic Signaling Pathway
11.4.1 AR Binding Assay (Rat Prostate Cytosol) (USEPA OPPTS 890.1150)
11.4.2 H295R Steroidogenesis Assay (USEPA OPPTS 890.1550)
11.4.3 Hershberger Bioassay in Rats for Androgenicity (USEPA OCSPP 890.1400; OECD 441)
11.4.4 Pubertal Male Rat Assay (USEPA OPPTS 890.1500)
11.4.5 Strengths and Limitations of Assays for Interference with Androgen Action
11.5 Assays for the Detection of Chemicals that Alter the HPT Axis
11.5.1 Amphibian Metamorphosis Assay (OPPTS 890.1100)
11.5.2 Strengths and Limitations of Thyroid Disrupting Chemical Assays
11.6 The USEPA's EDSP21 Work Plan
11.6.1 The USEPA ToxCast Program
11.6.2 Tox21 HTS Programs
11.7 Conclusions and Future Prospects
Chapter 12 Trace Contaminants: Implications for Water Quality Sustainability
12.2 Trace Contaminants Sources in Water
12.3 Wastewater Reclamation Processes
12.3.1 Primary Treatment: Sedimentation/Coagulation
12.3.2 Secondary Treatment: Removal by Physical Methods or Biological Process
12.3.3 Tertiary Treatment: Redox Processes
12.4 Indirect Water Reuse Systems
12.4.1 Removal of Trace Contaminants for Potable Water Reuse Applications
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
Chapter 13 Policy and Regulatory Considerations for EDCs
13.2 Regulating Paradigm Shift in Conventional Toxicology
13.2.1 Downward Movement of Safe Thresholds
13.2.2 Nonmonotonic Low-Dose Effects (Nonthreshold substances)
13.2.3 Sensitivity of Development Periods
13.2.4 Cumulative Exposures to Multiple EDCs (Exposures can be Additive)
13.2.5 Long Latency Between Exposure and Effect (Delayed Effects)
13.3 Policy Options for EDC Regulation
13.3.1 Scientific Uncertainty and Precautionary Policy
13.3.2 Shifting the Burden of Proving Safe Products
13.3.3 Need to Broaden the Risk Assessment
13.3.4 Cutting-Edge Bioassays Showing Developmental Endpoints
13.4 Controversy on Regulatory Framework for EDCs
13.4.1 Diversity of Viewpoints of the Risk Assessors and the Endocrine Scientists
13.4.2 A Debate on EU Regulatory Framework for EDCs
13.5 Conclusions and Future Prospects
Chapter 14 Green Chemistry Principles in the Designing and Screening for Safe Chemicals and Remediation of EDCs
14.2 Benign by Design Chemicals
14.3 Chemical Endocrine Disruption Screening Protocol
14.3.1 Tiered Protocol for Endocrine Disruption
14.4 Green Oxidative Remediation of EDCs
14.4.1 Catalytic Oxidation Processes
14.5 Conclusions and Future Prospects
Endocrine Disruptors in the Environment
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