Endocrine Disrupters
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Preface ix
Contributors xi
1 Ecotoxicity Test Methods for Endocrine-Disrupting Chemicals: An Introduction 1
Peter Matthiessen
1.1 Background 1
1.2 Regulatory Concerns 2
1.3 Invertebrates 2
1.4 Vertebrates 3
1.5 Testing Schemes for EDCs 5
Reference 6
2 Endocrine Disruption inWildlife: Background, Effects, and Implications 7
Dick Vethaak and Juliette Legler
2.1 Background to Endocrine Disruption 8
2.2 Effects of EDCs on Wildlife 19
2.3 Weight of Evidence and Ecological Significance of ED Effects 32
2.4 Implications for Effect Assessment and Toxicity Testing 36
2.5 Need for More Field Studies and an Integrated Approach 38
2.6 Concluding Points 39
References 40
3 The Regulatory Need for Tests to Detect EDCs and Assess Their Hazards toWildlife 59
Hans-Christian Stolzenberg, Tobias Frische, Vicki L. Dellarco, Gary Timm, Anne Gourmelon, Taisen Iguchi, Flemming Ingerslev, and Mike Roberts
3.1 Emerging Concerns and Policy Responses: Focusing on EDCs as a Large Pseudo-Uniform Group of Substances 60
3.2 General Approaches in Substance-Related Regulatory Frameworks (EU) 80
3.3 How to Make EDC Definitions Operational for Substance-Related Regulatory Work 87
3.4 Future Perspectives 91
3.5 Conclusions 92
References 93
4 Techniques for Measuring Endocrine Disruption in Insects 100
Lennart Weltje
4.1 Introduction 100
4.2 Methods 105
4.3 Discussion 108
4.4 Conclusion 110
4.5 Acknowledgments 110
References 110
5 Crustaceans 116
Magnus Breitholtz
5.1 Introduction 116
5.2 Background to Crustacean Endocrinology 118
5.3 State of the Art: What Do We Know About Endocrine Disruption in Crustaceans? 121
5.4 Available Subchronic/Chronic Standard Test Protocols 128
5.5 Complementary Tools for Identification of Endocrine Disruption 129
5.6 Summary and Conclusions 132
References 134
6 Endocrine Disruption in Molluscs: Processes and Testing 143
Patricia D. McClellan-Green
6.1 Background and Introduction 143
6.2 What Constitutes the Endocrine System in Molluscs? 145
6.3 End Points and Biomarkers of Endocrine Disruption 154
6.4 Current Test Methods Using Molluscs 164
6.5 Proposed Test Methods 167
6.6 Conclusions 171
References 172
7 Using Fish to Detect Endocrine Disrupters and Assess Their Potential Environmental Hazards 185
Peter Matthiessen
7.1 Introduction 185
7.2 International Efforts to Standardize Fish-Based Methods for Screening and Testing Endocrine-Disrupting
7.3 Fish-Based Screens Developed by OECD for Endocrine-Disrupting Chemicals 189
7.4 Progress with Developing Fish Partial Life Cycle Tests for Endocrine Disrupters 194
7.5 Prospects for the Standardization of Fish Full Life Cycle and Multigeneration Tests 195
7.6 Strengths and Weaknesses of a Hazard Evaluation Strategy Based Partly on Available and Proposed Fish Screens and Tests 197
7.7 Conclusions 198
References 198
8 Screening and Testing for Endocrine-Disrupting Chemicals in Amphibian Models 202
Daniel B. Pickford
8.1 Introduction 202
8.2 Potential Uses of Amphibians in Endocrine Disrupter Screening and Testing Programs 203
8.3 Embryonic Development 205
8.4 Hatching 208
8.5 Larval Development 209
8.6 Higher-Tier Tests with Amphibians 224
8.7 Other and Emerging Test Methods 227
8.8 Summary and Conclusions 229
References 232
9 Endocrine Disruption and Reptiles: Using the Unique Attributes of Temperature-Dependent Sex Determination to Assess Impacts 245
Satomi Kohno and Louis J. Guillette, Jr.
9.1 Introduction 245
9.2 Approaches to Examine Effects of EDCs 252
9.3 Induction of Sex Reversal In Ovo 255
9.4 Analysis of Sex-Reversed Animals 260
9.5 Conclusions 265
References 266
10 Birds 272
Paul D. Jones, Markus Hecker, Steve Wiseman, and John P. Giesy
10.1 Introduction 272
10.2 Differences Between Birds and Mammals and Among Bird Species 275
10.3 In Vitro Techniques 278
10.4 Studies with Embryos 280
10.5 In Vivo Techniques 280
10.6 Examples of EDC Effects from Field Studies 285
10.7 Proposed Two-Generation Test 288
10.8 Conclusions 291
References 292
11 Mammalian Methods for Detecting and Assessing Endocrine-Active Compounds 304
M. Sue Marty
11.1 Introduction 304
11.2 Mammalian Tier 1 Screening Assays 306
11.3 Tier 2 Tests 326
11.4 Human and Wildlife Relevance of Estrogen, Androgen, and Thyroid Screening Assays 329
11.5 Potential Future Assays for Endocrine Screening 330
References 332
12 Application of the OECD Conceptual Framework for Assessing the Human Health and Ecological Effects of Endocrine Disrupters 341
Thomas H. Hutchinson, Jenny Odum, and Anne Gourmelon
12.1 Introduction 342
12.2 Overview of the OECD Revised CF 343
12.3 Application of the Klimisch Criteria to the EE2 and VIN Case Studies 346
12.4 Case Study: Data Examples for 17-Ethynylestradiol 346
12.5 Case Study: Data Examples for Vinclozolin 357
12.6 Conclusions 367
References 368
13 The Prospects for Routine Testing of Chemicals for Endocrine-Disrupting Properties and Potential Ecological Impacts 373
Peter Matthiessen
13.1 Introduction 373
13.2 Are There Gaps in the Test Suite for EDCs? 374
13.3 "New" Modes of Endocrine-Disrupting Action 376
13.4 How Should Tests for EDCs Be Deployed in an Integrated Fashion? 377
13.5 Use of Weight of Evidence when Assessing Possible EDCs 380
13.6 Conclusions 382
References 382
Index 385
