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This book describes methodology and applications for endocrine disrupter toxicity testing, an issue of considerable urgency, because of international regulatory authorities currently considering such testing schemes. The coverage examines major animal groups for sensitivity to endocrine disrupting chemicals (EDCs), identifying endpoints and procedures for testing guidelines. Three EDC screening methods (two using fish and one using amphibians) are examined in detail for their efficacy and applicability. Edited by, and with contributions from, a leading participant in regulatory efforts, the book outlines methods that combine sensitivity, efficiency, statistical power, acceptable cost, and minimum ethical concern.

Endocrine Disrupters: Hazard Testing and Assessment Methods

Preface ixContributors xi1 Ecotoxicity Test Methods for Endocrine-Disrupting Chemicals: An Introduction 1Peter Matthiessen1.1 Background 11.2 Regulatory Concerns 21.3 Invertebrates 21.4 Vertebrates 31.5 Testing Schemes for EDCs 5Reference 62 Endocrine Disruption inWildlife: Background, Effects, and Implications 7Dick Vethaak and Juliette Legler2.1 Background to Endocrine Disruption 82.2 Effects of EDCs on Wildlife 192.3 Weight of Evidence and Ecological Significance of ED Effects 322.4 Implications for Effect Assessment and Toxicity Testing 362.5 Need for More Field Studies and an Integrated Approach 382.6 Concluding Points 39References 403 The Regulatory Need for Tests to Detect EDCs and Assess Their Hazards toWildlife 59Hans-Christian Stolzenberg, Tobias Frische, Vicki L. Dellarco, Gary Timm, Anne Gourmelon, Taisen Iguchi, Flemming Ingerslev, and Mike Roberts3.1 Emerging Concerns and Policy Responses: Focusing on EDCs as a Large Pseudo-Uniform Group of Substances 603.2 General Approaches in Substance-Related Regulatory Frameworks (EU) 803.3 How to Make EDC Definitions Operational for Substance-Related Regulatory Work 873.4 Future Perspectives 913.5 Conclusions 92References 934 Techniques for Measuring Endocrine Disruption in Insects 100Lennart Weltje4.1 Introduction 1004.2 Methods 1054.3 Discussion 1084.4 Conclusion 1104.5 Acknowledgments 110References 1105 Crustaceans 116Magnus Breitholtz5.1 Introduction 1165.2 Background to Crustacean Endocrinology 1185.3 State of the Art: What Do We Know About Endocrine Disruption in Crustaceans? 1215.4 Available Subchronic/Chronic Standard Test Protocols 1285.5 Complementary Tools for Identification of Endocrine Disruption 1295.6 Summary and Conclusions 132References 1346 Endocrine Disruption in Molluscs: Processes and Testing 143Patricia D. McClellan-Green6.1 Background and Introduction 1436.2 What Constitutes the Endocrine System in Molluscs? 1456.3 End Points and Biomarkers of Endocrine Disruption 1546.4 Current Test Methods Using Molluscs 1646.5 Proposed Test Methods 1676.6 Conclusions 171References 1727 Using Fish to Detect Endocrine Disrupters and Assess Their Potential Environmental Hazards 185Peter Matthiessen7.1 Introduction 1857.2 International Efforts to Standardize Fish-Based Methods for Screening and Testing Endocrine-Disrupting7.3 Fish-Based Screens Developed by OECD for Endocrine-Disrupting Chemicals 1897.4 Progress with Developing Fish Partial Life Cycle Tests for Endocrine Disrupters 1947.5 Prospects for the Standardization of Fish Full Life Cycle and Multigeneration Tests 1957.6 Strengths and Weaknesses of a Hazard Evaluation Strategy Based Partly on Available and Proposed Fish Screens and Tests 1977.7 Conclusions 198References 1988 Screening and Testing for Endocrine-Disrupting Chemicals in Amphibian Models 202Daniel B. Pickford8.1 Introduction 2028.2 Potential Uses of Amphibians in Endocrine Disrupter Screening and Testing Programs 2038.3 Embryonic Development 2058.4 Hatching 2088.5 Larval Development 2098.6 Higher-Tier Tests with Amphibians 2248.7 Other and Emerging Test Methods 2278.8 Summary and Conclusions 229References 2329 Endocrine Disruption and Reptiles: Using the Unique Attributes of Temperature-Dependent Sex Determination to Assess Impacts 245Satomi Kohno and Louis J. Guillette, Jr.9.1 Introduction 2459.2 Approaches to Examine Effects of EDCs 2529.3 Induction of Sex Reversal In Ovo 2559.4 Analysis of Sex-Reversed Animals 2609.5 Conclusions 265References 26610 Birds 272Paul D. Jones, Markus Hecker, Steve Wiseman, and John P. Giesy10.1 Introduction 27210.2 Differences Between Birds and Mammals and Among Bird Species 27510.3 In Vitro Techniques 27810.4 Studies with Embryos 28010.5 In Vivo Techniques 28010.6 Examples of EDC Effects from Field Studies 28510.7 Proposed Two-Generation Test 28810.8 Conclusions 291References 29211 Mammalian Methods for Detecting and Assessing Endocrine-Active Compounds 304M. Sue Marty11.1 Introduction 30411.2 Mammalian Tier 1 Screening Assays 30611.3 Tier 2 Tests 32611.4 Human and Wildlife Relevance of Estrogen, Androgen, and Thyroid Screening Assays 32911.5 Potential Future Assays for Endocrine Screening 330References 33212 Application of the OECD Conceptual Framework for Assessing the Human Health and Ecological Effects of Endocrine Disrupters 341Thomas H. Hutchinson, Jenny Odum, and Anne Gourmelon12.1 Introduction 34212.2 Overview of the OECD Revised CF 34312.3 Application of the Klimisch Criteria to the EE2 and VIN Case Studies 34612.4 Case Study: Data Examples for 17-Ethynylestradiol 34612.5 Case Study: Data Examples for Vinclozolin 35712.6 Conclusions 367References 36813 The Prospects for Routine Testing of Chemicals for Endocrine-Disrupting Properties and Potential Ecological Impacts 373Peter Matthiessen13.1 Introduction 37313.2 Are There Gaps in the Test Suite for EDCs? 37413.3 "New" Modes of Endocrine-Disrupting Action 37613.4 How Should Tests for EDCs Be Deployed in an Integrated Fashion? 37713.5 Use of Weight of Evidence when Assessing Possible EDCs 38013.6 Conclusions 382References 382Index 385