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EDSP webinar 1: Background, lesson learned and the future

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This webinar will review the importance of the endocrine system for human health; EPA's regulatory history of how the current testing program developed; lessons learned from providing OSRI (Other Scientific Relevant Information) in response to Tier 1 Test Orders; conducting Tier 1 screens; and, integrating Tier 1 screening data with OSRI to generate Weight of Evidence documents that speak to whether further testing (Tier 2 studies) are needed and appropriate. More info at http://www.huntingdon.com/Chemical/Endocrinedisruptorscreeningprogram/Webinars

Text of EDSP webinar 1: Background, lesson learned and the future

  • 1. Endocrine Disruptor Screening Program Webinar week 20-23 January 2014 www.huntingdon.com
  • 2. EDSP: Background, lessons learned, and forecast for the future Elliot Gordon Elliot Gordon Consulting, LLC http://ebgfox.wix.com/elliot-gordon www.huntingdon.com
  • 3. Endocrine Update EDSP and You www.huntingdon.com 3
  • 4. Introduction Presumptions New to the Game www.huntingdon.com 4
  • 5. Introduction Presumptions New to the Game (First Test Orders from List 2) www.huntingdon.com 5
  • 6. Introduction Presumptions New to the Game (First Test Orders from List 2) List 1 but not done www.huntingdon.com 6
  • 7. Introduction Presumptions New to the Game (First Test Orders from List 2) List 1 but not done (List 2 Test Orders coming) www.huntingdon.com 7
  • 8. Introduction Presumptions New to the Game (First Test Orders from List 2) List 1 but not done (List 2 Test Orders coming) List 1 and done but Tier 2 looms www.huntingdon.com 8
  • 9. Introduction Presumptions New to the Game (First Test Orders from List 2) List 1 but not done (List 2 Test Orders coming) List 1 and done but Tier 2 looms Lessons learned www.huntingdon.com 9
  • 10. Your Attention Please! $1,000,000 per chemical. www.huntingdon.com 10
  • 11. $ $1,000,000 per chemical. Waivers based on OSRI. www.huntingdon.com 11
  • 12. $ $1,000,000 per chemical. Waivers based on OSRI. OSRI: Other Scientifically Relevant Information www.huntingdon.com 12
  • 13. $$ $1,000,000 per chemical. Waivers based on OSRI. Number of screens required. www.huntingdon.com 13
  • 14. $$$ $1,000,000 per chemical. Waivers based on OSRI. Number of screens required. Ability to form consortium. www.huntingdon.com 14
  • 15. $$$$ $1,000,000 per chemical. Waivers based on OSRI. Number of screens required. Ability to form consortium. Development of Weights of Evidence. www.huntingdon.com 15
  • 16. $$$$$ $1,000,000 per chemical. Waivers based on OSRI. Number of screens required. Ability to form consortium. Development of Weights of Evidence. Tier 2 studies, if required. www.huntingdon.com 16
  • 17. Definition A chemical that affects the endocrine system and results in adverse biologic effects. Not: a chemical that is included in Lists 1 or 2. Not: a chemical that may show an effect in a screening assay. www.huntingdon.com 17
  • 18. Timeline 1962 1970 1996 2009 2014 www.huntingdon.com 18
  • 19. Timeline 1962 Silent Spring 1970 1996 2009 2014 www.huntingdon.com 19
  • 20. Timeline 1962 Silent Spring 1970 1996 2009 2014 www.huntingdon.com 20
  • 21. Timeline 1962 Silent Spring 1970 1996 2009 2014 www.huntingdon.com 21
  • 22. Timeline 1962 1970 EPA 1996 2009 2014 www.huntingdon.com 22
  • 23. Timeline 1962 1970 EPA 1996 2009 2014 www.huntingdon.com 23
  • 24. Timeline 1962 1970 EPA 1996 2009 2014 www.huntingdon.com 24
  • 25. Timeline 1962 1970 1996 Our Stolen Future 2009 2014 www.huntingdon.com 25
  • 26. Timeline 1962 1970 1996 Our Stolen Future 2009 2014 www.huntingdon.com 26
  • 27. Timeline 1962 1970 1996 Our Stolen Future 2009 2014 www.huntingdon.com 27
  • 28. Timeline 1962 1970 1996 Our Stolen Future 2009 2014 Endocrine Disruptor www.huntingdon.com 28
  • 29. Timeline 1962 1970 1996 FQPA 2009 2014 www.huntingdon.com 29
  • 30. Timeline 1962 1970 1996 FQPA 2009 2014 www.huntingdon.com Food Quality Protection Act 30
  • 31. Timeline 1962 1970 1996 FQPA 2009 2014 James Delaney www.huntingdon.com 31
  • 32. Timeline 1962 1970 1996 FQPA 2009 Aggregate Risk 2014 www.huntingdon.com 32
  • 33. Timeline 1962 1970 1996 FQPA 2009 Aggregate Risk Cumulative Risk 2014 www.huntingdon.com 33
  • 34. Timeline 1962 1970 1996 FQPA 2009 Aggregate Risk Cumulative Risk Extra Safety Factors 2014 www.huntingdon.com 34
  • 35. Timeline 1962 1970 1996 FQPA 2009 2014 www.huntingdon.com Aggregate Risk Cumulative Risk Extra Safety Factors Registration every 15 years 35
  • 36. Timeline 1962 1970 1996 FQPA 2009 2014 www.huntingdon.com Thou shall test pesticides for estrogenic effects 36
  • 37. FQPA Triggers Acronyms EDSTAC EDMVS EDMVAC www.huntingdon.com 37
  • 38. FQPA Triggers Acronyms EDSTAC EDMVS EDMVAC Endocrine Disruptor Screening and Testing Advisory Committee www.huntingdon.com 38
  • 39. FQPA Triggers Acronyms EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EDMVS Endocrine Disruptor Methods Validation Subcommittee EDMVAC www.huntingdon.com 39
  • 40. FQPA Triggers Acronyms EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee EDMVS Endocrine Disruptor Methods Validation Subcommittee EDMVAC Endocrine Disruptor Methods Validation Advisory Committee www.huntingdon.com 40
  • 41. Timeline 1962 1970 1996 2009 List 1, Tier 1 Test Orders Issued 2014 www.huntingdon.com 41
  • 42. www.huntingdon.com 42
  • 43. HPV: High Production Volume www.huntingdon.com 43
  • 44. 58 PAIs + 9 HPV/inerts = 67 Total HPV: High Production Volume www.huntingdon.com 44
  • 45. Timeline 1962 1970 1996 2009 2014 List 2, Tier 1 Test Orders to be issued. www.huntingdon.com 45
  • 46. www.huntingdon.com 46
  • 47. FFDCA: Federal Food, Drug, and Cosmetics Act SDWA: Safe Drinking Water Act; PAI: Pesticide Active Ingredient www.huntingdon.com 47
  • 48. EPA Steps Screen www.huntingdon.com 48
  • 49. EPA Steps Screen Characterize www.huntingdon.com 49
  • 50. EPA Steps Screen Characterize Assess risks www.huntingdon.com 50
  • 51. EPA Steps Screen Characterize Assess risks Mitigate www.huntingdon.com 51
  • 52. 90 day clock, Registrant 150 day clock, Consortium www.huntingdon.com 52
  • 53. www.huntingdon.com 53
  • 54. www.huntingdon.com 54
  • 55. www.huntingdon.com 55
  • 56. www.huntingdon.com 56
  • 57. OSRI: Other Scientifically Relevant Information www.huntingdon.com 57
  • 58. www.huntingdon.com 58
  • 59. www.huntingdon.com 59
  • 60. www.huntingdon.com 60
  • 61. www.huntingdon.com 61
  • 62. or www.huntingdon.com 62
  • 63. Calendar List 1 www.huntingdon.com 63
  • 64. Calendar List 2 www.huntingdon.com 64
  • 65. Tier 2 Study List Two-generation rat reproduction study Japanese Quail Two-generation Test Medaka Multigeneration Toxicity Test Larval Amphibian Growth and Development Mysid Two-Generation Toxicity Test Harpacticoid Copepod Development & Reproduction Test www.huntingdon.com 65
  • 66. Registrant Groups Endocrine Policy Forum (EPF) CropLife America (CLA) American Chemistry Council (ACC) www.huntingdon.com 66
  • 67. Registrant Groups Endocrine Policy Forum (EPF) CropLife America (CLA) American Chemistry Council (ACC) EPF: Ellen Mihaich [email protected] www.huntingdon.com 67
  • 68. NGOs World Wildlife Fund (WWF) Environmental Working Group (EWG) Natural Resources Defense Council (NRDC) www.huntingdon.com 68
  • 69. Endocrine System Hypothalamus Pituitary Ovary Testes Thyroid www.huntingdon.com 69
  • 70. Endocrine System Hypothalamus Pituitary Ovary Testes Thyroid www.huntingdon.com 70
  • 71. Tier 1 Endpoints Mechanistic effects Apical effects www.huntingdon.com 71
  • 72. Tier 1 Endpoints Mechanistic effects Enzyme activity Apical effects Reproductive, developmental www.huntingdon.com 72
  • 73. Tier 1 Endpoints Mechanistic effects Enzyme activity Apical effects Reproductive, developmental Hypothalamic pituitary gonadal axis: Hypothalamic pituitary thyroid axis: www.huntingdon.com HPG axis HPT axis 73
  • 74. Tier 1 In Vitro 890.1150 890.1200 890.1250 890.1200 890.1550 www.huntingdon.com Androgen Receptor Binding Aromatase Estrogen Receptor Binding Estrogen Receptor Transcriptional Activation Steroidogenesis 74
  • 75. Tier 1 In Vivo Mammalian (Rats) 890.1600 890.1400 890.1450 890.1500 www.huntingdon.com Uterotrophic Hershberger Female Pubertal Male Pubertal 75
  • 76. Tier 1 In Vivo Non-Mammalian 890.1100 890.1350 www.huntingdon.com Amphibian Metamorphosis Fish Short-term Reproduction 76
  • 77. www.huntingdon.com 77
  • 78. www.huntingdon.com 78
  • 79. Electronic Data Entry www.huntingdon.com 79
  • 80. Chemical Properties Functional groups (reactivity) Purity Solubility Vapor pressure Stability www.huntingdon.com 80
  • 81. Chemical Properties Functional groups (reactivity) Purity Solubility Vapor pressure Stability Use one characterized batch for all studies www.huntingdon.com 81
  • 82. Laboratory Selection Experience Study Director Technical Staff Quality Assurance Unit (QAU) www.huntingdon.com 82
  • 83. Laboratory Selection Experience Study Director Technical Staff Quality Assurance Unit www.huntingdon.com Price Location Communications 83
  • 84. Assay Management Single Registrant/compound www.huntingdon.com 84
  • 85. Assay Management Single Registrant/compound More than one Laboratory. A dedicated manager is helpful. www.huntingdon.com 85
  • 86. Assay Management Multiple Registrants/compound www.huntingdon.com 86
  • 87. Assay Management Multiple Registrants/compound Form a Consortium. A Consortium manager is necessary. www.huntingdon.com 87
  • 88. Androgen Receptor Binding 890.1150 In vitro. Competitive binding to rat ventral prostate. Target: HPG axis. ( A) www.huntingdon.com 88
  • 89. Aromatase Assay 890.1200 In vitro. Enzymatic conversion by CYP 19 of androgen to estrogen (steriodogenesis). Target: HPG axis. (Synthesis of E) www.huntingdon.com 89
  • 90. Estrogen Receptor Binding 890.1250 In vitro. ER binding Rat Uterine Cytosol. Target: HPG axis. ( E) www.huntingdon.com 90
  • 91. Estrogen Receptor Transcriptional Activation 890.1300 In vitro. Binding of the estrogen receptor with a ligand. Activates a luciferase reporter gene. Target: HPG axis. (+ E) www.huntingdon.com 91
  • 92. Steroidogenesis 890.1550 In vitro. Production of testosterone and estradiol/estrone. Synthesis of T, E. www.huntingdon.com 92
  • 93. Uterotrophic 890.1600 In vivo estrogenic assay. Measure uterine weight in in immature or ovariectomized rats. Target: HPG axis. (+ E) www.huntingdon.com 93
  • 94. Hershberger 890.1400 In vivo Androgenic assay. Agonist or antagonist. Weight of five key organs. Target: HPG axis. ( A) www.huntingdon.com 94
  • 95. Female Pubertal 890.1450 In vivo study that targets HPT axis and HPG axis. ( E, synthesis of E) www.huntingdon.com 95
  • 96. Male Pubertal 890.1500 In vivo study that targets HPT axis and HPG axis. ( A, synthesis of T) www.huntingdon.com 96
  • 97. Amphibian Metamorphosis Assay 890.1100 Xenopus laevis tadpoles. Targets: HPT axis. www.huntingdon.com 97
  • 98. Fish Short-Term Reproduction 890.1350 In vivo. Fathead minnow, reproductive performance. Targets: HPG axis. ( E; A; Synthesis of E) www.huntingdon.com 98
  • 99. Mid-course Corrections Tier 1 Data SAPs (SAP: Scientific Advisory Panel) Science advances EPA procedures evolve www.huntingdon.com 99
  • 100. EPA procedures evolve Central Data Exchange http://www.epa.gov/cdx www.huntingdon.com 100
  • 101. Tox21: High-Throughput Screening David Dix: High-throughput programs (HTP) such as Tox21 will dramatically impact test orders for List 2 chemicals. www.huntingdon.com 101
  • 102. Scientific Advisory Panels JAN 2013 Tools to Prioritize Chemicals MAY 2013 Tier 1 Performance JUN 2013 Tier 2 Ecotoxicity Tests JUL 2013 Weight of Evidence www.huntingdon.com 102
  • 103. Whats on Your Mind? When is List 2 coming out? Is the waiver effort worth it? What Labs should be chosen? How long do we have to complete the studies? Is a Weight of Evidence document necessary? www.huntingdon.com 103
  • 104. www.huntingdon.com 104
  • 105. Data Review www.huntingdon.com 105
  • 106. Other webinars this week Tuesday 21st In vitro tests for endocrine disruption Leslie Wednesday 22nd EDSP Tier 1 In Vivo Mammalian Assays Bob Akhurst and Yen-Ling Cheung Parker Thursday 23rd Amphibian metamorphosis assay for the EPAs EDSP Carole Jenkins
  • 107. HLS EDSP expert team Ephi Gur Team lead and Regulatory Bob Parker Toxicology Will Davies Toxicology John Carter In vitro technologies Carole Jenkins Aquatic toxicology Contact via me [email protected] +44 (0) 1480 892031