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Innovative Science To Improve Public Health

Explore the impact and ongoing research of endocrine disruptors for public health improvement, including the development of predictive models and data gathering initiatives.

jrushing
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Innovative Science To Improve Public Health

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  1. EDKB: Endocrine Disruptors Knowledge Base at the FDA Huixiao Hong, Ph.D. Center for Bioinformatics Division of Systems Biology National Center for Toxicological Research US Food and Drug Administration 3900 NCTR Rd., Jefferson, AR 72079 The views in the presentation are my personal opinions and do not necessary reflect those of the US FDA Innovative Science To Improve Public Health

  2. Outline • Endocrine disruptors issues. • EDKB overview. • Ongoing research. Innovative Science To Improve Public Health

  3. Endocrine Disruptors (History) 1996 Our Stolen Future Theo Colborn Dianne Dumanoski John Peterson Myers Food Quality Protection Act Safe Drinking Water Act US Congress Innovative Science To Improve Public Health

  4. Importance to FDA Innovative Science To Improve Public Health

  5. Molecular Mechanisms Innovative Science To Improve Public Health Stefan O Mueller, Anal Bioanal Chem (2004) 378: 582-587

  6. EDKB Overview • Started the project in 1996 • Multidisciplinary team: • biologists/toxicologists, bio/cheminformaticians, computational chemists, software engineers, statisticians, regulatory agents • Collaborated with ACC and EPA • Worked with EPA over 3 years ( 2001-2004) on the ER predictive model and the AR assay validation for potential use in regulation • Three main accomplishments • Assayed over >200 chemicals for ER and AR binding, respectively • Developed a knowledge base that contains various in vitro and in vivo assay data (in house and literature), available from our website (http://edkb.fda.gov) • Developed predictive models for both ER and AR binding Innovative Science To Improve Public Health

  7. EDKB Overview: Data Innovative Science To Improve Public Health

  8. ED data from accumulated literature ED data from NCTR Oracle database Results Query User Interface Structure search Graphical view Summary table EDKB Overview: Data Flowchart Innovative Science To Improve Public Health

  9. EDKB Overview: Data Model Innovative Science To Improve Public Health

  10. EDKB Overview: Interface Individual chemical info and ref. Link to external resources, e.g., PubChem, ToxNet, etc. Chemical structure & similarity search Graphic Activity Profiles Query interface Excel-like spreadsheet for view and export Innovative Science To Improve Public Health

  11. EDKB Overview: Users Innovative Science To Improve Public Health

  12. Phase I Phase II Phase III Phase IV EDKB Overview: Priority setting Database Pre-Filters Active/Inactive Assignment Quantitative Predictions Hits Priority Setting Innovative Science To Improve Public Health

  13. EDKB Overview: Filters Innovative Science To Improve Public Health Nishihara: J Health Sci 46:282-298 (2000)

  14. EDKB Overview: Classification Decision tree model Molecular descriptors Innovative Science To Improve Public Health

  15. EDKB Overview: Quantitative model Innovative Science To Improve Public Health

  16. Ongoing Research: Data collection Literature Existing EDKB Enhanced EDKB NCTR NTP ToxCast Tox21 Innovative Science To Improve Public Health

  17. Ongoing Research: Data collection Innovative Science To Improve Public Health

  18. Ongoing Research: Data collection Innovative Science To Improve Public Health

  19. Ongoing Research: Future applications EPA ~86,000 Predictive Models ++ + FDA(SRS) ~23,000 -- - Innovative Science To Improve Public Health

  20. Innovative Science To Improve Public Health

  21. Thanks ? Innovative Science To Improve Public Health

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