| Eleventh meeting of the Committee on Emerging Issues and Data on Environmental Contaminants |
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| "Applications of Genomic Signatures" |
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December 7, 2005, Welches, Oregon |
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| 8:30 |
Introduction to Workshop Organization and Objectives |
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Peter Spencer, Oregon Health & Science University |
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Audio Clip |
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| 8:45 |
Questions About Regulatory Use of Toxicogenomic Information |
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Peter Lord, Johnson & Johnson |
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Download Presentation Slides | Audio Clip (Presentation) | Audio Clip (Discussion) |
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9:30 |
Acetaminophen Toxicogenomics Data: Application to Other |
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Compounds |
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Richard Paules, National Center for Toxicogenomics, NIEHS |
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Audio Clip (Presentation) | Audio Clip (Discussion) |
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General questions to be addressed in presentation: |
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What types of signatures evolve from these experiments?
What are the limitations on the interpretation of these results? |
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Specific questions to be addressed in presentation: |
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If these same data were generated for another chemical, would they be useful in establishing a threshold? At what time after dosing should this be tracked?
How does a genomic threshold correlate with a phenotypic threshold, whether that phenotype be a protein, a cell, a tissue, or a behavior
What is the genomic signature correlate of a phenotype dose-effect relationship? Are affected pathway genes simply modulated more strongly or do other pathways become involved as the dosage increases?
If these same data were generated for a new/unknown chemical, would they be useful in establishing a NOEL?
Are there genomic correlates of unusual dose-response profiles? |
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| 10:00 |
Panel Discussion of Questions Above |
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Peter Spencer, Moderator |
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John Leighton, FDA/CDER; Robert Kavlock, EPA; Carol Henry, ACC; Nigel Walker, National Toxicology Program; Richard Brennan, Iconix; William Mattes, Gene Logic |
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Audio Clip |
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Panel members clarifying questions (10 mins)
Panel members debate topics raised (20 mins) |
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| 10:30 |
Break |
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| 10:45 |
Endocrine Disrupter Toxicogenomics Data |
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George Daston, Proctor and Gamble |
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Download Presentation Slides | Audio Clip (Part 1) | Audio Clip (Part 2) |
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General questions to be addressed in presentation: |
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What types of signatures evolve from these experiments?
Does this set of experiments suggest one or more signatures reflecting attributes of policy significance? For what attributes?
What are the limitations on the interpretation of these results?
Are genomic data reliable adjuncts to more traditional sources of toxicology data?
What is the genomic signature correlate of a phenotype dose-effect relationship? Are affected pathway genes simply modulated more strongly, or do other pathways become involved as the dosage increases?
Is it possible to recognize a threshold for a genomic response? At what time after dosing should this be tracked? *How does a genomic threshold correlate with a phenotype threshold, whether that phenotype be a protein, a cell, a tissue, or a behavior? |
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Specific questions to be addressed in presentation: |
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Is there a signature representative of estrogenically active compounds? If so, what is it? How definitive is this? For what species/time period/groups etc. would this finding be applicable?
Is there a signature representative of a dose-response curve of a particular shape? If so, what is it?
Can data from experiments such as these be used to get a sense of comparative toxicity or be otherwise useful in prioritizing potency?
Is the signature of estrogenic substances enough to require or not require further animal testing? |
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| 11:15 |
Panel Discussion of Questions Above |
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Peter Spencer, Moderator |
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John Leighton, FDA/CDER; Robert Kavlock, EPA; Carol Henry, ACC; Nigel Walker, National Toxicology Program; Richard Brennan, Iconix; William Mattes, Gene Logic |
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Audio Clip |
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Panel members clarifying questions (10 mins)
Panel members debate topics raised (20 mins) |
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| 11:45 |
Lunch |
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| 12:45 |
Antifungal Toxicogenomic Data |
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David Dix, Environmental Protection Agency |
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Download Presentation Slides | Audio Clip (Part 1) | Audio Clip (Part 2) |
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General questions to be addressed in presentation: |
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What types of signatures evolve from these experiments?
Does this set of experiments suggest one or more signatures reflecting attributes of policy significance? For what attributes?
What are the limitations on the interpretation of these results? |
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Specific questions to be addressed in presentation: |
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• Do these data suggest particular modes of action/mechanisms of action?
• Do these data suggest multiple modes/mechanisms of action? If yes, how should this be interpreted?
• Can data from experiments such as these be used to get a sense of comparative hazard or be otherwise useful to prioritize?
• Are these signatures of hepatotoxicity enough to direct further animal testing?
• Is adequate detail of these genomic signatures made available in order that they can be validated or accepted for regulatory use? |
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| 1:15 |
Panel Discussion of Questions Above |
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Peter Spencer, Moderator |
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John Leighton, FDA/CDER; Robert Kavlock, EPA; Carol Henry, ACC; Nigel Walker, National Toxicology Program; Richard Brennan, Iconix; William Mattes, Gene Logic
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Panel members clarifying questions (10 mins)
Panel members debate topics raised (20 mins) |
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| 1:45 |
Introduction to breakout group tasks |
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| 2:00 |
Breakout groups to address questions at end of document |
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| 3:45 |
Break |
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| 4:00 |
Reports of breakout groups |
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Breakout Group 1 Download Summary | Audio Clip |
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Breakout Group 3 Download Summary | Audio Clip |
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Breakout Group 4 Download Summary | Audio Clip |
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| 4:45 |
Comments and discussion by the committee to the workshop findings |
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Peter Spencer (Moderator),
James Bus, Joseph DeGeorge, Kenneth Ramos, Cheryl Walker |
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Audio Clip |
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| 5:30 |
Adjourn |
