Safe Environmental Exposure Levels for RDX and TNT Using Toxicogenomic Data

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U.S. Army Engineer Research and Development Center

Want to use toxicogenomics data to calculate a safe environmental exposure level? Yeah, so do I! In this talk I discuss the steps we took to do this for TNT and RDX -- two explosives. For TNT, we take this all the way to a human risk screening level. For RDX, we focused on aquatic risk screening. Interested in using existing toxicogenomics data to set a risk screening level? Or do you need help analyzing your toxicogenomics data? Reach out to me on LinkedIn, and we'll see how my group at the US Army's ERDC can help!

Science

Safe Environmental Exposure Levels for
RDX and TNT Using Toxicogenomic Data
Lyle D. Burgoon, Ph.D.
Leader, Bioinformatics and Computational Toxicology
Group
Environmental Laboratory
The views presented here are those of the author and
do not necessarily reflect current or future opinion or
policy of the US Army.

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Safe Environmental Exposure Levels for RDX and TNT Using Toxicogenomic Data

1. Safe Environmental Exposure Levels for RDX and TNT Using Toxicogenomic Data Lyle D. Burgoon, Ph.D. Leader, Bioinformatics and Computational Toxicology Group Environmental Laboratory The views presented here are those of the author and do not necessarily reflect current or future opinion or policy of the US Army.

2. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Challenge  Urban Warfare Environment ► Too many chemicals ► Not enough time ► What chemicals can we not worry about?

3. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Answer  Risk Screening ► Is there a chemical level below which we don’t need to worry about a chemical? ► Ultimately, we need a Point of Departure • Margin of Exposure and Hazard Index approaches

4. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Point of Departure  The point on a dose-response curve where the exposed population begins to show an adverse response  No effect levels, No Adverse Effect Levels, Lowest Observed Adverse Effect Levels / 10, Benchmark Dose

5. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED.

6. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. How Can We Avoid Needing a Benchmark Response??  Interpolate curve data ► Spline-based metaregression  Menger Curvature ► Measures the curvature of a curve ► We identify the point of the maximal Menger Curvature in the interpolated curve ► This point is the POD

7. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Placing TNT Gene Expression in Biological Context AOPN: Steatosis and Primary Metabolism RfD Endpoint: Steatosis Sufficient Assay Endpoint: Acyl-CoA Synthetase

8. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED.

9. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. TNT Screening-RfD Synthesis for Steatosis In the future we will consider uncertainty at GFR

10. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Placing RDX Gene Expression in Biological Context

11. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. RDX Screening Level Synthesis for Steatosis  Zebrafish embryo: 0.17mg/L ► Neurodevelopmental toxicity  Recommend a margin of exposure of 100x  RDX Toxicogenomic Screening Level (aquatic organisms): 1.7ug/L  Recent aquatic screening levels not identified  Recent human health screening level: ► US EPA Superfund Program (tap water): 0.61ug/L

12. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. http://apps.cytoscape.org/apps/aopxplorer

13. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED. Acknowledgements  US Army Military Materials in the Environment ► NexGen Predictive (Eco)toxicity ToolBox Focus Area • Big Data Driven Hazard Screening Task  US Army ERDC ► Dr. Ed Perkins ► Dr. Natalia Vinas ► Dr. Keri Donohue ► Anne Mayo ► Mitchell Wilbanks  ILS (supporting NICEATM) ► Dr. Shannon Bell ► Dr. Dan Zang

14. Innovative solutions for a safer, better worldBUILDING STRONG® UNCLASSIFIED/DISTRIBUATION STATEMENT A. APPROVED FOR PUBLIC RELEASE. DISTRIBUTION IS UNLIMITED.

Safe Environmental Exposure Levels for RDX and TNT Using Toxicogenomic Data

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Safe Environmental Exposure Levels for RDX and TNT Using Toxicogenomic Data