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BioSeek EPA ToxCast Program

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Summary of BioSeek's work for the EPA's ToxCast (TM) program. BioSeek has been a contractor since 2007 for the EPA, using the company's human cell-based BioMAP(R) systems platform.

Summary of BioSeek's work for the EPA's ToxCast (TM) program. BioSeek has been a contractor since 2007 for the EPA, using the company's human cell-based BioMAP(R) systems platform.

Published in: Health & Medicine, Technology

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  • 1. BioSeek – EPA ToxCastTM Program Bridging the Gap From In Vitro to In Vivo1
  • 2. EPA ToxCastTM Program  EPA ToxCastTM Program  Program to develop a cost-effective approach for efficiently prioritizing the toxicity testing of thousands of chemicals  BioSeek has been a contractor since 2007  Three Phases  Phase I – Proof-of-concept  Phase II – Verification / Extension  Phase III – Reduction to Practice  http://www.epa.gov/ncct/toxcast/2
  • 3. ToxCastTM Program Timeline3
  • 4. ToxCastTM Program Details Number of Chemical Number of Cost per Target Phase Purpose Chemicals Criteria Assays Chemical Date Data Rich Signature I 320 552 $20k FY08 (pesticides) Development Ib 15 Nanomaterials Pilot 166 $10K FY09 Data Rich IIa >300 Validation >400 ~$20-25k FY09 Chemicals Known Human IIb >100 Extrapolation >400 ~$20-25k FY09 Toxicants Expanded Structure IIc >300 Extension >400 ~$20-25k FY10 and Use Diversity IId >12 Nanomaterials PMN >200 ~$15-20K FY09-10 Prediction and III Thousands Data poor >300 ~$15-20k FY11-12 Prioritization7/23/2012 CONFIDENTIAL4
  • 5. BioSeek ToxCastTM Data Now Posted on EPA’s ACToR Public Database http://actor.epa.gov/ ACToR Aggregated Computational Toxicology Resource5
  • 6. BioMAP® Analysis of ToxCastTM Phase I Chemicals Diversity of Mechanisms Distinguished NFB cAMP Elevation DNA Alkylation Mitochondrial DysfunctionReference: Houck, K.A., D.J. Dix, R.S. Judson, R.J. Kavlock, J.Yang and E.L. Berg. 2009. Profiling bioactivity of the ToxCast Tubulin Inhibitionchemical library using BioMAP primary human cell systems. J.Biomol. Screen, 2009, 14:1054-66.6
  • 7. BioMAP Endpoints (BSK) in Predictive Signatures Rat & Rabbit Developmental Toxicity Knudsen, T.B., Computational Toxicology and Prenatal Development, presentation for the EPAs Computational Toxicology Community of Practice (8/25/2011)7 Toxicol Sci. 2011, 124:109-27
  • 8. BioMAP® Analysis of Nanomaterials ToxCast Phase II Chemicals • Nanomaterials are active and distinguishable by composition • Reference: Wang, A., E.L. Berg, M. Polokoff, J. Yang; D. Reif, N. Kleinstreuer, S. Marinakos, A.R. Badireddy, S. Gangwal, C. Matson, M. Wiesner, and K. Houck. Nanomaterial (NM) bioactivity profiling by ToxCast high- throughput screening (HTS). Society of Toxicology Annual Meeting, March 12, 2012, San Francisco, CA.8 Confidential
  • 9. BioMAP® Profile of Titanium Oxide Nanoparticles Similarity to Paclitaxel • Paclitaxel – binds b-tubulin and causes microtubule stabilization • TiO2 nanoparticles interfere with microtubules (PMID: 18776989)9 Confidential
  • 10. BioMAP® Analysis of Failed Pharma Compounds  Nicole Kleinstreuer, Society of Toxicology Annual Meeting, March 12, 2012, San Francisco, CA10
  • 11. Publications with BioSeek ToxCastTM Data Sipes NS, Martin MT, Reif DM, Kleinstreuer NC, Judson RS, Singh AV, Chandler KJ, Dix DJ, Kavlock RJ, Knudsen TB. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data. Toxicol Sci. 2011, 124:109-27 Knudsen, T. B., K. A. Houck, N. Sipes, A. V. Singh, R. Judson, M. T. Martin, A. Weissman, N. Kleinstreuer, H. M. Mortensen, D. Reif, J. R. Rabinowitz, R. W. Setzer, A. M. Richard, D. J. Dix, And R. J. Kavlock. Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets. TOXICOLOGY. Elsevier Ireland Limited, Limerick, Ireland, 282(1-2):1-15, (2011). Kleinstreuer, N. C., R. S. Judson, D. M. Reif, N. S. Sipes, A. V. Singh, K. J. Chandler, R. Dewoskin, D. J. Dix, R. J. Kavlock, And T. B. Knudsen. Environmental Impact on Vascular Development Predicted by High Throughput Screening. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, Online Edition:1-34, (2011). doi:10.1289/ehp.1103412 Houck, K.A., D.J. Dix, R.S. Judson, R.J. Kavlock, J. Yang and E.L. Berg. 2009. Profiling bioactivity of the ToxCast chemical library using BioMAP primary human cell systems. J. Biomol. Screen, 2009, 14:1054-66. Judson RS, Houck KA, Kavlock RJ, Knudsen TB, Martin MT, et al. 2009, In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project. Environ Health Perspect 118(4): doi:10.1289/ehp.090139211
  • 12. Presentations with BioSeek ToxCastTM Data Kleinstreuer, N. C., vEmbryo in silico models:Predicting vascular developmental toxicity, Wiley- Blackwell Symposium on Computational Embryology: Integration and Modeling of Developmental Mechanisms, Teratology Society 2012, June 25, 2012, Baltimore, MD. Wang, A., E.L. Berg, M. Polokoff, J. Yang; D. Reif, N. Kleinstreuer, S. Marinakos, A.R. Badireddy, S. Gangwal, C. Matson, M. Wiesner, and K. Houck. Nanomaterial (NM) bioactivity profiling by ToxCast high-throughput screening (HTS). Society of Toxicology Annual Meeting, March 12, 2012, San Francisco, CA. Kleinstreuer, N. C., K. Houck, R. Judson, D. Reif, P. Kothiya, M. Martin, T. Knudsen, A. Richard, M. Polokoff, J. Yang, E.L. Berg, R. Kavlock, and D. Dix. Biological profiling of the ToxCast Phase II Chemical Library in Primary Human Cell CoCulture Systems. Society of Toxicology Annual Meeting, March 12, 2012, San Francisco, CA. Houck, K., Use of primary human cell systems for creating predictive toxicology profiles. SBS Annual Meeting, 2009, Lille, France. Houck, K. Evaluation of the ToxCast™ suite of cellular and molecular assay for prediction of in vivo toxicity. GlobalChem, 2009, Baltimore, MD. Houck, K., Characteristics of the ToxCast™ In Vitro Datasets from Biochemical and Cellular Assays (EPA/ORD/NCCT). ToxCast™ Data Analysis Summit, May 14, 2009, RTP, NC.12
  • 13. Contacts BioSeek, LLC 310 Utah, Suite 100 South San Francisco, CA 94030 650-416-7600 www.bioseekinc.com www.BioMAPSystems.com Bridging the Gap From In Vitro to In VivoBioSeek, LLC310 Utah, #100South San Francisco, CA 94080