Mode of Toxicity Studies

MetaMap® Tox - Metabolite Profiling in Toxicology:
Early Safety Enablement in Pharmaceutical R&D


What is MetaMap®Tox?

• A database of specific metabolomic patterns from rat plasma following treatment intervention
• Robust and reproducible patterns for different tox modes of action (MoA)
• To-date > 100 specific metabolite patterns validated for Tox-MoA

MetaMap®Tox – What do you get?

• Compound-specific metabolomic patterns
• Identification of critical tox MoA/target organs
• Comparison with reference compounds
• Expert assessment of underlying mechanisms

MetaMap®Tox – Utility
A novel technology for early safety enablement successfully evaluated by DSEC (The Drug Safety Executive Council )

The DSEC confirms value & utility of applying MetaMap®Tox complementary to a 28-day GLP standard tox study in the context use of:

• a. Assessment of Mechanism of Action
  In particular assessment of mechanism of toxicity/adverse reaction,
  e.g. in case of arbitrary results from short term toxicological studies
  
• b. Minimization of Toxicity / Adverse Reactions
  - Indicating/predicting systemic toxicity/adverse reactions (including idiosyncratic toxicities)
  - Detecting/monitoring onset/reversibility to toxicity/adverse reactions
  
• c. Final Lead Selection
  MetaMap®Tox provides a detailed and systemic answer to compound performance on safety issues
  

Successful external validation of MetaMap®Tox utility for safety enablement



MetaMap®Tox – Products
Enabling safety in early Pharma development




Please contact us for further information regarding MetaMap®Tox and your specific study request.


Back to Applications Overview

Further Reading on MetaMap®Tox

• V. Strauss, W. Mellert, Jan Wiemer, E. Leibold, Hennicke Kamp, Tilmann Walk, Ralf Looser, Alexandre Prokoudine, E. Fabian, G. Krennrich, Michael Herold, Bennard van Ravenzwaay
  (2012) Increased toxicity when fibrates and statins are administered in combination – A metabolomics approach with rats
  Toxicology Letters Volume 211 (2012), Issue 2, Pages 91-210
  Link to Elsevier publication
  
• Bennard van Ravenzwaay, Herold M, Kamp H, Kapp MD, Fabian E, Looser R, Krennrich G, Mellert W, Prokoudine A, Strauss V, Walk T, Wiemer J
  (2012) Metabolomics: A tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals-From QSAR to QBAR
  Mutation Research
  Link to PubMed.gov
• Gerd U. Balcke, S.N. Kolle, Hennicke Kamp, Biancs Bethan, Ralf Looser, S. Wagner, Robert Landsiedel, Bennard van Ravenzwaay
  (2011) Linking energy metabolism to dysfunctions in mitochondrial respiration – A metabolomics in vitro approach
  Toxicology Letters
  Link to Elsevier online publication
  


• MetaMap®Tox Poster: Bennard van Ravenzwaay et al. (SOT 2011) Impact of nutrition on the plasma metabolome in rats
  Link to Poster Download [PDF, 50 KB]
  


• MetaMap®Tox Poster: Bennard van Ravenzwaay et al. (SOT 2011) Reproducibility of metabolomics performed in plasma samples of 28 day rat systemic toxicity studies
  Link to Poster Download [PDF, 30 KB]
  


• Bennard van Ravenzwaay, G. Coelho-Palermo Cunha, V. Strauss, Jan Wiemer, E. Leibold, Hennicke Kamp, Tilmann Walk, W. Mellert, Ralf Looser, Alexandre Prokoudine, E. Fabian, G. Krennrich, Michael Herold
  (2010) The individual and combined metabolite profiles (metabolomics) of
  dibutylphthalate and di(2-ethylhexyl)phthalate following a 28-day dietary exposure in rats
  Toxicology Letters
  Link to Elsevier publication
  
• V. Strauss, Jan Wiemer, E. Leibold, Hennicke Kamp, Tilmann Walk,W. Mellert,
  Ralf Looser, Alexandre Prokoudine, E. Fabian, G. Krennrich, Michael Herold, Bennard van Ravenzwaay
  (2009) Influence of strain and sex on the metabolic profile of rats in repeated dose toxicological studies
  Toxicology Letters
  Link to Elsevier publication


• MetaMap®Tox Poster: Bennard van Ravenzwaay et al. (Innoforum 2008) Statistical Tools for Enhancing Metabolomic Profiling
  Link to Poster Download [PDF, 220 KB]
  


• Bennard van Ravenzwaay, G. Coelho-Palermo Cunha, E. Leibold,
  Ralf Looser , W. Mellert , Alexandre Prokoudine , Tilmann Walk, Jan Wiemer
  (2007) The use of metabolomics for the discovery of new biomarkers of effect
  Toxicology Letters
  Link to Elsevier publication