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Metabolomics in toxicology and preclinical research

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Tzutzuy Ramirez1§, Mardas Daneshian2§, Hennicke Kamp1, Frederic Y. Bois3, Malcolm R. Clench4, Muireann Coen5, Beth Donley6, Steven M. Fischer7, Drew R. Ekman8, Eric Fabian1, Claude Guillou9, Joachim Heuer10, Helena T. Hogberg11, Harald Jungnickel12, Hector C. Keun5, Gerhard Krennrich13, Eckart Krupp14, Andreas Luch12, Fozia Noor15, Erik Peter16, Bjoern Riefke17, Mark Seymour18, Nigel Skinner19, Lena Smirnova11,12, Elwin Verheij20, Silvia Wagner16, Thomas Hartung2,11§, Bennard van Ravenzwaay1§, and Marcel Leist2,21§
1 BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany;
2 Center for Alternatives to Animal Testing – Europe (CAAT-Europe), University of Konstanz, Konstanz, Germany;
3 Royallieu Research Center, Technological University of Compiegne, Compiegne, France;
4 Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK;
5 Imperial College London, London, UK;
6 Stemina Biomarker Discovery Inc., Madison, USA;
7 Agilent Life Sciences Group, Agilent Technologies, Santa Clara, USA;
8 U.S. EPA, National Exposure Research Laboratory, Ecosystems Research Division, Athens, GA, USA;
9 Joint Research Centre of the European Commission, Institute for Health & Consumer Protection, Ispra, Italy;
10 Federal Institute for Risk Assessment (BfR), Department of Scientific Services, Berlin, Germany;
11 Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, USA;
12 Federal Institute for Risk Assessment (BfR), Department of Product Safety, Berlin, Germany;
13 BASF SE, GVC/S Scientific Computing, Ludwigshafen, Germany;
14 Sanofi-Aventis Deutschland GmbH, Genetic & Investigative Toxicology, Frankfurt, Germany;
15 Biochemical Engineering, Saarland University, Saarbruecken, Germany;
16 metanomics GmbH, Berlin, Germany;
17 Bayer Pharma AG, Investigational Toxicology, Berlin, Germany;
18 Syngenta, Jealott’s Hill International Research Centre, Berkshire, UK;
19 Agilent Technologies, London, UK;
20 TNO Quality of Life, Zeist, The Netherlands ;
21 Doerenkamp-Zbinden chair for in vitro toxicology and biomedicine, Konstanz, Germany

Summary

Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context.

 

 

ALTEX 30(2), 209–225

DOI: 10.14573/altex.2013.2.209



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