Metabolomics in toxicology and preclinical research

Abstract

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.

Consensus report on the future of animal-free systemic toxicity testing

“…12) to use such data for systems biology modeling (Jennings et al, 2013;Krug et al, 2014;. toxicogenomics technologies (Ramirez et al, 2013) are important tools that cover a multitude of cellular events. However, it is important to apply them to the right biological models.…”

E-cigarettes and the need and opportunities for alternatives to animal testing

“…Many of these have been detailed in this series of articles as well as our workshop reports and shall not be reiterated here. The reader is referred to the respective papers for in vivo (Hartung, 2008a(Hartung, , 2013, in vitro (Hartung, 2007(Hartung, , 2013Hartung and Leist, 2008;Leist et al, 2008) and in silico approaches (Hartung and Hoffmann, 2009;Hartung, 2016c), in vitro work for testing cosmetics (Hartung, 2008b), chemicals (Hartung, 2010b), nanomaterials (Hartung, 2010a;Hartung and Sabbioni, 2011), pharmaceuticals (Rovida et al, 2015b) and food (Hartung and Koëter, 2008), organo-typic cultures (Alépée et al, 2014;Andersen et al, 2014;Hartung, 2014;Marx et al, 2016), refinement of animal testing (Zurlo and Hutchinson, 2014), Integrated Testing Strategies (Hartung et al, 2013a;Rovida et al, 2015a), pathways of toxicity (Hartung and McBride, 2011;Kleensang et al, 2014;Tollefsen et al, 2014), omics technologies (Bouhifd et al, 2013(Bouhifd et al, , 2015aRamirez et al, 2013), and high-content imaging (van Vliet et al, 2014). These approaches come with different advantages and disadvantages in general and in particular for testing e-cigarettes (Tab.…”

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

“…The second issue to be addressed is the definition of the initial maturity state of the cells, e.g., at the time when toxicant exposure starts. For the definition of maturity and for the effects of toxicants, modern omics methods may deliver richer information than traditional single endpoints (Balmer et al, 2012;Ramirez et al, 2013;Waldmann et al, 2014). this would also include information on the epigenetic state and changes of the cells (Balmer and leist, 2014).…”