Metabolomics in Regulatory Toxicology: Use Cases, Best Practice and Reporting Standards
Citation:
Viant, M., T. Ebbels, R. Beger, D. Epps, H. Kamp, P. Leonards, G. Loizou, J. MacRae, B. van Ravenzwaay, P. Rocca-Serra, R. Salek, T. Walk, R. Weber, AND D. Ekman. Metabolomics in Regulatory Toxicology: Use Cases, Best Practice and Reporting Standards. 2019 SETAC North America Annual Meeting, Toronto, CANADA, November 03 - 07, 2019.
Impact/Purpose:
This presentation will describe the efforts of an international team to define best practices for generating and analyzing metabolomics datasets for application to regulatory toxicology. The presentation should appeal to researchers working in environmental metabolomics as well as other omics tools who are working to develop these techniques for environmental regulation.
Description:
Researchers are increasingly using metabolomics to evaluate potential risks from exposure to environmental stressors. Much like the other OMICS approaches, metabolomics has proven to be a powerful tool for identifying and understanding contaminant mode(s) of action/adverse outcome pathways and discovering indicators of exposure/effects in ecologically relevant species. Despite these strengths, the application of metabolomics to regulatory toxicology has been limited. While several factors contribute to this slow translation, the roadblocks most commonly cited by chemical regulators and government and industry scientists is the lack of standardization, best practice guidelines, and data and metadata reporting formats. Here we will describe the final report of the MEtabolomics standaRds Initiative in Toxicology (MERIT) project, which brought together a team with a wide range of expertise from multiple sectors to address this need. MERIT sought to define best practice guidelines and minimal reporting standards for designing, undertaking, reporting and assessing the quality of both untargeted metabolomics and targeted metabolite analyses for application to regulatory toxicology. To provide context, the most relevant-use cases for metabolomics in toxicology were also identified, including discovery of chemical mode(s) of action and cross-species extrapolation of toxicity pathways. The MERIT guidelines included experimental design; QA/QC; sampling and extraction; data acquisition and processing of mass spectrometry and NMR spectroscopy assays; data processing and statistical analysis; and metabolite identification. A strategy and architecture for integrated data management, sharing and exploitation in regulatory toxicology was also developed. We concluded that most steps in the regulatory toxicology application of untargeted metabolomics and targeted metabolite assays are already well established, including significant recent progress in QA/QC. These and other aspects of the MERIT project will be presented along with recommendations for critical “next steps” to advance the use of metabolomics in regulatory toxicology. The contents of this abstract neither constitute nor reflect US EPA policy.