Evaluation of the use of untargeted metabolomics in the safety assessment of genetically modified crops

BACKGROUND: The safety assessment of foods and feeds from genetically modified (GM) crops includes the comparison of key characteristics, such as crop composition, agronomic phenotype and observations from animal feeding studies compared to conventional counterpart varieties that have a history of safe consumption, often including a near isogenic variety. The comparative compositional analysis of GM crops has been based on targeted, validated, quantitative analytical methods for the key food and feed nutrients and antinutrients for each crop, as identified by Organization of Economic Co-operation and Development (OCED). As technologies for untargeted metabolomic methods have evolved, proposals have emerged for their use to complement or replace targeted compositional analytical methods in regulatory risk assessments of GM crops to increase the number of analyzed metabolites. AIM OF REVIEW: The technical opportunities, challenges and strategies of including untargeted metabolomics analysis in the comparative safety assessment of GM crops are reviewed. The results from metabolomics studies of GM and conventional crops published over the last eight years provide context to enable the discussion of whether metabolomics can materially improve the risk assessment of food and feed from GM crops beyond that possible by the Codex-defined practices used worldwide for more than 25 years. KEY SCIENTIFIC CONCEPTS OF REVIEW: Published studies to date show that environmental and genetic factors affect plant metabolomics profiles. In contrast, the plant biotechnology process used to make GM crops has little, if any consequence, unless the inserted GM trait is intended to alter food or feed composition. The nutritional value and safety of food and feed from GM crops is well informed by the quantitative, validated compositional methods for list of key analytes defined by crop-specific OECD consensus documents. Untargeted metabolic profiling has yet to provide data that better informs the safety assessment of GM crops than the already rigorous Codex-defined quantitative comparative assessment. Furthermore, technical challenges limit the implementation of untargeted metabolomics for regulatory purposes: no single extraction method or analytical technique captures the complete plant metabolome; a large percentage of metabolites features are unknown, requiring additional research to understand if differences for such unknowns affect food/feed safety; and standardized methods are needed to provide reproducible data over time and laboratories.