Related to food safety aspects, the concept of substantial equivalence is a guiding tool for the assessment, developed by OECD and further elaborated by FAO/WHO. One of the safety concerns regarding GM crops pertains to the potential of unintended effects caused by processes of transgene insertion (DNA rearrangements) or from metabolic effects of novel gene product(s). Unintended effects are phenotypic, response or compositional effects which go beyond that of the original genetic modification and which might impact primarily on health. Unintended effects occur in both GM and non-GM crops; however, GM crops are better characterised. Conventional ‘targeted’ analytical approaches and animal feeding trials with whole foods may reveal unintended effects only by chance or if anticipated. Therefore, it is a scientific challenge to develop new methodology that allow for a ‘holistic’ simultaneous screening of potential alterations in the physiology of the GM crop at different biological integration levels. The present tendency is to include metabolomics (parallel analysis of a range of primary and secondary ...