International consensus has been reached on the principles regarding evalua
tion of the food safety of genetically modified plants. The concept of subs
tantial equivalence has been developed as part of a safety evaluation frame
work, based on the idea that existing foods can serve as a basis for compar
ing the properties of genetically modified foods with the appropriate count
erpart. Application of the concept is not a safety assessment per se, but h
elps to identify similarities and differences between the existing food and
the new product, which are then subject to further toxicological investiga
tion. Substantial equivalence is a starting point in the safety evaluation,
rather than an endpoint of the assessment. Consensus on practical applicat
ion of the principle should be further elaborated. Experiences with the saf
ety testing of newly inserted proteins and of whole genetically modified fo
ods are reviewed, and limitations of current test methodologies are discuss
ed. The development and validation of new profiling methods such as DNA mic
roarray technology, proteomics, and metabolomics for the identification and
characterization of unintended effects, which may occur as a result of the
genetic modification, is recommended. The assessment of the allergenicity
of newly inserted proteins and of marker genes is discussed. An issue that
will gain importance in the near future is that of postmarketing surveillan
ce of the foods derived from genetically modified crops. It is concluded, a
mong others that, that application of the principle of substantial equivale
nce has proven adequate, and that no alternative adequate safety assessment
strategies are available.