As a macronutrient, protein is an essential component of the human diet and consumption of proteins as a class of dietary substances is not inherently associated with adverse effects. Of the thousands of proteins that may be ingested daily, only a very small number have the potential to exert anti-nutritional or toxic effects, or elicit allergic reaction in previously sensitized individuals.
Assessing the safety of newly-expressed proteins produced in the edible portions of a genetically engineered food crop is an integral component of the overall safety assessment. As there is currently no single criterion that is sufficiently predictive of potential toxicity or allergenicity, a “weight-of-evidence” approach is recommended for hazard identification that considers the history of use, amino acid sequence similarity to known toxins or allergens, function or mode of action, digestibility under standardized in vitro conditions, stability to heat or processing, and expression levels and potential dietary exposure.
GR2E Golden Rice contains three newly expressed proteins:
- ZmPSY1 – phytoene synthase from another food crop, maize, which catalyzes the condensations of two molecules of geranylgeranyl diphosphate to form 11-cis-phytoene, the first committed step in the carotenoid biosynthetic pathway;
- CRTI – phytoene desaturase from a common bacterial species (Pantoea ananatis), which catalyzes the conversion of 11-cis-phytoene to all-trans-lycopene, an immediate precursor of beta-carotene; and
- PMI – phosphomannose isomerase from the bacterium Escherichia coli, a normal inhabitant of the intestinal flora of humans and animals, which allows for positive selection of transformed plants on media containing mannose as the sole carbon source.
Each of the newly expressed proteins in GR2E rice was evaluated using the “weight-of-evidence” approach, and for each protein:
- bioinformatics studies confirmed the lack of any significant amino acid sequence similarity to proteins known to be toxic via oral exposure or to allergens;
- digestibility studies confirmed rapid degradation in the presence of simulated gastric fluid containing pepsin; and
- heat stability studies demonstrated rapid inactivation at temperatures below those used for cooking or processing.
In addition, mouse acute oral toxicity testing of the CRTI and PMI proteins showed a lack of toxic effects at dosages thousands of times more than any realistically conceivable dietary exposure from consuming GR2E rice. Taken together, the evidence indicates that neither ZmPSY1, CRTI, or PMI are likely to be toxic or result in allergic reactions in humans or animals. Conventional white rice is not considered a source of toxins or a significant source of anti-nutritional factors, nor is it considered by allergists to be a common allergenic food, and the genetic modification resulting in GR2E Golden Rice has not altered this safety profile.