IMPORTANT LEGAL NOTICE - The information on this site is subject to a disclaimer and a copyright notice
Banner Research
  European Commission   > Research > GMO
EC-sponsored Research on Safety of Genetically Modified Organisms - A Review of Results
imageIntroductionimage Research areasimage Foodimage Project 05
Graphic element Graphic element Graphic element

 button Introduction
 button Foreword
 button Research areas
imageimageimage Plants
imageimageimage Plant  microbes
imageimageimage Biocontrol
imageimageimage Food
imageimageimage Bioremediation
imageimageimage Tools
imageimageimage Fish
imageimageimage Vaccines
 button Index of participants
image Development of new methods for safety evaluation of transgenic food crops

Background and objectives

The ability to manipulate the genetic material of crop plants through recombinant DNA technology may lead to food products with novel traits. The majority of gene transfer work has been performed on Bacillus thuringiensis (Bt) cry genes which convey resistance against pests such as Lepidoptera insects. Genetically modified organisms should be handled carefully and the putative hazards and risks should be carefully studied before their commercial release.

The objectives of this project were to study safety issues related to (i) the nutritional and toxicological consequences of inserted gene products, (ii) the potential of pleiotropic (unintended) effects in the host organism due to insertion, (iii) the allergenicity of expressed proteins and novel foodstuffs and (iv) the potential of gene transfer to human and animal gut flora.

Approach and methodology

We designed a strategy combining analytical in vitro and in vivo toxicological methods. The work consisted of (i) isolation of Bt-proteins from transgenic crops, (ii) development of methods to assess posttranslational modification differences, (iii) development of chemical fingerprint analysis to identify unintended effects, (iv) in vitro toxicological profiling of Bt-proteins and (v) application of the Brown Norway rat model for allergenicity testing. We studied the Bacillus thuringiensis (Bt) cry genes (e.g. Cry1Ab5.PGS1 and Cry9C.PGS2) in cauliflower, corn and tomato varieties together with marker gene proteins (e.g. NPTII, PAT).

Main findings and outcome

Immunocytochemical screening revealed no interactions of the Cry proteins with receptors in the gut of rodents and primates, including humans. Repeated dose feeding studies (28-days) in rodents showed that the proteins Cry1Ab5, NPTII and PAT are digested very rapidly and are unlikely to present a health risk for humans. The Cry9C protein resisted proteolysis in the stomach but showed a low bioavailability in rats and did not cause acute or systemic toxic effects. In the Brown Norway rat model, the Cry9C protein and related modified crops (e.g. corn) are capable of eliciting an IgE reaginic (antibodies associated with allergy) response under 'worse-case' conditions, but its potential as a human allergen is not proven as yet. No major changes were observed in the agronomic and resistance characteristics of greenhouse and field-tested crops, nor in the food processing characteristics of the Bt-tomato expressing the Cry1Ab5 and NPTII proteins. The Cry1Ab5 protein isolated from Bt-tomato fruit appeared to be glycosylated unlike the E. coli equivalent. We analysed the unintended effects of gene insertion by chemical fingerprinting techniques in conjunction with conventional chemical analysis of critical nutrients and key natural plant toxins. No significant changes were observed in key nutrients, a-tomatine, metabolite and N-glycan composition between Bt-crops and their non-modified counterparts. Thus initial results suggest that the Bt-tomato variety expressing the Cry1Ab5 protein is as safe as its traditionally bred counterpart when consumed on a regular basis.


Progress has been made with the development of the principle of substantial equivalence by establishing a hierarchy of comparisons, including the choice of comparators and appropriate statistical analysis. Application of these technologies improves current analytical testing of single compounds and complements and will eventually reduce animal feeding studies. The present approach provides a sound scientific basis for the evaluation of the food safety of genetically modified Bt-crop plants and derived foodstuffs. The technologies developed and the results obtained may serve as general framework for testing the safety and nutritional value of genetically modified crop plants.


Major publications

Lommen A., Weseman J.M., Smith G.O., Noteborn H.P.J.M., "On the detection of environmental effects on complex matrices combining off-line liquid chromatography and 1H-NMR".
Biodegradation, 9, 1998, pp. 513-525.

Noteborn H.P.J.M., Lommen A., van der Jagt R.C., Weseman J.M., "Chemical fingerprinting for the evaluation of unintended secondary metabolic changes in transgenic food crops".
Biotechnology, 77, 2000, pp. 103-114.

Noteborn H.P.J.M., Bienenmann-Ploum M.E., van den Berg J.H.J., Alink G.M., Zolla L., Reynaerts A., Pensa M. and Kuiper H.A., "Safety assessment of the Bacillus thuringiensis insecticidal crystal protein Cry1A(b) expressed in transgenic tomatoes", in Genetically Modified Foods. Safety Issues, Engel K.-H., Takeoka G.R., Teranishi R. (eds.), ACS Symposium Series 605, Washington DC, 1995, pp. 134-147.

Zeleny R, Altmann F, Praznik W., "Structural characterization of the N-linked oligosaccharides from tomato fruit".
Phytochemistry, 51, 1999, pp. 199-210.

Atkinson H.A.C., Meredith C., "Assessment of allergenic potential of novel proteins in food crops using the brown Norway rat model", in Proceedings 3rd Karlsruhe Nutrition Symposium: European research towards Safer and Better Food Part 1, Gaukel V, Spiess W.E.L. (eds.), Bundesforschungsanstalt für Ernährung, Karlsruhe, Germany, 1998, pp. 70-75.
image imageimage image
imageResearch project

Contract number

January 1995 - May 1998

H.P.J.M. Noteborn
State Institute for Quality Control of Agricultural Products (RIKILT)
Wageningen (NL)



A. Reynaerts
Aventis CropScience N.V.
Gent (BE)

S. Beeckmans
Vrije Universiteit Brussel
Sint-Genesius-Rode (BE)

W. Praznik
Institute for Agrobiotechnology (IFA)
Tulln (AT)

C. Meredith
BIBRA Toxicology International
Carshalton (UK)

Previous project | Food contents | Next project | Top