European Network Safety Assessment of Genetically Modified

European Network
Safety Assessment of
Genetically Modified
Food Crops
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Duration:
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01 2000
– 01
06 2003
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no: QLK1-1999-01182
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This project was subsidised by the European Commission
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through the 5 framework programme.
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Quality of Life Management of Living Resources, Key Action 1
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Main Conclusions &
Recommendations
www.entransfood.com
European Commission
Directorate General Research
Co-ordinator
ENTRANSFOOD:
RIKILT - Institute of
Food Safety
Wageningen UR
Wageningen
The Netherlands
Major Topics
in the Debate on the
Safety of Foods derived
from Genetically
Modified Crops
Introduction
1
The characteristics of food crops can nowadays be
altered by the application of modern recombinant
DNA technology. Genetically modified (GM) crops,
like soya, corn and cotton, currently cultivated, have
improved pest resistance and /or herbicide tolerance.
New GM crops are being developed with altered
nutritional characteristics.
While in the US, Canada and Argentina over 60 millions of hectares have been planted with these crops,
the cultivation area in Europe is very small. Consumer
and environmental groups have expressed concerns
about the safety of these crops for humans and the
environment, and have also raised more general
doubts on the impact of the technology on sustainable agriculture and on socio-economical aspects.
It was against this background that ENTRANSFOOD,
the EU funded Thematic Network on the Safety
Assessment of Genetically Modified Food Crops, has
started its activity. ENTRANSFOOD has in particular
evaluated issues of the safety of GM crop derived foods
and has also paid attention to issues like detection and
traceability and public attitudes towards GM food
crops.
Five Research Projects and Working Groups were set
up with more than 65 participants recruited from
academia, food industry, regulatory agencies and
consumer groups of 13 European countries.
2
ENTRANSFOOD Structure:
Safety Testing
of Transgenic
Foods
Detection of
Unintended
Effects
Gene
Transfer
Traceability and
Quality
Assurance
Societal
Aspects
Integrated Discussion Platform
Contributors from: Academia, Food Industry, Regulatory Agencies, Consumer Groups
3
Outcomes:
• Review and Position Papers
• Integrated Evaluation Document
• Recommendations
• Press releases, Information on Web Site
The outcomes of ENTRANSFOOD will be published as
scientific papers (Special issue of Food and Chemical
Toxicology), an Overarching Paper and an Executive
Summary. These documents will be published on the
ENTRANSFOOD Internet site:
www.entransfood.com
This flyer presents the main conclusions and recommendations of the topics investigated by ENTRANSFOOD.
The five research projects are:
1. SAFOTEST: New methods for the safety testing of
transgenic food. QLK1-1999-00651
2. GMOCARE: New methodologies for assessing the
potential of unintended effects in genetically
modified food crops. QLK1-1999-00765
3. GMOBILITY: Safety evaluation of horizontal gene
transfer from genetically modified organisms to
the microflora of the food chain and human gut.
QLK1-1999-00527
4. QPCRgmofood: Reliable, standardised, specific,
quantitative detection of genetically modified
foods. QLK1-1999-01301
5. GMOCHIPS: New technology in food sciences facing the multiplicity of new released GMO. Measurement & Testing, G6RD-CT2000-00419
Comparative Safety Assessment of GM Crop Plants
Main Conclusions:
GM crop
Conventional crop
Topic: Safety Testing of Transgenic Foods
Are current safety evaluation strategies for foods derived from GM
crops adequate to establish their safety?
Comparison of the GM crop and its conventional counterpart
(establishment of substantial equivalence)
Conclusion
The safety evaluation of foods derived from GM crops is carried out in
a comparative manner: i.e. differences between the GM crop and the
conventionally grown crop are identified and investigated with respect
to their impact on human or animal health (Concept of Substantial
Equivalence, see figure 1). The basic idea behind this approach is that
conventional foods have a long history of safe use. ENTRANSFOOD
has designed a detailed stepwise procedure to carry out the safety
assessment of GM crop derived foods on a case-by-case basis. The
approach comprises four steps: Characterisation of the parent crop,
which is genetically modified; characterisation of the genetic modification process; toxicological and allergenicity assessment of new gene
products (proteins and metabolites); and safety evaluation of the
whole GM food crop. A combination of existing test methods provides
a robust test regime and ensures that GM foods that have passed the
test procedure are as safe and nutritious as currently consumed plantderived foods. The designed approach is also applicable to new generations of GM food crops with extensive compositional changes.
Novel or differently
expressed proteins
Introduced
genes
Novel or differently
formed chemical
substances
Testing for toxicological and nutritional significance of the identified differences
Gene
transfer
Allergenicity
Degradability,
digestibility
Bio availability
Toxicity
Dietary
intake
Evaluation of safety and nutritional data
4
Additional testing
of whole foods, if
necessary
Recommendations
• In the future, based on our improved understanding of molecular
biology, toxicology and nutrition, further improvement of test
methods may be considered that will render the safety assessment of
foods even more effective and informative.
• Strategies for assessing the potential allergenicity of new proteins in current GM crops and of a possible alteration of the allergenic properties of
the GM crop are adequate and are based on evaluation of various
aspects. Further development of new in vitro methods and animal models to predict the allergenicity of food components is recommended.
• Post market monitoring of GM foods might be considered useful for
those foods with specifically changed nutritional properties and whose
intake can be followed through labelling. Post-market monitoring is
not recommended as routine practice for commodity GM foods.
Safety assessment of the GM crop
Figure 1
Topic: Detection of Unintended Effects
Topic: Gene Transfer
Is there a chance that the genetic modification used to develop GM
crops may result in unexpected effects on the composition of GM
food crops and that these changes pose health risks? Are the current analytical test methods robust and reliable enough to identify
such changes?
Is there a risk of transfer of genetic material from foods derived from
GM crops to a living cell or organism (horizontal gene transfer) and
would this have negative consequences? Could foreign DNA from
GM crops be transferred to human germ cells, or could transfer of
antibiotic resistance marker genes from GM plants to the microbial
population in the human gut occur and compromise the effectiveness of the antibiotic treatment of infections?
Conclusion
5
Unintended alteration in the composition of plants is a common
phenomenon that occurs when changing the genetic information of
a plant either by classical breeding methods or by GM technology.
There is no indication that unintended effects are more likely to
occur in GM crops.
Detection of unexpected effects in plants, which are developed by
GM technology, relies primarily on the comparative analysis of levels of selected key nutrients and toxic compounds present in the GM
crop and its traditional non-modified counterpart. Identified alterations in composition may fall within the natural range of variations
and thus not be of toxicological concern, or fall outside these ranges
and then need further toxicological or nutritional investigations. This
targeted approach has shown to be effective in conventional plant
breeding to identify alterations in composition.
In order to increase the probability of detecting unexpected effects,
profiling techniques are under development. These methods, based on
modern genomic, protein and metabolite detection techniques, are
able to provide a ‘global’ overview of gene expression and chemical
composition of the GM and non-GM crop (non-targeted approach).
Recommendations
• Profiling methods are primarily informative for elucidating metabolic pathways in plants, but need further development and validation before they can be used in routine risk assessment.
• The establishment and coupling of databases containing gene
expression, protein and metabolite profiles of food crops and their
natural variation patterns are recommended.
• A combination of targeted and non-targeted methods of analysis,
to be decided for on a case-by-case basis, is the best way forward
to evaluate the safety of GM and conventionally bred crops.
Conclusion
Horizontal gene transfer is at the origin of the variety of life itself.
The impact of horizontal gene transfer will depend among others on
the selective advantage for the bacterial population. There is little
reason to assume that the consumption of foods derived from GM
crops constitutes a specific risk. Whereas uptake of ingested recombinant (foreign) DNA by mammalian somatic cells has been demonstrated, there is no evidence that ‘consumed’ DNA will end up in
germline cells.
Transfer of antibiotic resistance marker genes from GM plant varieties
to the gut microflora of humans and their expression is most probably a rare event, given the low amounts ingested and degradative
conditions in the gastro-intestinal tract. However since gene transfer
cannot completely be excluded, ENTRANSFOOD has classified antibiotic resistance marker genes based on their distribution and therapeutic importance.
Recommendations
• To reduce the risk of gene transfer to the microbial population in
the gut the use of bacterial DNA in constructing GM plants should
be kept to a minimum.
• Marker genes, which code for resistance against clinically important antibiotics, should not be used. Some antibiotic resistance
marker genes such as the nptII gene and the hygromycin resistance gene can be used without the risk of compromising the use
of important clinically used antibiotics.
• The use of alternative markers should also undergo a thorough
safety evaluation.
Topic: Traceability and Quality Assurance
Topic: Societal Aspects
The consumer wants to be informed whether a food product contains ingredients that are derived from genetic modified food crops
or not. Are all systems such as traceability and detection methods
adequate to ensure this freedom of choice of the consumer?
How can transparency in risk assessment, risk management and risk
communication be improved in order to take account of consumer
concerns (and risk perception) and to meet the broader consumers’
concern about the introduction of the new technology?
Conclusion
Conclusion
The new EU regulations impose requirements of labelling of foods
or feed containing ingredients derived from GM food/feed crops or
containing traces of GM crops above a certain threshold (>0.9 %).
To facilitate control and to verify labelling claims or to facilitate
product recall when necessary, reliable documentation systems to
trace back the origin of the ingredients (traceability system) and
analytical methods to detect and quantify the amount of GM
derived ingredients have been developed.
Risk assessment of GM foods has focused on adverse health effects
for humans and the environment, but public concern is much
broader, focusing not only on risks, but also on who benefits, what
are the needs and how does it contribute to a sustainable agriculture. It is important to explicitly address public concerns, and to
develop new methods for stakeholders’ involvement and public consultation.
Recommendations
Recommendations
• Sequence information on the genetic modification as well as relevant reference material is crucial for the development of any GMO
detection and / or identification method and should therefore be
available to regulatory authorities and food control laboratories.
• With more GMOs being developed worldwide more efficient
GMO detection and identification methods will need to be developed, based on the latest developments in molecular biology, in
order to be able to adequately maintain GMO regulations within
the European Union.
• The use of traceability systems for post-marketing applications
requires new labelling systems that convey all necessary information on the presence of individual GMO varieties to the reader.
• Research is needed to determine the most effective form of food
labels, which take due account of cross-cultural differences in
information preferences where they exist.
• The optimal ways to formalise public engagement and consultation into new working procedures should be addressed in future
research projects, as well as impact on the risk analysis process, on
regulatory procedures and institutions involved.
• ENTRANSFOOD recommends the establishment of a Permanent
Evaluation and Discussion Platform on the assessment and introduction of new foods in Europe produced by different breeding
practices and production systems.
• There is a need for a general framework for risk analysis of all types
of new foods produced by different breeding and production
methods, taking scientific, economic and societal aspects into
account.
6
Participants:
1. RIKILT - Institute of Food Safety,
Wageningen University & Research
Center, Wageningen, The Netherlands (Dr. H.A. Kuiper, Dr. G.A.
Kleter, Dr. H.P.J.M. Noteborn,
Dr. H.J.P. Marvin, Dr. A.A.C.M.
Peijnenburg, Ir. E.J. Kok,
Dr. H.J.M. Aarts, Ir. J.P.P.F. van Rie)
2. Institute of Food Safety and
Toxicology, Danish Veterinary and
Food Administration, Søborg,
Denmark (Dr. I. Knudsen, Dr. M.
Poulsen, Dr. B.L. Jacobsen, Dr. B.
Holst, Dr. A. Wilcks, Dr. J. Pedersen)
3. Department of Agricultural and
Environmental Sciences, University
of Newcastle, Newcastle, United
Kingdom (Dr. A.M.R. Gatehouse)
4. Département d’Ecophysiologie
Végétale et de Microbiologie CEA
Cadarache, Saint Paul Lez Durance,
France (Dr. J.J. Leguay)
5. European Commission - Joint
Research Centre, Institute for Health
and Consumer Protection, Food
Products and Consumer Goods Unit,
Ispra, Italy (Dr. G. van den Eede)
6. Umweltbundesamt, Vienna, Austria
(Dr. A. Heissenberger)
7. Institute of Food Research, Food
Quality and Materials Science
Division, Diet Health & Consumer
Science, Norwich, United Kingdom
(Dr. I. Colquhoun, Dr. L. Frewer)
8. Rowett Research Institute,
Aberdeen, United Kingdom
(Dr. A. Chesson, Dr. H. Flint)
9. Unilever Research Colworth, SEAC
Toxicology Department, Colworth,
United Kingdom (Dr. R. Crevel)
10. Istituto Superiore di Sanitá, Section
of Cereal Chemistry, Laboratory of
Food, Rome, Italy (Dr. M. Miraglia)
11. Laboratoire Associe INRA-CEA d’lmmuno-Allergie Alimentaire, Service
de Pharmacologie et Immunologie,
Gif-sur-Yvette, France (Dr. J. M. Wal,
Dr. C. Créminon)
12. Institut National de la Recherche
Agronomique, UEPSD - Fonctions
des Bacteries Intestinales, Jouy-enJosas Cedex, France (Dr. G. Corthier)
13. Institute of Environmental
Medicine, Karolinska Institute,
Stockholm, Sweden (Dr. R.
Grafström, Dr. T. Midtvedt)
14. Lehrstuhl für Allgemeine Lebensmitteltechnologie, Technische
Universität München, München,
Germany (Dr. K.H. Engel)
15. Metapontum Agrobios, Plant
Biotechnology Department,
Metaponto, Italy (Dr. F. Cellini)
16. Agricultural Economics Research
Institute (LEI), Wageningen
University & Research Center,
The Hague, The Netherlands
(Dr. V. Beekman)
17. TNO Nutrition and Food
Research Institute, Zeist,
The Netherlands (Drs. J.W. van
der Kamp, Dr. A. Penninks,
Dr. J. van der Vossen)
18. Cellular & Environmental Physiology
Department, The Scottish Crop
Research Institute, Dundee, United
Kingdom (Dr. H. Davies)
19. Robert Koch Institut, Zentrum
Gentechnologie, Berlin, Germany
(Dr. H.J. Buhk)
20. International Life Sciences Institute,
ILSI Europe, Brussels, Belgium
(Dr. J. Kleiner)
21. Bundesinstitut für Gesundheitlichen
Verbraucherschutz und Veterinärmedizin (BgVV), Center for Novel
Foods and Genetic Engeneering,
Berlin, Germany (Dr. J. Zagon,
Dr. M. Schauzu)
22. Regulatory Toxicology, Herbicides
en Biotechnology, Aventis
CropScience, Sophia Antipolis
Cedex, France (Dr. E. Debruyne)
23. Institute of Food Technology,
General Food Technology and Food
Microbiology, Hohenheim
University, Stuttgart, Germany
(Dr. W.P. Hammes)
24. European Commission - Joint
Research Centre, Institute for
Reference Materials and Measurements, Reference Materials Unit,
Geel, Belgium (Dr. H. Schimmel)
25. Bureau Européen des Unions de
Consommateurs (BEUC), Brussels,
Belgium (Dr. B. Kettlitz)
26. Department of Biochemistry,
University of Kuopio, Kuopio,
Finland (Dr. S. Kärenlampi)
27. Institute of Applied Biotechnology,
University of Kuopio, Kuopio,
Finland (Dr. A. von Wright)
28. Scientific Affairs, Agricultural Sector,
Monsanto Service International,
Brussels, Belgium (Dr. A. Cockburn)
29. Quality and Safety Assurance, Nestlé
Research Centre, Lausanne, Switzerland (Dr. A. Constable, Dr. D. Toet
(now Unilever Rotterdam, NL))
30. National Veterinary Institute,
Section of Food and Feed
Microbiology, Oslo, Norway (Dr. A.
Holst-Jensen, Dr. K.G. Berdal)
31. Central Toxicology Laboratory,
Syngenta, Cheshire, United
Kingdom (Dr. I. Kimber)
32. Unilever Health Institute, Unilever
Research, Vlaardingen, The
Netherlands (Dr. M. Smith)
33. Swiss Quality Testing Services,
Food Testing Laboratory, Migros
Cooperatives, Courtepin,
Switzerland (Dr. J. Rentsch)
34. Swedish National Food
Administration, Uppsala, Sweden
(Dr. U. Hammerling)
35. Centre for Bioethics and Risk
Assessment, Research Department of
Human Nutrition, Royal Veterinary
and Agricultural University, Frederiksberg, Denmark (Dr. J. Lassen)
36. Centre for Market Surveillance,
Research and Strategy for the Food
Sector (MAPP), The Aarhus School
of Business, Aarhus, Denmark
(Dr. J. Scholderer)
37. Laboratoire de Biochimie Cellulaire,
Facultés Universitaires Notre-Dame
de la Paix, Namur, Belgium
(Dr. J. Remacle, Mr. S. Leimanis)
38. Harvard University, Kennedy School
of Government, Belfer Centre for
Science & International Affairs,
Cambridge, United States of
America (Dr. A. König)
39. Department of Genetics, Carl von
Ossietzky University, Oldenburg,
Germany (Dr. W. Wackernagel)
Further information:
RIKILT - Institute of Food Safety
Wageningen UR
Dr. H.A. Kuiper/Dr. H.J.P. Marvin
P.O. Box 230
6700 AE Wageningen, the Netherlands
Telephone: + 31 317 475 543
Fax:
+ 31 317 417 717
E-mail:
entransfood.rikilt@wur.nl
European Commission
Ms Dyanne Bennink
Directorate General Research
SDME 8/9
B-1049 Brussels, Belgium
Telephone: + 32 2 295 9183
Fax:
+ 32 2 296 4322
E-mail:
dyanne.bennink@cec.eu.int
graphic design by Daniël Loos
technical realisation by Propress BV, Wageningen
Visit our internet site:
www.entransfood.com