methods for the safety testing of transgenic food (SAFOTEST)
In 1997, the European Union Scientific Committee on Food (SCF) issued
a set of recommendations for the safety assessment of novel foods, including
food that has been prepared using genetically modified (GM) organisms.
The SCF suggested a decision tree approach, which for the toxicological
part may include a demand for separate animal studies to provide the missing
information. However, the SCF did not give specific advice on how to carry
out these studies, but stated that the design should be determined on
a case-by-case basis. As a consequence, in Europe, there is no precise
harmonisation of methodologies to assure the safety of transgenic food
products, it being difficult to use traditional animal feeding studies
for toxicological assessments. This clearly raises biosafety issues for
the use of GM products in food. In vivo and in vitro validated
nutritional-toxicological testing procedures are urgently required. The
overall objective of this project is to develop and validate the scientific
methodology which is necessary for assessing the safety of foods from
GM plants, in accordance with the European Union Regulation 258/97 of
January 27, 1997, concerning novel foods and novel food ingredients. The
project is designed to meet the immediate need for a sensitive and specific
testing strategy for GM foods in a scientifically valid and economically
Click to view
Approach and methodology
The project, subdivided into seven different stages, will examine a safety
testing procedure for food derived from GM plants. In stage I, three strains
of GM rice, containing introduced genes will be developed and characterised.
The genes that will be introduced encode three potentially insecticidal
proteins: the snowdrop lectin GNA (which do not have any known mammalian
toxicity, but which interact with the gut), the kidney bean lectin PHA-E
(which has high mammalian toxicity) and a bacterial toxin from Bacillus
thuringiensis (which has no known mammalian toxicity). In addition,
recombinant proteins will be expressed and purified for later use as 'spiking
materials' for the in vivo studies and test material for the in
vitro studies. In stage II, the three strains of transgenic rice will
be raised in sufficient quantities for in vivo testing, and their
genetic identity and stability will be assured. Stage III involves identification
and measurement of the critical nutrients, the critical toxic agents and
other critical chemical changes in the transgenic rice strains. In stage
IV, a study based on rat feeding and OECD 28 day toxicity measurements,
will be performed to ensure optimal diet composition and to measure suspected
lectin or Bt sensitive parameters for applications in stage VI. Stage
V involves measurement of the effects of lectins and Bt toxin in a number
of in vitro systems, in order to adjust the sensitivity and specificity
of parameters which will be investigated in the animal study with the
transgenic rice species in stage VI. Supplementary mechanistic and dose
response studies will also be carried out in vitro to supplement
the in vivo studies for the final risk assessment. In stage VI,
a 90-day OECD toxicity study in rats will be carried out with the three
transgenic strains of rice, with and without the relevant test protein.
In this study, the measurements of the lectin and Bt sensitive parameters
optimised in stages IV and V will be incorporated.
In the final stage, the results as well as the knowledge base acquired
from the first six stages, will be evaluated in order to assess the sensitivity,
specificity and efficacy of the safety testing approach recommended by
the European Union SCF.
If the outcome of the studies of this project is as expected, the data
will be of great re-assurance to European consumers, concerned over the
safety and 'wholesomeness' of his/her food supply derived from genetically
modified food plants. However, if the testing procedure investigated in
this project does not allow assessment of the toxicity of the gene products
introduced into the food product via the GM plants, the whole strategy
for the safety assessment of novel foods from GM plants will need to be
Knudsen I., "Conventional foods versus genetically modified
foods: Present knowledge and possible safety issues", in
Gentechnik und Ernährung, Erbersdobler, Hammes, Jany
(eds.), Wissenschaftliche Verlagsgesellshaft mbH, Stuttgart, 1995,
Engel K.-E., Gerstner G., Roß A., "Investigation of
glycoalkaloids in potatoes as example for the principle of substantial
equivalence", in Die Novel Foods Verordnung der Europäischen
Union - Verläßlichkeit der gesundheitlichen Bewertung,
M. Schauzu, K.-W. Bögl (Hrsg.), BgVV-Heft, 1998, pp. 197-209.
K.V., Rathore K.S., Hodges T.K., Fu X.D., Stoger E., Sudhakar
D., Williams S., Christou P., Bown D.P., Powell K.S., Spence J.,
Bharathi M., Gatehouse A.M.R., and Gatehouse J.A., "Expression
of snowdrop lectin (GNA) in the phloem of transgenic rice plants
confers resistance to rice brown planthopper".
The Plant Journal, 14, 1998, pp. 469-477.
Hal N.L.W., Vorst O., Kok E.J., Van Houwelingen A.M.M.L, Peijnenburg
A.A.C.M., van Tunen A.J., and Keijer J., "The application
of DNA micro-arrays in gene expression analysis".
J. Biotechnology, 78, 2000, pp. 271-280.
M.A., George L.A., Ross H.A., Davies H.V., "cDNA cloning
and characterisation of an alpha-glucosidase gene from potato".
The Plant Journal, 13, 1998, pp. 419-425.
February 2000 - February 2004
Institute of Food Safety and Toxicology
Technische Universität München
The Scottish Crop Research Institute
University of Newcastle (UK)
State Institute for Quality Control of Agricultural Products (RIKILT)
Institute of Food Safety and Toxicology