12 December 2001
06/02
DRAFT ASSESSMENT
(Full Assessment - s.15)Full Report [ pdf 243kb ]
An application was received from Monsanto Australia Limited on 29 May 2000 seeking approval for food derived from genetically modified (GM) corn line NK603 under Standard A18 - Food Produced Using Gene Technology, Volume 1 of the Australian Food Standards Code (Standard 1.5.2 in Volume 2). The line is modified for tolerance to the herbicide glyphosate, known commercially as Roundup Ò. This report describes the scientific assessment of the application.
Issues addressed during assessment
i. Safety Evaluation
Nature of the genetic modification
In this application, the glyphosate-tolerance trait has been introduced into corn plants by the addition of a bacterial gene encoding the EPSPS protein, a key enzyme in the biosynthesis of aromatic amino acids in plants and microbes. The mode of action of glyphosate is to bind to the plant EPSPS protein, thereby impairing its normal enzyme activity, subsequently resulting in plant cell death. The bacterial form of the enzyme (denoted as CP4 EPSPS) has a lower affinity for glyphosate, so that when present in plant cells, the activity of the introduced enzyme replaces the sensitive plant EPSPS enzyme. The result is that the engineered plant is able to function in the presence of the herbicide.
Line NK603 contains two linked copies of the CP4 EPSPS gene, each with separate regulatory sequences. One copy is expressed from the rice actin promoter and intron while the second is expressed from the enhanced cauliflower mosaic virus promoter, which have both been shown to direct constitutive protein expression in corn. Additional regulatory sequences in common include an optimised chloroplast transit peptide sequence, to direct translocation of the CP4 EPSPS protein to chloroplasts where the protein is functionally active, and a NOS 3 - untranslated region providing the appropriate eukaryotic polyadenylation signal. Because a purified segment of DNA was used in the transformation, no extraneous bacterial genes, including laboratory marker genes, were transferred.
General safety issues
Corn has undergone substantial genetic breeding by conventional methods over many centuries and has been safely consumed as food and feed for thousands of years. The bacterial gene used in corn line NK603 is derived from a common soil bacterium, Agrobacteriumsp. strain CP4 which is not pathogenic. Comprehensive analytical data on the modified corn is available. There is only one new protein, namely the CP4 EPSPS enzyme, produced by the genetic modification. This new protein is present in corn grain, however the family of EPSPS proteins are ubiquitous in plant and microbial food sources that are already part of human diets.
Toxicology issues
The chemical similarity, and functional identity, of the CP4 EPSPS protein to other EPSPS proteins already consumed as part of the human diet provide some evidence that there is no inherent toxicity associated with the introduced protein. This was supported by the results of an acute toxicity study in mice, where animals were given purified CP4 EPSPS protein at single dose levels up to 400 mg/kg. There were no clinical signs of toxicity and animals continued to grow normally for the duration of the 9 day study.
Similarly, there is no evidence to indicate that food derived from corn line NK603 would be more likely to cause allergies than food derived from the non-transformed counterpart. The CP4 EPSPS lacks similarity to known allergens and protein toxins, is rapidly degraded in simulated digestive systems and occurs at low levels in the protein fraction of the grain. In addition, there is no possibility for the transfer of marker genes to cells in the human digestive tract from the consumption of food products derived from NK603 corn as the transformation was achieved using a purified DNA segment that did not include extraneous genetic material or antibiotic resistance marker genes.
Nutritional issues
All parts of the grain may be used to produce food fractions including corn oil, flour, starch and sugars, particularly high fructose corn syrup. The results of extensive compositional analyses on glyphosate-treated plants grown at multiple locations demonstrate that the levels of the important components in NK603 corn grain (protein, total fat, carbohydrate, ash, fibre, fatty acids, amino acids, minerals and moisture) are not different from the non-transformed parental line. In addition, analyses for Vitamin E, phytic acid and trypsin inhibitor confirmed that the modification has not resulted in any variation to these minor components.
Statistical analysis of the results for fatty acids and amino acids showed that some minor differences between the transformed line and non-transformed control line occurred at one or two of the trial sites. However, the nature of the differences was not consistent across all sites in the two major studies and therefore the differences were considered to reflect random variation that is characteristic of large-scale plant analyses. Moreover, all compositional results from the transformed line were well within the ranges observed for commercial non-transformed lines for each of the parameters investigated.
Corn line NK603 was also shown to be equivalent to its non-transformed counterpart in the ability to support typical growth and well being when included in the diet of rapidly growing broiler chickens.
Conclusion of the safety assessment
EPSPS enzymes from various plant and microbial food sources have been part of the protein component of the human diet over thousands of years, and are not associated with any known health concerns. The safety of food derived from glyphosate-tolerant corn line NK603 is based on:
a) a thorough understanding of the genetic modification and identification of the new gene product;
b) characteristics of the CP4 EPSPS protein in relation to its potential toxicity or allergenicity;
c) compositional analysis of the modified corn line compared to traditional corn lines.
The conclusion from this assessment is that, on the basis of the available evidence, glyphosate-tolerant corn line NK603 is compositionally equivalent to unmodified corn varieties, and is therefore suitable for human food use with respect to its safety, nutritional properties and wholesomeness.
ii. Labelling
Under the current Standard A18, which remains in effect until 7 December 2001, food derived from glyphosate-tolerant corn line NK603 would not require labelling as it is regarded as 'substantially equivalent 'to food derived from the non-genetically modified counterpart.
When the amended Standard (A18 in Volume 1, 1.5.2 in Volume 2 of the Food Standards Code) comes into effect on 7 December 2001, food products derived from NK603 corn will require labelling if novel DNA and/or protein is present in the final food.
iii. Public Submissions
Six submissions were received in response to the public notification of this application, of which one was supportive. Those opposing the application did so primarily on the basis that they perceive foods produced from GM crops to be unsafe, irrespective of the specific nature of the modification. The food safety concerns raised in submissions have been addressed by the draft safety assessment report.
iv. Review by external panel
It was not considered necessary to seek comments on the draft safety assessment from members of the external panel of experts, as this application deals with the insertion of a bacterial gene encoding the CP4 EPSPS protein which confers tolerance to glyphosate. The same gene was used in other food commodities such as glyphosate-tolerant soybeans, cotton, canola and sugarbeet that have already been assessed by ANZFA. In addition, several other genetically modified corn lines have undergone a safety assessment. The Draft Assessment Report for each of these previously assessed foods has been referred for independent external review and the conclusions have subsequently been endorsed by the reviewers. In addition, with the exception of glyphosate-tolerant sugarbeet which has undergone recent assessment, all of the foods derived from commodities modified with the CP4 EPSPS gene have been approved by the Ministerial Council.
On the basis of the data submitted with the application, evidence obtained from the scientific literature and from information obtained from public submissions, it is concluded that:
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The introduced genes in NK603 corn are not considered to produce any additional public health and safety risk;
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Food derived from NK603 corn is as safe and wholesome as food from other commercially available corn varieties;
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From 7 December 2001, food products containing NK603 corn will require labelling if novel DNA and/or protein is present in the final food; and
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The proposed amendment to the Food Standards Code is consistent with the section 10 objectives of the Australia New Zealand Food Authority Act 1991 and the regulatory impact assessment.
ANZFA now seeks public comment on the proposed amendment in accordance with the procedures described in Section 16 of the Australia New Zealand Food Authority Act 1991.
Full Report [ pdf 243kb ]