Genetically modified maize line NK 603 expresses the CP4 EPSPS protein which confers tolerance to the glyphosate herbicides.

Products:

1.) Foods and food ingredients containing, consisting of, or produced from MON-ØØ6Ø3-6 maize
2.) Feed containing, consisting or produced from MON-ØØ6Ø3-6 maize
3.) Products other than food and feed containing or consisting of MON-ØØ6Ø3-6 maize for the same uses as any other maize with the exception of cultivation

Please see the EU relevant links below.

Method for detection: Event specific real-time quantitative PCR based method for genetically modified NK 603 maize Validated by the Joint Research Centre (JRC) of the European Commission, in collaboration with the European Network of GMO Laboratories (ENGL). Reference material: ERM®-BF415 accessible via the Joint Research Centre (JRC) of the European Commission, Institute for Reference Materials and Measurements (IRMM). Relevant links are provided below.

Glyphosate is the active ingredient of the proprietary herbicide Roundup® which is used widely as a non-selective agent for controlling weeds in primary crops. The corn is known commercially as Roundup Ready (RR) corn line NK603.

Glyphosate directly affects the shikimate biosynthetic pathway in plants. The mode of action of glyphosate is to specifically bind to and block the activity of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an essential enzyme involved in the biosynthesis of aromatic amino acids in all plants, bacteria and fungi. Blocking the enzyme results in the breakdown of the synthesis of essential aromatic amino acids in cells, ultimately leading to the death of the plant.

Biochemical studies on the EPSPS enzyme from a variety of different species have shown that a natural variation in glyphosate binding affinity exists, particularly across bacterial species (Schultz et al. 1985). Tolerance to glyphosate in plants can therefore be achieved by introducing a bacterial version of the EPSPS gene producing a protein with a reduced binding affinity for glyphosate, thus allowing the plant to function normally in the presence of the herbicide.

In glyphosate-tolerant corn line NK603, the herbicide-tolerance trait is generated in the plants through the addition of a bacterial EPSPS gene derived from a common soil bacterium, Agrobacterium sp. strain CP4 (CP4 EPSPS). The enzyme produced from the introduced gene has a reduced affinity for the herbicide compared with the corn enzyme, and thus imparts glyphosate tolerance to the whole plant.

The bacterial CP4 EPSPS is used also in Roundup Ready varieties of soybean, canola,
sugar beet and cotton. Foods derived from these modified crop lines have previously been assessed for safety by ANZFA and have been approved5 for food use in Australia and New Zealand under Standard A18 – Food Produced Using Gene Technology in Volume 1(Standard 1.5.2 in Volume 2) of the Food Standards Code.

Corn is used predominantly as an ingredient in the manufacture of breakfast cereals, baking products, extruded confectionery and corn chips. Maize starch is used extensively by the food industry for the manufacture of many processed foods including dessert mixes and canned foods.

Despite the diverse uses of corn products in many foods, corn is a relatively minor crop in both Australia and New Zealand, with a declining area planted over the last decade. Consequently, there is a requirement to import products such as high-fructose corn syrup and maize starch to meet manufacturing demand. The glyphosate-tolerance trait has not been introduced into sweet corn or popcorn varieties and therefore the whole kernel from corn line NK603 is not consumed directly as food, but rather is processed into various corn fractions.

commercial release of genetically modified glyphosate tolerant corn Roundup Ready 2 Event NK603

NK603 corn expresses glyphosate protein CP4 5-Enol-pyruvylshikimate-3-phosphate synthase (CP4 EPSPS). Weed control performed by glyphosate is due to inhibition of EPSPS enzyme naturally produced by the plant. The enzyme catalyzes a critical phase of the metabolic way of shikimic acid for biosynthesis of aromatic amino acids in plants and microorganisms. CP4 EPSPS proteins have low glyphosate affinity, when compared with the wild EPSPS protein. Therefore, when the NK603 corn expressing protein CP4 EPSPS is treated with glyphosate, the plants keep developing normally. The continuous action of glyphosate tolerant CP4 EPSPS enzyme catalyzes the synthesis of amino acids required for the normal development of the plant. The biosynthetic way of aromatic amino acids is not found in animals, which explains the glyphosate selective activity in plants and contributes towards low toxicity to mammals. Two cp4 epsps gene expression cassettes were introducing in the corn genome through a single insert, producing NK603 corn. The cp4 epsps gene is derived from a bacterium common in the soil, Agrobacterium sp. strain CP4, which codifies the expression of protein EPSPS naturally tolerant to glyphosate. The gene donor organism, A. tumefaciens strain CP4 is a bacterium commonly found in the soil and causes galls in susceptible plants, with no scientific evidence indicating that it may cause adverse effects to humans or animals. Toxicity tests were conducted with EPSPS-synthase enzyme isolated from transformed plants. Ingestion through gastric gavage of the protein molecule in doses 1000 times above the figure for modified seeds failed to cause any physiologic change in animals tested. Results of in vitro proteolysis also verified rapid digestion and innocuousness of the engineered protein, removing any suspicions of allergenicity. CP4 EPSPS protein is atoxic, as demonstrated by a oral acute toxicity stud, when CP4 EPSPS was administered to mice in one single high dose. The protein, produced and purified from Escherichia coli, was characterized and showed to be equivalent to the CP4 EPSPS produced in the corn. The purified protein was orally administered to mice for assessing its acute toxicity. Acute administration was deemed as appropriate in assessing the safety of CP4 EPSPS, since toxic proteins act by means of acute mechanisms. The no-observed-effect-level (NOEL) for oral toxicity in mice was 572 mg/kg, the highest tested dose. The result represented a safety margin of about 260,000 times, based on the average daily consumption of corn in the United States and average expression of the protein in the glyphosate tolerant genetically modified corn (assuming that there is no loss of CP4 EPSPS throughout processing). There were no statistically different differences in body weight, aggregate body weight or food consumption between control groups (with the vehicle or bovine albumin serum) and groups treated with the purified CP4 EPSPS protein. EPSPS proteins are ubiquitous in nature and are naturally present in foods derived from plant and microbial sources and do not show significant homology of amino acids with proteins known to be toxic or allergenic to mammals. Apparently, the CP4 EPSPS protein was rapidly digested by in vitro gastric and bowel fluids. Besides, EPSPS proteins that have a history of safe use are widely used in the diet, corn is a plant unable to survive in natural conditions, without technical assistance. Therefore there is no possibility that the corn shall be transformed in an invading plant or pest. Even in case of un unlikely genic escape, the possibility of fixation of an allele containing the genic sequence that grants tolerance to glyphosinate in the population is very reduced in the absence of selective pressure. The NK603 corn demonstrated to be equivalent to conventional corn, with the exception of its tolerance to glyphosate. Its basic interactions with other living organisms in the environment are not deemed to be different from the ones of conventional corn. Though there is a potential exposure of weed, pests and pathogens of corn culture to the CP4 EPSPS and CP4 EPSPS L214P proteins that are expressed in the NK603 corn, there are no concerns that the process may negatively affect such populations. Through trophic transfer and decomposition processes, organisms that are not targets to CP4 EPSPS and CP4 EPSPS L324P proteins, such as predators and preys of corn pests, may be exposed to very low levels of such proteins without, however, emerging any evidence of negative effects on the non-target organisms. Environment safety of the EPSPS protein family is widely accepted, since the proteins are ubiquitous in nature (bacteria, fungi, algae and higher plants), do not have known toxicity, are not associated to pathogenicity and fail to grant any selective advantage to plants that contain the proteins. For the foregoing, there are no restrictions to the use of the genetically modified corn and its derivatives, either as human of animal food. In addition, the proteins stem from the EPSPS protein family, with a long history of safe consumption and exposure, occurring ubiquitously in plants and microorganisms. Analytic studies comparing the composition of kernel and forage of NK603 with the conventional corn show that the genetically modified glyphosate tolerant NK603 corn is substantially equivalent to conventional corn. Based on studies conducted during the several years of marketing NK603 corn and other glyphosate tolerant cultures expressing the CP4 EPSPS protein, coupled with the safe history of the corn as a consumption source for human and animal food, one reaches the conclusion that glyphosate tolerant NK603 corn, or Roundup Ready 2 corn is substantially equivalent and as safe as conventional corn. Coexistence of cultivars of conventional (either improved or wild) corn and cultivars of transgenic corn is possible from the agronomic viewpoint and shall comply with the provisions of CTNBio Ruling Directive no. 4. According to Article 1 of Law no. 11,460, of March 21, 2007 ”research and cultivation of genetically modified organisms may not be conducted in Amerindian areas and conservation units”. Regarding the scope of Article 14 of Law no. 11,105/05, CTNBio holds that the request complies with applicable legislation and regulation aimed at securing biosafety of the environment, agriculture, human and animal health. CTNBio Technical Opinion 1. GMO Identification GMO name: Roundup Ready 2 Corn – Event NK603 Applicant: Monsanto do Brasil Ltda. Species: Zea mays – Corn Inserted Feature: Glyphosate herbicide tolerance Insertion method: Biobalistics (particle acceleration) method Prospective use: Production of silage and kernel for human and animal consumption from the GMO and its derivatives II. General Information Zea mays L., corn, is a species of the Maydae tribe, included in the subfamily Panicoidae, family Graminea (Poacea). Genera belonging to the Maydae tribe include Zea and Tripsacum in the Western Hemisphere. Corn is a separate species within the Zea subgenus, with a chromosome number 2n = 20,21,22,24(9). The wild species closest to corn is teosinte, found in Mexico and some other places of Central America, where it may cross with cultivated corn in production fields. Cultivated corn may also cross with a more distant genus, the Tripsacum. The crossing seldom happens and results in a sterile male progeny. Corn has a history of eight thousand years in the Americas. Out of all cultivated plants, corn is probably the one possessing the largest genetic variability. Today, about three hundred races of corn are identified and, within each such race, there are thousands of cultivars. Corn is currently the cultivated species that reached the highest degree of domestication and it may only survive in nature when raised by man(4). Normally, the maintenance of this genetic variability has been achieved through individualized storage, in germplasm banks, under controlled humidity and temperature. There are several germplasm banks, in Brazil and all over the world. Embrapa, the Brazilian Agricultural Research Agency, has two germplasm banks, one at Embrapa Recursos Genéticos e Biotecnologia, Embrapa Genetic Resources and Biotechnology, in Brasília, Federal District, Brazil, and another at Embrapa Milho e Sorgo, Embrapa Maize and Sorghum, in Sete Lagoas, Brazil. Corn is farmed in over 100 countries, with a total estimated production of 705 million tons per year. Corn is one of the most important food sources in the world and is the raw material for a large range of products. From 70% to 80% of corn produced in Brazil is consumed by the swine and poultry productive chain. Brazil is the world third largest corn producer, with an output of about 35 million tons in 2005, behind the United States of America (282 million tons) and China (139 million tons)(11).In Brazil, corn is planted basically in two different crops (summer and safrinha, or small crop) and is cultivated in practically all the domestic territory, with 92% concentrated in the Southern Region (47% of production), Southeastern Region (21% of production) and Center Western Region (24% of production)(8). Corn is one of the most efficient plants in converting solar energy in food and is used as raw material for several products. The increase in corn consumption exceeded 100 million tons between 1993 and 2001, representing an average yearly increase of 11.1 million tons per year. A large part of this increased production was due to genetic improvement, leading to ears containing about 1,000 seed-corns. Increased corn production and consumption all over the world is associated to its multiple uses, population growth, changes in feeding habits, and growth in the number of farmed swine and poultry. Brazil is the world third largest consumer of pesticides. The country has currently 142 pesticides registered for corn. There are several reports of resistance cases caused by the constant and indiscriminate use of herbicides in corn farming in Brazil. According to CUT(24) citing data from the World Health Organization (WHO), one million people are intoxicated each year by farm pesticides in Brazil. The Ministry of Health confirms that in sixteen Brazilian states, farm defensives are the largest cause affecting farmers’ health. The use of herbicide tolerant corn, such as NK603 corn, has given an opportunity for efficient management of pests and rotation of herbicide principles in corn farming(13). One impact recorded is the reduction of herbicide use in farming pre-emergence. Farmers have reduced the rates of pre-emergent herbicide applied to the soil and, through the use of wide spectrum herbicides, as glyphosate, have managed to control pests in an effective way. Replacement of several herbicides by a single herbicide with a wider spectrum has resulted in savings around $25/ha. Studies conducted in the United States with herbicide tolerant corn suggest positive economic yields with the single use of glyphosate or glyphosate associated to conventional herbicides in pre-emergence(25). The results establish that herbicide tolerant corn, including NK603, provides an increase in productivity while reducing herbicide costs(7). Glyphosate tolerant NK603 corn was released for the first time in the United States for farming and marketing in 2000, and is currently farmed, or has its consumption permitted, in twelve countries: Argentina, Australia, Canada, China, European Unit, Japan, Korea, Mexico, Philippines, South Africa, Taiwan and USA. NK603 corn expresses CP4 5-Enol-pyruvylshikimate-3-phosphate synthase (CP4 EPSPS) proteins that are glyphosate tolerant. CP4 EPSPS protein is one of several EPSPS proteins found in nature, which are produced by plants, bacteria and fungi, but not by animals, since those do not possess the metabolic way for its synthesis. Therefore, different versions of the EPSPS protein are normally present in all food derived from plants and microorganisms. The gene donor organism, Agrobacterium tumefaciens strain CP4, is a bacterium normally found in the soil. It causes galls in susceptible plants and there is no scientific evidence indicating that it may cause adverse effects in humans or animals. It is worth noticing that the history of farming, marketing, use and experience with other genetically modified cultures that express CP4 EPSPS protein since the first marketing of RR soy in 1994, has shown that the protein failed to display any risk to the environment, and to human and animal health. III. Description of the GMO and Proteins Expressed Gene cp4 epsps, which codifies a glyphosate tolerant form of the 5-Enol-pyruvylshikimate-3-phosphate synthase (EPSPS) was isolated from the bacterium Agrobacterium tumefaciens strain CP4 and inserted in corn through biobalistics (particle acceleration). The action of glyphosate, causing the death of plants, takes place due to its ability to block the activity of the target enzyme (EPSPS) belonging to the biosynthetic way of aromatic amino acids tyrosine, phenylalanine and tryptophan. Thus, plant cells that express protein CP4 EPSPS keep producing aromatic amino acids essential to their metabolism, even in the presence of glyphosate. Protein CP4 EPSPS is one of several EPSPS proteins found in nature, produced by plants, bacteria and fungi, but not by animals, which lack the metabolic way for the protein synthesis. Therefore, different versions of the EPSPS protein are normally present in all food derived from plants and microorganisms. The gene donor organism, Agrobacterium tumefaciens strain CP4, is a bacterium normally found in the soil that causes galls in susceptible plants and there is no scientific evidence indicating that it may cause adverse effects in humans or animals. NK603 corn was produced through genetic transformation of a LH82XB73 corn lineage using a DNA fragment of 6706 pairs of bases (pb) containing two adjoining cassettes of gene cp4 epsps to express the CP4 EPSPS protein. Each such cassettes, namely, the proximal cassette (closer to the 5’ end) and distal cassette (closer to the 3’ end) contained a single copy of the cp4 epsps gene and regulating sequences. In both cassettes, sequences of the cp4 epsps genes were linked to transit polypeptide sequences to chloroplast (CTP2) obtained from an epsps gene of Arabidopsis thaliana. The function of transit polypeptides is transporting the CP4 EPSPS protein to the chloroplasts where the metabolic way responsible for synthesizing aromatic amino acids operates. CTP4s are removed from protein CP4 EPSPS after its delivery at the chloroplast. In the proximal cassette, fragment ctp2-epsps was placed under the control of rice promoter actin1 and its intron and, in the distal cassette, placed under the control of CaMV 35S modified promoter (e35S). At the distal cassette, between promoter e35S and the CTP2 sequence, an intron of 0.8 kb, from a corn protein, was also introduced, involved in answers to thermal shocks (hsps70) with the purpose of increasing the levels of genetic transcription. In both cassettes, sequences cp4 epsps were connected to the sequence of 0.3 kb of nopaline synthase 3’ (not translated) named NOS 3’, with the purpose of providing a sign for polyadenylation of the messenger RNA (mRNA). The DNA fragment of 6706 pb was used in the genetic transformation was isolated from plasmid PV-ZMGT32L as a single fragment through digestion with a restriction enzyme MIuI and separation in electrophoresis gel. Therefore, this fragment did not contain other plasmid elements as origin of plasmid replication and the sequence of gene npt II codifying the neomycin transferase type II enzyme. This enzyme grants resistance to aminoglycoside antibiotics such as kanamicyn and neomycin used to select the bacteria during the construct and multiplication of the plasmid. Transformed cells were selected in tissue culture in the presence of glyphosate. The DNA fragment was characterized using analyses of Southern Blot, a Polymerase Chain Reaction (PCR) technique, and sequencing of the inserted fragment and its bordering regions in the transformed corn genome. Results showed that the NK603 corn genome contains a single exogenous DNA insertion and that no DNA of the plasmid replication structure had been detected in the NK603 corn genome. Inside the single insert, a complete copy of the 6706 pb DNA fragment used in the transformation was found and one 217 pb fragment in the region of the actin promoter that fails to contain the necessary elements to act as a promoter. Both the proximal and distal cassettes of the cp4 epsps gene are present in the single insert and their genetic components are intact. In the distal cassette, the cp4 epsps gene nucleotide sequence differs from the original sequence used in the process of transformation in two nucleotides. One nucleotide change was silent while the other resulted in the substitution of an amino acid in position 214. The changed nucleotide in position 214 pb resulted in the coding of a leucine instead of a proline. This new sequence came to be called cp4 epsps L214p. Analyses of PCR products of terminal 3’ of the inserted DNA revealed the co-integration of a 305 pb additional DNA fragment of a chloroplast DNA. Results of computational biology showed that the co-integrated DNA corresponds to a part of DNA sequences codifying the alpha subunit of RNA polymerase and the ribosome protein S11. It is believed that the origin of this DNA is the chloroplast of the transformed cell. Proteins CP4 EPSPS and CP4 EPSPS L214P are present in small concentrations in seeds and forage of NK603 corn since rice actin promoters and e35s act in a constitutive way. Studies show that there is equivalence of both with proteins produced in Escherichia coli containing plasmid of heterologous expression possessing homology with EPSPS proteins that are naturally produced by plants and microorganisms used in human and animal food. Regarding nutritional and environmental safety, both the EPSPS proteins naturally present in non-transgenic plants and microorganisms and the CP4 EPSPS proteins expressed in glyphosate tolerant genetically modified cultures belong to a family of proteins known for their absence of toxicity, non association to pathogenicity events and failure to grant any selective advantage to plants or microorganisms containing them. Although primary amino acid sequences in different members of the EPSPS protein family show considerable divergence, the expressed proteins are highly related in terms of structure and function. IV. Aspects related to Human and Animal Health Security assessment of food derived from genetically modified raw-materials is based on risk analysis, a scientific methodology that encompasses the phases of risk assessment, risk management and risk communication. In the risk assessment, one pursues the qualitative and quantitative characterization of potential adverse effects, based on the concept of substantial equivalence to identify any differences between the new food and its conventional correspondent. Assessing the security of a genetically modified food raw-material, or its equivalence to conventional food, it is recommended that four elements are analyzed, namely: (1) Parental variety, i.e. the plant originating the new genetically modified raw-material; (2) Transformation process, including a characterization of the construct used and the resulting event; (3) Product of the inserted gene and potential toxicity and allergenicity and, finally; (4) Composition of the new variety resulting from genetic transformation. The data set of such analyses shall enable identifying and characterizing any potential adverse effect associated with consumption of the new raw-material, providing information to the risk management and risk communication phases. Changes to NK603 corn were caused by introducing the gene cp4 epsps, granting tolerance to the presence of the herbicide glyphosate in the pos-emergence phase of the plant. The engineered gene of the EPSPS synthase is the most studied transformation in plants, mainly soy and corn, with a large technical and scientific bibliography covering different aspects resulting from such transformation. The organism donor of gene cp4 epsps was the soil bacterium Agrobacterium sp., CP4strain. This organism donor of the gen inserted in NK603 corn is not used in the production of, nor used as, food. Besides, Agrobacteria species are non pathogenic to humans and animals and there are not reports that the epsps gene may be a determinant of the pathogenicity associated with Agrobacterium in plants. The EPSPS proteins catalyze the conversion of shikimic acid into 5-Enol-pyruvylshikimate-3-phosphate, which is an intermediary in the synthesis of aromatic amino acids and phenolic compounds. For their functions, EPSPS are essential to normal growth of plants and microorganisms. There is no toxicity associated to this family of proteins, which has a long history of environmental and nutritional safety. Besides, EPSPS proteins are not known for their persistence in the environment nor for affecting the phenotype of the host organisms with negative properties, such as pathogenicity or potentially development into pests. Several researchers conducted comprehensive characterizations of the CP4 EPSPS protein and the results showed that this protein has enzymatic properties equivalent to the EPSPS proteins endogenous to plants and microorganisms(14). In addition, detailed studies showed that the CP4 EPSPS protein is susceptive to proteolysis and enzymatic digestion, as it would be expected for an EPSPS protein. Besides, the data available from acute oral toxicity studies, in vitro digestibility and bioinformatics comparison of CP4 EPSPS confirm its equivalence to EPSPS proteins. Toxicity tests were conducted with EPSPS-synthase isolated from transformed plants. Harrison et. al.(14) showed by means of ingestion by gastric gavage that protein molecule doses over one thousand times the one found in modified seeds fail to cause cause physiologic alterations in essayed animals. Results from in vitro proteolysis also confirm the prompt digestion and innocuousness of the engineered protein, removing any suspiciousness of allergenicity(14). In addition to the history of safe use of the EPSPS class proteins, studies were conducted that ratify the security of CP4 EPSPS proteins expressed in cultures such as soy, cotton, corn, canola and sugar beet. In one acute oral toxicity study, CP4 EPSPS was administered to mice, in one high dose, to confirm its safety(14). The results of such study showed that, as expected, the CP4 EPSPS protein is not toxic. The CP4 EPSPS protein was produced and purified from E. coli, was characterized and showed to be equivalent to the CP4 EPSPS produced in corn. The purified protein was orally administered to mice for acute toxicity assessment. Acute administration was deemed proper to assess the security of CP4 EPSPS, since toxic proteins act through acute mechanisms(23,18). The NOEL no observable effect for oral toxicity in mice was 572 mg/kg, the highest tested dose(12). The result represented a security margin of about two hundred and sixty thousand (260,000) times, based on the average daily consumption of corn in the United States and expression of the protein in the glyphosate tolerant genetically modified corn (assuming that there is no loss of CP4 EPSPS during processing). No statistically significant differences were observed in body weight, aggregate body weight or consumption of food among control groups (with the vehicle or bovine albumin serum) and groups treated with the purified CP4 EPSPS protein. This is an expected result, since most EPSPS proteins are atoxic. The CP4 EPSPS protein showed to be promptly digested in the gastric and bowel fluids in vitro. Besides, EPSPS proteins have a safe history of use, since they are present common diet. Dairy cows were fed with forage and with glyphosate tolerant genetically modified corn, while milk production and composition was assessed in comparison with the cows receiving the conventional plant(15). The results of this experiment indicate that there was no significant differences stemming from the food source, either in composition or yield of the milk produced by the animals. Sheep fed with glyphosate tolerant canola were assessed regarding digestibility and permanence time of the recombinant DNA in the gastrointestinal tract. The cp4 epsps gene and its fragments were monitored by PCR in real time and by conventional amplification of intestinal fluids incubated at 39ºC during periods of time from zero to 240 minutes. Results showed that genes present in fodder remained whole for a period relatively short, reducing the likelihood of its absorption by the animal, and indicate also that intestinal microorganisms are responsible for the rapid degradation of DNA at a pH 7(2). One long term study was conducted in salmons, with diets based on soybeans and corn modified with the cp4 epsps gene(22). Upon completion of the essays, the authors verified that there were no significant changes in corporeal development, pyloric cecum and middle intestine of the fish during the eight months of the experiment. CP4 EPSPS proteins are ubiquitous in nature and are naturally present in foods derived from plant and microbial sources. The proteins do not show significant homology of amino acids with proteins known to be toxic or allergenic to mammals. Besides, the CP4 EPSPS protein was rapidly digested by in vitro gastric and bowel fluids. Further, EPSPS proteins have a history of safe use and are widely present in our diet. Comparative allergenicity tests in sensibilized patients were conducted with conventional soybean and corn, genetically modified and the respective isolated heterolog proteins(5). Products tested proved to be safe regarding their allergenic potential, since there was no change in reactivity levels for modified kernel and the isolated proteins failed to cause any reaction in sensibilized individuals. Corn is not in the group of eight foods (milk, wheat, eggs, fish, crustaceans, peanuts, soybean and nuts) that answer for about 90% of allergies in humans. Allergy to corn may occur by ingestion of corn and its derivatives or through inhalation of its flour or pollen. Corn has a long history in human and animal feeding, with rare cases of harm caused to health. According to Metcalfe (2003), allergy cases reported in this plant species are not common, though recent studies show that previous diagnose methods may have underestimated the cases(21). Several very consistent scientific studies proved that the nutritional value of NK603 Corn, or Roundup Ready Corn is, on average, equal to that of conventional corn. We emphasize “on average” because both corn types record variations (deviations from average), and this variation was shown to be similar in both cases. Given the specific characteristics of the NK603 corn production process, one may foresee that, when cultivated under specific agronomic conditions (e.g., high competition with invading plants), the nutritional value of corn derived from such GMO is likely to be, in fact, higher than the conventional corn. V. Environmental Aspects Corn is a monoecious plant: a single individual has separately located male and female flowers. Corn plants are crossed fecundation plants and largely pollinated with the help of wind, insects, gravity and others. Introduction of the genic elements mentioned above did not change the reproductive characteristics of the plant. Therefore, the likelihood of crossed fecundation between hybrids and lineages of non genetically modified corn, and between plants of the NK603 event and other corn plants are the same. Corn is the species that reached the highest domestication level among cultivated plants, and has lost its ability to survive in nature such as, for instance, elimination of threshing. Thus, corn is a plant unable to survive in natural conditions, without technical assistance. Therefore there is no possibility that corn changes into an invading plant or pest. Genic flow in corn may take place through pollen transfer and through seed dispersion. Seed dispersion is easily controlled, since corn domestication eliminated the mechanisms for seed dispersion of the plant ancestors and the pollen movement is the only effective way for corn plant genes to escape. Studies on corn pollen dispersion have been conducted, and some show that corn pollen may cover long distances. However, the majority of the released pollen is deposited close to the culture, with a very low translocation rate outside the source culture. The main corn pollination agent is the wind and the distance that a viable pollen may cover depends on wind pattern, moistness and temperature. Luna et. al.(19) assessed the isolation distance and control of pollen, and showed that crossed pollination happens in a distance up to two hundred meters and no crossed pollination took place in distances exceeding three hundred meters from the pollen sources, when the corn ear still keeps the silk. Results indicate that pollen viability is kept for two hours and that crossed pollination was not observed in distances of three hundred meters from the pollen source. With low to moderate winds, estimates are that, comparing concentrations at 1m from the source culture, about 2% of pollen are recorded at 60m, 1.1% at 200m and 0,75-0,5% at 500m of distance. At 10m away from a field, on average, the number of pollen grains per unit of area is ten times lower than the figure recorded at 1m from the border. Therefore, if the established separation distances developed for production of corn seeds are observed, one expects that the transference of pollen to adjoining varieties is minimized, with no herbicide tolerant generic material. Even in case of a genic escape, the probability of allele fixation containing the genic sequence conferring tolerance to glyphosate in the population is very reduced in the absence of selection pressure. Cultivated corn is known for its interaction with different organisms in the environment, including microorganisms, wild animals and soil and aerial invertebrates. Besides, corn is known for its susceptibility to different fungi, viruses, bacteria, nematoids, pests caused by insects and acarine, use of pesticides and other agricultural practices, such as rotation of cultures and use of resistant or tolerant genotypes developed by classic improvement. Interaction of corn culture with wild vertebrates happen in large number and is well known, since corn is an excellent source of nutrition. Such interactions happen with birds and mammals that live or find shelter in the agricultural environment or close to this environment, in its borders, shrubs and dens. NK603 corn has shown to be equivalent to conventional corn, except for the glyphosate tolerant characteristic. Its basic interactions with other organisms in the environment are not held as different from interactions of conventional corn. Though there is the potential exposure of corn culture weeds, pests and pathogens to CP4 EPSPS and CP4 EPSPS L214P proteins that are expressed in NK603 corn, there are no concerns about the process causing adverse effects on such populations. Through trophic transference and decomposition process, organisms that are not targets of CP4 EPSPS and CP4 EPSPS L214P proteins, such as predators and preys of corn pests, may be exposed to very low levels of the proteins without evidence of negative effects on such organisms. Environment safety of the EPSPS protein family is well accepted, since the proteins are ubiquitous in nature (bacteria, fungi, algae and higher plants), have no known toxicity, association with pathogenicity and do not grant comparative selective advantage to plants that contain the proteins. Though EPSPS proteins are found in plants and microorganisms, primary amino acid sequences display considerable differences. Analyses of alignments using peptides (ALLPEPTIDES) show that members of the EPSPS protein family may have less than 25% of common identity in a window of about 450 amino acids (corresponding to the total size of CP4 EPSPS). Despite this low identity level of amino acid sequences, EPSPS family proteins are highly related in terms of structure and function(12). The EPSPS enzyme has no target organism, since it is an enzyme involved in the biochemical way of shikimic acid in plants and microorganisms. Any non target organism that interacts with a plant culture displays a close interaction with a number of plants and microorganisms and therefore is constantly exposed to EPSPS family proteins. Based on the history of occurrence and safe exposure of this protein family, there is no evidence that any EPSPS protein may display biological activity on a non target organism. VI. Restrictions to the use of the GMO and its derivatives According to Article 1 of Law no. 11,460, of March 21, 2007 ”research and cultivation of genetically modified organisms may not be conducted in Amerindian areas and conservation units”. Technical opinions related to agronomic performance reached a conclusion that there is equivalence between transgenic and conventional plants. Thus, this information suggest that transgenic plants are not fundamentally different from the non-transformed corn genotypes, except for the tolerance to glyphosate. Besides, there is no evidence of adverse reactions to the use of NK603 corn. For this reason, there are no restrictions to the use of this corn or its derivatives, either for human or animal feeding. The vertical genic flow to local varieties (the so-called Creole corns) of open pollination is possible and carries the same risk caused by the commercial genotypes available in the market (80% of the conventional corn farmed in Brazil come from commercial seeds that underwent a process of genetic improvement). Coexistence among cultivars of conventional (either cultivated of local varieties) and transgenic cultivars is possible from the agronomic viewpoint(6,20). After ten years of use in different countries, there was no problem detected for human and animal health, or to the environment that may be ascribed to transgenic maize. It shall be emphasized that the lack of negative results in cultivation of transgenic corn plants does not mean that this may not happen. Zero risk coupled with absolute safety is an inexistent combination in the biologic world, although there is a host of trustworthy scientific information and a safe historic of use of ten years that enable us to argue that the NK603 corn is as safe as conventional versions. Therefore, the applicant shall conduct post-commercial release monitoring under CTNBio Ruling Instruction no. 3. VII. Considerations on particulars of different regions of the country (information to supervising bodies) In Brazil, there are no kindred corn species in natural distribution. VIII. Conclusion Whereas: 1. Corn is the species that reached the highest domestication level among cultivated plants, and is unable to survive in nature with no human intervention. 2. In Brazil, there are no wild species with which corn may intercross, since the closest wild corn species is teosinte, found only in Mexico and in some Central America locations, where it may cross with corn cultivated in production fields. 3. There is established knowledge on safety of the use of corn in the human and animal food chain. 4. The transformation event in analysis failed to modify the composition and the nutritional value of corn. 5. There is no evidence that the transgene or the transformation event may cause adverse effects to human and animal health. 6. The history of NK603 corn use in the European Union (since 1999), USA (since 2000) and Canada (since 2001), in addition to the data on field tests conducted in Brazil (since 2000) give sufficient evidence that the kernel and products derived from Glyphosate Tolerant NK603 Corn are as safe as those of conventional corn. 7. There is robust scientific evidence that NK603 corn has no adverse effects on human and animal health, and this information is based in international scientific literature. 8. In 2003, the European Food Safety Authority (EFSA) examined a request for commercial release of NK603 corn and issue a favorable scientific opinion on December 4, 2003, with a conclusion that “NK603 corn is as safe as conventional corn and therefore the marketing of NK603 for processing and its use in human and animal food are unlikely to have any adverse effect on human and animal health or, in this context, on the environment.” 9. Given the detailed data provided by the applicant, the results obtained in control and security essays of the genetically modified organism in analysis, the elements credited to authors of scientific work mentioned and inexistence of evidence contrary to nutritional, toxicological and allergenic security, after thorough investigation, we are favorable to commercial release of NK603 corn for consumption in the human and animal food chain. 10. Corn is a plant that is unable to survive in natural conditions, without technical assistance. This way, there is no likelihood that corn may transform into an invading plant or weed. 11. Environmental safety of the EPSPS family proteins is well accepted, since the proteins are ubiquitous in nature (bacteria, fungi, algae and higher plants), exhibit no known toxicity, are not associated to pathogenicity and fail to grant any selective advantage to plants that do not contain such proteins. 12. In case of a genic escape, the likelihood of fixation of an allele containing the genic sequence that grants tolerance to glyphosate in the population is minimal in absence of selection pressure. 13. Basic interactions of NK603 corn with other organisms in the environment are not held different from interactions of conventional corn. 14. Organisms that are not targets of CP4 EPSPS and CP4 EPSPS L214P, such as predators and preys of corn pests, may be exposed to very low levels of the proteins without, however, evidence of negative effects on such organisms. 15. There is no evidence that any EPSPS protein will have biologic activity on non-target organisms. For the foregoing, and considering internationally accepted criteria in the process of risk analysis for genetically modified raw-materials, a conclusion emerges that Roundup Ready corn, derived from NK603, is as safe as its conventional equivalent. Third party independent scientific studies and publications provided by the applicant were also taken into consideration and consulted. CTNBio holds that the activity is not a potential cause of significant degradation to the environment nor of harm to human and animal health. Restrictions to the use of the GMO analyzed and its derivatives are conditioned to the provisions of CTNBio Ruling Resolutions no. 03 and 04. CTNBio analysis took into consideration opinions issued by members of the Commission and ad hoc consultants; documents delivered by applicant to CTNBio Office of the Executive Secretary; results from planned releases to the environment; lectures, texts and discussion of the public hearing held on 03.20.2007. Also taken into consideration were applicant’s studies and publications, conducted by third parties. According to Annex I of Ruling Resolution no. 5, of March 12, 2008, the applicant shall have thirty (30) days from the publication of this Technical Opinion to harmonize its proposal for post-commercial release monitoring. IX. Bibliography mentioned 1. AGBIOS. GM Database. 2008. Biotech Crop Database. Corn MON NK603. http://wwww.agbios.com 2. ALEXANDER T.W.; SHARMA R.; DENG M.Y; WHETSELL A.J.; JENNINGS J.C.; WANG Y.; OKINE E. DAMGAARD D.; McALLISTER T.A. 2004. Use of quantitative real-time and conventional PCR to assess the stability of the cp4 epsps transgene from Roundup Ready® canola in the intestinal, ruminal, and fecal contents of sheep. J. Biotechnol. 112: 255-266. 3. ARONSON A.I. 2000. Incorporation of protease k into larval insect membrane vesicles does not result in disruption of integrity or function of the pore-forming bacillus thuringiensis delta-endotoxin. Appl. Environ. Biol. 66: 4568-4570. 4. BAHIA FILHO A.F.C.; GARCIA J.C. 2000. Análise e avaliação do Mercado brasileiro de sementes de milho. In: UDY C.V.; DUARTE W.F. (Org.) Uma história brasileira do milho: O valor de recursos genéticos. Brasília: Paralelo 15. 167-172. 5. BATISTA R.; NUNES B.; CARMO M.; CARDOSO C.; JOSÉ H.; DE ALMEIDA A.; MANIQUE A.; BENTO L.; RICARDO C.; OLIVEIRA M. 2005 Lack of detectable allergenicity of transgenic maize and soya samples.J. allergy Clin. Immunol. 116: 403-10,2005. 6. BROOKES G.; BARFOOT P.; MELÉ E.; MESSEGUER J.; BÉNÉTRIX F. BLOC D.; FOUEILLASSAR C; FABIÉ A.; POEYDOMENGE C. 2004. Genetically modified maize: pollen movement and crop co-existence. Dorchester, UK: PG economics, 20pp (www.pgeconomics.co.uk/pdf/Maizepollennov2004final.pdf) 7. CARPENTER J.; FELSOT A; GOOGE T.; HAMMING M; ONSTAD D. E SANKULA S. 2002. Comparative environmental impacts of biotechnology-derived and traditional soybean, corn and cotton crops. Council for Agricultural and Science Technology Report, Ames, Iowa. 200p. Available at: www.cast-science.org. Sponsored by the United Soybean Board. www.unitedsoybean.org. (annex 1-2) 8. CONAB. Milho total (1ª e 2ª safra) Brasil – Série histórica de area plantada – safra 1976-77 a 2006-07. Disponível em http://www.conab.gov.br/download/safra/MilhoTotalSerieHist.xls 9. FABO/WHO – Food and agriculture Organization of the United Nations / World Health Organisation 2000. Grassland Index. Zea mays L. (http://www.fao.org/WAICENT/faoinfo/agricult/agp/agpc/doc/gbase/data/pf000342.htm) 10. FAO. 2007. FAOSTAT. Disponível em: http://faostat.fao.org.site.340/default.aspx. 11. FAOSTAT-Agriculture – Food And Agriculture Organization Of The United Nations – Disponível em: http://faostat.fao.org.site.340/default.aspx. Hain R & Schreier PH (1996) Genetic engineering in crop protection: opportunities, risks 12. FUCHS R.L. 1998. Assessment of the allergenic potential of foods derived from genetically engineered plants: glyphosate tolerant soybean as a case study. In: EISENBRAND G.; AULEPP H.; DAYAN M. (Eds.) Food Allergies And Intolerances Symposium. Weinheim: VCH Verlagsgesellschaft mbH, 17:212-221. 13. GIANESSI L.; SILVERS C.; SANKULA, S E CARPENTER J. 2002. Executive Summary-Plant Biotechnology – Current and Potential Impact for Improving Pest Management in Us Agriculture. An Analysis OF Case Studies. NCFAP. National Center for food and Agricultural Policy: 1-23. Disponível em http//www.ncfap.org/40caseStudies.htm 14. HARRISON L.A.; BAILEY M.R.; NAYLOR M.W.; REAM J.E.; HAMMOND B.G.; NIDA G.L.; BURNETTE B.L.; NICKSON T.E.; MITSKY T.A.; TAYLOR M.L.; FUCHS R.L.; PADGETTES.R. 1996. The expressed protein in glyphosate synthase from Agrobacterium sp. Strain CP4, is rapidly digested in vitro and is not toxic to acutely gavaged mice. J. Nutr. 126: 728-740. 15. IPHARRAGUERRE I.R.; YOUNKER R.S.; CLARK J.H. 2003 Performance of lactating dairy cows fed corn as whole plant silage and grain produced from a glyphosate-tolerant hybrids (event NK 603). J. Dairy Sci. 86: 1734-1741. 16. JOHNSON W.G.; BRADLEY P.R.; HART S.E.; BUESINGER M;L E MASSEY R.E.2000. Efficacy and economics of weed management in glyphosate-resistant corn (Zea mays). Weed Technol. 14: 57-65. 17. KLEIN T.M.; WOLF E.D.; WU R.; SANFORD J.C. 1987. High velocity microprojectiles for delivering nucleic acids into living cells. Nature 327:70-73. 18. KESSLER D.A.; TAYLOR M.R.; MARYANSKI J.H.; FLAMM E.L.; KAHL, L.S. 1992. The safety of foods developed by biotechnology. Science 256: 1747-1749. 19. LUNA S.V.; FIGUEROA J.M; BALTAZAR B.; GOMEZ L.T.; TOWNSEND R. E SCHOPER J.B. 2001. Maize pollen longevity and distance isolation requirements for effective pollen control. Crop Sci. 41: 1551-1557. 20. MESSEGUER J.; PEÑAS G.; BALLESTER J.; BAS M.; SERRA J. SALVIA J.; PAULADEMÁS M.; MELÉ E. 2006. Pollen-mediated gene flow in maize in real situations of coexistence. Plant Biotechnology Journal. 4: 633-645. 21. METCALFE D.D.2003. Introduction: What are the issues in addressing the allergenic potential of genetically modified foods? Environ. Health Perspect. 111: 1110-1113. 22. SANDEN M.; BERNTSSEN M.H.G..; KROGDAHL. Å.; HEMRE G.-I.; BAKKE-McKELLEP A.-M. 2005. An examination of the intestinal tract of Atlantic salmon, Salmo salar L., parr fed different varieties of soy and maize. J. Fish Dis. 28: 317-330. 23. SJOBLAD R.D.; MCCLINTOCK J.T.; ENGLER R. 1992. Toxicological considerations for protein components of biological pesticide products. Regul Toxicol Pharmacol. 15: 3-9. 24. SPALHANET. Descontrole: Uso de Agrotóxico é o Principal Problemas de Saúde dos Agricultores. 2006. Ano XXI N° 164. www.sinpaf.org.br 25. THARP B.E.; KELLS J.J. 1999. Influence of herbicide application rate, timing, and interrow cultivation on weed control and corn (Zea mays). Yield in glufosinate-resistance and glyphosate-resistant corn. Weed Technol. 13: 807-813. X. Bibliography consulted 1. ALTIERI M. A. 2005. The myth of coexistence: Why transgenic crops are not compatible with agroecologically based systems of production. Bull. Sci. Technol. & Soc. 25: 361-371. 2. AUMAITRE A.; AULRICH K.; CHESSON A.; FLACHOWSKY G.; PIVA G. 2002. New feeds from genetically modified plants: substantial equivalence, nutritional equivalence, digestibility, and safety for animals and the food chain. Livestock Prod. Sci. 74: 223-238. 3. BENBROOCK C. 2003. Impacts of genetically engineered crops on pesticide use in United States: The first eight years. Biotech Infonet Paper No., www.biotechinfo.net/technicalpapaer6.html. 4. BENEDITO V.A.; FIGUEIRA A. V. 2008. Segurança ambiental. In: Biotecnologia e Meio Ambiente. BOREM A.; GIUDICE M.; DEL P. p. 167-198. 5. BOREM A. 2001. Escape gênico & transgênicos. Viçosa, UFV 206 p. 6. BRINGOLF R.B.; COPE W.G.; MOSHER S.; BARNHART M.C.; SHEA D. 2007. Acute and chronic toxicity of glyphosate compounds to glochidia and juveniles of Lampsilis siliquoidea (Unionidae). Environ. Toxicol. Chem. 26: 2094-100. 7. BROOKES G. et al. 2004. GM Maize – Pollen Movement and Crop-existence. Dorchester, UK: PG Economics Ltda. http://www.pgeconomics.co.uk 8. BROOKES G.; BARFOOT P. 2006. Global Impact of Biotech Crops: Socio-Economic and Environmental Effects in the First Ten Years of Commercial Use. AgBioforum. 9: 139.151. 9. CHRENKOVA M.; SOMMER A.; CERESNAKOVA Z.; NITRAYOVA S.; PROSTREDNA M. 2002. Nutritional evaluation of genetically modified maize corn performed on rats. Archives of Animal Nutrition – Archiv Fur Tierernahrung 56: 229-235. 10. CODEX ALIMENTARIUS. 2003. Guideline for the conduct of Food safety assessment of food derived from recombinant-DNA plants. the codex Alimentarius Commission and the FAO/WHO Food standards Programme. Rome. CAC/GL 45-2003. ftp://ftp.fao.org/es/esu/food_guide_plants_en.pdf 11. COE JR. E.H. 2001. The origin of maize genetics. Nature Rev. Genetics 2:898-906. 12. CONNER A.; GLARE T.E.; NAP J-P. 2003. The release of genetically modified crops into the environment. Part II – Overview of ecological risk assessment. The Plant J. 33:19-46. 13. DEMANÈCHE S.; SANGUIN H.; POTÉ J.; NAVARRO E.; BERNILLON D.; MAVINGUI P.; WILDI W.; VOGEL T.M.; SIMONET P. 2008. Antibiotic-resistant soil bacteria in transgenic plant fields. Proc. Natl. Acad. Sci. USA. 105: 3957-3962. 14. DOMINGO J.L. 2000. Health Risks of GM foods.: Many opinions but few data. Science 288: 1748-1749. 15. EASTHAM K.; SWEET J. 2002. Genetically modified organisms (GMO): the significance of gene flow through pollen transfer. Copenhagen: European Environmental Agency. 16. DONKIN S.S.; VELEZ J.C; TOTTEN A.K; et al. 2003. Effects of feeding silage and grain from glyphosate-tolerant or insect-protected corn hybrids on feed intake, ruminal digestion, and milk production in dairy cattle. J. Dairy Sci. 86: 1780-1788. 17. DOUVILLEA M.; GAGNÉ F; ANDRÉA C.; BLAISEA C. 2008. Ocurrence of the transgenic corn cry1Ab gene in freshwater mussels (Elliptio companata) near corn fields: Evidence of Exposure by bacterial ingestion. Ecotoxicol. Environ. Saf. (in press). 18. EMBERLIN J. 1999. The dispersal of corn pollen Zea mays: A report based on evidence available from publications and internet sites. National Pollen Research Unit, University College, Worcester WR2 AJ, United Kingdom. 19. ERICKSON G.E.; ROBBINS N.D.; SIMON J.J.; et al. Effect of feeding glyphosate-tolerant (Roundup-Ready events GA21 or NK603) corn compared with reference hybrids on feedlot steer performance and carcass characteristics. J. An. Sci. 81: 2600-2608. 20. EUROPEAN COMMISSION. 2006. Technical Report EUR 22102 EM. New Case Studies on the Coexistence of GM and Non-GM Crops in European Agriculture. http://www.jrc.es/home/pages/eur22102enfinal.pdf 21. EUROPEAN FOOD SAFETY AUTHORITY (EFSA). 2006. Guidance document of the scientific panel on genetically modified organisms for risk assessment of genetically modified plants and derived food and feed. EFSA J. 99:1-100. 22. FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS . 2004. The State of Food and Agriculture. Agriculture Biotechnology. Meeting the Poor. Rome, 208pp. http://www.fao.org 23. FOOD SAFETY AND GMOS. 2004. Consensus Document. 10pp. http://www.cedab.it 24. FORSBACH A.; SCHUBERT D.; LECHTENBERG B.; GILS M.; SHIMIDT R. 2003. A Comprehensive characterization of single-copy T-DNA insertion in the Arabidopsis thaliana genome plant Mol. Biol. 52:161-176. 25. GARCIA M. A.; ALTIERI M. A. 2005. Transgenic crops: implications for biodiversity and sustainable agriculture. Bull. Sci. Technol. & Soc. 25: 335-353. 26. GELMINI G.A.; VICTORIA FILHO R.; NOVO M.C.S.S.; ADORYAN M.L. 2005. Resistência de Euphorbia heterophylla L. aos herbicidas inibidores das ALS na cultura da soja. Sci. Agric. 62: 452-457. 27. GERTZ JR. J.M.; VENCIL W.K.; HILL N.S.1999.Tolerance of transgenic soybean (Glycine max) to heat stress. In: Proceedings of the 1999 Brighton Conference Weeds ( The BCPC Conference). Vol. 3.; November 1999; Brighton, UK, p. 835.840 28. GIESY J.P.; DODSON S.; SOLOMON K.R. 2000. Ecotoxicological risk assessment for Roundup herbicide. Rev. Environ, Contam. Toxicol. 167: 35-120 29. GIULIETTI A.M.; HARLEY R.M.; QUEIROZ L.P; WANDERLEY M.G.L.; VAN DEN BERG C. 2005. Biodiversidade e conservação das plantas no Brasil. Megadiv. 1: 52-61. 30. GLADYSHEV E.A.; MESELSON M.; ARKHIPVA I.R.2008. Massive horizontal gene transfer in bdelloid rotifers. Science. 320: 1210-1213. 31. GLIESSMAN S.R. 2005. Agroecologia: processos ecológicos em agricultura sustentável. Porto Alegre: UFRGS. 652P. 32. HAMMOND B.G.; VICINI J.L. HARTNELL G.F.; NAYLOR M.W. KNIGHT C.D.; ROBINSON E.H.; FUCHS R.L.; PASGETTE S.R. 1996. The feeding value of soybeans fed to rats, chickens, catfish and dairy cattle is not altered by incorporation of glyphosate tolerance. J. Nutrs. 126: 717-727. 33. ICOZ I.; SAXENA D.; ANDOW D.A.; ZWAHLEN C.; STOTZKY G. 2008. Microbial populations and enzyme activities in soil in situ under transgenic corn expressing cry proteins from Bacillus thuringiensis. J. Environ. Qual. 37: 647-62. 34. JAMES C. 2006. Global status of commercialized Biotech/GM Crops. ISAAA Brief 35. ISAAA: Ithaca Ny. Website: http://www.isaaa.org 35. KAY R.; CHAN A.; MCPHERSON J. 1985. Duplication of CaMV 35S promoter sequences creates a strong enhancer for plant genes. Science 236: 1299-1302 36. KINUPP V.; BARROS I.B.I. 2004. Levantamento de dados e divulgação do potencial das plantas alimentícias alternativas no Brasil. Horticultura brasileira V.4. 37. KINUPP V. 2007. Plants alimentícias não convencionais na Região Metropolitana de Porto Alegre. Programa de Pós-Graduação em Fitotecnia – Faculdade de Agronomia –UFRGS. 590p. 38. KLEE H.J; MUSKOPF Y.M.; GASSER C.S. 1897. Cloning of an Arabidopsis thaliana gene encoding 5-enolpyruvylshikimate-3-phosphate synthase: sequence analysis and manipulation to obtain glyphosate-tolerant plants. Mol Gen Genet. 210: 437-442. 39. LATHAM J.R.; WILSON A.K.; STEINBRECHER R.A. 2006. The mutational consequences of plant transformation. J. of Biomed. Biotech. 2006: 1-7. 40. MALATESTA et. Al. 2002. Ultrastructural morphometrical and immunocytochemical of hepatocytenuclei from mice fed on genetically modified soybean. Cell structure and function. 27:173-180. 41. MESSEGUER J.; PEÑAS G.; BALLESTER J.; BAS M.; SERRA J.; PALAUDELMÀS M.; MELÉ E. 2006. Pollen-mediated gene flow in corn in real situations of coexistence. Plant Biotechnology Journal. 4:633-645. 42. MONIER J.M.; BERNILLON D.; KAY E.; FAUGIER A.; RYBALKA O.; DESSAUX Y.; SIMONET P.; VOGEL T.M. 2007. Detection of potential transgenic plant DNA recipients among soil bacteria. Environ Biosaf. Res. 6:71-83. 43. MONQUERO P.A; SILVA A.C. 2007. Efeito do período de chuva no controle Euphorbia heterophylla e Ipomea purpurea pelos herbicidas glyphosate e sulfotase. Planta Daninha 25:399-404. 44. MOREIRA M.S.; NICOLAI M.; CARVALHO S.J.P; CHRISTOFFOLETI P.J. 2007. Resistência de Conyza Canadensis e C. bonariensis ao herbicida glyphosate. Planta Daninha. 25: 157-164. 45. NIELSEN K.M.; BONES A.M.; SMALLA K.; VAN ELSAS J.D. 1998. horizontal gene transfer from transgenic plants to terrestrial bacterial – a rare avent? FEMS microbial Rev. 22: 79-103. 46. OECD. 2003. Considerations for the safety assessment of animal feedstuffs derived from genetically modified plants. Series on the safety of Novel Foods and Feeds, No. 9. Organization for Economical Co-operation and Development. ENV/JM/MONO ,10.46p. 47. OFFICIAL JOURNAL OF THE EUROPEAN UNION. http://www.agbios.com/docroot/decdocs/06-286.015pdf 48. PADGETTE S.R.; KOLACZ K.H.; DELANNAY X.; RE D.B.; LaVALLE B.J.; TINIUS C.N.; RHODES W.K.; OTERO Y.I.; BARRY G.F.; EICHHOLTZ D.A.; PESCHKE V.M.; NIDA D.L.; TAYLOR N.B; KISHORE G.M. 1995. Development, identification and characterization of a glyphosate-tolerant soybean line. Crop Sci. 35: 1451-1461. 49. PADGETTE S.R.; TAYLOR N.B.; NIVIA D.L.; BAULEY M.R.; MacDONALD J.; HOLDEN L.R.; FUCHS R.L. 1996. The composition of glyphosate-tolerant soybean seeds is equivalent to that of conventional soybeans. J. Nutr. 16:702.716. 50. PONTIROLI A.; SIMONET P.; FROSTEGARD A.; VOGEL T.M.; MONIVER J.M. 2007. Fate of transgenic plant DNA in the environment, Environ. Biosaf. Res. 6: 15-35. 51. PRAY C.E.; HUANG J. 2003. The Impact of Bt Cotton in China. In: Economic and Environmental Impacts of Agbiotech: A Global Perspective. KALAITZANDONAKES N. (Ed.). New York: Kluwer-Plenum Academic Publisher. 52. RAPOPORT E. H.; LADIO A.; RAFFAELE E.; GHERMANDI L.; SANZ E.H. 1998. Malezas Comestíbles. Hay yuyos y yuyos. Ciencia Hoy, v.9. n.49. 53. RAPOPORT E.H.; DRAUSAL B.S. 2001. Edible plants, In: Encyclopedia of biodiversity. LEVIN S. (ed). New York: Academic Press, 375-382. 54. SABHARWAL N.; ICOZ I., SAXENA D.; STOSZKY G. 2007. Release of the recombinant proteins, human serum albumin, beta-glucuronidase, glycoprotein B from human cytomegalovirus, and green fluorescent protein, in root exudates from transgenic tobacco and their effects on microbes and enzymatic activities in soil. Plant Physiol Biochem. 45: 464-469. 55. SAXENA D.; FLORES S.; STOTZKY G. 1999. Insecticidal toxin in root exudates from Bt corn. Nature 402: 480. 56. SHAN G.; EMBREY S.K.; HERMAN R.A.; MCCORMICK R. 2008. Cry1F protein not detected in soil after three years of transgenic Bt corn (1507 corn) use. Environ Entomol. 37:255-62. 57. SHEWRY P.R.; et al.; 2007, Are GM and conventionally Bred Cereals Really Different? Food Sci. Technol. 18: 201.209. 58. SIQUEIRA J.O.; TRANNIN. 2008. Agrossistemas transgênicos. In: Biotecnologia e Meio Ambiente. Borem A.; Giudice M. DEL P. p. 225-309. 59. TAYLOR M.L.; HARTNELL G.F.; RIORDAN S.G.; et al. 2004. Comparison of broiler performance when fed diets containing grain from Roundup Ready (NK603), YieldGard x Roundup Ready (MON 810 X NK603), non-transgenic control, or commercial corn, Poult. Sci. 83: 1758-1758. 60. TAYLOR M.L.; HARTNELL G.; NEMETH M.; KARUNANANDAA K.; GEORGE B. 2005. Comparison of broiler performance when fed diets containing corn grain with insect-protected (corn rootworm and European corn borer) and herbicide-tolerant (glyphosate) traits, control corn, or commercial reference corn-revisted. Poult. Sci. 84: 1493-1899. 61. NUFFIELD COUNCIL ON BIOETHICS. 2004. The use of genetically modified crops in developing countries. 122pp. http://www.nuffieldbioethics.org 62. TRAVIK T.; HEINEMANN J. 2007. Genetic Engineering and Omitted Health Research: Still No answers to ageing questions. Third Word Network, 36p. 63. U.S. FOOD AND DRUG ADMINISTRATION. 2006. Recommendations for the early food safety evaluation of new-pesticidal proteins produced by new plant varieties intended for food use. Center for Food Safety and Applied Nutrition. U.S. Food and Drug Administration. http://www.cfsan.fda.gov/~dms/bioprgu2.htmal 64. VARGAS L.; BIANCHI M.A.; RIZZARDI M.A.; AGOSTINETTO D.; DAL MAGRO T. Conyza bonariensis resiste ao glyphosate na região sul do Brasil. Planta Daninha 25: 573.578. 65. VARGAS L.; RIZZARDI M.A.; BIANCHIM A.; 2007. Manejo e controle de espécies tolerantes ou resistentes ao glifosato. Plantio Direto mar/abr. 2007: p.30-33 66. VIDAL R.A; TREZZI M.M.; STACHLER J., LOUX M. 2007. Definindo resistência aos herbicidas. Plantio Direto jul/ago.2007. 67. VIDAL R.A.Q.; LAMEGO F.P. TREZZI M.M. 2006. Diagnóstico da resistência aos herbicidas em plantas daninhas. Planta Daninha 24: 597-604. 68. WILLIAMS G.M.; KROES R.; MUNRO I.C. 2000. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul. Toxicol. Pharmacol. 31: 117-165. 69. WORD HEALTH ORGANIZATION (WHO). 2005. Modern Food Biotechnology, Hunan Health and Development: An Evidence-Based Study. 76pp. http//www.who.int/foodsafety 70. YASMIN S.; D’SOUZA D. 2007. Effect of pesticides on the reproductive output of Eisena Fetida. Bull. Environ, Contam. Toxical. 79: 529-532.

Molecular Traditional Methods.

The 603 line of corn (Zea maysL.) was developed through a specific genetic modification to be tolerant to glyphosate containing herbicides. This novel variety was developed from an inbred dent corn line by insertion of a bacterial 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) encoding gene which provides enhanced tolerance to glyphosate compared to the native corn EPSPS.

Glyphosate specifically binds to and inactivates EPSPS, which is involved in the biosynthesis of the aromatic amino acids tyrosine, phenylalanine and tryptophan. This enzyme is present in all plants, bacteria and fungi, but not in animals, which do not synthesize their own aromatic amino acids. Thus, EPSPS is normally present in food derived from plant and microbial sources. The modified corn line permits farmers to use glyphosate containing herbicides, such as Roundup®, for weed control in the cultivation of corn.

Please see decision document weblinks

Based on the risk assessment, it can be concluded that the event shows the same risks as its conventional counterpart. Therefore the National Technical Biosafety Committee for GMO use exclusively in Health and human consumption (CTNSalud) recommends its authorization.

Bayer West-Central Africa S.A. has applied requesting for authorisation of genetically modified Maize (Zea mays) Event NK 603 with the OECD unique identifier MON-ØØ6Ø3-6for direct use as food, feed or for processing in Ghana.

 

The Maize Event NK 603 expresses cp4 epsps gene which encodes CP4 EPSPS protein that confers tolerance to glyphosate, the active ingredient in Roundup®1 agricultural herbicides. This Maize Event has been reviewed and approved for diverse uses (food, feed, or for processing and/or cultivation in several countries. 

The Board of the NBA considered the recommendations from the Technical Advisory Committee (TAC) following the Committee's thorough evaluation of the applications submitted by the applicant using information available on: i. the Biosafety Clearing House (BCH), which is a mechanism set up by the Cartagena Protocol on Biosafety to facilitate the exchange of information on Living Modified Organisms (LMOs) and assist the Parties to better comply with their obligations under the Protocol and to which Ghana is a Party, ii. the Organisation for Economic Co-operation and Development (OECD) Biotrack Product Database, iii. the Food and Agriculture Organisation of the United Nations (FAO) genetically modifled foods platform. The following considerations were evaluated: J development of the modified events including the rnolecular biology data that characterizes the genetic change; ,/ proximate analyses; major constituents (fats, proteins, carbohydrates) and minor constituents (minerals and vitamins); J composition of, and nutritional information (including anti-nutrients) on the GM products compared to their conventional counterparts; '/ the potential for causing allergic reactions; ,/ microbiological and chemical safety of the event(s); J the potential for production of new toxins in the event(s); and, J the potential for any unintended or secondary effects;

Please see the relevant document below.

MON-ØØ6Ø3-6 - Roundup Ready™ maize for direct use as food or processing.

Competent National Authority: Ministry of Health and Medical Education- Food & Drug Administration. Risk Assessment file is uploaded. https://bch.cbd.int/en/database/RA/BCH-RA-IR-114039/2

Competent National Authority: Ministry of Health and Medical Education- Food & Drug Administration. Risk Assessment file is uploaded. https://bch.cbd.int/en/database/RA/BCH-RA-IR-114039/2

Competent National Authority: Ministry of Agriculture-Jehad, Agricultural Research, Education and Extension Organization (AREEO). Risk Assessment file is uploaded. https://bch.cbd.int/en/database/RA/BCH-RA-IR-114180/2

Please see the link below (in Japanese).

Please refer to uploaded document.

Authorization by COFEPRIS: 16

Maize tolerant to glyphosate herbicide (cp4 epsps, Zea mays subsp. mays (L.) Iltis).

UI OECD: MON-ØØ6Ø3-6 During the risk assessment of this GMO based on existing knowledge to date, no toxic or allergic effects neither substantial nutritional changes are observed. The event is as safe as its conventional counterpart. For more detail please find attached the risk assessment summary in this page.

Food derived from glyphosate-tolerant corn line NK603 has been evaluated according to the safety assessment guidelines prepared by ANZFA. The assessment considered the following issues: (1) the nature of the genetic modification; (2) general safety issues such as novel protein expression and the potential for transfer of novel genetic material to cells in the human digestive tract; (3) toxicological issues; and (4) nutritional issues. On the basis of the submitted scientific data and other available information, ANZFA has concluded that food derived from glyphosate-tolerant corn line NK603 is as safe and wholesome as food from other commercial varieties of corn.

The food and feed safety assessment was performed following the CODEX Guidelines. The Commercial Release Opinion of the National Commission for Agricultural and Forestry Biosafety (CONBIO), in its substantial part states: "...Recommends technically: (1) The commercial release of the event NK603 (2) In case of detection of an unexpected effect, the company is obliged to inform CONBIO".

Toxicological Assessment SDS-PAGE and Western blot methods were used in assessing the digestibility of corn NK603 CP4 EPSPS proteins (CP4 EPSPS and CP4 EPSPS L214P) in simulated gastric fluid (SGF, containing pepsin). Results from these experiments demonstrated that CP4 EPSPS produced from E. coli were rapidly digested after incubation in SGF. The SDS-PAGE Colloidal Blue gel staining method demonstrated that at least 98% of the E. coli-produced CP4 EPSPS proteins were digested in SGF within 15 seconds and the estimated T50 result for SGF is below 15 seconds. There were no observed protein bands due to degradation of the CP4 EPSPS. Western blot analysis confirmed that greater than 95% of the E. coliproduced CP4 EPSPS proteins were digested in SGF within 15 seconds. The estimated T50 CP4 EPSPS is less than 15 minutes and was determined in the temperature dependence studies which demonstrated that the enzymatic activity is eliminated after 15 minutes incubation at 65°C. The impact of heating and in vitro digestibility of CP4 EPSPS has also been confirmed by Okunuki et al. (2002). Upon comparison of amino acid sequences of the CP4 EPSPS to protein sequences in the toxin database using the FASTA sequence alignment tool, the protein shared sequence similarities to homologous EPSPS proteins which have not been described as toxins relevant to human health. No other significant structural homology was observed. Acute oral toxicity study was conducted with E. coli-produced CP4 EPSPS protein and was administered as a single dose by gavage to three groups of 10 male and 10 female CD-1 mice at dose levels up to 572 mg/kg. Results show that there were no treatment-related effects on survival, clinical observations, body weight gain, food consumption or gross pathology. Therefore, the No Observable Adverse Effect Level (NOAEL) for CP4 EPSPS was considered to be 572 mg/kg. Allergenicity Assessment The amino acid sequence of the CP4 EPSPS protein was compared to a database of protein sequences associated with allergy and celiac disease using the sequence alignment tool FASTA and demonstrated that CP4 EPSPS shared no structurally significant sequence similarity to sequences within the allergen database. In addition, the CP4 EPSPS sequence was compared to the allergen database using an algorithm that scans for a window of eight linearly contiguous identical amino acids and results showed that The CP4 EPSPS protein sequence does not share eight linearly contiguous amino acid identities to any sequence in the allergen database. These results confirm that the CP4 EPSPS protein does not share any relevant amino acid sequence similarities with known allergens, gliadins, or glutenins. Further analysis of the physicochemical and functional properties provides a detailed characterization of the corn NK603-produced CP4 EPSPS and CP4 EPSPS L214P proteins and establish its equivalence to the E. coli-produced CP4 EPSPS proteins. Nutritional Data Results of the study provided shows that there were no statistically significantly differences observed for proximate analysis in forage grain and antinutrients between corn NK603 and the conventional control. Reference grain and forage samples from the E.U. field trials also included 19 conventional, commercial hybrids (five hybrids per site with one hybrid planted at two sites), planted under the same environmental conditions. All test values of proximate were within the 99% tolerance interval established from the commercial varieties. The studies provided by the applicant show that all test values of forage, grain and antinutrients were within or similar to literature range or historical range. Differences observed in key nutrients were not biologically relevant and meaningful from a food and feed safety perspective.

1. Host Organism a. Generally, corn does not contain known allergens or produce significant toxins or antinutrients warranting analytical or toxicological tests. However, in some casestudies, allergenic reactions were reported [3][4]. b. Maize or corn is being consumed in varied forms. It can be eaten raw. Most of the human consumption of maize is in the form of maize-based ingredients such as high fructose corn syrup, starch, sweeteners, cereals, oil and alcohol [3]. 2. Transgenic Plant a. Corn NK603 has been reviewed and approved for food and/or feed use in many countries which were listed by the applicant. In terms of food and feed safety, results from compositional studies support the overall conclusion that corn NK603 was not a major contributor to variation in component levels in maize grain and forage and confirmed the compositional equivalence of corn NK603 to the conventional control in levels of these components [3][4][5]. b. Since corn NK603 was found to be substantially equivalent to conventional maize with similar genetic background, there is no anticipated change in the use pattern for the product [3][5]. 3. The Donor Organism a. Agrobacterium sp. strain CP4 is the donor organism for corn NK603 and is not known to be toxic or allergenic [3]. b. CP4 EPSPS protein is not known to be toxic or allergenic. CP4 EPSPS protein produced in corn NK603 is also present in many commercial biotechnologyderived crops and that a history of the safe use of CP4 EPSPS protein has been demonstrated [3]. 4. Transformation System a. Plasmid vector PV-ZMGT32 developed by Monsanto Company, was used for the transformation of maize to produce NK603 and a detailed description of the expression cassette was adequately provided by the applicant [3][6] [8]. b. Particle acceleration transformation was the method used and the complete experimental protocol was provided by the applicant [3]. 5. Inserted DNA Validation of the results from molecular analyses confirmed that corn NK603 contains a single copy of T-DNA containing the cp4 epsps expression cassettes that is 5 stably integrated at a single insertion site and no detectable additional genetic elements. The result was demonstrated sufficiently by Southern blot analysis and PCR and sequence analysis [3][8]. 6. Genetic Stability a. The potential for creating novel chimeric ORFs were tested by PCR and DNA sequencing which verified the 5’ and 3’ ends of the insert in corn NK603. The sequences flanking the insert were confirmed to be native to maize. Western blot confirmed the expression of the full-length CP4 EPSPS proteins in corn NK603 and results indicate that the two CP4 EPSPS proteins are indistinguishable in Western blot analysis with the available polyclonal antibody, since the proteins are essentially identical. The reported data support the conclusion that only the two full-length CP4 EPSPS proteins are encoded by the insert in corn NK603 [3][8]. b. The reported data show that corn NK603 does not contain backbone sequences from the backbone sequences. This was sufficiently demonstrated by Sacl restriction enzyme digestion, hybridization and Southern blotting. [3][7]. c. The reported results from Southern blot analysis demonstrated the stability of the DNA insert across multiple generations on F1 generation and the fifth generation of back-crossing of corn NK603. The analysis confirmed that a single integration locus was maintained through five generations of breeding, thereby confirming the stability of the insert [3][7]. 7. Expressed Material The reported mean level of CP4 EPSPS proteins in forage was 25.6 qg/g tissue on a fresh weight basis while the level of CP4 EPSPS proteins in grain from event NK603 was 10.9 tig/g tissue. This was measured by performing a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) from the collected forage and grain tissues from the field sites treated with glyphosate in the U.S. Other relevant information in this methodology was provided by the applicant [3][9]. 8. Toxicological Assessment a. SDS-PAGE and Western blot methods were used in assessing the digestibility of corn NK603 CP4 EPSPS proteins (CP4 EPSPS and CP4 EPSPS L214P) in simulated gastric fluid (SGF, containing pepsin). Results from these experiments demonstrated that CP4 EPSPS produced from E. coli were rapidly digested after incubation in SGF. The SDS-PAGE Colloidal Blue gel staining method demonstrated that at least 98% of the E. coli-produced CP4 EPSPS proteins were digested in SGF within 15 seconds and the estimated T50 result for SGF is below 15 seconds. There were no observed protein bands due to degradation of the CP4 EPSPS. Western blot analysis confirmed that greater than 95% of the E. coliproduced CP4 EPSPS proteins were digested in SGF within 15 seconds [3][10][11]. b. The estimated T50 CP4 EPSPS is less than 15 minutes and was determined in the 6 temperature dependence studies which demonstrated that the enzymatic activity is eliminated after 15 minutes incubation at 65°C. The impact of heating and in vitro digestibility of CP4 EPSPS has also been confirmed by Okunuki et al. (2002).[12][13]. c. Upon comparison of amino acid sequences of the CP4 EPSPS to protein sequences in the toxin database using the FASTA sequence alignment tool, the protein shared sequence similarities to homologous EPSPS proteins which have not been described as toxins relevant to human health. No other significant structural homology was observed [3][11][14]. d. Acute oral toxicity study was conducted with E. coli-produced CP4 EPSPS protein and was administered as a single dose by gavage to three groups of 10 male and 10 female CD-1 mice at dose levels up to 572 mg/kg. Results show that there were no treatment-related effects on survival, clinical observations, body weight gain, food consumption or gross pathology. Therefore, the No Observable Adverse Effect Level (NOAEL) for CP4 EPSPS was considered to be 572 mg/kg [3][15]. 9. Allergenicity Assessment a. The amino acid sequence of the CP4 EPSPS protein was compared to a database of protein sequences associated with allergy and celiac disease using the sequence alignment tool FASTA and demonstrated that CP4 EPSPS shared no structurally significant sequence similarity to sequences within the allergen database. b. In addition, the CP4 EPSPS sequence was compared to the allergen database using an algorithm that scans for a window of eight linearly contiguous identical amino acids and results showed that The CP4 EPSPS protein sequence does not share eight linearly contiguous amino acid identities to any sequence in the allergen database. c. These results confirm that the CP4 EPSPS protein does not share any relevant amino acid sequence similarities with known allergens, gliadins, or glutenins. Further analysis of the physicochemical and functional properties provides a detailed characterization of the corn NK603-produced CP4 EPSPS and CP4 EPSPS L214P proteins and establish its equivalence to the E. coli-produced CP4 EPSPS proteins [3][11][14][16]. 10.Nutritional Data a. Results of the study provided shows that there were no statistically significantly differences observed for proximate analysis in forage grain and antinutrients between corn NK603 and the conventional control [3][17][18][19][20]. b. Reference grain and forage samples from the E.U. field trials also included 19 conventional, commercial hybrids (five hybrids per site with one hybrid planted at two sites), planted under the same environmental conditions. All test values of proximate were within the 99% tolerance interval established from the 7 commercial varieties [3][17][18][19][20]. c. The studies provided by the applicant show that all test values of forage, grain and antinutrients were within or similar to literature range or historical range [3] [19][20] d. Differences observed in key nutrients were not biologically relevant and meaningful from a food and feed safety perspective [3][17][18][19][20]. 11.The Host Plant Environment a. Maize is a wind pollinated species with plant morphology that facilitates cross pollination [21]. b. The references provided by the applicant on hybridization with cultivated Zea mays L., wild annual species of subgenus Zea mays subsp. mexicana, wild perennial species of subgenus Tripsacum have described the possible formation of viable interspecific and/or intergeneric hybrids. From the studies provided, there are no scientific reports confirming the transfer of genetic material from maize to other species with which maize cannot sexually interbreed. Thus, the probability for horizontal gene flow to occur is negligible [22][23][24]. 12.The Consequences of Outcrossing a. In the Philippines, there is no known sexually compatible wild species. This among other factors reported by the applicant support that the assessment that the risk of loss of this wild species due to the development of the GM variety is very low [22][25]. b. There are no anticipated changes in habitat or geographic distribution. Corn NK603 has been shown to be no different from conventional maize in its phenotypic, ecological, and compositional characteristics, except for the introduced trait of glyphosate tolerance [6]. 13.Weediness Potential a. There is no adverse environmental impact is expected from the introduction of Corn NK603 to pests and/or diseases on current cultivation and management practices for maize. As shown by previous studies, corn NK603 has been shown to be no different from conventional maize in its phenotypic, ecological, and compositional characteristics, except for the introduced trait of glyphosate tolerance [6]. b. Mode of dissemination is through seeds. Plant produces a male (tassel) and female (ear) flower borne on the same plant but different positions. A well-developed ear shoot has 750 to 1,000 ovules (potential kernels), each producing a silk. However, under good conditions only 400 to 600 ovules will be fertilized and eventually produce kernels. Under favorable conditions, a pollen grain upon landing on a receptive silk will develop a pollen tube containing the male genetic material, develop and grow inside the silk, and fertilize the female ovary within 24 hours. 8 Pollen grains are borne in anthers, each of which contains a large number of pollen grains. The anthers open and the pollen grains pour out after dew has dried off the tassels. Pollen is light and can be carried considerable distances by the wind. However, most of it settles within 6 to 15 meters (20 to 50 feet). Pollen shed is not a continuous process. It stops when the tassel is too wet or too dry and begins again when temperature conditions are favorable [21]. STRP’S RECOMMENDATION Find sufficient evidence that the regulated article applied for direct use will not pose any significant risk to health and environment as its conventional counterpart and that any risks posed to health and environment could be managed by the following measures; 1. Continuous monitoring of planted sites for weed shifts and herbicide resistance development. 2. Product stewardship. 3. Provision of guidance on the planting of corn NK603 in hilly areas.

Glyphosate herbicide tolerance

 

Please to see link below(in Korean).

By all examined parameters, the data of complex safety assessment of transgenic maize line NK 603, tolerant to glyphosate, attest to the absence of any toxic, genotoxic, immune system modulating, or allergenic effects of this maize line. By chemical composition, transgenic maize line NK 603 was identical to conventional maize. Based on the results of the studies, the State Sanitation Service of the Russian Federation (Department of State Sanitation and Epidemiological Inspectorate) granted the Registration Certificate which allows the transgenic maize line NK 603 to be used in the food industry and placed on the market without restrictions. More information is on P. 158-175 of monograph ”Genetically Modified Food Sources. Safety Assessment and Control”, published by Elsevier Inc. Academic Press in 2013, the uploaded file.

Corn line NK603 (MON-00603-6) is tolerant to glyphosate. It is generated through the addition of a bacterial EPSPS gene derived from Agrobacterium sp. strain CP4 (CP4 EPSPS). The enzyme produced from the CP4 EPSPS gene has a reduced affinity for the herbicide compared with the corn enzyme, and thus confers glyphosate tolerance to the plant. NK603 contains two linked copies of the CP4 EPSPS gene, each with separate regulatory sequences. No extraneous bacterial genes were transferred. CP4 EPSPS protein and the sequence variant CP4 EPSPS L214P (which differs by one amino acid from the expected protein sequence as a result of a nucleotide change to one to the transferred CP4 EPSPS genes) are non-toxic and non-allergenic to humans. Composition analyses showed that grain from NK603 corn was equivalent in composition to that of other commercial corn varieties. Food derived from NK603 corn is considered as safe as food derived from other corn varieties.

Commodity : Corn / Maize (Zea mays L. )

Maize event NK603 has been genetically modified to expresses CP4 EPSPS protein which confers tolerance to glyphosate herbicide.

Application for food safety assessment.

The food safety assessment performed by the National Center for Genetic Engineering and Biotechnology (BIOTEC) as advisory and technical arm of Thai FDA. BIOTEC conduct food safety assessment according to codex guideline and based on the safety data and information provided by the applicant (as specified in Annex 2 attached to Notification of the Ministry of Public Health No.431). According to the existing scientific data and information available during the safety assessment, it is concluded that the maize event NK603 is substantially equivalent to its conventional counterpart in terms of morphology, nutrition, toxicity and allergenicity.

Commodity:Corn / Maize (Zea mays L.)

 

Maize event NK603 has been genetically modified to expresses CP4 EPSPS protein which confers tolerance to glyphosate herbicide.

Application for food safety assessment.

 

The food safety assessment performed by the National Center for Genetic Engineering and Biotechnology (BIOTEC) as advisory and technical arm of Thai FDA. BIOTEC conduct food safety assessment according to codex guideline and based on the safety data and information provided by the applicant (as specified in Annex 2 attached to Notification of the Ministry of Public Health No.431). According to the existing scientific data and information available during the safety assessment, it is concluded that the maize event NK603 is substantially equivalent to its conventional counterpart in terms of morphology, nutrition, toxicity and allergenicity.

 

Application for direct use as feed

 

Turkish Biosafety Law, entered in force in 2010, diverges from EU legislations in some points
 such as food and feed use require different separate applications, risk assessments and approvals.
  Addition, our Law forsees prision sentences in some circumtances of Law violation and joint
 reponsibilities for the violation. Therefore, GM product owners avoid to make application for approval
and non product developer have made application till now. Instead, some Turkish assosiations
 such as poultry producers assosiations, animal feed assosiations have applied to get approval
for import of GM products for their members. Thus, name of product applicants are not product
developers for our country.

 

Turkish Feed Manufacturer's Association
Turkish Poultry Meat Producers and Breeders Association
Turkish Egg Producers Association

 

After the evaluation of reports released by Scientific Risk Assessment Committee and Socio- economic Assessment Committee and also by considering public opinion, Biosafety Board has approved the use of genetically modified maize NK603 and products thereof for animal feed.

Corn
Trait 1 Added Protein: 5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS)
Source: Agrobacterium sp. strain CP4
Intended Effect: Tolerance to the herbicide glyphosate

Please consult the FDA website links below.

Please refer to uploaded document