Roundup Maize: NK603 (Monsanto)

NK603 was developed to widen the use of glyphosate for the cultivation of maize. Selling herbicide and seeds as a package is part of the business concept of US company Monsanto.

The authorisation of NK603 for food and feed for the European market in 2004 caused many controversies as a series of significant effects were found in a 90-day feeding study performed by Monsanto. Following these, the data was reassessed independently within the industry and French researchers consequently found signs for renal and hepatic toxicity and asked for further investigations (Spiroux de Vendômois et al., 2009). This conclusion was rejected by EFSA (2010) by referring to statistical standards. By doing so, EFSA defended its own positive opinions on NK603 (EFSA, 2009a; EFSA, 2003) and thus no more feeding trials or long-term or multi-generational studies were requested.

Inadvertently, the method of particle bombardment used to produce these plants led to additional gene fragments being integrated in the genome. Furthermore, the stop signal of the gene construct does not work which leads to the creation of so-called 'fusion genes' with the genes of neighbouring plants. On the whole these plants exhibit several technical deficiencies that have been shown to cause unexpected effects in the plants' metabolism and composition.

A basic prerequisite for risk assessment in this context are reliable data on residue loads from spraying with glyphosate formulations. The amount of these residues depends on the specific agronomic management used in the cultivation of the herbicide resistant plants. However, reliable data covering the actual range of residue load in the plants are not available (Kleter et al., 2011; EFSA, 2011b; Then, 2011). Without such data, no sound risk assessment of this product can be carried out. There are several reasons why risk assessment of genetically engineered plants with herbicide tolerance cannot leave aside the issue of residues from spraying (see also Dolezel et al., 2011). Several experts are warning that a higher toxicity has to be expected (Antoniou et al., 2010; Benachour et al., 2007; Paganelli et al., 2010; PAN AP, 2009). In this context, the additive POEA also has to be taken into account as it is even more toxic than glyphosate in the plants. In 2010, German authorities even prohibited the usage of certain glyphosate formulations with a high content of POEA for the production of animal feeds in order to avoid a risk of toxins being passed through the food chain (BVL, 2010). Risks related to spraying glyphosate formulations were not assessed.

The GMO panel decided to leave these questions concerning the risk assessment of residues from spraying to EFSA´s pesticide panel. In parallel, there is an ongoing EU process which is reviewing glyphosate under the pesticide regulation. Results were expected in 2012 but have in the meanwhile been delayed until 2015 (see EU Commission, 2002; Antoniou et al., 2011). Thus, the risk assessment of Roundup Ready crops suffers from two sides: From the work of the GMO panel and the European pesticide regulation.

EFSA also find that that adverse environmental effects can be caused by the application of glyphosate for the cultivation of crops: “These potential adverse environmental effects comprise (1) the evolution of less desirable weed assemblages leading to reductions in farmland biodiversity; (2) the evolution of weed resistance; and (3) effects on soil microbial communities. The magnitude of these potential adverse environmental effects will depend on the specific herbicide management applied at the farm level.”

However, EFSA does not include evidence that the cultivation of glyphosate tolerant plants puts populations of endangered species at risk e.g. protected butterflies. Brower et al. (2011) and Pleasants & Oberhauser (2012) have shown that in the US and Mexico, a reduction in milkweed species leads to a dramatic decline in the population of Monarch butterflies. In Europe, there would be similar hazards that would need assessment when it came to large-scale cultivation. This example shows that EFSA risk assessment is deficient in regard to even the most crucial elements in environmental risk assessment.

Cultivation of these herbicide resistant plants poses risks to biodiversity, plant health, soil fertility and enables the emergence of herbicide resistant weeds (see also Benbrook, 2009). In June 2011, a scientific database counted 21 different glyphosate resistant weeds (Heap, 2011). The massive usage of glyphosate in herbicide resistant crops endangers the health of rural communities, aquatic systems as well as impacting biodiversity and soil fertility (see also PAN AP, 2009). Contrary to EFSA´s opinion, there is substantial indication that plant diseases, e.g. increased infestation with fungal diseases (Johal & Huber, 2009), are caused by the large-scale cultivation of glyphosate tolerant crops. The negative impact on plant growth and plant health can even be transmitted to other plants cultivated in the same field in the following year (Bott et al., 2011, Bott et al., 2007).

Taking into account the observations on large-scale cultivation of herbicide tolerant crops in countries such as Argentina and the USA, the cultivation of these crops cannot be regarded as sustainable. The expectation that the negative impact of large-scale cultivation can be reduced by risk mitigation measures is a matter of theoretical expectation rather than one of practical experience.

Applicant: 

  • Monsanto

Plant: 

  • Maize

Trait: 

  • Herbicide tolerance

Event: 

  • NK603

Approval: 

  • Food and feed

Herbicide tolerance: 

  • Glyphosate

Transformation Method: 

  • Particle bombardement
Inserted gene: 

Two versions of ctp2-CP4 epsps, expressing two version of the EPSPS enzyme (CP4 EPSPS and CP4 EPSPS L214P)

Antibiotic resistance: 
no
Other important parts of the construct: 

35S CaMV Cauliflower mosaic virus promoter and rice actin promoter

Scope of application: 

  • Food and feed
Date of approval in the EU: 
Food and feed: 2004
Some approvals for cultivation worldwide: 
USA (2000)
Brazil (2008)
Argentina (2004)
Impact on the European market: 

So far the impact has been irrelevant with only minor imports, but costs are being incurred by contaminations for food producers that are committed to a production without genetically engineered plants.

Specific risks and unitended effects: 
  • The genetic transformation process caused unintended effects, numerous additional gene fragments such as additional gene sequences from chloroplasts can be found in the genome.
  • The stop signal of the gene construct does not work properly, so the additionally inserted genes produce unintended products from 'fusion genes' from the plant’s neighbouring DNA sequences. They show no similarity with any known protein.
  • The amount of additional proteins produced in the plant is highly variable. This may indicate genetic instability and result in unexpected reactions to specific environmental conditions. Several investigations show that genetically engineered plants can exhibit unexpected reactions under stress conditions (see for example: Matthews et al., 2005).
  • Compositional analysis showed several significant differences as compared to their conventional counterparts. This indicates an unintentional change in plant metabolism. The differences were not consistent over all field trials. The reason for this might be that these differences only emerge under particular environmental conditions.
  • A 90-day feeding study with rats showed several significant findings concerning blood parameters. These might indicate negative impact in kidneys and liver.
  • There are several proteins in maize that can cause allergic reactions. The newly introduced gene construct might, for example, enhance an immune response to these endogenous plant proteins.
  • These plants will be fed and they will possibly be eaten together with other genetically engineered plants. Tests have to be performed on potential effects such as combinatorial or accumulated effects.
  • Large-scale cultivation will bring many wildlife species into contact with these plants. Therefore, the impact on rodents, birds and other animal species should be assessed carefully.
  • Cultivation of these herbicide resistant plants poses risks to biodiversity, plant health, soil fertility and allows the emergence of herbicide resistant weeds. This is also admitted by EFSA.
  • Brower et al. (2011) and Pleasants & Oberhauser (2012) have shown that in the US and Mexico, a reduction in milkweed species leads to a dramatic decline in the population of Monarch butterflies. In Europe, there would be similar hazards that would need assessment when it came to large-scale cultivation.
  • There is substantial indication that plant diseases, e.g. increased infestation with fungal diseases (Johal & Huber, 2009), are caused by the large-scale cultivation of glyphosate tolerant crops. The negative impact on plant growth and plant health can even be transmitted to other plants cultivated in the same field in the following year (Bott et al., 2011; Bott et al., 2007).
  • Plants contain residues from spraying with herbicide formulations and their metabolites. As recent overviews of scientific literature show (Antoniou et al., 2010; Benachour et al., 2007; Paganelli et al., 2010; PAN AP, 2009; Then, 2011), the toxicity of glyphosate, its metabolites and its additives such as POEA (polyoxyethylene alkylamine) need to be re-evaluated.
Types of feeding trials: 
  • An acute toxicity study was performed feeding the enzyme that enables tolerance to glyphosate. These proteins were not isolated from the plants but produced by bacteria.
  • A 90-day feeding study with rats to investigate subchronic health effects was conducted using maize kernels.
  • Several studies to assess nutritional effects were conducted using maize kernels.
Overview of some shortcomings in the EFSA opinion: 
  • There was no assessment of risks stemming from residues from spraying with the pesticide formulations and their metabolites. Reliable data covering the actual range of residue load in the plants are not available (Kleter et al., 2011; EFSA, 2011b; Then, 2011). Without such data, no sound risk assessment of this product can be made. Risk assessment of genetically engineered plants with herbicide tolerance cannot leave aside the issue of residues from spraying.
  • Environmental risks of spraying glyphosate formulations in the fields were mentioned by EFSA but not included in the risk assessment.
  • No investigation under various defined environmental conditions was conducted to determine interactions between the genome and the environment.
  • There was no detailed investigation of changes in composition and agronomic performance under various defined environmental conditions.
  • Functional stability of the transgene under various defined environmental conditions was not shown. Genetic stability was only considered with regards the hereditary factors of the gene constructs for following generations.
  • No investigations were conducted to determine changes in plant gene activity or metabolic profile.
  • In comparison with its conventional counterparts, many significant differences in the compositional analysis were found but these were not investigated further. Instead references were made to unspecific and questionable 'historical' data from industry which was unrelated to the actual field trials.
  • Uncertainties regarding the risk assessment of unintended gene products from new fusion genes were discussed (EFSA, 2010) but not investigated further by more detailed metabolic profiling.
  • Risks were not investigated in detail despite significant findings from feeding trials, reassessed in peer reviewed publication, indicating potential negative impacts on human and animal health. The applicant was not asked to deliver further studies.
  • There have been no feeding studies over the whole lifetime of animals and none have included following generations.
  • No empirical investigations were performed concerning allergies or other impacts on the immune system.
  • No endocrinological studies were performed to investigate potential impacts on the reproductive system.
  • No specific testing was performed to find out if these plants can trigger immune reactions.
  • No investigations were conducted to assess the impact of a permanent ingestion of these plants on the intestinal microbial composition in humans and animals.
  • No investigation was conducted for DNA traces in animal tissue after feeding.
  • There was no assessment of combinatorial effects with other genetically engineered plants used in food and feed.
  • Field trials did not include assessment of the various bio-geographic regions within the EU.
  • Risks for wildlife were not included in risk assessment.
  • EFSA did not include evidence that the cultivation of glyphosate tolerant plants puts populations of endangered species at risk e.g. protected butterflies (Brower et al., 2011; Pleasants & Oberhauser, 2012). This example shows that EFSA risk assessment is deficient in regard to even the most crucial elements in environmental risk assessment.
  • EFSA did not place sufficient emphasis on possible impact on plant health.
Deficiencies in the monitoring plan: 
  • No plan for surveillance as required by European regulation was made available that would allow identification of particular health impacts that might be related to the use of these genetically engineered plants in food and feed.
  • Monitoring of environmental effects must include the risks associated with the spraying of glyphosate formulations.
  • Monitoring of health effects has to include the risks associated with the spraying of glyphosate formulations and their residues in the plants.
  • The usage of existing networks that are not specifically designed to monitor the impact of genetically engineered plants and the introduction of questionnaires to be filled in by farmers are not sufficient to fulfil requirements of general surveillance under practical conditions as foreseen by EU regulations.
Documents and publications: 

Antoniou, M., Brack, P., Carrasco, A., Fagan, J., Habib, M., Kageyama, P., Leifert, C., Nodari, R. O., Pengue, W. (2010) GM Soy: Sustainable? Responsible?, GLS Bank & ARGE gentechnikfrei, http://www.gmwatch.eu/?option=com_content&view=article&id=12479

Antoniou, M., Habib, M., Howard, C.V., Jennings, R.C., Leifert, C., Nodari, R. Robinson, C., Fagan, J. (2011) Roundup and birth defects – Is the public being kept in the dark? Earth Open Source, June 2011.

Benachour, N., Siphatur, H., Moslemi, S., Gasnier, C., Travert, C., Seralini, G. E. (2007) Time- and dose-dependent effects of Roundup on human embryonic and placental cells, Arch Environ Contam Toxicol 53: 126-33.

Benbrook, C. (2009) Impacts of Genetically Engineered Crops on Pesticide Use: The First Thirteen Years, www.organic-center.org/reportfiles/13Years20091116.pdf

Bott, S., Tesfamariam, T., Candan, H., Cakmak, I., Römheld, V., Neumann, G. (2008) Glyphosate-induced impairment of plant growth and micronutrient status in glyphosate-resistant soybean (Glycine max L.), Plant Soil, 312:185–194.

Bott, S., Tesfamariam, T., Kania, A., Eman, B., Aslan, N., Roemheld, V. Neumann, G. (2011) Phytotoxicity of glyphosate soil residues re-mobilise4d by phosphate fertilization. Plant Soil, 315: 2-11. doi: 10,1007/s11104-010-06989-3.

Brower, L.P., Taylor, O.R., Williams, E.H., Slayback D.A., Zubieta, R.R. Ramirez, M.I. (2011) Decline of monarch butterflies overwintering in Mexico: is the migratory phenomenon at risk? Insect Conservation and Diversity. doi: 10.1111/j.1752-4598.2011.00142.x

BVL (2010) Auflagen zum Schutz der Verbraucher bei Glyphosat-haltigen Pflanzenschutzmitteln und Zusatzstoffen.Federal Office of Consumer Protection and Food Safety. http://www.bvl.bund.de/DE/04_Pflanzenschutzmittel/05_Fachmeldungen/2010/...

Dolezel, M., Miklau, M., Hilbeck, A., Otto M., Eckerstorfer, M., Heissenberger, A., Tappeser, B., Gaugitsch, H., et al. (2011) Scrutinizing the current practice of the environmental risk assessment of GM maize applications for cultivation in the EU, Environmental Sciences Europe 2011, 23: 33. http://www.enveurope.com/content/23/1/33

EFSA (2003) Opinion of the Scientific Panel on Genetically Modified Organisms on a request from the Commission related to the safety of foods and food ingredients derived from herbicide-tolerant genetically modified maize NK603, for which a request for placing on the market was submitted under Article 4 of the Novel Food Regulation (EC) No 258/97 by Monsanto, The EFSA Journal (2003) 9: 1-14.

EFSA (2009a) Scientific Opinion of the Panel on Genetically Modified Organisms on applications (EFSA-GMO-NL-2005-22 and EFSA-GMO-RX-NK603) for the placing on the market of the genetically modified glyphosate tolerant maize NK603 for cultivation, food and feed uses and import and processing, and for renewal of the authorisation of maize NK603 as existing product. The EFSA Journal (2009) 1137: 1-50.

EFSA (2009 b) Comments and opinions submitted by Member States during the three-month consultation period, Annex to EFSA, 2009a, Scientific Opinion of the Panel on Genetically Modified Organisms on applications (EFSA-GMO-NL-2005-22 and EFSA-GMO-RX-NK603) for the placing on the market of the genetically modified glyphosate tolerant maize NK603 for cultivation, food and feed uses and import and processing, and for renewal of the authorisation of maize NK603 as existing product. The EFSA Journal (2009) 1137, 1-50, accessed via http://registerofquestions.efsa.europa.eu/roqFrontend/questionsListLoade...

EFSA (2010) Adopted part of the minutes1 of the 55th plenary meeting of the Scientific Panel on Genetically Modified Organisms held on 27-28 January 2010, GMO Panel deliberations on the paper by Spiroux et al. (2009, A Comparison of the Effects of Three GM Corn Varieties on Mammalian Health, International Journal of Biological Sciences, 5: 706-726), to be published at http://www.efsa.europa.eu/en/events/event/gmo100127.htm

EFSA (2011) 2009 EU Report on Pesticide Residues. EFSA Journal 2011; 9(11): 2430. [226 pp.] doi:10.2903/j.efsa.2011.2430. Available online: www.efsa.europa.eu/efsajournal

European Commission Peer Review Programme (2002) Glyphosate Review Report Rapporteur Member State: Germany, www.ec.europa.eu/food/plant/protection/evaluation/existactive/list1_glyp...

Heap, I. (2012) Glycines (G/9) resistant weeds by species and country. The International Survey of Herbicide Resistant Weeds, online. http://www.weedscience.org/Summary/UspeciesMOA.asp?lstMOAID=12&FmHRACGro...

Johal, G.R. and Huber, D.M. (2009) Glyphosate effects on diseases of plants. European J. Agron. 31: 144-152.

Kleter, G.A., Unsworth J.B., Harris C.A. (2011) The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues. Pest Management Science, 67(10): 1193–1210. doi: 10.1002/ps.2128

Matthews, D., Jones, H., Gans, P., Coates, St. & Smith, L.M.J. (2005) Toxic secondary metabolite production in genetically modified potatoes in response to stress. Journal of Agricultural and Food Chemistry, 10.1021/jf050589r.

Paganelli, A., Gnazzo, V., Acosta, H., López, S. L., Carrasco, A. E. (2010) Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signalling. Chem. Res. Toxicol., August 9. pubs.acs.org/doi/abs/10.1021/tx1001749

PAN AP, Pesticide Action Network Asian Pacific (2009) Monograph on Glyphosate, www.panap.net/en/p/post/pesticides-info-database/115

Pleasants, J.M & Oberhauser, K.S. (2012) Milkweed loss in agricultural fields due to herbicide use: Effect on the Monarch Butterfly population. Insect Conservation and Diversity, doi: 10.1111/j.1752-4598.2012.00196.x.

Spiroux de Vendômois, J.S., Roullier, F., Cellier, D. & Séralini, G.E. (2009) A Comparison of the Effects of Three GM Corn Varieties on Mammalian Health. Int J Biol Sci 2009, 5: 706–726.

Then, C. (2011) Vorsicht „Giftmischer“: Gentechnisch veränderte Pflanzen in Futter-und Lebensmitteln. Testbiotech-Report, http://www.testbiotech.de/node/463

Status of authorisation: 
Authorised in EU
Date of authorisation: 
June 2004
Updated: 
19 April, 2016