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Application of Food and Feed Safety Assessment Principles to Evaluate Transgenic Approaches to Gene Modulation in Crops

Parrott W, Chassy B, Ligon J, Meyer L, Petrick J, Zhou J, Herman R, Delaney B, Levine M
Food and Chemical Toxicology
January 1, 2010

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Task Force #8

Food and Chemical Toxicology. 2010;48:1773-1790

New crop varieties containing traits such as enhanced nutritional profiles, increased yield, and tolerance to drought are being developed. In some cases, these new traits are dependent on small RNAs or regulatory proteins such as transcription factors (TF) that modify the expression of endogenous plant genes. To date, the food and feed safety of genetically modified (GM) crops has been assessed by the application of a set of internationally accepted procedures for evaluating the safety of GM crops. The goal of this paper is to review the main aspects of the current safety assessment paradigm and to recommend scientifically sound principles for conducting a safety assessment for GM crops that are developed by technologies that modify endogenous plant gene expression. Key considerations for such a safety assessment include the following:

  1. RNA and TF are generally recognized as safe GRAS;
  2. Genes encoding RNAi and regulatory proteins such as TFs are an important component of the plant genome;
  3. Crops engineered using RNAi modifications are not expected to produce heterologous proteins;
  4. The modulation of TFs may result in quantitative differences in endogenous plant components, which can be assessed through agronomic performance and compositional analysis on a caseby-case basis.

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References

  • Abel et al., 1986. P.P. Abel, R.S. Nelson, B. De, N. Hoffmann, S.G. Rogers, R.T. Fraley, R.N. Beachy. Delay of disease development in transgenic plants that express the tobacco mosaic virus coat protein gene. Science, 232 (1986), pp. 738–743. LINK
  • Aeschbacher et al., 2005. K. Aeschbacher, R. Messikommer, L. Meile, C. Wenk. Bt176 corn in poultry nutrition: physiological characteristics and fate of recombinant plant DNA in chickens. Poult. Sci., 84 (2005), pp. 385–394. LINK
  • Agarwal et al., 2007. P. Agarwal, P.K. Agarwal, S. Nair, S.K. Sopory, M.K. Reddy. Stress-inducible DREB2A transcription factor from Pennisetum glaucum is a phosphoprotein and its phosphorylation negatively regulates its DNA-binding activity. Mol. Genet. Genomics, 277 (2007), pp. 189–198. LINK
  • AGBIOS, 2008. AGBIOS, 2008. MON 810 Food safety assessment case study. LINK (accessed 12.05.08).
  • Ambros, 2004. V. Ambros. The functions of animal microRNAs. Nature, 431 (2004), pp. 350–355. LINK
  • Andersson et al., 2006. M. Andersson, M. Melander, P. Pojmark, H. Larsson, L. Bulow, P. Hofvander. Targeted gene suppression by RNA interference: an efficient method for production of high-amylose potato lines. J. Biotechnol., 123 (2006), pp. 137–148. LINK
  • Astwood et al., 1996. J.D. Astwood, J.N. Leach, R.L. Fuchs. Stability of food allergens to digestion in vitro. Nat. Biotechnol., 14 (1996), pp. 1269–1273. LINK
  • Aukerman and Sakai, 2003. M.J. Aukerman, H. Sakai. Regulation of flowering time and floral organ identity by a MicroRNA and its APETALA2-like target genes. Plant Cell, 15 (2003), pp. 2730–2741. LINK
  • Baintner and Toth, 1986. K. Baintner, I. Toth. Failure to demonstrate intestinal absorption of RNA in the newborn pig. Preliminary communication. Acta Vet. Hung., 34 (1986), pp. 239–241. LINK
  • Baker et al., 2006. J.M. Baker, N.D. Hawkins, J.L. Ward, A. Lovegrove, J.A. Napier, P.R. Shewry, M.H. Beale. A metabolomic study of substantial equivalence of field-grown genetically modified wheat. Plant Biotechnol. J., 4 (2006), pp. 381–392. LINK
  • Batista et al., 2008. R. Batista, N. Saibo, T. Lourenco, M.M. Oliveira. Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion. Proc. Natl. Acad. Sci. USA, 105 (2008), pp. 3640–3645. LINK
  • Baum et al., 2007. J.A. Baum, T. Bogaert, W. Clinton, G.R. Heck, P. Feldmann, O. Ilagan, S. Johnson, G. Plaetinck, T. Munyikwa, M. Pleau, T. Vaughn, J. Roberts. Control of coleopteran insect pests through RNA interference. Nat. Biotechnol., 25 (2007), pp. 1322–1326. LINK
  • Beever and Kemp, 2000. D.E. Beever, C.F. Kemp. Safety issues associated with the DNA in animal feed derived from genetically modified crops. A review of scientific and regulatory procedures. Nutr. Abstr. Rev., 70 (2000), pp. 197–204. LINK
  • Behlke, 2006. M.A. Behlke. Progress towards in vivo use of siRNAs. Mol. Ther., 13 (2006), pp. 644–670. LINK
  • Berberich et al., 1996. S.A. Berberich, J.E. Ream, T.L. Jackson, R. Wood, R. Stipanovic, P. Harvey, S. Patzer, R.L. Fuchs. The composition of insect-protected cottonseed is equivalent to that of conventional cottonseed. J. Agric. Food Chem., 44 (1996), pp. 365–371. LINK
  • Bertheau et al., 2009. Y. Bertheau, J.C. Helbling, M.N. Fortabat, S. Makhzami, I. Sotinel, C. Audeon, A.C. Nignol, A. Kobilinsky, L. Petit, P. Fach, P. Brunschwig, K. Duhem, P. Martin. Persistence of plant DNA sequences in the blood of dairy cows fed with genetically modified (Bt176) and conventional corn silage. J. Agric. Food Chem., 57 (2009), pp. 509–516. LINK
  • Bonnet et al., 2006. E. Bonnet, Y. Van de Peer, P. Rouze. The small RNA world of plants. New Phytol., 171 (2006), pp. 451–468. LINK
  • Bradford et al., 2005. K.J. Bradford, A. Van Deynze, N. Gutterson, W. Parrott, S.H. Strauss. Regulating transgenic crops sensibly: lessons from plant breeding, biotechnology and genomics. Nat. Biotechnol., 23 (2005), pp. 439–444. LINK
  • Brown, 2002. T. Brown. Genomes. (second ed.)John Wiley and Sons, New York (2002).
  • Byzova et al., 2004. M. Byzova, C. Verduyn, D. De Brouwer, M. De Block. Transforming petals into sepaloid organs in Arabidopsis and oilseed rape: implementation of the hairpin RNA-mediated gene silencing technology in an organ-specific manner. Planta, 218 (2004), pp. 379–387. LINK
  • Carver and Walker, 1995. J.D. Carver, W.A. Walker. The role of nucleotides in human nutrition. J. Nutr. Biochem., 6 (1995), pp. 58–72. LINK
  • Catchpole et al., 2005. G.S. Catchpole, M. Beckmann, D.P. Enot, M. Mondhe, B. Zywicki, J. Taylor, N. Hardy, A. Smith, R.D. King, D.B. Kell, O. Fiehn, J. Draper. Hierarchical metabolomics demonstrates substantial compositional similarity between genetically modified and conventional potato crops. Proc. Natl. Acad. Sci. USA, 102 (2005), pp. 14458–14462. LINK
  • Cellini et al., 2004. F. Cellini, A. Chesson, I. Colquhoun, A. Constable, H.V. Davies, K.H. Engel, A.M. Gatehouse, S. Karenlampi, E.J. Kok, J.J. Leguay, S. Lehesranta, H.P. Noteborn, J. Pedersen, M. Smith. Unintended effects and their detection in genetically modified crops. Food Chem. Toxicol., 42 (2004), pp. 1089–1125. LINK
  • Century et al., 2008. K. Century, T.L. Reuber, O.J. Ratcliffe. Regulating the regulators: the future prospects for transcription-factor-based agricultural biotechnology products. Plant Physiol., 147 (2008), pp. 20–29. LINK
  • Chainark et al., 2006. P. Chainark, S. Satoh, T. Hino, V. Kiron, I. Hirono, T. Aoki. Availability of genetically modified soybean meal in rainbow trout Oncorhynchus mykiss diets. Fisheries Sci., 72 (2006), pp. 1072–1078. LINK
  • Chainark et al., 2008. P. Chainark, S. Satoh, I. Hirono, T. Aoki, M. Endo. Availability of genetically modified feed ingredient: investigations of ingested foreign DNA in rainbow trout Oncorhynchus mykiss. Fisheries Sci., 74 (2008), pp. 380–390. LINK
  • Chandler and Alleman, 2008. V. Chandler, M. Alleman. Paramutation: epigenetic instructions passed across generations. Genetics, 178 (2008), pp. 1839–1844. LINK
  • Chassy et al., 2004. Chassy, B., Hlywka, J.J., Kleter, G.A., Kok, E.J., Kuiper, H.A., McGloughlin, M., Munro, I.C., Phipps, R.H., Reid, J.E., 2004. Nutritional and safety assessments of foods and feeds nutritionally improved through biotechnology (prepared by Task Force of the ILSI International Food Biotechnology Committee). Comp. Rev. Food Sci. Food Safety 3, 38–104. (accessed 15.04.07). LINK
  • Chassy et al., 2008. B. Chassy, M. Egnin, Y. Gao, K. Glenn, G.A. Kleter, P. Nestel, M. Newell-McGloughlin, R.H. Phipps, R. Shillito. Recent developments in the safety and nutritional assessment of nutritionally improved foods and feeds. Comp. Rev. Food Sci. Food Safety, 7 (2008), pp. 50–113. LINK
  • Cheng et al., 2008. K.C. Cheng, J. Beaulieu, E. Iquira, F.J. Belzile, M.G. Fortin, M.V. Stromvik. Effect of transgenes on global gene expression in soybean is within the natural range of variation of conventional cultivars. J. Agric. Food Chem., 56 (2008), pp. 3057–3067. LINK
  • Cigan et al., 2005. A.M. Cigan, E. Unger-Wallace, K. Haug-Collet. Transcriptional gene silencing as a tool for uncovering gene function in maize. Plant J., 43 (2005), pp. 929–940. LINK
  • Clifford and Story, 1976. A.J. Clifford, D.L. Story. Levels of purines in foods and their metabolic effects in rats. J. Nutr., 106 (1976), pp. 435–442. LINK
  • Codex, 2003. Codex, 2003. Alinorm 03/34: Joint FAO/WHO Food Standard Programme, Codex Alimentarius Commission, Appendix III, Guideline for the conduct of food safety assessment of foods derived from recombinant-DNA plants (CAC/GL 45-2003), 25th Session, Rome, Italy, June 30–July 5, 2003, pp. 47–60. LINK(accessed 20.11.07).
  • Cong et al., 2008. B. Cong, L.S. Barrero, S.D. Tanksley. Regulatory change in YABBY-like transcription factor led to evolution of extreme fruit size during tomato domestication. Nat. Genet., 40 (2008), pp. 800–804. LINK
  • Constable et al., 2007. A. Constable, D. Jonas, A. Cockburn, A. Davi, G. Edwards, P. Hepburn, C. Herouet-Guicheney, M. Knowles, B. Moseley, R. Oberdorfer, F. Samuels. History of safe use as applied to the safety assessment of novel foods and foods derived from genetically modified organisms. Food Chem. Toxicol., 45 (2007), pp. 2513–2525. LINK
  • Crombez et al., 2007. L. Crombez, A. Charnet, M.C. Morris, G. Aldrian-Herrada, F. Heitz, G. Divita. A non-covalent peptide-based strategy for siRNA delivery. Biochem. Soc. Trans., 35 (2007), pp. 44–46. LINK
  • Czechowski et al., 2004. T. Czechowski, R.P. Bari, M. Stitt, W.R. Scheible, M.K. Udvardi. Real-time RT-PCR profiling of over 1400 Arabidopsis transcription factors: unprecedented sensitivity reveals novel root- and shoot-specific genes. Plant J., 38 (2004), pp. 366–379. LINK
  • Dale et al., 2002. P.J. Dale, B. Clarke, E.M. Fontes. Potential for the environmental impact of transgenic crops. Nat. Biotechnol., 20 (2002), pp. 567–574. LINK
  • Davis and Wurdack, 2004. C.C. Davis, K.J. Wurdack. Host-to-parasite gene transfer in flowering plants: phylogenetic evidence from Malpighiales. Science, 305 (2004), pp. 676–678. LINK
  • Davuluri et al., 2005. G.R. Davuluri, A. van Tuinen, P.D. Fraser, A. Manfredonia, R. Newman, D. Burgess, D.A. Brummell, S.R. King, J. Palys, J. Uhlig, P.M. Bramley, H.M. Pennings, C. Bowler. Fruit-specific RNAi-mediated suppression of DET1 enhances carotenoid and flavonoid content in tomatoes. Nat. Biotechnol., 23 (2005), pp. 890–895. LINK
  • Delaney et al., 2008. B. Delaney, J.D. Astwood, H. Cunny, R.E. Conn, C. Herouet-Guicheney, S. Macintosh, L.S. Meyer, L. Privalle, Y. Gao, J. Mattsson, M. Levine. Evaluation of protein safety in the context of agricultural biotechnology. Food Chem. Toxicol., 46 (Suppl. 2) (2008), pp. S71–S97. LINK
  • Della Vedova et al., 2005. C.B. Della Vedova, R. Lorbiecke, H. Kirsch, M.B. Schulte, K. Scheets, L.M. Borchert, B.E. Scheffler, U. Wienand, K.C. Cone, J.A. Birchler. The dominant inhibitory chalcone synthase allele C2-Idf (inhibitor diffuse) from Zea mays (L.) acts via an endogenous RNA silencing mechanism. Genetics, 170 (2005), pp. 1989–2002. LINK
  • Demaneche et al., 2008. S. Demaneche, H. Sanguin, J. Pote, E. Navarro, D. Bernillon, P. Mavingui, W. Wildi, T.M. Vogel, P. Simonet. Antibiotic-resistant soil bacteria in transgenic plant fields. Proc. Natl. Acad. Sci. USA, 105 (2008), pp. 3957–3962. LINK
  • Dennis and Peacock, 2004. Dennis, E.S., Peacock, W.J., 2004. Arabidopsis – what can crop breeders learn from a weed? In: New Directions for a Diverse Planet, Proceedings of the Fourth International Crop Science Congress, 26 Sep – 1 Oct 2004, Brisbane, Australia. Published on CDROM. LINK
  • Di Nicola-Negri et al., 2005. E. Di Nicola-Negri, A. Brunetti, M. Tavazza, V. Ilardi. Hairpin RNA-mediated silencing of plum pox virus P1 and HC-Pro genes for efficient and predictable resistance to the virus. Transgenic Res., 14 (2005), pp. 989–994. LINK
  • Dietzgen and Mitter, 2006. R.G. Dietzgen, N. Mitter. Transgenic gene silencing strategies for virus control. Australas. Plant Pathol., 35 (2006), pp. 605–618. LINK
  • Dixon et al., 2006. R.A. Dixon, D.R. Gang, A.J. Charlton, O. Fiehn, H.A. Kuiper, T.L. Reynolds, R.S. Tjeerdema, E.H. Jeffery, J.B. German, W.P. Ridley, J.N. Seiber. Applications of metabolomics in agriculture. J. Agric. Food Chem., 54 (2006), pp. 8984–8994. LINK
  • Doebley et al., 1997. J. Doebley, A. Stec, L. Hubbard. The evolution of apical dominance in maize. Nature, 386 (1997), pp. 485–488. LINK
  • Doerfler and Schubbert, 1997. W. Doerfler, R.F. Schubbert. DNA im Saugersystem. Deutsches Artzeblatt., 94 (1997), p. 2.
  • Drury et al., 2008. S.M. Drury, T.L. Reynolds, W.P. Ridley, N. Bogdanova, S. Riordan, M.A. Nemeth, R. Sorbet, W.A. Trujillo, M.L. Breeze. Composition of forage and grain from second-generation insect-protected corn MON 89034 is equivalent to that of conventional corn (Zea mays L.). J. Agric. Food Chem., 56 (2008), pp. 4623–4630. LINK
  • Dykxhoorn et al., 2006. D.M. Dykxhoorn, D. Palliser, J. Lieberman. The silent treatment: siRNAs as small molecule drugs. Gene Ther., 13 (2006), pp. 541–552. LINK
  • EFSA, 2006. EFSA, 2006. Guidance document of the Scientific Panel on Genetically Modified Organisms for the risk assessment of genetically modified plants and derived food and feed. (accessed 17.04.07) LINK
  • EFSA, 2008. EFSA, 2008. Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials: report of the EFSA GMO Panel Working Group on Animal Feeding Trials. Food Chem. Toxicol. 46 (Suppl 1), S2–S70..LINK
  • El Sanhoty et al., 2004. R. El Sanhoty, A.A. El-Rahman, K.W. Bogl. Quality and safety evaluation of genetically modified potatoes spunta with Cry V gene: compositional analysis, determination of some toxins, antinutrients compounds and feeding study in rats. Nahrung, 48 (2004), pp. 13–18. LINK
  • Evans, 1998. L.T. Evans. Feeding the Ten Billion: Plants and Population Growth. Cambridge University Press, Cambridge, UK (1998).
  • FAO, 1996. FAO, 1996. Biotechnology and food safety. Report of Joint FAO/WHO Consultation. FAO Food and Nutrition Paper No. 61. Food and Agriculture Organization of the United Nations, Rome, Italy. LINK
  • FAO/WHO, 2000. FAO/WHO, 2000. Safety aspects of genetically modified foods of plant origin. Report of a Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology, Geneva, Switzerland, 29 May–2 June 2000. Food and Agriculture Organization of the United Nations/World Health Organization, Geneva, Switzerland. LINK
  • FAO/WHO, 2001. FAO/WHO, 2001. Evaluation of allergenicity of genetically modified foods. Report of a Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology, Rome, Italy, 22–25 January 2001. Food and Agriculture Organization of the United Nations/World Health Organization, Rome, Italy. LINK
  • FAO/WHO, 2007. FAO/WHO, 2007. Alinorm 07/30/34. Joint FAO/WHO Food Standards Programme Codex Alimentarius Commission: Report of the Sixth Session of the Codex Ad Hoc Intergovernmental Task Force on Foods Derived from Biotechnology. Chiba, Japan, 27 November–1 December 2006. Food and Agriculture Organization of the United Nations/World Health Organization, Rome, Italy. LINK
  • Fiehn et al., 2008. O. Fiehn, G. Wohlgemuth, M. Scholz, T. Kind, Y. Lee do, Y. Lu, S. Moon, B. Nikolau. Quality control for plant metabolomics: reporting MSI-compliant studies. Plant J., 53 (2008), pp. 691–704. LINK
  • Fire et al., 1998. A. Fire, S. Xu, M.K. Montgomery, S.A. Kostas, S.E. Driver, C.C. Mello. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391 (1998), pp. 806–811. LINK
  • FSANZ, 2005. FSANZ, 2005. GM foods: safety assessment of genetically modified foods. LINK (accessed 17.04.07).
  • Fu et al., 2002. T.J. Fu, U.R. Abbott, C. Hatzos. Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid-a comparative study. J. Agric. Food Chem., 50 (2002), pp. 7154–7160. LINK
  • Fusaro et al., 2006. A.F. Fusaro, L. Matthew, N.A. Smith, S.J. Curtin, J. Dedic-Hagan, G.A. Ellacott, J.M. Watson, M.B. Wang, C. Brosnan, B.J. Carroll, P.M. Waterhouse. RNA interference-inducing hairpin RNAs in plants act through the viral defence pathway. EMBO Rep., 7 (2006), pp. 1168–1175. LINK
  • Galun, 2005. E. Galun. RNA silencing in plants. In Vitro Cell. Dev. Biol. – Plant, 41 (2005), pp. 113–123. LINK
  • Gao et al., 2006. G. Gao, Y. Zhong, A. Guo, Q. Zhu, W. Tang, W. Zheng, X. Gu, L. Wei, J. Luo. DRTF: a database of rice transcription factors. Bioinformatics, 22 (2006), pp. 1286–1287. LINK
  • Gay and Gillespie, 2005. P.B. Gay, S.H. Gillespie. Antibiotic resistance markers in genetically modified plants: a risk to human health?. Lancet Infect. Dis., 5 (2005), pp. 637–646. LINK
  • George et al., 2004. C. George, W.P. Ridley, J.C. Obert, M.A. Nemeth, M.L. Breeze, J.D. Astwood. Composition of grain and forage from corn rootworm-protected corn event MON 863 is equivalent to that of conventional corn (Zea mays L.). J. Agric. Food Chem., 52 (2004), pp. 4149–4158. LINK
  • Gheysen and Vanholme, 2007. G. Gheysen, B. Vanholme. RNAi from plants to nematodes. Trends Biotechnol., 25 (2007), pp. 89–92. LINK
  • Goldstein et al., 2005. D.A. Goldstein, B. Tinland, L.A. Gilbertson, J.M. Staub, G.A. Bannon, R.E. Goodman, R.L. McCoy, A. Silvanovich. Human safety and genetically modified plants: a review of antibiotic resistance markers and future transformation selection technologies. J. Appl. Microbiol., 99 (2005), pp. 7–23. LINK
  • Goodman, 2006. R.E. Goodman. Practical and predictive bioinformatics methods for the identification of potentially cross-reactive protein matches. Mol. Nutr. Food Res., 50 (2006), pp. 655–660. LINK
  • Goodman et al., 2005. R.E. Goodman, S.L. Hefle, S.L. Taylor, R. van Ree. Assessing genetically modified crops to minimize the risk of increased food allergy: a review. Int. Arch. Allergy Immunol., 137 (2005), pp. 153–166. LINK
  • Goodman et al., 2008. R.E. Goodman, S. Vieths, H.A. Sampson, D. Hill, M. Ebisawa, S.L. Taylor, R. van Ree. Allergenicity assessment of genetically modified crops – what makes sense? Nat. Biotechnol., 26 (2008), pp. 73–81. LINK
  • Guo et al., 2005. A. Guo, K. He, D. Liu, S. Bai, X. Gu, L. Wei, J. Luo. DATF: a database of Arabidopsis transcription factors. Bioinformatics, 21 (2005), pp. 2568–2569. LINK
  • Hamilton and Baulcombe, 1999. A.J. Hamilton, D.C. Baulcombe. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 286 (1999), pp. 950–952. LINK
  • Hamilton et al., 2004. K.A. Hamilton, P.D. Pyla, M. Breeze, T. Olson, M. Li, E. Robinson, S.P. Gallagher, R. Sorbet, Y. Chen. Bollgard II cotton: compositional analysis and feeding studies of cottonseed from insect-protected cotton (Gossypium hirsutum L.) producing the Cry1Ac and Cry2Ab2 proteins. J. Agric. Food Chem., 52 (2004), pp. 6969–6976. LINK
  • Hammond et al., 2004. B. Hammond, R. Dudek, J. Lemen, M. Nemeth. Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn. Food Chem. Toxicol., 42 (2004), pp. 1003–1014. LINK
  • Harrigan et al., 2007. G. Harrigan, S. Martino-Catt, K.C. Glenn. Metabolomics, metabolic diversity, and genetic variation in crops. Metabolomics (2007), pp. 259–272. LINK
  • Harrison et al., 1996. L.A. Harrison, M.R. Bailey, M.W. Naylor, J.E. Ream, B.G. Hammond, D.L. Nida, B.L. Burnette, T.E. Nickson, T.A. Mitsky, M.L. Taylor, R.L. Fuchs, S.R. Padgette. The expressed protein in glyphosate-tolerant soybean, 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacterium sp. strain CP4, is rapidly digested in vitro and is not toxic to acutely gavaged mice. J. Nutr., 126 (1996), pp. 728–740. LINK
  • Health Canada, 2006. Health Canada, 2006. Guidelines for the safety assessment of novel foods. LINK (accessed 17.05.08).
  • Heisel et al., 2008. S.E. Heisel, Y. Zhang, E. Allen, L. Guo, T.L. Reynolds, X. Yang, D. Kovalic, J.K. Roberts. Characterization of unique small RNA populations from rice grain. PLoS ONE, 3 (2008), p. e2871. LINK
  • Helm and Burks, 2002. R.M. Helm, A.W. Burks. Animal models of food allergy. Curr. Opin. Allergy Clin. Immunol., 2 (2002), pp. 541–546. LINK
  • Herbel and Montag, 1987. W. Herbel, A. Montag. Nucleo-compounds in protein-rich food. Z. Lebensm. Unters Forsch., 185 (1987), pp. 119–122. LINK
  • Herman, 2005. E. Herman. Soybean allergenicity and suppression of the immunodominant allergen. Crop Sci., 45 (2005), pp. 462–467. LINK
  • Herman et al., 2004. R.A. Herman, A.M. Phillips, R.A. Collins, L.A. Tagliani, F.A. Claussen, C.D. Graham, B.L. Bickers, T.A. Harris, L.M. Prochaska. Compositional equivalency of Cry1F corn event TC6275 and conventional corn (Zea mays L.). J. Agric. Food Chem., 52 (2004), pp. 2726–2734. LINK
  • Herman et al., 2007a. R.A. Herman, N.P. Storer, A.M. Phillips, L.M. Prochaska, P. Windels. Compositional assessment of event DAS-59122-7 maize using substantial equivalence. Regul. Toxicol. Pharmacol., 47 (2007), pp. 37–47. LINK
  • Herman et al., 2007b. R.A. Herman, M.M. Woolhiser, G.S. Ladics, V.A. Korjagin, B.W. Schafer, N.P. Storer, S.B. Green, L. Kan. Stability of a set of allergens and non-allergens in simulated gastric fluid. Int. J. Food Sci. Nutr., 58 (2007), pp. 125–141. LINK
  • Herouet et al., 2005. C. Herouet, D.J. Esdaile, B.A. Mallyon, E. Debruyne, A. Schulz, T. Currier, K. Hendrickx, R.J. van der Klis, D. Rouan. Safety evaluation of the phosphinothricin acetyltransferase proteins encoded by the pat and bar sequences that confer tolerance to glufosinate-ammonium herbicide in transgenic plants. Regul. Toxicol. Pharmacol., 41 (2005), pp. 134–149. LINK
  • Hotopp et al., 2007. J.C. Hotopp, M.E. Clark, D.C. Oliveira, J.M. Foster, P. Fischer, M.C. Torres, J.D. Giebel, N. Kumar, N. Ishmael, S. Wang, J. Ingram, R.V. Nene, J. Shepard, J. Tomkins, S. Richards, D.J. Spiro, E. Ghedin, B.E. Slatko, H. Tettelin, J.H. Werren. Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science, 317 (2007), pp. 1753–1756. LINK
  • Huang et al., 2006. G. Huang, R. Allen, E.L. Davis, T.J. Baum, R.S. Hussey. Engineering broad root-knot resistance in transgenic plants by RNAi silencing of a conserved and essential root-knot nematode parasitism gene. Proc. Natl. Acad. Sci. USA, 103 (2006), pp. 14302–14306. LINK
  • ILSI, 2003. ILSI, 2003. Best practices for the conduct of animal studies to evaluate crops genetically modified for input traits. ILSI, Washington, DC. <LINK> (accessed 27.11.07).
  • ILSI, 2007. ILSI, 2007. Best practices for the conduct of animal studies to evaluate crops genetically modified for output traits. ILSI, Washington, DC. <LINK> (accessed 27.11.07).
  • ILSI, 2008. ILSI. Nutritional and safety assessments of foods and feeds nutritionally improved through biotechnology: case studies, prepared by a task force of the International Life Sciences Institute, Washington, DC. Comp. Rev. Food Sci. Food Safety, 7 (2008), pp. 50–112.
  • ISB, 2002. ISB, 2002. Proceedings of a Workshop on: Criteria for Field Testing of Plants with Engineered Regulatory, Metabolic, and Signaling Pathways. <LINK> (accessed 27.11.07).
  • Ivanciuc et al., 2009. O. Ivanciuc, T. Garcia, M. Torres, C.H. Schein, W. Braun. Characteristic motifs for families of allergenic proteins. Mol. Immunol., 46 (2009), pp. 559–568. LINK
  • Ivashuta et al., 2009. S.I. Ivashuta, J.S. Petrick, S.E. Heisel, Y. Zhang, L. Guo, T.L. Reynolds, J.F. Rice, E. Allen, J.K. Roberts. Endogenous small RNAs in grain: semi-quantification and sequence homology to human and animal genes. Food Chem. Toxicol., 47 (2009), pp. 353–360. LINK
  • Jacobsen and Schouten, 2007. E. Jacobsen, H.J. Schouten. Cisgenesis strongly improves introgression breeding and induced translocation breeding of plants. Trends Biotechnol., 25 (2007), pp. 219–223. LINK
  • James, 2010. James, C., 2010. Global status of commercialized biotech/GM crops: 2009. ISAAA Brief. <LINK> (accessed 07.03.10).
  • Jennings et al., 2003a. J.C. Jennings, L.D. Albee, D.C. Kolwyck, J.B. Surber, M.L. Taylor, G.F. Hartnell, R.P. Lirette, K.C. Glenn. Attempts to detect transgenic and endogenous plant DNA and transgenic protein in muscle from broilers fed YieldGard Corn Borer Corn. Poult. Sci., 82 (2003), pp. 371–380. LINK
  • Jennings et al., 2003b. J.C. Jennings, D.C. Kolwyck, S.B. Kays, A.J. Whetsell, J.B. Surber, G.L. Cromwell, R.P. Lirette, K.C. Glenn. Determining whether transgenic and endogenous plant DNA and transgenic protein are detectable in muscle from swine fed Roundup Ready soybean meal. J. Anim. Sci., 81 (2003), pp. 1447–1455. LINK
  • Jonas et al., 1996. D.A. Jonas, E. Antignac, J.M. Antoine, H.G. Classen, A. Huggett, I. Knudsen, J. Mahler, T. Ockhuizen, M. Smith, M. Teuber, R. Walker, P. De Vogel. The safety assessment of novel foods. Guidelines prepared by ILSI Europe Novel Food Task Force. Food Chem. Toxicol., 34 (1996), pp. 931–940. LINK
  • Jonas et al., 2001. D.A. Jonas, I. Elmadfa, K.H. Engel, K.J. Heller, G. Kozianowski, A. Konig, D. Muller, J.F. Narbonne, W. Wackernagel, J. Kleiner. Safety considerations of DNA in food. Ann. Nutr. Metab., 45 (2001), pp. 235–254. LINK
  • Jorgensen, 1990. R. Jorgensen. Altered gene expression in plants due to trans interactions between homologous genes. Trends Biotechnol., 8 (1990), pp. 340–344. LINK
  • Jorgensen, 1991. R. Jorgensen. Silencing of plant genes by homologous transgenes. AgBiotech. News Info., 4 (1991), pp. 265N–273N.
  • Kapoor et al., 2002. S. Kapoor, A. Kobayashi, H. Takatsuji. Silencing of the tapetum-specific zinc finger gene TAZ1 causes premature degeneration of tapetum and pollen abortion in petunia. Plant Cell, 14 (2002), pp. 2353–2367. LINK
  • Kier and Petrick, 2008. L.D. Kier, J.S. Petrick. Safety assessment considerations for food and feed derived from plants with genetic modifications that modulate endogenous gene expression and pathways. Food Chem. Toxicol., 46 (2008), pp. 2591–2605. LINK
  • Kobayashi et al., 2007. T. Kobayashi, Y. Ogo, R.N. Itai, H. Nakanishi, M. Takahashi, S. Mori, N.K. Nishizawa. The transcription factor IDEF1 regulates the response to and tolerance of iron deficiency in plants. Proc. Natl. Acad. Sci. USA, 104 (2007), pp. 19150–19155. LINK
  • Komatsuda et al., 2007. T. Komatsuda, M. Pourkheirandish, C. He, P. Azhaguvel, H. Kanamori, D. Perovic, N. Stein, A. Graner, T. Wicker, A. Tagiri, U. Lundqvist, T. Fujimura, M. Matsuoka, T. Matsumoto, M. Yano. Six-rowed barley originated from a mutation in a homeodomain-leucine zipper I-class homeobox gene. Proc. Natl. Acad. Sci. USA, 104 (2007), pp. 1424–1429. LINK
  • Konishi et al., 2006. S. Konishi, T. Izawa, S.Y. Lin, K. Ebana, Y. Fukuta, T. Sasaki, M. Yano. An SNP caused loss of seed shattering during rice domestication. Science, 312 (2006), pp. 1392–1396. LINK
  • Krieger et al., 2008. E. Krieger, E. Allen, L. Gilbertson, J. Roberts, W.R.S. Hiatt. The Flavr Savr Tomato, an early example of RNAi technology. HortScience., 43 (2008), pp. 962–964. LINK
  • Kusaba, 2004. M. Kusaba. RNA interference in crop plants. Curr. Opin. Biotechnol., 15 (2004), pp. 139–143. LINK
  • Kusaba et al., 2003. M. Kusaba, K. Miyahara, S. Iida, H. Fukuoka, T. Takano, H. Sassa, M. Nishimura, T. Nishio. Low glutelin content1: a dominant mutation that suppresses the glutelin multigene family via RNA silencing in rice. Plant Cell, 15 (2003), pp. 1455–1467. LINK
  • Lassek and Montag, 1990. E. Lassek, A. Montag. Nucleic acid components in carbohydrate-rich food. Z. Lebensm. Unters Forsch., 190 (1990), pp. 17–21. LINK
  • Latham et al., 2006. J.R. Latham, A.K. Wilson, R.A. Steinbrecher. The mutational consequences of plant transformation. J. Biomed. Biotechnol., 2006 (2006), p. 25376. LINK
  • Lay et al., 2006. J.O. Lay, R. Liyanage, S. Borgmann, C.L. Wilkins. Problems with the “omics”. TrAC Trends Anal. Chem., 25 (2006), pp. 1046–1056. LINK
  • Lehesranta et al., 2005. S.J. Lehesranta, H.V. Davies, L.V. Shepherd, N. Nunan, J.W. McNicol, S. Auriola, K.M. Koistinen, S. Suomalainen, H.I. Kokko, S.O. Karenlampi. Comparison of tuber proteomes of potato varieties, landraces, and genetically modified lines. Plant Physiol., 138 (2005), pp. 1690–1699. LINK
  • Li et al., 2006. C. Li, A. Zhou, T. Sang. Rice domestication by reducing shattering. Science, 311 (2006), pp. 1936–1939. LINK
  • Li et al., 2008. W.X. Li, Y. Oono, J. Zhu, X.J. He, J.M. Wu, K. Iida, X.Y. Lu, X. Cui, H. Jin, J.K. Zhu. The Arabidopsis NFYA5 transcription factor is regulated transcriptionally and posttranscriptionally to promote drought resistance. Plant Cell, 20 (2008), pp. 2238–2251. LINK
  • Liu et al., 1998a. B. Liu, J.M. Vega, M. Feldman. Rapid genomic changes in newly synthesized amphiploids of Triticum and Aegilops. II. Changes in low-copy coding DNA sequences. Genome, 41 (1998), pp. 535–542. LINK
  • Liu et al., 1998b. B. Liu, J.M. Vega, G.l. Sega, S. Abbo, M. Rodova, M. Feldman. Rapid genome changes in newly synthesized amphidiploids of Triticum and Aegilops. I. Changes in low-copy noncoding DNA sequences. Genome, 41 (1998), pp. 272–277. LINK
  • Liu et al., 2002. Q. Liu, S.P. Singh, A.G. Green. High-stearic and high-oleic cottonseed oils produced by hairpin RNA-mediated post-transcriptional gene silencing. Plant Physiol., 129 (2002), pp. 1732–1743. LINK
  • Lu et al., 2005. C. Lu, S.S. Tej, S. Luo, C.D. Haudenschild, B.C. Meyers, P.J. Green. Elucidation of the small RNA component of the transcriptome. Science, 309 (2005), pp. 1567–1569. LINK
  • Lundry et al., 2008. D.R. Lundry, W.P. Ridley, J.J. Meyer, S.G. Riordan, M.A. Nemeth, W.A. Trujillo, M.L. Breeze, R. Sorbet. Composition of grain, forage, and processed fractions from second-generation glyphosate-tolerant soybean, MON 89788, is equivalent to that of conventional soybean (Glycine max L.). J. Agric. Food Chem., 56 (2008), pp. 4611–4622. LINK
  • MacKenzie et al., 2007. S.A. MacKenzie, I. Lamb, J. Schmidt, L. Deege, M.J. Morrisey, M. Harper, R.J. Layton, L.M. Prochaska, C. Sanders, M. Locke, J.L. Mattsson, A. Fuentes, B. Delaney. Thirteen week feeding study with transgenic maize grain containing event DAS-O15O7-1 in Sprague–Dawley rats. Food Chem. Toxicol., 45 (2007), pp. 551–562. LINK
  • Mallory and Vaucheret, 2006. A.C. Mallory, H. Vaucheret. Functions of microRNAs and related small RNAs in plants. Nat. Genet., 38 (Suppl.) (2006), pp. S31–S36. LINK
  • Mansoor et al., 2006. S. Mansoor, I. Amin, M. Hussain, Y. Zafar, R.W. Briddon. Engineering novel traits in plants through RNA interference. Trends Plant Sci., 11 (2006), pp. 559–565. LINK
  • Mao et al., 2007. Y.B. Mao, W.J. Cai, J.W. Wang, G.J. Hong, X.Y. Tao, L.J. Wang, Y.P. Huang, X.Y. Chen. Silencing a cotton bollworm P450 monooxygenase gene by plant-mediated RNAi impairs larval tolerance of gossypol. Nat. Biotechnol., 25 (2007), pp. 1307–1313. LINK
  • Martens, 2000. M.A. Martens. Safety evaluation of genetically modified foods. Int. Arch. Occup. Environ. Health, 73 (Suppl.) (2000), pp. S14–S18. LINK
  • McCann et al., 2005. M.C. McCann, K. Liu, W.A. Trujillo, R.C. Dobert. Glyphosate-tolerant soybeans remain compositionally equivalent to conventional soybeans (Glycine max L.) during three years of field testing. J. Agric. Food Chem., 53 (2005), pp. 5331–5335. LINK
  • McClain and Bannon, 2006. S. McClain, G. Bannon. Animal models of food allergy: opportunities and barriers. Curr. Allergy Asthma Rep., 6 (2006), pp. 141–144. LINK
  • Metcalfe et al., 1996. D.D. Metcalfe, J.D. Astwood, R. Townsend, H.A. Sampson, S.L. Taylor, R.L. Fuchs. Assessment of the allergenic potential of foods derived from genetically engineered crop plants. Crit. Rev. Food Sci. Nutr., 36 (Suppl.) (1996), pp. S165–S186. LINK
  • Miller et al., 2006. A.K. Miller, G. Galiba, J. Dubcovsky. A cluster of 11 CBF transcription factors is located at the frost tolerance locus Fr-Am2 in Triticum monococcum. Mol. Genet. Genomics, 275 (2006), pp. 193–203. LINK
  • Moritoh et al., 2005. S. Moritoh, D. Miki, M. Akiyama, M. Kawahara, T. Izawa, H. Maki, K. Shimamoto. RNAi-mediated silencing of OsGEN-L (OsGEN-like), a new member of the RAD2/XPG nuclease family, causes male sterility by defect of microspore development in rice. Plant Cell Physiol., 46 (2005), pp. 699–715. LINK
  • Müller, 2006. A.E. Müller. Applications of RNA interference in transgenic plants. CAB reviews: perspectives in agriculture, veterinary science. Nutr. Nat. Resour., 1 (2006), pp. 1–13. LINK
  • Naito et al., 2006. K. Naito, E. Cho, G. Yang, M.A. Campbell, K. Yano, Y. Okumoto, T. Tanisaka, S.R. Wessler. Dramatic amplification of a rice transposable element during recent domestication. Proc. Natl. Acad. Sci. USA, 103 (2006), pp. 17620–17625. LINK
  • Napoli et al., 1990. C. Napoli, C. Lemieux, R. Jorgensen. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell, 2 (1990), pp. 279–289. LINK
  • Nelson et al., 2007. D.E. Nelson, P.P. Repetti, T.R. Adams, R.A. Creelman, J. Wu, D.C. Warner, D.C. Anstrom, R.J. Bensen, P.P. Castiglioni, M.G. Donnarummo, B.S. Hinchey, R.W. Kumimoto, D.R. Maszle, R.D. Canales, K.A. Krolikowski, S.B. Dotson, N. Gutterson, O.J. Ratcliffe, J.E. Heard. Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres. Proc. Natl. Acad. Sci. USA, 104 (2007), pp. 16450–16455. LINK
  • Nemeth et al., 2004. A. Nemeth, A. Wurz, L. Artim, S. Charlton, G. Dana, K. Glenn, P. Hunst, J. Jennings, R. Shilito, P. Song. Sensitive PCR analysis of animal tissue samples for fragments of endogenous and transgenic plant DNA. J. Agric. Food Chem., 52 (2004), pp. 6129–6135. LINK
  • Nielsen et al., 1997. K.M. Nielsen, F. Gebhard, K. Smalla, A.M. Bones, J.D. van Elsas. Evaluation of possible horizontal gene transfer from transgenic plants to the soil bacterium Acinetobacter calcoaceticus BD413. Theor. Appl. Genet., 95 (1997), pp. 815–821. LINK
  • Oberdoerfer et al., 2005. R.B. Oberdoerfer, R.D. Shillito, M. de Beuckeleer, D.H. Mitten. Rice (Oryza sativa L.) containing the bar gene is compositionally equivalent to the nontransgenic counterpart. J. Agric. Food Chem., 53 (2005), pp. 1457–1465. LINK
  • Obert et al., 2004. J.C. Obert, W.P. Ridley, R.W. Schneider, S.G. Riordan, M.A. Nemeth, W.A. Trujillo, M.L. Breeze, R. Sorbet, J.D. Astwood. The composition of grain and forage from glyphosate tolerant wheat MON 71800 is equivalent to that of conventional wheat (Triticum aestivum L.). J. Agric. Food Chem., 52 (2004), pp. 1375–1384. LINK
  • OECD, 1993. OECD, 1993. Safety evaluation of foods derived by modern biotechnology – concepts and principles. (accessed 05.05.09). LINK
  • OECD, 1996. OECD. Food Safety and Evaluation. Organisation for Economic Co-operation and Development, Paris, France (1996).
  • OECD, 1997. OECD. Report of OECD Workshop on the Toxicological and Nutritional Testing of Novel Foods. Organisation for Economic Co-operation and Development, Paris, France (1997). LINK
  • OECD, 2001a. OECD, 2001a. Consensus document on key nutrients and key toxicants in low erucic acid rapeseed (canola). In: Environmental Directorate: Joint Meeting of Chemical Committee and the Working Party on Chemicals, Pesticides and Biotechnology: Series on the Safety of Novel Foods and Feeds. Organisation for Economic Co-operation and Development, Paris, France. LINK
  • OECD, 2001b. OECD, 2001b. Consensus document on compositional considerations for new varieties of soybean: key food and feed nutrients and anti-nutrients. In: Environmental Directorate: Joint meeting of Chemical Committee and the Working Party on Chemicals, Pesticides and Biotechnology: Series on the Safety of Novel Foods and Feeds. Organisation for Economic Co-operation and Development, Paris, France. LINK
  • OECD, 2002. OECD, 2002. Consensus document on compositional considerations for new varieties of Maize (Zea mays): key food and feed nutrients, anti-nutrients and secondary plant metabolites. In: Environmental Directorate: Joint meeting of Chemical Committee and the Working Party on Chemicals, Pesticides and Biotechnology: Series on the Safety of Novel Foods and Feeds. Organisation for Economic Co-operation and Development, Paris, France. LINK
  • OECD, 2004a. OECD, 2004a. Consensus document on compositional considerations for new varieties of rice (Oryza sativa): key food and feed nutrients and anti-nutrients. In: Environmental Directorate: Joint meeting of Chemical Committee and the Working Party on Chemicals, Pesticides and Biotechnology: Series on the Safety of Novel Foods and Feeds. Organisation for Economic Co-operation and Development, Paris, France. LINK
  • OECD, 2004b. OECD, 2004b. Consensus document on compositional considerations for new varieties of cotton (Gossypium hirsutum and Gossypium barbadense): key food and feed nutrients and anti-nutrients. In: Environmental Directorate: Joint meeting of Chemical Committee and the Working Party on Chemicals, Pesticides and Biotechnology: Series on the Safety of Novel Foods and Feeds. Organisation for Economic Co-operation and Development, Paris, France. LINK
  • Ogita et al., 2003. S. Ogita, H. Uefuji, Y. Yamaguchi, N. Koizumi, H. Sano. Producing decaffeinated coffee plants. Nature, 423 (2003), p. 823. LINK
  • Okunuki et al., 2002. H. Okunuki, R. Teshima, T. Shigeta, J. Sakushima, H. Akiyama, Y. Goda, M. Toyoda, J. Sawada. Increased digestibility of two products in genetically modified food (CP4-EPSPS and Cry1Ab) after preheating. Shokuhin Eiseigaku Zasshi, 43 (2002), pp. 68–73. LINK
  • Ossowski et al., 2008. S. Ossowski, R. Schwab, D. Weigel. Gene silencing in plants using artificial microRNAs and other small RNAs. Plant J., 53 (2008), pp. 674–690. LINK
  • Peng et al., 1999. J. Peng, D.E. Richards, N.M. Hartley, G.P. Murphy, K.M. Devos, J.E. Flintham, J. Beales, L.J. Fish, A.J. Worland, F. Pelica, D. Sudhakar, P. Christou, J.W. Snape, M.D. Gale, N.P. Harberd. ‘Green Revolution’ genes encode mutant gibberellin response modulators. Nature, 400 (1999), pp. 256–261. LINK
  • Petrovska et al., 2005. N. Petrovska, X. Wu, R. Donato, Z. Wang, E.-K. Ong, E. Jones, J. Forster, M. Emmerling, A. Sidoli, R. O’Hehir, G. Spangenberg. Transgenic ryegrasses (Lolium spp.) with down-regulation of main pollen allergens. Mol. Breed., 14 (2005), pp. 489–501. LINK
  • Phipps et al., 2003. R.H. Phipps, E.R. Deaville, B.C. Maddison. Detection of transgenic and endogenous plant DNA in rumen fluid, duodenal digesta, milk, blood, and feces of lactating dairy cows. J. Dairy Sci., 86 (2003), pp. 4070–4078. LINK
  • Poulsen et al., 2007. M. Poulsen, S. Kroghsbo, M. Schroder, A. Wilcks, H. Jacobsen, A. Miller, T. Frenzel, J. Danier, M. Rychlik, Q. Shu, K. Emami, D. Sudhakar, A. Gatehouse, K.H. Engel, I. Knudsen. A 90-day safety study in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol., 45 (2007), pp. 350–363. LINK
  • Regina et al., 2006. A. Regina, A. Bird, D. Topping, S. Bowden, J. Freeman, T. Barsby, B. Kosar-Hashemi, Z. Li, S. Rahman, M. Morell. High-amylose wheat generated by RNA interference improves indices of large-bowel health in rats. Proc. Natl. Acad. Sci. USA, 103 (2006), pp. 3546–3551. LINK
  • Reuter and Aulrich, 2003. T. Reuter, K. Aulrich. Investigations on genetically modified maize (Bt-maize) in pig nutrition: fate of feed-ingested foreign DNA in pig bodies. Eur. Food Res. Technol., 216 (2003), pp. 185–192. LINK
  • Reuter et al., 2005. T. Reuter, K. Aulrich, W. Schnackel, T.A. McAllister. Detection of feed-ingested plant DNA fragments in a raw meat product for human consumption. Can. J. Anim. Sci., 85 (2005), pp. 541–543. LINK
  • Rhee et al., 2005. G.S. Rhee, D.H. Cho, Y.H. Won, J.H. Seok, S.S. Kim, S.J. Kwack, R.D. Lee, S.Y. Chae, J.W. Kim, B.M. Lee, K.L. Park, K.S. Choi. Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats. J. Toxicol. Environ. Health A, 68 (2005), pp. 2263–2276. LINK
  • Ridley et al., 2002. W.P. Ridley, R.S. Sidhu, P.D. Pyla, M.A. Nemeth, M.L. Breeze, J.D. Astwood. Comparison of the nutritional profile of glyphosate-tolerant corn event NK603 with that of conventional corn (Zea mays L.). J. Agric. Food Chem., 50 (2002), pp. 7235–7243. LINK
  • Ridley et al., 2004. W.P. Ridley, R.D. Shillito, I. Coats, H.-Y. Steiner, M. Shawgo, P. Dussold, A. Phillips, L. Kurtyka. Development of the International Life Sciences Institute crop composition database. J. Food Comp. Anal., 17 (2004), pp. 423–438. LINK
  • Riechmann and Ratcliffe, 2000. J.L. Riechmann, O.J. Ratcliffe. A genomic perspective on plant transcription factors. Curr. Opin. Plant Biol., 3 (2000), pp. 423–434. LINK
  • Riechmann et al., 2000. J.L. Riechmann, J. Heard, G. Martin, L. Reuber, C. Jiang, J. Keddie, L. Adam, O. Pineda, O.J. Ratcliffe, R.R. Samaha, R. Creelman, M. Pilgrim, P. Broun, J.Z. Zhang, D. Ghandehari, B.K. Sherman, G. Yu. Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes. Science, 290 (2000), pp. 2105–2110. LINK
  • Rossi et al., 2005. F. Rossi, M. Morlacchini, G. Fusconi, A. Pietri, R. Mazza, G. Piva. Effect of Bt corn on broiler growth performance and fate of feed-derived DNA in the digestive tract. Poult. Sci., 84 (2005), pp. 1022–1030. LINK
  • Safford et al., 1998. R. Safford, S.A. Jobling, C.M. Sidebottom, R.J. Westcott, D. Cooke, K.J. Tober, B.H. Strongitharm, A.L. Russell, M.J. Gidley. Consequences of antisense RNA inhibition of starch branching enzyme activity on properties of potato starch. Carbohydr. Polym., 35 (1998), pp. 155–168. LINK
  • Salaman, 1933. R.N. Salaman. Protective inoculation against a plant virus. Nature, 131 (1933), p. 468. LINK
  • Sanders and Hiatt, 2005. R.A. Sanders, W. Hiatt. Tomato transgene structure and silencing. Nat. Biotechnol., 23 (2005), pp. 287–289. LINK
  • Schluter et al., 1995. K. Schluter, J. Futterer, I. Potrykus. “Horizontal” gene transfer from a transgenic potato line to a bacterial pathogen (Erwinia chrysanthemi) occurs–if at all–at an extremely low frequency. Biotechnology, 13 (1995), pp. 1094–1098. LINK
  • Schroder et al., 2007. M. Schroder, M. Poulsen, A. Wilcks, S. Kroghsbo, A. Miller, T. Frenzel, J. Danier, M. Rychlik, K. Emami, A. Gatehouse, Q. Shu, K.H. Engel, I. Altosaar, I. Knudsen. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol., 45 (2007), pp. 339–349. LINK
  • Schubbert et al., 1997. R. Schubbert, D. Renz, B. Schmitz, W. Doerfler. Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA. Proc. Natl. Acad. Sci. USA, 94 (1997), pp. 961–966. LINK
  • Schubbert et al., 1998. R. Schubbert, U. Hohlweg, D. Renz, W. Doerfler. On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus. Mol. Gen. Genet., 259 (1998), pp. 569–576. LINK
  • Schubert et al., 2004. D. Schubert, B. Lechtenberg, A. Forsbach, M. Gils, S. Bahadur, R. Schmidt. Silencing in Arabidopsis T-DNA transformants: the predominant role of a gene-specific RNA sensing mechanism versus position effects. Plant Cell, 16 (2004), pp. 2561–2572. LINK
  • Schwachtje and Baldwin, 2008. J. Schwachtje, I.T. Baldwin. Why does herbivore attack reconfigure primary metabolism?. Plant Physiol., 146 (2008), pp. 845–851. LINK
  • Schwall et al., 2000. G.P. Schwall, R. Safford, R.J. Westcott, R. Jeffcoat, A. Tayal, Y.C. Shi, M.J. Gidley, S.A. Jobling. Production of very-high-amylose potato starch by inhibition of SBE A and B. Nat. Biotechnol., 18 (2000), pp. 551–554. LINK
  • Segal et al., 2003. G. Segal, R. Song, J. Messing. A new opaque variant of maize by a single dominant RNA-interference-inducing transgene. Genetics, 165 (2003), pp. 387–397. LINK
  • Shewry et al., 2007. P.R. Shewry, M. Baudo, A. Lovegrove, S. Powers, J.A. Napier, J.L. Ward, J.M. Baker, M.H. Beale. Are GM and conventionally bred cereals really different?. Trends Food Sci. Technol., 18 (2007), pp. 201–209. LINK
  • Sidhu et al., 2000. R.S. Sidhu, B.G. Hammond, R.L. Fuchs, J.N. Mutz, L.R. Holden, B. George, T. Olson. Glyphosate-tolerant corn: the composition and feeding value of grain from glyphosate-tolerant corn is equivalent to that of conventional corn (Zea mays L.). J. Agric. Food Chem., 48 (2000), pp. 2305–2312. LINK
  • Sidorenko and Peterson, 2001. L.V. Sidorenko, T. Peterson. Transgene-induced silencing identifies sequences involved in the establishment of paramutation of the maize p1 gene. Plant Cell, 13 (2001), pp. 319–335. LINK
  • Song et al., 1995. K. Song, P. Lu, K. Tang, T.C. Osborn. Rapid genome change in synthetic polyploids of Brassica and its implications for polyploid evolution. Proc. Natl. Acad. Sci. USA, 92 (1995), pp. 7719–7723. LINK
  • Soutschek et al., 2004. J. Soutschek, A. Akinc, B. Bramlage, K. Charisse, R. Constien, M. Donoghue, S. Elbashir, A. Geick, P. Hadwiger, J. Harborth, M. John, V. Kesavan, G. Lavine, R.K. Pandey, T. Racie, K.G. Rajeev, I. Rohl, I. Toudjarska, G. Wang, S. Wuschko, D. Bumcrot, V. Koteliansky, S. Limmer, M. Manoharan, H.P. Vornlocher. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature, 432 (2004), pp. 173–178. LINK
  • Stam et al., 1998. M. Stam, A. Viterbo, J.N. Mol, J.M. Kooter. Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats: implications for posttranscriptional silencing of homologous host genes in plants. Mol. Cell Biol., 18 (1998), pp. 6165–6177. LINK
  • Steeves et al., 2006. R.M. Steeves, T.C. Todd, J.S. Essig, H.N. Trick. Transgenic soybeans expressing siRNAs specific to a major sperm protein gene suppress Heterodera glycines reproduction. Funct. Plant Biol., 33 (2006), pp. 991–999. LINK
  • Stoutjesdijk et al., 2002. P.A. Stoutjesdijk, S.P. Singh, Q. Liu, C.J. Hurlstone, P.A. Waterhouse, A.G. Green. HpRNA-mediated targeting of the Arabidopsis FAD2 gene gives highly efficient and stable silencing. Plant Physiol., 129 (2002), pp. 1723–1731. LINK
  • Sunilkumar et al., 2005. G. Sunilkumar, L.M. Campbell, M. Hossen, J.P. Connell, E. Hernandez, A.S. Reddy, C.W. Smith, K.S. Rathore. A comprehensive study of the use of a homologous promoter in antisense cotton lines exhibiting a high seed oleic acid phenotype. Plant Biotechnol. J., 3 (2005), pp. 319–330. LINK
  • Sunilkumar et al., 2006. G. Sunilkumar, L.M. Campbell, L. Puckhaber, R.D. Stipanovic, K.S. Rathore. Engineering cottonseed for use in human nutrition by tissue-specific reduction of toxic gossypol. Proc. Natl. Acad. Sci. USA, 103 (2006), pp. 18054–18059. LINK
  • Tabara et al., 1998. H. Tabara, A. Grishok, C.C. Mello. RNAi in C. Elegans: soaking in the genome sequence. Science, 282 (1998), pp. 430–431. LINK
  • Taylor et al., 1999. N.B. Taylor, R.L. Fuchs, J. MacDonald, A.R. Shariff, S.R. Padgette. Compositional analysis of glyphosate-tolerant soybeans treated with glyphosate. J Agric Food Chem., 47 (1999), pp. 4469–4473. LINK
  • Thelen and Ohlrogge, 2002. J.J. Thelen, J.B. Ohlrogge. Metabolic engineering of fatty acid biosynthesis in plants. Metab. Eng., 4 (2002), pp. 12–21. LINK
  • Thomas et al., 2004. K. Thomas, M. Aalbers, G.A. Bannon, M. Bartels, R.J. Dearman, D.J. Esdaile, T.J. Fu, C.M. Glatt, N. Hadfield, C. Hatzos, S.L. Hefle, J.R. Heylings, R.E. Goodman, B. Henry, C. Herouet, M. Holsapple, G.S. Ladics, T.D. Landry, S.C. MacIntosh, E.A. Rice, L.S. Privalle, H.Y. Steiner, R. Teshima, R. Van Ree, M. Woolhiser, J. Zawodny. A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regul. Toxicol. Pharmacol., 39 (2004), pp. 87–98. LINK
  • Thomas et al., 2005. Thomas, K., Bannon, G., Hefle, S., Herouet, C., Holsapple, M., Ladics, G., MacIntosh, S., Privalle, L., 2005. In silico methods for evaluating human allergenicity to novel proteins. International Bioinformatics Workshop Meeting Report, 23–24 February 2005. Toxicol. Sci. 88, 307–310. LINK
  • Thomas et al., 2007. K. Thomas, G. Bannon, C. Herouet-Guicheney, G. Ladics, L. Lee, S.I. Lee, L. Privalle, B. Ballmer-Weber, S. Vieths. The utility of an international sera bank for use in evaluating the potential human allergenicity of novel proteins. Toxicol. Sci., 97 (2007), pp. 27–31. LINK
  • Tian et al., 2004. A.G. Tian, G.Z. Luo, Y.J. Wang, J.S. Zhang, J.Y. Gai, S.Y. Chen. Isolation and characterization of a Pti1 homologue from soybean. J. Exp. Bot., 55 (2004), pp. 535–537. LINK
  • Timmons and Fire, 1998. L. Timmons, A. Fire. Specific interference by ingested dsRNA. Nature, 395 (1998), p. 854. LINK
  • Timmons et al., 2001. L. Timmons, D.L. Court, A. Fire. Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene, 263 (2001), pp. 103–112. LINK
  • Tomari and Zamore, 2005. Y. Tomari, P.D. Zamore. Perspective: machines for RNAi. Genes Dev., 19 (2005), pp. 517–529. LINK
  • Tony et al., 2003. M.A. Tony, A. Butschke, H. Broll, L. Grohmann, J. Zagon, I. Halle, S. Danicke, M. Schauzu, H.M. Hafez, G. Flachowsky. Safety assessment of Bt 176 maize in broiler nutrition: degradation of maize-DNA and its metabolic fate. Arch. Tierernahr., 57 (2003), pp. 235–252. LINK
  • Tuteja et al., 2004. J.H. Tuteja, S.J. Clough, W.C. Chan, L.O. Vodkin. Tissue-specific gene silencing mediated by a naturally occurring chalcone synthase gene cluster in Glycine max. Plant Cell, 16 (2004), pp. 819–835. LINK
  • UN Protein Advisory Group, 1972. UN Protein Advisory Group. Production of Single Cell Protein for Human Consumption, Guideline 12. FAO/WHO/UNICEF Advisory Group, United Nations, New York (1972).
  • Urwin et al., 2002. P.E. Urwin, C.J. Lilley, H.J. Atkinson. Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to RNA interference. Mol. Plant Microb. Interact., 15 (2002), pp. 747–752. LINK
  • USDA-APHIS, 2008. USDA-APHIS, 2008. Additional guidance on agronomic performance data on corn. LINK (accessed 15.05.08).
  • Vagujfalvi et al., 2005. A. Vagujfalvi, A. Aprile, A. Miller, J. Dubcovsky, G. Delugu, G. Galiba, L. Cattivelli. The expression of several Cbf genes at the Fr-A2 locus is linked to frost resistance in wheat. Mol. Genet. Genomics, 274 (2005), pp. 506–514. LINK
  • van der Krol et al., 1988. A.R. van der Krol, P.E. Lenting, J. Veenstra, I.M. van der Meer, R.E. Koes, A.G.M. Gerats, J.N.M. Mol, A.R. Stuitje. An anti-sense chalcone synthase gene in transgenic plants inhibits flower pigmentation. Nature, 333 (1988), pp. 866–869. LINK
  • van der Krol et al., 1990. A.R. van der Krol, L.A. Mur, P. Lange, A.G.M. Gerats, J.N.M. Mol, A.R. Stuitje. Antisense chalcone synthase genes in petunia: Visualization of variable transgene expression. Mol. Gen. Genet., 220 (1990), pp. 204–212. LINK
  • Wang et al., 2005. H. Wang, T. Nussbaum-Wagler, B. Li, Q. Zhao, Y. Vigouroux, M. Faller, K. Bomblies, L. Lukens, J.F. Doebley. The origin of the naked grains of maize. Nature, 436 (2005), pp. 714–719. LINK
  • Wang et al., 2006. W. Wang, H. Zheng, C. Fan, J. Li, J. Shi, Z. Cai, G. Zhang, D. Liu, J. Zhang, S. Vang, Z. Lu, G.K. Wong, M. Long, J. Wang. High rate of chimeric gene origination by retroposition in plant genomes. Plant Cell, 18 (2006), pp. 1791–1802. LINK
  • Warthmann et al., 2008. N. Warthmann, H. Chen, S. Ossowski, D. Weigel, P. Herve. Highly specific gene silencing by artificial miRNAs in rice. PLoS ONE, 3 (2008), p. e1829. LINK
  • Watson et al., 2005. J.M. Watson, A.F. Fusaro, M. Wang, P.M. Waterhouse. RNA silencing platforms in plants. FEBS Lett., 579 (2005), pp. 5982–5987. LINK
  • Wesley et al., 2001. S.V. Wesley, C.A. Helliwell, N.A. Smith, M.B. Wang, D.T. Rouse, Q. Liu, P.S. Gooding, S.P. Singh, D. Abbott, P.A. Stoutjesdijk, S.P. Robinson, A.P. Gleave, A.G. Green, P.M. Waterhouse. Construct design for efficient, effective and high-throughput gene silencing in plants. Plant J., 27 (2001), pp. 581–590. LINK
  • WHO, 1991. WHO. Report of a Joint FAO/WHO Consultation: Strategies for Assessing the Safety of Foods Produced by Biotechnology. World Health Organization, Geneva, Switzerland (1991). LINK
  • WHO, 1995. WHO, 1995. Report of WHO Workshop WHO/FNU/FOS/95.1: Application of the principles of substantial equivalence to the safety evaluation of foods and food components from plants derived by modern biotechnology. World Health Organization, Geneva, Switzerland. LINK
  • Wilson et al., 2006. A.K. Wilson, J.R. Latham, R.A. Steinbrecher. Transformation-induced mutations in transgenic plants: analysis and biosafety implications. Biotechnol. Genet. Eng. Rev., 23 (2006), pp. 209–237. LINK
  • Wraight et al., 2000. C.L. Wraight, A.R. Zangerl, M.J. Carroll, M.R. Berenbaum. Absence of toxicity of Bacillus thuringiensis pollen to black swallowtails under field conditions. Proc. Natl. Acad. Sci. USA, 97 (2000), pp. 7700–7703. LINK
  • Wu et al., 2006. H. Wu, C. Sparks, H. Jones. Characterisation of T-DNA loci and vector backbone sequences in transgenic wheat produced by Agrobacterium-mediated transformation. Mol. Breed., 18 (2006), pp. 195–208. LINK
  • Xiang et al., 2006. S. Xiang, J. Fruehauf, C.J. Li. Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat. Biotechnol., 24 (2006), pp. 697–702. LINK
  • Xin et al., 2007. Z. Xin, A. Mandaokar, J. Chen, R.L. Last, J. Browse. Arabidopsis ESK1 encodes a novel regulator of freezing tolerance. Plant J., 49 (2007), pp. 786–799. LINK
  • Yadav et al., 2006. B.C. Yadav, K. Veluthambi, K. Subramaniam. Host-generated double stranded RNA induces RNAi in plant-parasitic nematodes and protects the host from infection. Mol. Biochem. Parasitol., 148 (2006), pp. 219–222. LINK
  • Yu et al., 1993. L.M. Yu, C.J. Lamb, R.A. Dixon. Purification and biochemical characterization of proteins which bind to the H-box cis-element implicated in transcriptional activation of plant defense genes. Plant J., 3 (1993), pp. 805–816. LINK
  • Zhang, 2003. J.Z. Zhang. Overexpression analysis of plant transcription factors. Curr. Opin. Plant Biol., 6 (2003), pp. 430–440. LINK
  • Zhang et al., 2006. J. Zhang, F. Zhang, T. Peterson. Transposition of reversed Ac element ends generates novel chimeric genes in maize. PLoS Genet., 2 (2006), p. e164. LINK
  • Zhou et al., 2007. J. Zhou, X. Wang, Y. Jiao, Y. Qin, X. Liu, K. He, C. Chen, L. Ma, J. Wang, L. Xiong, Q. Zhang, L. Fan, X.W. Deng. Global genome expression analysis of rice in response to drought and high-salinity stresses in shoot, flag leaf, and panicle. Plant Mol. Biol., 63 (2007), pp. 591–608. LINK
  • Zhu et al., 2007. Q.H. Zhu, A.Y. Guo, G. Gao, Y.F. Zhong, M. Xu, M. Huang, J. Luo. DPTF: a database of poplar transcription factors. Bioinformatics, 23 (2007), pp. 1307–1308. LINK