Weight of the evidence: independent research projects confirm industry conclusions on the safety of insect-protected maize MON 810

References

• ISAAA. Global status of commercialized biotech/GM Crops in 2018: biotech crops continue to help meet the challenges of increased population and climate change. Ithaca (New York): International Service for the Acquisition of Agri-biotech Applications; 2018.
   Google Scholar
• Brookes G, Barfoot P. Environmental impacts of genetically modified (GM) crop use 1996–2015: impacts on pesticide use and carbon emissions. GM Crops Food. 2017;8:117–47. doi:10.1080/21645698.2017.1309490.
   Google Scholar
• Kouser S, Qaim M. Impact of Bt cotton on pesticide poisoning in smallholder agriculture: A panel data analysis. Ecol Econ. 2011;70:2105–13. doi:10.1016/j.ecolecon.2011.06.008.
   Google Scholar
• Kouser S, Qaim M. Valuing financial, health, and environmental benefits of Bt cotton in Pakistan. Ag Econ. 2013;44:323–35. doi:10.1111/agec.12014.
   Google Scholar
• Huang J, Hu R, Pray C, Qiao F, Rozelle S. Biotechnology as an alternative to chemical pesticides: a case study of Bt cotton in China. Ag Econ. 2005;29:55–67. doi:10.1111/j.1574-0862.2003.tb00147.x.
   Google Scholar
• ILSI. A review of the food and feed safety of the Cry1Ab protein. Washington (D.C): ILSI Research Foundation; 2016.
   Google Scholar
• EPA, U.S. Reregistration eligibility decision (RED): bacillus thuringiensis. Washington (D.C): U.S. Environmental Protection Agency; 1998.
   Google Scholar
• FDA U.S. Statement of policy: foods derived from new plant varieties. Fed Regist. 1992;57:22984–3005.
   Google Scholar
• Glenn KC, Alsop B, Bell E, Goley M, Jenkinson J, Liu B, Martin C, Parrott W, Souder C, Sparks O, et al. Bringing new plant varieties to market: plant breeding and selection practices advance beneficial characteristics while minimizing unintended changes. Crop Sci. 2017;57:2906–21. doi:10.2135/cropsci2017.03.0199.
   Google Scholar
• Conko G, Kershen DL, Miller H, Parrott W. A risk-based approach to the regulation of genetically engineered organisms. Nature Biotechnol. 2016;34:493–503. doi:10.1038/nbt.3568.
   Google Scholar
• Herman RA, Price WD. Unintended compositional changes in genetically modified (GM) crops: 20 years of research. J Agric Food Chem. 2013;61:11695–701. doi:10.1021/jf400135r.
   Google Scholar
• Schnell J, Steele M, Bean J, Neuspiel M, Girard C, Dormann N, Pearson C, Savoie A, Bourbonnière L, Macdonald P. A comparative analysis of insertional effects in genetically engineered plants: considerations for pre-market assessments. Transgenic Res. 2015;24:1–17. doi:10.1007/s11248-014-9843-7.
   Google Scholar
• Weber N, Halpin C, Hannah LC, Jez JM, Kough J, Parrott W. Editor’s choice: crop genome plasticity and its relevance to food and feed safety of genetically engineered breeding stacks. Plant Physiol. 2012;160:1842–53. doi:10.1104/pp.112.204271.
   Google Scholar
• Hirsch CN, Hirsch CD, Brohammer AB, Bowman MJ, Soifer I, Barad O, Shem-Tov D, Baruch K, Lu F, Hernandez AG, et al. Draft assembly of elite inbred line PH207 provides insights into genomic and transcriptome diversity in maize. Plant Cell. 2016;28:2700–14. doi:10.1105/tpc.16.00353.
   Google Scholar
• Lisch D. How important are transposons for plant evolution? Nature Rev Genet. 2013;14:49–61. doi:10.1038/nrg3374.
   Google Scholar
• Dolan LC, Matulka RA, Burdock GA. Naturally occurring food toxins. Toxins. 2010;2:2289–332. doi:10.3390/toxins2092289.
   Google Scholar
• Codex Alimentarius. Guideline for the conduct of food safety assessment of foods derived from recombinant-DNA plants. Codex Alimentarius Commission. Rome (Italy): Joint FAO/WHO Food Standards Programme, Food and Agriculture Organization of the United Nations; 2003.
   Google Scholar
• Codex Alimentarius. Foods derived from modern biotechnology. Codex Alimentarius Commission. Rome (Italy): Joint FAO/WHO Food Standards Programme, Food and Agriculture Organization of the United Nations; 2009.
   Google Scholar
• Codex Alimentarius. Foods derived from modern biotechnology. Codex Alimentarius Commission. Rome (Italy): Joint FAO/WHO Food Standards Programme, Food and Agriculture Organization of the United Nations; 2004.
   Google Scholar
• EFSA. Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials. Food ChemToxicol. 2008;46:S2–S70. doi:10.1016/j.fct.2008.02.008.
   Google Scholar
• FAO-WHO. Safety aspects of genetically modified foods of plant origin. Report of a joint FAO/WHO expert consultation on foods derived from biotechnology. Geneva (Switzerland), Food and Agriculture Organization of the United Nations, World Health Organization, 2000.
   Google Scholar
• Bartholomaeus A, Parrott W, Bondy G, Walker K. The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations. Crit Rev Toxicol. 2013;43 (Suppl 2):1–24. doi:10.3109/10408444.2013.842955.
   Google Scholar
• Zeljenková D, Alácˇová R, Ondrejková J, Ambrušová K, Bartušová M, Kebis A, Kovrižnych J, Rollerová E, Szabová E, Wimmerová S, et al. One‑year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE). Arch Toxicol. 2016;90:2531–62. doi:10.1007/s00204-016-1798-4.
   Google Scholar
• Zeljenková D, Ambrušová K, Bartušová M, Kebis A, Kovrižnych J, Krivošíková Z, Kuricová M, Líšková A, Rollerová E, Spustová V, et al. Ninety‑day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE). Arch Toxicol. 2014;88:2289–314. doi:10.1007/s00204-014-1374-8.
   Google Scholar
• FAO-WHO. Joint FAO/WHO expert consultation on biotechnology and food safety. Rome (Italy): Food and Agriculture Organization of the United Nations, World Health Organization, 1996.
   Google Scholar
• OECD. Safety evaluation of foods derived by modern biotechnology: concepts and principles. Paris (France): Organisation for Economic Co-operation and Development; 1993.
   Google Scholar
• Sanders PR, Lee TC, Groth ME, Astwood JD, Fuchs RL. Safety assessment of insect-protected corn. In: Thomas JA, editor. Biotechnology and safety assessment. New York,NY: Taylor and Francis; 1998. p. 241–56.
   Google Scholar
• EPA, U.S. Biopesticides Registration Action Document - Bt Plant-Incorporated Protectants. 2001. https://www3.epa.gov/pesticides/chem_search/reg_actions/pip/bt_brad2/2-id_health.pdf
   Google Scholar
• EFSA. EFSA panel on genetically modified organisms. Scientific opinion on the annual post-market environmental monitoring (PMEM) report from Monsanto Europe S.A. on the cultivation of genetically modified maize MON 810 in 2010. EFSA Jl. 2012;10:2610.
   Google Scholar
• Hammond BG, Koch MS. A review of the food safety of Bt crops. In: Sansinenea E, editor. Bacillus thuringiensis Biotechnology. 2012. p. 305–25. Dordrecht: Springer. doi: 10.1007/978-94-007-3021-2_16.
   Google Scholar
• Koch MS, Ward JM, Levine SL, Baum JA, Vicini JL, Hammond BG. The food and environmental safety of Bt crops. Front Plant Sci. 2015;6:283. doi:10.3389/fpls.2015.00283.
   Google Scholar
• Huber HE, Lüthy P. Bacillus thuringiensis δ-endotoxin: composition and activation. In: Davidson EW, editor. Pathogenesis of invertebrate microbial diseases. Totowa (New Jersey): Allanheld, Osman & Co. Publishers.; 1981. p. 242–55.
   Google Scholar
• Shukla R, Cheryan M. Zein: the industrial protein from corn. Ind Crops Prod. 2001;13:171–92. doi:10.1016/S0926-6690(00)00064-9.
   Google Scholar
• Bravo A, Gomex I, Conde J, Munoz-Garay C, Sanchez J, Miranda R, Zhuang M, Gill SS, Soberón M. Oligomerization triggers binding of a Bacillus thuringiensis Cry1Ab pore-forming toxin to aminopeptidase N receptor leading to insertion into membrane microdomains. Biochim Biophys Acta. 2004;1667:38–46. doi:10.1016/j.bbamem.2004.08.013.
   Google Scholar
• Fernandez LE, Gomez I, Pacheco S, Arenas I, Gilla SS, Bravo A, Soberón M. Employing phage display to study the mode of action of Bacillus thuringiensis Cry toxins. Pept. 2008;29:324–29. doi:10.1016/j.peptides.2007.07.035.
   Google Scholar
• Pardo-Lopez L, Gomez I, Munoz-Garay C, Jimenez-Juarez N, Soberon M, Bravo A. Structural and functional analysis of the pre-pore and membrane-inserted pore of Cry1Ab toxin. J Invertebr Pathol. 2006;92:172–77. doi:10.1016/j.jip.2006.02.008.
   Google Scholar
• Pena-Cardena A, Grande R, Sanchez J, Tabashnik BE, Bravo A, Soberon M, Gomez, I. The C-terminal protoxin region of Bacillus thuringiensis Cry1Ab toxin has a functional role in binding to GPI-anchored receptors in the insect midgut. J Biol Chem. 2018;293:20263–72. doi:10.1074/jbc.RA118.005101.
   Google Scholar
• Flannagan RD, Cao-Guo Y, Mathis JP, Meyer TE, Shi X, Siqueira HAA, Siegfried BD. Identification, cloning and expression of a Cry1Ab cadherin receptor from European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: crambidae). Insect Biochem Mol Biol. 2005;35:33–40. doi:10.1016/j.ibmb.2004.10.001.
   Google Scholar
• Gomez I, Arenas I, Benitez I, Miranda-Rios J, Becerril B, Grande R, Almagro JC, Bravo A, Soberón M. Specific epitopes of domains II and III of Bacillus thuringiensis Cry1Ab toxin involved in the sequential interaction with cadherin and aminopeptidase-N receptors in Manduca sexta. J Biol Chem. 2006;281:34032–39. doi:10.1074/jbc.M604721200.
   Google Scholar
• Noteborn HPJM, Bienenmann-Ploum ME, van Den Berg JHJ, Alink GM, Zolla L, Reynaerts A, et al. Safety assessment of bacillus thuringiensis insecticidal protein CRY1A(b) expressed in transgenic tomato. In: Engel K-H, Takeoka GR, Teranishi Reditors. Genetically modified foods: safety issues American Chemical Society. Washington (D.C.); 1995. p. 134–47.
   Google Scholar
• Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–402. doi:10.1093/nar/25.17.3389.
   Google Scholar
• Dantzig AH, Hoskins JA, Tabas LB, Bright S, Shepard RL, Jenkins IL, Duckworth DC, Sportsman JR, Mackensen D, Rosteck PR. Association of intestinal peptide transport with a protein related to the cadherin superfamily. Sci New York, N.Y. 1994;264:430–33. doi:10.1126/science.8153632.
   Google Scholar
• U.S. EPA. Biopesticides registration action document: cry1Ab and Cry1F Bacillus thuringiensis (Bt) corn plant-incorporated protectants. Washington (D.C.): U.S. Environmental Protection Agency; 2010.
   Google Scholar
• Liang R, Fei YJ, Prasad PD, Ramamoorthy S, Han H, Yang-Feng TL, Hediger MA, Ganapathy V, Leibach FH. Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J Biol Chem. 1995;270:6456–63. doi:10.1074/jbc.270.12.6456.
   Google Scholar
• Adibi SA. The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterol. 1997;113:332–40. doi:10.1016/s0016-5085(97)70112-4.
   Google Scholar
• Wang CY, Liu S, Xie XN, Tan ZR. Regulation profile of the intestinal peptide transporter 1 (PepT1). Drug Des Devel Ther. 2017;11:3511–17. doi:10.2147/dddt.s151725.
   Google Scholar
• Andreassen M, Bøhn T, Wikmark O.G, Bodin J, Traavik T, Løvik M, Nygaard UC. Investigations of immunogenic, allergenic and adjuvant properties of Cry1Ab protein after intragastric exposure in a food allergy model in mice. BMC Immunol. 2016;17:10. doi:10.1186/s12865-016-0148-x.
   Google Scholar
• Batista R, Nunes B, Carmo M, Cardoso C, Jose HS, de Almeida AB, Manique A, Bento L, Ricardo CP, Oliveira MM. Lack of detectable allergenicity of transgenic maize and soya samples. J Allergy Clin Immunol. 2005;116:403–10. doi:10.1016/j.jaci.2005.04.014.
   Google Scholar
• Betz FS, Hammond BG, Fuchs RL. Safety and advantages of Bacillus thuringiensis-protected plants to control insect pests. Regul Toxicol Pharmacol. 2000;32:156–73. doi:10.1006/rtph.2000.1426.
   Google Scholar
• McClintock JT, Schaffer CR, Sjoblad RD. A comparative review of the mammalian toxicity of Bacillus thuringiensis-based pesticides. Pestic Sci. 1995;45:95–105. doi:10.1002/ps.v45:2.
   Google Scholar
• ILSI. A review of the environmental safety of the Cry1Ab protein. Washington (D.C): ILSI Research Foundation; 2011.
   Google Scholar
• Rehout V, Kadlec J, Citek J, Hradecka E, Hanusova L, Hosnedlova B, Lád F. The influence of genetically modified Bt maize MON 810 in feed mixtures on slaughter, haematological and biochemical indices of broiler chickens. J Anim Feed Sci. 2009;18:490–98. doi:10.22358/jafs/66423/2009.
   Google Scholar
• Swiatkiewicz S, Swiatkiewicz M, Koreleski J, Kwiatek K. Nutritional efficiency of genetically-modified insect resistant corn (MON 810) and glyphosate-tolerant soybean meal (Roundup Ready) for broilers. J Vet Res. 2010;54:43–48.
   Google Scholar
• Taylor ML, Hartnell GF, Riordan SG, Nemeth MA, Karunanandaa K, George B, Astwood JD. Comparison of broiler performance when fed diets containing grain from YieldGard (MON810), YieldGard x Roundup Ready (GA21), nontransgenic control, or commercial corn. Poult Sci. 2003;82:823–30. doi:10.1093/ps/82.5.823.
   Google Scholar
• Donkin SS, Velez JC, Totten AK, Stanisiewski EP, Hartnell GF. 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. 2003;86:1780–88. doi:10.3168/jds.S0022-0302(03)73763-1.
   Google Scholar
• Steinke K, Guertler P, Paul V, Wiedemann S, Ettle T, Albrecht C, Meyer HHD, Spiekers H, Schwarz FJ. Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows. J Anim Physiol Anim Nutr (Berl). 2010;94:e185–e193. doi:10.1111/j.1439-0396.2010.01003.x.
   Google Scholar
• Buzoianu SG, Walsh MC, Rea MC, Cassidy JP, Ross RP, Gardiner GE, Lawlor PG. Effect of feeding genetically modified Bt MON810 maize to similar to 40-day-old pigs for 110 days on growth and health indicators. Anim. 2012;6:1609–1619. doi:10.1017/s1751731112000249.
   Google Scholar
• Buzoianu SG, Walsh MC, Rea MC, Cassidy JP, Ryan TP, Ross RP, Gardiner GE, Lawlor PG. Transgenerational effects of feeding genetically modified maize to nulliparous sows and offspring on offspring growth and health. J Anim Sci. 2013;91:318–30. doi:10.2527/jas.2012-5360.
   Google Scholar
• Sartowska KE, Korwin-Kossakowska A, Sender G. Genetically modified crops in a 10-generation feeding trial on Japanese quails–evaluation of its influence on birds’ performance and body composition. Poult Sci. 2015;94:2909–16. doi:10.3382/ps/pev271.
   Google Scholar
• Korwin-Kossakowska A, Sartowska K, Tomczyk G, Prusak B, Sender. G. Health status and potential uptake of transgenic DNA by Japanese quail fed diets containing genetically modified plant ingredients over 10 generations. Br Poult Sci. 2016;57:415–23. doi:10.1080/00071668.2016.1162281.
   Google Scholar
• Hammond BG, Dudek R, Lemen JK, Nemeth MA. Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn. Food ChemToxicol. 2006;44:1092–99. doi:10.1016/j.fct.2006.01.003.
   Google Scholar
• Ricroch AE, Boisron A, Kuntz M. Looking back at safety assessment of GM food/feed: an exhaustive review of 90-day animal feeding studies. Int J Biotechnol. 2014;13:230–56. doi:10.1504/IJBT.2014.068940.
   Google Scholar
• Van Eenennaam AL, Young AE. Prevalence and impacts of genetically engineered feedstuffs on livestock populations. J Anim Sci. 2014;92:4255–78. doi:10.2527/jas.2014-8124.
   Google Scholar
• Snell C, Bernheim A, Bergé J-B, Kuntz M, Pascal G, Paris A, Ricroch AE. Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: A literature review. Food ChemToxicol. 2012;50:1134–48. doi:10.1016/j.fct.2011.11.048.
   Google Scholar
• Tufarelli V, Selvaggi M, Dario C, Laudadio V. Genetically modified feeds in poultry diet: safety, performance, and product quality. Crit Rev Food Sci Nutr. 2015;55:562–69. doi:10.1080/10408398.2012.667017.
   Google Scholar
• OECD. Test no. 408: Repeated dose 90-day oral toxicity study in rodents. Paris (France): Organization of Economic Cooperation and Development; 1998.
   Google Scholar
• EFSA. Scientific Opinion: guidance on conducting repeated-dose 90-day oral toxicity study in rodents on whole food/feed. Parma (Italy): European Food Safety Authority; 2011. EFSA Journal 9(12): 2438.
   Google Scholar
• OECD. Test No. 452: Chronic toxicity studies. Paris (France): Organization of Economic Cooperation and Development; 2009.
   Google Scholar
• Coumoul X, Servien R, Juricek L, Kaddouch-Amar Y, Lippi Y, Berthelot L, Naylies C, Morvan M-L, Antignac J-P, Desdoits-Lethimonier C, et al. The GMO90+ project: absence of evidence for biologically meaningful effects of genetically modified maize based-diets on Wistar rats after 6-months feeding comparative trial. Toxicol Sci. 2019;168:315–38. doi:10.1093/toxsci/kfy298.
   Google Scholar
• Delaney B, Astwood JD, Cunny H, Conn RE, Herouet-Guicheney C, MacIntosh S, Meyer LS, Privalle L, Gao Y, Mattsson J, et al. Evaluation of protein safety in the context of agricultural biotechnology. Food ChemToxicol. 2008;46:S71–S97. doi:10.1016/j.fct.2008.01.045.
   Google Scholar