ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
"Biotechnologia Acta" V. 9, No 1, 2016
https://doi.org/10.15407/biotech9.01.007
Р. 7-25, Bibliography 93, English
Universal Decimal Classification: 604.6
PROBLEM OF GENETICALLY MODIFIED FOODS SAFETY: A TOXICOLOGIST’S VIEW
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kiyv
This study aimed to analyze the published literature regarding the problem of safety of consuming food products containing genetically modified organisms. Genetically modified food products are given a brief definition, purpose and methods of their production are described, and the pro- and contra- arguments for their consumption are presented. The discussion is mostly focused on results of evaluating possible toxicity of such foods and their safety for macroorganism using traditional methods of toxicological analysis. Test results for long-term toxic effects, namely allergenicity, carcinogenicity, reproductive toxicity, and the possibility of mutagenic effects of these food products on the human body and the intestinal microflora are discussed separately. These data are based on the current understanding of the laws of the penetration and functioning of foreign genetic material outside the body, its entry and the possibility of integration into the genome during intake of foods manufactured by genetic engineering. The basic principles of the toxicological and hygienic regulation of these food products are also considered.
An analysis of published experimental results allowed to draw a general conclusion about the absence of reliable scientific information indicating the presence of the toxic properties of genetically modified foods, and therefore of credible evidence of the dangers of consuming for humans and pets.
Key words: genetically modified foods, toxicity, safety.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2016
References
1. Biological Engineering. http://www.be.usu.edu. 2011.
2. Blum Ya., Borlaug N., Sugik L., Sivolap Yu. Modern biotechnology. Calling time. Kyiv: PA NOVA. 2002, 102 p. (In Russian).
3. Blum Ya., Novogilov O. The transgenic plant organisms: economic impact and risks to biota. International Symposium "Problems of biological safety of genetically modified organisms, new scientific approaches, regulation and public perception" (May 10–14 2006, Yalta). Visnyk Natsionalnoi Akademii nauk Ukrainy. 2006, N 9, P. 56–59. (In Ukrainian).
4. Glazko V. I. Genetically modificated organisms: from bacteria to human. Kyiv: КVITS. 2002, 210 p. (In Russian).
5. Rudishin S. D. Transgenic plants and problems of biosafety. Proceedings of scientific articles ІІІ Ukrainian meeting of ecologists with international specialists. Vinnytsia. 2011, V. 1, P. 250–253. (In Ukrainian). http://eco.com.ua/.
6. The Safety of Genetically Modified Foods Produced through Biotechnology. Oxford J. Med. Health Toxicol. Sci. 2003, V. 71, Issue 1, P. 2–8.
7. Modern food biotechnology, human health and development: an evidence-based study. Food safety department. World health organization. 2005.
8. Utembayeva N. T. Estimate of influence of genetically modificated food products on rat reproduction system and their posterity. Avtoreferat dis. kand. med. nauk. Moskva. 2011, 86 p. (In Russian).
9. Aksyuk I. N., Anisimova O. V., Kirpatovsky N. A., Kravchenko L. V., Kirpichnikov M. P., Mazo V. K., Onishchenko G. G., Rogov I. A., Semenov B. F., Skryabin K. G., Sorokin E., Tutelian V. A., Tyshko N. V., Chernysheva O. (eds. Tutelian V. A.). Genetically modified food: evaluation of safety and control. Moskva: Izd-vo RAMN. 2007, 440 p. (In Russian).
10. Sasson A. Biotechnology: Accomplishments and Hopes. Moskva: Mir. 1987, 412 p. (In Russian).
11. Glick B., Pasternak Ch. Molecular Biotechnology. Principles and Applications. Moskva: Mir. 2002, 590 p. (In Russian).
12. Biotechnology. Wikipedia. 2015.https://uk.wikipedia.org/wiki (In Russian).
13. Ellingsen J. E., Lyngstadaas S. P. Bio-Implant Interface: Improving Biomaterials and Tissue Reactions. CRC Press. 2003, 464 p.
14. Bronzino J. D. The Biomedical Engineering Handbook, Third Edition. CRC Press. 2006, 3800 p. ISBN 978-0-8493-2124-5. http://crcpress.com/product/isbn/9780849321245.
15. Wood A. Physiology, Biophysics and Biomedical Engineering. CRC Press Textbook. 2012, 782p.
16. Ermichine A. P., Podpisskih V. E., Voronkov V. E., Anoshenko B. Yu., Zarkov V. M. Biotechnology, Biosafety, Bioethics. Minsk: Tehnalogiya. 2005, 430 p. (In Russian).
17. Kozub N. A., Pilipenko L. A., Sozіnov І. O., Blume Y. B., Sozіnov O. O. Genetically modified plants and plant protection problems: achievements and assessment of potential risks. Tsytolohiia i henetyka. 2012, 46 (4), 73–78. (In Ukrainian).
18. Tutelyan V. A. (edit.). Genetically Modified Food Sources. Academic Press. 2013, 333 p. (In Russian).
19. Kurlandskiy B. A., Filov V. A. (ed.) General Toxicology. Moskva: Medicina. 2002, 608 p. (In Russian).
20. Global Status of Commercialized Biotech/GM Crops. 2014, N 49.
21. Ladics G. S., Bartholomaeus A., Bregitzer P., Doerrer N. G., Gray A., Holzhauser T., Jordan M., Keese P., Kok E., Macdonald P., Parrott W., Privalle L., Raybould A., Rhee S. Y., Rice E., Romeis J., Vaughn J., Wal J. M., Glenn K. Genetic basis and detection of unintended effects in genetically modified crop plants. Transg. Res. 2015, 24 (4), 587–603. doi: 10.1007/s11248-015-9867-7.
22. Fergal O’Gara. Biosafety research directed at more sustainable food production. A decade of EU-funded GMO research. European Commission. 2001–2010, P. 44–47; Kuiper H. A. Chapter 2. GMO and food safety. P. 128–133; Van der Vossen J. M. B. M. Safety evaluation of horizontal gene transfer from genetically modified organisms to the microflora of the food chain and human gut. Conclusions. P. 138–141.
23. Einspanier R., Klotz A., Kraft J., Aulrich K., Poser R., Schw?gele F., Jahreis G., Flachowsky G. The fate of forage plant DNA in farm animals: a collaborative case-study investigating cattle and chicken fed recombinant plant material. Europ. Food Res. Technol. 2001, 212 (1), 129–134. http://dx.doi.org/10.1007/s002170000248
24. Federation of Animal Science Societies. 2005. References pertaining to transgenic DNA and protein and livestock products (meat, milk, eggs). http://www.fass.org/references/Transgentic_DNA.htm.
25. Rizzi A., Raddadi N., Sorlini C., Nordgrd L., Nielsen K. M., Daffonchio D. Review. The stability and degradation of dietary DNA in the gastrointestinal tract of mammals: implications for horizontal gene transfer and the biosafety of GMOs. Crit. Rev. Food Sci. Nutr. 2012, 52 (2), 142–161. http://dx.doi.org/10.1080/10408398.2010.499480
26. Van Eenennaam A. Does genetically engineered DNA or protein get into milk, meat or eggs? Genet. Engineer. Animal Feed. 2014, V. 8, P. 41–48.
27. Beever, D. E., Kemp C. F. Safety issues associated with the DNA in animal feed derived from genetically modified crops. A review of scientific and regulatory procedures. Nutrition Abstracts Reviews, series B Livestock Feeds and Feeding. 2000, 70 (3), 175–182.
28. Mazza R., Soave M., Morlacchini M., Piva G., Marocco A. Assessing the transfer of genetically modified DNA from feed to animal tissues. Transg. Res. 2005, 14 (5), 775–784.
http://dx.doi.org/10.1007/s11248-005-0009-5
29. Spis?k S., Solymosi N., Ittz?s P., Bodor A., Kondor D., Vattay G., Bart?k B. K., Sipos F., Galamb O., Tulassay Z., Sz?ll?si Z., Rasmussen S., Sicheritz-Ponten T., Brunak S., Moln?r B., Csabai I. Complete Genes May Pass from Food to Human Blood. PLoS One. 2013, 8 (7), e69805. http://dx.doi.org/10.1371/journal.pone.0069805
30. Phipps R. H., Beever D. E., Humphries D. J. Detection of transgenic DNA in milk from cows receiving herbicide tolerant (CP4EPSPS) soyabean meal. Livesock Sci. 2002, V. 74, Issue 3, P. 269–273. doi: http://dx.doi.org/10.1016 /S0301-6226(02)00038-6.
31. Hohlweg U., Doerfler W. On the fate of plant or other foreign genes upon the uptake in food or after intramuscular injection in mice. Mol. Genet. Genomics. 2001, 265 (2), 225–233.
http://dx.doi.org/10.1007/s004380100450
32. Van Schaik W. The human gut resistome. Philos. Trans. R Soc. Lond. B Biol. Sci. 2015, 370 (1670), 20140087. doi: 10.1098/rstb.2014.0087.
http://dx.doi.org/10.1098/rstb.2014.0087
33. Ramesh S. V. Non-coding RNAs in crop genetic modification: considerations and predictable environmental risk assessments (ERA). Mol. Biotechnol. 2013, 55 (1), 87–100. doi: 10.1007/s12033-013-9648-6. http://dx.doi.org/10.1007/s12033-013-9648-6
34. Petrick J. S., Brower-Toland B., Jackson A. L., Kier L. D. Safety assessment of food and feed from biotechnology-derived crops employing RNA-mediated gene regulation to achieve desired traits: a scientific review. Regul. Toxicol. Pharmacol. 2013, 66 (2), 167–176. doi: 10.1016/j.yrtph.2013.03.008. http://dx.doi.org/10.1016/j.yrtph.2013.03.008
35. Hammond B. G., Jez J. M. Impact of food processing on the safety assessment for proteins introduced into biotechnology-derived soybean and corn crops. Food. Chem. Toxicol. 2011, 49 (4), 711–721. doi: 10.1016/j.fct.2010.12.009. Epub 2010 Dec 16.
36. Hammond B. G., Kough J., Herouet-Guicheney C., Jez J. M. Toxicological evaluation of proteins introduced into food crops. Crit. Rev. Toxicol. 2013, Suppl. 2, P. 25–42. doi: 10.3109/10408444.2013.842956.
37. Lutz B., Wiedemann S., Einspanier R., Mayer J., Albrecht C. Degradation of Protein from Genetically Modified Maize in the Bovine Gastrointestinal Tract. J. Agric. Food Chem. 2005, 53 (5), 1453–1456. doi: 10.1021/jf049222x.
38. Veriovka S. V. Peculiarities of the structure of the transgenic protein and the resulting risks. Bіotehnologіya. 2008, N 2, P. 13–23. (In Russian).
39. Ermakova I. V. Effect of soybean EPSPS CP4 gene on the physiological condition and the reproductive function of rats in the first two generations. Sovr. probl. nauki i obrazovaniya. 2009, N 5, P. 15–21. (In Russian).
40. Ewen S. W., Pusztai A. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet. 1999, 354 (9187), 1353–1354.
http://dx.doi.org/10.1016/S0140-6736(98)05860-7
41. Seralini G. E., Clair E., Mesnage R., Gress S., Defarge N., Malatesta M. Hennequin D., de Vendomois J. S. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food. Chem. Toxicol. 2012, 50 (11), 4221–4231.
http://dx.doi.org/10.1016/j.fct.2012.08.005
42. Reddit B. C. Study linking GM maize to rat tumours is retracted. Nature. 2013, V. 28, P. 14268. doi:10.1038/nature.2013.
43. Ozkok G. A. Genetically Modified Foods and the Probable Risks on Human Health. Int. J. Nutr. Food Sci. 2015, 4 (3), 356–363. doi: 10.11648/j.ijnfs. 20150403.23.
44. Devos Y., Sanvido O., Tait J., Raybould A. Towards a more open debate about values in decision-making on agricultural biotechnology. Transg. Res. 2014, 23 (6), 933–943.
http://dx.doi.org/10.1007/s11248-013-9754-z
45. Ozdogan S., Ekmen Z. I. What is genetic engineering? http://www.yunus. hacettepe.edu.tr/aacorner/GEN/02/genetik.htm/2002. Access to Date: 20. 12. 2002.
46. Tapp H., Stotzky G. Persistence of the insecticidal toxins from Bacillus thurigiensissusp, kurstaki in soil. Soil Biol. Biochem. 1998, V. 30, P. 471–476.
http://dx.doi.org/10.1016/S0038-0717(97)00148-X
47. Kili? A., Akay M. T. A three generation study with genetically modified Bt corn in rats: Biochemical and histopathological investigation. Food. Chem. Toxicol. 2008, 46 (3), 1164–1170. doi: 10.1016/j.fct.2007.11.016.
48. Koch M. S., Ward J. M., Levine S. L., Baum J. A., Vicini J. L., Hammond B. G. The food and environmental safety of Bt-crops. Front. Plant. Sci. 2015, V. 6, P. 283. doi: 10.3389/fpls.2015.00283.
49. Domingo J. L. Toxicity studies of genetically modified plants: a review of the published literature. Crit. Rev. Food Sci. Nutr. 2007, 47 (8), 721–733. doi: 10.1080/10408390601177670.
50. Domingo J. L., Gin? B. J. A literature review on the safety assessment of genetically modified plants. Environ Int. 2011, 37 (4), 734–742. doi: 10.1016/j.envint.2011.01.003.
51. Bronzino J. D. The Biomedical Engineering Handbook, Third Edition. CRC Press. 2006, 3800 p. ISBN 978-0-8493-2124-5. http:// crcpress.com/ product/isbn/ 9780849321245.
52. Wood A. Physiology, Biophysics, and Biomedical Engineering. CRC Press Textbook. 2012, 782p.
53. Nicolia A., Manzo A., Veronesi F., Rosellini D. An overview of the last 10 years of genetically engineered crop safety research. Crit. Rev. Biotechnol. 2014, 34 (1), 77–88. doi: 10.3109/07388551.2013.823595.
54. Zhu Y., He X., Luo Y., Zou S., Zhou X., Huang K., Xu W. A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in Sprague-Dawley rats. Food. Chem. Toxicol. 2013, 51 (2), 280–287. doi: 10.1016/j.fct.2012. 9.008.
55. 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 (1), Suppl. 2, P. 1–24. doi: 10.3109/10408444.2013.842955.
56. Alink G., Barlow S., Cockburn A., Flachowsky G. Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials. Food. Chem. Toxicol. 2008, Suppl. 1, P. 2–70. doi: 10.1016/j.fct.2008. 02.008.
57. Kuiper H. A., Kleter G. A., H. P Noteborn. J. M., Kok E. J. Assessment of the food safety issues related to genetically modified foods. Plant J. 2001, V. 27, Is. 6, P. 503–528.
58. Tzotzos G. T., Head G. P., Hull R. Genetically modified plants. Assessing safety and managing risk. Acad. Press. 2009, 240 p.
59. U. S. General Accounting Office (2002). Genetically Modified Foods: Experts view regimen of safety tests as adequate, but FDA’s evaluation process could be enhanced. Document GAO-02–566.
60. Chemical and Biological Safety. 2004, 3–4 (15–16), 3–7.
61. Doerfler W. (2000). Foreign DNA in Mammalian Systems. Wiley-VCH, Weinheim.
62. Herman E. M., Helm R. M., Jung R., Kinney A. J. Genetic Modification Removes an Immunodominant Allergen from Soybean. Plant Physiol. 2003, V. 132, P. 36–43.
http://dx.doi.org/10.1104/pp.103.021865
63. Sunilkumar G., Campbell L. M., Puckhaber L., Rathore K. S. Engineering cottonseed for use in `12human nutrition by tissue-specific reduction of toxic gossypol. Proc. Natl. Acad. Sci. USA. 2006, 103 (48), 18054–18059. doi:10.1073/pnas.0605389103.
64. Taylor S. L., Hefle S. L. Will genetically modified foods be allergenic? J. Allergy Clin. Immunol. 2001, 107 (5), 765–771. http://dx.doi.org/10.1067/mai.2001.114241
65. Helm R. M. Food biotechnology: is this good or bad? Implications to allergic diseases. Ann. Allergy Asthma Immunol. 2003, 90 (6), Suppl 3, 90–98.
http://dx.doi.org/10.1016/S1081-1206(10)61668-7
66. NRC (2000). Genetically Modified Pest-Protected Plants: Science and Regulation. Committee on Genetically Modified Pest-Protected Plants, National Research Council. National Academy Press, Washington, DC.
67. Adel-Patient K., Guimaraes V. D., Paris A., Drumare M. F., Ah-Leung S., Lamourette P., Nevers M.C., Canlet C., Molina J., Bernard H., Cr?minon C., Wal J. M. Immunological and metabolomic impacts of administration of Cry1Ab protein and MON 810 maize in mouse. PLoS One. 2011, 6 (1), e16346. doi: 10.1371/journal.pone.0016346.
68. Reiner D., Lee R. Y., Dekan G., Epstein M. M. No adjuvant effect of Bacillus thuringiensis-maize on allergic responses in mice. PLoS One. 2014, 9 (8), e103979. doi: 10.1371/journal.pone.0103979. eCollection 2014.
69. Andreassen M., B?hn T., Wikmark O. G., van den Berg J., L?vik M., Traavik T., Nygaard U. C. Cry1Ab protein from Bacillus thuringiensis and MON810 cry1Ab-transgenic maize exerts no adjuvant effect after airway exposure. Scand. J. Immunol. 2015, 81 (3), 192–200. doi: 10.1111/sji.12269.
70. Tyshko N. V., Zhminchenko V. M., Pashorina V. A., Selyaskin K. E., Saprykin V. P., Utembayeva N. T., Tutelian V. A. Assessment of GM plant on development of the offspring of rats in three generations. Voprosy pitaniya. 2011, 80 (1), 14–28. (In Russian).
71. Batista R., Saibo N., Lourenco T., Oliveira M. M. Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion. Proc. Natl. Acad. Sci. USA. 2008, 4 (105), 3640–3645. doi: 10.1073/ pnas.0707881105.
72. Gershenzon S. M. Mutagenic effects of DNA and the problem of directed mutations. Genetika. 1966, N 5, P. 3–13. (In Russian).
73. Gershenzon S. M. Mutagenic action of some biopolymers in Drosophila. Jap. J. Genet. 1969, V. 44, Suppl. 1, P. 114–119.
74. Gershenzon S. M., Alexandrov Yu. N. Mutagenic effects of natural and synthetic nucleotides and the problem of directed mutations. Zn. obshchey biologii. 1982, 43 (6), 747–763. (In Russian).
75. Piven O. A., Lukash L. L. Effect of exogenous proteins in the mutation process. Citologiya i genetika. 2011, 45 (1), 68–79. (In Russian).
76. Val Giddings L. A National Framework for the Review and Labeling of Biotechnology in Food. U. S. House of Representatives Energy & Commerce Subcommittee on Health. 18 June 2015.
77. Kunakh V. A. Mobile genetic elements and plasticity of the genome of plants. Kyiv: Logos. 2013, 299 p. (In Ukrainian).
78. Levitsky E. L. Mechanisms and age characteristics of the replication of nuclear DNA. Ukr. biokhim. zh. 1984, 56 (4), 460–472. (In Russian).
79. Levitsky E. L. DNA polymerase activity of adult and old rats livers. Ukr. biokhim. zh. 1986, 58 (3), 72–74. (In Russian).
80. Ichas M. Genetic code. Moskva: Mir. 1971, 351 p. (In Russian).
81. Ratner V. A. The genetic code as the system. Soros obrazovatelniy zh. 2000, 6 (3), 17–22. (In Russian).
82. Hesin R. B. Variability of the genome. Moskva: Nauka. 1984, 482 p. (In Russian).
83. GMOs vs. mutagenesis vs. conventional breeding: Which wins? December 3, 2013. FAO publication: Induced Plant Mutations in the Genomics Era, Food and Agriculture Organization of the United Nations. http://www.geneticliteracyproject.org/2013/12/03/gmos-vs-mutagenesis-vs-conventional-breeding-which-wins/
84. Knudsen I., Poulsen M. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event. Regul. Toxicol. Pharmacol. 2007, 49 (1), 53–62.
http://dx.doi.org/10.1016/j.yrtph.2007.07.003
85. Royal Society (2002). Genetically Modified Plants for Food Use and Human Health – An Update. Policy Document 4/02. The Royal Society, London.
86. FDA/CFSAN/OFAS. 2004 (update). Redbook 2000, Toxicological principles for the safety assessment of food ingredients. Food and Drug Admin/Center for Food Safety and Applied Nutrition. Office of Food Additive Safety, Washington, DC.
87. Kuriakov I. A., Gayduchenko Yu. S., Ischak E. P. Genetically modified foods are harmful or helpful? Sibirskiy torgovo-ekonomicheskiy zh. 2012, N 16. http://cyberleninka.ru/journal/n/sibirskiy-torgovo-ekonomicheskiy-zhurnal. (In Russian).
88. Herman R. A., Ekmay R. Do whole-food animal feeding studies have any value in the safety assessment of GM crops? Regul. Toxicol. Pharmacol. 2014, 68 (1), 171–174.
doi: 10.1016/j.yrtph.2013.07.003. Epub 2013 Jul 11.
http://dx.doi.org/10.1016/j.yrtph.2013.07.003
89. Nielsen K. M. Biosafety Data as Confidential Business Information. PLoS Biol. 2013, 11 (3), e1001499. doi: 10.1371/journal.pbio.1001499. PMCID: PMC3589341.
http://dx.doi.org/10.1371/journal.pbio.1001499
90. Dona A., Arvanitoyannis I. S. Health Risks of Genetically Modified Foods. Crit. Rev. Food Sci. Nutrition. 2009, 49 (2), 164–175. doi:10.1080/ 10408390701855993.
91. Bonnefoi M. S., Belanger S. E., Devlin D. J., Doerrer N. G. Human and environmental health challenges for the next decade (2010–2020). Crit. Rev. Toxicol. 2010, 40 (10), 893–911. http://dx.doi.org/10.3109/10408444.2010.506640
92. Doerfler W. Foreign DNA in Mammalian Systems. Wiley-VCH, Weinheim. Chapter 11. Uptake of foreign DNA from the environment: the gastrointestinal tract and the placenta as portals of entry. 2000, P. 147–158.
93. Val Giddings L. A National Framework for the Review and Labeling of Biotechnology in Food. U. S. House of Representatives Energy & Commerce Subcommittee on Health. 2015, 1599 p.