Safety Studies of Metal Oxide Nanoparticles Used in Food Industry

  • Verónica Freyre-Fonseca
  • Norma L. Delgado-Buenrostro
  • Yolanda I. Chirino
  • Gustavo Fidel Gutiérrez-LópezEmail author
Part of the Food Engineering Series book series (FSES)


Nanotechnology has led us to the exponential use of nanoparticles (NP) grouped into four types: (1) carbon and fullerenes, (2) base metals, (3) dendrimers, and (4) metal composites. All of them are integrated in eight industrial sectors: (a) automotive, (b) aerospace, (c) electronic and computing, (d) energy and environment, (e) food and agriculture, (f) construction, (g) medicine and pharmacy, and (h) personal care. NP effects on different systems depend on the type, properties, and location of the system and appear in the form of aggregates or conglomerates of different sizes so that they may have a number of different effects when in contact with a human being. Therefore, it is necessary to evaluate and regulate on the effects that products containing NP have on human health. This is focused on the usage and the security of metal oxide NP in contact with food-related products either intentionally or accidentally.


Nanoparticles Metal oxides Nanoparticle characterization Toxicity Regulations Food additives Human health 


  1. Allouni ZE, Cimpan MR, Høl PJ, Skodvin T, Gjerdet NR (2009) Agglomeration and sedimentation of TiO2 nanoparticles in cell culture medium. Colloid Surface B 68(1):83–87CrossRefGoogle Scholar
  2. Al-Rawi M, Diabaté S, Weiss C (2011) Uptake and intracellular localization of submicron and nano-sized SiO2 particles in HELA. Arch Toxicol 85(7):813–826CrossRefGoogle Scholar
  3. Arnall AH (2003) Future technologies, today’s choices: nanotechnology, artificial intelligence and robotics; a technical, political and institutional map of emerging technologies. Greenpeace Environmental Trust, LondonGoogle Scholar
  4. Bao YX, Cao Q, Yang Y, Mao R, Xiao L, Zhang H, Zhao HR, Wen H (2013) Expression and prognostic significance of Golgi glycoprotein 73 (GP73) with epithelial-mesenchymal transition (EMT) related molecules in hepatocellular carcinoma (HCC). Diagn Pathol 8:197CrossRefGoogle Scholar
  5. Baun A, Sorensen SN, Rasmussen RF, Hartmann NB, Koch CB (2008) Toxicity and bioaccumulation of xenobiotic organic compounds in the presence of aqueous suspensions of aggregates of nano-C(60). Aquat Toxicol 86:379–387CrossRefGoogle Scholar
  6. Brausch KA, Anderson TA, Smith PN, Maul JD (2010) Effects of functiolalized fullerenes on bifenthrin and tribufos toxicity to Daphia magna: survival, reproduction and growth rate. Environ Toxicol Chem 29:2600–2606CrossRefGoogle Scholar
  7. Bergeson LL, Hester T (2008) Nanotechnology deskbook. Environmental Law Institute, Eli Press, Washington, DCGoogle Scholar
  8. Chau CF, Wu SH, Yen GC (2007) The development of regulations for food nanotechnology. Trends Food Sci Technol 18:269–280CrossRefGoogle Scholar
  9. Chaudhry Q, Aitken R, Scotter R, Blackburn J, Ross B, Boxall A, Castle L, Watkins R (2008) Applications and implications of nanotechnologies for the food sector. Food Addit Contam 25(3):241–258CrossRefGoogle Scholar
  10. Chen M, Von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305:51–62CrossRefGoogle Scholar
  11. Cheng X, Kan AT, Tomson MB (2004) Naphthalene adsorption and desorption from aqueous C60 fullerene. J Chem Eng Data 49:675–683CrossRefGoogle Scholar
  12. Cheng S, Yan D, Chen JT, Zhuo RF, Feng JJ, Li HJ, Feng HT, Yan PX (2009) Soft-template synthesis and characterization of ZnO2 and ZnO hollow spheres. J Phys Chem C 113:13630–13635CrossRefGoogle Scholar
  13. Cho W-S, Duffin R, Bradley M, Megson IL, MacNee W, Howie1 SEM, Donaldson K (2012) NiO and Co3O4 nanoparticles induce lung DTH-like responses and alveolar lipoproteinosis. Eur Respir J 39:546–557CrossRefGoogle Scholar
  14. Dasari TP, Hwang HM (2013) Effect of humic acids and sunlight on the cytotoxicity of engineered zinc oxide and titanium dioxide nanoparticles to a river bacterial assemblage. J Environ Sci 25(9):1925–1935CrossRefGoogle Scholar
  15. De Bie E Doyen P (1962) Cobalt oxides and salts. Cobalt 15:3–13Google Scholar
  16. EFSA (European Food Safety Authority) (2005) Opinion of the Scientific Panel of food additives, flavourings, processing aids and materials in contact with food on a request from the commission related to 2 Isopropyl thioxanthone (ITX) and 2 ethylhexyl-4-dimethylaminobenzoate (EHDAB) in food contact materials. The EFSA J 293:1–15Google Scholar
  17. EFSA (2008) Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on safety of aluminium from dietary intake. EFSA J 754:1–34Google Scholar
  18. EFSA (2009) Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food. Calcium silicate and silicon dioxide/silicic acid gel added for nutritional purposes to food supplements. EFSA J 1132:1–24Google Scholar
  19. EFSA (2011) Panel on food contact materials, enzymes, flavourings and processing aids (CEF). Scientific opinion on the safety evaluation of the substance, silver zeolite A (silver zinc sodium ammonium alumino silicate), silver content 2–5 %, for use in food contact materials. EFSA J 9(2):1999Google Scholar
  20. EFSA (2012) Scientific Opinion on the use of animal-based measures to assess welfare in pigs. EFSA J 10(1):2512 [85 pp.]Google Scholar
  21. Escuderos ME, García M, Jiménez A, Horrillo MC (2012) Edible and non-edible olive oils discrimination by the application of a sensory olfactory system based on tin dioxide sensors. Food Chem 136(3–4):1154–1159Google Scholar
  22. Freyre-Fonseca V, Delgado-Buenrostro NL, Gutiérrez-Cirlos EB, Calderón-Torres CM, Cabellos-Avelar T, Sánchez-Pérez Y, Pinzón E, Torres I, Molina-Jijón E, Zazueta C, Pedraza-Chaverri J, García-Cuellar CM, Chirino YI (2011) Titanium dioxide nanoparticles impair lung mitochondrial function. Toxicol Lett 202(2):111–119CrossRefGoogle Scholar
  23. Gambardella C, Gallus L, Gatti AM, Faimali M, Carbone S, Antisari LV, Falugi C, Ferrando S (2014) Toxicity and transfer of metal oxide nanoparticles from microalgae to sea urchin larvae. Chem Ecol 30(4):308–316CrossRefGoogle Scholar
  24. Gentile F, Ferrari M, Decuzzi P (2008) The transport of nanoparticles in blood vessels: the effect of vessel permeability and blood rheology. Ann Biomed Eng 36(2):254–261CrossRefGoogle Scholar
  25. Ginley DS, Bright C (2000) Transparent conducting oxides. MRS Bull 25(15):15–18CrossRefGoogle Scholar
  26. Gordon SC, Butala JH, Carter JM, Elder A, Gordon T, Gray G, Sayre PG, Schulte PA, Tsai CS, West J (2014) Workshop report: strategies for setting occupational exposure limits for engineered nanomaterials. Regul Toxicol Pharm 68:305–311CrossRefGoogle Scholar
  27. Gopinath P, Gogoi SK, Sanpuic P, Paul A, Chattopadhyay A, Ghosh SS (2010) Signaling gene cascade in silver nanoparticle induced apoptosis. Colloid Surface B 77:240–245CrossRefGoogle Scholar
  28. Gui S, Zhang Z, Zheng L, Cui Y, Liu X, Li N, Sang X, Sun Q, Gao G, Cheng Z, Cheng J, Wang L, Tang M, Hong F (2011) Molecular mechanism of kidney injury of mice caused by exposure to titanium dioxide nanoparticles. J Hazard Mater 195(15):365–370CrossRefGoogle Scholar
  29. Gramowski A, Flossdorf J, Bhattacharya K, Jonas L, Lantow M, Rahman Q, Schiffmann D, Weiss DG, Dopp E (2010) Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips. Environ Health Persp 118(10):1363–1369CrossRefGoogle Scholar
  30. Hanini A, Schmitt A, Kacem K, Chau F, Ammar S, Gavard J (2011) Evaluation of iron oxide nanoparticle biocompatibility. Int J Nanomed 6:787–794Google Scholar
  31. Hsin YH, Chen CF, Huang S, Shih TS, Lai PS, Chueh PJ (2008) The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 179:130–139CrossRefGoogle Scholar
  32. Hyun-Joo C, Sung-Wook C, Sanghoon K, Hyang-Sook C (2011) Effect of particle size of zinc oxides on cytotoxicity and cell permeability in Caco-2 cells. Int J Food Sci Nutr 16:174–178CrossRefGoogle Scholar
  33. Izak-Nau E, Voetz M, Eiden S, Duschl A, Puntes VF (2013) Altered characteristics of silica nanoparticles in bovine and human serum: the importance of nanomaterial characterization prior to its toxicological evaluation. Part Fibre Toxicol 10(1):56CrossRefGoogle Scholar
  34. Jing S, Shaochuang W, Dong Z, Hun FH, Lei W, Hui L (2011) Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells. Cell Biol Toxicol 27:333–342CrossRefGoogle Scholar
  35. Jung T, Kamm W, Breitenbach A, Kaiserling E, Xiao JX, Kissel T (2000) Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? Eur J Pharm Biopharm 50:147–160CrossRefGoogle Scholar
  36. Kalpana Sastry R Anshul S Rao NH (2012) Nanotechnology in food processing sector-An assessment of emerging trends. J Food Sci Technol 50(5):831–841CrossRefGoogle Scholar
  37. Li CH, Shen CC, Cheng YW, Huang SH, Wu CC, Kao CC, Liao JW, Kang JJ (2011) Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice. Nanotoxicology 6(7):746–756CrossRefGoogle Scholar
  38. Li M, Jiang Y, Ding R, Song D, Yu H, Chen Z (2013) Hydrothermal synthesis of anatase TiO2 nanoflowers on a nanobelt framework for photocatalytic applications, J Electr Mater 42(6):1290–1296CrossRefGoogle Scholar
  39. Linsinger TPJ, Chaudhry Q, Dehalu V, Delahaut P, Dudkiewicz A, Grombe R, Von der Kammer F, Larsen EH, Legros S, Loeschner K, Peters R, Ramsch R, Roebben G, Tiede K, Weigel S (2013) Validation of methods for the detection and quantification of engineered nanoparticles in food. Food Chem 138:1959–1966CrossRefGoogle Scholar
  40. Lomer MC, Hutchinson C, Volkert S, Greenfield SM, Catterall A, Thompson RP, Powell JJ (2004) Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn’s disease. Br J Nutr 92:947–955Google Scholar
  41. McCracken C, Zane A, Knight DA, Dutta PK, Waldman WJ (2013) Minimal intestinal ephitelial cell toxicity in response to short and long term food relevant inorganic nanoparticle exposure. Chem Res Toxicol 26(10):1514–1525CrossRefGoogle Scholar
  42. Miura N, Shinohara Y (2009) Cytotoxic effect and apoptosis induction by silver nanoparticles in HeLa cells. Biochem Biophys Res Commun 390:733–737CrossRefGoogle Scholar
  43. Morris VJ (2011) Emerging roles of engineered nanomaterials in the food industry. Trends Biotechnol 29:509–516CrossRefGoogle Scholar
  44. Moulin JJ, Wild P, Mur JM, Fournier-Betz M, Mercier-Gallay M (1993) A mortality study of cobalt production workers: An extension of the follow-up. Am J Ind Med 23:281–288CrossRefGoogle Scholar
  45. Mu Q, David CA, Galceran J, Rey-Castro C, Krzemiński L, Wallace R, Bamiduro F, Milne SJ, Hondow N, Brydson RM, Vizcay-Barrena G, Routledge M, Jeuken LJ, Brown AP (2014) A systematic investigation of the physico-chemical factors that contribute to the toxicity of ZnO nanoparticles. Chem Res Toxicol 27:558–567CrossRefGoogle Scholar
  46. NIOSH (National Institute for Occupational Safety and Health) Department of health and human services. Centers for disease control and prevention. Occupational exposure to titanium dioxide. Bulletin 63:1–119CrossRefGoogle Scholar
  47. Naura AS, Sharma R (2009) Toxic effects of hexaammine cobalt(III) chloride on liver and kidney in mice: Implication of oxidative stress. Drug Chem Toxicol 32(3):293–299CrossRefGoogle Scholar
  48. Omura K, Veluchamy P, Tsuji M, Nishio T, Murojono D (1999) A SnO2 : F thin films from dimethyltin dichloride. J Electrochem Soc 146:2113–2116CrossRefGoogle Scholar
  49. Onuma K, Sato Y, Ogawara S, Shirasawa N, Kobayashi M, Yoshitake J, Yoshimura T, Iigo M, Fuji J, Okada F 2009. Nano-scaled particles of titanium dioxide convert bening mouse fibrosarcoma cells into aggressive tumor cells. Am J Pathol 175(5):2171–2183CrossRefGoogle Scholar
  50. Papis E, Rossi F, Raspanti M, Dalle-Donne I, Colombo G, Milzani A, Bernardini G, Gornati R (2009) Engineered cobalt oxide nanoparticles readily enter cells. Toxicol Lett 189:253–259CrossRefGoogle Scholar
  51. Paustenbach D, Tvermoes B, Unice K, Finley B, Kerger B (2013) A review of the health hazards posed by cobalt: potential importance of free divalent cobalt ion equilibrium in understanding systemic toxicity in humans. Crit Rev Toxicol 43:316–362CrossRefGoogle Scholar
  52. Polak N, Read DS, Jurkschat K, Matzke M, Kelly FJ, Spurgeon DJ, Stürzenbaum SR (2014) Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans. Compar Biochem Physiol C 160:75–85Google Scholar
  53. Rocco MC (2005) Environmentally responsible development of nanotechnology. Environ Sci Technol 39:106A–112ACrossRefGoogle Scholar
  54. Römer I, White TA, Baalousha M, Chipman K, Viant MR, Lead JR (2011) Aggregation and dispersion of silver nanoparticles in exposure media for aquatic toxicity tests. J Chromatogr A 1218:4226–4233CrossRefGoogle Scholar
  55. Sahu D, Kannan GM, Vijayaraghavan R (2014) Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes. J Toxicol Environ Health A 77(4):177–191CrossRefGoogle Scholar
  56. Sanguansri P, Augustin MA (2006) Nanoscale materials development: a food industry perspective. Trends Food Sci Technol 17:547–556CrossRefGoogle Scholar
  57. Sekar D, Falcioni ML, Barucca G, Falcioni G (2011) DNA damage and repair following in vitro exposure to two different forms of titanium dioxide nanoparticles on trout erythrocyte. Environ Toxicol 117–127CrossRefGoogle Scholar
  58. Seok SH, Cho WS, Park JS, Na Y, Jang A, Kim H, Cho Y, Kim T, You JR, Ko S, Kang BC, Lee JK, Jeong J, Che JH (2013) Rat pancreatitis produced by 13 week administration of zinc oxide nanoparticles: Biopersistence of nanoparticles and possible solutions. J Appl Toxicol 33(10):1089–1096CrossRefGoogle Scholar
  59. Shannahan JH, Lai X, Ke, PC, Podila R, Brown JM, Witzmann FA (2013) Silver nanoparticle protein corona composition in cell culture media. Plos One 8(9) e74001Google Scholar
  60. Sharma V, Singh P, Pandey AK, Dhawan A (2012) Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles. Mutat Res 745(1–2):84–91CrossRefGoogle Scholar
  61. Sompol P, Ittarat W, Tangpong J, Chen Y, Doubinskaia I, Batinic-Haberle I, Abdul HM, Butterfield DA, St Clair DK (2008) A neuronal model of Alzheimer’s disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Neuroscience 153(1):120–130CrossRefGoogle Scholar
  62. Smith MP, Wayne A (2007) Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease. Neuroscience 144:1057–1066CrossRefGoogle Scholar
  63. Stone V, Nowack B, Baun A, Van den Brink N, Kammer F, Dusinska M, Handy R, Hankin S, Hassellöv M, Joner E, Fernandes TF (2010) Nanomaterials for environmental studies: classification, reference material issues, and strategies for physico-chemical characterisation. Sci Total Environ 408:1745–1754CrossRefGoogle Scholar
  64. Syama S, Reshma SC, Sreekanth PJ, Varma HK, Mohanan PV (2013) Effect of Zinc Oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver. Toxicol Environ Chem 95(3):495–503CrossRefGoogle Scholar
  65. Tadeev AV, Delabouglise G, Labeau M (1998) Influence of Pd and Pt additives on the microstructural and electrical properties of SnO2-based sensors. Mater Sci Eng B 57(1):76–83CrossRefGoogle Scholar
  66. Tanaka A, Hirata M, Homma T, Kiyohara Y (2010) Chronic pulmonary toxicity study of indium-tin oxide and indium oxide following intratracheal instillations into the lungs of hamsters. J Occup Health 52:14–22CrossRefGoogle Scholar
  67. Tang J, Xiong L, Wang S, Wang S, Wang J, Liu L, Li J, Yuan F, Xi T (2009) Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol 9(8):4924–4932CrossRefGoogle Scholar
  68. Tiede K, Boxall BA, Tear SP, Lewis J, David H, Hassellov M (2008) Detection and characterization of engineered nanoparticles in food and the environment. Food Addit Contam A 25(7):795–821CrossRefGoogle Scholar
  69. Tuchsen F, Andersen O, Olsen J (1996) Referral bias among health workers in studies using hospitalization as a proxy measure of the underlying incidence rate. J Clin Epidemiol 49:791–794CrossRefGoogle Scholar
  70. United States Government Accountability Office (2010) Nanomaterials are widely used in commerce, but EPA faces challenges in regulating risk. GAO-10-549Google Scholar
  71. Vilhena MS, Costa ML, Berredo JF (2013) Accumulation and transfer of Hg, As, Se, and other metals in the sediment-vegetation-crab-human food chain in the coastal zone of the northern Brazilian state of Pará (Amazonia). Environ Geochem Health 35(4):477–494CrossRefGoogle Scholar
  72. Wang J, Gerlach JD, Savage N, Cobb GP (2013) Necessity and approach to integred nanomaterial legislation and governance. Sci Total Environ 442:56–62CrossRefGoogle Scholar
  73. Weir A, Westerhoff P, Fabricious L, Von Goertz N (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46(4):2242–2250CrossRefGoogle Scholar
  74. Weiss J, Takhistov P, McClements J (2006) Functional materials in food nanotechnology. J Food Sci 71:R107–R116CrossRefGoogle Scholar
  75. World Health Organization International Agency for Research on Cancer (2006) Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. IARC Monog Eval Carc 86:68–73Google Scholar
  76. World Health Organization International Agency for Research on Cancer (2010) Carbon black, titanium dioxide, and talc. IARC Monog Eval Carc 93:1–452Google Scholar
  77. Ye Y, Liu J, Xu J, Sun L, Chen M, Lan M (2010) SiO2 induces apoptosis vía activation of p53 and Bax mediated by oxidative stress in human hepatic cell line. Toxicol In Vitro 24(3):751–758CrossRefGoogle Scholar
  78. Zelikoff J, Willis D, Degheidy H, Zhang Q, Umbreit T, Goering P (2013) Immune cell profiles in response to silver nanoparticles associated with medical devices (P3357). J Immunol 190:202.1Google Scholar
  79. Zhaoxia J, Xue J, Saji G, Tian X, Huan M, Xiang W, Suárez E, Zhang H, Hoek EM, Godwin H, Nel A, Zink JI (2010) Dispersion and stability optimization of TiO2 nanoparticles in cell culture media. Environ Sci Technol 44:7309–7314CrossRefGoogle Scholar

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© Springer Science + Business Media New York 2015

Authors and Affiliations

  • Verónica Freyre-Fonseca
    • 1
    • 2
  • Norma L. Delgado-Buenrostro
    • 2
  • Yolanda I. Chirino
    • 2
  • Gustavo Fidel Gutiérrez-López
    • 1
    Email author
  1. 1.Departamento de Graduados e Investigación en Alimentos. Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMéxicoMéxico
  2. 2.Laboratorio 10, Unidad de Biomedicina, Facultad de Estudios Superiores-IztacalaUniversidad Nacional Autónoma de MéxicoLos Reyes IztacalaMéxico

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