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Bioactivity of Engineered Nanoparticles pp 259–319Cite as

Experimental Research into Metallic and Metal Oxide Nanoparticle Toxicity In Vivo

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Part of the book series: Nanomedicine and Nanotoxicology ((NANOMED))

Abstract

We studied purposefully produced silver, gold, iron oxide, copper oxide, nickel oxide, manganese oxide, lead oxide, and zinc oxide nanoparticles using two experimental models: (a) a single intratracheal (IT) instillation in low doses 24 h before the bronchoalveolar lavage to obtain a fluid for cytological and biochemical assessment; (b) repeated intraperitoneal (IP) injections during 6–7 weeks in non-lethal doses to assess the thus induced subchronic intoxication by a lot of functional and morphological indices and by the distribution and elimination of respective nanoparticles. Along with assessing the toxicity of these metallic nanoparticles (Me-NPs) acting separately, we also studied the same effects of some practically relevant Me-NP combinations. Besides, we carried out a 10-month inhalation experiment with an iron oxide (Fe2O3) nano-aerosol. We demonstrated that Me-NPs are much more noxious as compared with their fine micrometric counterparts although physiological mechanisms of their elimination from lungs proved highly active. At the same time, the in situ cytotoxicity, organ-systemic toxicity and in vivo genotoxicity of Me-NPs having a given geometry strongly depends on their chemical nature as well as on the specific mechanisms of action characteristic of a given metal. Even though being water-insoluble, Me-NPs are significantly solubilized in some biological milieus, and this process plays an important part in their biokinetics in vivo. In toto, Me-NPs are one of the most dangerous occupational and environmental hazards due to their cytotoxicity and genotoxicity, and therefore standards or recommended values of presumably safe Me-NP concentrations in the workplace and ambient air should be significantly lower as compared with those established for their micrometric counterparts. At the same time, the toxicity and even genotoxicity of Me-NPs can be significantly attenuated by background or preliminary administration of adequately composed combinations of some bioactive agents in innocuous doses.

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Notes

  1. 1.

    In this chapter, we use this term collectively for particles of elemental metals and of their oxides not only because many of the important mechanisms of their toxicity are similar but also taking into consideration that “most metal nanoparticles (NPs), except noble metal NPs, rapidly form a thin surface oxide in ambient conditions” [1].

  2. 2.

    The most probable explanation of this fact is that particles which are more cytotoxic for AMs due to a smaller diameter (as in the abovementioned case of Fe3O4—see Fig. 11.5) or to a specific chemical nature (as in case of nanoAg vs. nanoAu) produce a higher mass of the macrophage breakdown products which as we demonstrated long ago [113] stimulate dose-dependently the macrophageal phagocytosis. Let us remind that the more avid is the latter, the higher surface concentration of plasma membrane invaginations (i.e., of “pits”).

References

  1. Hedberg YS, Pradhan S, Cappellini F, Karlsson ME, Blomberg E, Karlsson HL, Odnevall Wallinder I, Hedberg JF (2016) Electrochemical surface oxide characteristics of metal nanoparticles (Mn, Cu and Al) and the relation to toxicity. J Electrochim Acta 212:360–371

    Article  Google Scholar 

  2. Katsnelson BA, Privalova LI, Degtyareva TD, Sutunkova MP, Minigalieva IA, Kireyeva EP, Khodos MY, Kozitsina AN, Shur VY, Nikolaeva EV, Vazhenin VA, Potapov AP, Morozova MV, Valamina IE, Tulakina LG, Pichugova SV, Beikin JB (2010) Experimental estimates of the toxicity of iron oxide Fe3O4 (magnetite) nanoparticles. Cent Eur J Occup Environ Med 16:47–63

    Google Scholar 

  3. Katsnelson BA, Privalova LI, Kuzmin SV, Degtyareva TD, Sutunkova MP, Yeremenko OS, Minigalieva IA, Kireyeva EP, Khodos MY, Kozitsina AN, Malakhova NA, Glazyrina JA, Shur VY, Shishkin EI, Nikolaeva EV (2010) Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: are we defenseless against nanoparticles? Int J Occup Environ Health 16:503–519

    Article  Google Scholar 

  4. Katsnelson BA, Degtyareva TD, Minigalieva IA, Privalova LI, Kuzmin SV, Yeremenko OS, Kireyeva EP, Sutunkova MP, Valamina II, Khodos MY, Kozitsina AN, Shur VY, Vazhenin VA, Potapov AP, Morozova MV (2011) Sub-chronic systemic toxicity and bio-accumulation of Fe3O4 nano- and microparticles following repeated intraperitoneal administration to rats. Int J Toxicol 30:59–68

    Article  Google Scholar 

  5. Katsnelson BA, Privalova LI, Kuzmin SV, Gurvich VB, Sutunkova MP, Kireyeva EP, Minigalieva IA (2012) An approach to tentative reference levels setting for nanoparticles in the workroom air based on comparing their toxicity with that of their micrometric counterparts: a case study of iron oxide Fe3O4. ISRN Nanotechnol 143613

    Google Scholar 

  6. Katsnelson BA, Privalova LI, Sutunkova MP, Khodos MY, Shur VY, Shishkina EV, Tulakina LG, Pichugova SV, Beikin JB (2012) Uptake of some metallic nanoparticles by, and their impact on pulmonary macrophages in vivo as viewed by optical, atomic force, and transmission electron microscopy. J Nanomed Nanotechnol 3:1–8

    Google Scholar 

  7. Katsnelson BA, Privalova LI, Sutunkova MP, Tulakina LG, Pichugova SV, Beykin JB, Khodos MJ (2012) The “in vivo” interaction between iron oxide Fe3O4 nanoparticles and alveolar macrophages. J Bull Exp Biol Med 152:627–631

    Article  Google Scholar 

  8. Katsnelson BA, Privalova LI, Gurvich VB, Makeyev OH, Shur VY, Beikin YB, Sutunkova MP, Kireyeva EP, Minigalieva IA, Loginova NV, Vasilyeva MS, Korotkov AV, Shuman EA, Vlasova LA, Shishkina EV, Tyurnina AE, Kozin RV, Valamina IE, Pichugova SV, Tulakina LG (2013) Comparative in vivo assessment of some adverse bio-effects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver’s effects with a complex of innocuous bioprotectors. Int J Mol Sci 14:2449–2483

    Article  Google Scholar 

  9. Katsnelson BA, Minigalieva IA, Privalova LI, Sutunkova MP, Gurvich VB, Shur VY, Shishkina EV, Varaksin AN, Panov VG (2014) Lower airways response in rats to a single or combined intratracheal instillation of manganese and nickel nanoparticles and its attenuation with a bio-protective pre-treatment. J Toksicol Vestn 6:8–14

    Google Scholar 

  10. Katsnelson BA, Privalova LI, Gurvich VB, Kuzmin SV, Kireyeva EP, Minigalieva IA, Sutunkova MP, Loginova NV, Malykh OL, Yarushin SV, Soloboyeva JI, Kochneva NI (2014) Enhancing population’s resistance to toxic exposures as an auxilliary tool of decreasing environmental and occupational health risks (a self-overview). J Environ Prot 5:1435–1449

    Article  Google Scholar 

  11. Privalova LI, Katsnelson BA, Loginova NV, Gurvich VB, Shur VY, Beikin YB, Sutunkova MP, Minigalieva IA, Shishkina EV, Pichugova SV, Tulakina LG, Beljayeva SV (2014) Some characteristics of free cell population in the airways of rats after intratracheal instillation of copper-containing nano-scale particles. Int J Mol Sci 15:21538–21553

    Article  Google Scholar 

  12. Privalova LI, Katsnelson BA, Loginova NV, Gurvich VB, Shur VY, Valamina IE, Makeyev OH, Sutunkova MP, Minigalieva IA, Kireyeva EP, Rusakov VO, Tyurnina AE, Kozin RV, Meshtcheryakova EY, Korotkov AV, Shuman EA, Zvereva AE, Kostykova SV (2014) Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors. Int J Mol Sci 15:12379–12406

    Article  Google Scholar 

  13. Minigalieva IA, Katsnelson BA, Privalova LI, Sutunkova MP, Gurvich VB, Shur VY, Shishkina EV, Valamina IE, Makeyev OH, Panov VG, Varaksin AN, Grigoryeva EV, Meshtcheryakova EY (2015) Attenuation of combined nickel(II) oxide and manganese(II, III) oxide nanoparticles’ adverse effects with a complex of bioprotectors. Int J Mol Sci 16(9):22555–22583

    Article  Google Scholar 

  14. Katsnelson BA, Privalova LI, Sutunkova MP, Privalova LI, Varaksin AN, Gurvich VB, Sutunkova MP, Shur VY, Shishkina EV, Valamina IE, Makeyev OH (2015) Some patterns of metallic nanoparticles’ combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles. J Food Chem Toxicol 86:351–364

    Article  Google Scholar 

  15. Katsnelson BA, Panov VG, Minigaliyeva IA, Varaksin AN, Privalova LI, Slyshkina TV, Grebenkina SV (2015) Further development of the theory and mathematical description of combined toxicity: an approach to classifying types of action of three-factorial combinations (a case study of manganese–chromium–nickel subchronic intoxication). Toxicology 334:33–44

    Article  Google Scholar 

  16. Katsnelson BA, Privalova LI, Sutunkova MP, Minigalieva IA, Gurvich VB, Shur VY, Makeyev OH, Valamina IE, Grigoryeva EV (2015) Is it possible to enhance the organism’s resistance to toxic effects of metallic nanoparticles? Toxicology 337:79–82

    Article  Google Scholar 

  17. Sutunkova MP, Katsnelson BA, Privalova LI, Gurvich VB, Konysheva LK, Shur VY, Shishkina EV, Minigalieva IA, Solovjeva SN, Grebenkina SV, Zubarev IV (2016) On the contribution of the phagocytosis and the solubilization to the iron oxide nanoparticles retention in and elimination from lungs under long-term inhalation exposure. Toxicology 363:19–28

    Article  Google Scholar 

  18. Zhu MT, Feng WY, Wang B, Wang TC, Gu YQ, Wang M, Wang Y, Ouyang H, Zhao YL, Chai ZF (2008) Comparative study of pulmonary responses to nano- and submicron ferric oxide in rats. Toxicology 247:102–111

    Article  Google Scholar 

  19. Mahmoudi M, Simchi A, Milani AS, Stroeve P (2009) Cell toxicity of superparamagnetic iron oxide nanoparticles. J Colloid Interface Sci 336(2):510–518

    Article  Google Scholar 

  20. Naqvi S, Samim M, Abdin MZ, Ahmed FJ, Maitra A, Prashant C, Dinda AK (2010) Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. Int J Nanomed 5:983–989

    Article  Google Scholar 

  21. Singh N, Jenkins GJS, Asadi R, Doak SH (2010) Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). J Nano Rev 1:5358

    Article  Google Scholar 

  22. Wu X, Tan Y, Mao H, Zhang M (2010) Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells. Int J Nanomed 5:385–399

    Article  Google Scholar 

  23. Mahmoudi M, Laurent S, Shokrgozar MA, Hosseinkhani M (2011) Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell “vision” versus physicochemical properties of nanoparticles. J ACS Nano 5(9):7263–7276

    Article  Google Scholar 

  24. Markides H, Rotherham M, El Haj AJ (2012) Biocompatibility and toxicity of magnetic nanoparticles in regenerative medicine. J Nanomater 2012:1–11

    Article  Google Scholar 

  25. Soenen SJ, De Cuyper M, De Smedt SC, Braeckmans K (2012) Investigating the toxic effects of iron oxide nanoparticles. J Methods Enzymol 509:195–224

    Article  Google Scholar 

  26. Barhoumi L, Dewez D (2013) Toxicity of superparamagnetic iron oxide nanoparticles on green alga Chlorella vulgaris. BioMed Res 647974

    Google Scholar 

  27. Liu G, Gao J, Ai H, Chen X (2013) Applications and potential toxicity of magnetic iron oxide nanoparticles. J Small 9(9–10):1533–1545

    Article  Google Scholar 

  28. Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. J Toxicol Appl Pharmacol 233:404–410

    Article  Google Scholar 

  29. Arora S, Jain J, Rajwade JM, Paknikar KM (2009) Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells. J Toxicol Appl Pharmacol 236:310–318

    Article  Google Scholar 

  30. Ahamed M, AlSalhi MS, Siddiqui MKJ (2010) Silver nanoparticles applications and human health. J Clin Chim Acta 411:1841–1848

    Article  Google Scholar 

  31. Choi JE, Kim S, Ahn JH, Youn P, Kang JS, Park K, Yi J, Ryu DY (2010) Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. J Aquat Toxicol 100:151–159

    Article  Google Scholar 

  32. Kim YS, Song MY, Park JD, Song KS, Ryu HR, Chung YH, Chang HK, Lee JH, Oh KH, Kelman BJ, Hwang IK, Yu IJ (2010) Subchronic oral toxicity of silver nanoparticles. J Part Fibre Toxicol 7(1):20

    Article  Google Scholar 

  33. Li T, Albee B, Alemayehu M, Diaz R, Ingham L, Kamal S, Rodriguez M, Bishnoi SW (2010) Comparative toxicity study of Ag, Au, Ag-Au bimetallic nanoparticles on Daphnia magna. J Anal Bioanal Chem 398:689–700

    Article  Google Scholar 

  34. Park EJ, Bae E, Yi Y, Kim Y, Choi K, Lee SH, Yoon J, Lee BC, Park K (2010) Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nano-particles. J Environ Toxicol Pharmacol 30:162–168

    Article  Google Scholar 

  35. Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker W Jr, Hussain SM, Ali SF (2010) Silver nanoparticle induced blood-brain barrier inflammation and increased permeability in primary rat brain micro vessel endothelial cells. J Toxicol Sci 118:160–170

    Article  Google Scholar 

  36. Ahmadi F, Kordestany AH (2011) Investigation on silver retention in different organs and oxidative stress enzymes in male broiler fed diet supplemented with powder of nano silver. Amer-Eurasian J Toxicol Sci 3:28–35

    Google Scholar 

  37. Foldbjerg R, Dang DA, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. J Arch Toxicol 85:743–750

    Article  Google Scholar 

  38. Hackenberg S, Scherzed A, Kessler M, Hummel S, Technau A, Froelich K, Ginzkey C, Koehler C, Hagen R, Kleinsasser N (2011) Silver nanoparticles: evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cell. J Toxicol Lett 201:27–33

    Article  Google Scholar 

  39. Kim HR, Kim MJ, Lee SY, Oh SM, Chung KH (2011) Genotoxic effects of silver nanoparticles stimulated by oxidative stress in human normal bronchial epithelial (BEAS-2B) cells. J Mutat Res 726:129–135

    Article  Google Scholar 

  40. Park MV, Neigh AM, Vermeulen JP, de la Fonteyne LJ, Verharen HW, Briedé JJ, van Loveren H, de Jong WH (2011) The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials 32:9810–9817

    Article  Google Scholar 

  41. Singh S, D’Britto V, Prabhune AA, Ramana CV, Dhawan A, Prasad BLV (2011) Cytotoxic and genotoxic assessment of glycolipid-reduced and -capped gold and silver nanoparticles. New J Chem 34:294–301

    Article  Google Scholar 

  42. Srivastava M, Singh S, Self WT (2011) Exposure to silver nanoparticles inhibits selenoprotein synthesis and the activity of thioredoxin reductase. J Environ Health Perspect 120:56–61

    Article  Google Scholar 

  43. Stebounova LV, Adamcakova-Dodd A, Kim JS (2011) Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model. J Part Fibre Toxicol 8(1):5

    Article  Google Scholar 

  44. Asare N, Instanes C, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, Brunborg G (2012) Citotoxic and genotoxic effects of silver nanoparticles in testicular cell. Toxicology 291:65–72

    Article  Google Scholar 

  45. Flower NAL, Brabu B, Revathy M, Gopalakrishnan C, Raja SV, Murugan SS, Kumaravel TS (2012) Characterization of synthesized silver nanoparticles and assessment of its genotoxicity potentials using the alkaline comet assay. J Mutat Res 742:61–65

    Article  Google Scholar 

  46. Karlsson HL, Gliga AR, Kohonen P, Wallberg A, Fadeel B (2012) Genotoxic and epigenetic effects of silver nanoparticles. J Toxicol Lett 211S:S35–S42

    Google Scholar 

  47. Li Y, Chen DH, Yan J, Chen Y, Mittelstaedt RA, Zhang Y, Biris AS, Heflich RH, Chen T (2012) Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro micronucleus assay. J Mutat Res 745:4–10

    Article  Google Scholar 

  48. Lim DH, Jang J, Kim S, Kang T, Lee K, Choi IH (2012) The effects of sub-lethal concentrations of silver nanoparticles on inflammatory and stress in human macrophages using cDNA microarray analysis. Biomaterials 33:4690–4699

    Article  Google Scholar 

  49. Tavares P, Balbino F, de Oliveira HM, Fagundes GE, Venâncio M, Ronconi JVV, Merlini A, Streck EL, da Silva Paula MM, de Andrade VM (2012) Evaluation of genotoxic effect of silver nanoparticles (Ag-NPs) in vitro and in vivo. J Nanopart Res 14(4):1–7

    Article  Google Scholar 

  50. Beer C, Foldbjerg R, Hayashi Y, Sutherland DS, Autrup H (2012) Toxicity of silver nanoparticles—nanoparticle or silver ion? J Toxicol Lett 208:286–292

    Article  Google Scholar 

  51. Cronholm P, Karlsson HL, Hedberg J, Lowe TA, Winnberg L, Elihn K, Wallinder IO, Möller L (2013) Intracellular uptake and toxicity of Ag and CuO nanoparticles: a comparison between nanoparticles and their corresponding metal ions. J Small 8:970–982

    Article  Google Scholar 

  52. Gomes T, Araújo O, Pereira R, Almeida AC, Cravo A, Bebianno MJ (2013) Genotoxicity of copper oxide and silver nanoparticles in the mussel Mytilus galloprovincialis. J Mar Environ Res 84:51–59

    Article  Google Scholar 

  53. Bakri SJ, Pulido JS, Mukerjee P, Marler RJ, Mukhopadhyay D (2008) Absence of histologic retinal toxicity of intravitreal nanogold in a rabbit model. J Retina 28:147–149

    Article  Google Scholar 

  54. Chen YSh, Hung YCh, Huang GS (2009) Assessment of the in vivo toxicity of gold nanoparticles. J Nanoscale Res Lett 4:858–864

    Article  Google Scholar 

  55. Pan Y, Leifert A, Ruau D, Neuss S, Bornemann J, Schmid G, Brandau W, Simon U, Jahnen-Dechent W (2009) Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. J Small 5:2067–2076

    Article  Google Scholar 

  56. Balasurbamanian SK, Jittiwat J, Manikandan J, Ong CN, Yu LE, Ong WY (2010) Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. J Biomater 31:2034–2042

    Article  Google Scholar 

  57. Zhang Q, Hitchins VM, Schrand AM, Hussain SM, Goering PL (2010) Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of proinflammatory mediators. Nanotoxicology 5:284–295

    Article  Google Scholar 

  58. Glazer ES, Zhu C, Hamir AN, Borne A, Thompson CS, Curley SA (2011) Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model. Nanotoxicology 5:459–468

    Article  Google Scholar 

  59. Li JJ, Lo SL, Ng CT, Gurung RL, Hartono D, Hande MP, Ong CN, Bay BH, Yung LY (2011) Genomic instability of gold nanoparticle treated human lung fibroblast cells. J Biomater 32:5515–5523

    Article  Google Scholar 

  60. Mustafa T, Watanabe F, Monroe W, Mahmood M, Xu Y, Saeed LM, Karmakar A, Casciano D, Ali S, Biris AS (2011) Impact of gold nanoparticle concentration on their cellular uptake by MC3T3-E1 mouse osteoblastic cells as analyzed by transmission electron microscopy. J Nanomed Nanotechnol 2:1–8

    Google Scholar 

  61. Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, Schlager JJ, Oldenburg SJ, Paule MG, Slikker W Jr, Hussain SM, Ali SF (2011) Brain microvessel endothelial cells responses to gold nanoparticles: in vitro pro-inflammatory mediators and permeability. J Nanotoxicol 5:479–492

    Article  Google Scholar 

  62. Choi SY, Jeong S, Jang SH, Park J, Park JH, Ock KS, Lee SY, Joo SW (2012) In vitro toxicity protein-adsorbed citrate-reduced gold nanoparticles in human lung adenocarcinoma cells. J Toxicol In Vitro 26:229–237

    Article  Google Scholar 

  63. Dykman L, Khlebtsov N (2012) Gold nanoparticles in biomedical applications: recent advances and perspectives. J Chem Soc Rev 41:2256–2282

    Article  Google Scholar 

  64. Rudolf R, Friedrich B, Stopic S, Anzel I, Tomic S, Colic M (2012) Cytotoxicity of gold nanoparticles prepared by ultrasonic spray pyrolysis. J Biomater Appl 26:595–612

    Article  Google Scholar 

  65. Shulz M, Ma-Hock L, Brill S, Strauss V, Treumann S, Gröters S, van Ravenzwaay B, Landsiedel R (2012) Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. J Mutat Res 745:51–57

    Article  Google Scholar 

  66. Chen Z, Meng H, Xing G, Chen C, Zhao Y, Jia G, Wang T, Yuan H, Ye C, Zhao F, Chai Z, Zhu C, Fang X, Ma B, Wan L (2006) Acute toxicological effects of copper nanoparticles in vivo. J Toxicol Lett 25:109–120

    Article  Google Scholar 

  67. Karlsson H, Cronholm P, Gustafsson J, Moller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. J Chem Res Toxicol 21:1726–1732

    Article  Google Scholar 

  68. Studer AM, Limbach LK, Van Duc L, Krumeich F, Athanassiou EK, Gerber LC, Moch H, Stark WJ (2010) Nanoparticle cytotoxicity depends on intracellular solubility: comparison of stabilized copper metal and degradable copper oxide nanoparticles. J Toxicol Lett 1:169–174

    Article  Google Scholar 

  69. Bondarenko O, Ivask A, Käkinen A, Kahru A (2012) Sub-toxic effects of CuO nanoparticles on bacteria: kinetics, role of Cu ions and possible mechanisms of action. J Environ Pollut 169:81–89

    Article  Google Scholar 

  70. Magaye R, Zhao J, Bowman L, Ding M (2012) Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles. J Exp Ther Med 4:551–561

    Google Scholar 

  71. Pang C, Selck H, Misra SK, Berhanu D, Dybowska A, Valsami-Jones E, Forbes VE (2012) Effects of sediment-associated copper to the deposit-feeding snail, Potamopyrgus antipodarum: a comparison of Cu added in aqueous form or as nano- and micro-CuO particles. J Aquat Toxicol 15:114–122

    Article  Google Scholar 

  72. Akhtar MJ, Kumar S, Alhadlaq HA, Alrokayan SA, Abu-Salah KM, Ahamed M (2013) Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells. J Toxicol Ind Health 32:5

    Google Scholar 

  73. Alarifi S, Ali D, Verma A, Alakhtani S, Ali BA (2013) Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. Int J Toxicol 32:296–307

    Article  Google Scholar 

  74. Cuillel M, Chevallet M, Charbonnier P, Fauquant C, Pignot-Paintrand I, Arnaud J, Cassio D, Michaud-Soret I, Mintz E (2014) Interference of CuO nanoparticles with metal homeostasis in hepatocytes under sub-toxic conditions. J Nanoscale 16:1707–1715

    Article  Google Scholar 

  75. Xu J, Li Z, Xu P, Xiao L, Yang Z (2013) Nanosized copper oxide induces apoptosis through oxidative stress in podocytes. J Arch Toxicol 87:1067–1073

    Article  Google Scholar 

  76. Zhang Q, Yukinori K, Sato K, Nakakuki K, Kohyama N, Donaldson K (1998) Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J Toxicol Environ Health 53:423–438

    Article  Google Scholar 

  77. Morimoto Y, Hirohashi M, Ogami A, Oyabu T, Myojo T, Hashiba M, Mizuguchi Y, Kambara T, Lee BW, Kuroda E, Tanaka I (2011) Pulmonary toxicity following an intratracheal instillation of nickel oxide nanoparticle agglomerates. J Occup Health 53(4):293–295

    Article  Google Scholar 

  78. Magaye R, Zhao J (2012) Recent progress in studies of metallic nickel and nickel-based nanoparticles’ genotoxicity and carcinogenicity. Environ Toxicol Pharmacol 34(3):644–650

    Article  Google Scholar 

  79. Capasso L, Camatini M, Gualtieri M (2014) Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells. Toxicol Lett 226(1):28–34

    Article  Google Scholar 

  80. Pang H, Zhang B, Du J, Chen J, Zhanga J, Lia S (2012) Porous nickel oxide nanospindles with huge specific capacitance and long-life cycle. J RSC Adv 2:2257–2261

    Article  Google Scholar 

  81. Hussain SM, Javorina AK, Schrand AM, Duhart HM, Ali SF, Schlager JJ (2006) The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. J Toxicol Sci 92(2):456–463

    Article  Google Scholar 

  82. Singh SP, Kumari M, Kumari SI, Rahman MF, Mahboob M, Grover P (2013) Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure. J Appl Toxicol 33(10):1165–1179

    Article  Google Scholar 

  83. Bellusci M, La Barbera A, Padella F, Mancuso M, Pasquo A, Grollino MG, Leter G, Nardi E, Cremisini C, Giardullo P, Pacchierotti F (2014) Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process. Int J Nanomed 9:1919–1929

    Google Scholar 

  84. Wang B, Fen WY, Wang TC, Jia G, Wang M, Shi JW, Zhang F, Zhao YL, Chai ZF (2006) Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice. J Toxicol Lett 161(2):115–123

    Article  Google Scholar 

  85. Cho WS, Duffin R, Howie S, Scotton CJ, Wallace WA, Macnee W, Bradley M, Megson IL, Donaldson K (2011) Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. J Part Fibre Toxicol. 8:27

    Google Scholar 

  86. Adamcakova-Dodd A, Stebounova LV, Kim JS, Vorrink SU, Ault AP, O’Shaughnessy PT, Grassian VH, Thorne PS (2014) Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. J Part Fibre Toxicol. 11:15

    Google Scholar 

  87. Jacobsen NR, Stoeger T, van den Brule S, Saber AT, Beyerle A, Vietti G, Mortensen A, Szarek J, Budtz HC, Kermanizadeh A, Banerjee A, Ercal N, Vogel U, Wallin H, Møller P (2015) Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories. Food Chem Toxicol 85:84–95

    Article  Google Scholar 

  88. Gao F, Ma NJ, Zhou H, Wang Q, Zhang H, Wang P, Hou H, Wen H, Li L (2016) Zinc oxide nanoparticles induced epigenetic change and G2/M arrest are associated with apoptosis in human epidermal keratinocytes. Int J Nanomed 11:3859–3874

    Article  Google Scholar 

  89. Shaikh SM, Shyama SK, Desai PV (2015) Absorption, LD50 and effects of CoO, MgO and PbO nanoparticles on mice “Mus musculus”. IOSR-JESTFT 9(2):32–38

    Google Scholar 

  90. Amiri A, Mohammadi M, Shabani M (2016) Synthesis and toxicity evaluation of lead oxide (PbO) nanoparticles in rats. Electron J Biol 12(2):110–114

    Google Scholar 

  91. Ali SF, Boulton MC, Braydish-Stolle LK, Murdock RC, Jiang H, Rongzhu L, Miltatovic D, Aschner M, Schlager JJ, Hussain SM (2009) Cytotoxic effects of manganese nanoparticles using different solvent system in astrocytes and neuronal cultured cell. FASEB 23(1), suppl.759.3

    Google Scholar 

  92. Ngwa H, Kanthasamy A, Gu Y, Fang N, Anantharam V, Kanthasamy AG (2011) Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells. J Toxicol Appl Pharmacol 256(3):227–240

    Article  Google Scholar 

  93. Geiser M, Kreyling WG (2010) Deposition and biokinetics of inhaled nanoparticles. J Part Fibre Toxicol 7(1):2

    Article  Google Scholar 

  94. ICRP (1994) Human respiratory tract model for radiological protection. A report of a Task Group of the International Commission on Radiological Protection. Ann. ICRP, vol 24, pp 1–482

    Google Scholar 

  95. Kreyling WG, Geiser M (2009) Dosimetry of inhaled nanoparticles. In: Marijnissen JCM, Gradon L (eds) Nanoparticles in medicine and environment, inhalation and health effects. Springer, Dordrecht

    Google Scholar 

  96. Fröhlich E, Salar-Behzadi S (2014) Toxicological assessment of inhaled nanoparticles: role of in vivo, ex vivo, in vitro, and in silico studies. Int J Mol Sci 15:4795–4822

    Article  Google Scholar 

  97. Sadauskas E, Wallin H, Stolenberg M, Vogel U, Doering P, Larsen A, Danscher G (2007) Kupffer cells are central in the removal of nanoparticles from the organism. J Part Fibre Toxicol 4:10–16

    Article  Google Scholar 

  98. Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Sadagopa Ramanujam VM, Urayama A, Vergara L, Kogan MJ, Soto C (2010) Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. J Biochem Biophys Res Commun 393:649–655

    Article  Google Scholar 

  99. Rylova ML (1964) Methods of investigating long-term effects of noxious environmental agents in animal experiments. Meditsina, Leningrad

    Google Scholar 

  100. Abeyemi OO, Yemitan OK, Taiwo AE (2006) Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphianitida nitida AFZEL. Ethnopharmacology 106:312–316

    Article  Google Scholar 

  101. Fernandez SP, Wasowski C, Loscalzo LM, Granger RE, Johnston GA, Paladini AC, Marder M (2006) Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol 539:168–176

    Article  Google Scholar 

  102. Donaldson K, Stone V, Tran CK, Kreyling W, Borm PJ (2004) Nanotoxicology (editorial). J Occup Environ Med 61:727–728

    Article  Google Scholar 

  103. Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studied of ultrafine particles. J Environ Health Perspect 113:823–839

    Article  Google Scholar 

  104. Fadeel B (2012) Clear and present danger? Engineered nanoparticles and the immune system. J Swiss Med Wkly 142(24):w13609

    Google Scholar 

  105. Kilburn KH (1969) Alveolar clearance of particles. A bullfrog lung model. J Arch Environ Health 18:556–563

    Article  Google Scholar 

  106. Renwick L, Brown D, Clouter K, Donaldson K (2004) Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types. J Occup Environ Med 61:442–447

    Article  Google Scholar 

  107. Stoeger T, Reinhard C, Takenaka Sh, Schroeppel A, Karg E, Ritter B, Heyder J, Schulz H (2006) Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. J Environ Health Perspect 114(3):328–333

    Article  Google Scholar 

  108. Sager TM, Porter DW, Robinson VA, Lindsley WG, Schwegler-Berry DE, Castranova V (2007) Improved method to disperse nanoparticles in vitro and in vivo investigation of toxicity. Nanotoxicology 1:118–129

    Article  Google Scholar 

  109. Grassian VH, O’Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS (2007) Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. J Environ Health Perspect 115:397–402

    Article  Google Scholar 

  110. Warheit DB, Reed KL, Sayes CM (2009) A role fore surface reactivity in TiO2 and quartz-related nanoparticle pulmonary toxicity. Nanotoxicology 3:181–187

    Article  Google Scholar 

  111. Privalova LI (1990) Hygienic dimensions of non-specific action of low-soluble dust particles. Dissertation, The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

    Google Scholar 

  112. Privalova LI, Katsnelson BA, Sharapova NY, Kislitsina NS (1995) On the relationship between activation and the breakdown of macrophages in pathogenesis of silicosis. Med Lav 86:511–521

    Google Scholar 

  113. Katsnelson BA, Konysheva LK, Privalova LY, Morosova KI (1992) Development of a multicompartmental model of the kinetics of quartz dust in the pulmonary region of the lung during chronic inhalation exposure of rats. Brit J Ind Med 49:172–181

    Google Scholar 

  114. Katsnelson BA, Konyscheva LK, Sharapova NY, Privalova LI (1994) Prediction of the comparative intensity of pneumoconiotic changes caused by chronic inhalation exposure to dusts of different cytotoxicity by means of a mathematical model. J Occup Environ Med 51:173–180

    Article  Google Scholar 

  115. Katsnelson BA, Konysheva LK, Privalova LY, Sharapova NY (1997) Quartz dust retention in rat lungs under chronic exposure simulated by a multicompartmental model: further evidence of the key role of the cytotoxicity of quartz particles. J Inhalation Toxicol 9:703–715

    Article  Google Scholar 

  116. Minigalieva IA, Katsnelson BA, Panov VG, Privalova LI, Varaksin AN, Gurvich VB, Sutunkova MP, Shur VY, Shishkina EV, Valamina IE, Makeyev OH, Grigoryeva EV, Klinova SV (2017) In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors. Toxicology 380:72–93

    Article  Google Scholar 

  117. Bastus NG, Casals E, Socorro VC, Puntes V (2008) Reactivity of engineered inorganic nanoparticles and carbon nanostructures in biological media. Nanotoxicology 2(3):99–112

    Article  Google Scholar 

  118. Fröhlich E (2013) Cellular targets and mechanisms in the cytotoxic action of non-biodegradable engineered nanoparticles. J Curr Drug Metab 14:976–988

    Article  Google Scholar 

  119. Privalova LI, Katsnelson BA, Osipenko AB, Yushkov BN, Babushkina LG (1980) Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity. J Environ Health Perspect 35:205–218

    Article  Google Scholar 

  120. Katsnelson BA, Privalova LI (1984) Recruitment of phagocytizing cells into the respiratory tract as a response to the cytotoxic action of deposited particles. J Environ Health Perspect 55:313–325

    Article  Google Scholar 

  121. Privalova LI, Katsnelson BA, Yelnichnykh LN (1987) Some peculiarities of the pulmonary phagocytotic response, dust kinetics, and silicosis development during long term exposure of rats to high quartz levels. Brit J Ind Med 44:228–235

    Google Scholar 

  122. Utembe W, Potgieter K, Stefaniak AB, Gulumian M (2015) Dissolution and biodurability: important parameters needed for risk assessment of nanomaterials. J Part Fibre Toxicol 12(1):11

    Article  Google Scholar 

  123. Tong T, Wilke CM, Wu J, Binh CT, Kelly JJ, Gaillard JF, Gray KA (2015) Combined toxicity of nano-ZnO and nano-TiO2: from single- to multinanomaterial systems. Environ Sci Technol 49(13):8113–8123

    Article  Google Scholar 

  124. Varaksin AN, Katsnelson BA, Panov VG, Privalova LI, Kireyeva EP, Valamina IE, Beresneva OY (2014) Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead. Food Chem Toxicol 64:144–156

    Article  Google Scholar 

  125. Panov VG, Katsnelson BA, Varaksin AN, Privalova LI, Kireyeva EP, Sutunkova MP, Valamina IE, Beresneva OYu (2015) Further development of mathematical description for combined (a case study of lead–fluoride combination). Toxicol Rep 2:297–307

    Article  Google Scholar 

  126. Box GEP, Draper NR (2007) Response surfaces, mixtures, and ridge analyses. Wiley, Hoboken

    Book  Google Scholar 

  127. Tallarida RJ (2001) Drug synergism: its detection and applications. J Pharmacol Exp Ther 298(3):865–872

    Google Scholar 

  128. Euling S, Gennings C, Wilson EM, Kemppainen JA, Kelce WR, Kimmel CA (2002) Response-surface modeling of the effect of 5α-dihydrotestosterone and androgen receptor levels on the response to the androgen antagonist vinclozolin. Toxicol Sci 69(2):332–343

    Article  Google Scholar 

  129. Myers JP, vom Saal FS, Akingbemi BT, Arizono K, Belcher S, Colborn T, Chahoud I, Crain DA, Farabollini F, Guillette LJ Jr, Hassold T, Ho SM, Hunt PA, Iguchi T, Jobling S, Kanno J, Laufer H, Marcus M, McLachlan JA, Nadal A, Oehlmann J, Olea N, Palanza P, Parmigiani S, Rubin BS, Schoenfelder G, Sonnenschein C, Soto AM, Talsness CE, Taylor JA, Vandenberg LN, Vandenbergh JG, Vogel S, Watson CS, Welshons WV, Zoeller RT (2009) Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: the case of bisphenol A. J Environ Health Perspect 117(3):309–315

    Article  Google Scholar 

  130. CDC and NIOSH: Current Intelligence Bulletin 63: (2011) Occupational exposure to titanium dioxide. US Department of Health and Human Services, NIOSH, Cincinnati

    Google Scholar 

  131. Safe Work Australia (2010) Hazardous Substances Information System (HSIS). http://hsis.safeworkaustralia.gov.au/. Accessed 1 Nov 2009

  132. Katsnelson BA, Privalova LI, Kuzmin SV, Degtyareva TD, Soloboyeva JI (2008) “Biological prophylaxis”—One of the ways to proceed from the analytical environmental epidemiology to the population health protection. Cent Eur J Occup Environ Med 14:41–42

    Google Scholar 

  133. Morosova KI, Aronova GV, Katsnelson BA, Velichkovski BT, Genkin AM, Elnichnykh LN, Privalova LI (1982) On the defensive action of glutamate on the cytotoxicity and fibrogenicity of quartz dust. Brit J Ind Med 39:244–252

    Google Scholar 

  134. Karki P, Webb A, Smith K, Lee K, Son DS, Aschner M, Lee E (2013) CREB and NF-kappaB mediate the tamoxifen-induced up-regulation of GLT-1 in rat astrocytes. J Biol Chem 288(40):28975–28986

    Article  Google Scholar 

  135. White LD, Cory-Slechta DA, Gilbert ME, Tiffany-Castiglioni E, Zawia NH, Virgolini M, Rossi-George A, Lasley SM, Qian YC, Basha MR (2007) New and evolving concepts in the neurotoxicology of lead. J Toxicol Appl Pharmacol 225(1):1–27

    Article  Google Scholar 

  136. Desole MS, Esposito G, Migheli R, Sircana S, Delogu MR, Fresu L, Miele M, de Natale G, Miele E (1997) Glutathione deficiency potentiates manganese toxicity in rat striatum and brainstem and in PC12 cells. J Pharmacol Res 36(4):285–292

    Article  Google Scholar 

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Authors and Affiliations

  1. The Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str, Ekaterinburg, 620014, Russia

    Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Ilzira A. Minigalieva & Vladimir B. Gurvich

  2. School of Natural Sciences and Mathematics, The Ural Federal University, Ekaterinburg, Russia

    Vladimir Y. Shur & Ekaterina V. Shishkina

  3. The Ural State Medical University, Ekaterinburg, Russia

    Oleg H. Makeyev & Irene E. Valamina

  4. The Institute of Industrial Ecology, The Ural Branch of the Russian Academy of Sciences, Ekaterinburg, Russia

    Anatoly N. Varaksin & Vladimir G. Panov

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  1. Boris A. Katsnelson
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  2. Larisa I. Privalova
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  3. Marina P. Sutunkova
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  8. Oleg H. Makeyev
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  10. Anatoly N. Varaksin
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  11. Vladimir G. Panov
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Correspondence to Boris A. Katsnelson .

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Editors and Affiliations

  1. School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, China

    Bing Yan

  2. School of Environment, Jinan University, Guangzhou, Guangdong, China

    Hongyu Zhou

  3. Department of Chemistry, University of Texas at El Paso, El Paso, Texas, USA

    Jorge L. Gardea-Torresdey

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Katsnelson, B.A. et al. (2017). Experimental Research into Metallic and Metal Oxide Nanoparticle Toxicity In Vivo. In: Yan, B., Zhou, H., Gardea-Torresdey, J. (eds) Bioactivity of Engineered Nanoparticles. Nanomedicine and Nanotoxicology. Springer, Singapore. https://doi.org/10.1007/978-981-10-5864-6_11

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