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Toxicity Testing of Nanomaterials

  • Amanda M. SchrandEmail author
  • Liming Dai
  • John J. Schlager
  • Saber M. Hussain
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 745)

Abstract

The large-scale production and consumer exposure to a variety of nanotechnology innovations has stirred interest concerning the health consequences of human exposure to nanomaterials. In order to investigate these questions, in vitro systems are used to rapidly and inexpensively predict the effects of nanomaterials at the cellular level. Recent advances in the toxicity testing of nanomaterials are beginning to shed light on the characteristics, uptake and mechanisms of their toxicity in a variety of cell types. Once the nanomaterials have been satisfactorily characterized, the evaluation of their interactions with cells can be studied with microscopy and biochemical assays. The combination of viability testing, observation of morphology and the generation of oxidative stress provide clues to the mechanisms of nanomaterial toxicity. The results of these studies are used to better understand how the size, chemical composition, shape and functionalization may contribute to their toxicity. This chapter will introduce the reader to the impact of nanomaterials in the workplace and marketplace with an emphasis on carbon-based and metal-based nanomaterials, which are most commonly encountered. While most purified carbon nanomaterials were nontoxic to many cell lines, many metal nanoparticles (e.g., silver or manganese) were more toxic. Other side- effects of nanoparticle interactions with cells can also occur, such as increased branching and dopamine depletion. Further investigation into the characteristics, uptake and mechanisms of nanomaterial toxicity will continue to elucidate this fascinating and rapidly growing area of science.

Keywords

Carbon Nanotubes Silver Nanoparticles Reactive Oxygen Species Generation Alveolar Macrophage Toxicity Testing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Dai L, ed. Carbon Nanotechnology: Recent Developments in Chemistry, Physics, Materials Science and Device Applications. Amsterdam: Elsevier, 2006:633–675.Google Scholar
  2. 2.
    Bianco A, Kostarelos K, Partidos C et al. Biomedical applications of functionalized carbon nanotubes. Chem Commun 2005; 5:571–577.CrossRefGoogle Scholar
  3. 3.
    Elechiguerra J, Burt J, Morones J et al. Interaction of silver nanoparticles with HIV-1. J Nanobiotechnol 2005; 3(6):1–14.Google Scholar
  4. 4.
    Stupp S, Donners J, Li L et al. Expanding frontiers in biomaterials. MRS Bulletin 2005; 30:864.CrossRefGoogle Scholar
  5. 5.
    Beck-Speier I, Dayal N, Karg E et al. Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles. Free Radic Biol Med 2005; 38:1080–1092.PubMedCrossRefGoogle Scholar
  6. 6.
    Nel A, Xia T, Madler L et al. Toxic potential of materials at the nanolevel. Science 2006; 311:622–627.PubMedCrossRefGoogle Scholar
  7. 7.
    Foley S, Crowley C, Smaihi M et al. Cellular localisation of a water-soluble fullerene derivative. Biochem Biophys Res Commun 2002; 294:116–119.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhang Q, Kusaka Y, Sato K et al. Toxicity of ultrafine nickel particles in lungs after intratracheal instillation. J Occup Health 1998; 40(3):171–176.CrossRefGoogle Scholar
  9. 9.
    Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A Tox Hazard Subst Environ Eng 2006; 41:2699–2711.PubMedGoogle Scholar
  10. 10.
    Oberdorster G, Ferin J, Gelein R et al. Role of the alveolar macrophage in lung injury-studies with ultrafine particles. Environ Health Perspect 1992; 97:193–199.PubMedGoogle Scholar
  11. 11.
    Ferin J, Oberdorster G, Penney DP. Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 1992; 6:535–542.PubMedGoogle Scholar
  12. 12.
    Kim JS, Yoon TJ, Yu KN et al. Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicol Sci 2006; 89:338–347.PubMedCrossRefGoogle Scholar
  13. 13.
    Oberdorster G, Maynard A, Donaldson K et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2005; 2:8.PubMedCrossRefGoogle Scholar
  14. 14.
    Oberdorster G, Yu CP. Lung dosimetry-considerations for noninhalation studies. Exp Lung Res 1999; 25:1–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Donaldson K, Li XY, MacNee W. Ultrafine (nanometer) particle mediated lung injury. J Aerosol Sci 1998; 29:553–560CrossRefGoogle Scholar
  16. 16.
    Johnston CJ, Finkelstein JN, Mercer P et al. Pulmonary effects induced by ultrafine PTFE particles. Toxicol Appl Pharmacol 2000; 168:208–215.PubMedCrossRefGoogle Scholar
  17. 17.
    Bergamaschi E, Bussolati O, Magrini A et al. Nanomaterials and lung toxicity: interactions with airways cells and relevance for occupational health risk assessment. Int J Immunopathol Pharmacol 2006; 19:3–10.PubMedGoogle Scholar
  18. 18.
    Duffin R, Gilmour PS, Schins RPF et al. Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause inflammation, chemokine expression and Nuclear Factor-B Activation. Toxicol Appl Pharmacol 2001; 176:10–17.PubMedCrossRefGoogle Scholar
  19. 19.
    Brown DM, Stone V, Findlay P et al. Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components. Occup Environ Med 2000; 57:685–691.PubMedCrossRefGoogle Scholar
  20. 20.
    Rehn B, Seiler F, Rehn S et al. Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: Untreated and surface treated. Toxicol Appl Pharmacol 2003; 189:84–95.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen HW, Su SF, Chien CT et al. Titanium dioxide nanoparticles induce emphysema-like lung injury in mice. FASEB J 2006; 20:2393–2395.PubMedCrossRefGoogle Scholar
  22. 22.
    Hoet P, Bruske-Hohlfeld I, Salata O. Nanoparticles: known and unknown health risks. J Nanobiotechnol 2004; 2:12.CrossRefGoogle Scholar
  23. 23.
    Zhang X, Prasad S, Niyogi S et al. Guided neurite growth on patterned carbon nanotubes. Sensors and Acuators 2005; 106:843–850.CrossRefGoogle Scholar
  24. 24.
    Maynard A, Baron P, Foley M et al. Exposure to carbon nanotube material: Aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health 2004; 67:87–107.CrossRefGoogle Scholar
  25. 25.
    Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: A review. Ann Occup Hyg 2005; 49:575–585.PubMedCrossRefGoogle Scholar
  26. 26.
    Olanow CW. Manganese-induced parkinsonism and parkinson’s disease. Ann NY Acad Sci 2004; 1012:209–223.PubMedCrossRefGoogle Scholar
  27. 27.
    Hussain S, Hess K, Gearhart J et al. In vitro toxicity of nanoparticles in BRL-3A rat liver cells. Toxicol In Vitro 2005; 19:975–983.PubMedCrossRefGoogle Scholar
  28. 28.
    Williams D, Carter B, eds. Transmission Electron Microscopy: A Textbook For Materials Science. New York: Plenum Press, 1996:621–635.Google Scholar
  29. 29.
    Goldstein J, Newbury D, Joy D et al, eds. Scanning Electron Microscopy and X-Ray Microanalysis. New York: Plenum Publishers, 2003:195–241.CrossRefGoogle Scholar
  30. 30.
    McGown, E. MAXline microplate readers application note 32, 1999. Available at: http://www.moleculardevices.com/pages/instruments/190.html.Google Scholar
  31. 31.
    Eisenbrand G, Pool-Zobel B, Baker V et al. Methods of in vitro toxicology. Food Chem Toxicol 2002; 40:193–226.PubMedCrossRefGoogle Scholar
  32. 32.
    Barile FA, ed. Introduction to In Vitro Cytotoxicology: Mechanisms and Methods, 1st ed. Boca Raton: CRC Press, 1994.Google Scholar
  33. 33.
    Hussain S, Frazier J. Cellular toxicity of hydrazine in primary hepatocytes. Toxicol Sci 2002; 69:424–432.PubMedCrossRefGoogle Scholar
  34. 34.
    Trohalaki S, Zellmer R, Pachter R et al. Risk assessment of high-energy chemicals by in vitro toxicity screening and quantitative structure-activity relationships. Toxicol Sci 2002; 68:498–507.PubMedCrossRefGoogle Scholar
  35. 35.
    Clemedson C, Barile F, Chesne C et al. MEIC Evaluation of acute systemic toxicity. Par VII. Prediction of human toxicity by results from testing of the first 30 reference chemicals with 27 further in vitro assays. Altern Lab Anim-ATLA 2000; 28:159–200.Google Scholar
  36. 36.
    Freitas RA Jr, ed. Nanomedicine, Vol IIA: Biocompatibility. Georgetown: Landes Bioscience, 2003: Available at: http://www.nanomedicine.com/NMIIA.htm.Google Scholar
  37. 37.
    Schrand A, Huang H, Carlson C et al. Are diamond nanoparticles cytotoxic? J Phys Chem Lett B 2007; 111(1):2–7.CrossRefGoogle Scholar
  38. 38.
    Yu S, Kang M, Chang H et al. Bright fluorescent nanodiamonds: No photobleaching and low toxicity. J Am Chem Soc 2005; 127:17604–17605.PubMedCrossRefGoogle Scholar
  39. 39.
    Cui D, Tian F, Ozkan C et al. Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 2005; 155:73–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Monteiro-Riviere N, Nemanich R, Inman A et al. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 2005; 155:377–384.PubMedCrossRefGoogle Scholar
  41. 41.
    Manna S, Sarkar S, Barr J et al. Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-KB in human keratinocytes. Nano Lett 2005; 5(9):1676–1684.PubMedCrossRefGoogle Scholar
  42. 42.
    Sayes C, Liang F, Hudson J et al. Functionalization density dependence of single-walled carbon nanotubes toxicity in vitro. Toxicol Lets 2005; 161(2):135–142.CrossRefGoogle Scholar
  43. 43.
    Jia G, Wang H, Yan L et al. Toxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube and fullerene. Environ Sci Technol 2005; 39(5):1378–1383.PubMedCrossRefGoogle Scholar
  44. 44.
    Cherukuri P, Bachilo S, Litovsky S et al. Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. J Am Chem Soc 2004; 126:15638–15639.PubMedCrossRefGoogle Scholar
  45. 45.
    Monteiro-Riviere N, Inman A. Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 2006; 44:1070–1078.CrossRefGoogle Scholar
  46. 46.
    Magrez A, Kasas S, Salicio V et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett 2006; 6(6):1121–1125.PubMedCrossRefGoogle Scholar
  47. 47.
    Sato Y, Yokoyama A, Shibata K et al. Influence of length on toxicity of multi-walled carbon nanotubes against human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue of rats in vivo. Mol BioSyst 2005; 1:176–182.PubMedCrossRefGoogle Scholar
  48. 48.
    Sato Y, Shibata KI, Kataoka H et al. Strict preparation and evaluation of water-soluble hat-stacked carbon nanofibers for biomedical application and their high biocompatibility: influence of nanofiber surface functional groups on toxicity. Mol BioSyst 2005; 1:142–145.PubMedCrossRefGoogle Scholar
  49. 49.
    Fiorito S, Serafino A, Andreola F et al. Effects of fullerenes and single-wall carbon nanotubes on murine and human macrophages. Carbon 2006; 44:1100–1105.CrossRefGoogle Scholar
  50. 50.
    Soto K, Carrasco A, Powell T et al. Comparative in vitro toxicity assessment of some manufactured nanoparticulate materials characterized by transmission electron microscopy. Nanoparticle Res 2005; 7:145–169.CrossRefGoogle Scholar
  51. 51.
    Limbach LK, Li Y, Grass RN et al. Oxide nanoparticle uptake in human lung fibroblasts: Effects of particle size, agglomeration and diffusion at low concentrations. Environ Sci Technol 2005, 39:9370–9376.PubMedCrossRefGoogle Scholar
  52. 52.
    Murr L, Garza K, Soto K et al. Toxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment. Int J Environ Res Public Health 2005; 2(1):31–42.PubMedCrossRefGoogle Scholar
  53. 53.
    Smart S, Cassady A, Lu G et al. The biocompatibility of carbon nanotubes. Carbon 2006; 44:1034–1047.CrossRefGoogle Scholar
  54. 54.
    Flahaut E, Durrieu M, Remy-Zolghadri M et al. Investigation of the toxicity of CCVD carbon nanotubes towards human umbilical vein endothelial cells. Carbon 2006; 44:1093–1099.CrossRefGoogle Scholar
  55. 55.
    Chlopek J, Czajkowska B, Szaraniec B et al. In vitro studies of carbon nanotubes biocompatibility. Carbon 2006; 44:1106–1111.CrossRefGoogle Scholar
  56. 56.
    Hurt RH, Monthioux M, Kane A. Toxicology of carbon nanomaterials: Status, trends and perspectives on the special issue. Carbon 2006; 44:1028–1033.CrossRefGoogle Scholar
  57. 57.
    Donaldson K, Aitken R, Tran L et al. Carbon nanotubes: A review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 2006; 92(1):5–22.PubMedCrossRefGoogle Scholar
  58. 58.
    Carmichael J, DeGraff W, Gazdar A et al. Evaluation of a tetrazolium-based semi automated colorimetric assay: Assessment of chemo sensitivity testing. Cancer Res 1987; 47:936–942.PubMedGoogle Scholar
  59. 59.
    Braydich-Stolle L, Hussain S, Schlager J et al. In vitro toxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 2005; 88(2):412–419.PubMedCrossRefGoogle Scholar
  60. 60.
    Carlson C. In vitro toxicity assessment of silver nanoparticles in rat alveolar macrophages. Masters Thesis. Dayton: Wright State University, 2006.Google Scholar
  61. 61.
    Lorenz MR, Holzapfel V, Musyanovych A et al. Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells. Biomaterials 2006; 27:2820–2828.PubMedCrossRefGoogle Scholar
  62. 62.
    Cherukuri A, Frye J, French T et al. FITC-poly-D-lysine conjugates as fluorescent probes to quantify hapten-specific macrophage receptor binding and uptake kinetics. Cytometry 1998; 31:110–124.PubMedCrossRefGoogle Scholar
  63. 63.
    Patil NS, Wong DL, Collier KD et al. Fluorescent derivatization of a protease antigen to track antigen uptake and processing in human cell lines. BMC Immunology 2004; 5:12.PubMedCrossRefGoogle Scholar
  64. 64.
    Huang M, Ma Z, Khor E et al. Uptake of FITC-chitosan nanoparticles by A549 cells. Pharmac Res 2002; 19(10):1488–1494.CrossRefGoogle Scholar
  65. 65.
    Huang M, Khor E, Lim LY. Uptake and toxicity of chitosan molecules and nanoparticles: Effects of molecular weight and degree of deacetylation. Pharmac Res 2004; 21(2):344–353.CrossRefGoogle Scholar
  66. 66.
    Ma Z, Lim LY. Uptake of chitosan and associated insulin in a Caco2 cell monolayers: A comparison between chitosan molecules and chitosan nanoparticles. Pharmac Res 2003; 20(11):1812–1819.CrossRefGoogle Scholar
  67. 67.
    Maselli A, Laevsky G, Knecht DA. Kinetics of binding, uptake and degradation of live fluorescent (DsRed) bacteria by Dictyostelium. Microbiology 2002; 148:413–420.PubMedGoogle Scholar
  68. 68.
    Chenevier P, Veyret B, Roux D et al. Interaction of cationic colloids at the surface of J774 Cells: A kinetic analysis. Biophys J 2002; 79:1298–1309.CrossRefGoogle Scholar
  69. 69.
    Saxena V, Sadoqi M. Tiny bubbles. SPIE’s Magazine 2004; September 21-23.Google Scholar
  70. 70.
    Qaddoumi MG, Ueda H, Yang J et al. The characteristics and mechanisms of uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell layers. Pharmac Res 2004; 21(4):641–648.CrossRefGoogle Scholar
  71. 71.
    Zhang Y, Huang N. Intracellular uptake of CdSe-ZnS/Polystyrene Nanobeads. J Biomed Mater Res Part B Appl Biomaterials 2005; 76B:161–168.CrossRefGoogle Scholar
  72. 72.
    Schulze K, Koch A, Petri-Fink A et al. Uptake and biocompatibility of functionalized poly(vinylalcohol) coated superparamagnetic maghemite nanoparticles by synoviocytes in vitro. J Nanosci Nanotechnol 2006; 6(9–10):2829–2840.CrossRefGoogle Scholar
  73. 73.
    Yang P, Sun X, Chiu J et al. Transferrin-mediated gold nanoparticle cellular uptake. Bioconjugate Chem 2005; 16:494–496.CrossRefGoogle Scholar
  74. 74.
    John TA, Vogel SM, Tiruppathi C et al. Q uantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. Am J Physiol. Lung Cell Mol Physiol 2003; L187–L196.Google Scholar
  75. 75.
    Bianco A, Hoebeke J, Godefroy S et al. Cationic carbon nanotubes bind to CpG Oligodeoxynucleotides and enhance their immunostimulatory properties. J Am Chem Soc 2004; 127:58–59.CrossRefGoogle Scholar
  76. 76.
    Schubbe S, Kube M, Scheffel A et al. Characterization of a spontaneous nonmagnetic mutant of magnetospirillium gryphiswaldense reveals a large deletion comprising a putative magnetosome island. J Bacteriol 2003; 185(19):5779–5790.PubMedCrossRefGoogle Scholar
  77. 77.
    Moore A, Marecos E, Bogdanov A et al. Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model. Radiol 2000; 214:568–574.Google Scholar
  78. 78.
    Hussain SM, Javorina AK, Schrand AM et al. The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. J Toxicol Sci 2006; 92(2):456–463.CrossRefGoogle Scholar
  79. 79.
    Skebo J, Grabinski C, Schrand A et al. Assessment of metal nanoparticle agglomeration, uptake and interaction using a high illuminating system. Int J Tox 2007; 26(2):135–141.CrossRefGoogle Scholar
  80. 80.
    Foster B. Focus on microscopy: A technique for imaging live cell interactions and mechanisms. Am Lab 2004; 11:21–27.Google Scholar
  81. 81.
    Vodyanoy V. High resolution light microscopy of live cells. Microscopy Today 2005; 13:26–28.Google Scholar
  82. 82.
    Gileadi O, Sabban A. Squid sperm to clam eggs: Imaging wet samples in a scanning electron microscope. Biol Bull 2003; 205:177–179.PubMedCrossRefGoogle Scholar
  83. 83.
    Thiberge S, Nechushtan A, Sprinzak D et al. Scanning electron microscopy of cells and tissues under fully hydrated conditions. Proc Natl Acad Sci USA 2004; 101(10):3346–3351.PubMedCrossRefGoogle Scholar
  84. 84.
    Ruach-Nir I. An innovative method for imaging and chemical analysis of wet samples in scanning electron microscopes. Microscopy Today 2005:10–14.Google Scholar
  85. 85.
    Behar V. Applications of a novel SEM technique for the analysis of hydrated samples. Microsc Microanal 2005; 19(4).Google Scholar
  86. 86.
    Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005; 113(7):823–839.PubMedCrossRefGoogle Scholar
  87. 87.
    Wang H, Joseph JA. Q uantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 1999; 27:612–616.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Amanda M. Schrand
    • 1
    • 2
    Email author
  • Liming Dai
    • 2
  • John J. Schlager
    • 1
  • Saber M. Hussain
    • 1
  1. 1.Applied Biotechnology Branch, Human Effectiveness DirectorateAir Force Research LaboratoryWright-Patterson AFBUSA
  2. 2.Department of Chemical and Materials EngineeringUniversity of DaytonDaytonUSA

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