Toxicity Studies of Carbon Nanotubes

  • Jelena Kolosnjaj
  • Henri Szwarc
  • Fathi Moussa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 620)

Abstract

As for fullerenes, the potential and the growing use of CNT and their mass production have raised several questions about their safety and environmental impact. Research on the toxicity of carbon nanotubes has just begun and the data are still fragmentary and subject to criticisms. Preliminary results highlight the difficulties in evaluating the toxicity of this new and heterogeneous carbon nanoparticle family. A number of parameters including structure, size distribution and surface area, surface chemistry and surface charge, and agglomeration state as well as purity of the samples, have considerable impact on the reactivity of carbon nanotubes. However, available data clearly show that, under some conditions, nanotubes can cross the membrane barriers and suggests that if raw materials reach the organs they can induce harmful effects as inflammatory and fibrotic reactions. Therefore, many further studies on well-characterized materials are necessary to determine the safety of carbon nanotubes as well as their environmental impact.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Saito R, Dresselhaus G, Dresselhaus MS. Physical properties of carbon nanotubes. London: Imperial College Press, 1998.Google Scholar
  2. 2.
    Popov VN. Carbon nanotubes: Properties and application. Mater Sci Eng 2004; R43:61–102.Google Scholar
  3. 3.
    Baughman RH, Zakhidov AA, De Heer WA. Carbon nanotubes-The route toward applications. Science 2002; 297:787–792.PubMedCrossRefGoogle Scholar
  4. 4.
    Special issue on carbon nanotubes. Acc Chem Res 2002; 35:997–1113.Google Scholar
  5. 5.
    Balavoine F, Richard C, Mioskowski C et al. Helical crystallization of proteins on carbon nanotubes: A first step towards the development of new biosensors. Angew Chem Int Ed 1999; 38:1912–1915.CrossRefGoogle Scholar
  6. 6.
    Bekyarova E, Ni Y, Malarkey EB et al. Applications of carbon nanotubes in biotechnology and biomedicine. J Biomed Nanotechnol 2005; 1:3–17.CrossRefGoogle Scholar
  7. 7.
    Lin Y, Taylor S, Li H et al. Advances toward bioapplications of carbon nanotubes. J Mater Chem 2004; 14:527–541.CrossRefGoogle Scholar
  8. 8.
    Richard C, Balavoine F, Mioskowski C et al. Supramolecutar self-assembly of lipid derivatives on carbon nanotubes. Science 2003; 300:775–778.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang J, Musameh M, Lin Y. Solubilization of carbon nanotubes by nafion toward the preparation of amperometric biosensors. J Am Chem Soc 2003; 125:2408–2409.PubMedCrossRefGoogle Scholar
  10. 10.
    Wang S, Delduco DF, Lustig SR et al. Peptides with selective affinity for carbon nanotubes. Nat Mater 2003; 2:196–200.PubMedCrossRefGoogle Scholar
  11. 11.
    Mattson MP, Haddon RC, Rao AM. Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth. J Mol Neurosci 2000; 14:175–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen X, Lee GS, Zettl A et al. Biomimetic engineering of carbon nanotubes by using cell surface mucin mimics. Angew Chem Int Ed 2004; 43:6112–6116.Google Scholar
  13. 13.
    Park KH, Chhowalla M, Iqbal Z et al. Single-walled carbon nanotubes are a new class of ion channel blockers. J Biol Chem 2003; 278:50212–50216.PubMedCrossRefGoogle Scholar
  14. 14.
    Bianco A, Kostarelos K, Partidos CD et al. Biomedical applications of functionalised carbon nanotubes. Chem Commun 2005; 571–577.Google Scholar
  15. 15.
    Bianco A, Prato M. Can carbon nanotubes be considered useful tools for biological applications? Adv Mater 2003; 15:1765–1768.CrossRefGoogle Scholar
  16. 16.
    Barone PW, Baik S, Heller D et al. Near-infrared optical sensors based on single-walled carbon nanotubes. Nature Materials 2005; 4:86–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Lu X, Chen Z. Curved pi-conjugation, aromaticity, and the related chemistry of small fullerenes (<C60) and single-walled carbon nanotubes. Chem Rev 2005; 105(10):3643–96.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen RJ, Zhang Y, Wang D et al. Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization. J Am Chem Soc 2001; 123:3838–3839.PubMedCrossRefGoogle Scholar
  19. 19.
    Minko T. Soluble polymer conjugates for drug delivery. Curr Drug Discov Technol 2005; 2:15–20.Google Scholar
  20. 20.
    Sinha N, Yeow JT. Carbon nanotubes for biomedical applications. IEEE Trans Nanobioscience 2005; 4(2):180–195.PubMedCrossRefGoogle Scholar
  21. 21.
    Islam MF, Rojas E, Bergey DM et al. High weight fraction surfactant solubilization of single-wall carbon nanotubes in water. Nano Lett 2003; 3:269–273.CrossRefGoogle Scholar
  22. 22.
    Moore VC, Strano MS, Haroz EH et al. Individualy suspended single-walled carbon nanotubes in various surfactants. Nano Lett 2003; 3:1379–1382.CrossRefGoogle Scholar
  23. 23.
    Star A, Stoddart JF, Steuerman D et al. Preparation and properties of polymer-wrapped single-walled carbon nanotubes. Angew Chem Int Ed 2001; 40:1721–1725.CrossRefGoogle Scholar
  24. 24.
    Niyogi S, Hu H, Hamon MA et al. Chromatographic purification of soluble single-walled carbon nanotubes. J Am Chem Soc 2001; 123:733–734.PubMedCrossRefGoogle Scholar
  25. 25.
    Ziegler KJ, Gu Z, Peng H et al. Controlled oxidative cutting of single-walled carbon nanotubes. J Am Chem Soc 2005; 127:1541–1547.PubMedCrossRefGoogle Scholar
  26. 26.
    Shvedova AA, Castranova V, Kisin ER et al. Exposure to carbon nanotube material: Assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 2003; 66(20):1909–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Shvedova AA, Kisin ER, Murray AR et al. Exposure of human bronchial epithelial cells to carbon nanotubes causes oxidative stress and cytotoxicity. Ioannina, Greece: 2004:91–103, (Proc Soc Free Rad Research Meeting, European Section, June 26–29, 2003).Google Scholar
  28. 28.
    Cui D, Tian F, Ozkan CS et al. Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 2005; 155(1):73–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Jia G, Wang H, Yan L et al. Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol 2005; 39(5):1378–83.PubMedCrossRefGoogle Scholar
  30. 30.
    Monteiro-Riviere NA, Nemanich RJ, Inman AO et al. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 2005; 155(3):377–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Murr LE, Garza KM, Soto KF et al. Cytotoxicity 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
  32. 32.
    Sato Y, Yokoyama A, Shibata K et al. Influence of length on cytotoxicity 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(2):176–82.PubMedCrossRefGoogle Scholar
  33. 33.
    Ghibelli L, De Nicola M, Somma G et al. Lack of direct cytotoxic effect of intracellular nanotubes. G Ital Med Lav Ergon 2005; 27(3):383–4.PubMedGoogle Scholar
  34. 34.
    Manna SK, Sarkar S, Barr J et al. Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. Nano Lett 2005; 5(9):1676–84.PubMedCrossRefGoogle Scholar
  35. 35.
    Reelfs O, Tyrrell RM, Pourzand C. Ultraviolet A radiation-induced immediate iron release is a key modulator of the activation of NF-kappaB in human skin fibroblasts. J Invest Dermatol 2004; 122(6):1440–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Bottini M, Bruckner S, Nika K et al. Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 2006; 160(2):121–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Sayes CM, Liang F, Hudson JL et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 2006; 161(2):135–42.PubMedCrossRefGoogle Scholar
  38. 38.
    Fenoglio I, Tomatis M, Lison D et al. Reactivity of carbon nanotubes: Free radical generation or scavenging activity? Free Radic Biol Med 2006; 40(7):1227–33.PubMedCrossRefGoogle Scholar
  39. 39.
    Watts PCP, Fearon PK, Hsu WK et al. Carbon nanotubes as polymer antioxidants. J Mater Chem 2003; 13:491–495.CrossRefGoogle Scholar
  40. 40.
    Krusic PJ, Wasserman E, Keizer PN et al. Radical reaction of C60. Science 1991; 254:1183–1185.PubMedCrossRefGoogle Scholar
  41. 41.
    Fiorito S, Serafino A, Andreola F et al. Effects of fullerenes and single-wall carbon nanotubes on murine and human macrophages. Carbon 2006; 44(6):1100–1105.CrossRefGoogle Scholar
  42. 42.
    Tsien M, Morris D, Petruska J et al. Redox cycling and DNA damage induced by iron-containing carbon nanomaterials Abstracts of Papers. Proceedings of the 229th ACS National Meeting, San Diego, CA, United States. IEC-075. Washington, DC: American Chemical Society, 2005;13–17.Google Scholar
  43. 43.
    Worle-Knirsch JM, Pulskamp K, Krug HF. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 2006; 6(6):1261–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Magrez A, Kasas S, Salicio V et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett 2006; 6(6):1121–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Kagan VE, Tyurina YY, Tyurin VA et al. Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: Role of iron. Toxicol Lett 2006; 165(1):88–100.PubMedCrossRefGoogle Scholar
  46. 46.
    Simon A, Thiebault C, Reynaud C et al. Toxicity of oxide nanoparticles and carbon nanotubes on cultured pneumocytes: Impact of size, structure and surface charge. Toxicology Letters 2006; 164(1):20, (S222).Google Scholar
  47. 47.
    Witzmann FA, Monteiro-Riviere NA. Multi-walled carbon nanotube exposure alters protein expression in human keratinocytes Nanomedicine: Nanotechnology, Biology and Medicine. 2006; 2(3):158–168.CrossRefGoogle Scholar
  48. 48.
    Soto KF, Carrasco A, Powell TG et al. Biological effects of nanoparticulate materials: Materials Science and Engineering. 2006; 26(8):1421–1427.CrossRefGoogle Scholar
  49. 49.
    Tian F, Cui D, Schwarz H et al. Cytotoxicity of single-wall carbon nanotubes on human fibroblasts. Toxicol In Vitro 2006; 20(7):1202–12.PubMedCrossRefGoogle Scholar
  50. 50.
    Davoren M, Herzog E, Casey A et al. In vitro toxicity evaluation of single walled carbon nanotubes on human A549 lung cells. Toxicology in Vitro 2006 (doi:10.1016/j.tiv.2006.10.007).Google Scholar
  51. 51.
    Casey A, Davoren M, Herzog E et al. Probing the interaction of single walled carbon nanotubes within cell culture medium as a precursor to toxicity testing. Carbon doi:10.1016/j.carbon.2006.08.009.Google Scholar
  52. 52.
    Monteiro-Riviere NA, Inman AO. Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 2006; 44(4):1070–1078.CrossRefGoogle Scholar
  53. 53.
    Meng J, Song L, Meng J et al. Using single-walled carbon nanotubes non-woven films as scaffolds to enhance long-term cell proliferation in vitro. J Biomed Mater Res A 2006; 79(2):298–306.PubMedGoogle Scholar
  54. 54.
    Pulskamp K, Diabaté S, Krug HF. Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicology Letters doi: 10.1016/j.toxlet.2006.11.001.Google Scholar
  55. 55.
    Mattson MP, Haddon RC, Rao AM. Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth. J Mol Neurosci 2000; 14:175–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Pantarotto D, Briand JP, Prato M et al. Translocation of bioactive peptides across cell membranes by carbon nanotubes. Chem Commun (Camb) 2004;(1):16–7.Google Scholar
  57. 57.
    Shi Kam NW, Jessop TC, Wender PA et al. Nanotube molecular transporters: Internalization of carbon nanotube-protein conjugates into Mammalian cells. J Am Chem Soc 2004; 126(22):6850–1.PubMedCrossRefGoogle Scholar
  58. 58.
    Nimmagadda A, Thurston K, Nollert MU et al. Chemical modification of SWNT alters in vitro cell-SWNT interactions. J Biomed Mater Res A 2006; 76(3):614–25.PubMedGoogle Scholar
  59. 59.
    Dumortier H, Lacotte S, Pastorin G et al. Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells. Nano Lett 2006; 6(7):1522–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Huczko A, Lange H. Carbon nanotubes: Experimental evidence for a null risk of skin irritation and allergy. Fullerene Sci Tech 2001; 9(2):247–50.Google Scholar
  61. 61.
    Maynard AD, Baron PA, 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 A 2004; 67(1):87–107.PubMedCrossRefGoogle Scholar
  62. 62.
    Lam CW, James JT, McCluskey R et al. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 2004; 77(1):126–34.PubMedCrossRefGoogle Scholar
  63. 63.
    Warheit DB, Laurence BR, Reed KL et al. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 2004; 77(1):117–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Warheit DB. What is currently known about the health risks related to carbon nanotube exposures? Carbon 2006; 44(6):1064–1069.CrossRefGoogle Scholar
  65. 65.
    Muller J, Huaux F, Moreau N et al. Respiratory toxicity of multi-wall carbon nanotubes. Toxicol Appl Pharmacol 2005; 207(3):221–31.PubMedGoogle Scholar
  66. 66.
    Shvedova AA, Kisin ER, Mercer R et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 2005; 289(5):L698–708.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhu Y, Zhao Q, Li Y et al. The interaction and toxicity of multi-walled carbon nanotubes with Stylonychia mytilus. J Nanosci Nanotechnol 2006; 6(5):1357–64.PubMedCrossRefGoogle Scholar
  68. 68.
    Koyama S, Endo M, Kim YA et al. Role of systemic T-cells and histopathological aspects after subcutaneous implantation of various carbon nanotubes in mice. Carbon 2006; 44(6):1079–1092.CrossRefGoogle Scholar
  69. 69.
    Pantarotto D, Partidos CD, Hoebeke J et al. Immunization with peptide-functionalized carbon nanotubes enhances virus-specific neutralizing antibody responses. Chem Biol 2003; 10(10):961–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Singh R, Pantarotto D, Lacerda L et al. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc Natl Acad Sci USA 2006; 103(9):3357–62.PubMedCrossRefGoogle Scholar
  71. 71.
    Carrero-Sanchez JC, Elias AL, Mancilla R et al. Biocompatibility and toxicological studies of carbon nanotubes doped with nitrogen. Nano Lett 2006; 6(8):1609–16.PubMedCrossRefGoogle Scholar
  72. 72.
    Robichaud CO, Tanzil D, Weilenmann U et al. Relative risk analysis of several manufactured nanomaterials: An insurance industry context. Environ Sci Technol 2005; 39(22):8985–94.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Jelena Kolosnjaj
    • 1
    • 2
  • Henri Szwarc
    • 1
  • Fathi Moussa
    • 1
  1. 1.UMR CNRS 8612, Faculté de PharmacieUniversité Paris-Sud 11Châtenay-MalabryFrance
  2. 2.Pharmacy DepartmentUniversity of LjubljanaLjubljanaSlovenia

Personalised recommendations