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Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes

  • Inorganic Compounds
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Abstract

Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10–15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10–15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation–mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.

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References

  • Aillon KL, Xie Y, El-Gendy N, Berkland CJ, Forrest ML (2009) Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv Drμg Deliv Rev 61:457–466

    Article  CAS  Google Scholar 

  • Aubin-Tam ME, Hamad-schifferli K (2008) Structure and function of nanoparticle-protein conjugates. Biomed Mater 3:1–17

    Article  Google Scholar 

  • Bianco A, Kostarelos K, Partidos CD, Prato M (2005) Biomedical applications of functionalised carbon nanotubes. Chem Commun 5:571–577

    Article  Google Scholar 

  • Bonnemann H, Richards RM (2001) Nanoscopic metal particles-synthetic methods and potential applications. Eur J Inorg Chem 10:2455–2480

    Article  Google Scholar 

  • Bottini M, Tautz L, Huynh H, Monosov E, Bottini N, Bellucci S, Mustelin T (2005) Covalent decoration of multiwalled carbon nanotubes with silica nanoparticles. Chem Commun 6:758–760

    Article  Google Scholar 

  • Bottini M, Bruckner S, Nika K, Bottini N, Bellucci S, Magrini A, Bergamaschi A, Mustelin T (2006) Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 160:121–126

    Article  PubMed  CAS  Google Scholar 

  • Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412–419

    Article  PubMed  CAS  Google Scholar 

  • Cui D, Tian F, Ozkan CS, Wang M, Gao H (2005) Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73–85

    Article  PubMed  CAS  Google Scholar 

  • Di Sotto A, Chiaretti M, Carru GA, Bellucci S, Mazzanti G (2009) Multi-walled carbon nanotubes: lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett 184:192–197

    Article  PubMed  Google Scholar 

  • Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22

    Article  PubMed  CAS  Google Scholar 

  • Gooding JJ, Wibowon R, Liu JQ, Yang WR, Losic D, Orbons S, Mearns FJ, Shapter JG, Hibbert DB (2003) Protein electrochemistry using aligned carbon nanotube arrays. J Am Chem Soc 125:9006–9007

    Article  PubMed  CAS  Google Scholar 

  • Helland A, Wick P, Koehler A, Schmid K, Som C (2007) Reviewing the environmental and human health knowledge base of carbon nanotubes. Environ Health Perspect 115:1125–1131

    Article  PubMed  CAS  Google Scholar 

  • Hu H, Ni YC, Montana V, Haddon RC, Parpura V (2004) Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett 4:507–511

    Article  PubMed  CAS  Google Scholar 

  • Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983

    Article  PubMed  CAS  Google Scholar 

  • IARC (1977) Monographs on the evaluation of carcinogenic risk to chemicals on man: Asbestos. 14:1–106

  • Kam NWS, Liu Z, Dai HJ (2005) Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J Am Chem Soc 127:12492–12493

    Article  PubMed  CAS  Google Scholar 

  • Korean Agency for Technology and Standards (2009) Korean Industrial Standards D 2717, Evaluation method for the degree of macrodispersion of carbon nanotubes using UV-VIS-NIR absorption spectroscopy

  • Lee JY, Kim JS, An KH, Lee K, Kim DY, Bae DJ, Lee YH (2005) Electrophoretic and dynamic light scattering in evaluating dispersion and size distribution of single-walled carbon nanotubes. J Nanosci Nanotechnol 5:1045–1049

    Article  PubMed  CAS  Google Scholar 

  • Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49

    Article  PubMed  CAS  Google Scholar 

  • Lin Y, Taylor S, Li H, Fernando SKA, Qu L, Wang W, Gu L, Zhou B, Sun YP (2004) Advances towards bioapplications of carbon nanotubes. J Mater Chem 14:527–541

    Article  CAS  Google Scholar 

  • Lindberg HK, Falck GC, Suhonen S, Vippola M, Vanhala E, Catalán J, Savolainen K, Norppa H (2009) Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. Toxicol Lett 186:166–173

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Sun XM, Nakayama-Ratchford N, Dai HJ (2007a) Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 1:50–56

    Article  PubMed  Google Scholar 

  • Liu Z, Winters M, Holodniy M, Dai HJ (2007b) SiRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed 46:2023–2027

    Article  CAS  Google Scholar 

  • MacGregor JT, Heddle JA, Hite M, Margolin BH, Ramel C, Salamone MF, Tice RR, Wild D (1987) Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutat Res 189:103–112

    Article  PubMed  CAS  Google Scholar 

  • Maron DM, Ames BN (1983) Reviewed methods for the Salmonella mutagenicity test. Mutat Res 113:173–215

    PubMed  CAS  Google Scholar 

  • Mattson MP, Haddon RC, Rao AM (2000) Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth. J Mol Neurosci 14:175–182

    Article  PubMed  CAS  Google Scholar 

  • Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW (2007) Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 150:552–558

    Article  PubMed  CAS  Google Scholar 

  • Murphy CJ (2002) Materials science: nanocubes and nanoboxes. Science 298:2139–2141

    Article  PubMed  CAS  Google Scholar 

  • OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 471, bacterial reverse mutation test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France

  • OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 473, In vitro mammalian chromosome aberration test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France

  • OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 474, Mammalian erythrocyte micronucleus test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France

  • Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760

    Article  PubMed  CAS  Google Scholar 

  • Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, Stone V, Brown S, Macnee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428

    Article  PubMed  CAS  Google Scholar 

  • Porter D, Sriram K, Wolfarth M, Jefferson A, Schwegler-Berry D, Andrew ME, Castranova V (2008) A biocompatible medium for nanoparticle dispersion. Nanotoxicology 2:144–154

    Article  CAS  Google Scholar 

  • Schmid W (1976) The micronucleus test for cytogenetic analysis. In: Hollaender A (ed) Chemical mutagens: principles and methods for their detection, vol 4. Plenum Press, New York, pp 31–53

    Google Scholar 

  • Szendi K, Varga C (2008) Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res 28:349–352

    PubMed  CAS  Google Scholar 

  • Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J (2008) Induction of mesothelioma in p53 ± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105–116

    Article  PubMed  CAS  Google Scholar 

  • Tran CL, Hankin SM, Ross B, Aitken RJ, Jones AD, Donaldson K, Stone V, Tantra R (2008) An outline scoping study to determine whether high aspect ratio nanoparticles (HARN) should raise the same concerns as do asbestos fibres, IOM Report on Project CB0406, Edinburgh, UK

  • Wirnitzer U, Herbold B, Voetz M, Ragot J (2009) Studies on the in vitro genotoxicity of baytubes®, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). Toxicol Lett 186:160–165

    Article  PubMed  CAS  Google Scholar 

  • You CC, De M, Rotello VM (2005) Monolayer-protected nanoparticle–protein interactions. Curr Opin Chem Biol 9:639–646

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the financial support (R&D program) of the National Institute of Environmental Research (NIER) of the Republic of Korea.

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Authors and Affiliations

  1. Biosafety Evaluation Headquarter, Korea Environment and Merchandise Testing Institute, Incheon, South Korea

    Jin Sik Kim, Hyun Sun Cho, Ki Heon Kim, Kyung Seuk Song & Il Je Yu

  2. Department of Physics, Center for Nanotubes and Nanostructured Composites, Sungkyunkwan Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon, South Korea

    Kyu Lee & Young Hee Lee

  3. Risk Assessment Division, National Institute of Environmental Research, Incheon, South Korea

    Kyung Hee Choi & Sang Hee Lee

  4. Fusion Technology Research Institute, Hoseo University, 165 Sechul-ri, Baebang-myun, Asan, 336-795, South Korea

    Chang Soo Kang & Il Je Yu

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  1. Jin Sik Kim
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Correspondence to Il Je Yu.

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Kim, J.S., Lee, K., Lee, Y.H. et al. Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes. Arch Toxicol 85, 775–786 (2011). https://doi.org/10.1007/s00204-010-0574-0

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