Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 7 (2009), No 1, p 1-13




Carbon nanotubes: toxicological impact on human health and environment

Gracial Tejral, Nagender Reddy Panyala, Josef Havel

Address: Josef Havel, Department of Chemistry, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic
Havel@chemi.muni.cz

Received 25th December 2008.
Revised 23rd January 2009.
Published online 10th March 2009.

Full text article (pdf)
Full text article (html)

SUMMARY
Nanotechnology is an emerging field of science which is producing nano-sized materials. Some nanomaterials are having a significant impact in health care. Of these, carbon nanotubes (CNTs) represent one of the most promising materials in the field of nano-science and technology. Their potential in industrial applications has brought them much attention and the wide spectrum of usage has made it imperative that the impact of CNTs on human health and the environment is investigated thoroughly. In addition to their various beneficial applications, there is a potential for hazardous effects on human health. For example, the potential hazards through inhalation of CNTs have not been sufficiently evaluated. CNTs produce reactive oxygen species (ROS) which are associated with diminishing cellular activities, such as a decrease in the mitochondrial membrane potential etc. This paper reviews the hazardous influence of CNTs on human health and the environment. Specifically, the effects of CNTs on lung toxicity, skin irritation and CNTs cyto-toxicity on various cell lines are reviewed. Biomedical applications and biocompatibility of carbon nanotubes are also summarized.

KEY WORDS
carbon nanotubes; nano-materials; nanotechnology; cytotoxicity; lung toxicity; skin irritation; biocompatibility


REFERENCES
Allen TM, Cullis PR: Drug delivery system: Entering the main stream. Science 303:1818-1822, 2004.

Ausman KD, Piner R, Lourie O, Ruoff RS: Organic solvent dispersions of single-walled carbon nanotubes: Toward solutions of pristine nanotubes. J Phys Chem B 104:8911-8915, 2000.

Balani K, Anderson R, Lahaa T, Andaraa M, Terceroa J, Crumplerb E, Agarwala A: Plasma-sprayed carbon nanotube reinforced hydroxyapatite coatings and their interaction with human osteoblasts in vitro. Biomaterials 28:618-624, 2007.

Bauer C, Buchgeister J, Hischier R, Poganietz WR, Schebek L, Warsen J: Towards a framework for life cycle thinking in the assessment of nanotechnology. J Cleaner Production 16:910-926, 2008.

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

Bianco A, Kostarelos K, Prato M: Applications of carbon nanotubes in drug delivery. Current Opinion in Chem Biol 9:674-679, 2005.

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

Cai D, Mataraza JM, Qin ZH, Huang Z, Huang J, Chiles TC, Carnahan D, Kempa K, Ren Z: Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing. Nature Meth 2:449-454, 2005.

Cheng J, Flahaut E, Cheng SH: Effect of carbon nanotubes on developing zebra fish (Danio rerio) embryos. Environ Toxicol Chem 26:708-716, 2007.

Chlopek J, Czajkowska B, Szaraniec B, Frackowiak E, Szostak K, Beguin F: In vitro studies of carbon nanotubes biocompatibility. Carbon 44:1106-1111, 2006.

Colvin VL: The potential environmental impacts of engineered nanomaterials. Nature Biotechnol 21:1166-1170, 2003.

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

Deng X, Jia G, Wang H, Sun H, Wang X, Yang S, Wang T, Liu Y: Translocation and fate of multi-walled carbon nanotubes in vivo. Carbon 45:1419-1424, 2007.

Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A: Carbon Nanotubes: A Review of Their Properties in Relation to Pulmonary Toxicology and Workplace Safety. Toxicol Sci 92:5-22, 2006.

Donaldson K, Tran CL: Inflammation caused by particles and fibres. Inhal Toxicol 14:5-27, 2002.

Dong L, Joseph KL, Witkowski CM, Craig MM: Cytotoxicity of single-walled carbon nanotubes suspended in various surfactants. Nanotechnol 19:255702, 2008.

Elosta S, Gajdosova D, Havel J: MALDI TOF MS of selected mycotoxins in barley. J Appl Biomed 5:39-47, 2007.

Foldvari M, Bagonluri M: Carbon nanotubes as functional excipients for nanomedicines: I. pharmaceutical properties. Nanomed Nanotechnol Biol Med 4:183-200, 2008.

Foldvari M, Bagonluri M: Carbon nanotubes as functional excipients for nanomedicines: II. drug delivery and biocompatibility issues. Nanomed Nanotechnol Biol Med 4:173-182, 2008.

Grobert N: Carbon nanotubes - becoming clean. Materials Today 10:28-35, 2007.

Hassellov M, James Readman JW, Ranville JF, Tiede K: Nanoparticle analysis and characterization methodologies in environmental risk assessment of engineered nanoparticles. Ecotoxicol 17:344-361, 2008.

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

Hirano S, Kanno S, Furuyama A: Multi-walled carbon nanotubes injure the plasma membrane of macrophages. Toxicol Appl Pharmacol 232:244-251, 2008.

Hou PX, Xu ST, Ying Z, Yang QH, Liu C, Cheng HM: Hydrogen adsorption/desorption behavior of multi-walled carbon nanotubes with different diameters. Carbon 41:2471-2476, 2003.

Huczko A, Lange H, Bystrzejewski M, Baranowski P: Pulmonary toxicity of 1-D nanocarbon materials. Fullerenes Nanotubes. Carbon Nanostruct 13:141-145, 2005.

Huczko A, Lange H, Calko E, Grubek-Jaworska H, Droszcz P: Physiological testing of carbon nanotubes: are they asbestos like? Fullerene Sci Tech 9:251-254, 2001.

Huczko A, Lange H: Carbon nanotubes: experimental evidence for a null risk of skin irritation and allergy. Fullerene Sci Tech 9:247-250, 2001.

Jia G, Wang H, Yan L, Wang X, Pei R, Yan T, Zhao Y, Guo X: Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube and fullerene. Environ Sci Technol 39:1378-83, 2005.

Johnston DE, Islam MF, Yodh AG, Johnson AT: Electronic devices based on purified carbon nanotubes grown by high-pressure decomposition of carbon monoxide. Nat Mater 4:589-592, 2005.

Jorio A, Saito R, Hafner JH, Lieber CM, Hunter M, McClure T, Dresselhaus G, Dresselhaus MS: Structural (n, m) determination of isolated single-wall carbon nanotubes by resonant Raman scattering. Phys Rev Lett 86:1118-1121, 2001.

Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA: Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett 165:88-100, 2006.

Kam NWS, Dai HJ: Carbon nanotubes as intracellular protein transporters: Generality and biological functionality. J Am Chem Soc 127:6021-6026, 2005.

Kam NWS, Jessop TC, Wender PA, Dai HJ: Nanotube molecular transporters: Internalization of carbon nanotube-protein conjugates into mammalian cells. J Am Chem Soc 126:6850-6851, 2004.

Kleiner K, Hogan J: How safe is nanotech? New Scientist pp. 14-15, 2003.

Klumpp C, Kostarelos K, Prato M, Bianco A: Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404-412, 2006.

Kohler AR, Som C, Helland A, Gottschalk F: Studying the potential release of carbon nanotubes throughout the application life cycle. J Cleaner Production 16:927-937, 2008.

Koyama S, Endo M, Kim YA, Hayashi T, Yanagisawa T, Osaka K, Oyama H, Haniu H, Kuroiwa N: Role of systemic T-cells and histopathological aspects after subcutaneous implantation of various carbon nanotubes in mice. Carbon 44:1079-1092, 2006.

Lam C, James JT, McCluskey R, Hunter R: Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126-134, 2004.

Li Z, Hulderman T, Salmen R, Chapman R, Leonard SS, Young SH, Shvedova A, Luster M, Simeonova PP: Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ Health perspect 115:377-382, 2007.

Liu Y, Wu DC, Zhang WD, Jiang X, He CB, Chun TS, Goh SH, Leong KW: Polyethylenimine-grafted multi-walled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. Angew Chem Int Ed 44:4782-4785, 2005.

Liu A, Sun K, Yang J, Zhao D: Toxicological effects of multi-wall carbon nanotubes in rats. J Nanopart Res 10:1303-1307, 2008.

Lu C, Su F: Adsorption of natural organic matter by carbon nanotubes. Separation Purification Technol 58:113-121, 2007.

Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice-Ficht AC, Ramesh GT: Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappa B in human keratinocytes. Nano Lett 5:1676-1684, 2005.

Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova V: Exposure to carbon nanotube material: Aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health Part A 67:87-100, 2004.

Mondal KC, Coville NJ, Witcomb MJ, Tejral G, Havel J: Boron mediated synthesi sof multiwalled carbon nanotubes by chemical vapor deposition. Chem Phys Lett 437:87-91, 2007.

Monteiro-Riviere NA, Inman AO: Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 44:1070-1078, 2006.

Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE: Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377-384, 2005.

Moore VC, Strano MS, Haroz EH, Hauge RH, Smalley RE: Individually suspended single-walled carbon nanotubes in various surfactants. Nano Lett 3:1379-1382, 2003.

Motta M, Li YL, Kinloch I, Windle A: Mechanical properties of continuously spun fibers of carbon nanotubes. Nano Lett 5:1529-1533, 2005.

Muller J, Huaux F, Lison D: Respiratory toxicity of carbon nanotubes: how worried should we be? Carbon 44:1048-56, 2006.

Muller J, Huaux F, Moreau N, Misson P, Heiler JF, Delos M, Arras M, Fonseca A, Nagy JB, Lison D: Respiratory toxicity of multi-wall carbon nanotubes. Toxicol App Pharmacol 207:221-31, 2005.

Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, Lison D, Kirsch-Vloders M: Clastogenic and aneugenic effects of multi-walled carbon nanotubes in epithelial cells. Carcinogenesis 29:427-433, 2008.

Murr LE, Garza KM, Soto KF, Carrasco A, Powell TG, Ramirez DA, Guerrero PA, Lopez DA, Venzor J III: 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 2:31-42, 2005.

Murr LE: Microstructures and nanostructures for environmental carbon nanotubes and nanoparticulate soots. Int J Environ Res Public Health 5:321-336, 2008.

Oberdorster E, Ortiz-Acevedo A, Xie H, Pantano P, Baughman RH, Musselman IH, Draper RK: Exposure of fathead minnow to fullerene and single-walled carbon nanotubes. J Soc Toxicol 84(S1):325, 2005.

Oberdorster E, Zhu S, Blickley TM, McClellan-Green P, Haasch ML: Ecotoxicology of carbon-based engineered nanoparticles: effects of fullerene (C60) on aquatic organisms. Carbon 44:1112-1120, 2006.

Panhuis MIH: Vaccine delivery by carbon nanotubes. Chem Biol 10:898-899, 2003.

Panyala NR, Eladia MPM, Havel J: Silver or silver nanoparticles: a hazardous threat to the environment and human health? J Appl Biomed 6:117-129, 2008.

Pohanka M, Jun D, Kuca K: Mycotoxin assays using biosensortechnology: A review. Drug and Chem Toxicol 30:253-261, 2007.

Pulskamp K, Worle-Knirsch JM, Hennrich F, Kern K, Krug HF: Human lung epithelial cells show biphasic oxidative burst after single-walled carbon nanotube contact. Carbon 45(11):2241-2249, 2007.

Pulskamp K, Diabate S, Harald F. Krug HF: Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 168:58-74, 2007.

Rao GP, Lu C, Su F: Sorption of divalent metal ions from aqueous solution by carbon nanotubes: A review. Separation and Purification Technology 58:224-231, 2007.

Sato Y, Motomiya K, Jeyadevan B, Tohji K, Sato G, Ishida H, Hirata T, Hatakeyama R: Effect of cerium ions in an arc peripheral plasma on the growth of radial single-walled carbon nanotubes. J Appl Phys 98:94313-94500, 2005.

Sayes CM, Liang F, Hudson JL, Mendez J, Guo W, Beach JM, Moore VC, Doyle CD, West JL, Billups WE, Ausman KD, Colvin VL: Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 161:135-142, 2005.

Shvedova AA, Castranova V: Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A 66:1909-1926, 2003.

Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antoini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V Baron P: Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol-Lung Cell Mol Physiol 289:698-708, 2005.

Smart SK, Cassady AI, Lu GQ, Martin DJ: The biocompatibility of carbon nanotubes. Carbon 44:1034-1047, 2006.

Tamura K, Takashi N, Akasaka T, Roska ID, Uo M, Totsuka Y, Watari F: Effects of micro/nano particle size on cell function and morphology. Key Eng Mater 254-6:919-22, 2004.

Tian F, Cui D, Schwarz H, Estrada GG, Kobayashi HK: Cytotoxicity of single-wall carbon nanotubes on human fibroblasts. Toxicol In Vitro 20:1202-1212, 2006.

Trojanowicz M: Analytical applications of carbon nanotubes: a review. TrAC Trends in Analytical Chemistry 25:480-489, 2006.

Valcarcel M, Cardenas S, Simonet BM, Moliner-Martinez Y, Lucena R: Carbon nanostructures as sorbent materials in analytical processes. Trends in Analytical Chemistry 27:34-43, 2008.

Walters DA, Ericson LM, Casavant MJ, Liu J, Colbert DT, Smith KA, Smalley RE: Elastic strain of freely suspended single-wall carbon nanotube ropes. Appl Phys Lett 74:3803-3805, 1999.

Wang W, Yokoyama A, Liao S, Omori M, Zhu Y, Uo M, Akasaka T, Watari F: Preparation and characteristics of a binderless carbon nanotube monolith and its biocompatibility. Mater Sci Eng C 7:1082-1086, 2007.

Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GAM, Webb TR: Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77:117-125, 2004.

Wei Y, Qiu L, Yu JCC, Lai EPC: Molecularly imprinted solid phase extraction in a syringe needle packed with polypyrrole-encapsulated carbon nanotubes for determination of ochratoxin a in red wine. Intl Food Sci Tech 13:375-380, 2007.

Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, Stark WJ, Bruinink A: The degree and kind of agglomeration affectcarbon nanotube cytotoxicity. Toxicol Lett 168:121-131, 2007.

Witzmann FA, Monteiro-Riviere NA: Multi-walled nanotube exposure alters protein expression in human keratinocytes. Nanomed Nanotechnol Biol Med 2:158-168, 2006.

Worle-Knirsch JM, Pulskamp K, Krug HF: Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:1261-1268, 2006.

Yao Dong-sheng, Cao H, Wen S, Liu Da-ling, Bai Y, Zheng Wen-jie: A novel biosensor for sterigmatocystin constructed by multi-walled carbon nanotubes (MWNT) modified with aflatoxin-detoxifizyme (ADTZ). Bioelectrochem 68:126-133, 2006.

Yang M, Kostov Y, Rasooly A: Carbon nanotubes based optical immuno detection of Staphylococcal enterotoxin B (SEB) in food. Intl J Food Microbiol 127:78-83, 2008.

Yang K, Zhu L, Xing B: Adsorption of Polycyclic Aromatic Hydrocarbons by Carbon Nanomaterials. Environ Sci Technol 40:1855-1861, 2006.

Yu JCC, Lai EPC: Molecularly imprinted polypyrrole modified carbon nanotubes on stainless steel frit for selective micro solid phase pre-concentration of ochratoxin A. Reactive and Functional polymers 66:702-711, 2006.

Yu MF, Files BS, Arepalli S, Ruoff RS: Tensile loading of ropes of single wall carbon nanotubes and their mechanical properties. Phys Rev Lett 84:5552-5555, 2000.

Zhang MF, Yudasaka M, Koshio A, Iijima S: Thermogravimetric analysis of single-wall carbon nanotubes ultrasonicated in monochlorobenzene. Chem Phys. Lett 364:420-426, 2002.

Zeni O, Palumbo R, Zeni L, Sarti M, Scarfi MR: Cytotoxicity investigation on cultured human blood cells treated with single-wall carbon nanotubes. Sensors 8:488-499, 2008.
CITED

Goh PS, Ismail AF, Ng BC. Carbon nanotubes for desalination: Performance evaluation and current hurdles. Desalination. 308: 2-14, 2013.

Shao CY, Chen SZ, Su BH, Tseng YFJ, Esposito EX, Hopfinger AJ. Dependence of QSAR Models on the Selection of Trial Descriptor Sets: A Demonstration Using Nanotoxicity Endpoints of Decorated Nanotubes. J Chem Inform Modeling. 53: 142-158, 2013.

Singh RP, Das M, Thakare V, Jain S. Functionalization Density Dependent Toxicity of Oxidized Multiwalled Carbon Nanotubes in a Murine Macrophage Cell Line. Chem Res Toxicol. 25: 2127-2137, 2012.

Vardharajula S, Ali SZ, Tiwari PM, Eroglu E, Vig K, Dennis VA, Singh SR. Functionalized carbon nanotubes: biomedical applications. Int J Nanomed. 7: 5361-5374, 2012.

Kasi AK, Afzulpurkar N, Kasi JK, Tuantranont A, Dulyaseree P. Utilization of cracks to fabricate anodic aluminum oxide nanoporous tubular and rectangular membrane. J Vac Sci Technol B. 29: 04D107, 2011.

Dolatabadi JEN, Omidi Y, Losic D. Carbon Nanotubes as an Advanced Drug and Gene Delivery Nanosystem. Curr Nanosci. 7: 297-314, 2011.

Cena LG, Peters TM. Characterization and Control of Airborne Particles Emitted During Production of Epoxy/Carbon Nanotube Nanocomposites. J Occup Environ Hyg. 8: 86-92, 2011.

Tiwari AJ, Marr LC. The Role of Atmospheric Transformations in Determining Environmental Impacts of Carbonaceous Nanoparticles. J Environ Quality. 39: 1883-1895, 2010.

Pohanka M, Vlcek V, Kuca K, Bandouchova H, Pikula J. Pesticide sorption in typical Central European soils evaluated using a photometric microplate assay based on acetylcholinesterase inhibition. J Appl Biomed. 8: 41-46, 2010.

Kim J, Van der Bruggen B. The use of nanoparticles in polymeric and ceramic membrane structures: Review of manufacturing procedures and performance improvement for water treatment. Environ Pollut. 158: 2335-2349, 2010.

Aruguete DM, Hochella MF. Bacteria-nanoparticle interactions and their environmental implications. Environ Chem. 7: 3-9, 2009.

Dong LF, Witkowski CM, Craig MM, Greenwade MM, Joseph KL. Cytotoxicity effects of different surfactant molecules conjugated to carbon nanotubes on human astrocytoma cells. Nanoscale Res Lett. 4: 1517-1523, 2009.

McRae R, Bagchi P, Sumalekshmy S, Fahrni CJ. In situ imaging of metals in cells and tissues. Chem Rev. 109: 4780-4827, 2009.

Pohanka M. Monoclonal and polyclonal antibodies production - preparation of potent biorecognition element. J Appl Biomed. 7: 115-121, 2009.

BACK