References

medlit

Гигиена и санитария

Hygiene and Sanitation

0016-99002412-0650

Federal Scientific Center of Hygiene named after F.F. Erisman

10.47470/0016-9900-2017-96-2-176-186

medlit-765

Research Article

ПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕ

PREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATION

Углеродные нанотрубки: механизмы действия, биологические маркеры и оценка токсичности in vivo (обзор литературы)

Carbon nanotubes: mechanisms of the action, biological markers and evaluation of the (review of literature)

Гмошинский

Иван Всеволодович

Gmoshinsky

Ivan V.

gmosh@ion.ru

Хотимченко

С. А.

Khotimchenko

S. A.

noemail@neicon.ru

Ригер

Н. А.

Riger

N. A.

noemail@neicon.ru

Никитюк

Д. Б.

Nikityuk

D. B.

noemail@neicon.ru

ФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи»Federal Research Centre of Nutrition and Biotechnology

2017

21102020

962176186

2020

Гмошинский И.В., Хотимченко С.А., Ригер Н.А., Никитюк Д.Б.

Gmoshinsky I.V., Khotimchenko S.A., Riger N.A., Nikityuk D.B.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.rjhas.ru/jour/article/view/765

Статья содержит анализ и обобщение данных о механизмах токсического действия углеродных нанотрубок (УНТ) на организм и результатах токсикологической оценки УНТ при ингаляционном и пероральном путях поступления. Выявление клеточных и молекулярных механизмов токсичности УНТ позволяет обосновать список наиболее чувствительных биохимических маркеров токсичности, которые могли быть использованы для мониторирования вредного действия УНТ на производстве и послужить перспективными мишенями для соответствующих фармакологических и иммунофармакологических интервенций в целях специфической профилактики и терапии заболеваний, вызываемых УНТ. Значительный объем экспериментальных данных, полученных на моделях in vivo при ингаляционном пути поступления УНТ, позволяет осуществить в настоящее время их гигиеническое нормирование в воздухе рабочей зоны. Что же касается безопасных уровней при пероральном поступлении УНТ, то для их надежной оценки требуются дополнительные исследования. Поиск и отбор источников для обзора осуществлены с использованием открытых баз данных, включая (в порядке релевантности) PubMed, Scopus, Google Scholar и РИНЦ, за период с 2004 по 2016 г.

The article contains the review and analysis of data on the mechanisms of the toxic action of carbon nanotubes (CNTs) on the body and available results of CNT toxicological evaluation after inhalation and oral routes of the action. Identification of cellular and molecular mechanisms of CNTs toxicity allows to justify the list of the most sensitive biochemical toxicity markers that could be used for monitoring the occupational effects of CNTs and serve as a promising target for the corresponding pharmacological and immunopharmacological interventions aimed on specific prophylaxis and therapy of diseases caused by CNT. A considerable amount of experimental data obtained in vivo on inhalation animal models allows to establish the hygienic standardfor CNT in the air of the working area. As to safe levels of the oral route of CNT it needs further study for their reliable assessment. The search and selection of sources for the review was executed with the use of public databases, including (in order of relevance) PubMed, Scopus, Google Scholar, and RISC, for the period from 2004 to 2017.

углеродные нанотрубкитоксичностьбиомаркерыгигиеническое нормированиеcarbon nanotubestoxicitybiological markershygienic standards

References1

Iijima S. Helical microtubules of graphitic carbon. Nature. 1991; 354: 56-8.

Shvedova A.A., Kisin E.R., Porter D., Schulte P., Kagan V.E., Fadeel B. et al. Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus? Pharmacol. Ther. 2009; 121(2): 192-204.

Future Markets Inc: The global market for carbon nanotubes to 2020. Dublin, Ireland, Future Markets Inc. 2013; 70: 1-229.

Varshney K. Carbon nanotubes: a review on synthesis, properties and applications. Int. J. Eng. Res. Gen. Sci. 2014; 2(4): 660-77.

Раков Э.Г. Нанотрубки и фуллерены. Учебное пособие. М: Университетская книга, Логос; 2006.

Scown T.M., van Aerle R., Tyler C.R. Review: Do engineered nanoparticles pose a significant threat to the aquatic environment. Crit. Rev. Toxicol. 2010; 40(7): 653-70.

Саяпина Н.В., Сергиевич А.А., Баталова Т.А., Новиков М.А., Асадчева А., Чайка В.В. и др. Экологическая и токсикологическая опасность углеродных нанотрубок: обзор российских публикаций. Известия Самарского научного центра Российской академии наук. 2014; 16(5): 949-53.

Фатхутдинова Л.М., Халиуллин Т.О., Шведова А.А. Оценка риска здоровью при воздействии углеродных нанотрубок: от токсикологии к эпидемиологическим исследованиям (обзор современного состояния проблемы). Российские нанотехнологии. 2015; 10(5-6): 144-50.

Фатхутдинова Л.М., Халиуллин Т.О., Залялов Р.Р. Токсичность искусственных наночастиц. Казанский медицинский журнал. 2009; 90(4): 578-84.

Dutta D., Sundaram S.K., Teeguarden J.G., Riley B.J., Fifield L.S., Jacobs J.M. et al. Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. Toxicol. Sci. 2007; 100(1): 303-15.

Jin H., Heller D.A., Sharma R., Strano M.S. Size-dependent cellular uptake and expulsion of single-walled carbon nanotubes: single particle tracking and a generic uptake model for nanoparticles. ACS Nano. 2009; 3(1): 149-58.

Tabet L., Bussy C., Amara N., Setyan A., Grodet A., Rossi M.J. et al. Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells. J. Toxicol. Environ. Health A. 2009; 72(2): 60-73.

Haniu H., Saito N., Matsuda Y., Kim Y.A., Park K.C., Tsukahara T. et al. Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. Int. J. Nanomedicine. 2011; 6: 3295-307.

Romero G., Rojas E., Estrela-Lopis I., Donath E., Moya S.E. Spontaneous confocal Raman microscopy - a tool to study the uptake of nanoparticles and carbon nanotubes into cells. Nanoscale Res. Lett. 2011; 6(1): 429.

Shi X., von dem Bussche A., Hurt R.H., Kane A.B., Gao.H. Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nat. Nanotechnol. 2011; 6(11): 714-9.

Yang S.T., Luo J., Zhou Q., Wang H. Pharmacokinetics, metabolism and toxicity of carbon nanotubes for biomedical purposes. Theranostics. 2012; 2(3): 271-82.

Monteiro-Riviere N.A, Nemanich R.J., Inman A.O., Wang Y.Y., Riviere J.E. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol. Lett. 2005; 155(3): 377-84.

Sabuncu A.C., Kalluri B.S., Qian S., Stacey M.W., Beskok A. Dispersion state and toxicity of mwCNTs in cell culture medium with different T80 concentrations. Colloids. Surf. B Biointerfaces. 2010; 78(1): 36-43.

Schrand A.M., Schlager J.J., Dai L., Hussain S.M. Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy. Nat. Protoc. 2010; 5(4): 744-57.

Al-Jamal K.T., Kostarelos K. Assessment of cellular uptake and cytotoxicity of carbon nanotubes using flow cytometry. Methods Mol. Biol. 2010; 625: 123-34.

Raffa V., Ciofani G., Orazio V., Riggio C., Cuschieri A. Physicochemical properties affecting cellular uptakeof carbon nanotubes. Nanomedicine. 2010; 5(1): 89-97.

Sohaebuddin S.K., Thevenot P.T., Baker D., Eaton J.W., Tang L. Nanomaterial cytotoxicity is composition, size, and cell type dependent. Part. Fibre Toxicol. 2010; 7: 22.

Geys J., Nemery B., Hoet P.H. Assay conditions can influence the outcome of cytotoxicity tests of nanomaterials: better assay characterization is needed to compare studies. Toxicol. In Vitro. 2010; 24(2): 620-9.

Gusev A.A., Fedorova I.A., Tkachev A.G., Godymchuk A.Yu., Kuznetsov D.V., Polyakova I.A. Acute toxic and cytogenetic effects of carbon nanotubes on aquatic organisms and bacteria. Nanotechnol. Russia. 2012; 7(9-10): 509-16.

Schrand A.M., Johnson J., Dai L., Hussain S.M., Schlager J.J., Zhu L. et al. Cytotoxicity and genotoxicity of carbon nanomaterials. In: Webster T.J., ed.Safety of Nanoparticles, Nanostructure Science and Technology. New York: Springer; 2009: 159-187.

Madani S.Y., Mandel A., Seifalian A.M. A concise review of carbon nanotube’s toxicology. Nano Rev. 2013; 4: 21521.

Lyon D.Y., Thill A., Rose J., Alavarez P.J., Ecotoxicological impacts of nanomaterials. In: Weisner R., Bottero J.Y., eds. Environmental Nanotechnology: Applications and Implications of Nanomaterials. New York: McGrawHill; 2007: 445-79.

Kolosnjaj J., Szwarc H., Moussa F. Toxicity studies of carbon nanotubes. In: Warren C.W., ed. BioApplications of Nanoparticles. New York: Springer; 2007: 181-204.

Schranda A.M., Daia L., Schlager J.J., Hussain S.M., Osawa E. Differential biocompatibility of carbon nanotubes and nanodiamonds. Diamond Relat. Mater. 2007; 16 (12): 2118-23.

Shvedova A.A., Castranova V., Kisin E.R., Schwegler-Berry D., Murray A.R., Gandelsman V.Z. 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.

Cui D., Tian F., Ozkan C.S., Wang M., Gao H. Effects of single wall carbon nanotubes on human HEK293 cells. Toxicol. Lett. 2005; 155(1): 73-85.

Panessa-Warren B.J., Maye M.M., Warren J.B., Crosson K.M. Single walled carbon nanotube reactivity and cytotoxicity following extended aqueous exposure. Environ. Pollut. 2009; 157(4): 1140-51.

Migliore L., Saracino D., Bonelli A., Colognato R., D’Errico M.R., Magrini A. et al. Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells. Environ. Mol. Mutagen. 2010; 51(4): 294-303.

Satomi F., Okazaki Y., Ito D., Asakawa A., Nagai H., Masafumi T. et al. Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. J. Clin Biochem. Nutr. 2015; 56(2): 111-7.

Patlolla A., Patlolla B., Tchounwou P. Evaluation of cell viability, DNA damage, and cell death in normal human dermal fibroblast cells induced by functionalized multiwalled carbon nanotube. Mol. Cell Biochem. 2010; 338(1-2): 225-32.

Coccini T., Roda E., Sarigiannis D.A., Mustarelli P., Quartarone E., Profumo A. et al. Effects of water-soluble functionalized multiwalled carbon nanotubes examined by different cytotoxicity methods in human astrocyte D384 and lung A549 cells. Toxicology. 2010; 269(1): 41-53.

Genaidy A., Tolaymat T., Sequeira R., Rinder M., Dionysiou D. Health effects of exposure to carbon nanofibers: systematic review, critical appraisal, meta analysis and research to practice perspectives. Sci. Total. Envi. 2009; 407(12): 3686-701.

Park K.H., Chhowalla M., Iqbal Z., Sesti F. Single-walled carbon nanotubes are a new class of ion channel blockers. J. Biol. Chem. 2003; 278(50): 50212-6.

Ma X., Zhang L.H., Wang L.R., Xue X., Sun J.H., Wu Y. et al. Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function. ACS Nano. 2012; 6(12): 10486-96.

Liu H.L., Zhang Y.L., Yang N., Zhang Y.X., Liu X.Q., Li C.G. et al. A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt-TSC2-mTOR signaling. Cell Death Dis. 2011; 2(5): e159.

Dong J., Ma Q. Advances in mechanisms and signaling pathways of carbon nanotube toxicity. Nanotoxicology. 2015; 9(5): 658-76.

Hussain S., Sangtian S., Anderson S., Snyder R., Marshburn J.D., Rice A.B. et al. Inflammasome activation in airway epithelial cells after multi-walled carbon nanotube exposure mediates a profibrotic response in lung fibroblasts. Part. Fibre Toxicol. 2014; 11: 28.

Shipkowski K.A., Taylor A.J., Thompson E.A., Glista-Baker E.E., Sayers B.C., Messenger Z.J., et al. An allergic lung microenvironment suppresses carbon nanotube-induced inflammasome activation via STAT6-dependent inhibition of caspase-1. PLoS One. 2015; 10(6): e0128888.

Vietti G., Lison D., van den Brule S. Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP). Part. Fibre Toxicol. 2015; 13: 11.

Girtsman T.A., Beamer C.A., Wu N., Buford M., Holian A. IL-1R signalling is critical for regulation of multi-walled carbon nanotubesinduced acute lung inflammation in C57Bl/6 mice. Nanotoxicology. 2014; 8(1): 17-27.

Katwa P., Wang X., Urankar R.N., Podila R., Hilderbrand S.C., Fick R.B. et al. Carbon nanotube toxicity paradigm driven by mast cells and the IL-33/ST2 axis. Small. 2012; 8(18): 2904-12.

Wang X., Shannahan J.H., Brown J.M. IL-33 modulates chronic airway resistance changes induced by multi-walled carbon nanotubes. Inhal. Toxicol. 2014; 26(4): 240-9.

Tsukahara T., Matsuda Y., Haniu H. The role of autophagy as a mechanism of toxicity induced by multi-walled carbon nanotubes in human lung cells. Int. J. Mol. Sci. 2015; 16(1): 40-8.

Azad N., Iyer A.K., Wang L., Liu Y., Lu Y., Rojanasakul Y. Reactive fibrogenic and angiogenic responses. Nanotoxicology. 2013; 7(2): 157-68.

Polimeni M., Gulino G.R., Gazzano E., Kopecka J., Marucco A., Fenoglio I. et al. Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway. Part. Fibre Toxicol. 2015; 13: 27.

Huizar I., Malur A., Patel J., McPeek M., Dobbs L., Wingard C. et al. The role of PPARγ in carbon nanotube-elicited granulomatous lung inflammation. Respir Res. 2013; 14(1): 7.

Di Y.P., Tkach A.V., Yanamala N., Stanley S., Gao S., Shurin M.R. et al. Dual acute proinflammatory and antifibrotic pulmonary effects of short palate, lung, and nasal epithelium clone-1 after exposure to carbon nanotubes. Am. J. Respir. Cell. Mol. Biol. 2013; 49(5): 759-67.

Халиуллин Т.О., Кисин Е.Р., Мюррэй Р.Э., Залялов Р.Р., Шведова А.А., Фатхутдинова Л.М. Токсические эффекты углеродных нанотрубок в культурах клеток макрофагов и бронхиального эпителия. Вестник Томского государственного университета. Биология. 2014; (1): 199-210.

Patlolla A., McGinnis B., Tchounwou P. Biochemical and histopathological evaluation of functionalized single-walled carbon nanotube in Swiss-Webster mice. J. Appl. Toxicol. 2011; 31(1): 75-83.

Monteiro-Rivere N.A., Inmam A.O. Challenges for assessing carbon nano-material toxicity to the skin. Carbon. 2006; 44: 1070-8.

Jacobsen N.R., Møller P., Jensen K.A., Vogel U., Ladefoged O., Loft S. et al. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice. Part. Fibre Toxicol. 2009; 6: 1.

Han S.G., Andrews R., Gairola C.G. Acute pulmonary response of mice to multi-wall carbon nanotubes. Inhal. Toxicol. 2010; 22(4): 340-7.

Crouzier D., Follot S., Gentilhomme E., Flahaut E., Arnaud R., Dabouis V. et al. Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung. Toxicology. 2010; 272(1-3): 39-45.

Murphy F.A., Schinwald A., Poland C.A., Donaldson K. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells. Part. Fibre Toxicol. 2012; 9: 8.

Халиуллин Т.О., Кисин Е.Р., Залялов Р.Р., Шведова А.А., Фатхутдитнова Л.М. Биологические эффекты многослойных углеродных нанотрубок при легочной экспозиции in vivo. Токсикологический вестник. 2013; (4): 17-21.

Fatkhutdinova L.M., Khaliullin T.O., Vasil’yeva O.L., Zalyalov R.R., Mustafin I.G., Kisin E.R. et al. Fibrosis biomarkers in workers exposed to MWCNTs. Toxicol. Appl. Pharmacol. 2016; 299: 125-31.

Manke A., Luanpitpong S., Dong C., Wang L., He X., Battelli L. et al. Effect of fiber length on carbon nanotube-induced fibrogenesis. Int. J. Mol. Sci. 2014; 15(5): 7444-61.

Мезенцева М.В., Руссу Л.И., Лосева Е.В., Логинова Н.А., Панов Н.В., Щетвин М.Н. и др. Изменение синтеза цитокинов, но не экспрессии c-fos в мозге крыс при интраназальном введении однослойных углеродных нанотрубок. Нанотехнологии: разработка, применение - XXI век. 2015: 7(2): 26-32.

Мезенцева М.В., Руссу Л.И., Лосева Е.В., Логинова Н.А., Панов Н.В., Щетвин М.Н. и др. Изменение синтеза цитокинов, но не экспрессии c-fos в мозге крыс при интраназальном введении однослойных углеродных нанотрубок. Биомедицинская радиоэлектроника. 2014; (8): 38-43.

Sager T.M., Wolfarth M.W., Andrew M., Hubbs A., Friend S., Chen T. et al. Effect of multi-walled carbon nanotube surface modification on bioactivity in the C57BL/6 mouse model. Nanotoxicology. 2014; 8(3): 317-27.

Jessop F., Holian A. Extracellular HMGB1 regulates multi-walled carbon nanotube-induced inflammation in vivo. Nanotoxicology. 2015; 9(3): 365-72.

Trifonova O.P., Il’in V.A., Kolker E.V., Lisitsa A.V. Big Data in Biology and Medicine: Based on material from a joint workshop with representatives of the international Data-Enabled Life Science Alliance, July 4, 2013, Moscow, Russia. Acta naturae. 2013; 5(3): 13-6.

Ding L.H., Stilwell J., Zhang H.J., Elboudwarej O., Jiang H., Selegue J.P. et al. Molecular characterization of the cytotoxic mechanism of multiwall carbon nanotubes and nanoonions on human skin fibroblast. Nano Lett. 2005; 5(12): 2448-64.

Alazzam A., Mfoumou E., Stiharu I., Kassab A., Darnel A., Yasmeen A. et al. Identification of deregulated genes by single wall carbonnanotubes in human normal bronchial epithelial cells. Nanomedicine. 2010; 6(4): 563-9.

Poulsen S.S., Jacobsen N.R., Labib S., Wu D., Husain M., Williams A. et al. Transcriptomic analysis reveals novel mechanistic insight into murine biological responses to multi-walled carbon nanotubes in lungs and cultured lung epithelial cells. PLoS One. 2013; 8(11): e80452.

Tilton S.C., Karin N.J., Tolic A., Xie Y., Lai X., Hamilton R.F. et al. Three human cell types respond to multi-walled carbon nanotubes and titanium dioxide nanobelts with cell-specific transcriptomic and proteomic expression patterns. Nanotoxicology. 2014; 8(5): 533-48.

Fujita K., Fukuda M., Fukui H., Horie M., Endoh S., Uchida K. et al. Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression. Nanotoxicology. 2015; 9(3): 290-301.

Dymacek J., Snyder-Talkington B.N., Porter D.W., Mercer R.R., Wolfarth M.G., Castranova V. et al. mRNA and miRNA regulatory networks reflective of multi-walled carbon nanotube-induced lung inflammatory and fibrotic pathologies in mice. Toxicol. Sci. 2015; 144(1): 51-64.

Snyder-Talkington B.N., Dong C., Sargent L.M., Porter D.W., Staska L.M., Hubbs A.F. et al. mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma following multi-walled carbon nanotube inhalation exposure in mice. J. Appl. Toxicol. 2016; 36(1): 161-74.

Labib S., Williams A., Yauk C.L., Nikota J.K., Wallin H., Vogel U. et al. Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes. Part. Fibre Toxicol. 2016; 13: 15.

Nikota J., Williams A., Yauk C.L., Wallin H., Vogel U., Halappanavar S. Meta-analysis of transcriptomic responses as a means to identify pulmonary disease outcomes for engineered nanomaterials. Part. Fibre Toxicol. 2015; 13: 25.

Shwedova A.A., Yanamala N., Kisin E.R., Khailullin T.O., Birch E.M., Fatkhutdinova L.M. Integrated analysis of dysregulated ncRNA and mRNA expression profiles in humans exposed to carbon nanotubes. PLoS One. 2016; 11(3): e0150628.

Witzmann F.A., Monteiro-Riviere N. Multi-walled carbon nanotube exposure alters protein expression in human keratinocyte. Nanomedicine. 2006; 2(3): 158-68.

Haniu H., Matsuda Y., Takeuchi K., Kim Y.A., Hayashi T., Endo M. Proteomics-based safety evaluation of multi-walled carbon nanotubes. Toxicol. Appl. Pharmacol. 2010; 242(3): 256-62.

Shen Z.L., Nie H.Y., Wang H.F., Yang B., Zhong L.J., Zou X.J. et al. Two types of MWNTs with different surface modifications induce differential expression of proteins in RAW264.7 cells. Beijing Da Xue Xue Bao. 2010; 42(3): 345-50. (in Chinese)

Li J., Zhang G., Zhang X., Jia Z., Gao X., Jiang Y. et al. Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in A549 cells. PLoS One. 2014; 9(1): e84974.

Hilton G.M., Taylor A.J., McClure C.D., Parsons G.N., Bonner J.C., Beremana M.S. Toxicoproteomic analysis of pulmonary carbon nanotube exposure using LC-MS/MS. Toxicology. 2015; 329: 80-7.

Ray S., Chandra H., Srivastava S. Nanotechniques in proteomics: current status, promises and challenges. Biosens Bioelectron. 2010; 25(11): 2389-401.

Li P., Lai X., Witzmann F.A., Blazer-Yost B.L. Bioinformatic analysis of differential protein expression in Calu-3 cells exposed to carbon nanotubes. Proteomes. 2013; 1(3): 219-39.

Lai X., Blazer-Yost B.L., Clack J.W., Fears S.L., Mitra S., Ntim S.A. et al. Protein expression profiles of intestinal epithelial co-cultures: effect of functionalised carbon nanotube exposure. Int. J. Biomed. Nanosci. Nanotechnol. 2013; 3(1-2): 10.

Baron P.A., Deye G.J., Chen B.T., Schwegler-Berry D.E., Shvedova A.A., Castranova V. Aerosolization of single-walled carbon nanotubes for an inhalation study. Inhal. Toxicol. 2008; 20(8): 751-60.

Oberdörster G., Castranova V., Asgharian B., Sayre P. Inhalation exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF): methodology and dosimetry. J. Toxicol. Environ. Health B Crit. Rev. 2015; 18: 121-212.

Aschberger K., Johnston H.J., Stone V., Aitken R.J., Hankin S.M., Peters S.A. et al: Review of carbon nanotubes toxicity and exposure - appraisal of human health risk assessment based on open literature. Crit. Rev. Toxicol. 2010; 40(9): 759-90.

Van der Zande M., Junker R., Walboomers X.F., Jansen J.A. Carbon nanotubes in animal models: a systematic review on toxic potential. Tissue Eng. Part B Rev. 2011; 17(1): 57-69.

Silva R.M., Doudrick K., Franzi L.M., Tee S.C., Anderson D.S., Wu Z. et al. Instillation versus inhalation of multiwalled carbon nanotubes: exposure-related health effects, clearance, and the role of particle characteristics. ACS Nano. 2014; 8(9): 8911-31.

Shvedova A.A., Kisin E.R., Mercer R.R., Murray A.R., Johnson V.J., Potapovich A.I. 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): 698-708.

Chou C.C., Hsiao H.Y., Hong Q.S., Chen C.H., Peng Y.W., Chen H.W. et al. Single-walled carbon nanotubes can induce pulmonary injury in mouse model. Nano. Lett. 2008; 8(2): 437-45.

Lam C.W., James J.T., McCluskey R., Hunter R.L. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci. 2004; 77(1): 126-34.

Kisin E.R., Murray A.R., Keane M.J., Shi X.C., Schwegler-Berry D., Gorelik O. et al. Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells. J. Toxicol. Environ. Health A. 2007; 70(24): 2071-9.

Teeguarden J.C., Webb-Robertson B.J., Waters K.M., Murray A.R., Kisin E.R., Varnum S.M. et al. Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice. Toxicol. Sci. 2011; 120(1): 123-35.

Рыбалкин С.П., Михина Л.В., Онацкий Н.М., Алдобаев В.Н., Блохин В.А., Третьякова А.В. и др. Изучение токсичности наноструктурированного углерода в форме одностенных углеродных нанотрубок и укороченных одностенных углеродных нанотрубок при ингаляционном пути поступления крысам. Прикладная токсикология. 2013; 4(1): 32-9.

Lam C.W., James J.T., McCluskey R., Arepalli S., Hunter R.L. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit. Rev. Toxicol. 2006; 36(3): 189-217.

Shvedova A.A., Yanamala N., Kisin E.R., Tkach A.V., Murray A.R., Hubbs A. et al. Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons. Am. J. Physiol. Lung Cell. Mol. Physiol. 2014; 306(2): L170-82.

Li J.G., Li W.X., Xu J.Y., Cai X.Q., Liu R.L., Li Y.J. et al. Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation. Environ. Toxicol. 2007; 22(4): 415-21.

100

Wang X., Katwa P., Podila R., Chen P., Ke P.C., Rao A.M. et al. Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice. Part. Fibre Toxicol. 2011; 8: 24.

101

Hamilton R.F., Wu Z., Mitra S., Shaw P.K., Holian A. Effect of MWCNT size, carboxylation, and purification on in vitro and in vivo toxicity, inflammation and lung pathology. Part. Fibre Toxicol. 2013; 10: 57.

102

Mercer R.R., Hubbs A.F., Scabilloni J.F. Wang L., Battelli L.A., Friend S. et al. Pulmonary fibrotic response to aspiration of multiwalled carbon nanotubes. Part. Fibre Toxicol. 2011: 8: 21.

103

Aiso S., Yamazaki K., Umeda Y. Pulmonary toxicity of intratracheally instilled multiwall carbon nanotubes in male Fischer 344 rats. Ind. Health. 2010; 48(6): 783-95.

104

Mercer R.R., Scabilloni J.F., Hubbs A.F., Wang. L., Battelli L.A., McKinney W. et al. Extrapulmonary transport of MWCNT following inhalation exposure. Part. Fibre Toxicol. 2013; 10: 38.

105

Ma-Hock L., Strauss V., Treumann S., Küttler K., Wohlleben W., Hofmann T. et al. Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black. Part. Fibre Toxicol. 2013; 10: 23.

106

Porter D.W., Hubbs A.F., Chen B.T., McKinney W., Mercer R.R., Wolfarth M.G., et al. Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes. Nanotoxicology. 2013; 7(7): 1179-94.

107

Umeda Y., Tatsuya K., Misae S., Kondo H., Tadao T., Shigetoshi A. et al. Two-week toxicity of multi-walled carbon nanotubes by whole-body inhalation exposure in rats. J. Toxicol. Pathol. 2013; 26(2): 131-40.

108

Porter D.W., Hubbs A.F., Mercer R.R., Wu N., Wolfarth M.G., Sriram K. et al. Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology. 2010; 269(2-3): 136-47.

109

Pauluhn J. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. Toxicol. Sci. 2010; 113(1): 226-42.

110

Pothmann D., Simar S., Schuler D., Dony E., Gaering S., Le Net J.L. et al. Lung inflammation and lack of genotoxicity in the comet and micronucleus assays of industrial multiwalled carbon nanotubes Graphistrength© C100 after a 90-day nose-only inhalation exposure of rats. Part. Fibre Toxicol. 2015; 12: 21.

111

Bergin I.L. Witzmann F.A. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. Int. J. Biomed. Nanosci. Nanotechnol. 2013; 3:1.

112

Buford M.C., Hamilton J., Raymond F., Holian A. A comparison of dispersing media for various engineered carbon nanoparticles. Part. Fibre Toxicol. 2007; 4: 6.

113

Rastogi R., Kaushal R., Tripathi S.K., Sharma A.L., Kaur I., Bharadwaj L.M. Comparative study of carbon nanotube dispersion using surfactants. J. Colloid. Interface Sci. 2008; 328(2): 421-8.

114

Jackson P., Jacobsen N.R., Baun A., Birkedal R., Kühnel D., Jensen K.A. et al. Bioaccumulation and ecotoxicity of carbon nanotubes. Chem. Cent. J. 2013; 7: 154.

115

Jachak A., Lai S.K., Hida K., Suk J.S., Markovic N., Biswal S. et al. Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus. Nanotoxicology. 2012; 6(6): 614-22.

116

Coyuco J.C., Liu Y., Tan B.J., Chiu G.N. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery. Int. J. Nanomedicine. 2011; 6: 2253-63.

117

Ju L., Zhang W., Wang X., Hu J., Zhang Y. Aggregation kinetics of SDBS-dispersed carbon nanotubes in different aqueous suspensions. Colloids Surf. A Physicochem. Eng. Asp. 2012; 409: 159-66.

118

Lim J.H., Kim S.H., Lee I.C., Moon C., Kim S.H., Shin D.H. et al. Evaluation of maternal toxicity in rats exposed to multi-wall carbon nanotubes during pregnancy. Environ, Health Toxicol. 2011; 26: e2011006.

119

Philbrook N.A., Walker V.K., Afrooz A.R., Saleh N.B., Winn L.M. Investigating the effects of functionalized carbon nanotubes on reproduction and development in Drosophila melanogaster and CD-1 mice. Reprod. Toxicol. 2011; 32(4): 442-8.

120

Folkmann J.K., Risom L., Jacobsen N.R., Wallin H., Loft S., Møller P. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ. Health Perspect. 2009; 117(5): 703-8.

121

Szendi K., Varga C. Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res. 2008; 28(1A): 349-52.

122

Kolosnjaj-Tabi J., Hartman K.B., Boudjemaa S., Ananta J.S., Morgant G., Szwarc H. et al. In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice. ACS Nano. 2010; 4(3): 1481-92.

123

Васюкова И.А., Гусев А.А., Халиуллин Т.О., Фатхутдинова Л.М., Убогов А.Ю. Многостенные углеродные нанотрубки и их влияние на показатели мужской репродуктивной системы. Нанотехнологии и охрана здоровья. 2014: 6(1): 10-5.

124

Масютин А.Г., Ерохина М.В., Сычевская К.А., Гусев А.А., Васюкова И.А., Ткачев А.Г. и др. Многостенные углеродные нанотрубки индуцируют патологические изменения в органах пищеварительной системы мышей. Бюллетень экспериментальной биологии и медицины. 2016; 161(1): 143-8.

125

Masyutin A., Erokhina M., Sychevskaya K., Gusev A., Vasyukova I., Smirnova E. et al. Multi-walled carbon nanotubes: biodegradation by gastric agents in vitro and effect on murine intestinal system. IOP Conf. Series: Materials Science and Engineering. 2015; 98: 012008.

126

Хрипач Л.В., Рахманин Ю.А., Михайлова Р.И., Князева Т.Д., Коганова З.И., Железняк Е.В. и др. Влияние углеродных нанотрубок и активированного угля на биохимические показатели состояния организма при хроническом введении препаратов крысам с питьевой водой. Гигиена и санитария. 2014; 93(5): 36-42.

127

Горшенева Е.Б. Дозозависимый эффект многостенных углеродных нанотрубок и частиц сажи при пероральном введении лабораторным мышам. Нанотехнологии и охрана здоровья. 2014; 6(1): 48-55.

128

Zhu Y., Zhao Q., Li Y., Cai X., Li W. The interaction and toxicity of multiwalled carbon nanotubes with Stylonychia mytilus. J. Nanosci. Nanotechnol. 2006; 6(5): 1357-64.

129

Ferguson P.L., Chandler G.T., Templeton R.C., Demarco A., Scrivens W.A., Englehart B.A. Influence of sediment-amendment with single-walled carbon nanotubes and diesel shoot on bioaccumulation of hydrophobic organic contaminats by bentic invertebrates. Environ. Sci. Technol. 2008; 42(10): 3879.

130

Bourdiol F., Mouchet F., Perrault A., Fourquaux I., Datas L., Gancet C. et al. Biocompatible polymer-assisted dispersion of multi walled carbon nanotubes in water, application to the investigation of their ecotoxicity using Xenopus laevis amphibian larvae. Carbon. 2013; 54: 175-91.

131

Al Faraj A., Fauvelle F., Luciani N., Lacroix G., Levy M., Crémillieux Y. et al. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques. Int. J. Nanomedicine. 2011; 6: 351-61.

132

Cherukuri P., Gannon C.J., Leeuw T.K., Schmidt H.K., Smalley R.E., Curley S.A. et al. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. PNAS. 2006; 103(50): 18882-6.

133

Mercer R.R., Scabilloni J.F., Hubbs A.F., Battelli L.A., McKinney W., Friend S. et al. Distribution and fibrotic response following inhalation exposure to multi-walled carbon nanotubes. Part. Fibre Toxicol. 2013; 10: 33.

134

Shinohara N., Nakazato T., Ohkawa K., Tamura M., Kobayashi N., Morimoto Y. et al. Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation. J. Appl. Toxicol. 2016; 36(4): 501-9.

135

Sturmcorres R. Clearance of carbon nanotubes in the human respiratory tract - a theoretical approach. Ann. Transl. Med. 2014; 2(5): 46.

136

Shityakov S., Salvador E., Pastorin G., Förster C. Blood-brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate. Int. J. Nanomedicine. 2015; 10: 1703-13.

137

Albini A., Pagani A., Pulze L., Bruno A., Principi E., Congiu T. et al. Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition. Int. J. Nanomedicine. 2015; 10: 6133-45.

The authors declare that there are no conflicts of interest present.