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Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice

Authors Sobajima A, Haniu H, Nomura H, Tanaka M, Takizawa T, Kamanaka T, Aoki K, Okamoto M, Yoshida K, Sasaki J, Ajima K, Kuroda C, Ishida H, Okano S, Ueda K, Kato H, Saito N

Received 9 March 2019

Accepted for publication 11 June 2019

Published 12 August 2019 Volume 2019:14 Pages 6465—6480

DOI https://doi.org/10.2147/IJN.S208129

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Farooq Shiekh

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


Atsushi Sobajima,1 Hisao Haniu,1,2 Hiroki Nomura,1 Manabu Tanaka,1 Takashi Takizawa,1 Takayuki Kamanaka,1 Kaoru Aoki,1,3 Masanori Okamoto,1 Kazushige Yoshida,1 Jun Sasaki,1 Kumiko Ajima,2 Chika Kuroda,1,2 Haruka Ishida,2 Satomi Okano,2 Katsuya Ueda,2 Hiroyuki Kato,1 Naoto Saito1,2

1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Matsumoto, Nagano, Japan

Purpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs.
Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight).
Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin.
Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.

Keywords: multiwalled carbon nanotubes, rasH2 transgenic mouse, carcinogenicity, organ accumulation, dispersion

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