title: Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation.
abstract: As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml(-1) Triton-X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12-month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15- and 0.38-mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364-day study period (<0.04 mg per liver, < 0.006 mg per brain).
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Shinohara
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakazato
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ohkawa
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Moritaka
authors.initials: M
authors.lastname: Tamura
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.|National Institute of Health Sciences, Kamiyouga 1-18-1, Setagaya, Tokyo, 158-0098, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.affiliation: Graduate School of Engineering, Hiroshima University, Kagamiyama 1-4-1, Higashi Hiroshima, Hiroshima, 739-8527, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tao
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ema
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.|BioSafety Research Center (BSRC), Shioshinden 582-2, Iwata, Shizuoka, 437-1213, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Naya
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki, 305-8569, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nakanishi
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057230:Limit of Detection; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D037742:Nanotubes, Carbon
keywords: intratracheal instillation; multi-walled carbon nanotube; nanomaterial; pulmonary clearance; toxicokinetics