Biological response and morphological assessment of individually dispersed multi-wall carbon nanotubes in the lung after intratracheal instillation in rats.
Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single intratracheal instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60 nm and 1.5 μm, respectively. Groups of male Sprague-Dawley rats were intratracheally instilled with 0.04, 0.2, or 1 mg/kg of the individually dispersed MWCNT suspension. After instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, liver, kidney, spleen, and cerebrum were histopathologically evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure. Transient pulmonary inflammatory responses were observed only in the lungs of the group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in the lungs of rats was assessed using light microscopy and transmission electron microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in the lungs of the rats were typically phagocytosed by the alveolar macrophages and these macrophages were consequently accumulated in the alveoli until 6-month post-exposure. The 400 TEM images obtained showed that all MWCNTs were located in the alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were not located in the cells of the interstitial tissues. There was no evidence of chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT instillation. These results suggest that MWCNTs were being processed and cleared by alveolar macrophages.
Kobayashi
Norihiro
N
Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology, 16-1 Onagawa, Tsukuba, Ibaraki 305-8569, Japan. norihiro-kobayashi@aist.go.jp
Naya
Masato
M
Ema
Makoto
M
Endoh
Shigehisa
S
Maru
Junko
J
Mizuno
Kohei
K
Nakanishi
Junko
J
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000008:administration & dosage / Q000633:toxicity; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000633:toxicity; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D037742:Nanotubes, Carbon / Q000633:toxicity* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
D007155:Immunologic Factors; D018836:Inflammation Mediators; D037742:Nanotubes, Carbon