A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats

Abstract

We compared long-term pulmonary toxicities after a single intratracheal instillation of two types of dispersed single-wall carbon nanotubes (SWCNTs), namely, those with relatively long or short linear shapes with average lengths of 8.6 and 0.55 µm, respectively. Both types of SWCNTs were instilled intratracheally in male F344 rats at 0.2 or 1.0 mg/kg (long SWCNTs) or 1.0 mg/kg (short SWCNTs). Pulmonary responses were characterized at 26, 52 and 104 weeks after a single instillation. Inflammatory changes, test substance deposition, test substance engulfment by macrophages, and alveolar wall fibrosis were observed in the lungs of almost all test rats at 52 and 104 weeks after short nanotube instillation. The incidences of these changes were much lower in the long nanotube-treated groups. In almost all rats of the long nanotube-treated groups, fibrosis and epithelium loss in the terminal bronchiole with test substance deposition were observed. These bronchiolar changes were not observed after administering short nanotubes. Both bronchiolo-alveolar adenoma and carcinoma were found in the negative-control group, the high-dose long-nanotube group, and the short-nanotube group at 104 weeks post-instillation, although the incidences were not statistically different. The genotoxicity of the SWCNTs was also evaluated by performing in vivo comet assays with lung cells obtained 26 weeks post-instillation. No significant changes in the percent tail deoxyribonucleic acid were found in any group. These findings suggested that most long SWCNTs were deposited at the terminal bronchioles and that a considerable amount of short SWCNTs reached the alveolus, resulting in chronic inflammatory responses, but no genotoxicity in the lungs.

Keywords:

• Intratracheal instillation
• length effect
• long-term study
• lung toxicity/inflammation
• nanomaterial
• single-walled carbon nanotube

Acknowledgments

The authors would like to thank Dr. Junko Nakanishi for advice on the study design, Dr. Shuji Abe and Dr. Kazuhiro Yamamoto for helpful discussions, Ms. Emiko Kobayashi for help in TEM analysis, and Ms. Sawae Obara for revising the manuscript. The pathological findings were reviewed by Dr. Isao Narama, D.V.M., Diploma of the Japanese Society of Toxicologic Pathology, Diploma of the Japanese College of Veterinary Pathologist. A part of this study was based on the results obtained from a project entitled: “Innovative Carbon Nanotubes Composite Materials Project toward Achieving a Low-Carbon Society (P10024),” which was commissioned by the New Energy and Industrial Technology Development Organization (NEDO) in Japan.

Disclosure statement

No potential conflict of interest was reported by the authors.