Thirteen-week study of toxicity of fiber-like multi-walled carbon nanotubes with whole-body inhalation exposure in rats

Abstract

Cancer development due to fiber-like straight type of multi-walled carbon nanotubes (MWCNTs) has raised concerns for human safety because of its shape similar to asbestos. To set concentrations of MWCNT for a rat carcinogenicity study, we conducted a 13-week whole body inhalation study. F344 male and female rats, 6-week-old at the commencement of the study, were exposed by whole-body inhalation to MWCNT at concentrations of 0, 0.2, 1 and 5 mg/m³ with a generation and exposure system utilizing the cyclone sieve method. Measured concentrations in the exposure chambers were 0.20 ± 0.02, 1.01 ± 0.11 and 5.02 ± 0.25 mg/m³ for 13 weeks. The MMAD (GSD) of MWCNT were 1.4–1.6 μm (2.3–3.0), and mean width and length were 94.1–98.0 nm and 5.53–6.19 μm, respectively, for each target concentration. Lung weights were increased 1.2-fold with 1 mg/m³ and 1.3-fold with 5 mg/m³ in both sexes compared to the controls. In the bronchoalveolar lavage fluid (BALF) analyses, inflammatory parameters were increased concentration-dependently in both sexes from 0.2 mg/m³. Granulomatous changes in the lung were induced at 1 and 5 mg/m³ in females and even at 0.2 mg/m³ in males. Focal fibrosis of the alveolar wall was observed in both sexes at 1 mg/m³ or higher. Inflammatory infiltration in the visceral pleural and subpleural areas was induced only at 5 mg/m³. In conclusion, we determined 0.2 mg/m³ as the low-observed-adverse-effect level (LOAEL) for respiratory tract toxicity in the present inhalation exposure study of rats.

• Aerosol
• inhalation toxicity
• lung burden
• lung deposition

Acknowledgements

We are deeply indebted to all members of the committee set up in the Japan Industrial Safety and Health Association to oversee building the system for aerosol generation and inhalation exposure to nanomaterials (chaired by Dr. Norihiko Kohyama, Professor of Toyo University), for their warm encouragement and fruitful discussions throughout the present study. In addition, we deeply appreciated that Dr. Naohide Shinohara (National Institute of Advanced Industrial Science and Technology) had assisted us in data analysis as well as its evaluation. We also gratefully acknowledge the technical support of Mr. Tadao Toya, Mr. Shigeyuki Hirai, Mr. Yasutomo Sasaki, Mr. Masahiro Yamamoto and Ms. Yuko Minoshima.

Declaration of interest

The present studies were contracted and supported by the Ministry of Health, Labour and Welfare of Japan. The authors declare that they have no conflicts of interest.

Supplementary material available online

Supplementary Figures 1–4.