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

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.