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/m(3) 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/m(3) 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/m(3) and 1.3-fold with 5 mg/m(3) 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/m(3). Granulomatous changes in the lung were induced at 1 and 5 mg/m(3) in females and even at 0.2 mg/m(3) in males. Focal fibrosis of the alveolar wall was observed in both sexes at 1 mg/m(3) or higher. Inflammatory infiltration in the visceral pleural and subpleural areas was induced only at 5 mg/m(3). In conclusion, we determined 0.2 mg/m(3) as the low-observed-adverse-effect level (LOAEL) for respiratory tract toxicity in the present inhalation exposure study of rats.