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.