Abstract
Background
Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure.
Methods
Rats were divided into six groups: Untreated, Vehicle, 3 DWCNT groups (0.12mg/rat, 0.25mg/rat and 0.5mg/rat), and MWCNT-7 (0.5mg/rat). The test materials were administrated by intratracheal - intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice at weeks 52 and 104.
Results
DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids.
Conclusions
Our results demonstrate that DWCNTs are biopersistent in the rat lung and induce chronic inflammation. Moreover, rats treated with 0.5 mg DWCNT developed pleural fibrosis. While our results do not show that DWCNT is carcinogenic in the rat lung, total tumor incidence was significantly increased in the 0.5 mg DWCNT group. Taken together, these findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and carcinogenic cannot be ignored.