ToxSci Advance Access published online on May 8, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp100
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Absence of carcinogenic response to multi-wall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat
1 Industrial Toxicology and Occupational Medicine unit, Catholic University of Louvain, Avenue E. Mounier, 53.02, 1200 Brussels, Belgium 2 Laboratory of Pathology, University Hospital of Mont-Godinne, Catholic University of Louvain, 5530 Yvoir, Belgium
* Corresponding Author E-mail: dominique.lison{at}uclouvain.be
Received April 8, 2009; revision received April 29, 2009; accepted April 30, 2009
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Abstract |
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Toxicological investigations of carbon nanotubes have shown that they can induce pulmonary toxicity, and similarities with asbestos fibers have been suggested. We previously reported that multi-wall carbon nanotubes (MWCNT) induced lung inflammation, granulomas and fibrotic reactions. The same MWCNT also caused mutations in epithelial cells in vitro and in vivo. These inflammatory and genotoxic activities were related to the presence of defects in the structure of the nanotubes. In view of the strong links between inflammation, mutations and cancer, these observations prompted us to explore the carcinogenic potential of these MWCNT in the peritoneal cavity of rats.
The incidence of mesothelioma and other tumors was recorded in 3 groups of 50 male Wistar rats injected intraperitoneally with a single dose of MWCNT with defects (2 or 20 mg/animal) and MWCNT without defects (20 mg/animal). Two additional groups of 26 rats were used as positive (2 mg UICC crocidolite /animal) and vehicle controls.
After 24 months, while crocidolite induced a clear carcinogenic response (34.6% animals with mesothelioma vs 3.8% in vehicle controls), MWCNT with or without structural defects did not induce mesothelioma in this bioassay (4, 0 or 6%, respectively). The incidence of tumors other than mesothelioma was not significantly increased across the groups.
The initial hypothesis of a contrasting carcinogenic activity between MWCNT with and without defects could not be verified in this bioassay. We discuss the possible reasons for this absence of carcinogenic response, including the length of the MWCNT tested (<1 µm on average), the absence of a sustained inflammatory reaction to MWCNT, and the capacity of these MWCNT to quench free radicals.
Key Words: carbon nanotubes; carcinogenesis; mesothelioma.