Approaches on MWCNT diameters and its relation to tumor development

Question: Some forms of carbon nanotubes (CNT) have been found to exhibit carcinogenic potential depending on their morphological characteristics and catalyst impurities. The use of CNTs therefore requires appropriate risk and safety assessment. Correlation of hazards of biodurable fibres to specific morphologies is an approach that has been successfully developed for microscale fibres. The derived "fibre toxicological paradigm" achieves morphology-based hazard classification for a broad class of materials. The present study aims at contributing to an extension of this paradigm to the world of nanoscale fibres. Methods: CNTs of different diameters will be compared with respect to tumor development after intraperitoneal (i.p.) injection. It will be studied whether a diameter based threshold for CNT carcinogenicity can be identified. Rats will be administered a single i.p. injection. The tumor incidence will be histopathologically approximately evaluated performed after two years post application. Additionally, an interim sacrifice will be inflammatory three month to investigate potential effects in the peritoneum. Five different types of CNT will be tested in two concentrations (0.1 and 1.0 x 109 WHO-fibers): One single-walled CNT type, one multi-walled CNT type with an average diameter of 10 nm and a length of > 5 µm, two custom-synthesized multi-walled CNTs with average diameters of 20 and of 30 nm and a length > 5 µm, and one short MWCNT (max. 4-5 µm) with a diameter of > 40 nm. Amosite will be used as positive control. All nanomaterials will be comprehensively characterized before and after dispersion to reliable determine administered diameter distributions together with other characteristics that potentially influence toxicity, including length, purity and rigidity. Conclusion: The generated data is expected to provide information on morphology induced modes-of-action of CNTs including inflammation and carcinogenicity. The data is expected to contribute to the development of a morphology-based classification approach for CNTs and other inert nanofibres. This project is funded by the German FederalInstitute for Occupational Safety and Health (F2376).