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Investigations on classification and mechanisms of MWCNT-Induced carcinogenicity

: Schwotzer, Daniela; Schaudien, Dirk; Rittinghausen, Susanne; Meyer-Plath, Asmus; Eckert, V.; Leonhardt, A.; Creutzenberg, Otto H.; Gebel, Thomas

The Toxicologist 162 (2018), Nr.1, S.407, Abstract PS 2687
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <57, 2018, San Antonio/Tex.>
Fraunhofer ITEM ()

Carbon nanotubes (CNT) are of great interest for toxicological research due to similarities to asbestos as shape, size, biopersistency, and toxic modes of action. It is widely accepted that fiber-specific characteristics like diameter or rigidity can affect their toxic potential. Larger diameters (> 35 nm), for instance, have been shown to contribute to tumor development. Although there are still uncertainties about the exact role of CNT thickness to carcinogenicity, a classification based on morphological characteristics could help to improve risk assessment and safe use of CNTs. This study therefore aims at providing data on the toxicity of multiwalled CNTs with narrow diameter ranges, in order to test whether a threshold for tumor development could be set for a specific fiber thickness. For this purpose, rats will be administered a single intraperitoneal injection of CNTs. Two different doses will be tested, 0.1 and 1.0 x 109 WHO-fibers, and five different types of CNT within and outside of the tumor-sensitive diameter or length range will be compared. Those include one single-walled CNT, one multiwalled CNT (MWCNT) with an average diameter of 10 nm and a length of > 5 µm, two customized MWCNT with an average diameter of 20 and 30 nm and > 5 µm in length, as well as one short MWCNT (max. 4-5 µm) with a diameter of > 40 nm. Amosite will be used as positive control. Approximately two years post-application animals will be histopathologically examined for tumors. Additionally, an interim group will be included for investigation of inflammatory reactions in the peritoneum three months after substance administration. Detailed characterization of the test materials will be presented, including determination of aspect ratios. Rigidities will be used to test whether differentiation between the five fiber types and observed responses can be achieved. The approach also aims at supporting the determination of guidelines for a standardized characterization procedure for CNTs. The project is funded by the German Federal Institute for Occupational Safety and Health (F2376).