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Toxic effects of multiwall carbon nanotubes (MWCNT) in vivo and in vitro

: Hackbarth, Anja; Schaudien, Dirk; Bellmann, Bernd; Ernst, Heinrich; Ziemann, Christina; Leonhardt, A.; Heinrich, Uwe; Rittinghausen, Susanne


Pneumologie 67 (2013), No.12, pp.695
ISSN: 0934-8387
Scientific Symposium "Good Particles - Bad Particles - Interaction of (Carbon) Nano Particles with Lung Cells" <2013, Borstel>
Journal Article, Conference Paper
Fraunhofer ITEM ()

MWCNTs have excellent technological features and there is rapid growth in MWCNT development and production. However, concerns of asbestos-like toxic effects of certain MWCNTs exist due to their length and fiber-like shape. Therefore, potential adverse biological effects of MWCNTs are investigated in vivo (rat) and in vitro (human peritoneal mesothelial LP9/TERT-1 cells) in a project funded by the BMBF (contract No. 03X0109A). Custom made MWCNTs with different lengths and diameters were synthesized and suspended in artificial lung-like or culture medium by ultrasonic treatment. For both the in vivo and the in vitro experiments, long amosite asbestos served as the positive control and milled MWCNTs and Printex 90® were used as non-fibrous material controls. For two in vivo studies, separated MWCNTs were injected intraperitoneally (i.p.) in rats (low dose: 1 × 109, high dose: 5 × 109 MWNTs with WHO fiber definition). Cell proliferation in the diaphragmatic peritoneum was investigated as a short-term screening test, 3, 6 and (12) months after i.p. injection, using bromodeoxyuridine (BrdU) immunohistochemistry. An i.p. carcinogenicity and a subchronic inhalation study were also initiated with the same set of MWCNTs. Distribution and size of the MWCNTs were monitored by SEM. In vitro, LP9/TERT-1 cells were incubated with the custom made MWCNTs, Baytubes®, or the respective controls for 24h. Relative increase in cell count (RICC) was calculated to estimate the direct cytotoxic potential. The i.p. study revealed mesotheliomas and a dose-dependent increase in BrdU-positive-cells in the diaphragmatic peritoneum of rats treated with MWCNT1high (length: 7.9 µm; diam.: 37nm), MWCNT2low/high (length: 10.2 µm; diam.: 40nm), and MWCNT3low/high (length: 8.6 µm; diam.: 85nm). Additionally, MWCNT2high, MWCNT3low/high, and amosite (length: 14.0 µm; diam.: 390nm) treatment caused a significant, dose-dependent thickening of the diaphragmatic peritoneum after 3 and 6 months, compared to the non-fibrous and verhicle controls. In vitro, at 5 µg/cm2 MWCNT1, 2, 3, and 3a (length: 9.3 µm; diam.: 62nm) inhibited cell proliferation and caused cell death comparable to amosite. In conclusion, MWCNT tested were cytotoxic in mesothelial cells in vitro, and enhanced cell proliferation in rat diaphragmatic peritoneum and induced mesotheliomas after i.p. application in rats.