Biologische Wirkungen synthetisch hergestellter Multiwall-Carbon-Nanotubes am Tiermodell und in der Zellkultur

The aim of this study was to determine whether long, straight MWCNT have an asbestos-like effect and whether possibly carcinogenic and other adverse effects can be detected in in vitro screening assays and in in vivo assays with short durations. For this purpose, a carcinogenicity test was conducted and a BrdU test was developed. Inhalation tests (short-term and 90 day inhalation) were performed to determine MWCNT migration and clearance. In addition, in vitro experiments were carried out as a screening test to enable early prediction of possible toxicity or carcinogenicity. In this study, it could be shown that all four MWCNT tested in the carcinogenicity test caused a dose-dependent increase in mesothelioma and mortality in rats. These results, however, did not enable any conclusion to be drawn as to whether the length or the diameter of MWCNT is decisive for mesothelioma development. There was evidence though that a more needlelike and rigid structure of MWCNT leads to a higher mesothelioma rate. The BrdU test after a single i.p. injection of MWCNT is suitable for earty detection of a possible carcinogenic potential. The best time for this determination was found to be three months after treatment with MWCNT. A subchronic (90 day) inhalation test hardly demonstrated any migration of the MWCNT. Macrophage accumulations (particle- or fiber-loaded) were found in all treatment groups throughout the observation period. In addition, inflammatory reactions (microgranuloma and fibrosis) were observed in the MWCNT, Printex 90 (no microgranuloma) and amosite-exposed groups. Findings were more pronounced in animals after Printex 90 and amosite inhalation. These effects were not reversible in MWCNT 1-exposed animals and in Printex 90 or amosite-exposed animals, compared with MWCNT 2 and 3a-exposed animals. Retention analysis revealed a strongly delayed dearance in MWCNT 1 and 2-exposed animals. MWCNT 3a-exposed animals showed a processing-induced, unusually short clearance of 38 days for WHO fibers (length-to-diameter ratio: >= 3/1 , length > 5 m and diameter m). For MWCNT 3, hydrolysis of the lungs would have to be optimized. In a short-term inhalation test with 60Co-activated MWCNT, migration of MWCNT from the lungs to the blood-rich organs was measured. The strongest migration was found after one day. High 60Co activity, however, was also measured in the gastrointestinal tract, so that it must be assumed that the animals swallowed a large proportion of MWCNT during inhalation. In the in vitro tests, treatment especially with MWCNT 3 showed an increased toxic potential in the RICC test, LOH assay, and comet assay. Among the in vitro methods evaluated in this study, the most suitable screening test for in vivo experiments seems to be the RICC test, in which MWCNT 1, 2 and 3a led to a reduction of cell growth or an increase in cell mortality. At present, in vitro experiments can thus provide a first indication of increased toxicity, but subsequent in vivo tests are so far inevitable