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ICONS - Integrated testing strategy for mechanistically assessing the respiratory toxicity of functionalized MWCNT

: Creutzenberg, Otto H.; Lison, D.; Brule, S. van den; Simon, S.; Bonner, J.C.; Ziemann, Christina

The Toxicologist 168 (2019), No.1, Abstract PS 2232
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <58, 2019, Baltimore/Md.>
Fraunhofer ITEM ()

Multiwalled carbon nanotubes (MWCNT) show promising technical properties (e.g. composite enforcement; electrical conductivity). MWCNT, meeting WHO criteria, exhibit straight or curved/tangled morphology, depending on length and diameter. Evident fiber toxicity was observed for the rigid fiber type, i.e carcinogenicity in the rat model after intraperitoneal injection. Tangled type MWCNT (not carcinogenic) may show an altered toxic potential regarding fibrotic or genotoxic effects following surface modification with functional groups such as -NH2 or -COOH. The ERA-NET SIINN project ICONS (International Collaboration On Nanotube Safety) aimed at mechanistically evaluating and ranking the pro-fibrotic and genotoxic potential of tangled MWCNT, focusing on impact of core purification and surface functionalization. A batch of industrially relevant Nanocyl NC7000 was therefore chemically or thermally purified and surface functionalized (-COOH and -NH2). At Fraunhofer ITEM, the eight resulting MWCNT (pristine, milled, purified, and functionalized) were tested for sterility and endotoxin. For in vitro use, they were dispersed using an ultrasound-based protocol, and characterized by light and scanning electron microscopy. Subsequent in vitro (geno)toxicity testing with MRC-5 primary human lung fibroblasts revealed differential inhibition of proliferation (RICC, mitotic index), induction of membrane damage and micronuclei, and loss of chromosomes. Based on these results and existing in vivo data (generated by LTAP and NCSU; oro-pharyngeal aspiration tests), two functionalized MWCNT will be selected for a 4-wk inhalation test in rats (based on OECD TG 412), including a 4-wk recovery (validation test). Completed pre-trials demonstrated feasibility of generating respirable MWCNT aerosols by dry dispersion with pressurized air. This project is funded by the German BMBF (FKZ: 03XP0063).