Pilot study on mice reports asbestos-like pathogenicity of carbon nanotubes
|This study evaluates the effects of an intraperitoneal (i.p.) injection of four preparations of MWCNT compared to i.p. injections of long-fibre mosite (LFA) and short-fibre amosite (SFA) in mice. Results showed clear differences between long and short/tangled MWNTs.|
Reviewed by Annette Santamaria, PhD, MPH, DABT. ENVIRON International Corporation.
- Poland, C. A., Duffin, R., Kinloch, I., Maynard, A., Wallace, W. A. H., Seaton, A., Stone, V., Brown, S., MacNee, W., and Donaldson, K., "Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study," Nature Nanotechnology 3 (2008) 423 - 428. DOI: 10.1038/nnano.2008.111
Concern has been expressed in the scientific and regulatory communities about the potential for the induction of pulmonary toxicity following inhalation exposure to carbon nanotubes (CNT). The potential similarity in size and shape between CNT and asbestos fibers has led to some concern that there may be potential respiratory health risks associated with workplace and environmental exposure to CNT because the high aspect ratio of CNT is physically similar to the high aspect ratio of asbestos.
This study was conducted to evaluate the effects of an intraperitoneal (i.p.) injection of four preparations of MWCNT compared to i.p. injections of long-fibre mosite (LFA) and short-fibre amosite (SFA) in mice. In addition, a nanoparticulate carbon black (NPCB) sample was used as a non-fibrous graphene control. The four samples of MWNTs were chosen to assess the role of long rigid fibres in stimulating a mesothelial response similar to that caused by LFA. Two of the MWNT samples, NTlong1 and NTlong2, contained a substantial proportion of long straight fibres longer than 20 mm, and the other two samples, NTtang1 and NTtang2, consisted of CNTs arranged in low-aspect-ratio tangled aggregates.
Female C57Bl/6 mice were treated with intraperitoneal (abdominal) injections of 50 μg of vehicle control, NPCB, SFA, LFA, NTtang1, NTtang2, NTlong1, or NTlong2. After 24 hours and 7 days post-exposure, the mice were killed and the peritoneal cavity lavaged. The lavageate was analyzed for the presence of proteins and cells hours later. Histological quantification of granulomas on the peritoneal side of the diaphragm and foreign body giant cells (FBGCs) was carried out after 7 days.
The samples that contained long fibers (LFA, NTlong1 and NTlong2) caused significant increases in polymorphonuclear macrophages (PMN) and protein levels, exudation, FBGCs, and granulomas on the peritoneal side of the diaphragm. Particle samples that did not contain detectable long fibers – NPCB, SFA, NTtang1 and NTtang2—failed to cause any significant inflammation at 1 day or FBGC formation at 7 days. There was a small, nonsignificant granuloma response in one of three of the NTtang2 treated mice that the investigators concluded may have been a consequence of a contamination of long fibers that was so low that they were not detected in the fiber size analysis.
Long MWNTs produced inflammation, elevated FBGCs, and granulomas that were qualitatively and quantitatively similar to the foreign body inflammatory response caused by long asbestos. In contrast, NPCB did not cause peritoneal inflammation, indicating that fibrous shape dominates over simple graphene chemistry in effects on the mesothelium. The authors concluded that their results showed clear differences between long and short/tangled MWNTs and that although short CNTs do not mimic the behavior of long asbestos, the results cannot preclude the possibility that short CNTs are harmful by conformation to some other paradigm that was not addressed here, such as intrinsic toxicity as particles, as opposed to fibers. Importantly, this study did not address whether the mice that were exposed to long MWCT developed inflammatory and granulomatous changes or would go on to develop mesotheliomas.
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