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HARN - Nanotech Regulatory Document Archive

HARN - Nanotech Regulatory Document Archive

‘frustrated

‘frustrated phagocytosis’ is well known in fibre toxicology (Manning et al., 2002). This study has demonstrated that MWCNT length can interfere with the ability of macrophages to phagocytose just like asbestos. In a study published in Nature Nanotechnology Poland et al., 2008 specifically asked whether carbon nanotubes satisfied the fibre paradigm rule regarding length –in other words were long carbon nanotube fibres harmful whilst short fibres were not. This is the case with asbestos as has been shown in several key studies (e.g. Davis et al 1986). The study focused on the mesothelium, the cells that line the pleura and other body cavities, since asbestos -exposed individuals develop a number of conditions of the pleura, including the tumour mesothelioma; so this seems a special target for harmful fibres. Nanotubes were chosen that were long and straight (i.e. one dimension longer than about 15 microns) and also nanotubes that were long tangled or short tangled (shorter than about 5 microns in any dimension). The short-term response of the mesothelium in the rat peritoneal cavity was analysed and only the long carbon nanotubes caused damage, inflammation and scarring (granuloma formation). As has been shown for long amphibole asbestos, these endpoints are linked to longer term effects, like mesothelioma. The short carbon nanotubes had no effect. We included a long and a short asbestos control - the long caused damage and inflammation whilst the short had no effect. Nanoparticulate carbon black was included as a control nanoparticle, since they are compact particles composed of graphene in particle, not tubular form -this had no effect on the mesothelium. The conclusions were clear that in terms of the toxicological rules governing fibre pathogenicity multiwalled carbon nanotubes that are long satisfy the criterion of a pathogenic fibre whilst multiwalled carbon nanotubes that are short satisfy the criterion of non-harmful. Asbestos also satisfies the same rules. As for the other rules –carbon nanotubes are very thin and they are durable in preliminary studies that have been carried out. These studies have suggested that physical characteristics of HARN, such as length and biopersistence control pathogenicity for nanotubes, as is the case with asbestos and so long nanotubes may initiate adverse effects in the lung similar to those caused by asbestos exposure. It is important to note that the current data available are related to CNT only. Page 32

4.6 A RESEARCH STRATEGY TO DETERMINE THE POTENTIAL TOXICITY OF HARN There are accumulating data regarding the potential toxicity of HARN, but as demonstrated in the reviews above, the existing information is mainly related to CNT. This is no doubt a result of the production volume of this material, being substantially greater than any other HARN. Information on other HARN such as nanowires and nanorods is clearly lacking. There are two possible paradigms that HARN could follow to produce toxicity – a particle-based paradigm and a fibre paradigm-based toxic effect. This document concentrates on the fibre-like effects, using asbestos as the example. However, research is need to determine whether HARN as particles/aggregates (

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