CNT Pulmonary applications and toxicity

....risks from certain nanoscale substances would be addressed through the Regulation if they were identified as being 'substances of very high concern' as defined in Article 57, for example being persistent, bioaccumulative and toxic (PBT). The EC are funding research to address methodologies for identifying the hazards of nanoscale substances through the 7th Research Framework Programme (FP7) and point out 'it will also be necessary to carefully monitor over the next few years whether the [1 tonne per year] threshold for registration and the information requirements under REACH are adequate to address potential risks from particles on a nanoscale.'

A particularly relevant example for consideration is that of carbon nanotubes (CNTs). 'Carbon' (EINECS number 231-153-3) has recently been removed from the list of exempt substances under REACH (Annex IV). If upon registration under REACH, CNTs are deemed to be the chemical equivalent of carbon or carbon black (and thus registered using the EINECS / CAS numbers for carbon or carbon black), a registrant of carbon nanotubes would need only to supply the same technical information as they would for carbon or carbon black. However, if carbon nanotubes and carbon / carbon black are deemed to be different chemical substances for the purpose of registration, then before the carbon nanotubes were permitted entry into the market, the registrant would be required to submit a technical dossier to include guidance on their safe use, as specified by Article 10 of the REACH Regulation.

At this time, it is still unclear if the EC will consider nanoscale substances as equivalent to their bulk counterparts. Fullerenes have been recently assigned CAS numbers, so there does seem to be scope for ECHA to consider nanoscale substances as separate entities. However, if nanoscale substances are treated as 'existing' chemicals due to their chemical composition being comparable to their micro or macro counterpart under REACH, there is the danger that the regulation may fail to adequately control nanoscale materials in the presence of scientific uncertainty regarding their toxicity.

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http://www.safenano.org/nanoREACH.aspx



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Meta analysis

There is no established guideline for research question on potentials of NPs toxicity – therefore studies have used variety of methods that are difficult to extrapolate and find conclusive results. NPs characteristics has to be clearly defined in terms of solubility, surface area, charge, modifications, shape, number composition, etc.
For instance positively charged NPs showed increased of accumulation in lungs.
Administration of Chitosan-DNA showed to inhibit virus infection and allergic reactions.

Carbon black, fullerenes, silica, and metal-based nanoparticles have also been studied for their ability to induce inflammatory and fibrotic responses in the lungs of experimental animals following delivery via instillation, aspiration, and/or inhalation (Table 2). Increased lung inflammation resulting from exposure to nano-sized particles compared with that resulting from an equivalent mass of micron-sized particles has been demonstrated in some studies (16, 45, 49, 54, 82, 118, 160), whereas others have found this not to be the case (9, 120, 135, 149). Potential factors in the increased inflammatory profile observed for nanoscale materials in some studies include their size, increased number, and higher surface area per unit mass compared with that of larger particles of the same material (15, 98, 104). Titanium dioxide is a good example of how both the size and form of a nanoparticle can influence its pulmonary toxicity, as a nanoscale anatase form of titanium dioxide was found to induce greater lung inflammatory responses than those resulting from a nanoscale rutile form and from a micron-sized anatase form following intratracheal administration in rats (148). The increased ratio of surface area to mass for nanoparticles means that a greater percentage of the atoms or molecules of a given particle are present on the surface of the particle, thereby providing an increased number of potential reactive groups at the particle surface that may influence toxicity. Although this appears to be a useful metric for assessing the toxic potential of some nanoparticles, there is consensus among experts in the field that no single dose metric (i.e., particle number, size, surface area, or other) has emerged to be useful for assessment of the reactivity and potential toxicity of nanoparticles in general (89, 144). Rather, it is likely that the most appropriate means of expressing dose-related toxicity for nanoparticles of interest will continue to be determined on an individual basis.(1)

(1) Card J et al, 2008, Pulmonary applications and toxicity of engineered nanoparticles, Am J Physiol Lung Cell Mol Physiol 295: L400-L411
http://ajplung.physiology.org/cgi/content/abstract/295/3/L400


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