Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 366

in terms of their properties and quality. Not only do they differ greatly between
different sources, but even the same laboratory/manufacturing process can gener-
ate vastly different samples from day to day. Add to this the fact that composition,
length, wall number and catalyst can all be manipulated, then it is clear that it is
still too early to disregard inhalation as a feasible route of exposure.
Some of the fi rst studies to investigate SWCNT respiratory toxicology used pha-
ryngeal aspiration as a means of delivery to mice (up to 40 g/mouse) (Shvedova

et al. , 2005). The SWCNT generated an acute infl ammatory response with increased
neutrophils at day 1 and macrophages at day 7. In addition, fi brosis of two forms
was generated within 28 days at a dose of 20 or 40

µ

g/mouse. The fi rst presented as
granulomas mainly associated with hypertrophied epithelial ells surrounding
SWCNT aggregates. The second consisted of diffuse fi brosis and alveolar wall
thickening. Biochemical markers of lung damage included increased bronchoalveo-
lar lavage protein, lactate dehydrogenase (LDH) and g-glutamyl transferase activ-
ity. Induction of oxidative stress was indicated by increased 4-hydroxynonenal and
glutathione depletion of lung tissue.
Another study delivered MWCNT to rats via instillation into the lung (0.5, 2 or
5 mg/animal) (Muller et al. , 2005). In this study MWCNT were compared with
ground MWCNT. Both samples persisted in the lung tissue for 60 days, induced
infl ammation and resulted in fi brosis (2 mg/rat). The pathology developed into a
collagen rich granuloma by two months, caused by the accumulation of agglomer-
ates of MWCNT in the airways. Ground MWCNT were better dispersed but still
caused infl ammation and fi brosis. Interestingly, this study compared the MWCNT
with nanoparticle carbon black; they found the MWCNT to be more pathogenic.
Other studies comparing SWCNT with nanoparticle carbon black have made
similar observations (Warheit et al. , 2004 ; Lam et al. , 2004 ).
The reason for the relative potency of single- and multi-walled carbon nanotubes
compared to nanoparticle carbon black remains unclear, but could include chemical
differences in the graphitic surface of the particles or the physical size of the aggre-
gates produced in the studies, as suggested by Warheit et al. (2004). In the study by
Lam et al. (2004) the SWCNT was found to be more potent at inducing granulomas
and fi brotic lesions than quartz, a well known fi brotic and carcinogenic respirable
particle. The different studies quoted here vary in terms of the source of the carbon
nanotubes, metal contamination and particle dimensions. A systematic approach is
required to identify the physicochemical characteristics that drive the pathogenic
responses observed in these studies. All of the studies described above have involved
delivery of a bolus dose of aggregated or agglomerated nanoparticles. To date,
inhalation studies of airborne multi-walled or single-walled carbon nanotubes have
not been published.
As mentioned previously one of the main defence mechanisms from the lung
involves clearance by macrophages. Kagan et al. (2006) compared SWCNT that
either contained iron (26 wt-% of iron) or were iron depleted (0.23 wt-% of iron).
In a cell-free system the iron content determined the ability of the SWCNT to
generate free radicals. In the same study, the authors treated the RAW 264.7 mac-
rophage cell line in vitro with SWCNT and found that the iron rich sample induced
markers of oxidative stress such as glutathione depletion and lipid peroxidation,

µ