Carbon Nanotubes and Pulmonary Toxicity - Biointeractions of Nanomaterials - page 135

generated DNA damage. Intratracheal installations of SWCNTs to mice caused genotoxicity in their
bronchoalveolar cells as measured by the Comet assay (Jacobsen et al., 2009). The inhalation of
SWCNTs in mice for 4 days caused significant K-ras gene mutations. This gene mutation is associ-
ated with lung cancer (Shvedova et al., 2008a).

6.5 PULMONARY TOXICITY OF MWCNTs
MWCNTs can have a mean length of 4 μm and a diameter of 50 nm, which makes them more fiber
like; they are similar in structure to collagen fibers of the alveolar interstitium (Porter et al., 2010,
Mercer and Crapo, 1990). An acute pulmonary response in mice to MWCNTs was investigated
and a single treatment with MWCNTs was found to cause lung cytotoxicity and inflammation in
the mice when administered by oropharyngeal aspiration (Han et al., 2010). When mice aspirated
MWCNTs, they had transient inflammation and pulmonary damage, as shown by a rapid granulo-
matous response and progressive interstitial fibrosis (Mercer et al., 2011). Rats were intratracheally
exposed to MWCNTs, which caused lung cytotoxicity and inflammation as shown by collagen-rich
granulomas and an overproduction of TNF-α (Muller et al., 2005). Mice, when given MWCNTs
by oropharyngeal aspiration, developed lung cytotoxicity and inflammation as measured by granu-
loma formation and increased inflammatory cell infiltration (Wang et al., 2011). Rats were treated
with MWCNTs via intratracheal instillation and they developed lung cytotoxicity and inflammation
as measured by fibrosis formation and increased inflammatory cell infiltration (Aiso et al., 2010).
Mice were exposed to MWCNTs by either inhalation or intratracheal instillation. Inhalation led to
the proliferation and thickening of the alveoli, and intratracheal instillation led to the inflamma-
tion of the bronchi and alveolar damage. The differences in toxicity observed by the two exposure
routes are probably due to the MWCNTs' aggregation size and distribution in the mouse lungs (Li
et al., 2007). Rats were exposed to MWCNTs via inhalation, which caused pulmonary granuloma-
tous and neutrophilic inflammation (Ma-Hock et al., 2009). Human lung epithelial cells exposed to
MWCNTs caused genotoxicity as measured by the Comet assay (Karlsson et al., 2008). The major
pulmonary toxicities are listed in Table 6.3.

6.6 METALLIC CONTAMINATION OF CNTs AND PULMONARY TOXICITY
Arsenic (As), iron (Fe), and nickel (Ni) are some examples of metal catalysts used in the synthesis
of CNTs and may contribute from 25% to 40% of the CNTs' weight. It is impossible to entirely
remove catalyst metal contaminants in CNTs without destroying the structural entity. These metal
contaminants significantly contribute to oxidative stress, indicated by the formation of free radicals
and the accumulation of peroxidative products, the depletion of total antioxidant reserves, and a
loss of cell viability (Shvedova et al., 2003, Firme and Bandaru, 2010). The zymosan-stimulated

TABLE 6.3
Pulmonary Toxicity of MWCNTs

Species Toxicity References

Mouse Lung cytotoxicity and inflammation Han et al. (2010)

Mouse Lung cytotoxicity and inflammation Mercer et al. (2011)

Rat Lung cytotoxicity and inflammation Muller et al. (2005)

Mouse Lung cytotoxicity and inflammation Wang et al. (2011)

Rat Lung cytotoxicity and inflammation Aiso et al. (2010)

Mouse Lung cytotoxicity and inflammation Li et al. (2007)

Rat Lung inflammation Ma-Hock et al. (2009)

Human Genotoxicity of lung epithelial cells Karlsson et al. (2008)