BIOMEDICAL AND BIOMEDICINE APPLICATIONS OF CNTs - Bio-Inspired and Nanoscale Integrated Computing - page 504

associated with carbon nanotube production, with the primary risk being CNT
inhalation and epidermal exposure [94-101]. Because the production of CNTs
includes the use of metal catalysts such as iron and nickel, toxic effects from these
metal particles should also taken into consideration. Preliminary in vivo studies in
rats and mice revealed the development of pulmonary epethilial granulomas and
mortality from intratracheally-instilled, unpurified SWCNTs. The extent of
toxicity due to catalyst particles is unclear from this rat study although in the
mouse study granulomas were observed regardless of metal content from various
SWCNT samples. However, these studies used excessive amounts of SWCNTs,
administered in a nonphysiological manner, thus making it difficult to interpret
results [97]. In the rat study, mortality was attributed to blockage of the upper
airways by the instillate and not inherently by SWCNTs. Mortality in the mouse
study was suggested to have been caused from the known toxicity of residual
catalyst particles in the sample.
In vitro studies have also been conducted using human keratinocyte epidermis
cells and alveolar macrophage cells (these being the first line of defense within the
lung against foreign particulates). The keratinocyte study specifically addressed
the toxic effect of ferrous iron from residual catalyst particles, citing its effect of
catalyzing the decomposition of hydrogen peroxide and lipid peroxides, thus
resulting in the generation of free radical species that enhance oxidative stress. In
the macrophage study, high levels of toxicity were observed although (again) the
extent of toxicity attributed to catalyst content is unknown.
The toxicity of MWCNTs has also been studied in vitro on keratinocytes and
was found to elicit an inflammatory effect but no severe toxicity [99]. In fact, the
discussed SWCNT studies on alveolar macrophage cells compared the toxicity of
SWCNTs to MWCNTs and found the latter to be less toxic. A more recent study
compared the in vivo and in vitro effects of SWCNTs on mice and mice cells. The
study used purified SWCNT samples with less catalyst content than was present in
previous studies, and the method of SWCNT administration was refined through
the use of pharyngeal aspiration, as well as consideration of relevant dose as
compared to the permissible exposure limits (PEL) for graphene particles
established by the United States Operational Safety and Health Administration.
The in vivo study revealed distinct effects due to aggregated and dispersed
SWCNT particles where aggregates induced granulomas due to macrophage
accumulation, while dispersed particles resulted in a fibrogenic response. Further-
more, exposure to SWCNTs affected pulmonary function by inhibiting bacterial
clearance. The in vitro study was conducted on macrophage cells and found that
the cells exhibited changes in gene expression but no severe toxic effects.
From examining the degree of airborne particulate generation by simulating a
SWCNT manufacturing environment and from the in vivo results to date, it has
been determined that particulate release from SWCNT manufacturing can
produce dangerous exposure levels. However, the administration of SWCNTs in
these in vivo experiments has not simulated physiological conditions (the most
accurate being the sudden dose of total PEL for 20 work days while bypassing the
nose and with the possibility of the incorporation of nonrespirable particles).