Biomedical Engineering Reference
In-Depth Information
intraperitoneal injection of high doses of crocidolite asbestos (1 × 1010 fibers, i.e., 3 mg in 1 mL of
water) or MWCNT (1 × 109 fibers, i.e., 3 mg in 1 mL of water) to a sensitive p53 ± mouse strain
for 120 days, the ability of MWCNTs to induce mesotheliomas exceeded the ability of crocidolite
asbestos. In another study when Fischer 344 rats were given a single intrascrotal dose of 1 mg/kg
MWCNT to induce exposure of the mesothelial lining of the intraperitoneal cavity, MWCNTs had a
much higher potential to induce mesotheliomas in these animals than a comparable dose of crocido-
lite asbestos. In all studies in which MWCNTs have been given intraperitoneally [73], MWCNTs
formed agglomerates or bundles, and single MWCNTs were not present. This type of agglomeration
is also typical of MWCNTs and SWCNTs in occupational environments when the material exists in
aerosol [97]. These observations suggest that agglomerates consisting of MWCNTs (or SWCNTs)
may have the ability to induce mesotheliomas and asbestos-like morphological changes when in
contact with the mesothelial lining of the abdominal cavity. This exposure mode has been criticized
because the exposure is via the abdominal cavity rather than lungs [98]. It is also obvious that these
data cannot be used to assess risks of exposure to CNT, but they may provide useful information
for the identification of the possible hazard, that is, carcinogenic potential, of CNT. The issues to be
considered when assessing the potential of MWCNTs to induce carcinogenicity include the route of
exposure, the high dose given as a single bolus, fiber length, the possibility of removing the material
from the peritoneal cavity, as well as the impact of the high concentrations at a given time in the
abdominal cavity having a potential effect on agglomeration and aggregation of the material.
When MWCNTs were introduced into the abdominal cavity of mice, they induced asbestosis-
like pathogenic changes in the mesothelial lining of the abdominal cavity. The typical changes were
an increased number of inflammatory cells and protein exudates in the cavity as well as lesions in
the mesothelium. These data provide evidence that MWCNTs, when in contact with mesothelial
lining and mesothelial cells
in vivo
, have the capability to induce asbestos-like changes, even meso-
theliomas, providing useful data for hazard assessment of these materials. High doses of MWCNTs
do not induce mesotheliomas in Wistar rats after intraperitoneal injection.
19.7.3.5 Effects of Engineered Nanomaterial on Circulation
Urban nanosized aerosols have been shown to be associated with increased cardiac mortality in
humans. The mechanisms of this effect have been delineated in several studies [67] and have been
shown to be associated with oxidative stress in the blood vessel endothelial lining [99]. Engineered
nanomaterials have also been assumed to have adverse effects on circulation, but so far, data on
such effects have been scanty. The nanosized carbon black particles exert thrombogenic, that is,
fibrinogen deposition and platelet adhesion, but not inflammatory effects in the microcirculation of
healthy mice. The intratracheal exposure to particulate matter (diameter 0.1-2.5 μm) of rats impairs
systemic microvascular endothelium-dependent dilatation and associated inflammation in the ves-
sel wall. The inhalational exposure of rats to low concentrations of nanosized titanium dioxide-
engineered nanomaterial augments particle-dependent microvascular dysfunction. Furthermore,
the SWCNTs and MWCNTs induce platelet aggregation and vascular thrombosis. These findings
provide evidence that at least some types of engineered nanomaterial can reach the systemic circu-
lation through inhalation, and once in the bloodstream, they have the capacity to have a disturbing
effect on microcirculation. This is an important observation because once in the bloodstream, the
engineered nanomaterial can potentially induce its effects in any organ in the body as shown, for
example, by some of the translocation studies [100].
19.7.3.6 Other Remarks on the Effects of Engineered Nanomaterial
Observations that engineered nanomaterials can reach the brain via the bloodstream once they have
found an access to the systemic circulation have evoked much concern [100]. In an
in vitro
setting, it
has been observed that the increased production of ROS in immortalized brain microglial cells and,
in fact, convincing evidence on the effects of engineered nanomaterial in the neuronal cells is very
limited. In another
in vivo
study with intranasal exposure to manganese oxide NPs [100] by using
