Biomedical Engineering Reference
In-Depth Information
circulation, genotoxic and possible carcinogenic effects, as well as some brief remarks on the effects
of engineered nanomaterial on the brains. Other organs and their significance may only be briefly
mentioned.
19.7.3.1 Translocation of Engineered Nanomaterial into the Body
The intravenously injected radioactive iridium191 NPs are rapidly excreted in the urine, but the
fraction of dose is widely distributed to a number of organs in the body. The inhaled manganese
oxide NPs enter into the olfactory bundle under the forebrain via the axons of the olfactory nerve in
the nose, that is, in the olfactory epithelium, and they can reach other parts of the brain also through
systemic inhalation. The inhalation of nanosized titanium dioxide NPs reached systemic circulation
in rats. The inhaled engineered nanomaterial can reach systemic circulation in the body and via this
route, can be distributed to a number of different target organs including the brain, liver, kidney,
immunological system, and vessel walls. These findings emphasize the importance of exploring
the ability of different engineered nanomaterials to reach the body via different routes of which the
inhalation route is the most likely. Other routes such as the GIT or the skin will not be dealt with in
this context. The former is less relevant in occupational safety and health or even in the consumer
context, and penetration of the skin by engineered nanomaterial is not likely. However, titanium
dioxide is increasingly being used, for example, in sunblock creams but its ability to penetrate
beyond the stratum corneum is controversial [79]. In the future, when nanotechnology applications
will become much more widespread and will be increasingly used in, for example, food items such
as food additives or materials for food packaging, the significance of oral exposure and gastrointes-
tinal absorption of engineered nanomaterial may considerably increase.
19.7.3.2 Pulmonary Inflammation Induced by Engineered Nanomaterial
Nanomaterial-induced pulmonary inflammation includes intratracheal installation or pharyngeal
aspiration of engineered nanomaterial suspension. These models provide results of nanomaterial in
the lungs that are similar or even identical to those induced through inhalational exposure, thereby
providing evidence that the relevance of these models is quite good. It has been shown that CNTs,
when introduced into the lungs, induce a strong pulmonary response in this organ at moderate doses
of the material whether intratracheal installation, pharyngeal aspiration, or inhalational exposure
have been used. It seems that these exposure models lead to relatively even distribution of the
CNTs applied into the lung tissue. However, there seem to be slight differences when the effects
of inhalational exposure with the other exposure models are compared. Intratracheal installation
of SWCNTs suspension to rats at doses of 1 or 5 mg/kg, induced multifocal granulomas that were
inconsistent with the lack of toxicity in bronchoalveolar lavage fluid (BAL), lack of lung toxic-
ity based on proliferation parameters, and lack of dose-effect relationship. Whereas, exposure of
SWCNTs to mice induced pulmonary inflammation and granulomas in a dose-dependent fashion
subsequent to pharyngeal aspiration of SWCNTs at lower or similar doses. It was also observed that
oxidative stress played an important role in SWCNT-induced pulmonary toxicity by using reduced
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase deficient in C57BL/6 mice. The
NADPH-oxidase null mice responded to SWCNTs with a marked exposure of polymorphonuclear
leukocytes and elevated levels of apoptotic cells in the lungs, an increased production of proinflam-
matory cytokines, and lower levels of collagen deposition as compared to C57BL/6 control mice,
providing new insight on the role of oxidative stress in SWCNT-induced pulmonary toxicity. The
exposure of SWCNT in C57BL/6 mice by pharyngeal aspiration at doses of 0, 10, 20, and 40 μg/
animal evoked a dose-dependent increase in the severity of acute pulmonary inflammation and
progressive fibrosis and granulomas. Whereas, single long-term inhalational studies in Wistar rats
exposed to MWCNTs at exposure levels of 0, 0.1, 0.5, or 2.5 mg/m
3
for 3 months, induced granulo-
matous-type inflammation.
It has been found that exposure of mice to titanium dioxide-engineered nanomaterial may cause
pulmonary inflammation with elevated numbers of inflammatory cells together with increased
