Biomedical Engineering Reference
In-Depth Information
by proteases in the gut (Hardman 2006). It is still unclear as to how NMs may be metabolized in the
body. Therefore, studies need to be conducted to address these unanswered questions.
1.6.2.2.4 Elimination
NMs can be eliminated from the body via various routes, such as exhalation; urination (via the kid-
neys) (Singh et al. 2006); defecation (via the biliary duct) (Hardonk et al. 1985, Renaud et al. 1989);
perspiration; and through the saliva, seminal fluids, and mammary glands. Their fate of elimina-
tion, again, depends on their physicochemical properties. For example, hydroxyl functionalized
SWCNT accumulate in the liver and kidneys and are excreted in the urine within 18 days (Wang
et al. 2004a). On the other hand, ammonium functionalized SWCNT show neither liver uptake not
fast, renal excretion (Singh et al. 2006). Contrary to that, QD are not excreted and remain intact
in
vivo
(Fischer et al. 2006, Yang et al. 2007) unless they have a coating. This has been proven in the
case of QDs coated with cysteine, which were excreted in mice urine (Choi et al. 2007). Studies
should focus on identifying organs that could be stressed by exposure to NMs, possibly providing
a molecular basis for the stress response. If there is an association found with specific organ cells
and NMs characteristics (e.g., size, surface chemistry, aggregation and composition, shape), then it
would be possible to establish correlations between the toxic effects of NMs and specific NM prop-
erties. Demonstrated pharmacokinetic studies of various NMs will be discussed in greater detail in
the later chapters.
1.6.3 e
ffects
of
N
aNoMaterIals
oN
o
rgaN
s
ysteMs
There are numerous, inevitable, exposure routes by which NMs can enter the human body to elicit
potential adverse effects. The specific routes are the respiratory, reticuloendothelial, cardiovascular,
central nervous, and integumentary systems.
1.6.3.1 Pulmonary System
The respiratory system serves as a major entry portal for ambient particulate materials. The short-
term exposure of inhaled, ultrafine carbon black, nickel, and TiO
2
particles were found to produce
an enhanced inflammatory response in the rat respiratory system, as compared to fine-sized par-
ticles of similar chemical compositions (Grassian et al. 2007, Pettibone et al. 2008, Wani et al. 2011,
Warheit et al. 2006). The micron-sized particles are largely trapped and cleared by the upper airway
mucociliary escalator system, whereas particles less than 2.5 μm can travel to the alveoli. Inhaled
NPs can become deposited in the alveolar region (Arora et al. 2012, Curtis et al. 2006, Hagens et al.
2007). The toxicity of NMs may initiate with the development of exaggerated lung responses, char-
acterized by increased and persistent levels of pulmonary inflammation, subsequently transformed
into cellular proliferation, fibro proliferative effects, and inflammatory-derived mutagenesis, which
ultimately results in the development of lung tumors. As previously mentioned, various factors that
are likely to influence the pulmonary toxicity of NPs are the size and number of particles, surface
dose and coating, degree of aggregation, surface charges, and the method of particle synthesis
(Lyon et al. 2006, Wani et al. 2011).
1.6.3.2 Gastrointestinal Tract
NMs can reach the GIT directly through the ingestion of food, water, cosmetics, drugs, and by the
use of drug delivery devices, as well as after mucociliary clearance from the respiratory tract through
the nasal region (Arora et al. 2012, Hagens et al. 2007). The acute toxicity of ingested nanocopper
material was found to be more toxic than bulk copper material in mice. The occurrence of systemic
argyria after the ingestion of colloidal nanosilver proves its secondary toxic effects after translocation
from the intestinal tract (Arora et al. 2012). Reports were found for the uptake of fluorescently labeled,
polystyrene NPs by intestinal lymphatic tissue (Peyer's patches) (Morishita and Peppas 2006).
