Biomedical Engineering Reference
In-Depth Information
DNA damage in the lung (Table 8.5). Similar results have been observed for 50 nm
pure rutile TiO
2
and 30-200 nm ZnO nanoparticles. Landsiedel et al. reported that
these particles did not display genotoxicity neither
in vitro
(Ames' Salmonella gene
mutation 22 test and V79 MN chromosome mutation test) nor
in vivo
(mouse bone
marrow MN test 23 and comet DNA damage assay in lung cells from rats exposed by
inhalation) (Landsiedel et al. 2010). Also for smaller TiO
2
nanoparticles with higher
anatase content (21 nm, 74% anatase, 26% rutile), no DNA damage in lung epithelial
cells or genotoxic effects on micronuclei in bone marrow polychromatic erythro-
cytes could be observed after inhalation exposure for 5 days (0.8, 7.2, 28.5 mg/cm
−3
,
4 h/day) (Lindberg et al. 2012). Even after chronic inhalation for 2 years to 10.4 mg/
m
3
of 15-20 nm TiO
2
nanoparticles, no DNA adduct formation could be detected in
the peripheral lung tissue (Gallagher et al. 1994). However, for P25 nanoparticles and
for 33 nm anatase TiO
2
nanoparticles genotoxic effects detected by the comet assay
and the MN test have been found after oral gavage to mice for 5 days (500 mg P25/kg
body weight) or 7 days (40, 200, 1000 mg 33 nm TiO
2
/kg body weight), respectively
(Trouiller et al. 2009; Sycheva et al. 2011), for review see Magdolenova et al. (2013).
To summarize on surface properties, none of the surface-coated SiO
2
or ZrO
2
materials exhibited significant adverse effects in inhalation. In contrast, the func-
tionalization of SiO
2
.naked nanoparticles decreased inflammatory effects. Other
studies with different TiO
2
materials also demonstrated that particle surface prop-
erty rather than particle form or size determines the inhalation toxicity of particles
in the lung (Warheit et al. 2006, Warheit et al. 2007, Madl and Pinkerton 2009).
Weak and transient effects were observed exclusively for SiO
2
.amino and ZrO
2
.
TODS, which are the only particles with neutral/positive surface charge. On the
other extreme, BaSO
4
and ZrO
2
.acryl carried the highest negative charge and had
the lowest toxic potency in the lung. The analysis of the interaction of the particles
with proteins, including the formation of lipid/protein corona (Chapter 4) and asso-
ciation with cell membranes and internalization as well as intracellular trafficking
(Chapter 7), does not necessarily simplify the grouping of materials, if as-produced
parameters (Chapter 1) such as charge were considered sufficient to prioritize
materials for testing (Chapter 16).
8.4.3 e
ffeCts
of
m
etal
o
xide
n
anoPartiCles
on
a
nimals
With
a
llergiC
a
irWay
i
inflammation
Active AM and an effective epithelial layer can usually prevent adverse effects of
nanomaterials in intact lungs. These protective mechanisms are impaired when
nanomaterial exposure occurs in a lung damaged by a mild or severe disease. This
situation was studied in a model of allergic airway inflammation.
Allergic airway inflammation is characterized by inflammatory cell infiltration,
mucus cell hyperplasia, and airway hyperresponsiveness. These effects are closely
linked and interdependent. Lymphocytes and eosinophils are considered to be the
key effector cells: soluble factors derived principally from T cells play an essential
role in recruiting inflammatory cells in the lungs (Gavett et al. 1994). Eosinophil
accumulation and activation with the subsequent release of cationic proteins in the
airways have been implicated in many pathological processes and in the subsequent
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