Biomedical Engineering Reference
In-Depth Information
TABLE 8.5 (
continued
)
Effects of 50 mg/m³ Metal Oxide Nanoparticles Observed in Short-Term
Inhalation Studies (nanoGEM) Directly after Exposure or after an Additional
3-Week Recovery Period
Property or
Effect
SiO
2
.
Naked
SiO
2
.
PEG
SiO
2
.
Amino
SiO
2
.
Phosph.
ZrO
2
.
Acryl
ZrO
2
.
TODS
Time Point
Units
(Multi)focal
inflammation
After
exposure
-
0
(1)
0
0
0
0
After
recovery
-
2
‡
0
0
0
0
0
Macrophage
aggregation
with
eosinophilic
content
After
exposure
-
2
‡
(1)
0
0
0
0
After
recovery
-
2
‡
0
0
0
0
0
Comet assay
5d inhal.,
21d rec.,
50 mg/m³
% tail
intensity
n.e.
n.e.
2.0%-
3.9%
n.e.
3.2%-
5.2%
n.e.
Concurrent
control
% tail
intensity
n.e.
n.e.
1.3%-
3.3%
n.e.
2.7%-
3.2%
n.e.
Abbreviations:
n.e., not examined; **, statistically significant
p
< 0.01; *, statistically significant
p
<
0.05;
‡
, adverse effect.
With regard to SiO
2
-based particles, adverse effects were only observed in ani-
mals exposed to SiO
2
Levasil
®
200 nanoparticles. SiO
2
.PEG induced a few adaptive
effects in lung and larynx without any changes in lavage parameters. SiO
2
.amino
induced a weak and transient influx of neutrophils directly after exposure, confirm-
ing the effect of neutral/positive charge observed on ZrO
2
.TODS. SiO
2
.phosphate
did not cause any effects on pathology and clinical chemistry (Table 8.5). These data
showed that the
surface modification
did reduce the inhalation toxicity of SiO
2
par-
ticles. An influence of surface modification on clearance and translocation behavior
could not be detected within this project. The lung clearance of all SiO
2
variants was
faster than expected for granular poorly soluble particles (
t
½ approximately 20 ver-
sus 60 days) (Morrow 1988). While SiO
2
may partially dissolve in specific cellular
compartments, ZrO
2
is almost insoluble under all relevant conditions, including pH
value inside phagolysosomes, and was rapidly cleared from the lung with about the
same half-time. It is interesting to note that the affinity to surfactant proteins from
the lung lining fluid (Figure 4.3) provides the same identification of SiO
2
.naked and
SiO
2
.phosphate as extreme cases.
Based on the examination of hematological and clinical chemical parameters in
blood, there was no indication of potential systemic toxicity for any of the tested
substances. The MN assay in bone marrow and the comet assay in lung showed that
ZrO
2
.acryl and SiO
2
.amino were not mutagenic in bone marrow and did not cause
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