Biomedical Engineering Reference
In-Depth Information
TABLE 8.3
Genotoxicity Testing of Naked and Coated Metal Oxide Nanoparticles
Cytotoxic/Toxic to
Bacteria
Particles
Test
Result
AlO(OH)
Micronucleus (MN) assay
in vitro
>50 µg/mL
Not genotoxic
Ames test
No
Not mutagenic
Comet assay
No
Not genotoxic
SiO
2
MN assay
in vitro
>250 µg/mL
Not genotoxic
Ames test
No
Not mutagenic
Comet assay
No
Genotoxic
SiO
2
.phosphate
MN assay
in vitro
>100 µg/mL
Not genotoxic
Ames test
No
Not mutagenic
Comet assay
No
Genotoxic
SiO
2
.PEG
MN assay
in vitro
No
Not genotoxic
Ames test
No
Not mutagenic
Comet assay
No
Not genotoxic
induced DNA damage (detected via the comet assay). They suggested that intrinsic
particle properties rather than soluble ions were responsible for the genotoxic effects
(Sharma, Anderson, and Dhawan 2012). This was also discussed by other groups
(Gojova et al. 2007; Lin et al. 2009).
Differences in the genotoxic responses of HepG2 cells after exposure to 25 nm
anatase and 100 nm rutile TiO
2
were suggested to be dependent not only on their
different particle size but also on their different
crystalline structure
(Petkovic et al.
2011). However, other studies could not clearly demonstrate an impact of nanopar-
ticles' crystal structure on genotoxicity. Exposure of human peripheral blood lym-
phocytes to 15-30 mm anatase TiO
2
, for instance, did not lead to genotoxic effects
(comet assay) albeit the nanoparticles were detected in the nucleus (Hackenberg
et al. 2011b). Similarly, other authors reported that neither rutile TiO
2
NP nor P25
TiO
2
particles induce chromosomal aberrations or mutagenicity (Warheit et al. 2007;
Bhattacharya et al. 2009).
In the nanoGEM project, the metal oxide nanomaterials AlO(OH) (37 nm), SiO
2
.
naked (15 nm), SiO
2
.PEG (15 nm), and SiO
2
.phosphate (15 nm) (compare properties
in Table 1.2), some of which are of commercial relevance, were investigated for their
ability to induce chromosomal breaks, aneuploidy, or point mutations in the absence
or presence of an extrinsic metabolizing system using the MN and the Ames test,
respectively. This was one of the first studies in which both assays were performed
according to OECD guidelines (Ames: OECD TG471, MN: OECD TG487) upon
adaptation/modification of the testing procedure to meet special requirements of the
manufactured nanomaterials. In addition, the comet assay was performed using 3D
bronchial models (EpiAirway
TM
, MatTek, Ashland, USA).
The results show that none of the investigated nanoparticles, independent of
their size, chemical composition, and coating, were able to induce mutagenic effects
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