Though there are
many toxicological studies on metal nanoparticles
(NPs), it remains difficult to explain discrepancies observed between
studies, largely due to the lack of positive controls and disconnection
between physicochemical properties of nanomaterials with their toxicities
at feasible exposures in a specified test system. In this study, we
investigated effects of particle size and surface charge on in vitro
mutagenic response and in vivo embryonic toxicity for newly synthesized
silver nanoclusters (AgNCs) at human or environmental relevant exposure
and compared the new findings with one of the most common nanoscale
particles, titanium dioxide NPs (TiO
2
NPs as a positive
control). We hypothesized that the interaction of the test system
and physicochemical properties of nanomaterials are critical in determining
their toxicities at concentrations relevant with human or environmental
exposures. We assessed the mutagenicity of the AgNCs (around 2 nm)
and two sizes of TiO
2
NPs (i.e., small: 5–15 nm,
big: 30–50 nm) using a
Salmonella
reverse mutation assay (Ames test). The smallest size of AgNCs showed
the highest mutagenic activity with the
Salmonella
strain TA100 in the absence and presence of the S9 mixture, because
the AgNCs maintained the nano-size scale in the Ames test, compared
with two other NPs. For TiO
2
NPs, the size effect was interfered
by the agglomeration of TiO
2
NPs in media and the generation
of oxidative stress from the NPs. The embryonic toxicity and the liver
oxidative stress were evaluated using a chicken embryo model at three
doses (0.03, 0.33, and 3.3 μg/g egg), with adverse effects on
chicken embryonic development in both sizes of TiO
2
NPs.
The non-monotonic response was determined for developmental toxicity
for the tested NPs. Our data on AgNCs was different from previous
findings on AgNPs. The chicken embryo results showed some size dependency
of nanomaterials, but they were more well correlated with lipid peroxidation
(malondialdehyde) in chicken fetal livers. A different level of agglomeration
of TiO
2
NPs and AgNCs was observed in the assay media of
Ames and chicken embryo tests. These results suggest that the test
nanotoxicities are greatly impacted by the experimental conditions
and the nanoparticle’s size and surface charge.