Toxicological Effects of Metal Oxide Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 180

and well suited to correlate in vitro and in vivo data, if experiments were carried
out with supra-threshold concentrations. As such this approach appears to be able
to predict from in vitro assays whether or not a functionalization of the surface of a
nanoparticle may alter the acute biological activity or the toxicity of a given type of
particle in vivo .
8.6 SUMMARY AND CONCLUSION
In this chapter, we have described the effects of metal oxide nanoparticles on human
cells and rodent lungs. Albeit the majority of metal oxide nanoparticle types tested so
far display no or only moderate toxicity, we have selected reports from those particle
varieties that display adverse effects in an effort to illustrate what attributes are most
influential in driving nanoparticle toxicity. Since for many different nanoparticle
types adverse effects could not be observed in vitro and in vivo up to a certain dose, it
is reasonable to assume that the nanodimension per se does not account for toxicity.
In fact, a larger specific surface area associated with the nanosize leads to a greater
surface activity and affects particle toxicity indirectly, for example, by enhancing
potentially harmful particle effects such as metal ion release, ROS generation, or
protein adsorption.
The toxicity of certain metal oxide nanoparticles has been demonstrated to have
inflammogenic, oxidative, and genotoxic consequences. While the studies presented
here cannot be considered to be representative for all metal oxide nanoparticles, it
becomes apparent that the biological effects of metal oxide nanoparticles are not
solely determined by their chemical nature but rather can be mediated by several
physicochemical properties. Apart from chemical composition, crystalline structure,
solubility, and surface chemistry influence nanoparticle toxicity both in vitro and
in vivo . The contribution of crystalline structure to toxic behavior has been demon-
strated for TiO 2 nanoparticles with anatase TiO 2 inducing more adverse effects than
rutile TiO 2 in vitro and in vivo . Solubility of metal oxide nanoparticles (ZnO) seems to
be responsible for inducing cytotoxic and inflammatory responses both in vitro and in
vivo . From the in vitro studies in correlation with the inhalation studies reported here,
one can conclude that nanoparticles with a high oxidative potential generally display a
greater toxic potential confirming the influence of chemical composition on nanopar-
ticle toxicity. Surface chemistry (CeO 2 ) and organic surface modification (TiO 2 , SiO 2 )
were found to be associated with biological activity in the studies conducted within
the NanoCare and nanoGEM projects. Previously, surface coatings have directly been
associated with a relative decrease in toxicity for SiO 2 nanoparticles (Pan et al. 2009).
Considering the overall in vitro and in vivo data obtained for SiO 2 nanoparticles with
different surface modifications within the nanoGEM project, the influence of surface
modifications on toxic behavior could be clearly confirmed.
It is of vital importance that the physicochemical properties responsible for the
toxicity of metal oxide nanoparticles are used to generate structure-activity models,
which can provide guidance for a safe design of nanomaterials. Taking into account
the nanoGEM nanomaterials in vitro and in vivo toxicity results, we were able to
separate nanoparticles with considerable toxic potential from those displaying no or
only very low toxicity based on a principle component analysis (Figure 8.2).