Toxicological Effects of Metal Oxide Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 158

overview of nanomaterial containing consumer products in the US declared by the
manufacturer is available at the Wilson Center Project on Emerging Nanotechnologies
Consumer Products Inventory (http://www.nanotechproject.org/cpi).
On the other side, nanomaterials may have unpredictable effects on human health
and the environment. Hazard information generated for bulk metal oxides is usually
not suitable for characterizing the toxic potential of nanoparticles. Titanium dioxide
(TiO 2 ) nanoparticles, for instance, have been found to induce a much greater pul-
monary inflammatory response in rats when compared to fine-sized TiO 2 materials
(Oberdorster, Oberdorster, and Oberdorster 2005). In general, nanomaterials with a
primary particle size below 20 nm seem to be particularly critical because this can
lead to enhancement of interfacial reactivity with impact on biological effects (Nel
et al. 2009). Apart from primary particle size, other properties such as shape, surface
charge, agglomeration state, crystalline phase, or the ability to trigger the generation
of reactive oxygen species (ROS) may influence the toxic behavior of metal oxide
nanoparticles. Moreover, some metal oxide nanoparticles can release ions that, in
turn, may exert detrimental effects on cells. The contribution of ions to nanomate-
rial toxicity has been studied in detail for ZnO (Cho et al. 2012; Xia et al. 2011; Kao
et al. 2012). Since nanoscaled metal oxides have a larger surface area and a greater
tendency to release ions than their larger counterparts, toxic effects emanating from
released ions will be enhanced and smaller particles may therefore display greater
toxic potential.
In addition, many metal oxide nanoparticles exhibit high surface energy and may
interact differently with biomolecules such as proteins and DNA. In biological fluids,
they adsorb proteins leading to the formation of a dynamic protein corona, which
may influence particle effects in multiple ways. Intrinsic physicochemical properties
(size, surface, surface charge, structure, and shape) and aggregation of nanoscaled
particles will change when they become coated with proteins (Cedervall et al. 2007;
Maiorano et al. 2010; Wells et al. 2012). Conversely, nanoparticles may alter the
structure of biological macromolecules with important impact on normal cell func-
tions, for example (Deng et al. 2011; Xu, Wang, and Gao 2010), see Chapter 5 for
further details.
Correlating physicochemical properties with toxic effects of metal oxide nanopar-
ticles is a major challenge for nanotoxicology. Currently, each nanomaterial type
has to be tested individually and carefully characterized with respect to its physico-
chemical properties. Even if the size and chemical composition of nanoparticles are
the same, other attributes of nanoparticles produced by different manufacturers may
differ such that even different batches of the same or only slightly different nanopar-
ticles need to be tested individually.
Ava i lable in vivo data are much less numerous compared to published in vitro
results and are mainly limited to acute or subchronic effects, hardly any chronic
effects have been addressed. In contrast, numerous in vitro studies have been pub-
lished; however, the relevancy of the results has to be carefully analyzed since some
approaches may not reflect realistic nanoparticle exposure concentrations and/or
routes of entry to cells and tissues. In addition, the individual in vitro assay con-
cepts and conditions should be validated for the use with a specific nanomaterial.
Especially for cell culture-based studies, it has been demonstrated that metal oxide