Toxicological Effects of Metal Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 204

(Chang, Khosravi, and Egbert 2006). Apart from skin discoloration, Trop et al. also
found increased levels of liver enzymes indicating hepatotoxicity as a consequence
of the treatment with wound dressings for 6 days (Trop et al. 2006). These data do
not yet allow for a risk-benefit assessment but safe utilization of nanosilver-based
wound healing products requires further studies.
9.5 SUMMARY AND CONCLUSION
The summary of the presented metal nanoparticle data shows a simpler picture com-
pared to metal oxide nanomaterials. Metal nanoparticles tested so far are often much
smaller and have well-defined sizes, which allow for a better correlation of size and
biological effects. Moreover, the tested metal NM exposure routes differ from those
of metal oxides. Inhalation studies on metal particles are less frequent and do not yet
cover all aspects necessary for a sound evaluation of potential health risks.
A comparison between in vitro and in vitro studies, as outlined in Chapter 8 for
metal oxide nanomaterials, has been carried out for at least some types of silver
NPs in the nanoGEM project. It appears that a ranking of acute toxic effects can
be similarly made from in vitro and in vivo studies. Nonetheless, evidence is accu-
mulating that particle size and biodistribution seem to contribute to nanoparticle
toxicity with smaller particles generally displaying greater effects. This has also
been repeatedly reported for metal oxide nanoparticles (see Chapter 8). To compare
nanomaterials of different sizes, it is, however, of relevance to apply particles at an
equal mass-dose, which has not always been considered in the studies published so
far. Generally, doses are calculated on the mass of particles applied per ml particle
suspension (cell culture) or per kg body weight (animals). For a reliable assessment
of the impact of size on the toxicity of metal nanoparticles, the data obtained also
have to be compared on an equal particle number or on the basis of equal surface
area. This requires comprehensive data on particle size, number, and surface area
and emphasizes the need for interdisciplinary studies. Importantly, such data would
also be necessary after application to the biological system, that is, when NPs are
located in or close to cells in a possibly agglomerated form. Moreover, because some
of the metal nanoparticles dissolve in solution, it will be of relevance to determine
the dissolution rates in situ . This appears especially important for nanosilver and
copper nanoparticles which partially dissolve in solution. Currently, knowledge is
still lacking regarding the toxic effects contributed by locally released metal species,
a phenomenon often referred to as the “trojan horse effect.” Albeit soluble particle
fractions are known to be involved in the antimicrobial behavior of silver and copper,
some groups reported that the toxicity of these nanomaterials is also reliant on the
particle as a whole (Midander et al. 2009; Bouwmeester et al. 2011). It is, however,
still unclear to what extent the toxicity of particles can be explained by the soluble or
released metal fraction or by the specific particle. The most important nanoparticle
property or a combination of these that governs toxicity has not yet been sufficiently
explored. But from the literature presented here, it is likely that both size and solu-
bility act in concert to mediate metal oxide toxicity. In addition, studies with sur-
face-modified particles clearly demonstrate the impact of surface-coatings, -charge,
and -impurities on the toxic effects observed for metal nanoparticles (Wang et al.