Toxicological Effects of Metal Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 191

their biological effects on the cellular and systemic levels. From a toxicological view,
it is therefore decisive to address the question of how specific physicochemical prop-
erties affect the toxic potential of nanoparticles, for example, by modifying molecu-
lar interaction with biomolecules or by influencing cellular behavior and uptake of
the nanomaterials.
Especially for gold nanoparticles many studies report toxic effects and the migra-
tion through biological barriers by particles smaller than 10 nm (Semmler-Behnke
et al. 2008). Most of these materials were only intended for research use. The small
size and the simplicity of labeling—for example, with proteins—enable studies on
the uptake and biodistribution of gold particles. Here, we focus on metal nanoma-
terials manufactured for industrial use which range from 3 to 90 nm (see Woodrow
Wilson database of nanotechnology-based products http://www.nanotechproject.
org/cpi/products/). The biological effects of metal nanomaterials will be outlined in
three main sections. In the first section, we will summarize studies on cultured cells.
Subsequently, the impact of metal nanomaterials on alveolar macrophages (AM) is
described. The third main section focuses on in vivo studies in nonmammalians,
rodents, and humans with respect to the different testing strategies used.
9.2 EFFECTS OF METAL NANOMATERIALS
ON CULTURED HUMAN CELLS
Inflammation, oxidative stress, cytotoxicity, and genotoxicity have been detected
after exposure to silver nanoparticles in different cell lines and all these effects seem
to be inherently linked to one another (Johnston et al. 2010). However, data are not
complete and not consistent. Nanosilver exists in manifold sizes and shapes and is
further functionalized with a multitude of surface coatings such as citrate, organic
polymers, peptides, or sugars, all of which might influence the biological effects
(Johnston et al. 2010).
9.2.1 o xidative s tress /C ell v iaBility /i inflammation
Various publications report on cytotoxicity and oxidative stress upon uptake of silver
nanoparticles. For instance, Arora et al. used spherical silver (7-20 nm) in primary
fibroblast and liver cells, where both cytotoxicity and oxidative stress responses
could be detected (Arora et al. 2009). A size- and coating-dependent effect for cyto-
toxicity and oxidative stress (ROS formation) was detected with different sized silver
nanoparticles (10, 15, 25-30, and 80 nm) and two differently coated nanosilver par-
ticles in spermatogonal stem cells (Braydich-Stolle et al. 2010). Trickler et al. have
included three sizes (28, 48, and 102 nm) and could detect a size-dependent cytotox-
icity in primary rat brain microvessel endothelial cells as well as a size-dependent
effect on inflammation (IL-1β and TNF-α). In CaCo-2 cells, the effects of 20, 34, 61,
and 113 nm nanosilver were assessed and again a size-dependent effect on cytotoxic-
ity was observed (Trickler et al. 2010). In addition, other authors analyzed transcrip-
tomic responses using an in vitro model for the human intestinal epithelium. They
found upregulation of genes involved in several stress responses (oxidative stress,
endoplasmic stress, and apoptosis). These effects were at least partially triggered by