Toxicological Effects of Metal Oxide Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 159

nanoparticles at concentrations higher than 50 µg/mL tend to interfere with assay
components or the assay readout procedure thereby introducing artifacts (Monteiro-
Riviere, Inman, and Zhang 2009; Kroll et al. 2012).
The main exposure routes for humans are dermal, oral uptake, and inhalation.
When assessing nanoparticle toxicity in vitro , cell systems of the skin, gut, and lung
should thus be applied. Recent evidence suggests that particles may translocate
from their site of exposure and reach or even accumulate in remote tissues includ-
ing lymph nodes, liver, spleen, and kidney. Thus, in vitro studies focusing on cell
cultures carefully selected to represent these organs can provide useful toxicity data
as well. Standardized cell lines provide high reproducibility but are often dedif-
ferentiated and transformed tumor cells with low responsiveness to toxic agents.
Furthermore, single cell types can hardly reflect the complex response of tissues
leading, for example, to an inflammatory process or to a slowly proceeding neoplas-
tic alteration such as lung fibrosis.
This chapter deals with metal oxide nanoparticles of widespread use in consumer,
medical, and industrial applications such as ZnO, TiO 2 , ZrO 2 , SiO 2 , or CeO 2 . Many
metal oxide nanoparticle types have been found to exhibit no or only very low toxic-
ity in numerous in vitro and in vivo studies. However, it is not possible to categori-
cally define metal oxide nanoparticles as toxic or nontoxic merely by considering
their chemical composition. TiO 2 nanoparticles, for instance, cannot generally be
regarded as biologically inactive per se since a few TiO 2 nanoparticle types with
definite crystalline structure (anatase) can cause adverse effects in contrast to the
majority of the TiO 2 nanoparticle types tested so far that displayed no toxicity. This
chapter will provide an overview on the effects of metal oxide nanomaterials and
review data published in the literature as well as data obtained in the German proj-
ects nanoGEM and NanoCare. Initially, in vitro results will be summarized focusing
on biological effects of metal oxide nanoparticles on cultured cell lines with respect
to different toxicological end points followed by a section on more elaborated in
vitro models using primary cells such as primary alveolar macrophages. Finally, this
chapter reviews results from in vivo studies with a special emphasis on pulmonary
toxicity revealed via different experimental models.
Bearing in mind that most metal oxide nanoparticles do not cause toxic effects
when applied at reasonable concentrations, this chapter focuses on the physicochem-
ical characteristics that seem to contribute to nanoparticle toxicity under experimen-
tal conditions and highlight those metal oxide particle types that have been shown to
exert toxic effects in cell or animal models. The nanoparticle properties that seem to
contribute to the biological effects reported here are marked in italics.
8.2 EFFECTS OF METAL OXIDE NANOPARTICLES
ON CULTURED CELLS
In comparison to animal models, in vitro studies allow for a simpler, faster, and more
cost-efficient determination of defined toxicity end points. In addition, in vitro stud-
ies help to elucidate the mechanisms of toxicity and affected pathways. On the other
hand, one of the major disadvantages of in vitro assays is that a single specific cell
type cannot represent the numerous characteristics and features of a complex organ.