Case Study Paints and Lacquers with Silica Nanoparticles - Safety of Nanomaterials along Their Lifecycle - page 390

by the release of toxicants from the surface. In a recent study, it was found that silica
nanoparticles doped with cadmium expectedly caused more oxidative stress than
uncoated silica in rats after intratracheal instillation (Coccini et al. 2012). This shows
that increased hazard can occur when silica is coated with a more toxic material.
The aforementioned review and selected studies on relevant silica nanoparticles
show that silica MN in some cases may be inflammogenic in animal models for
human toxicity and that doping of silica MN with, for example, toxic metals may
cause increased toxicity compared to pure silica MN. Other surface modifications
used for improving dispersibility may, but not always, reduce the toxicity of silica
NM when compared to the unmodified analogues. As a new end point, it may be
necessary to investigate the potential adjuvant effects of exposure to silica MN. No
DNA damage was observed or reported in any of the studies.
17.4.2 i n v itro t oxiCity of n anosiliCa
The recent review (Fruijtier-Poelloth 2012) concludes that there is also no evidence
for mutagenicity of silica nanoparticles in vitro. Genotoxicity was observed in some
of the reviewed in vitro studies, but this most often occurred at doses where cyto-
toxicity was also observed. As an example in a recent in vitro test of nanosilica,
four synthetic amorphous silica samples (NM-200, NM-201, NM-202, and NM-203)
from the OECD Working Party on Manufactured Nanomaterials (WPMNM) also
did not show any genotoxicity using the human lymphocyte micronucleus assay
associated with any of these industrial grade MN. No effects were observed even
after exposure to 1.25 mg/ml (Tavares et al. 2014).
Even though limited hazardous effects have been observed for silica MN, recent
studies including new toxicological end points suggest that both traditional and doped
silica MN may disturb the biochemical function on the intracellular level. Christen
and Fent (Christen and Fent 2012) showed that fumed silica nanoparticles (Sigma
Aldrich) and Ag-doped silica (1 and 5 wt% Ag) (produced by flame spray pyrolysis)
affected human liver cells (Huh7) by affecting the CYP1A enzyme activity as well
as perturbation of the endoplasmic reticulum (ER), which lead to stress response.
By number, 50% of all three silica particles were smaller than 100 nm and mainly
occurred in aggregates. ER stress affects the cellular protein homeostasis. It is worth
noting that the effects were observed for both silica and Ag-doped silica. The level of
toxicity increased systematically as function increased Ag-doping and was to some
degree related to the amount of dissolved Ag. The authors state that the ER stress
response appears to be a new mechanism of MN toxicity. The observed effect remains
to be demonstrated in cells relevant to the respiratory tract and in vivo.
17.4.3 t oxiCity of s anding d ust P artiCles from P aints and l aCquers
In contrast to the presence of several studies on the biological effects of pure sil-
ica nanoparticles, data on the toxicity of silica included in a paint or binder matrix
are currently only found for three nanosilica materials (Table 17.2). These were
all included in the Danish NanoKem study previously mentioned. The toxicologi-
cal tests were completed on the Axilat™ Ultrafine LS5000 (Axilat) and Bindzil