Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 371

(2007) investigated the effect on the pulmonary toxicity of diesel exhaust fumes
generated from CeO 2 supplemented diesel. This study used lung slices exposed to
the freshly generated fumes, and no impact on viability (ATP and intracellular
glutathione), ) and antioxidant

enzyme activity (glutathione peroxidase, Mn Superoxide Dismutase) could be
detected. The antioxidant enzyme catalase was elevated, probably as a defence
response. The authors concluded, on the basis of these results and data relating to
exposure concentrations, that there is very little risk associated with exposure to
diesel fume generated from CeO 2 supplemented diesel fuel.
Park et al. (2007) also screened the toxicity of CeO 2 using a battery of in vitro
protocols including a skin irritant test, cytotoxicity assay (BS EN ISO 10993- 5) and
a test of mutagenicity (Ames Test). The CeO 2 was found not to have the potential
to be a skin irritant, showed no evidence of cytotoxicity and did not possess any
detectable mutagenic activity. In addition, Park et al. (2007) also investigated the
effects of CeO 2 on the water fl ea, Daphnia magna , and no toxic effects were
observed during a 48-hour exposure. Our own studies confi rm this observation
(unpublished data), but also suggest that longer exposures (greater than fi ve days)
to very high concentrations (10 mg/l) of CeO 2 nanoparticles (

pro - infl ammatory mediator expression (TNF α

25 nm) result in
signifi cant lethality to Daphnia magna . Concentrations of 3 mg/l had no impact on
lethality for up to 21 days (unpublished data). Sub-lethal effects have yet to be
investigated in this organism.
Other studies have identifi ed CeO 2 induced toxicity. A study by Lin et al. (2006b)
investigated the effects of CeO 2 (20 nm diameter) on a human lung caner cell line.
Cells were treated at concentrations up to 23

<

g/ml and for times of up to 72 hours.
The authors observed a dose and time dependent increase in cytotoxicity, oxidative
stress (glutathione and

µ

-tocopherol depletion) and lipid peroxidation. The differ-
ences in results between studies could be accounted for by the source and charac-
teristics of the nanoparticles used, which although they are both CeO 2 could differ
by as yet unknown physico-chemical characteristics or contaminants.
Nanoparticle silica (SiO 2 ) is often assumed or reported to be amorphous rather
than crystalline. The crystallinity of silica is very important in relation to its toxicity.
Crystalline respirable silica (alpha-quartz) is classifi ed by IARC as a class I carcino-
gen (IARC, 1997). There is much evidence that crystalline silica induces lung cancer
and silicosis (fi brosis) of the lung (Donaldson et al. , 2001b). Until recently, amor-
phous silica has considered to be relatively benign when inhaled, although much
of the evidence used to draw this conclusion is based upon micron sized particles,
with little knowledge for silica nanoparticles.
One study by Kaewamatawong et al. (2006) has investigated the effects of
colloidal nanoparticle silica particles on the mouse lung. Particles were suspended
in saline and instilled into the lungs via the trachea, at doses ranging from 0.3 to
100

α

g per mouse. At the two highest doses (30 and 100 ug) the colloidal silica
nanoparticles induced a transient acute and moderate infl ammatory reaction. In
addition, there was evidence of increased apoptosis as well as oxidative DNA
damage.
Lin et al. (2006a) compared the toxicity of silica nanoparticles (15 and 46 nm
diameter) with a well characterised and studied form of crystalline silica (Min-U-Sil

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