Small size - large impact - Nanowerk

(PM) which is measured by mass and related to adverse
effects in patients with lung and cardiovascular disease.
Combustion nanoparticles have also been denominated
as ultrafine particles and are primary particles or
agglomerates with a diameter smaller than 100 nm.
These ultrafine particles are a small mass fraction of
total anthropogenic particulate emissions, described
with total suspended particles (TSP), particulate matter
(PM) or PM beyond a specific size in micrometres
(PM10, PM2.5, PM1). It is estimated that 50,000
kg/year of nano-sized materials are being produced
through these unintended anthropogenic sources. This
and later studies estimate that per 10 µg/m3 increase
in the concentration of PM2.5, overall mortality
increases by 0.9%, while deaths from specific respiratory
diseases can increase by as much as 2.7%. There is ample
evidence that a small proportion of the mass, but large
proportions of the number of the particles in ambient
air, are ultrafine in size. Numerous toxicological studies
have now forwarded that these ultrafine particles are
responsible for adverse effects, but so far few human
studies have been able to investigate this.
Interestingly, most of the experimental, toxicological
work on nanoparticles has been generated with a small
set of bulk nanoparticles. These nanoparticles have been
found in industry for a number of decades and are
produced in many tons per year, the largest production
volume being in 2004 for colloidal silica, titanium
dioxide, and various iron-oxides. All these bulk
nanoparticles were considered to be so-called nuisance
dusts until it was observed that upon prolonged exposure
in rats, inflammation and lung tumors could occur
(reviews: Donaldson et al, 2002; Oberdorster, 2001;
Borm et al, 2004; Borm & Kreyling, 2004). In summary,
these findings set the stage for the current discussion on
risks of nanoparticles illustrated as a triangle in Figure 1.
Bulk NP
(TiO2, CB)
Combustion NP
(diesel)
?
Engineered NP
Figure 1.
lllustration of the different sources and applications of nanoparticles
(NP) and the evidence for their relation with adverse effects in
humans or animals. Epidemiology and toxicology have demonstrated
acute effects of combustion NP in humans, as well chronic effects of
NP in animals. Still an open question is whether the hazards and risks
found with those types of NP can be extrapolated to engineered NP,
which is illustrated by the question marks.
?
The key question is whether the different pieces of
toxicological and epidemiological evidence on different
nanoparticles can be mutually used or whether a more
sophisticated approach is necessary.
A look forward
Nanotechnology has the potential to launch our current
economy into a new era, much as coal mining did more
then 100 years ago. Some even say, “Nanotechnology will
reverse all the harm done by The Industrial Revolution”.
It may take at least 50 years to test these statements,
but in the meantime, it may be useful to learn lessons
from the development, economical impact and health
implications of other technologies. Although
biotechnology is most frequently mentioned for
comparison, I have indicated the similarity of events
to that induced by the worldwide development of coal
mining (Borm, 2002). Coal mining in Europe has been
at the basis of the current European Union, and its
precursor ECSC starting in 1956. This consortium has
stimulated and endorsed research and development
programmes to ensure safe and sustainable coal mining
and related industries. Research programmes on safety
and health risks have led to basic understanding and
pragmatic measures to reduce exposure and familiarity
with the mechanisms of coal dust-related diseases. The
further technological development of nanoscience requires
research and regulation on safety aspects and health issues
for producers, users and consumers (Colvin, 2003).
Toxicity testing of nanomaterials
While there is a considerable amount of data on the
toxicity of NP, this data is mainly based on a small panel
of NP (diesel, TiO2, CB) and the assumption that a number
of effects by PM are driven by the ultrafine particles
in it (Donaldson et al, 2002). Due to this background
of the data and the specificity of most preparations of
engineered nanoparticles, a great deal of work needs to
be done with regard to characterisation and biological
testing of engineered NP. In this regard, it is recommended
to perform testing driven by the anticipated application
and classification by risk rather than by hazard.
Exposure and distribution
The ultimate risk of NP is dependent on both the hazards
and the exposure. The risk is mainly driven by exposure
to and uptake of NP at different routes of uptake. Different
uptake routes may exist (skin, oral, lung) and NP can
distribute from site of entry to other sites in the body,
including the brain and placenta. Studies with NP in drug
delivery have shown that NP can accumulate in areas with
increased permeability and cross barriers such as the bloodbrain
barrier and placenta. Little is known about conditions
and co-exposures that may cause increased uptake and
altered distribution upon exposure to NP. In addition, there
is a need for simple methods to assess airborne exposure to
NP, and assess contribution to the total body burden of NP.
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