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Caption: Human lung cells were exposed to harmless
Siliconoxide (SiO2) nanoparticles for three days. The cells stick
to the bottom and have a spindle like form. This is how a healthy
cellular culture looks like. (the beam is about 20 micrometers
long.)
Since the start of the „nano age“, heretofore
unimagined possibilities present themselves to material scientists.
Nanoparticles, that is infinitesimal small particles with a
diameter of a few nanometers, often just a few molecules thick,
show differing chemical and physical properties than bigger
particles of the same material. Thus, for the first time, novel
materials with specially designed characteristics can be produced.
Dirt repellant shirts, non burning frying pans, scratch free
surfaces, better computer hard disks and more effective sun
protectors – the nanoproducts range is indeed impressive. But
how does the human organism react to these small particles? And
what possible effects have nanoparticles on cells and tissues?
Since nanoproducts are similar in size to a cell’s protein
molecules, they can easily penetrate a cell’s membrane and be
absorbed. But what happens then to the cell? Many questions and few
answers remain.
Peter Wick, Arie Bruinink and their colleagues at Empa decided
it is high time to dedicate their research efforts to these
„nanotoxicity“ questions. „Should these novel
materials be mass produced, it is imperative that we determine if
the use of these new physical-chemical products will have
unexpected adverse impacts on humans“, declared cell biologist
Wick.
Cellular cultures as laboratory guinea pigs for toxicity
testing
The goal of the Empa researchers was to develop a quick and
relatively simple test for an initial evaluation of
nanoparticles’ toxicity, without resorting to animal
experimentation. Ideal candidates for such investigations are
cellular cultures often used in toxicity tests of various
chemicals. „However, we had to conclude rather quickly that
this sort of test is not that simple when it comes to nanoparticles
testing“, related Wick. The problem is that these small
particles bind themselves to each other very fast. „As we
introduced the nanoparticles into cellular food solutions, we got
clumps as big as a whole cell rather than individual particles",
recalls Wick. „Thank god we have wonderful materials
scientists here at Empa“, he continued, who helped the
biologists with several „tricks“, suspending the
nanopowdered particles in cellular food solutions and then
examining them in an electron microscope. This allowed the Empa
researchers to determine exactly in what form and size the
nanoparticles exist in the cell. In the meantime, they also
succeeded in separating the nanoparticles from each other according
to their size and form. „Many of the previous studies of the
toxicity of nanoparticles were conducted by biologists who were not
fully convinced, as we were at first, about the eventual form in
which these particles react within the cell. This is good biology
but poor material science“, according to Wick. If you simply
introduce nanoparticles into the cell, one can never be sure which
of these particles in which form are responsible for the observed
effect.
Not all nanoparticles damage cells equally
Following their materials science „homework“, Wick and
his colleagues at Empa have examined the toxic effects of seven
important industrial nanoparticles on cells. These ranged from the
harmless Siliconoxide used as a food additive for a long time in
such items as ketchup, to Titanium and Zincoxide used in cosmetics,
and to Ceroxide and Zirconoxide, materials employed in the
production of electronics. For comparisons sake asbestos fibers
whose toxic effects on cells are well known and researched were
also tested (asbestos fibers, whose average length is around ten
micrometers, and whose diameter is around one micrometer, are not,
however, actually considered nanoparticles). The researchers also
used as laboratory „guinea pigs“ two kinds of cells
regularly used in toxicity testing: human lung cells and mice
fibroblasts. The cells metabolism, their division rates and speeds
as well as the cell’s observed appearance under the
microscope were used by the scientists as criteria for the relative
health of the cell. The conclusion of the study, which will be
published in the next editon of the scientific journal
„Environmental Science and Technology“: „Not all
nanoparticles are equally toxic“.
The Empa team could devise a kind of a „range of
toxicity“ scale between asbestos and Siliconoxide: While
Ironoxide and Zincoxide particles appeared to impair human lung
cells, Tricalcium phosphate (used in medical implants) exhibited
similar toleration properties as Siliconoxide. Titaniumoxide,
Ceroxide and Zirconoxide caused a temporary enlargement of the cell
but are clearly less toxic than asbestos. Alltogether, the human
lung cells showed a definite greater sensitivity to nanoparticles
than mice fibroblasts. „Lung cells are therefore better suited
for these kind of toxicity studies“ according to Wick,
„and our goal is to develop a cellular culture testing method
which comes closest to animal experimentation“. Hence the Empa
researchers intend to examine now various kind of cells among which
are three kinds of lung cells as well as freshly isolated chicken
nerve cells.
Carbon nanotubes: more toxic when they clump
together
In a not yet published study, Wick and his colleagues examined
carefully carbon nanotubes. In contrast to nanoparticles, nanotubes
became more damaging to cells when they clumped together in a
larger needle like form. „These agglomerates, similar in form
and toxicity to asbestos fibers seem therefore to be
unfavorable“, said Wick.
Next, Wick wants to understand what exactly happens inside a
cell when nanoparticles are introduced into it. He is therefore
analyzing the activities of thousands of genes with the aid of so
called DNA chips. „We can thus see the effect these
nanoparticles have on the cell, i.e. which genetic codes are turned
on and off“, informed Wick.
„NanoRisk“ study examines also the impact of
nanotechnology on society as a whole
The results of Wick’s studies – coupled with data from
various animal experimentations and research analyses about the
diffusion of nana particles in the environment – are also used
by researchers from Lorenz Hilty’s Laboratory of Technology
and Society at Empa, to carry out a risk assessment study of
nanoparticles and nanotubes. The researchers analyze published
studies of nanotoxicology and consult with experts in order to
evaluate the validity of these studies. Thus far it appears that
there exist few significant research studies in this field, and
some of these even show conflicting conclusions. Such results may
have come about by not completely analyzing the properties of the
nanoparticles used in the various experiments, so that the
researchers conducting them may not have been fully aware of, or
familiar, with the form and size of the particles they studied.
In the second phase of their risk assessments studies, the Empa
researchers will examine the practical application of nanotubes as
it relates to their fabrication, the manufacturing of nanoparticles
containing products and the eventual disposition of such products.
The goal of these „lifecycle“ analyses is to obtain exact
data about releasing nanoparticles in varying quantities into the
environment, in order to devise possible precautionary
strategies.
Dr. Peter Wick, Empa, Lab of Materials Biology Interactions, , Tel. +41
71 274 76 84
Prof. Dr Wendelin Stark, ETH, Institut für Chemie und
Biowissenschaften, , Tel. +41 44 632 09
80
Claudia Som, Empa, Lab. of Technology and Society, , Tel. +41
71 274 78 43
Dr. Michael Hagmann, Empa, Communication, ,
Tel. +41 44 823 45 92.
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