Ci-dessous une compilation envoyée par Jim Thomas, animateur de la campagne nanotech chez ETC. Plusieurs références à des études sur la toxicité des produits issus des nanotechnologies.
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From: Jim
1. Health impacts of Nanoparticles - Nature Biotechnology letters.
2. Tiny particles 'threaten brain' - BBC Online
3. Scientists warn on potential nanotech health risk - reuters
4. Research on tiny particles could damage brain, scientists warn - The
Guardian (UK)
5. Cancer fears spark call for nanoscience safety rules - The Times.
6. Carbon nanotubes show drug delivery promise - Carbon nanotubes are
adept at entering the nuclei of cells, researchers have discovered.
7. Nanotox 2004 Daresbury Laboratories, Warrington, UK.. 13/01/2004 -
14/01/2004 (NEXT WEEK)
1. Nature Biotechnology, Vol 22, no.1 January 2004 p19
Health impact of Nanomaterials
Letter to the Editor:
The Perspective in the October issue on "the potential environmental
impact of engineered nanomaterials" by Vicki Colvin (Nat Biotechnol 21,
1166-1170, 2003) is a welcome contribution to the recent debate on the
issue of nanoparticle exposure and possible health effects. The main
strength of the Perspective is that the author as a 'nanotechnology
researcher' rather than toxicologist or health scientist openly
addresses the potential impact of nanomaterials on the health of workers
or consumers (and not so much on the environment). However in our
opinion, the article and its conclusion suffer from a rather
pro-technology bias. Though we agree with Colvin that the Paucity of
sound data renders it premature to formulate any definitive risk
assessment about engineered nanomaterials, several other important
issues require close attention.
Engineered nanomaterials must not be considered as a uniform group of
substances. Differences in size, shape, surface area, chemical
composition and biopersistence require that the possible environmental
and health impact be assessed for each type of nanomaterial in its own
right. This statement may sound simplistic, but many years of
toxicological researchand experience have shown that closely similar
compounds may induce substantially different health effects. This is a
well known feature of, for example, metallic agents, the speciation of
which may strongly influence biological effects.
Agents that seemed to be innocuous when administered by the oral or
dermal routes have proven surprisingly toxic to the lungs. Numerous
studies have shown that biological interactions between solid-state
materials and cellular targets depend on the size, surface area and
surface activity of the particles, and this is particularly true for
nanosized materials. Nanoparticles, even when they aggregate, likely to
exert biological effects different from those caused by micron-sized
particles.
The potential health risks of inhaled nanofibers cannot be disassociated
from the well known adverse effects of asbestos fibers. The concern is
particularly applicable to fibers with high biopersistence. In this
respect we feel that Colvin is too optimistic in her interpretation of
the two articles that have reported on the pulmonary effects of a
single intratracheal instillation of single walled carbon nanotubes in
experimental animals. Although one of the articles cited expressed
serious concern about the finding of pulmonary inflammation and
granulomas in mice, Colvin espouses the hasty conclusion of the other
article, which plays down similar observations in rats. Admittedly some
aspects of these animal experiments, such as the mode of administration
and the high doses given, preclude reaching definitive conclusions.
However the fact that "granulomas are not commonly observed in pulmonary
toxicology" is not a serious reason for dismissing this type of response
(especially when it appears so pronounced) and stating that "their
medical significance has not been established" completely ignores the
existence of a large array of granulomatous lung disorders.
It has recently been shown not only that inhaled ultrafine particles
exert respiratory effects, but that they may also translocate, at least
to some extent, from the lung into systemic circulation and this may
result in cardiovascular and other extrapulmonary effects. These
observations are probably of general relevance for assessing the health
risk of nanomaterials.
Colvin also sounds reassuring about the poor water solubility of
nanomaterials. However, low aqueous Solubility (generally expressed as a
high octane-water partition coefficiant) generally favours persistence
of a chemical in the environment and its absorption by biological
sytems, where it can persist for long periods of time and even
bioaccumulate, as has been shown for DDT (di (para-chlorophenyl)-
trichloroethane) or dioxins. Whether this is relevant for nanomaterials
is not established but our point is that the poor water solubility of
nanomaterials is not necessarily a reason for complacency.
In conclusion, we consider that producers of nanomaterials have a duty
to provide relevant toxicity test results for any new material,
according to prevailing international guidelines on risk assessment.
Even some 'old' chemical agents may need to be reassessed if their
physical state is substantially different from that which existed when
they were assessed initially. Thus if pulmonary exposure of the
nanomaterial is expected, but the bulk material was never tested by
inhalation, then appropriate tests are needed to evaluate its toxicity.
Obviously the actual health risk will depend not only on the intrinsic
hazard of the agent but also on the likely exposure. However one should
not conclude too rapidly that exposure will be negligible, certainly not
if the material proves to be highly toxic. In view of the fact that many
nanomaterials, new and/or miniaturized bulk particles, are ready to
enter the market, it is probably wise that authorities and legislators
support fundamental research to construct a scientifically valid
low-cost fas t-throughput toxicity test battery to screen nanomaterials
for toxicity and biopersistence.
By Peter H Mhoet, Abderrahim Nemmar and Benoit Nemery
Katholieke Unviversiteit Leuven, Pneumologie, longtoxicicologie, Campus
GHB, Herestraat 49, Leuven B-3000.Belgium.
Email: Peter.hoet@med.kuleuven.ac.be
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2. http://news.bbc.co.uk/1/hi/sci/tech/3379759.stm
Thursday, 8 January, 2004, 16:05 GMT
Tiny particles 'threaten brain'
By Alex Kirby
BBC News Online environment correspondent
Microscopic pollutant particles given off by traffic and industry can
enter the bloodstream and the brain after being inhaled, scientists have
found.
The particles are known to cause lung damage in susceptible patients,
and are implicated in cardiovascular disease.
Experiments on rats and humans have now discovered they can penetrate
further into the body, with unknown results.
UK scientists are calling for vigilance over the finding, and over the
possible effects of a new group of particles.
Many of us are routinely exposed to particles from diesel vehicle fumes
(these are normally known as PM10, from their size), which penetrate
buildings and are ubiquitous in
cities. Some cooking stoves emit high levels of particles as well.
There is also occupational exposure for people making products like
sunblock cream, inks, photocopier toners, and working with welding
equipment. Subtle infiltrators
Ken Donaldson, Professor of Respiratory Medicine at the University of
Edinburgh, UK, said these sorts of particle were known to cause damage
at the point of entry to the human body.
What was new, he said, was the discovery by researchers in Europe and
the US that they "can get to areas that bigger particles cannot reach".
Patients who inhaled radioactive ultrafine carbon particles displayed
traces of it in their bloodstream not long afterwards.
Experimental rats which inhaled similar particles showed a marked
decline in particulate level in their lungs after six or seven days.
In the olfactory bulb and other parts of the brain, though, levels
(although lower than in the lungs) remained relatively stable over the
same period.
These very small pieces of matter are called nanoparticles, defined a
anything smaller than 100 nanometres in size. A nanometre is
one-billionth of a metre, 80,000 times smaller than a human hair.
Professor Donaldson said: "We are already exposed to nanoparticles of
different kinds. We already recognise that there is some ill-health
associated with these exposures.
"But they may also translocate away from their point of entry into the
blood or the brain. We are not sure what the consequences of this are
yet.
Unknown hazard
"The nanotechnology revolution may design particles that are very
different chemically from the ones we are exposed to, and they might
have very different properties that made them more harmful. We should be
vigilant."
He told BBC News Online: "I think there could be an increased future
risk for all of us, and also a higher risk for people exposed at present
to nanoparticles at work, though it's impossible to say how much bigger
their risk is.
"These particles are not things you can trap with a filter. But they do
disperse rapidly, unlike asbestos."
Nanotechnology involves building working devices, systems and materials
molecule by molecule, and exploiting the unique and powerful electrical,
physical and chemical properties found at that scale.
It has developed from advances in microscopy, materials science,
molecular-level manipulation, and the relationship between classical and
quantum physics.
The UK's Royal Microcopical Society and the Institute of Physics are
holding a conference on the health implications of nanoparticles on 13
and 14 January at the Daresbury Laboratories in northern England.
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3. Scientists warn on potential nanotech health risk
Reuters, January 8, 2004
By Ben Hirschler
LONDON, Jan 8 (Reuters) - British scientists called on Thursday for
more research into the safety of nanoparticles, materials so small that
their dimensions can be measured in atoms, following evidence they can
lodge in the brain.
Nanotechnology, which could revolutionise the healthcare, consumer
goods and construction industries, has been touted by advocates as a
potential multibillion dollar industry.Prophets of doom have painted a
nightmare scenario of self-replicating robots turning the Earth into a
"grey goo".
But Ken Donaldson, Professor of Respiratory Toxicology at the
University of Edinburgh, said the real risk lay in breathing in
designer materials so small that they can slip through membranes inside
the body. Research on rats has shown nanoparticles deposited in the nose
can migrate to the brain and move from the lungs into the bloodstream,
he told reporters.
So far, it is unclear whether this poses any health threat to humans.
But Donaldson, who will address a scientific conference next week on the
potential hazards of nanotech at the Daresbury Laboratory research
centre in northern England, urges caution.
"The big worry would be if a nanotechnology business designs
nanoparticles that are fundamentally different from the ones we are
already exposed
to and seem to cope with reasonably well," he said.
Modern humans breathe in considerable numbers of nanoparticles on a
daily basis in traffic fumes and even from cooking. In some individuals
they can trigger asthma or even cardiovascular problems, by setting off
an inflammatory response from the body's immune system.
The new materials being developed through nanotechnology -- which
involves manipulating matter on a scale of a billionth of a metre, or
about 80,000 times smaller than the thickness of a human hair -- might
trigger more severe reactions.
Mike Horton, professor of Medicine at University College London and
co-director of the new London Centre for Nanotechnology, said scientists
were treating the issue "very seriously" and had learnt the lessons of
public disquiet over genetic engineering.
He called for more experiments to establish how nanoparticles reached
the brain and what the impact might be. But he dismissed the idea of a
moratorium on nanotechnology.
"The impact would be exactly the same as the moratorium on genetic
modification in Germany which wiped out a whole area of biological
science for 30 years. That would be a disaster," he said.
Copyright 2004, Reuters News Service
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4. Research on tiny particles could damage brain, scientists warn
Ian Sample, science correspondent
Friday January 9, 2004
The Guardian, UK
Nanotechnology - the science of the incredibly small - may pose a real
threat to human health, scientists warned yesterday. Research shows that
nanoparticles, the ultrafine powders produced by the nanotechnology
industry, can build up in the brain if they are inhaled.
The study, which was carried out on rats, was designed to investigate
what might happen if nanoparticles were released into the atmosphere,
either as a slow trickle of industrial pollution, or as a catastrophic
leak from a nanotechnology production plant.
Because the particles are so fine, they could remain in the atmosphere
for some time.
The researchers found that once tiny carbon nanoparticles were inhaled,
they accumulated not only in the lungs, but found their way to parts of
the brain. Although the rats appeared to be unaffected by the particles,
scientists believe they could ultimately lead to brain damage.
"We should certainly care about this," said Professor Gunter Oberdorster
at the University of Rochester in New York, who led the study.
"It's too early to be alarmed, because we don't yet know what the
particles might do in humans. We shouldn't stop working with them, we
should just look for what adverse effects these particles might cause,"
he said. The report is due to appear in the journal Inhalation
Toxicology.
Nanotechnology deals with material on the scale of a few billionths of a
metre, or 80,000 times smaller than the width of a human hair.
Nanoparticles are among the most common materials to come out of the new
science, being used in anything from sun block to car bumpers.
Only small quantities of nanoparticles are currently produced in
Britain. The first production plant dedicated to making nanoparticles,
owned by the defence research company Qinetiq in Farnborough, Hampshire
was switched on last summer and is capable of producing a few kilos of
material an hour.
But it is a growing industry which is expected to be worth billions
within a decade.
Scientists fear that the more companies start producing nanoparticles,
the greater the risk they may get into the atmosphere where they could
be inhaled.
Some nanoparticles are already widespread in the air we breathe, largely
due to the burning of fossil fuels and vehicle exhaust fumes. In a busy
street, each breath we take contains around 25m nanoparticles.
Scientists already suspect that nanoparticles from diesel fumes
exacerbate heart disease, asthma and other respiratory diseases. What
concerns them now is that new types of nanoparticles could cause
unexpected health problems.
"This is the first documented evidence that an innocent particle like
carbon, if it's small enough, can find its way into the brain," said
Professor Ken Donaldson, a toxicologist at Edinburgh University. "The
worry would be if the nanotechnology business designs nanoparticles
which are fundamentally different from the ones which we are already
exposed to, and seem to cope with reasonably well. If very different
nanoparticles are manufactured, there's a concern that they might have a
different effect in the body."
Another unpublished study by Prof Oberdorster's team has found that the
nanoparticles travel into the brain after getting stuck in the nasal
cavity. Preliminary tests on rats have also shown that the areas of the
brain where the nanoparticles get lodged become inflamed.
While Prof Oberdorster says it is too early to confirm how much damage,
if any, the inflammation causes, at least some damage is likely.
"Your sense of smell could be affected, or more seriously, if these
particles travel further into the brain and get to more sensitive
regions, they could cause damage," he said.
Scientists cautioned that the finding did not warrant a moratorium on
nanotechnology.
Next week scientists are due to gather in Daresbury, Cheshire, to
discuss the health implications of nanoparticles at a conference by the
Institute of Physics.
5. Cancer fears spark call for nanoscience safety rules
January 09, 2004
By Mark Henderson, Science Correspondent, The Times (london)
REGULATIONS are needed to ensure that the products of industrial
nanotechnology do not pose unexpected risks to human health, British
scientists say.
They called yesterday for safety protocols for industrial chemicals to
be redrawn to consider the different properties that some materials have
when manufactured as nanoparticles, which can be up to 800 times thinner
than a human hair. As the behaviour of some chemicals changes at this
scale, there are fears that some nanoparticles may be found to be toxic
or carcinogenic, even though larger particles of the same substance are
harmless.
The different properties of nanoparticles arise because their surface
area is much larger in proportion to their mass than larger molecules.
Also, they are so small that they evade both man-made filters and
natural filters within the body, such as the epithelium that lines the
lungs.
At present companies proposing to make nanoparticles for non-medical
purposes are not required to show that their products are safe. But this
had to change if public fears were to be calmed, and for the benefits of
the field to be harnessed, Ken Donaldson, Professor of Respiratory
Technology at the University of Edinburgh, said.
There was increasing evidence that inhaled nanoparticles could cause
lung inflammation and enter the blood and the brain, with unpredictable
consequences, he said. While this did not necessarily mean that they
were dangerous, more research was required.
"There are problems with very small particles even if their contents are
very innocent," Professor Donaldson said. "If very different
nanoparticles are manufactured, we need to be concerned that they might
have very different effects in the body."
Nanoparticles can occur naturally, through burning, for instance, but
they are increasingly being manufactured for industrial and medical
applications. Carbon "nanotubes", for example, are a hundred times
stronger than steel, yet lighter than aluminium, making them very
valuable in engineering.
Other forms of nanoparticle are used in cosmetics, medical dressings and
contrast agents for magnetic resonance imaging. In the longer term
scientists hope to be able to build "nanosubs" that swim through the
bloodstream to deliver drugs precisely to the diseased tissues that need
them.
Mike Horton, Professor of Medicine at University College London and
co-director of the London Centre for Nanotechnology, said that the
problem did not lie with nanoparticles designed for medical use, as
these had to undergo the same toxicology tests as any new drug.
Companies that are using nanoparticles for products as diverse as
sunscreens, tennis rackets and strengthened steel cables, however, do
not have to conduct any special toxicity assessments. "If we're
manufacturing thousands of tonnes of nanotubes a year, whatever you do
there is going to be significant loss," Professor Horton said. "There
could be issues there."
The health implications of nanoparticles are to be discussed next week
at a conference at Daresbury Laboratory in Cheshire, organised by the
Institute of Physics and the Royal Microscopical Society. The Royal
Society and the Royal Academy of Engineering are conducting a similar
inquiry in response to calls from the Prince of Wales and several green
groups for a moratorium.
It is known that when concentrations of particles measuring less than 10
microns (PM10s) rise in the air, there is an increase in lung diseases
and cardiovascular disorders.
PM10s include larger molecules as well as nanoparticles, but experts
believe the latter group to be more dangerous.
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6. Carbon nanotubes show drug delivery promise
14:43 16 December 03 NewScientist.com news service
Carbon nanotubes are adept at entering the nuclei of cells, researchers
have discovered, and may one day be used to deliver drugs and vaccines.
The modified nanotubes have so far only been used to ferry a small
peptide into the nuclei of fibroblast cells. But the researchers are
hopeful that the technique may one day form the basis for new
anti-cancer treatments, gene therapies and vaccines. "Our research is
still in its earliest stages, but it shows great promise," says Alberto
Bianco, at the CNRS Institute in Strasbourg, France. "The nanotubes seem
to migrate mainly to the nucleus, so we can imagine them being used to
deliver gene constructs." "We can also imagine them being used to
deliver drugs to specific compartments of the cell," he told New
Scientist.
Rapid migration
Off-the-shelf carbon nanotubes were used by Bianco's team as the basis
for their 'nano delivery vehicle'. The tubes were modified by heating
them for several days in dimethylformamide, which enabled short linking
chains of triethyleneglycol (TEG) to be attached. Then, a small peptide
was bonded to the TEG molecule. When the modified nanotubes were mixed
with cultures of human fibroblast cells they rapidly entered and
migrated towards the nucleus. At low doses the nanotubes appeared to
leave the cells unharmed, but as the concentration increased cells began
to die.
"The nanotubes do not appear to be highly toxic," says Bianco. "But we
do now have to work out what happens to the nanotubes in the body."
Custom delivery
In principle, a wide range of different molecules could be attached to
the nanotubes, raising the possibility of an easily customised way of
ferrying molecules into cells. This has begun to excite other
researchers. Ruth Duncan, who works on drug delivery mechanisms at
Cardiff University, UK, told New Scientist: "There's a lot of evidence
that other nanoparticles could be useful in delivering drugs so this is
a very interesting and exciting area. But I am completely baffled about
how the nanotubes manage to get into the cells." Duncan says researchers
have tried without much success to use buckyballs - a spherical form of
carbon nanotubes - as a way of ferrying anti-cancer drugs and
radionucleotides into cells.
Journal Reference: Chemical Communications (DOI: 10.1039/b311254c)
Danny Penman
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7. Nanotox 2004
Location: Daresbury Laboratories, Warrington, UK
Date: 13/01/2004 - 14/01/2004
Contact: Clare Oxenbury
Tel: 01865 248768
Fax: 01865 791237
Email: clare@rms.org.uk
Description: ADVANCED BOOKING FOR THIS EVENT IS NECESSARY DUE TO
SECURITY PROCEDURES IN PLACE AT THE VENUE
Nano Particles and Nanostructured Materials: Implications for Health
Organisers:
Vyvyan Howard (Liverpool), Serena Best, Mick Brown (Cambridge), Jonathan
Grigg (Leicester), Doug Imeson (DSTL), David Cockayne (Oxford), Rik
Brydson (Leeds)
Meeting Theme
There is accumulating evidence that nanoparticles can have very toxic
properties. Many nanoparticle systems are known to have exotic
structural, electronic and hence chemical properties, when compared to
their bulk counterparts, principally as a result of their reduced
dimensions. However very little is known about the interaction between
the surface chemistry of nanoparticles and 'wet' biochemistry.
There are a variety of novel materials that have become part of the
human environment over the past fifty years; some are unintentionally
inhaled or ingested, whilst others are introduced into the body
intentionally and have been studied in detail, for example prosthetic
implants. The revolution in nanotechnology is currently driving these
and other biointeractive devices to smaller and smaller lengthscales.
Other groups are actively engaged in interfacing biomolecules into
'biocomputing devices'.
The primary aim of this meeting is to bring together experts in the
science of materials, particularly nanoscale materials, with biomedical
scientists studying the health effects of nanoparticle exposure. This
meeting will attempt to advance understanding of the molecular
mechanisms for toxicity and develop novel methods of research based on
the latest technologies.
This two day meeting follows on from two highly successful previous
meetings held at RMS Micro 1998 on particulate aerosols (ref:
Particulate Matter: properties and effects upon health ? eds. RL Maynard
& CV Howard Bios 1999 ISBN 1-85996-172-X ), and at the Royal Society in
2000 (see Phil. Trans. Roy. Soc vol. 358, pp 2561-2797 2000).
Venue
The venue for the meeting is the world famous Daresbury Laboratories in
Cheshire, home of the UK synchrotron facility since 1980. Daresbury is
also home to the new SuperSTEM atomic resolution analysis facility
consisting of a suite of aberration-corrected scanning transmission
electron microscopes capable of sub-Angstrom chemical imaging and
spectroscopy ideal for the study of nanoparticles. For further details
about the facility see the SuperSTEM website:
http://www.superstem.co.uk. There will be guided tours of this new
academic and industrial facility during the course of the scientific
programme.
Scientific Programme
Invited speakers will include:
Professor Peter Goodhew (Liverpool)
Aberration corrected STEM for the analysis of small particles
Dr David Jefferson (Cambridge)
Dr Jonathan Grigg (Leicester)
Dr Jonathan Powell (Kings College London)
Professor Ken Donaldson (Edinburgh University)
Particle surface area and the toxicity of ultrafines
Professor Steffen Loft (Copenhagen, Denmark)
Professor Paul Borm (Dusseldorf, Germany)
Chances and risks of nanoparticles in life sciences
Dr Sam Motherwell (Cambridge)
Using the Cambridge structural database to study hydrogen-banding in the
solid state
Dr Vicki Stone (Napier University)
The impact of particle induced oxidative stress on cell signalling
pathways
Professor Adam Curtis ( Glasgow)
The biocompatibility of nanoparticles and nanofeatured surfaces
Professor Paul O'Brien (Manchester)
Professor Peter Weightmann (Liverpool)
Biological interactions at surfaces: clues from surface science
Professor Denis Henshaw (Bristol)
Air ions and the nucleation of nano-particles
Provisional Programme
Tuesday 13th January
. Microscopy Techniques Tutorial
. Nanoparticle Catalysis Tutorial
. Nanoparticles and Health Tutorial
. Reactivity and Structure Session
. Whole-body In-Vivo Interaction Session
. SuperSTEM Tour
. Conference Dinner
Wednesday 14th January
. Biomarkers Session
. Particle and Surface Modelling Session
. Biomolecular Interactions Session
. Applications Session
. Discussion
. SuperSTEM Tour
Abstract Submission
As an integral part of this meeting, the organisers are actively seeking
contributed papers relevant to the theme of nanoparticles and their
biological activity. Contributions can be either oral or poster-based.
Please submit your contribution as a 1 page A4 abstract by post or email
before 1st October 2003
Accommodation
Limited accommodation is available for the 12th, 13th and 14th January
both onsite at the Daresbury Laboratories Hostel (£37 per night B&B) or
at the nearby conference dinner venue, the Hannover Hotel in Warrington
(£89 per night). For further details, or to book a room, please contact
Alison Mutch, CLRC Daresbury Laboratory, Daresbury, Warrington WA4 4AD,
tel: +44 (0) 1925 603363, email: A.M.Mutch@dl.ac.uk (quote reference
Nanotox 2004).