Examination of Witnesses (Questions 240
TUESDAY 5 MAY 2009
Professor Ken Donaldson, Dr Qasim Chaudhry, Dr Jonathan
Powell and Professor Michael Depledge
Just to be clear about the last point you mademany things
that we inhale end up being swallowed in the end?
Professor Donaldson: Absolutely, almost all
of what we inhale, otherwise our lungs would be bunged up by nowafter
60 years or so in my caseso it is cleared upwards all the
time; and you swallow mucus containing particles all the time.
Regardless of what we ingest in food, we are ingesting a lot of
material that is just floating around in the air around us, including
Professor Donaldson: Yes.
Professor Depledge: I just wanted to return
to the issue. You were saying about the intricacy of the debate
that we were getting into, but I think if you want to think about
really big problems that we face, ultimately if we want to devise
toxicity tests for nanomaterials in foods, then I think we should
think about the practicality of doing that because there are likely
to be a myriad of different forms of nanomaterials in foods; some
of which we put in deliberately; others which get there for reasons
of environmental contamination and access to food. If you think
about evaluating the toxicity of these various forms of nanomaterial
and nanotubes, it would take years and years and years to get
through the list. In terms of protecting the public, what happens
in the meantime?
Dr Chaudhry: I just want to add, in this whole
scenario an independent industry body is missing which can look
at the whole scenario of publications. Not every application of
science here is going to give us any major concerns or any hazards
or any risks. The body needs to separate those applications that
have no or low risk, and those applications can go ahead: but
because of the nanotechnology label everything seems to be static.
For example, we know from our own experiments that nanoparticles
hardly ever move from packaging material into food; so that application,
as far as tests show, may not cause any risk to the consumer and
can go ahead: but because of the nanotechnology label, companies
are afraid of declaring that it is nanotechnology-derived. Even
if we do not know about hazards or exposure or many other uncertainties,
we can divide applications on the basis of whether nanoparticles
are free, whether they are soluble, digestible or insoluble; and
we can form those categories very quickly on a hypothetical basis,
whether an area of application is going to be in the high risk
category or in the low risk category. We have attempted that and
I have a handout if you would like to look at that.
Chairman: Perhaps you could leave that
with the Committee clerk afterwards. I would like to move on now
to Baroness Neuberger.
Q242 Baroness Neuberger:
We have been talking about persistence. I would really like to
ask you what the state of knowledge is regarding the actual accumulation
of nanoparticles in the body once we know we have been ingesting
them? How do they accumulate? How many of them do we not get rid
of which you have been talking about earlier?
Dr Powell: The work we have done is purely around
the gut and, again, around these larger nanoparticles, so generally
upwards of 100 nm but not solely. We have shown that certain areas
of the gut, the lymphoid tissue, does with increasing age accumulate
these particles. Presumably they only represent a very small percentage
of what has been taken up, so there probably is a clearance mechanism;
but quite clearly accumulation does occur. As I also mentioned,
we have been unable in any way to link that accumulation to any
type of disease, disorder or impact upon health. We have not in
our work looked beyond the gut in terms of accumulation, but I
know others have and it may be some other members of the panel
are better to answer that.
Professor Donaldson: There is a body of work
that has been done on model nanoparticles starting from various
portals of entry: inhalation and injection into the blood predominantly;
not much through the skin because they do not seem to pass very
readily through the skin; and virtually nothing through the gut
at the moment has been published at least. If you inhale nanoparticles
they find their way to the blood. Something like a per cent or
so of all the material that deposits in the lung will get into
the bloodlet us say a per centand that circulates
round the body and accumulates in various organs at low levels.
The liver is a good place for particles to stop in. The liver
monitors the blood and it has cells that grab things in the blood
and it grabs particles, so they are focussed in the liver. Nobody
really knows what happens to them in the liver. Do they just remain
there? If someone was to get a chronic exposure through food or
a particle that did get into the blood, what would be the consequence
of a lifetime's accumulation of such particles in the liver? Nobody
knows that. There have been no long-term studies done to know
the outcome of that. There is also evidence that they get into
the brain at a low level from the blood as well, and into the
bone marrow and some other organs. Again, it is hard to imagine
what the clearance system would be from the brain but it is not
like the lungs which have a clearance system; so it comes back
to this issue that Professor Depledge has mentioned about the
fact that there are unintended consequences when particles get
to places where particles should not get because there is no system
there to clear them.
Q243 Baroness Neuberger:
That actually comes back to Lord May's point, does it not? If
you started explaining that and said what was not known, people
might have quite good reason to get concerned; and we do not,
from what you are saying, have a very adequate answer for them;
we just do not know?
Professor Donaldson: No, we do not know.
Q244 Baroness Neuberger:
Can I just add one other thing: we know that nanotechnology is
used to encapsulate substances to make them more easily absorbed
to target specific cells, organs or whatever. Do we think there
may be some particular risks associated with that, so that you
get exposure to certain substances from that kind of technology
to too great an extent; or that they get through to some part
of the body they would not normally go to; so either your liver
or your brain?
Professor Donaldson: Through medical uses.
Q245 Baroness Neuberger:
Yes, medical uses, with drugs, for instance.
Professor Donaldson: That is very interesting
and concerning to a particle toxicologist. For example, one of
the widest uses of nanoparticles is to image the plaques, the
coronary artery plaques that cause most people's deathsmost
deaths are from cardiovascular diseases when this plaque, this
lesion in the blood vessels near the heart, ruptures. To know
when a plaque would ruptureit is called a "vulnerable
plaque"cardiologists would really like to know what
a vulnerable plaque is. If you inject these iron nanoparticles
into the blood, which are now licensed to be used and are used
by cardiologists, they seem to localise to these plaques and you
find them in the plaques if you section the plaques. The cardiologists
can image these plaques using that methodology, and that is one
reason they are used. That seems to me to be a really risky thing
to do. One of the most powerful signals in the air pollution literature
is that exposure to particles in the environment causes these
plaques to rupture. It seems to me you are inviting disaster.
It seems to be being used, and maybe it is a baseless concern,
but to me it seems a considerable worry.
Q246 Baroness Neuberger:
It is only being used diagnostically. It is not being used for
any form of treatment, is it?
Professor Donaldson: No, it is not.
Q247 Baroness Neuberger:
Professor Donaldson: There is also an idea that
such particles can be used to deliver drugs to the plaques and
to other places in the body. There seems to be considerable potential
for the accumulation over time if the therapy went on and on.
Clearly imaging only happens maybe once or twice; but for therapy
you would give protracted treatment so you might get a long-term
accumulation of nanoparticles in places and, as we have already
said, you do not know what these places are, or the extent.
Q248 Baroness Neuberger:
The last thing I would really like to ask you, maybe you have
already given us some of the answer: is there research being done
into any of this, about what the short or the long-term effects
Professor Donaldson: The long-term I do not
know. In Edinburgh we are doing some studies and the Department
of Health has funded a student in our department to look at these
superfine paramagnetic iron particlesto look at the effect
that these might have. We have a mouse model that develops plaques
and we are going to put these into the mouse model and see if
they go to the plaques and if they cause the plaques to grow and
become more likely to rupture and more vulnerable. I imagine there
is other research as well but I do not know what that is.
Dr Powell: We are undertaking research at MRC
Human Nutrition Research both in terms of short-term effects of
very small mineral nanoparticles; these are iron oxide and other
oxide nanoparticles in gut cells; and we are also, howeverand
have been for a long timeundertaking long-term studies
in terms of the effects of larger nanoparticles on the human gut
tissue. That research is time-consuming. It takes a very long
time to get the data but we have made good progress and I hope
that within a year or so we will start to see the fruits of that
labour. There is work going on but it is quite tricky work.
Q249 Baroness Neuberger:
Do you know of other institutions that are doing it?
Dr Powell: Yes, we have now hooked up with two
institutions in Germany who have both just started to work on
the gut; but prior to that we knew of no other group, certainly
within Europe, who was working on large or small nanoparticles
and the gut; but we have just started to work with two in Germany,
as I have mentioned.
Q250 Lord Methuen:
Do nanotubes feature at all in this discussion? I understand they
are being used for some purposes; but are they relevant and might
they come into this argument?
Professor Donaldson: I do not think they are
used in food.
Dr Chaudhry: Their properties are such that
they are no use in food. Their features are that they give huge
tensile strength to whatever material they are put in; and also
they are electrically conductive. These two features have nothing
to do with food. They may find some use in food packaging but
not in food per se.
Q251 Lord Methuen:
Do they form a risk if they are in packaging?
Dr Chaudhry: If they are in the environment
and they get into food as a contaminant or into the environment
as a contaminant, yes, certainly. I think Professor Donaldson
is best placed to answer that.
Professor Donaldson: Even when you burn gas
rings you make nanotubesnot very many, but it is surprising
what has been found in the air when you burn gas rings. Most forms
of combustioneven probably coal burning and wood burningproduces
some degree of nanotubes, so it is not a new exposure. The workplace
exposure to mg and µg/m3 of the stuff is probably fairly
new. The concern has been that it has a particle hazard; it could
be a harmful particle; but also they are long and thin like asbestos
so they could behave like asbestos. There are two kinds of hazard
associated with these materials. The question is: are people generally
exposed to the particles, or to the long thin ones; because the
dangers are different and the hazards are different for the two.
Really it is a case where we need more exposure data. We really
do not know what people are being exposed to in workplaces with
this material. Certainly it has now increased to be one of the
major products of the nanotechnology industry so it is being handled
in tens of hundreds of tonnes in workplaces.
Q252 Lord Haskel:
Is there anything that we could learn from ecotoxicology about
the dangers or the potential risks to humans of ingesting nanoparticles?
Professor Depledge: I think we can look at this
in a number of ways. First of all, I think the potential use of
animal models is very valuable. There has been work done with
lower organisms, which are easier to deal with in experimental
situations. Of course some of the conditions in the guts of lower
organisms are somewhat similar to those that are in humans, so
there is a model organism kind of approach. There is a great deal
to be learnt there. I think it is very important to understand
what routes of contamination are possible for our food items.
For example, if you like eating snails or if you like eating shellfish,
some of which are filter feeding organisms, they are exactly the
kind of organisms which are likely to take up nanomaterials from
sediment or from water bodies, and they filter vast amounts of
water and so may accumulate nanoparticles. Looking at contamination
of food by nanomaterials involves ecotoxicological approaches
to see which organisms are mostly likely to do that. Then there
is the issue of food chain transfer. If you happen to be a top
predator that eats lots and lots of shellfish, do the nanomaterials
accumulate in fish and so on? I think those are very important
points. The other thing I would mention is that, earlier this
year, I attended a meeting in the USA at Rice University where
they have a major centre for nanotechnology. The discussion there
turned to the use of nanomaterials in agriculture. This was voiced
by the experts attending that meeting as one of their greatest
concerns. There may be ways of delivering pesticides attached
to nanoparticles, or phosphates and nitrates and other fertilisers
and so on, and also maybe agriceuticals and pharmaceuticals that
are given to domesticated animals, cows, sheep and so on; and
we have no idea, to my knowledge at least, of how these materials
might get into the food products that we eat. I think there is
some evidence from the literature that if you expose fungi to
nanomaterials, they will take up certain kinds of nanomaterials.
You can see the uptake of nanomaterials in the roots of plants.
You can actually get nanomaterials into plants by spraying them
on the leaves. Then of course the organisms eating those plants
and fungi are likely to be subjected to those nanomaterials as
contaminants. There is plausibility of uptake by those routes
but actual evidence of uptake into humans and where it ends up
in humans I think is absent at the moment, or I am not aware of
Q253 Lord Haskel:
People have been eating snails for years, they have been eating
shellfish for years, they have been using agricultural chemicals
for years. If we have been ingesting nanoparticles from that source,
we have been doing for hundreds or thousands of years. Can we
take any comfort from that?
Professor Depledge: I do not think so and the
reason I do not think so is because you are quite right, we have
been taking up nanoparticles by that route but we have not been
taking up engineered nanoparticles by that route for long. Particular
types of nanomaterials are engineered to do specific things. If
something like nanomedicines were to become widely used in the
futureand we have heard about nanoimaging materials and
so onone should be aware that these materials do end up
in the environment, just as the pharmaceuticals that we use in
our daily lives: antibiotics, analgesics and even cancer chemotherapy
agents can be detected in British rivers having passed through
sewage works and so on. If we ended up with that kind of issue
with nanomedicines being delivered into rivers or being deposited
in sewage sludge on fields, with the potential uptake into plants,
again the plausibility of getting our nanomaterials excreted back
again should be investigated, in my view.
Q254 Lord Haskel:
Is there any work going on to investigate this?
Professor Depledge: Not to my knowledge at the
moment, other than studies in the laboratory where a variety of
fungi, plants, animals, bacteria are being exposed in laboratory
tests in a very limited range of nanomaterials.
Could I just clarify in my own mind your comment about a possible
accumulation in the food chain, rather like the story with DDT
where it was concentrated in the top predators and that, in a
sense, was the danger signalthe canary in the coal mine
that warned us of the risk. Have there been studies of accumulation
in higher predators in the food chain that perhaps consume molluscs
or other invertebrates that may be the primary filter and absorbers?
Professor Depledge: Not to my knowledge and
at the meeting that I attended in the US where many of the experts
were gathered together nobody mentioned that as an issue.
Q256 Lord Methuen:
What research has taken place into the health and safety risks
associated with nanomaterials, and how much in the UK and how
Professor Donaldson: There is a lot now. It
is safe to say, though, that that is focused fairly much on the
lungs and inhalation exposure. As I said, perhaps 10 or 20:1 against
the skin and hardly at all for the gut. So in the UK there is
funding from all the major research councils now, MRC, NERC and
the EPSRC I think as well. The European Union FP7 has funded large
studies, several of which I have been involved in. In the USA
the Nanotechnology Programme is huge in NIOSH and in EPA. In Japan
and Korea again they all have big programmes. There is a huge
amount of ongoing research but it is focused very much on environmental
exposures to the lung and I think increasingly in ecotoxicology.
Q257 Lord Methuen:
Are you worried about the lack of attention to what happens with
food in the gut?
Dr Chaudhry: There is one project call that
has come out from the Food Standards Agency recently, which is
very topical, which aims to study toxicokinetics; i.e. how these
nanoparticles move out of the gut, where they go and what sort
of toxic effects they have, but that project is still to be started
and done. The funding call has just been announced.
Q258 Lord Methuen:
We have already talked about the range of these particles and
how you know which ones to concentrate on. Is that not the real
Professor Depledge: I agree with you; I think
it is a real problem. Currently there are in a broad sense something
like 600 or 700 products on the market that contain nanomaterials,
according to the Woodrow Wilson Center in the US, and they have
been through standard toxicity testing, and we have some doubts
about how well it works. I think there is a general consensus
that conventional toxicity testing is not very useful, and so
the OECD has set up a programme to develop new toxicity tests
specifically designed to evaluate nanomaterials. They have chosen
14 model substances that are being investigated, two per country,
and I think some of these model materials have not actually been
taken up by anybody yet, but they are trying to develop full characterisation
of these particles and also develop toxicity tests. To my mind,
that will be of value but of limited value in the sense that we
do not know that we are looking at the right kinds of nanomaterials
and whether you can actually use 14 different representative nanomaterials
from the myriad of different forms that have been produced I have
Lord Methuen: I find it quite frightening.
Q259 Lord May of Oxford:
I wanted to ask: is this general area of research one at which
the UK is as well represented among the leaders as it is in many
things? I have in mind the fact that if you look, for example,
at some of the eastern European or the EU accession countries,
they are very good at the physical sciences but not quite so at
the cutting edge in life science because the mechanisms are less
agile than those that have characterised the Scandinavian, Anglo
and other countries? Some of the things that have happened in
some of the research councils that are deliberately trying to
identify applications and so on, I just wonder whether you feel
these things are helping or hindering and just more generally
what is the state of British facility in this area on the world
Professor Donaldson: If you take human toxicology,
the UK has always punched above its weight in terms of particle
toxicology historically because there was such a focus in the
UK in the dusty industries and dusty trades. For instance, the
Coal Board is the seat of particle toxicology in the UK and it
was in Wales and it was in Edinburgh. That is why I am in Edinburgh
because I went to work for the Coal Board first of all. I think
the Coal Board was very important in driving forward in the UK
particle toxicology and it took over the Asbestosis Research Council.
That is not to say that there was not also a recognition of a
particle toxicology problem in the US or in other places; there
certainly was in Germany for instance a very famous history of
particle toxicology. We have punched above our weight but there
was not very much funding in the UK until relatively recently.
We have kind of caught up but we were slow to get off the mark
compared to America, definitely.