Examination of Witnesses (Questions 220
- 239)
TUESDAY 5 MAY 2009
Professor Ken Donaldson, Dr Qasim Chaudhry, Dr Jonathan
Powell and Professor Michael Depledge
Q220 Earl of Selborne:
In order to determine potential toxicity, is it sensible to look
not just at size, which you say could be relevant, but reactivity,
shape, any other factors?
Professor Donaldson: Reactivity per unit surface
area and shape.
Professor Depledge: Could I just add to that,
when we were gathering evidence for the Royal Commission report
some of the evidence we received suggested that the term "nanotechnology"
was really not a very useful term and might disappear within ten
to 15 years. I think the conclusion you will find in the Royal
Commission's report is that it is really the functionality—the
functions of the particles—that is more important when it
comes to classifying them in toxicological terms.
Q221 Earl of Selborne:
Eventually one would hope in Europe there would have to be detailed
risk assessment and legislation; and there needs to be some assessment
as to how this can be best determined in legislation. I understand
that the European Food Safety Authority has recommended that an
additional metric, taking your point of specific surface area,
should be included in the definition of nanoscale materials, which
is currently based solely on size. Is this measure of surface
area going to be adequate to catch the high-risk nanoparticles?
Professor Donaldson: With surface area alone
there are a large amount of nanoparticle types currently in use,
like aluminosilica and titanium dioxide, and there are already
many materials handled in workplaces, which are classified as
low toxicity materials. The toxicity per unit surface of these
is very low; as far as a particle toxicologist can ascertain,
it is about as low as it gets; they have virtually no activity;
but enough of them in the lung, for instance, does stir up problems
in the lung. Certainly the idea that then you move up into a particle
which has lots of surface area but that surface area is already
active then you would start to multiply the harm.
Dr Powell: There are two answers I would like
to give in response to that. Firstly, that nanosize per se
does not to my mind make a particle a nanoparticle. I say that
because there are plenty of naturally occurring substances that
are nanosized but they behave chemically, biologically in many
different ways. They may behave as soluble molecules or—at
the other end of the scale they may be a virus, for example; these
will be recognised in different ways. The term "nanotechnology"
or "nanoparticulate" to our mind means that that characteristic,
that nanosize, has become the dominant characteristic that
drives the behaviour of the material. It does not mean that everything
that is nanosized should be considered a nanoparticle. The second
point I would like to make is that surface area may well be important
in terms of the acute effect, these radical-inducing effects of
particles within cells, or their potential ability to produce
these radicals; it will not, however, give us a lot of information
about the more long-term chronic effects. I think, therefore,
there is a challenge ahead in terms of testing these particles
for their chronicity; ie their long-term adverse effects rather
than their acute pro-inflammatory effects.
Q222 Lord Methuen:
What types of nanoparticles are likely to be used in food or packaging?
Would you class any of these particles as a high potential risk?
Dr Powell: I have mentioned earlier that from
what we have seen there are two types of nanoparticles that are
either being used or planning to be used. The first type are the
larger nanoparticles, and within the definition that people tend
to think of nanoparticles, i.e. less than 100 nm in diameter;
these would fall either on the edge or outside that definition;
but those are already used in food in large amounts and we ingest
large amounts. We have been studying these for many years and
we still know very little about them. They include aluminosilicates,
titanium dioxide and silicate particles; and these are used as
food additives. The second type are the smaller particles. These
are either being used in other countries, not in the UK, or are
on the horizon and include nano-silver, the nano-clays, as well
as nano-silica; and we are concerned mostly about those that show
either partial persistence—ie they get through the gut lumen
and into the gut cells where they may be broken down but that
does not stop them being toxic—or they show whole persistence,
and that means that they cannot be broken down at the cellular
level either. I suspect, of those particles, nano-silver, nano-clays
and nano-silica in particular will all fall into the latter categories.
Q223 Lord Methuen:
Those are mainly used for packaging at the moment?
Dr Powell: Yes, the nano-silica has been introduced
into at least one drink that we know of in the USA; as far as
I know, it is not available in the UK, except were someone to
bring it in or via the internet. That is used in one food; but
the others, you are absolutely correct, are much more in packaging.
Q224 Lord Methuen:
What was meant to be the benefit in this drink?
Dr Powell: The idea is that you can promote
the interaction between a substance adsorbed onto the nanoparticle
surface, in this case cocoa, and the tastebud; so that this provides
a longer lasting interaction between the two, which then gives
you a stronger flavour burst and, the idea of that being, you
can use less sugar, you can use less fat and you will still get
the same delivery effect but in a "more healthy" drink.
Q225 Chairman:
Can I just pick up on a couple of points. One is that you mentioned
that titanium dioxide is used as an additive in food. If my memory
serves me correctly, when we took evidence from the Food and Drink
Federation they seemed to be unaware of the fact that titanium
dioxide was used in food. They thought it was used in cosmetics
but not in food. Can you be more specific and definite that it
is used as a food additive?
Dr Powell: I can be very definite about that.
It is a piece of work that we have done. We have done it both
by direct analysis of the foods, and also by looking at people's
diets. We have shown that the average intake is around 5 mg/day;
that is not large in terms of weight but in terms of number of
particles that is about 1012, one million million particles; so
it is a large number of particles that are ingested per day. It
is used as a brightening or whitening agent, so it is an artificial
additive that makes foods whiter or brighter. It is also added
to a number of medications as an excipient; also to some toothpastes,
few but some toothpastes; and also particularly to food supplements
where it might be involved again in giving a slightly different
colour effect to that supplement.
Q226 Chairman:
I think it might be worth just checking that the Food and Drink
Federation still stand by the statement they made last week, which
I believe was that it is used in cosmetics and sunscreens but
not in food.
Professor Donaldson: I think you have to be
careful, because the word "nano" has become such a bogey
term that, if you are not careful, they take the question to be,
"Is there nano TiO2 in food", and you say, "No";
but there is lots of bigger titanium dioxide in food. White cream—the
cream that comes out of a can—that is white because it is
titanium dioxide.
Q227 Chairman:
Coming back to Dr Powell, whether particles you referred to—1012
that are ingested every day—were those within the definition
that we have been talking about? Were those nanoparticles, or
were they particles?
Dr Powell: These are within the definition that
we have been talking about. They have an average diameter of 200
nm. You will find a small proportion that are smaller ie below
100 nm; but the majority will have greater than 100 nm diameter.
Q228 Chairman:
May I just ask one other question before moving on. In the MRC's
evidence—again this is picking up on the question of risks
in current use—you refer to nanodelivery systems that enhance
the absorption of antioxidants. However, many of these antioxidants
are normally poorly observed and may not be well tolerated at
a high level and may result in too much of a good thing. These
are components of a diet that may be valuable to you in very small
doses but toxic in larger doses. Is that something from the health
and safety point of view one should be really concerned about;
or were you simply speculating in a more general way that this
is a possibility?
Dr Powell: It was more general speculation.
There are a number of nutraceuticals or antioxidant-type substances
that occur in diets in very, very small amounts and they are absorbed
often in very, very small amounts. We were simply speculating
that were you to create a scenario where you could get much greater
absorption, such as through nano-encapsulation, it might not just
be the nanoparticle you have to be concerned about but the substance
within.
Q229 Lord Haskel:
Dr Powell said that titanium dioxide was used in toothpaste as
brightener. Is that correct?
Dr Powell: I believe it is used in a few now.
There is a particle that is used in much greater amounts in toothpaste
and that is the aluminosilicate; but I believe titanium dioxide
is still used in a few toothpastes, yes.
Q230 Lord Haskel:
If you go into a pharmacy there are lots of toothpastes that say
they will brighten your teeth but we have been led to understand
that these things are hardly used at all. Because everybody uses
toothpaste, quite a number of people must be brushing their teeth
with titanium dioxide?
Dr Powell: If I could just clarify. I am not
an expert in this area but I think I am right in saying that titanium
dioxide is used to make the food, or in this case the toothpaste,
brighter. I do not think it itself is responsible for the
brightening action on the teeth.
Q231 Lord May of Oxford:
We have been talking about nanoparticles in the gut, but I am
curious what actually are the risks associated with ingesting
nanoparticles in the gastrointestinal tract? What are the risks
that we know about? What are the things we suspect we know about?
What are the unknown unknowns?
Dr Chaudhry: There are more unknowns than knowns
in this case. Very little is known in fact.
Q232 Lord May of Oxford:
I was not meaning to knock Rumsfeld, I should say. I thought it
was one of few intelligent things he said!
Dr Chaudhry: This is a very, very topical question.
What is not known is whether nanoparticles added to food will
remain free; whether they agglomerate; aggregate; bind to food;
whether they will be digested; whether they will be broken down
by stomach acids or enzymes; or will be excreted. These aspects
are completely normal for the majority of nanoparticles. Because
these interactions of behaviour and fate aspects are very important
in determining what sort of risks they may pose—risk is
not only hazard, it is also exposure—if they never leave
the gut and are excreted from the body then obviously there is
no risk; but these aspects are largely not known.
Dr Powell: I would like to point out the gut
is a rather unusual organ, in that it is naturally tolerant, unlike
many tissues; and that is because of course we are throwing food
at it every day.
Q233 Lord May of Oxford:
It has got to be!
Dr Powell: Bacteria live in there, and so it
has developed in a rather tolerant fashion. That, in the main,
of course is a good thing and it protects us. Just occasionally
that tolerance can be broken, and broken in the most unusual ways.
Unfortunately we know so little about either that process or,
indeed, about particles and nanoparticles, that trying to tie
those two aspects together would be nothing better than speculation,
which probably would not be very useful to the Committee. Suffice
to say, in my view, there really is nothing known.
Professor Depledge: If you think about the developments
that are underway with nanomedicines, they are designing many,
many different kinds of medicines using nanomaterials that may
gain greater use in the future. Of course, some of those are designed
for uptake through the gut so there are possibilities. It is plausible
that particles can pass through the gut and be taken up in that
way. The other thing is that it seems that many of the engineered
or manufactured nanoparticles have not been fully characterised
in terms of their properties and what they can do; so there are
surprises with some nanomaterials that are being used, that they
do other things that we do not discover until later down the line.
I think, again, there may be surprises in store.
Q234 Lord May of Oxford:
Specifically we have already mentioned silver. I know nano-silver
is used as an antimicrobial in packaging and in foods and, for
that matter, in clothing; most of the hiking kit these days tells
you it has got nano-silver particles in the shirts and pants so
you will not pong at the end of the day. What do we know about
the negative consequences, either because they are in food or
because you have accidentally got them from the packaging or something,
for nano-silver on gut flora?
Dr Powell: We have not worked on that, I am
afraid.
Dr Chaudhry: I know IFR has worked on that but
very, very preliminary work. Yes, it has been reported and that
is why companies are selling them because of their antimicrobial
action. So antimicrobial action is known; but the effect on gut
microflora, very few studies and not yet published.
Professor Donaldson: My understanding is it
is not the particles so much as the silver ion, which is the chemical
soluble form, that is released that is toxic. That is why in wound
dressings and so on nanoparticles of silver do not generally leave
the dressing; the ions flow from the particles. It is a chemical
toxicity as much as particle toxicity.
Q235 Lord May of Oxford:
Are we similarly not in a state of full understanding about the
proportion of ingested nanoparticles that are able to be absorbed
into the body, whereabouts and so on? Do any of you actually worry—or
particularly if you are more in the food industry and the research
industry, would you worry—about a second attempt to demonise
this technology, as it was successful in the second attempt to
demonise GM foods? Given that, the answer at least to many of
the putative objections to GM foods, there were experiments and
understanding, for example, that would answer the worry about
super weeds—if people were to come again at this in a campaign,
should we not be worrying about the fact that we would say, unlike
what we could say with GM foods, "We don't know this; we
don't know that; we don't know the other thing. We don't know
if the particles that are aggregated together can be broken down
in the gastrointestinal tract. We don't know where they are absorbed.
We don't know how, for example, absorption of nanoparticles in
the gastrointestinal tract might affect diseases like inflammatory
bowel syndrome and things like that". Would that be a fair
statement of the current position? How disturbing do you find
it?
Professor Donaldson: I am concerned about demonisation
because I think we already have had massive exposure to nanoparticles
of all sorts, in the air for instance in traffic particles. We
know that there is not no impact of that, but there is
not a huge impact and we have evolved to deal with that. Not all
nanoparticles are the same; and there is a whole generation or
type of nanoparticles, these low toxicity ones, that are low toxicity.
I do not think we should consider all nanoparticles to be the
same. That is the first mistake people would make, to think the
one word "nanoparticles" embraces all particles. It
does not tell you anything about the widespread of toxicity of
nanoparticles.
Q236 Lord May of Oxford:
I would turn that argument around and say there are of course
lots of nanoparticles we have been familiar with for a couple
of hundred thousand years and they do not seem to be doing us
much harm; but now we are doing specifically different things.
Nanosilver has not been part of our ingestion process; and should
we not, in view of some of the other unintended consequences of
well intentioned actions, be trying to know more about it?
Professor Donaldson: Yes, we should. The whole
issue of demonisation—it sounds as if nanoparticles are
one thing. Nobody would call big particles "a particle";
because it could be traffic dust and it could be asbestos. Nobody
uses the word "particle" in generic terms. Yet people
use the term "nanoparticles" in a generic way, and I
think that can lead to demonisation. Scientists are human; they
do not like to study things that are bland; we tend to study the
toxic things; so the kind of message that goes out is that nanoparticles
can be very harmful. There are a whole slew of nanoparticles that
are not very harmful at all. That is really important but that
message does not come out.
Q237 Lord May of Oxford:
I just feel, if I want to run a campaign against this, to build
the membership of my organisation, or some other reason, I have
got the material to do a pretty good job.
Professor Depledge: I made the point at the
beginning, and Professor Donaldson has just made it again, about
the diversity of nanomaterials. I also made the point, when asked
about defining nanotechnologies, that it is not a very helpful
thing to do. In terms of risk assessment, I think it is hugely
important that we do look at functionality, and what particular
things a particular kind of nanomaterial is designed to
do; and that would help in making risk assessments. Titanium dioxide,
for example, has been used as we have said for many years, and
there is not much evidence that it is doing any harm at all. I
do agree with you that we need to emphasise the benefits of some
kinds of nanomaterials. I think it is about opening up this whole
debate and making it much clearer.
Chairman: The answers are quite technical
answers to a very broad bush campaign in Lord May's terms. If
the simple question is: "Are there substantial areas of uncertainty
and lack of knowledge about the risks?", to come back and
say, "Well, you've got to look at different definitions;
you've got to look at this and that" is not going to be very
helpful if people are looking for a yes or no answer.
Lord May of Oxford: I, in particular,
have the belief nanosilver has been put into foods as an antimicrobial
preservative; but if we do not know the effect on the gut flora,
which in a somewhat broad sense resembles two microbes, that is
a legitimate thing that you really ought to know more about before
you do it.
Q238 Chairman:
Is that fair?
Dr Powell: Yes, I think it is very fair. As
I have mentioned earlier, we have been exposed to nanoparticles
throughout evolution; I think the difference there is that they
tend to be nanoparticles that we have established mechanisms to
deal with; and that there is genuinely now the concern that new
nanoparticles are coming along that we have no mechanism to deal
with; ie persistent nanoparticles. I cannot think of a natural
example of a persistent nanoparticle. I can think of many natural
examples of persistent larger particles but not persistent nanoparticles.
So were you running your campaign, I think this would be a very
good starting point. I believe therefore genuinely these are areas
we need to understand more about. That is not to say that it is
a problem; but simply to say that the unknown exists; and where
the unknown exists we should perhaps try and change that.
Q239 Chairman:
I think one or two other members of the witness panel would like
to come in? Professor Donaldson?
Professor Donaldson: I think the nano particle
that we are most exposed to and is persistent is soot. It is made
of graphene and it is highly persistent. It is like sheets of
graphite—pencil lead. It is the nanoparticle we are most
used to. The average soot particle out in the street here—and
there is lots of it around here—is 60 nm and there is lots
of it in here. We are breathing billions of them a day if you
work in here. Billions of them are depositing in your lungs every
day; so we are experienced through the lungs; and 99.9 per cent
of all particles deposited in the lung get cleared up by the mucus
escalator and we swallow them. The gut gets delivered to it large
amounts of soot. I do not know what happens to soot in the stomach,
but soot particles are extremely tough. I would be surprised if
they are not persistent.
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