Examination of Witnesses (Questions 214
- 219)
TUESDAY 5 MAY 2009
Professor Ken Donaldson, Dr Qasim Chaudhry, Dr Jonathan
Powell and Professor Michael Depledge
Q214 Chairman:
Good morning. I would like to start by welcoming our four witnesses
today, as well as the members of the public sitting behind; to
remind you that the proceedings today are being webcast so the
public can observe what is going on; and also to draw the attention
of members of the public to the information note which sets out
members' declared interests; so we will not be declaring interests
as we go through the questioning. I would like to kick off by
asking each of our four witnesses to introduce themselves for
the record. If there are any points you would like to make in
a brief opening statement please feel free to do so. Perhaps I
could start with Dr Powell and then go along the row?
Dr Powell: I am Jonathan Powell from the Medical
Research Council Human Nutrition Research Unit based in Cambridge.
My area of expertise is minerals, particularly nanominerals in
the gut.
Dr Chaudhry: I am Qasim Chaudhry. I work for
the Food and Environment Research Agency of Defra. I am a research
scientist and we have been working on the safety of nanoparticles
through human health and the environment.
Professor Donaldson: My name is Ken Donaldson.
I am Professor of Respiratory Toxicology in the University of
Edinburgh, and I specialise in the harmful effects of inhaled
particles on the lungs and the cardiovascular system.
Professor Depledge: I am Michael Depledge. I
am Professor of Environment and Human Health at the Peninsula
Medical School in south-west Britain. I am a member of the Royal
Commission on Environmental Pollution. As you may be aware, the
Royal Commission conducted a study on novel materials, and in
particular nanomaterials, over the last two years and I have been
deeply involved in that particular study. I am an ecotoxicologist
and have worked on nanomaterials in lower animals.
Q215 Chairman:
Thank you very much indeed. Perhaps I could kick off with an opening
question of a fairly general nature and any of you might wish
to respond to this. As you will understand, part of the focus
of our inquiry is about possible or potential health and safety
concerns relating to the use of nanomaterials and nanotechnologies
in the food sector. You are all experts in this area and I wonder
if you would like to express to us what you think are the potential
health and safety concerns, and what evidence is available to
address those?
Dr Powell: I think we know quite a lot about
the uptake of particles in the gut, in terms of the route of entry;
and we know a reasonable amount about the likely cellular targets.
We know very, very little about what happens once those particles
meet those cells. We would certainly consider persistence to be
important, so that were you to ingest a particle that was broken
down in the gut lumen prior to meeting its cellular target, it
would in our eyes have a toxicology related to its chemistry,
i.e. the components, rather than to its nanoparticulate sizing.
We do believe that more work needs to be done in terms of both
nanoparticles and the larger nanoparticles or microparticles,
i.e. those larger than 100 nm in diameter, in terms of what happens
inside the gut.
Dr Chaudhry: In our view there are two fundamental
concerns about the health and safety of nanomaterials, and both
relate to oral intake of food products that contain free nanoparticles
that are insoluble, indigestible and that can translocate from
the gut in particulate form to other parts of the body. Essentially
that category of particles is of most concern. The first concern
is the ability to cross cellular barriers, and there is scientific
evidence for that. Cellular barriers prevent entry of larger insoluble
particulate material; but nanoparticles, because of their very
small size, can override that principle and potentially reach
new targets in the body, for example the brain. The second concern
is the potential effects of nanoparticles, and that will depend
on the chemical nature of nanoparticles, as Dr Powell mentioned.
If the chemicals that constitute nanoparticles are toxic then
it can be perceived that they deliver toxic chemicals to new targets
in the body where those chemicals would otherwise have not gone,
had they not been in nanoparticle form. The other concern is that
many nanoparticles have a reactive surface and they can interfere
with cellular processes, for example oxygen metabolism, and this
can lead to the emission of oxyradicals. This has been shown in
a number of studies. This can lead to inflammatory reactions and
oxidative damage. There are other concerns: for example, some
nanoparticles or nanodelivery systems can carry harmful substances
out of the gut into the blood circulation from where they can
lead to other parts of the body. Another concern is about antimicrobial
effects of some metallic nanoparticles; when ingested they can
have a harmful effect on gut natural microflora, which can ultimately
harm consumers' health.
Professor Donaldson: As a non-specialist in
terms of the gut, my main concern is that there is so little research
on what is happening with nanoparticles in the gut; whereas there
are fairly huge amounts of research funding pouring into Europe
and the USA into the lungs, the inhalation hazard, and to some
extent the skin, although less so. The research into the gut is
much, much less. I do not think you can generalise from the effects
of particles in the lungs or on the skin to the effects on the
gut. The gut is a wholly different environment to me to these
other situations in terms of the extremity of the conditions,
for instances of acidity in the stomach. My main concern would
be the lack of research in the non-generalisability of existing
research to the gut.
Professor Depledge: Just to add I think it is
worth emphasising the diversity of nanotechnologies and the diverse
nature of nanomaterials. It is very difficult, I think, to make
general statements about nanomaterials: some are very reactive;
some are not; some are very persistent; some are not. I think
we need to focus on that. The second point concerns nanomaterials
in food, some of them are put there intentionally, and some are
unintentional occupants of food, as it were. I certainly agree
with the idea that the amount of evidence available with regard
to the effects of nanomaterials, delivered through food or in
food, is very, very small indeed and there is an urgent need to
conduct many more studies. I also think that we ought to consider
plausibility. We know that some of these nanomaterials are designed
to be highly reactive. We know that some of them have very highly
reactive surface properties; and there are little bits of evidence
which show that they can convert chemicals from one form into
another: so it may not be the nanomaterial itself that is toxic
but the role it plays in converting substances that are non-toxic
to be toxic. There is a lot of plausibility that needs investigating.
Q216 Chairman:
When you look at the current developments in the use of nanotechnologies
and nanomaterials in food in the evidence that both MRC and CSL
submitted, you referred to various examples. Do those examples
themselves trigger concerns about the lack of knowledge of toxicological
effects and risk?
Dr Powell: The examples I think you are referring
to are those such as nano-silver, nano-silica and nano-clays.
I believe those do trigger concerns, in particular that, as has
already been mentioned, when a substance is nanosized, in doing
so its major cellular interaction and biochemistry may be driven
by its nanoparticulate nature. If that becomes the major characteristic
that drives its reactivity, then there is no doubt that some of
those materials will have different properties compared with bulk
materials—and I think of nano-silica in particular. The
other point to make is that, as a nanoparticle in the gut, there
is always the possibility of picking up local soluble molecules
onto the surface, such as bacterial toxins, and that those then
become delivered with almost a Trojan horse effect into cells
of the gut; and of course, as has been explained by Dr Chaudhry,
with the possibility of dissemination to other organs as well.
Dr Chaudhry: I think the main point is that
if nanomaterials are solubalised, digested or degraded within
the gut then they are of least concern, because then their properties
or effects will be dependent on what sort of chemical composition
they had, i.e. what chemical constituted the nanoparticle. The
main concern is on insoluble, indigestible, non-degradable nanoparticles
than can survive mechanisms in the gut and can come out of the
gut.
Q217 Chairman:
From the point of view of a toxicologist, I wonder if you might
think that particular groups of consumers would be more at risk
than others? If there were a risk would you think, for example,
young children or elderly people would be more at risk? I think
one of the points the MRC made in its evidence is that the way
the body responds to free nanoparticles is an immunological response.
I think that is what you said. Bearing that in mind, would you
expect particular population subgroups to be more or less susceptible?
Professor Depledge: I have certainly read one
study—I say one because it emphasises the scarcity
of information—which involved rats and looking at the uptake
of iodine labelled polystyrene microspheres of more than 50 nm.
They have demonstrated uptake of these microspheres. It was suggested
in that particular study that people, or animals with inflammatory
bowel disease of one form or another, would be at greater risk.
I am not aware of any other evidence.
Professor Donaldson: I think there is maybe
one case where the lung data might come to hand here. Certainly
in the human lung the adverse susceptibility to particles is greatly
enhanced in those people who have inflammatory conditions of the
lung, asthma and COPD especially. If you have inflammation already
in your airways then the effect of the particles are worse. That
is very strong data to support that. One would imagine that the
gut would be exactly the same. The effect of particles in the
gut may be much worse in someone who has got some inflammation
in their gut.
Dr Powell: I can add to that in two forms: firstly,
that gut permeability is enhanced in the presence of certain disease,
including chronic diarrhoea; and there is good evidence that small
particles or large molecules will have enhanced permeability under
these conditions. The second point to make is to pick up on Professor
Donaldson's point, which is that we have looked in inflamed cells
from patients with inflammatory bowel disease; we have challenged
them with particles and we have shown that they will have enhanced
pro-inflammatory effects; again, I stress this is ex vivo,
and there is little or no data as far as I know in vivo.
Dr Chaudhry: There is no evidence in scientific
terms but nanoparticles may act as seeds for crystallisation of
certain chemicals, but this has been shown in test tube experiments.
Concerns have been raised that if nanoparticles get into, for
example, the kidney and the kidney is inflamed, they might act
as seeds for calcification there; but there is no scientific evidence
for that.
Q218 Lord Haskel:
Could I just put the layman's question: if you do get some nanoparticles
in your gut and they have the reaction you describe, what can
you do about it? Is there an antidote, or something like that?
Dr Chaudhry: I think, depending on the chemical
nature of nanoparticles, they may not cause toxicity there and
then. If they are excreted from the body, metabolised, broken
down, that is another story because they will be eliminated from
the body. The concern is if they become lodged into the cells
and tissues and remain there and get accumulated over time and
what sort of effects they may have. We are not talking about immediate
effects; we are talking about medium to long-term effects.
Professor Donaldson: Jonathan would know better
than me, but if we go back to the situation where someone has
an inflammatory bowel condition and he already takes some medication,
they would take more of it more often, I would imagine; which
is the case with asthma and air pollution; people use their asthma
medication more when the air pollution is high. You would make
the same argument, one would imagine.
Professor Depledge: The point I would like to
make is I think this demonstrates what I was saying earlier about
plausibility. You can imagine scenarios of what might happen,
but we are operating in an area of profound ignorance. Certainly
we do not have a comprehensive understanding; I am not sure we
have any real understanding of what would happen in those circumstances
and whether you could pull nanomaterials out. It is actually extremely
difficult to find the nanomaterials in the first place
Q219 Earl of Selborne:
I would like to ask our toxicologists today how they would define
nanotechnologies and nanomaterials from a toxicological point
of view?
Professor Donaldson: There is an immediate problem
there because the standard definition (which has been considered
and thought about extensively by various nomenclature committees
which Qasim has sat on) that a nanoparticle is a particle with
one dimension at least less than 100 nm or 0.1 of a micron, there
is no toxicological basis whatsoever for that. The idea that a
102 nm particle is safe and a 99 nm particle is not is just plain
daft, it does not work that way. It is a sliding scale: we may
talk later on about surface area, but as particles get smaller
their surface area per unit mass increases; and it is surface
area that interacts with biological systems. You can talk about
smallness as well, but surface area matters a lot in terms of
delivering harm.
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