Memorandum by Professor Ken Donaldson,
University of Edinburgh
I am a lung particle toxicologists and so I
will start of there. Nanoparticles are ubiquitous in the environment
from natural and anthropogenic sources and have been throughout
evolutionary time. Combustion-derived nanoparticles (CDNP; soots)
are present in air, and to a greater extent in the last few hundred
years than in previous times, and they are considered to drive
a number of adverse effects in the lungs and cardiovascular system
that are well-documented These arise, in the opinion of many experts,
primarily from inflammatory effects in the lungs. There is a hypothesis
that there is also translocation of such NP to the blood and the
brain and there is restricted evidence that there is limited translocation,
using animal and experimentally-generated NP. There is no evidence
currently that translocation of NP out of the lungs occurs in
humans or leads to any adverse effects, although it is possible,
even likley. I personally have come to believe that there is minor
redistribution of very small particles from the lungs. The question
is whether this translocation is important in any adverse effects,
compared to the systemic effects caused of the inflammation at
the primary site of deposition in the lungs, acting on other sites
like atherosclerotic plaques or even the brain. This remains unanswered
at the moment.
For manufactured NP, effects will depend on
exposure and on the intrinsic hazard (eg surface reactivity, fibrous
shape). The majority of bulk-produced NP (silica, alumina, TiO2,
carbon black) presently are low toxicity but there is concern
over carbon nanotubes and other high aspect ratio nanoparticles
(HARN) because of their superficial similarity to asbestos. There
may be higher hazard NP to which there will be exposure and so
there must be vigilance but this can be foreseen with adequate
testing. All-in-all it seems unlikely that there will be any large-scale
pandemic of lung disease from bulk-manufacture NP if sensible
hygiene standards are used but we must be watchful for increasing
production of unusual NP like HARN and some metals (Copper, silver,
possibly).
The gut can be considered to have undergone
similar evolutionary forces to allow it to deal with nanoparticles
over evolutionary time. The gut will certainly be evolved to deal
with natural particles which has always been present on food and
probably only in the last few hundred years will these have been
thoroughly removed by washing prior to preparation/eating. So
nanoparticles in soils will be able to be dealt with by the gut.
A key question is whether the gut has evolved to deal with the
traffic of CDNP from the lungs that it encounters from the normal
process of mucociliary clearance. This delivers 99.9 per cent
of all particles that deposit in the airspaces to the gut. Its
true that the stomach and its acid environment stands a key gatekeeper
and that all particles will be acid-treated prior to entering
the gut, but many particle will not be dissolved by the acid in
the stomach and will continue, albeit with surface modification
due to acid treatment, to the intestine. One of these modifications
could be to the aggregation status (I don't know if it would cause
more or less aggregation) and that could be important in subsequent
effects on the intestine. The PM10 epidemiology literature,
which documents in large part the adverse effects of CDNP, since
the CDNP is probably the most pathogenic fraction of the PM cloud,
does not pick up an adverse effect on the gut. This may be a result
of some quirk of reporting/death certificates etc but, taken at
face value, it does suggest that the delivery of CDNP to the gut
from the lung does not have an adverse effect on the gut.
The question is whether any manufactured NP
might have such an effect. The ante is greatly increased when
the NP are added to food purposely. All toxicity is dose-related
and so the likelihood of an adverse effect increases with dose
and so adding NP to food definitely increases the likelihood of
adverse effects. It is to be hoped that the companies that make
the food have testing procedures in animals that demonstrate no
ill-effects—such data should be made available to the Committee.
The likely effects might include pro-inflammatory effects and
immunological abnormalities.
Another problem lies with the normal flora of
the gut, which could well be unbalanced if there was selective
toxicity toward commensals—silver NP seem a particular threat
in this area.
There is a suggestion that asbestos exposure
is linked to cancer of the stomach and colon although this is
disputed, and would arise from the delivery of fibres to the gut
via mucociliary clearance. It is just possible that a HARN might
be especially active in this regard.
Use of NP in food will greatly increase the
likelihood for release of NP into the environment during manufacture
and disposal and in human waste, where there might be ecotoxicological
effects that are not in my area of expertise.
20 March 2009
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