Nanotechnologies and Food - Science and Technology Committee Contents

Examination of Witnesses (Questions 260 - 277)


Professor Ken Donaldson, Dr Qasim Chaudhry, Dr Jonathan Powell and Professor Michael Depledge

  Q260  Lord May of Oxford: There does seem to me, and I may be wrong, that it is a subject which is inherently at the interface between the physical and the life sciences, so that it does require a certain amount of willingness to cross boundaries that not everyone is good at.

  Professor Donaldson: That is absolutely right. It is an interdisciplinary undertaking. To study the environmental and human health consequences of particles, you have to understand the particle and you have to understand the toxicology and the toxicity, so you definitely have to have a multidisciplinary team.

  Professor Depledge: I think that is right; it has to be a multidisciplinary activity. I think in the UK the ecotoxicological investigations of nanomaterials are again punching above their weight. There are a number of groups around the country, but I would point out that I think the amount of resource available for undertaking research on the effects of nanomaterials on the environment and human health is extremely small compared with the amount of money that is being invested in the development of new nanotechnologies, in new materials. It is tiny in comparison with the investment. It is also to me very interesting that we have some of the research councils in the UK providing resources to look at the impacts on the environment and human health, whereas other research councils are actually promoting the development of new nanotechnologies and new applications, so you have one chasing the other. This is happening at a grand scale in Europe where in the Framework 7 programme, the environment and climate part, there is relatively limited resource available for looking at the impacts of nanomaterials on the environment and human health, but in other programmes within the EU there are vast amounts of money available for stimulating European industries to adopt nanotechnology methodologies, and indeed there is a suggestion that one-third of all industrial manufacture in Europe will involve nanotechnologies within 10 to 15 years.

  Dr Powell: Just to add very quickly concerning your specific remit here, I think there is little or no work, either in the UK, Europe or even on the world scale, in terms of the gut, foods and nanoparticles. Most of what we know about comes from the work, as Ken Donaldson said, from the lung, a little bit from the skin and the tiny amount that has been done in the gut. In terms of what is going to happen, I believe that there is now access to certain research grants. What needs perhaps to be done is to try and enhance the interest so that more work around the gut is undertaken around foods and I think, again as Ken has said, in the UK we should be fairly well placed at the global level to be leaders in this area.

  Q261  Chairman: If we focus that question very specifically on the regulatory requirements for risk assessments, if you had to summarise in a few sentences what would be the top research priorities for risk assessment of nanotechnologies, nanomaterials in food and packaging in relation to regulation, what would you pick out?

  Dr Powell: I would argue that because of where we are currently at, that is to say we have nanoparticulates coming through already, if not in this country I am sure soon to come and certainly in other countries, and yet we do not have regulations and knowing how slow the latter are compared to the former, we need to do something fairly quickly. For me therefore the priority would be a logic model, and that logic model would unfold in a fairly simple way, starting with the question of: are these particles degraded in the lumen—ie do they reach the cells? If they do not, then we consider them one way. If they do reach the cells, are they degraded in the cell? Do they bind constituents of the gut lumen? Then, if they do not get degraded within the cells, where do they go thereafter and what are the basic cellular aspects; are there concerns for toxicity. I would like to see a fairly rapid logic model develop because I think it will address the gap.

  Q262  Chairman: Once the model is developed, can it be populated or do you need new research to populate those different stages?

  Dr Powell: I think the model I would try to run with would use current techniques and current technologies that are fairly easily available. That is not to say it is foolproof because it will not be but I do believe it will address to a large extent our concerns and it will at least get us to a point where we can say that there is no logical reason to worry about this particle or, yes, there is a logical reason to worry this particle. The second very quick point to make is that we need to consider how necessary are these particles. So we have titanium dioxide, we have heard about earlier, which is completely unnecessary—it makes food whiter or brighter, which is not necessary—versus particles which might contribute to food safety in this country, which clearly is very necessary. So I think that would be an important part of this model.

  Professor Donaldson: You could do a lifetime feeding studying rats of some selected nanoparticles. All right, there is a problem to choose which ones but you might choose some of the ones that are most commonly used in foods. You could start with titanium dioxide, I would suggest. A lifetime feeding study in rats, including toxicokinetics, to their full life span, could be undertaken, just to see if you find any adverse effects in these animals. Also, there are a number of genetic models you get nowadays, and is there a mouse model for an inflammatory bowel condition that could be used, Professor Powell?

  Dr Powell: There are a number of mouse models, yes.

  Professor Donaldson: That could perhaps be coupled with some studies in these mouse models where they have an inflammatory gut condition. Looking at toxicokinetics in these I think would go a long way to allay people's fears, if a couple of these studies came up showing nothing very much, and, if they did come up with something, then that should raise some warning flags.

  Professor Depledge: I wholeheartedly agree with those two comments. The other thing that I think that is important is to build into the design of some of these materials ways of getting them to biodegrade, for example in the pH of the gut into harmless forms. A great deal more could be done with the design of these materials to ensure that they do not have a protracted lifetime.

  Dr Chaudhry: I agree with the comments made by Dr Powell and Professor Donaldson that long-term studies are needed but also they need to be linked with histopathology. We do not know which new targets in the model might arise because of nanoparticles, so not only long-term studies but also linked with histopathology to find if there are any novel targets for these particles.

  Q263  Lord Haskel: We are learning that nanotechnology is a huge field. Are there any other areas of research in nanotechnology which can help research into nanotoxicology? Do we learn from any other areas?

  Dr Powell: I think certainly in terms of imaging and analysis there is a very good cross-over between the two areas and really our success in detecting these particles in tissue, the histopathology that Dr Chaudhry has referred to, has on many occasions relied on physics and such technicological advances to allow us to look at them. To my mind, and we do a lot of work in the imaging and analysis area, that has been wholeheartedly down to advances technologically on the physics and the engineering.

  Dr Chaudhry: Another area which has a cross-over is nanomedicines and nanomedicines are being developed for oral intake and they are supposed to leave the gut and take the medicines and deliver them to specific tissues and organs. A lot can be learnt from that mechanism about how particles can translocate out of the gut and where they go and where they end up.

  Q264  Lord Haskel: What about nanomedicines? Professor Depledge has mentioned nanomedicines a couple of times. Is there anything we can learn from that?

  Professor Depledge: Yes, I think there is a great deal we can learn from that because we can study the design of nanomedicines where we are trying specifically to deliver nanomaterials or drugs or coatings or whatever to particular parts of the body. So I do think that that is important. Clearly in nanomedicine imagining techniques are being driven forward in that area too. It is also interesting—and whether it is possible to do it I am not sure—that the military have a wide variety of applications for nanomaterials and are also developing techniques for measuring nanoparticles in the environment. There may be some cross-over there in appropriate circumstances.

  Q265  Lord Haskel: There are more and more nanomaterials being used in our clothing. Is there anything that we can gather from that about the toxicology?

  Professor Depledge: I think there is a great deal that can be gained from that but again it spills over into where do these materials end up. We are talking about measurement techniques. It is hard enough to visualise nanomaterials in tissues and in organs in humans, but imagine the problem of detecting nanomaterials actually in the environment because there is a background of nanomaterials around that are just naturally produced and to actually identify engineered nanomaterials against that background is a terrific problem. Nanomaterials are one of the few kinds of materials that we put into the environment about which we do not know how much is there, how long they persist, what they transform into, where they go. We do not know the answers to those questions.

  Professor Donaldson: I think there is an informative example also from nanomedicine. The nanomedical people have designed a nanoparticle that crosses from the blood into the brain. The blood-brain barrier is usually a very tight barrier and most things do not pass over. The brain is very privileged and protected. The nanomedical people have designed particles that cross the blood-brain barrier, so there should be something that tells us if somebody came up with a particle having a similar surface as that one, then it should not be used for any other purpose. You do not want these things locating to the brain unless you want them to locate to the brain. I think there are lessons to be learnt generically about a big picture of what it is about particles generally that makes them do anything. Just a big structure activity relationship for particles is what we need. If you had that, you would be home and dry really, but that is not going to happen tomorrow.

  Q266  Chairman: I know that at least two of you are authors on this large report that we have recently received called EMERGNANO produced by the Institute of Occupational Medicine in Edinburgh. I have to confess to not having read it page by page, line by line—I am sure you have all read it—but the bottom line seems to be that there are still major gaps in the knowledge base with regard to characterisation, exposure of toxicology of nanoparticles and nanomaterials. In terms of us drafting our report, would you recommend us to take this as an assessment of the current state of knowledge on health risks and risk assessment?

  Professor Donaldson: Not really; it is not a review of literature but a review of ongoing, research funding by government at European level. It is not a review of the literature. It is quite important to appreciate that it is research that is going on and us saying that the research is not looking in this and that place. It is quite well focused (for instance nanotubes get quite a lot of attention) but it does show the kind of flightiness of research that is very dependent on fashion. When you look across the research, you can see that nobody seems to be interested in the gut but everybody wants to look at nanotubes for example. It is a problem.

  Q267  Chairman: Would you say, as a follow-up to that, and one of the issues we have been talking about is gaps in knowledge as far as risk assessment is concerned, that one of the issues is the capacity in the UK or elsewhere in terms of toxicological experts working on absorption through the gut? Is that one of the limiting factors? I think we have heard previously from Dr Powell that he collaborates with others in Germany but not with others in the UK, presumably because there are not other groups doing gut absorptive nanoparticles?

  Dr Powell: I think the joined-up-ness between the two groups is going to be very important. I have seen a number of early studies, either started or proposed, not in this country but elsewhere, which in terms of the gut and in terms of the dietary aspects have schoolboy errors in them. They have been undertaken by toxicologists. I am sure the toxicology downstream would be fantastic. I am sure were we to try to address toxicology alone, we similarly would make errors, and therefore it is important that the two sides get together, people such as ourselves who have expertise in particles and the gut and diet and those who have expertise with the toxicological outcomes. I do not think that has happened and that probably needs to happen.

  Professor Donaldson: I think we are reaping what we sowed. If we look at the Royal Academy/Royal Society report, there was a really important paragraph that there should be a central core-funded chunk of research and expertise brought together to design a programme that would look systematically at nanoparticle toxicology, and that was ignored. We had response mode funding where people just put forward what they wanted to do, so what you get is piecemeal. There is no cohesive approach to trying to understand particles as a whole. Until we have a proper structure function view of all particles, then there will we will not be home and dry. The only way you can do that is to have a central core-funded programme that looks at all the different aspects and target organs and brings people together to try and drive forward such a programme. You do not get it from response mode funding; you get the kind of expertise that is already out there multiplied up. People who do work on the lung, all put money in for work on the lung and there is nobody doing work on the gut, so nobody puts forward research on the gut. If you had a programme that recognised the gaps and saw the big picture, then you would go down all these pathways. We are reaping what we sowed.

  Q268  Chairman: The view is that that recommendation has not been effectively taken up?

  Professor Donaldson: No, it was not taken up.

  Q269  Chairman: Is it being taken up in any other country?

  Professor Donaldson: The best is America probably.

  Professor Depledge: The US is taking it up and they have set up a number of centres. They started off with just one or two centres. One of the biggest was at Rice University, but now they have set up some other centres as well and they are trying to bring together diverse groups of scientists. Just going back to what we were saying, I think the point that there is a lack of toxicologists and ecotoxicologists in the UK and also across Europe is being widely recognised now.

  Q270  Baroness Neuberger: We have been talking about the need for, if you like, a strategic programme of research. If you were looking at what industry should do, and you have already said that there is a need for an independent industry-wide body, Dr Chaudhry, what health and safety research would you expect industry to be doing now and what methodologies would you expect them to be looking for when they are looking at a new food product containing nanoparticles to make sure that it is safe for the consumer?

  Dr Chaudhry: First of all, I think detection technologies are missing in the whole scenario. People can detect nanoparticles in neat solutions and in isolated cells and all that. When it comes to very complex matrices like food and varieties of foods, then it suddenly becomes very difficult. This is being taken up at the European Commission level and at the Seventh Framework Programme they are going to fund some of the projects specifically designed to develop and validate methodologies for that purpose. That will be done or it is being addressed. The other issues are in terms of safety; what are the long-term effects. We are not talking about short-term or acute types of effect because maybe you need very high doses for that, which may not be present in food products which contain nanoparticles. We are talking about long-term effects and again long-term studies coupled with histopathology to find out what is going on in the body—animal models, in vitro tests. Some of the in vitro tests can show, for example, initial indications of mutagenicity. Particle exposure may lead to mutagenicity. This is what industry needs to do so that if they are going to use nanomaterials for a specific purpose or a composition, they can ensure that all the safety aspects are being addressed.

  Q271  Baroness Neuberger: Do you expect them to have done that for a new product?

  Dr Chaudhry: This has been debated for some time by industry and by some other quarters. Industry's view was that these are not new materials. Because the regulations did not at that time recognise them as new materials, then they thought: We are already using titanium, why should we worry about nanotitanium; if we are using iron, why should we be worried about iron and things like that. But now there is a realisation and there are proposals to change some of the legislation so that it is clear in the word of the law that if someone is going to use food additives, even if they are already approved but someone starts making a nano form of them, then they will be recognised as having been made by a different process; i.e. a new material. That means that the company is going to have to produce safety data to show that these are safe to be put in food. Also, if someone is developing a normal food with nanotechnology, the wording of the law was a bit unclear and it did not clarify whether any food produced using nanotechnology would automatically be qualified to be considered as novel food, but now there is a proposal which will go into European legislation to make it clear. In the next few years hopefully we will see lots of clarification at a legalistic level. That will then trigger companies to ensure that they do not put anything into the food which they assume is already approved.

  Q272  Baroness Neuberger: There is a real issue, is there not, coming back to Lord May's point, that if this is something that was widely known—and we are waiting for the law to clarify before people have to be seen to do be doing those kinds of health and safety studies—it is not very satisfactory for the consumer, is it?

  Dr Chaudhry: Our food laws come under national legislation. They are made in Europe and then filtered through down to national level. This is now being taken up at European level and then it will come down to national level.

  Q273  Baroness Neuberger: Coming down to national level, do you think the FSA or some other body ought to be responsible for holding a whole register somehow of health and safety research by industry to ensure that the work that is done is fit for purpose and that the lessons learnt and the methodologies can be shared, which I think was your point about having an industry-wide body?

  Dr Chaudhry: To be fair, government has done quite a lot. They have founded the Nanotechnology Research Co-ordination Group (NRCG) which is headed by Defra; the FSA and other agencies are part of that. It deals with across-the-board issues and then every agency is responsible for its own remit. In that sense, the FSA are responsible for the food area. Usually what happens is that a new technology emerges and regulation and technology feed each other and that is how the system goes, but this technology has taken everyone by surprise. It emerged out of lab benches and suddenly people thought: let us put these materials into products—cosmetics, food, paints and coatings, and variety of other things. The production volume certainly started to increase from milligrams to grams to kilograms to multi-tonne and now we are talking about thousands of tonnes of some materials. It has taken everyone by surprise. To be fair, regulators are doing what is needed. They may have been a bit slow but everything is being done, in my view as much as possible.

  Dr Powell: I just want to make a couple of very quick points. We do of course have at least one example which has been mentioned a couple of times here from the USA where one particular particle that was passed as safe to use by the FDA was never in any way intended to be in nanoparticulate form and never was but, as legislation did not prevent that, it suddenly came into being in a nanoparticulate form. I do believe that there are fairly simple procedures and tests that could be undertaken and, if not within the industry itself, certainly they could be outsourced reasonably cheaply. That would in the short to mid term, whilst we are getting our act together in terms of understanding and legislation, provide I think a fairly rational approach to determining nanoparticulate safety in the foods I talked about.

  Q274  Baroness Neuberger: Do you think that would be a relatively easy thing to do?

  Dr Powell: Yes. As I said earlier, I do not think it is going to provide 100 per cent proof but, in terms of effectiveness for 80 to 90 per cent, this would really be a pretty quick, cheap and easy way to proceed. These are not complicated assays that I am talking about.

  Q275  Chairman: Could you just clarify what you are talking about?

  Dr Powell: Yes. I am thinking firstly about simply in vitro assays, test tube assays that will allow us to ask the question: under simulated conditions of digestion, is this nanoparticle persistent or does it get broken down? Secondly, if we take two simple cell types, the one that lines the gut (the epithelial cell) and the underlying immune cells and we challenge those with the nanoparticles in the presence and absence of some bacterial toxins that are found in the gut, do we then see effects on those cells in terms of maybe three simple outcomes that are quite well established—reactive oxygen species, cytokines and cell surface markers—and look at degradation of the particle. If we see no effects there and we see degradation of the particle, I would be fairly well reassured that that is likely to be safe. If however we see effects on the cells, or we do not see degradation of the particles, I might then suggest that we look into just how necessary is that particle to bring into the food environment at the moment.

  Q276  Chairman: Are there any other points that any of you as witnesses would like to make? We have reached the end of our questioning but there may be a point that you feel we have not covered or issues you would like to raise at this stage. No. Of course, if at a later stage you feel that there are points you would like to write in about again, and already a number of you have submitted written evidence, please feel free to do so to the committee clerk sitting on my left. Also, I should remind you that there will be a transcript of this session and you will have a chance to comment on it before it is finalised. Just in closing and in thanking you for coming to give evidence to us, I would like to revert back to an earlier question to be absolutely clear. In the early part of this morning's discussion, you all in different ways emphasised the heterogeneity of what might be considered to be nanoparticles and considered issues like whether they were persistent or not, their reactivity or lack of reactivity on the nanoscale. I just wanted to go back to cases that we have heard about of potential application which are really of nanoengineering of items that are already in the diet. For example we have heard about the notion of nanosized salt particles to increase the surface area and therefore the saltiness so you can have less salt in food. Another example was a mayonnaise with a nanoemulsion with I think fat droplets enclosed in water droplets, or maybe the other way round, I cannot remember how it was. I want to ask you whether the concerns that you expressed in relation to unknowns about risk assessment would apply to those engineered, naturally occurring, already existing components of food or whether it was more to the components that are not already existing or naturally occurring.

  Professor Donaldson: Obviously with something soluble like sodium chloride, like salt, all that would happen in a nano form is that it would be much more rapidly soluble. I cannot see that changing the toxicity or lack of toxicity in general that salt has at all. Likewise, changing the size of micelles, lipid micelles, I do not think would have a big effect. Our concern here is, for want of a better word, about hard particles or things that are added in. That is my feeling.

  Dr Powell: I completely agree with that. I would also just add however one small caveat. It is still possible to take naturally occurring soluble molecules and make them nanoparticulate but not make them rapidly biodegradable. Just because they have naturally occurring components does not immediately transfer to safety.

  Dr Chaudhry: This is the area, going on from Dr Powell's comment on nanoparticles naturally occurring but made into less degradable ones, that is the basis of a nano delivery system, so that they take materials out of the gut. Although they may be composed of naturally occurring molecules, they may take things out of the gut into other cells and tissues.

  Professor Depledge: My concerns are the materials that are added to food that are designed to be toxic in one way or another, perhaps to bacteria or those kinds of things. I also emphasise again that contaminant nanoparticles in food are important, things that are designed to be toxic but somehow or other end up contaminating food. With later generations of nanomaterials, in the third or fourth generation where they combine with other systems, synthetic biology systems and so on, for the future there needs to be even greater care taken.

  Professor Donaldson: If I can I say one word in closing, it is not to be too hung up on the 100 nanometre cut-off and to be concerned at things of 200. I do not know where the cut-off is to say that things are fairly close to the size that nature makes, maybe 500 per micron, but certainly we should not be too struck on the idea that 100 nanometres means harmfulness beneath it and harmlessness above it.

  Q277  Chairman: That is a very helpful comment and one we have heard before.

  Dr Powell: I am sorry but there is just one brief point, which is that I would like to re-emphasise something we probably have not said enough about today and that is that the gut lumen is a very unusual environment; it is full of bacterial toxins and ingested particles really have the ability to bind to their surface these kinds of toxins and other molecules and can, at least in theory, and we now have evidence for this, carry them across into the gut mucosa. You are dealing with quite a complex situation.

  Chairman: You did mention that earlier but it is useful that you remind us of it. I would like to draw the session to a close and thank all of our witnesses for an excellent session. You have answered our questions patiently and very clearly and been very helpful to us. Thank you all very much indeed.

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