House of Lords - Nanotechnologies and Food - Science and Technology Committee

Nanotechnologies and Food - Science and Technology Committee Contents

CHAPTER 4: Health and Safety

Known risk factors associated with nanomaterials

4.1. The application of nanotechnologies to the food sector offers potential benefits (see Chapter 3). But concerns have also been raised about possible health and safety risks to consumers. Whilst much of the discussion is about potential risks, some instances of actual health consequences have been reported. For example, one study found that multi-walled carbon nanotubes injected into rodents caused lesions in the peritoneal (abdominal) cavity not dissimilar to those that occur in the pleural (lung) cavity with asbestos exposure.[12] Another report published in 2009 described immune responses to foreign bodies and the collection of fluid in the lung cavity following exposure by inhalation to polyacrylate nanoparticles.[13] We received no evidence, however, of instances where ingested nanomaterials have harmed human health.

4.2. The novel properties of nanomaterials may affect how such materials interact with the body and the risks they present to human health. A report, by the European Union Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), published in 2009, listed a number of physical and chemical properties which affect the risk associated with nanomaterials.[14] The evidence we received focused on six properties that may be particularly relevant when considering how nanomaterials interact with the body after they have been ingested and enter the gastro-intestinal (GI) tract.

4.3. Nanomaterials offer a vast range of different properties, and the risks they present will vary accordingly. While some types of nanomaterials may well pose little threat to human health (pp 112, 335) others may prove to be more hazardous.

SIZE

4.4. The small size of nanomaterials may give rise to a risk to human health irrespective of any other novel properties. Dr Qasim Chaudhry, Senior Scientist at DEFRA's Food and Environment Research Agency, explained that: "Cellular barriers prevent the entry of larger insoluble particulate material; but nanoparticles, because of their very small size, can override that" (Q 215). The MRC Collaborative Centre for Human Nutrition Research reported that, as a rough guide, particles smaller than 100nm "will be taken up by cells through a different pathway to that of larger particles, meaning that they will access different cellular compartments and have different cellular effects" (p 113). Research indicates that nanoparticles are able to penetrate cell membranes of the lining cells of the gut (the epithelium) (p 111). If they pass through the entire epithelium they will enter either the tissue wall of the gut, or lymphatic vessels, or directly into the bloodstream, either as free particles or, following their ingestion, into circulating white blood cells.[15]

4.5. The exceptional mobility of nanomaterials, both inside and outside cells, gives them the potential to "access all areas of the body, even the brain and all areas of the cell, including even the nucleus. It is this … property", suggested the MRC Collaborative Centre for Human Nutrition Research, "that probably makes very small nanoparticles most worrisome to scientists" (p 113). Professor Vyvyan Howard, Professor of Bio-imaging at the University of Ulster and an adviser to the Soil Association agreed (Q 283). Professor Ken Donaldson, Professor of Respiratory Toxicology at the University of Edinburgh, described his work on the impact of nanoparticles in the lungs: "there is a hypothesis that there is also translocation of … nanoparticles to the blood and the brain", and although "there is no evidence currently that the translocation of nanoparticles out of the lung occurs in humans or leads to any adverse effect … it is possible, even likely" (p 101).

SOLUBILITY AND PERSISTENCE

4.6. Another concern is whether ingested nanomaterials which can enter cells and migrate to different parts of the body will accumulate in certain organs. The question is whether a nanomaterial entering the body is broken down into its constituent parts (and either metabolised or the components excreted), in which case its toxicity is related to its chemical composition rather than its size (Q 215), or whether it enters the gut with the novel properties associated with the nanoscale intact. In Dr Chaudhry's view, "if nanomaterials are solubilised, digested or degraded within the gut then they are of least concern … The main concern is on insoluble, indigestible, non-degradable nanoparticles that can survive mechanisms in the gut" (Q 216). Dr Kampers agreed: "toxicologists agree that the persistent nanoparticles, especially those that are non-biologically degradable, inorganic, the inorganic metal oxides and metals, are the particles that pose the most risk" (Q 89).

4.7. Persistent nanomaterials might be harmful because they could "become lodged into the cells and tissues … and get accumulated over time", causing adverse effects in the "medium to long-term" (Q 218). The European Food Safety Authority's (EFSA) Scientific Opinion on nanomaterials stated: "There are only limited data on potential, long-term accumulation/persistence of ENMs [Engineered Nanomaterials]. However the limited data available suggest that insoluble ENMs may be retained for a long time and accumulate"[16]; and a joint statement on nanomaterials toxicology by the UK Committees on Toxicity, Mutagenicity and Carcinogenicity of Chemicals in Food, Consumer Products and Environment (COT, COM, COC) warned that "nanoparticles resistant to degradation could accumulate in secondary lysosomes, which in cells with a long survival such as neurones or hepatocytes might lead to chronic toxicity".[17] Dr Jonathan Powell, Head of Biomineral Research at the MRC Collaborative Centre for Human Nutrition Research, told us that "certain areas of the gut … with increasing age accumulate these [nano]particles … quite clearly accumulation does occur" (Q 242). Professor Donaldson agreed that a nanomaterial that reaches the blood "circulates round the body and accumulates in various organs at low levels" (Q 242), and added that the impact of this accumulation is unknown.

CHEMICAL AND CATALYTIC REACTIVITY

4.8. The large surface area to mass ratio of nanomaterials means that they tend to be very reactive. This can be harmful. Dr Chaudhry, for example, said that it might cause them to interfere with normal cellular processes, causing "inflammatory reactions and oxidative damage" (Q 215). The MRC Collaborative Centre for Human Nutrition Research made a similar point, stating that the direct toxicity of particles is mediated through "free radical" activity and such activity is considerably greater in smaller particles than in the same mass of larger particles (p 112). Recent studies in fish[18] have shown not only uptake of nanomaterials into the gills and gut, but also evidence of an inflammatory response which was also present in the brain and other organs.[19]

4.9. Furthermore, because of their reactivity, nanomaterials will bond with other substances in the product in which they are ingested or in the GI tract itself (for example, bacterial toxins), thereby providing a vehicle by which these toxins can be delivered across cellular barriers which they could not normally cross—described by Dr Powell as a "Trojan Horse effect" (Q 216). According to Dr Powell, "the gut … is full of bacterial toxins" and particles "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" (Q 277). Dr Chaudhry also described how nanomaterials could "carry harmful substances out of the gut into the blood circulation from where they can lead to other parts of the body" (Q 215).

SHAPE

4.10. The shape of a particle may have an impact on the possible harmfulness of nanomaterials (p 112). Professor Donaldson, for example, referred to the potential toxicity of "carbon nanotubes and other high aspect ratio nanoparticles (HARN) because of their superficial similarity to asbestos" (p 101); and whilst this particular concern has tended to focus on damage to the lungs and pleural lining, it might also possibly apply to the gut (pp 101-102).

ANTI-MICROBIAL EFFECTS

4.11. Nanomaterials which are used because of their anti-microbial properties, for example nanosilver (also used to coat devices such as refrigerators (p 55)), may be ingested through food packaging or food supplements. Dr Chaudhry expressed a concern that their ingestion might have a harmful effect on the natural flora in the gut (Q 215). Professor Donaldson agreed: "another problem lies with the normal flora of the gut, which could well be unbalanced if there was selective toxicity towards commensals [bacteria naturally present in the body]—silver nanoparticles seem a particular threat in this area" (p 101).

4.12. According to the FSA, silver hydrosol, a form of nanosilver, was recently evaluated by the EFSA for inclusion on a European Union list of vitamins and minerals authorised for use in food supplements. The EFSA was unable to complete a safety evaluation since there was insufficient information available to determine the potential effects of nanosilver on the human body, and as a result, silver hydrosol is likely to be banned from January 2010 (pp 2-3).

AGGREGATION AND AGGLOMERATION

4.13. The large surface area, reactivity and electrical charge of nanomaterials create the conditions for what is described as 'particle aggregation' (physical forces) or 'particle agglomeration' (chemical forces), where individual nanoparticles join together to form larger particles.[20] Just as the particle size can dramatically increase through these processes, under different conditions—for example in the gut or inside cells—collections of nanoparticles could disaggregate, thereby altering their physicochemical properties and reactivity. Such reversible phenomena add to the difficulty in understanding the behaviour and toxicology of nanomaterials.

Additional risk factors

4.14. Certain types of medical conditions may make people more susceptible to the potential risks posed by ingested nanomaterials. Diseases which cause gastrointestinal inflammation, such as inflammatory bowel disease or chronic diarrhoea, may allow nanomaterials to penetrate the intestinal wall more easily. In the human lung the adverse susceptibility to particles is greatly enhanced in those people who have inflammatory conditions of the lung; Professor Donaldson speculated that, in this case, "one would imagine the gut would be exactly the same" (Q 217). Dr Powell agreed: "gut permeability is enhanced in the presence of certain disease, including chronic diarrhoea; and there is good evidence that small particles … will have enhanced permeability under these conditions" (Q 217), a point also made by Professor Michael Depledge, Professor of Environment and Human Health at the Peninsula Medical School (Q 217).

Knowledge gaps

CONTEXT

4.15. Our knowledge of the risks associated with the use of nanomaterials is incomplete. Significant gaps remain. The Government's Nanotechnology Research Coordination Group (NRCG), a research coordination body for publicly-funded nanotechnology research (see paragraph 4.29 below), published a report in November 2005 which identified 19 research objectives, grouped into five areas (Q 18):

Metrology, characterisation and standardisation
Fate and behaviour in the environment
Human toxicology
Exposure, sources and pathways
Social engagement.

4.16. In 2007, the Council for Science and Technology (CST) carried out a review of the Government's progress on its policy commitments following the RS/RAEng 2004 report. The CST concluded that they had "placed insufficient emphasis on the need to investigate the health, toxicology and environmental effects of nanomaterials, despite such research being vital if commercialisation is to ultimately succeed"[21] and that "the balance between research that develops new applications of nanotechnologies and that which provides the necessary underpinning for its safe and responsible development must be addressed".[22] The RCEP's 2008 report echoed this conclusion: "we are very conscious of the extent to which knowledge about the potential health and environmental impacts of nanomaterials lags significantly behind the pace of innovation".[23]

4.17. Evidence suggests that this remains the case. In many areas there are still large gaps in our understanding of how nanomaterials behave or affect the biology of living organisms and, especially, human health. Our attention was drawn to a number of areas where further research is said to be needed in order to enable an effective risk assessment of nanotechnologies used in the food sector:

Characterisation and detection of nanomaterials
Behaviour of nanomaterials in the gut (including local effects, absorption and subsequent distribution)
Effects on the human foetus
Food specific research
Subsequent movement of nanomaterials within the body (toxicokinetics)
Chronic effects (toxicodynamics)
Development of validated toxicological tests

CHARACTERISATION, DETECTION AND MEASUREMENT

4.18. Any understanding of nanomaterials must begin with being able to detect, measure and characterise them—in particular, since many food products are naturally structured at the nanoscale, any regulation or risk assessment must distinguish between manufactured nanomaterials and those naturally occurring in food (see Chapter 5). This is far from straightforward. According to the FSA, "there are difficulties in characterising, detecting and measuring engineered nanomaterials in food, feed and biological matrices" (p 4), a point also made by Professor Depledge who said "it is actually extremely difficult to find the nanomaterials in the first place" (Q 218). When we visited Unilever's R&D facility in Colworth, we were shown the complex laboratory-based equipment necessary to detect nanoparticles, including sophisticated technologies for sample preparation and various forms of electron microscopy. Dr Knowles referred to there being "a dearth of analytical methods which would allow us to measure those … particles in a food matrix or any biological matrix" (Q 170), a view shared by Dr Chaudhry (Q 270).

BEHAVIOUR OF NANOMATERIALS IN THE GUT[24]

4.19. The ingestion of nanomaterials is not a new phenomenon. As well as nanomaterials that occur naturally in food (see paragraph 1.4), human beings have always been exposed to naturally occurring nanomaterials (for example, particles from volcanic eruptions and natural fires) and exposure to man-made nanomaterials (for example, those from fossil fuel combustion) has taken place for decades (pp 101, 106). A large percentage of inhaled nanoparticles are transported into the gut (p 101).

4.20. The GI tract is well adapted to facilitate the uptake of certain nanomaterials (p 111). Some, those which either break down into their chemical components when ingested or pass through the digestive system intact, tend to pose less risk to human health than nanoparticles which do not break down and which may be absorbed through different sites in the GI tract (see paragraphs 4.6 and 4.7 above). Dr Powell identified four mechanisms through which the gut might absorb nanomaterials (p 110).

4.21. To date, little research has been undertaken into the impact, behaviour and interaction of nanomaterials in the GI tract, including their effect on natural gut flora. In contrast, a significant amount of research has taken place into the effects of nanomaterials on the lung-according to Dr Knowles, "most research has been, and continues to be, on inhalation" (Q 170). But this work may not assist in understanding the effect of nanomaterials that enter the body through ingestion because, as Professor Donaldson told us, you cannot generalise from the effects of particles in the lungs or on the skin to the effects in the gut: "The gut is a wholly different environment to me to these other situations in terms of the extremity of conditions" (Q 215).

4.22. It appears that a great deal of work still needs to be done on the effect of nanomaterials in the gut. Dr Powell, for example, said: "more work needs to be done in terms of both nanoparticles and the larger nanoparticles or microparticles, those larger than 100nm in diameter, in terms of what happens inside the gut" (Q 215). Professor Depledge argued: "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 more studies" (Q 215). Other witnesses agreed (QQ 123, 232, 256). The EFSA stated: "the understanding of the potential toxicity after oral intake of ENMs is in its infancy. Only a very limited number of ENMs have been studied after oral administration … The ENMs used in the toxicity studies were often characterised only to a very limited extent".[25]

EFFECTS ON THE HUMAN FOETUS

4.23. When asked whether a human foetus might be at risk from nanomaterials ingested by the pregnant mother, the Research Councils told us that, although there was little data available, "it … seems very unlikely that nanoparticles can enter the foetus through simple diffusion unless they are very small and simple molecules … It seems unlikely that transport to the foetus can be completely prevented, but the concentration of any nanoparticles will be substantially less than in the mother" (p 220). The European Union SCENIHR report (see paragraph 4.2 above), however, noted that "distribution [of nanoparticles] to the foetus in utero has also been observed" and recommended that further research should be done in this area.[26] The EFSA also noted that "there is some information that certain ENMs can pass across the placenta"[27].

FOOD SPECIFIC RESEARCH

4.24. Evidence suggests also that more work needs to be done on how the incorporation of nanoparticles into food products might affect their subsequent behaviour both in the GI tract and, once absorbed, in the body more generally. Professor Morris, for example, said: "there is a need for specialised, directed research on the interplay between food matrices and nanoparticles, both in terms of the release and uptake of the nanoparticles themselves, and also of the consequences of the adsorption of biologically-active materials released from food … and their subsequent uptake and transport within the body" (p 56). LFI took the same view: "specific research within the food and drink model is essential" (p 52).

TOXICOKINETICS

4.25. Nanomaterials are carried to different parts of the body by a mechanism which begins with their ingestion by white blood cells which protect the body by ingesting harmful foreign particles (phagocytic cells). These cells are equipped with enzymes that have the capacity to degrade proteins and complex carbohydrates. If a nanomaterial is non-biodegradable, these cells will carry the particles to organs such as the spleen, liver and bone marrow.[28] Particles will either remain in these organs or be transported on to organs such as the brain and kidney. Understanding of the factors which determine the pattern of the accumulation and distribution of nanoparticles within the body is rudimentary (see Appendix 4).[29] In their Scientific Opinion, the EFSA said: "there is limited information on the distribution pattern of ENMs after oral exposure"[30] and, further, "there are only limited data on potential, long-term accumulation/persistence of ENMs".[31]

CHRONIC EFFECTS OF NANOMATERIALS

4.26. In common with the risk assessment of many substances, long-term, "chronic" effects are more difficult to detect than immediate toxic impacts. Any chronic effects of nanomaterials on the human body might take years to become manifest. Professor Howard told us: "it is chronic long-term pathology which may be rather more worrying than short-term toxicity" (Q 284). A similar point is made by the SCENIHR report: "knowledge of the long-term behaviour of nanoparticles is very limited, a conservative estimate must assume that insoluble nanoparticles may accumulate in secondary target organs during chronic exposure with consequences not yet studied".[32] This concern was echoed by Professor Donaldson (Q 242). The report recommended that more research should be undertaken.

VALIDATED TOXICOLOGICAL TESTS

4.27. Further work is also needed on the development of new toxicological tests. Professor Depledge told us that "there is a general consensus that conventional toxicology testing is not very useful" (Q 258). The British Standards Institute (BSI) highlighted the need for "suitable and validated test and measurement methods developed through standardisation" (p 224), a point also made by the NIA (pp 241-245) and Dr Chaudhry (Q 270). Some work has been done: the United Kingdom is taking part in an Organisation for Economic Co-operation and Development (OECD) programme to develop toxicity tests for 14 nanomaterials (see paragraph 4.55), although Professor Depledge thought that this work might be of "limited value" given the "myriad of different forms" of nanomaterials (Q 258).

Filling the knowledge gaps

4.28. In 2004, the RS/RAEng report concluded that, if nanotechnologies were to expand and nanomaterials become commonplace, it was important that "research into health, safety and environmental impacts keep pace with the predicted developments".[33] A recent review of worldwide progress made on the Government's 19 research objectives (ROs) (see paragraph 4.15), EMERGNANO, conducted by the Institute of Occupational Medicine in Edinburgh and sponsored by DEFRA, found that, while progress has been made, major gaps in the knowledge base remained: "in all of the major thematic areas (characterisation, exposure, toxicology and ecotoxicology), and all of the specific ROs, there is a substantial [amount of] work remaining to be done. We conclude that the programme of research activity has yet to develop step changes in the knowledge base on these issues".[34] Lord Drayson acknowledged that more work was needed: "I recognise that this area of technology is moving at a speed which is leading to people's concerns. Thankfully there have been no safety issues raised at present, but there is the sense … that there are gaps in our knowledge" (Q 561).

RESEARCH CO-ORDINATION IN THE UK

4.29. Publicly-funded nanotechnologies research in the United Kingdom is co-ordinated through the NRCG, a cross-departmental group, chaired by DEFRA, which includes Government departments and agencies, the Research Councils and devolved administrations. Within the Research Councils, the RCUK Nanotechnology Group, under the chairmanship of EPSRC, coordinates a cross-Council programme on nanotechnologies (Q 385). Several Research Councils have their own nanotechnology-related research programme, such as the EPSRC's programme 'Nanoscience through engineering to application' or the co-funded 'Environmental Nanoscience initiative' involving the Natural Environment Research Council (NERC), DEFRA and the Environment Agency (EA). As chairman of the Ministerial Group on Nanotechnologies, Lord Drayson said that he was responsible for ensuring that Government strategy on nanotechnologies, including health and safety research, was carried out (QQ 553, 557).

4.30. Within this structure, responsibility for fundamental research, which will underpin the development of effective toxicological tests for risk assessment, lies with the Research Councils. Dr Mulkeen explained: "We see the Research Councils' primary responsibility as making sure that the fundamentals of the generic science base that regulators need to work with that could be applied to whatever products come out is well developed. That is what people would look to the Research Councils to do first and foremost" (Q 394). Once this fundamental research has been done, Government departments and agencies have a responsibility to fund any further research necessary to carry out their regulatory role (Q 558). This might include, for example, ensuring that the fundamental science is developed through to the production of validated tests and methodologies for risk assessment. Gillian Merron MP, Minister of State for Public Health, told us that the FSA had a £22 million research budget for funding applied research (Q 639). Dr Mulkeen emphasised the importance of a "team approach" in which coordination bodies such as the NRCG ensure that information about gaps in the basic science required for regulation or safety assessment are fed back to the Research Councils (Q 428), while Lord Drayson explained: "if the FSA, for example, felt that there was a gap in fundamental research which was needed to be filled to enable them to develop an effective regulatory framework, then that is something which would be taken into account by Research Councils, and therefore the responsibility for the allocation of their funding made by the Research Councils" (Q 560).

4.31. The RS/RAEng 2004 report concluded that nanotechnologies posed a number of potential hazards to human health and recommended that "the UK Research Councils assemble an interdisciplinary centre … to undertake research into the toxicity, epidemiology, persistence and bioaccumulation of manufactured nanoparticles and nanotubes, to work on exposure pathways and to develop measurement methods".[35] This research centre would "ensure that the understanding of health, safety and environmental risks of nanoparticulates keeps pace with developments in the field".[36] The Government did not adopt this recommendation and continued to fund research into nanotechnologies through the established channels of response-mode grants through Research Councils and Government departments, coordinating its efforts through the NRCG.

4.32. When asked about the performance of the NRCG in coordinating research into the health and safety aspects of nanotechnologies, Lord Drayson said that "cross-cutting research coordination across the Research Councils is of growing effectiveness … I do not have any sense this is not working well: quite the opposite" (Q 556). Mr John Roberts, Head of Chemicals and Nanotechnologies at DEFRA, told us: "It has taken a while to get momentum on the research, but it is true to say that the research is now accelerating" (Q 18).

4.33. The 2007 report of the CST, however, pointed to a "need for greater strategic cross-Government action across different departments and agencies"[37] and concluded that in order to drive forward progress in this field, a Government body should be given "responsibility and power to allocate funds and instigate action" and that Government must "embark upon an immediate programme of strategic research spending in order to achieve the objectives identified by the Nanotechnology Research Coordination Group".[38] The RCEP's 2008 report Novel Materials, also concluded that "there is an urgent need for standardisation and co-ordination of research effort and focus in this field [of nanotoxicology]".[39] Despite these comments, the Government appear to remain confident about the role of the NRCG. Lord Drayson said: "Although the Royal Commission argued for a more coordinated approach to the direction of research, this is not something we are pursuing at present" (Q 552).

4.34. We are less sanguine. Given the evidence of continuing knowledge gaps about the effects of nanotechnologies and also the concerns that have been raised about the coordination of work in this area, we question whether NRCG is achieving its purpose effectively. We note that the EMERGNANO report indicates that, in areas where further research is needed, progress has continued to be slow. For example, with regard to human health, the EMERGNANO report states that "this review of ongoing studies has failed to demonstrate that there is any comprehensive attempt to gain the toxicokinetic … data required to reach the aims of hazard identification" and there have been "no systematic studies on the potential of different kinds of nanoparticles to get into the blood, the lymph or the brain".[40] We find this conclusion worrying.

4.35. While the NRCG initially made good progress in identifying areas where further work is needed, it has not been so effective at ensuring that funding is allocated for research projects which address these knowledge gaps. There appear to be a number of reasons for this:

The ineffectiveness of current mechanisms employed by the Research Councils to promote research in these areas;
The relatively low amount of funding allocated for health and safety research in the UK when set against other research priorities;
The limited capacity of the toxicology research community to conceive and undertake the studies needed to fill the knowledge gaps.

RESEARCH COUNCIL FUNDING MECHANISMS

4.36. Lord Drayson made clear that the Government cannot dictate how the Research Councils allocate their funding: "it is not for ministers to direct where research takes place or which specific research projects should be funded [by the Research Councils]" (Q 552). It is, therefore, the responsibility of the Research Councils to ensure that research into knowledge gaps in the fundamental research base, as identified by the NRCG, is adequately funded.

4.37. This does not seem to have occurred. For example, Research Objective 11 of the Government's 19 ROs is set out as follows:

"Research to establish a clear understanding of the adsorption of nanoparticles via the lung, skin and gut and their distribution in the body (i.e. toxicokinetics), identifying potential target organs/tissues for toxicity assessment".[41]

The MRC was assigned responsibility for RO 11.[42] Yet four years later the EMERGNANO progress report concluded that "a … largely un-researched area is ingestion as a route of exposure … Given the potential for this route to expose very large numbers of individuals … the lack of activity in this area is surprising".[43] We find this lack of progress extremely concerning.

4.38. The 2007 review by the CST concluded that the primary reason for the Government's slow progress on health and safety research was due "to an over-reliance by Government on responsive mode funding, rather than on directed programmes by Government departments to deliver the necessary research".[44] A number of witnesses supported this view. Professor Donaldson, for example, told us:

"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" (Q 267).

Professor Jones also alluded to the relative strength of research investigating nanoparticle toxicology in the lung compared to a lack of research into the gut as a result of response-mode funding (Q 494).

4.39. In response to the CST review, since March 2007, the Research Councils have been actively promoting proposals in areas related to nanotoxicology and safety (Q 388), and have issued a "highlight notice" for nanotoxicology which specifies the research areas where they would like to attract proposals (Q 411). As a result, the MRC has committed £3 million to six projects looking at nanotoxicology.

4.40. None of these projects, however, is food-related (QQ 402, 413) and the MRC recognised this as a deficiency. Dr Mulkeen told us: "From the MRC's point of view we are generally happy with the progress we have made since we put out the highlight notice and started promoting application of this in this area more actively in March 2007 … A weakness I would concede is that the response has not included enough gut work" (Q 396). Dr Mulkeen said also that the MRC was funding only one research group working on nanomaterial toxicology in the gut,[45] and even that group was working on safety only in part (QQ 397-398).

4.41. While we welcome the efforts that have been made to encourage the submission of applications in nanotoxicology as a whole, the slow rate of progress in areas such as the gut suggests that the Research Councils have not put a high enough priority on ensuring that projects covering the range of research objectives identified by the NRCG are encouraged and funded. Dr Mulkeen told us that in summer 2009 the Research Councils intended to "put out a new statement to the community of what we now think the deficiencies are and what the next step of gaps that we want to see addressed are" (Q 402). We understand that this statement has been delayed so the MRC can consider the recommendations of this report, and of EMERGNANO, when determining its focus.

4.42. We are disappointed and concerned that the Research Councils have not adopted a more pro-active approach to encourage and stimulate research bids in areas where existing mechanisms have so far proved ineffective. Dr Mulkeen told us that the MRC would take "more active steps if needed" to develop research into the safety of nanotechnologies (Q 420). We feel that a more pro-active stance is essential given the lack of progress in several key areas to date.

4.43. We recommend that the Research Councils should establish more pro-active forms of funding to encourage the submission of research bids to address the severe shortfalls in research required for risk assessment of nanomaterials as set out in the EMERGNANO report, and ensure that submissions are reviewed by a committee with appropriate expertise in this field.

4.44. We further recommend that, as part of any strategy to address the research shortfalls identified in the EMERGNANO report, the Government should ensure that specific research is focused on the gut and the other knowledge gaps we have identified above (paragraphs 4.18-4.27) with relevance to the risk assessment of nanomaterials in food or food contact materials.

4.45. We are aware that the FSA intends to commission research into "the fate of nanomaterials in the gut" (Q 635) and we welcome this development. We felt it was regrettable, and surprising, that the FSA, when giving evidence, was unwilling to tell us how many applications had been received in response to the call for the work (Q 641, p 290). This is unnecessary and inappropriate secrecy.

FUNDING FOR ENVIRONMENTAL, HEALTH AND SAFETY RESEARCH

4.46. The total public spending in the United Kingdom on human health and safety research into nanotechnologies is unclear. The NRCG report, Characterising the Potential Risks posed by Engineered Nanoparticles: A Second UK Government Research Report, published in 2007, stated that Government departments and agencies spent £10 million on Environmental, Health and Safety (EHS)-related research into nanotechnologies in 2005 to 2008, which was additional to research in this area funded by the Research Councils.[46] We asked DEFRA how much the United Kingdom had spent on health and safety research into nanotechnologies. Their response, based on the EMERGNANO report, said that United Kingdom spending on nanotechnologies EHS research over the period 2004 to 2008 was £3.3 million, compared to £63 million within the European Union,[47] and £37 million in the United States (p 47). The EMERGNANO report does not, however, include any MRC-funded projects in the United Kingdom figure—which is surprising given that the MRC told us they spent £3.8 million on research into nanotechnology (including nanotoxicology) in 2007-08 alone (p 202). As regards spending in the United States, the US National Nanotechnology Initiative states that EHS funding was $35 million in 2005 and $68 million in 2006[48]—substantially more than the figures DEFRA supplied to us based on the EMERGNANO report.

4.47. In its response to the 2004 RS/RAEng report, the Government made a commitment to funding independent reviews of its progress against the actions set out in the report after two and five years.[49] The CST report in 2007 was the first; the second is due to be commissioned shortly. In order to assist the second review, we believe that there needs to be greater clarity about spending on EHS research in this area.

4.48. We therefore recommend that the Government ensure that a breakdown of annual public spending on nanotechnology-related environmental, health and safety research within the United Kingdom is compiled and available when the five-year review of its progress against the 2004 Royal Society and Royal Academy of Engineering report is carried out.

4.49. Although the figures vary, what is clear is that spending on EHS research is a small proportion of overall spending on other areas of nanotechnologies development—the EPSRC alone spent £220 million on nanotechnologies research in the last five years (see paragraph 3.28). Professor Depledge told us the amount of money for health and safety research is "tiny" in comparison to the amount "invested in the development of new nanotechnologies" (Q 260). The 2007 CST report supported a recommendation in the RS/RAEng report that a minimum of £5-6 million a year, over 10 years, should be spent on researching toxicology, health and environmental effects of nanomaterials.[50] Current EHS spending clearly falls short of this target.

CAPACITY OF THE TOXICOLOGICAL COMMUNITY

4.50. A number of witnesses expressed concern about the capacity of toxicologists in the United Kingdom to carry out the volume of work required. Dr Wadge, for example, said that there needed to be a considerable quantity of research undertaken in the area of nanotechnologies and the food sector and that this raised "bigger, wider questions about whether we have the appropriate capacity of toxicologists within the UK" (Q 29), a concern echoed by Dr Mulkeen (Q 389). In response to the 2007 CST review, Malcolm Wicks MP, then Minister of State for Science and Innovation, stated that the uptake of response-mode funding for research into the health implications of nanotechnologies was disappointing, but that "the problem is not that funding is not available. Rather, it is that the community of toxicologists in the UK is small and has not been submitting applications".[51] The 2008 report of the RCEP also concluded that there was an urgent requirement for trained toxicologists to take on the challenges of nanotechnologies and recommended that "more attention is given to toxicology training in our higher education institutes" to increase the number of qualified individuals.[52]

4.51. In 2009, the Government published a report (commissioned by DEFRA) entitled An Evaluation of the UK Skills Base for Toxicologists and Ecotoxicologists. It stated clearly: "there are not enough scientists to meet the predicted future workloads".[53] The report recommended recruiting new staff and investing in the training of existing scientists. Lord Drayson indicated that he was aware of the problem:

"we are looking actively now at how we can most effectively influence students to participate in those courses for which there are skills gaps, where there are clear needs … which are needed for national priorities and research. I hope that we are able to come forward with some new policies addressing this issue over this year" (Q 568).

4.52. We endorse the recommendation contained in the 2008 report of the Royal Commission on Environmental Pollution that more attention should be paid to toxicology training. We welcome, therefore, the Government's commitment to tackling the shortage of trained toxicologists and ecotoxicologists and also their commissioning of an evaluation of the United Kingdom skills base for toxicologists and ecotoxicologists. However, the policies to address the shortfall promised for this year have not yet been launched. We look for urgent progress on this issue and ask that the Government update the Committee on its activity in this area.

INTERNATIONAL COORDINATION

4.53. A number of witnesses commented on the importance of international coordination of health and safety research into nanotechnologies (Q 111). As Mr Roberts told us, "the issue is global; there is a lot of experience in other countries and we can get much better results if we coordinate our research programmes" (Q 18).

4.54. Support for increased international cooperation on information-sharing and driving forward a shared research agenda appears strong. In 2008, for example, the Intergovernmental Forum on Chemical Safety issued the 'Dakar Statement on Manufactured Nanomaterials' which recommended that governments should increase their efforts to fill knowledge gaps, promote information sharing and "develop, fund, and share effective research strategies on potential risks to human health and the environment"[54] Yet the 2009 EMERGNANO report concluded that "while many … [national and international] agencies and organisations have developed and published research strategies, and although attempts are being now made to link up … until now there has been little effective international co-ordination on research activity. As a result, funded projects are unlikely to provide coherent or comprehensive coverage of the issues".[55]

4.55. A forum where international coordination is already taking place is the OECD. Dr Wadge told us that "probably what is most important from a scientific point of view is that we have international agreement on the risk assessment procedures and that is where the OECD work has a really important part to play" (Q 54). 14 of the most commonly used nanoparticles have been shared out among member states in the OECD for analysis. The UK is taking forward the characterisation and testing of two: cerium oxide and zinc oxide (Q 18). Yet questions have been raised about the OECD's relatively restricted membership, a lack of transparency and limited stakeholder involvement. Friends of the Earth Australia was concerned about the OECD's role as a vehicle for communication about risk research and policy responses, given that "a lot of the world is not represented in OECD, and a lot of the OECD's communication is happening exclusively in English" (Q 304). A 2009 Chatham House report by Dr Falkner, Senior Lecturer in International Relations at the London School of Economics, Securing the Promise of Nanotechnologies, stated that outsiders not directly involved with the process often find it difficult to follow the progress of work, and that the complex process of declassifying reports from its working parties can cause significant delays in publication. It concluded that it was "desirable for the nanotechnology working parties' inclusiveness and transparency to be enhanced in order to facilitate broader participation and openness" although it acknowledged that this would be difficult to accomplish given the OECD's existing structure.[56] Despite these concerns, we recognise that at the present time the OECD has a central role to play in the coordination of research efforts for the development of test methodologies for risk assessment which will underpin the regulation of nanotechnologies.

4.56. The International Organization for Standardization (ISO) has an important role to play in developing standards for nanotechnologies, including definitions, which are likely to feed directly into national and international regulatory developments (p 179). Other examples of coordination include the Environmental Nanoscience Initiative, set up by NERC, DEFRA and the EA. The Initiative is moving into its second phase in cooperation with the EPAin the United States which is providing almost half of the £4.5 million funding (Q 18).

4.57. The European Union has provided €40 million in funding for nanomaterials safety research in the last three years, along with another €10 million in 2009 (Q 594). The research that the European Commission funds is coordinated through Programme Committees, where the United Kingdom is represented, as well as through more informal consultations between Commission Directorates and Member States (Q 596). Ms Merron told us that the FSA's research programmes "take account of relevant research in Europe and the wider international context" and that the FSA can provide co-funding for "European projects where these align with our priorities" (p 290). For example, the FSA is contributing to a three-year European Union project which will be examining methods of measuring nanomaterials in food (Q 635). In addition, the FSA is a partner in the European project SAFEFOODERA, which "aims to co-ordinate national research in food safety across some 19 European countries". This project has recently issued two jointly funded research calls (p 290).

4.58. Whilst we welcome the collaboration that is taking place, more could usefully be done. In particular, we are not convinced that the Research Councils are making the necessary efforts to coordinate their research into the health and safety implications of nanotechnologies with other EU member states. We asked the Research Councils how they coordinated their work in an EU and international context: they informed us of the work of the OECD (see paragraph 4.55 above) but made no reference to any form of systematic coordination or collaboration with other EU Member States (Q 433). When asked the same question, Lord Drayson told us that "a significant proportion of research which is funded by research communities is of proposals which are international collaborations or research groups across both Europe and with the United States", but acknowledged that "it is not perfect" (Q 575). He added: "I do believe that ensuring there is better coordination internationally of the understanding of research priorities is an area where more work needs to be done" (Q 575).

4.59. Regulatory agencies within other Member States will be regulating the same products, under laws implementing the same EU legislation, within the single market. There are opportunities for research to be further coordinated and targeted to share the burden of work and to avoid unnecessary duplication of effort. Research funders in the United Kingdom should work towards not simply the joint funding of research projects with other nations, but coherent strategies that ensure research agendas are aligned towards common goals and priorities where appropriate.

4.60. We recommend that the Government work more closely with other EU Member States on research related to the health and safety risks of nanomaterials to ensure that knowledge gaps are quickly filled without duplication of effort, while continuing to support coordinated research in this area at an international level through appropriate international organisations including the International Organization for Standardization and Organisation for Economic Cooperation and Development.

THE ROLE OF INDUSTRY

4.61. Dr Knowles told us that industry had a role to play in funding some aspects of health and safety research: "I ... agree 100 per cent with you that it [research in the gut] has to be funded by both industry and the Government" (Q 170). However, he noted that, at the moment, it was the chemical and pharmacological industries, rather than the food industry, which was funding most of research into the basic toxicology of nanomaterials (Q 170).

4.62. Dr Knowles talked about cooperation between the food industry, academia and the EU on "pre-competitive research" concerning the nature of nanomaterials rather than on possible applications in food which companies would view as commercial research. He told us that food companies are collaborating with the EFSA, looking at "how one should organise the research that you are talking about in terms of in vivo ingestion of these materials as opposed to inhalation". He also told us of coordination that is taking place between industry and academia, and gave as an example a joint project with the Dutch Public Health Service on the measurement of nanomaterials in food matrices. He added that he hoped eventually it would be "translated into a major, multicentre project", funded half by the European Commission and half by industry (Q 207). Another example is Nanocare, a collaborative project in Germany bringing together representatives from industry, Government and academia. It will be looking at, among other areas, the publication of data on the known and unknown impact of nanomaterials on the environment and health, as well as a "combination of industrial manufacturing and toxicity research" (p 17).

4.63. Professor Jones told us that, in the United Kingdom, the TSB is "putting together industry consortia to do research, both in bringing research to market and in dealing with toxicological and eco-toxicological issues" (Q 492). The TSB's main instrument for promoting research in health and safety issues is the SAFENANO project, a website run by the Institute of Occupational Medicine and funded by the TSB, initially for three years, which aims to provide impartial and independent information to stakeholders on potential health and safety risks from nanomaterials. The project has the remit to collect, interpret and disseminate emerging scientific evidence on these issues.[57] Professor Jones said that industry had contributed to this project, in particular "the NIA has been active … in identifying the research needs of NIA members and feeding into the TSB" (Q 492). We commend this initiative.

4.64. Lord Drayson confirmed to us that there is no central database for health and safety data from academia, industry and Government in the United Kingdom, although the OECD's Working Party on Manufactured Nanomaterials has recently launched a database of global research conducted into the safety of nanomaterials (p 271). While we welcome the creation of an international database, we can also see a need for further sharing of information at a national level between industry and government.

4.65. We asked Dr Knowles whether companies would share information about the safety-testing of new products before they were released on to the market. He thought that they would not, although the information would become publicly available when health and safety-testing information was submitted to the EFSA for pre-market risk assessment purposes. (QQ 208-209). We asked whether he felt commercial confidentiality was an inhibition on the effective sharing of safety information: "At the time when it is commercialised, no, the safety information is circulated" (Q 210). On the other hand, the Royal Society suggested that a reluctance by industry to share proprietary information could delay the implementation of necessary regulatory controls and pointed to the example of the cosmetics sector, where "attempts to assess methods [of risk assessment] have been hampered by industry reluctance to provide the SCCP [European Commission's Scientific Committee on Consumer Products] with information on the use of nanoparticles and methods employed for their risk assessment" (p 364). Professor Owen told us that there is "insufficient co-ordinated research and … inadequate governance processes" to ensure that information about nanomaterials used by industry is "presented in a timely way" (Q 446). Dr Wadge also felt that "commercial pressures" would make companies unwilling to talk about technical developments in public fora (Q 40).

4.66. We recognise that the industry wishes to protect sensitive commercial information, yet industry also has a great deal to gain from cooperating with Government to share information about health and safety data and other information that regulators can use to inform the development of risk assessment procedures and help regulation keep pace with technical developments in the science. Mr Trevor Maynard, Emerging Risks Manager at Lloyd's, told us that a database of information on nanomaterials used by industry would "assist in the process of … risk assessment" (Q 445), while Ms Merron told us that Government had to work with industry to "make them realise that it is in their interests" to share information with the Government (Q 649). Yet past attempts at voluntary reporting schemes to build up a database of information on nanomaterials used by industry have often been ineffective.

4.67. DEFRA has run a voluntary reporting scheme for nanomaterials since September 2006 which aimed to obtain information from companies about what difficulties they were experiencing and "what research priorities might need to be addressed" (Q 580). Response to the scheme has been "disappointing" (Q 582) because, Mr Roberts told us, "there is a challenge … between industry's desire for confidentiality of new developments and our interest in knowing what they are doing" (Q 39). Dr Friedrichs said that this was due to the complicated and extensive nature of the information requested (Q 508), but Lord Drayson, Minister for Science, defended the scheme: "these are issues of some complexity and therefore require considerable information from the companies concerned" (Q 582). Lord Drayson said that he planned to take into account feedback from the industry when deciding how to develop the scheme but warned: "I have to say really quite clearly that I do expect industry to respond effectively. It is not good enough to see this level of response" (Q 582).

4.68. In 2008, in the United States, a Nanoscale Materials Stewardship Program was launched by the EPA "to help provide a firmer scientific foundation for regulatory decisions" by encouraging companies to submit information about the nanomaterials they were working on.[58] The response rate to this scheme was also disappointing and the EPA said that they were now considering a mandatory scheme (see Appendix 6). Other countries are also considering moving to mandatory reporting schemes. For example, Canada has announced a mandatory register of nanomaterials which will include information on safety data. France has announced its intention to consider a similar scheme (Q 303).

4.69. Dr Falkner argued for a mandatory reporting scheme on the basis that it would "level the playing field" and avoid the dangers of a voluntary scheme in which companies that are transparent and which provide information might be placed at a commercial disadvantage (Q 343). Ms Davies suggested that the poor response to the DEFRA scheme indicated that any scheme would have to be mandatory in order to ensure a useful level of participation from industry (Q 299). Ms Miller and Mr Maynard agreed (QQ 302, 446). Professor Nick Pidgeon, Professor of Environmental Psychology at Cardiff University, told us that, when considering public confidence in a technology, "people are very suspicious that industry will not voluntarily report, so that would be the benefit of a mandatory system" (Q 376).

4.70. Some witnesses, including Professor Derek Burke, former Chair of the Advisory Committee on Novel Foods and Processes, (Q 332) and Dr Friedrichs, favoured a voluntary register to ensure that it was "inclusive rather than exclusive" (Q 507). Ms Merron said that she would prefer a voluntary scheme and one which was not too onerous for industry (Q 649).

4.71. Lord Drayson's view was that: "A perfect scheme would be one which had the full support and engagement of industry on a voluntary basis and provided us with sufficient information on what the individual companies were doing to enable us to feel we had a firm handle on the development and potential application of these technologies in future products" (Q 582). Lord Drayson recognised however that this was an ideal which was unlikely to occur (Q 584).

4.72. We recommend that the Food Standards Agency develop, in collaboration with the food industry, a confidential database of information about nanomaterials being researched within the food sector to inform the development of appropriate risk assessment procedures, and to aid in the prioritisation of appropriate research. Industry participation in this database should be mandatory, given the failure of similar voluntary schemes in the United Kingdom and elsewhere.

12 Donaldson K et al., "Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathology in a pilot study", Nature Nanotechnology, 2008, 3, pp 423-428. Back

13 Song Y et al., "Exposure to nanoparticles related to plural effusion, pulmonary fibrosis and granuloma", European Respiratory Journal, 2009, 34, pp 559-567. Back

14 SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks), Risk assessment of products of nanotechnologies, 19 January 2009, pp 15-16. Back

15 Dobrovolskaia MA et al., "Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution", Molecular Pharmaceutics, 2008, 5 (4), pp 487-495. Back

16 Scientific Opinion of the Scientific Committee of the European Food Safety Authority on a request from the European Commission on the Potential Risks Arising from Nanoscience and Nanotechnologies on Food and Feed Safety. The EFSA Journal, 2009, 958, p 18, para 4.3.5. Back

17 Committees on Toxicity, Mutagenicity and Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COT,COM, COC), Joint Statement on Nanomaterial Toxicology, 2005, p 4, para 9. Back

18 Handy RD et al., "Manufactured nanoparticles: their uptake and effects on fish--a mechanistic analysis", Ecotoxicology. 2008, 17 (5), pp 396-409. Back

19 Ramsden CS et al., "Dietary exposure to titanium dioxide nanoparticles in rainbow trout, (Oncorhynchus mykiss): no effect on growth, but subtle biochemical disturbances in the brain", Ecotoxicology, 2009, 18 (7), pp 939-51 and Federici G et al., "Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): gill injury, oxidative stress, and other physiological effect", Aquatic Toxicology, 2007, 84 (4), pp 415-30. Back

20 Mann S, "Self-assembly and transformation of hybrid nano-objects and nanostructures under equilibrium and non-equilibrium conditions", Nature Materials, 2009, 8(10), pp 781-92. Back

21 Council for Science and Technology (CST), Nanosciences and Nanotechnologies: A Review of the Government's Progress on its Policy Commitments, 2007, p 15, para 36. Back

22 Ibid, CST, Review of the Government's Progress, p 5. Back

23 Royal Commission on Environmental Pollution (RCEP), Novel Materials in the Environment: The case of nanotechnology, 2008, p 76, para 5.3. Back