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COMMITTEE ON THE MEDICAL EFFECTS OF AIR POLLUTANTS
ITEM 1. APOLOGIES FOR ABSENCE AND ANNOUNCEMENTS 1. Apologies for absence had been received from Dr Burr, Professor Burney, Professor Tattersfield, Dr Gavin, Dr Carter (DETR), Dr Tromans (Welsh Assembly) and Dr Cooper (MRC). 2. The Chairman noted that Dr Gideon Lack and Mr Paul Burrows would be attending for Item 5, and that Dr Rushton would be in attendance for Item 7. 3. On behalf of himself and the Committee, The Chairman congratulated Dr Maynard on being awarded a CBE in the New Years Honours List. ITEM 2. MINUTES OF THE MEETING HELD ON 8 OCTOBER 1999 COMEAP/MIN/99/3 4. The minutes were reviewed page by page and the following amendments in relation to Item 7 were agreed: The second sentence of paragraph 30 was reworded to say: "….with the result that vehicle emissions were now a few percent less than they had been prior to the 1970s. The penultimate sentence of paragraph 30 was amended to say: "….and the effects of various types of fuel additives on emissions." Subject to these amendments the minutes were agreed as an accurate record of the meeting1. 5. Members' attention was drawn to a tabled paper giving the Secretariat's view on public availability of papers from the last meeting. It was noted that the BBC had confirmed that the section of the minutes referring to itself (paragraphs 16 to 19) could be made publicly available, and the associated paper on communicating with the public could also be made available if requested. The Secretariat commented that it might be appropriate for the Committee to move towards a system where Members thought about whether papers should be made publicly available at the time they first received and read them, rather than doing this retrospectively for the previous meeting. To this end, a form had been circulated with the papers, and Members were asked to fill this in and hand it to a member of the Secretariat. 6. The Secretariat further noted that there was currently a long delay between a particular meeting and the release of the minutes after the next meeting. Whilst it was acknowledged that it was inevitable that some time needed to be taken to write up the full minutes of the meeting and agree them with Members, the Secretariat commented that it believed that it should be possible to produce a very brief summary immediately. Members' views on this were welcomed. 7. Members agreed that it was, in principle, a good idea to release a statement of the Committee's decisions as soon as possible after a meeting had been held, but had some reservations on the grounds that decisions might change after further discussion at the next meeting. It was also pointed out that inevitably, not all Members were able to attend every meeting, and therefore, might be put into a position of having to defend a decision, the discussion of which they had taken no part. It was suggested that any resume of the meeting should make clear the distinction between confirmed and unconfirmed decisions. After some further discussion, it was agreed that the Secretariat should undertake to produce a brief summary of the meeting immediately and that Members be asked to agree this either at the time or by E-mail in the days immediately following the meeting. It was agreed that this system should commence at the meeting in June. [ACTION: Secretariat] ITEM 3. MATTERS ARISING FROM THE MINUTES 3.1 Draft Guidelines on Investigating the Health Impact of Emissions to Air From Local Industry: A Consultation Document 8. Members were informed that the Draft Guidelines on Investigating the Health Impact of Emissions to Air from Local Industry had been issued for consultation on 17 February and had been tabled for information. 3.2 Living Near Opencast Coal Mining Sites and Children's Respiratory Health 9. The Secretariat drew attention to the tabled paper, which had recently been published in the journal Occupational and Environmental Medicine, after the successful launch of the detailed report earlier in the year. This was circulated for information. The point was raised that Table 5 of the paper seemed to indicate that in both the control communities and the communities living near opencast mines there were effects on respiratory health on exposure to levels of particles (PM10) below 50 µg/m3. ITEM 4. HEALTH EFFECTS OF EXPOSURE TO METHYL-TERTIARY BUTYL ETHER (MTBE) IN PETROL. COMEAP/2000/1 10. No interests were declared in this item. It was felt that this paper should not be made publicly available since it contained extracts from a draft review of MTBE for the Existing Substances Regulations. 11. Members' attention was drawn to COMEAP/2000/1 which outlined the background to this issue. They were reminded that MTBE is an oxygenating agent that has been added to petrol in the UK for a number of years and informed that since the composition of petrol was not currently regulated with regard to all its components the Department had, on occasions, been approached for a view on the effects on health of exposure to specific additives in petrol. In this case, the Department had agreed to look at MTBE in response to a parliamentary question. Members were told that in the United States, use of MTBE had given rise to two groups of complaints: complaints of symptoms, including headache, dizziness and nausea after short-term exposure in communities in which MTBE had been introduced into petrol; and secondly, complaints relating to contamination of water supplies from seepage of petrol containing MTBE from underground tanks. The Secretariat commented that it would welcome Members' views on the toxicity of this compound and acknowledged that in light of the requests from some Members for further information, particularly in respect to carcinogenicity, it would not be possible to agree a final statement on MTBE until the next meeting. 12. It was agreed that the principal questions of concern with respect to MTBE were in regard to its potential carcinogenicity. The point was made that, although tumours were seen in exposed animals, there was evidence to suggest that these were tumours that arise for incidental reasons and were not relevant to human exposure. It was also noted that MTBE was not a genotoxic carcinogen in animals, and therefore, argued that MTBE per se did not pose a risk to health at the levels of exposure currently being encountered. There was some discussion of the tissues used and the need for an exogenous metabolic activation system to show mutagenicity in vitro. It was also noted that there were some deficiencies in the toxicological database, particularly with respect to developmental effects and was argued that more needed to be known about what was actually emitted from car exhausts when MTBE was added to petrol, since the effects upon health of exposure to these compounds might be of concern. 13. A question was raised about the effects of inhalation of compounds added to petrol such as MTBE on susceptible groups, such as asthmatics. It was pointed out that formaldehyde was formed during the combustion process, and that this compound had been suggested as a cause of occupational asthma. 14. The apparent lack of information in the paper on the metabolism of MTBE in the lung, nasal or olfactory epithelium was noted. It was agreed that an earlier section of the draft review for the Existing Substances Regulations, which might contain such information, should be circulated if it was available. [ACTION: Secretariat] 15. There was some discussion about the volatility of MTBE with Members noting that the UK does not have Stage II recovery systems at petrol stations, in contrast to America, so that there was the potential for higher short-term exposure levels to occur. Ambient levels might also be higher because the UK vehicle fleet was less advanced that that in the US. Members felt that more information was needed on the situation in the UK and Europe and that information from the US could not be relied upon in this context. In reply to the suggestion that ethanol might be a more appropriate agent to add to petrol, it was pointed out that MTBE was used because of its tertiary butyl structure that gave rise to butyl radicals; ethanol did not give rise to these species. A query was also raised as to whether MTBE had a major effect on the nature of particles emitted. It was stated, in reply, that petrol was not thought to be a major source of particles. 16. Turning to the draft statement, it was felt that there was a public health issue to be addressed but that a careful balance between the reasons for and against adding this substance to petrol was required. For example, the addition of MTBE might reduce the levels of other pollutants which had health effects. There was a need to take account of the fact that most of the evidence available was based on information from the US and not the UK fleet. Consideration of the effects of MTBE metabolites and of the products of MTBE in the fuel combustion was also necessary. After some further discussion, it was agreed that Members should inform the Secretariat of any further papers they required within a fortnight. It was also agreed that the Secretariat would circulate these to Members as soon as possible. The issue would then be reconsidered at the meeting in June.
17. No interests were declared in this item. It was agreed that the paper could be made publicly available. The Chairman welcomed Dr Gideon Lack, Consultant in Paediatric Allergy and Immunology at St Mary's Hospital and Dr Paul Burrows from the Advisory Committee on Releases to the Environment (ACRE) to this discussion. Professor Jean Emberlin (Pollen Research Unit) was unable to attend the meeting but sent in written views which were circulated to COMEAP members after this meeting. These views are attached at Annex A. 18. It was explained to Members that this issue had been raised in a Parliamentary Question by Norman Baker, MP for Lewes and attention was drawn to a copy of the question and the reply attached at Annex A of COMEAP/2000/2. The Committee was informed that the Advisory Committee on Novel Foods and Processes (ACNFP) had been examining the safety issues surrounding genetically modified crops since 1991 and extracts from its Annual Reports for 1991 and 1992 had been attached at Annex B. It was also noted that the Government takes advice on the regulation of GM crops from ACRE. ACRE currently checks applications for the release of GM crops to ensure whether the genetic modification is likely to indicate the production of a protein product, such as pollen, that is more allergenic than protein produced by the parent plant. The Secretariat commented that DH received a regular round of complaints each year about effects attributed to pollen from oil seed rape, ie, eye and upper respiratory tract irritation in some people who live near rape fields. (It was noted later in the discussion that proven allergy to oil seed rape pollen was relatively rare - the symptoms might also be due to direct irritation). This was one of the crops which had been approved by ACRE to be genetically modified. The Secretariat concluded by asking whether Members considered that there were any additional concerns about the allergenicity of GM pollen and its interaction with chemical pollutants which the Committee might wish to pass on to ACRE. 19. There followed a general summary of some of the main issues surrounding genetically modified crops and pollens. It was explained that, at present, the tenet that genetic modification was likely to produce a protein that was more allergenic than that produced by the parent plant was only a theoretical possibility. So far, there were no firm data to confirm this. Members were told that the possible impacts of pollen from GM crops were not restricted to respiratory health alone, but might impact on other forms of allergy. For example, it was known that pollen was a cause of hayfever. Thirty to forty percent of people who had hay fever often developed asthma. Members were also reminded that the issues of cross reactivity and impacts on people with food allergy, needed to be considered. This was particularly relevant for example, in people with birch pollen allergy who also often presented with oral allergy to certain fruits, such as apples. 20. There was some explanation of how GM crops might affect allergies. Alteration of pollination processes per se could have important consequences for dispersal of pollen, the levels found in the ambient environment and the duration of pollen season. The duration of the pollen season, for example, could have important consequences for health if extended to six months. It was noted that pollen grains were often too large to penetrate deep into the lung, but recent work had indicated that changes in humidity resulted in fragmentation of pollen and production of allergens in the respirable range (< 4.5 µm). Genetic modification might also change the likelihood of fragmentation occurring. It was also noted that the introduction of a new gene or transgene into a plant might be expressed in the pollen products. However, it was recognised that new genes could be also be introduced into plants by traditional plant breeding. 21. The approach adopted by ACRE was then explained. Members were informed that ACRE had a remit to advise Ministers on the risks to human health and the environment from the release of genetically modified organisms (GMOs). It is a statutory committee set up under section 124 of the Environmental Protection Act (1990). No GMOs may be released in the UK without Ministerial consent, and it was explained that ACRE reviews critically each application to release GM crops and considers a wide range of issues in conducting the overall risk assessment. These included whether or not the GM plant and/or its pollen was likely to be any more allergenic or irritating to the respiratory tract than the parental line. In reaching a view ACRE drew on its knowledge of crop plant breeding and biochemistry and the known toxins/allergens associated with each crop. ACRE also studied the transgenic insert at the molecular level and its likely novel peptide products in order to assess whether the new peptide products were likely to be of increased allergenicity. It was noted that companies were also required to submit data on the heat stability or resistance to acid-hydrolysis of novel peptides, since these features were often good indicators of allergenic potential. Information on whether any problems had been noticed in people working with the plant during the containment stage was also considered. It was noted that ACRE had been concerned to point out that changing allergenicity of pollen could occur by cross-linking or genetic manipulation and thus could not be regarded as a specific GMO issue. The point was also made that in the case of mutagenicity breeding where seeds were exposed to radiation to induce mutations randomly and then selected for what was wanted, a wide range of changes could be introduced into crops that potentially could have wide ranging effects on health. 22. During the discussion the following points were made. It was confirmed that there was now some limited evidence that modified genes could be passed into pollen grains. It was remarked that it would be wrong to assume that a transgene had not passed into pollen. The question was also raised as to whether there was now clear information available which could be used to predict whether something was likely to be an allergen. It was replied that at present, it was not possible to talk about rules of allergenicity. Allergies which were previously very rare were becoming much more common and the Committee was informed that changes in heat stability or acid hydrolysis might affect the allergenic properties of a protein/peptide. A considerable database of peptide sequences was now available, and this had demonstrated that there were homologies between inhalant allergens and food allergens. However, it was suggested that enough was not yet known to easily predict allergenicity from peptide sequences. It was asked whether there was any link between biological activity of a gene product and its allergenicity. There had also been some concerns expressed by members of ACRE with respect to the limited ability to predict allergenicity of a product. MAFF was now funding research on a project to develop an animal model to predict food allergenicity for the ACNFP. 23. COMEAP was concerned that any modification to grass pollen could have wide implications because it was such a common allergen. It was confirmed that research was being conducted into the genetic modification of grass pollens. However, the view of ACRE on this issue was that careful consideration was required because of the potentially very large impact on the environment of grass spreading. (Grass was already a very invasive species.) Members of COMEAP felt that this was important. There was some general discussion about the introduction of crops new to the UK but not new elsewhere. These were not genetically modified crops but could nonetheless lead to changes in the allergies found in the population. For example, kiwi fruit allergy and chickpea allergy were conditions that had not previously presented in the UK, but were now becoming more common. It was also mentioned that the introduction of a new plant to Kuwait, the mesquite tree, had been associated with an increase in asthma. 24. Some Members commented that the advantages of introducing GM products should not be overlooked. For example, genetic modification could be used as a tool to reduce pollen allergenicity. This was already the case in the context of some specific foods, such as hypoallergenic rice and peanuts, and was being taken further in the context of developing therapeutically safe vaccines to treat allergies. 25. The question of the interaction between air pollutants and allergens was raised. It was noted that there was emerging evidence that some pollutants, for example, diesel exhaust particles, could augment sensitisation of allergens. The mechanism underlying this effect was not fully understood, but it was suggested that ACRE might need to be aware of this. It was further commented that there needed to be information on whether exposure to pollutant gases, including nitrogen dioxide and ozone, potentiated the effects of allergens in people who already had allergies. It was also confirmed that the issues raised during discussion related not only to pollen, but also to any aerosolised plant material. After some further discussion, it was agreed that the Secretariat would prepare a response to ACRE in the light of the above comments. [ACTION: Secretariat] ITEM 6. TRANSPORT AND HEALTH IN LONDON: A REPORT FOR THE NHS EXECUTIVE, LONDON. COMEAP/2000/3 and COMEAP/2000/4 26. Lord Harris declared some interests in this item. He was the Chairman of the Association of London Government and a member of the London Health Strategy Steering Group. He was also a prospective candidate for the Greater London Assembly. It was agreed that the paper should not be publicly available - it contained views under development which would be superceded by the final statement. 27. Members were advised that this report, circulated as COMEAP/2000/3, had been commissioned by the NHS Executive, and had attracted a large amount of media attention. The main thrust of the media comments were that the report had shown that the effects of air pollutants on health in London had been exaggerated. A commentary on the report had been prepared by the Secretariat, and a draft statement circulated as COMEAP/2000/4. There were particular concerns that the report had quoted, very selectively, from a number of the Committee's reports, misrepresented the Committee's views on carcinogens, and had ignored the possible long-term effects of air pollution on health. These issues were addressed in the draft statement. The Secretariat commented that it would be important to agree a final statement on this issue as quickly as possible and welcomed comments and advice from Members. 28. There followed some general discussion and comment on the report by Glaister et al. It was commented that the general public in London would have received very confused messages from this report. Air pollution is generally perceived to be a problem in London: the report's conclusion on this was counter-intuitive. It was also felt that it was very poor science to produce imprecise summaries of work from other groups such as COMEAP which were then quoted completely out of context, and in some cases, incorrectly. Other Members agreed with this, but pointed out that the report also made some good points, and felt that this should be reflected in any statement from the Committee. 29. Some Members commented that it was very disappointing that the NHS Executive for London had commissioned such a report from a group of people without recognised health expertise, when it was clear that the report was always going to be focussed on the health aspects. The comment was made that it was not helpful to compare London with cities such as Cairo, where conditions, eg of climate, meteorology and traffic characteristics, were completely different. 30. However, the point was also made that this was a long overdue attempt to overview the effects on health of transport in London, and that there was a case for public health professionals looking at this area. Air pollution was only one of many aspects of transport that have a negative impact. 31. Attention was drawn to the May Guidelines. These had been produced by Sir Robert May and set out a code of practice for the use of scientific advice in policy making2. It was agreed that these guidelines should be made available to Members. [ACTION: DETR] 32. Members proceeded to give further consideration to the draft statement (COMEAP/2000/4). There was some discussion of to whom the statement was directed: this would have a direct bearing on the style of the statement issued by the Committee. The Secretariat replied that it was felt that those members of the public who had read the report should also have access to the statement. However, it would also be made available to officials in DH, DETR, DTI, etc., to help to correct any misconceptions which may have been raised. It was also noted that the London Regional Office was keen to have a COMEAP response to put alongside the report on its website. 33. With respect to the statement itself, it was commented that mention should be made that, surprisingly, the report did not quote any direct evidence of air pollution health effects in London of which there was much available, that it should also be made clear that this was not the authors' area of expertise. There was, in fact, substantial local evidence on health effects in London presented in the context of other European cities (the APHEA studies). It was also felt that the statement should say more clearly that the report incorrectly implied that COMEAP discounted NOx, CO, benzene etc, as pollutants that might have some impact on health. It was also ggested that references should be added to the COMEAP statement. After some further comments, it was agreed that the statement should be redrafted in the light of comments made by Members, and that it would be agreed by E-mail as soon as possible. The final agreed statement would be made publicly available on the COMEAP website. [ACTION: Secretariat, Members] ITEM 7. CONCAWE REPORT ON THE APHEA (Air Pollution and Health: a European Approach) PROJECT 34. The Committee was reminded that over the last five years, time-series epidemiological studies had become very important as a means of understanding the effects of exposure to air pollution on health. Many studies had been pursued worldwide, and a large database of published information was now available. However, it was felt that it was important to critically review the studies in order to ascertain where the methodology might be improved. Therefore, CONCAWE, (the oil companies' European organization for environment, health and safety) had commissioned a review of the APHEA Project, which was undertaken by the MRC Institute for Environment and Health. It was noted that CONCAWE had requested this from a non-industry organisation not actively involved in air pollution research, in order to gain a completely new look at the data and results. 35. The CONCAWE report was based on all published papers on APHEA up to a certain date but not the raw data or the original protocols. It noted that APHEA had provided information on effects of air pollution in Europe at a time when most research related to the US. Another major strength was the use of an agreed protocol across the studies in different cities. However, individual studies had not always followed this. This was sometimes unavoidable, for example, the number of pollutant monitors per city varied. The report noted that only 6 studies reported results for the control disease group (gastrointestinal complaints), each city used its own best-fit model, the size of the relative risks for the confounding factors was not reported and a standardised format was not used to report the meta-analyses. 36. It was agreed that the CONCAWE report provided a very useful summary of the APHEA studies which had not been brought together in one report before. The main question was had the problems noted in the CONCAWE report made a significant difference to the interpretation of the APHEA studies? The CONCAWE report did not come to an overall view on this. It was noted that the studies had been peer-reviewed and published so the problems had not been regarded as serious flaws. Any misclassification of exposure would be expected to result in an underestimation not an overestimation of the effect. The use of different best-fit models for each city could be regarded as a strength since confounding factors could vary in importance between cities. If different models had not been used, the studies could have been criticised for taking insufficient account of confounding factors in some cities. Several of the issues raised in the CONCAWE report would be addressed by APHEA II e.g. an a priori position on lags (sum of lag 0 and lag 1) and a more systematic examination of reasons for heterogeneity between cities. 37. The CONCAWE report had discussed some limitations of time-series studies in general. It suggested that spurious associations could result from incomplete control for confounding factors. However, Members noted that the Health Effects Institute in the United States had done an extensive analysis of the issue of confounders and had concluded that the effects reported in time-series studies could not be explained by confounding by weather. The report had also suggested that cohort studies were needed to assess causality. Members agreed that cohort studies were useful but that they had a different purpose and could also have problems. Data on other aspects were needed to come to an overall view about causality and the CONCAWE report was not intended to address this. 38. Members did not agree with the statement in the CONCAWE report that the regression coefficients obtained from the time-series studies could not be used for quantification purposes. Dr Rushton (IEH) clarified this statement explaining that, in her view, the time-series coefficients should not be used to quantify individual risk but could be used for population risk. The Committee agreed that time-series studies were designed to assess population risk not individual risk and considered that the coefficients could be used to quantify the size of effects on the population with appropriate qualifications. 39. The Committee confirmed that, in their view, the time-series methodology was sound and the APHEA studies were a good example. The statement in the 1995 COMEAP Report on particles that it was imprudent not to regard the associations (from time-series studies) as causal remained valid. 40. It was noted that there had recently been a discussion of the advantages and disadvantages of time-series methodology at a Royal Statistical Society meeting to discuss a paper by Dominici on combining evidence on air pollution and mortality from 20 cities in the US. It was agreed that this paper would be circulated for information. The report of the Royal Statistical Society discussion, a commentary on the paper from Mr Hurley and a further paper from the John Hopkins Group aimed at epidemiologists rather than statisticians would be circulated in due course. [ACTION: SECRETARIAT, MR HURLEY] ITEM 8. COMMUNICATING WITH THE PUBLIC. COMEAP/2000/5 41. No interests were declared for this item. It was agreed that this paper could be made publicly available. 42. Members were informed that attached in the Annex to COMEAP/2000/5 was text which had been revised in the light of comments made at the last meeting in October. It was noted that there were a number of different parts of the text where the same points were made, and the Secretariat felt that there was probably a case for extracting elements from most of the passages and having a separate section that concentrated on the actions that could be taken by individuals, the local community, national Government and in Europe. It was also suggested that the section on diet might also usefully be placed there. The Secretariat commented further that if Members were content with this revised text, giving in simple language, the Committee's views of the effects of air pollution on people's health, the text could be placed on the Committee's website and the text revisited once a year. In the mean time, it was suggested that these views could be used as the basis for constructing information to the public in revised leaflets by the Departments of Health and Environment, Transport and the Regions. 43. Members agreed that it would be sensible to have a separate section concentrating on the actions that could be taken by individuals. It was also suggested that the effects of environmental tobacco smoke should be specifically referred to in paragraph 6. There was some discussion of the inclusion of the effects of diet; some Members felt that this might be being given too much importance, and noted that there were many other things that people could do that might be equally as important, if not more so, for respiratory health in general. The point was also made that this advice should not conflict with advice given elsewhere. For example, care should be taken not to imply that people should only eat fresh fruit in the summer when ozone was high. Other Members agreed with this, making the point that whilst they were keen to see positive information such as that regarding dietary habits being included, the Committee should not suggest that there was a clear understanding of exactly why eating plenty of fresh fruit and vegetables was good for respiratory health. It was probably not due to any specific vitamin, and it was agreed that it would be better just to recommend a healthy balanced diet including plenty of fruit and vegetables. 44. It was commented that some passages of the text tended to be tentative and needed to be made firmer and Members agreed to submit further comments to the Secretariat in writing. After some final discussion, it was agreed that the advice should be amended and agreed with the Chairman by correspondence after which it would be placed on the Committee's website. [ACTION: Members, Secretariat] 45. With respect to the DETR banding system, it was reported that there had been few developments since this had been discussed at the previous meeting. Members were told that the alert thresholds for SO2 and NO2 specified in an EC Directive would need to be introduced. The new ozone directive, which contained a proposed alert threshold for ozone, was likely to reach a final position in the next few months. Further information on this should be available at June meeting. ITEM 9. COMEAP CONSIDERATIONS ON "OCCASIONAL PAPERS". COMEAP/2000/6 46. The Secretariat reminded Members that the publication of detailed reports by MAAPE and later, by COMEAP had been an important contribution to work on the effects of air pollutants on health in the UK. However, the production of such reports was time-consuming and it was noted that the rapid expansion of the field had meant that the literature that would have to be surveyed to produce, for example, a new report on ozone or particles, was now very large. The field was also moving so rapidly that a report that took 1-2 years to appear would be likely to look dated as soon as it appeared. Therefore, the Secretariat was of the opinion that this might now be the appropriate time to move away from the pattern of MAAPE and COMEAP reports and to embark on a series of "COMEAP Occasional Papers". The idea was that these would be smaller (similar in size to EPAQS reports) and much more focused. It was suggested that the Occasional Papers would be published both in hard copy and on the Internet and would be amenable to rapid updating as needed. This would enable response to a rapidly moving body of evidence and also to DH and DETR policy priorities. The Secretariat went on to suggest that individual members should be contracted to produce draft papers for discussion by the Committee with literature searching and collating being undertaken by DH or other appropriate bodies. Each paper would seek to provide a view on a pressing problem on which a limited and well defined body of evidence could be identified and would be about 10-15 pages in length supported by not more than perhaps 20 key references. The views of Members on this new initiative were welcomed. 47. The Committee felt that this was an excellent idea. The concept of producing timely and up-to-date information was attractive and would add greatly to the Committee's standing in the scientific community. Some Members made the point that this had been suggested on previous occasions, and that on some subjects it could be difficult to produce small reviews that would be regarded as authoritative. However, it was felt that it should be possible to choose topics that were new and exciting, that would have a relatively small body of literature to support it. It was also suggested that the time period over which the literature search had been conducted could be made very clear in the document. It was commented that the relationship of the individual author to the overall Committee would need consideration. This could be overcome by commenting that whilst the views expressed in a particular paper might not be those of the Committee as a whole, the paper was accepted as part of a COMEAP series. The papers could be offered to peer-reviewed journals; this could increase access to the information. After some final comment, Members agreed to submit further ideas for suitable subjects to the Secretariat in writing within the next few weeks. [ACTION: Members] ITEM 10. COMEAP UPDATE REPORT - ORAL UPDATE FROM PROFESSOR ANDERSON AND NOTE OF UPDATE MEETING. COMEAP/2000/7 48. Members were informed that work on the epidemiological database had begun shortly before Christmas, when a meeting had been held to discuss priorities for interrogation of the system. It was noted that bibliographies including all relevant references, whether or not they were summarised in the database would be produced. Two search strategies had been used to compile the lists of relevant references. These divided the information into panel studies and time-series studies. Literature searches of MEDLINE and EMBASE and examination of information in other major reviews had now been undertaken. A series of quality sifts of the information had been conducted and the next stage of the project, that of placing the information into a relational database was now beginning. Members were told that it was intended that summaries would be provided to the individual chapter authors by Easter. ITEM 11. ANY OTHER BUSINESS 11.1 Appointments 49. The Secretariat commented that an advertisement for new members of the Committee had recently been placed in various journals, the closing date for applications having been 14 February. A sift of the applicants was to be undertaken shortly, and it was hoped that the new members would be appointed in time to attend the next meeting of the Committee to be held in June. It was also agreed that a list of all members, including first names, contact addresses, E-mail addresses, and a short summary of biographical details would be compiled and circulated to the Committee by the Secretariat. This would be helpful and could be given to new members. [ACTION: Secretariat] ITEM 12. DATES OF FUTURE MEETINGS 50. The following dates were noted: Friday 16 June 2000 Friday 3 November 2000. ACTION SHEET
1 It was noted that the text in quotation marks in paragraph 11 of the minutes could be take to imply that asthmatics caused air pollution. The quote was in fact correct, so the minutes would not be changed, but the text on communicating with the public would be amended accordingly. 2 The recommendations include taking advice of the highest calibre and ensuring that the advice is drawn from a sufficiently wide range of the best expert sources. Office of Science and Technology. The Use of Scientific Advice in Policy Making - a Note by the Chief Scientific Adviser Sir Robert May DTI, March 1997. The allergenicity of pollen and plant material from genetically modified crops Some key points and references Summary from Professor Jean Emberlin Feb 2000 A literature research was conducted on the potential alterations in allergenicity of pollen from genetically modified crops but no specific publications were found. In contrast, a substantial number of papers have been published on the allergenicity of foods containing GM material. Many of the proteins in the pollen grains are the same or similar to those found elsewhere in the plant so this research has some relevance to the question of allergenicity of the pollen. The quantities of protein inhaled with aeroallergens are obviously very different from those ingested with food. During the peak pollen season an adult inhales approximately 1 µg pollen per day depending on location, activity etc. Seasonal dosages of inhaled pollen allergens usually total no more than 0.06-1 µg for adults (Marsh and Freidhoff 1993). Even at these low amounts pollen may be regarded as a type of food contaminant: for instance Moneret-Vautrin (1998), states that "…aeroallergens … when ingested as food contaminants, are also likely to cause varied symptoms which must be considered as a peculiar kind of food allergy". Also many cross reactions are known between allergies to aeroallergens and foods due to similarities in proteins, eg, between the major allergen of birch Bet v 1 and apples. Background A llergy to food proteins affects around 5% of infants and 2% of adults. For both populations 50% of the allergens are of plant origin (Moneret-Vautrin, 1998). Where food allergey is indicated clinically, patients usually are allergic to only one or two taxonomically related foods (Astwood and Fuchs, 1996). The production of transgenic foods raises two major concerns regarding allergenicity: 1. The transfer of an allergenic protein from a food with known allergenicity Nordlee et al (1996) have shown that this can be a potentially serious problem in a study of a case in which Brazil nut genes were inserted into soya to improve the protein content of the crop. Immunological techniques identified that the Brazil nut allergen (thought to be 2S albumin) was transferred to the GM soya; furthermore, the GM soya produced an allergic reaction in individuals sensitive to Brazil nuts. Immunological assays such as RAST or ELISA can be used to determine the allergic potential of GM foods when compared to non-GM strains (such technology has also allowed the distribution of some well known aeroallergens to be better understood (Charpin and Veroloet, 1997). These studies indicate that when the gene source is from a known allergen, it is possible to determine whether the allergen content of the GM line is altered relative to non-GM lines (Lehrer and Rees, 1997). The identification of the specific nature of allergens is not a simple task, even when types are suspected (see Valenta et al, 1991). Even when a protein is positively identified there may be some dispute as to whether it is a major or minor allergen (Nordlee et al, 1996). 2. The transfer of an allergenic protein from a food, or other sources, without recognized allergenicity For food sources Wal (1999) has suggested a number of direct or indirect methods to evaluate allergenicity where the source of the protein is a food without recognised allergenicity. 1. Animal models. 2. Structure analysis/sequence comparisons (database has been suggested, Gendel et al, 1998). 3. Study of physical and chemical properties. 4. Level of new protein in GM food. 5. Potential interactions between a transgene and endogenous allergens. The power of GM techniques allows incorporation of new sequences from very diverse sources including proteins that are not found in conventional foods; in turn this may lead to exposure to a new range of potentially allergenic proteins. There are no tests as yet available to predict the allergenicity of a "novel" protein in a wholly reliable and objective manner (Gendel, 1998; Wal, 1999; Opara et al, 1998). General points Once an allergenic protein is identified it may well be possible to apply genetic engineering to produce hypo-allergenic strains (Moneret-Vauntrin, 1998). Genetic engineering techniques can also be used to isolate specific allergens including common aeroallergens (eg, tree pollen allergens: van Hage-Hamsten et al, 1999; Niederberger et al, 1998) to be used for immunotherapy. These plant allergens may also be able to be genetically engineered to give reduced anaphylactic activity, again for use in immunotherapy (Singh et al, 1999) References Astwood JD, Fuchs RL (1996). Allergenicity of foods derived from transgenic plants. Monogr Allergy 32: 105-20. Charpin D, Vervloet D (1997). New aero-allergens. Interactions between allergens and the environment. (Article in French). Bull Acd Natl Med. 181(8): 1551-61. Gendel SM (1998). Sequence databases for assessing the potential allergenicity of proteins used in transgenic foods. Adv Food Nutr Res 42: 63-92. Lehrer SB, Rees G (1997). Recombinant proteins in newly developed foods: identification of allergenic activity. Int Arch Allergy Immunol. 113(1-3): 122-4. Marsh DG, Freidhoff LR (1993). HLA genes determining susceptibility to allergy. In: Kraft D, Sehon A, editors. Molecular biology and immunology of allergens. Boca Raton, FL: CRC Press Inc, p1-9. Moneret-Vautin DA (1998). Modifications of allergenicity linked to food technologies. Allerg Immunol 30:9-13. Niederberger V, Pauli G, Gronlund H, Froschl R, Rumpold H, Kraft D, Valenta R, Spitzauer S (1998). Recombinant birch pollen allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel and oak pollen: a quantitative IgE inhibition study with sera from different populations. J Allergy Clin Immunol 102(4 Pt 1): 579-91. Nordlee JA, Taylor SL, Townsend JA, Thomas LA, Bush RK (1996). Identification of a Brazil-nut allergen in transgenic soybeans. N Engl J Med 334(11): 688-692. Opara EI, Oehlschlager SL, Hanley AB (1998). Immunoglobulin E mediated food allergy. Modelling and application of diagnostic and predictive tests for existing and novel foods. Biomarkers 3(1): 1-19. Singh MB, de Weerd N, Bhalla PL (1999). Genetically engineered plant allergens with reduced anaphylactic activity. Int Arch Allergy Immunol 119(2): 75-85. Van Hage-Hamsten M, Krondvist M, Setterstrom O, Johansson E, Miederberger V, Vrtala S, Gronlund H, Gronneberg R, Valenta R (1999). Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, bet v 1: results obtained with a mix of two recombinant bet v 1 fragments and recombinant bet v 1 trimer in a Swedish population before the birch pollen season. J Allergy Clin Immunol 104(5): 969-77. Valenta R, Duchene M, Pettenburger K, Sillaber C, Valent P, Bettelhiem P, Breitenbach M, Rumpold H, Kraft D, Scheiner O (1991). Identification of profilin as a novel pollen allergen. Science 253: 557-560. Wal JM (1999). Assessment of allergic potential of (novel) foods. Nahrung 43(3): 168-74.
Additional sources Donaldson L, May R (1999). Health Implications of Genetically Modified Foods. Department of Health. www.doh.gov.uk Lelieveld HL, Bachmayer H, Boon B, Brunius G, Burki K, Chmiel A, Collins CH, Crooy P, Doblhof-Dier O, Economidis I, Elmqvist A, Frommer W, Frontali-Botti C, Havenaar R, Haymerele H, Hussey C, Kappeli O, Lex M, Lund S, Mahler J, Marris R, Mosgaard, Normand-Plessier C, Rudan F, Simon R, Logtenberg M, Werner R (1995). Safe biotechnology. Part 6. Safety assessment, in respect of human health, of microorganisms used in biotechnology. Appl Microbiol Technol 43(3): 389-93. Ludwicki JK (1998). Genetically modified organisms (GMO): toxicological aspects. (Article in Polish). Rocz Panstw Zakl Hig 49(3): 253-63. Metcalfe DD, Astwood JK, Townsend R, Sampson HA, Taylor SL, Fuchs RL (1996). Assessment of the allergenic potential of foods derived from genetically engineered crop plants. Crit Rev Food Sci Nutr 36(Suppl): S165-86. Nestle M (1996). Allergies to transgenic foods - questions of policy (Editorial). N Engl J Med 344(11): 726-728. Ruibal Mendieta NL, Nagy AM, Lints FA (1997). The potential allergenicity of novel foods. J Sci Food Agric 75(4): 405-411. Taylor SL (1997). Food from genetically modified organisms and potential for food allergy. Environ Toxicol Pharmacol 4(1-2): 121-126. Vik H, Elsayed S (1986). Comparative studies on tree pollen allergens. XI. Trials on the regulation of IgE response in mice using modified birch pollen allergens. Int Arch Appl Immunol 81(4): 315-321. Wuthrich B (1999). Food additives and genetically modified food - a danger for allergic individuals? Praxis 88: 609-618. |
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