Agendas for Meetings of the Committee on Mutagenicity of Chemicals in Food, Consumer Products and the Environment (COM)
AGENDA - 4th February 1999
1. Apologies for absence
2. Minutes for meeting held 15 October 1998
2.1 Conclusions from meeting on 15 October 1998
3. Matters arising not covered by later agenda items
3.1 CS spray
3.2 Openness: Press Release
4. Malachite green
5. TCDD
6. MCPD (3 Monochloro propane 1,2 Diol)
7. Ozone/mutational signatures
8. Conduct and interpretation of genotoxicity assays 1994-8
9. Annual Report 1998
10. Role of CMO Advisory Committees
11. Guidance document for members
12. Revision of guidelines
12.1 Implications for carcinogenesis
12.2 Genetic diseases in humans
12.3 Monitoring human populations
12.4 Members views on relevant new assays
12.5 Recommended test systems/strategies
13. For information:
13.1 Expert Panel Report on Significance of DNA adducts
13.2 DH paper on Communicating about risks to public health
13.3 Article on flawed statistics
13.4 Improved arrangements for Openness
14. Any other business
15. Date of next meeting: 20 May 1999
MINUTES - 4th February 1999
Minutes of the meeting held on Thursday 4 February 1999 at 10.30 am, in Room 136/7B, Skipton House, 80 London Road, Elephant and Castle, London SE1 6LH
Present:
Chairman:
Professor J M Parry
Members:
Professor J Ashby
Dr P E Bryant
Professor D Davies
Professor MHL Green
Dr S Venitt
Secretariat:
Dr R J Fielder (Scientific)
Mr J Battershill (Minutes)
Mr K N Mistry (Administrative)
Assessors:
Mr A Browning (VMD)
Dr J Sims (MCA)
Dr A Smith (HSE)
Dr JP Tromans (Welsh Office)
In attendance
Miss J Andrews (DH)
Professor A Boobis (ICSTM)
Dr C Boyle (DH)
Dr A Davies (MAFF-JFSSG)
Dr J Greig (DH-JFSSG)
Mr G Kowalcyzk (DH)
Mr D Renshaw (DH-JFSSG)
CONTENTS
| Item | Paragraph | |
| 1. | Apologies for absence Announcements | 1-2 |
| 2. | Minutes for meeting held 15th October 1998 | 3 |
| 2.1 Conclusions from meeting on 15th October 1998 | 4-5 | |
| 3. | Matters arising not covered by later agenda items | |
| 3.1 In-Vitro Micronucleus test | 6 | |
| 3.2 CS Spray | 7 | |
| 3.3 Openness: Press Release | 8 | |
| 4. | Malachite Green | 9 |
| 5. | TCDD | 10-13 |
| 6. | MCPD (3 Monochloro propane 1,2 diol) | 14-15 |
| 7. | Ozone/mutational signatures | 16-18 |
| 8. | Conduct and interpretation of genotoxicity assays 1994-1998 | 19 |
| 9. | Annual Report 1998 | 20 |
| 10. | Role of CMO Advisory Committees | 21-22 |
| 11. | Guidance document for members | 23-24 |
| 12. | Revision of guidelines | 25 |
| 12.1 Implications for carcinogenesis | ||
| 12.2 Genetic diseases in humans | ||
| 12.3 Monitoring human populations | ||
| 12.4 Members views on relevant new assays | ||
| 12.5 Recommended test systems/strategies | ||
| 13. | Any Other business | 26 |
| 14. | For Information | 27 |
| 13.1 Expert Panel report on significance of DNA adducts | ||
| 13.2 DH paper on Communicating risks to the public on health matters | ||
| 13.3 Article on flawed statistics | ||
| 13.4 Improved arrangements for Openness | ||
| 13.5 Mouse Lymphoma Assay | ||
| 15. | Date of next meeting: 20th May 1999 | 28 |
ITEM 1: APOLOGIES FOR ABSENCE
1. Apologies for absence were received from Professor Cooper and Professor Newbold, Dr Shillaker (PSD) and Dr C Fisher (MAFF-JFSSG).
Announcements
2. Members were reminded of the need to declare any interests. The Committee welcomed back Dr Andrew Smith as the HSE assessor who had spent a period of secondment at the Chemicals Directorate at Ispra, Italy. Members asked for a short presentation of his work at a future COM meeting.
ITEM 2: MINUTES OF MEETING HELD ON 5 OCTOBER 1998- MUT/MIN/98/3
3. The minutes of the meeting held on 10 October 1998 were agreed subject to a number of minor typographical amendments.
DRAFT CONCLUSIONS FROM MEETING HELD ON 5 OCTOBER 1998
Comet Assay (Item 5)
4. The conclusions were agreed subject to revision of conclusion iii) "useful supplementary data on a case by case basis to provide data to complement the in-vitro..."
5. Members heard that a major investigation had recently been completed by a Japanese research group and agreed to review the results when published in the scientific literature.
ITEM 3: MATTERS ARISING NOT COVERED BY LATER AGENDA ITEMS
In-vitro Micronucleus Assay
6. Members heard that a common position had been reached by the EEMS regarding the draft protocol for this test. It was hoped that the document would be submitted to the OECD in the very near future
CS Spray
7. Members were told that the COT had endorsed the COM conclusions at their meeting of 27 October 1998. The COT would undertake further discussions regarding CS spray during 1999 before finalising its conclusions.
Openness
8. Members were told that Professor Donaldson (CMO) had issued a press release on the 26 January 1999 announcing changes to the procedures of the COT/COM/COC which would result in greater openness of Committee business including the publication of agendas, minutes, conclusions and statements subject to arrangements for dealing with confidential data. Arrangements had also been put in hand to appoint a lay member to the COM and COC.
ITEM 4: MALACHITE GREEN AND LEUCOMALACHITE GREEN: USE IN FISH FARMING (MUT/99/1)
9. The minutes and COM conclusions of this item will be made available upon publication of the COT consideration of malachite green.
ITEM 5: TCDD (MUT /99/2)
10. Members recalled that there were 75 possible chlorinated polychlorinated-para-dioxins (PCDDs) and 135 possible polychlorinated-para-dibenzofurans (PCDFs), and that a number of these congeners might be present in small amounts as contaminants in food. The toxicological properties and potencies of PCDDs and PCDFs could all be related to the known effects 2,3,7,8-TCDD or TCDD (2,3,7,8-tetrachlorodibenzo[b,e][1,4]dioxin) through the use of toxic equivalency factors (TEFs). The IARC concluded in 1997 that TCDD should be regarded as a known human carcinogen. Previously it had been classified as 2A (probable human carcinogen). This change in view prompted the Department of Health to request COC to review their earlier conclusion. The COC concluded in 1998 that there were insufficient epidemiological and toxicological data on TCDD to conclude a causal link with cancer in humans, but it would be prudent to consider TCDD as a 'probable weak human carcinogen'. The IARC working group concluded that the "experimental data indicated that 2,3,7,8-TCDD and probably other PCDDs and PCDFs are not direct-acting genotoxic agents and that TCDD is considered a non-genotoxic substance." The previous COM evaluation of TCDD was completed in 1987 and it is therefore timely for the committee to reconsider its previous conclusions. The discussion paper Annex 2 to MUT/99/2 presented a review of genotoxicity studies published since 1987 but did not include investigations on inter-cellular communication and tumour promotion studies. Studies of particular note had been appended as Annexes 3 and 4 to MUT/99/2.
11. Members agreed that negative results had been obtained in the in-vitro mutagenicity tests conducted in Salmonella and in L5178Y tk+/tk- cells mouse lymphoma cells. However TCDD induced micronuclei formation had been reported in one study using human lymphocytes and the cytochalasin B technique. The same research group had also noted sister chromatid exchange (SCE) in a subsequent publication. Members commented that it was not possible to draw any conclusions based on these results particularly in view of the unusually long incubation period of 71 hours prior to harvesting the cells. The Committee agreed that a repeat test would be desirable in order to validate the method used in these investigations.
12. The Committee agreed that negative results had been obtained in mouse hepatocytes following dosing of animals with up to 150 µg/kg (i.p). No increase in SCE in peripheral blood lymphocytes was noted in Rhesus monkeys 2 years post administration of a diet containing 25 ppt TCDD for 4 years. However, a small, but statistically significant increase in SCEs in peripheral blood lymphocytes had been documented in a limited study in rats given weekly gavage doses of 5 µg/kg for 2 weeks but not at 0.5 µg/kg . Evidence of TCDD induced single strand DNA breaks in peritoneal lavage cells from rats given an oral dose of up to 100µg/kg. In addition a positive result had been reported in deletion recombination spot test but not in a separate study which used a similar dosing regime. Members considered that no weight could be attached to this investigation in view of the limited study design and the negative findings reported in a mouse spot test by a separate research group.
13. The Committee agreed that the new information did not alter the position adopted in 1987, namely that weight of evidence from the large amount of data indicated that TCDD was not genotoxic. The Secretariat were asked to draft a short statement to this effect.
ITEM 6: 3-MONOCHLORO PROPANE 1,2 DIOL (IN DRINKING WATER) (MUT/99/9)
14. 3-monochloro propane 1,2 diol (3-MCPD) can arise as a contaminant in the use of polyamine flocculants to treat drinking water. It can also be present in certain savoury foods as a contaminant of acid hydrolysed vegetable protein. No interests were declared.
15. The minutes and COM conclusions on this item will be made available when the COC has finalised its conclusions.
ITEM 7: OZONE: MUTATIONAL SIGNATURES (MUT/99/3)
16. Ozone was considered by the COM in 1998 when it was concluded that it should be regarded as a potential in vivo mutagen. Much emphasis was placed on the specific A-T transversion of codon 61 of K ras seen in tumour tissue derived from the mouse lung, the target site for carcinogenicity. The COC had not reached agreement regarding the interpretation of the carcinogenicity data on ozone, particularly as to whether the lung tumours arose as a result of a genotoxic mechanism. The COM had therefore been asked to further consider the significance of the mutations found in lung tumours
in the light of a discussion paper prepared by Imperial College of Science Technology and Medicine (ICSTM). The secretariat had asked ICSTM to specifically present proposals on the minimum data regarding mutations in tumours which would be required in order to draw conclusions on mutagenicity of chemicals.
17. Members considered the generic arguments outlined in Annex 2 to MUT/99/3 and agreed that it was theoretically possible that selection of spontaneous mutations with particular effect, or in particular genes could give rise to differences between treated and control animals with respect to mutational signatures of tumours. The proposal outlined in the paper to establish whether a compound could induce specific mutations in neutral situations, ie where there is no selection through growth advantage as occurs in a tumour, was acceptable, although Members considered that it would be difficult to conduct such experiments with ozone. There were a number of uncertainties to be resolve in developing a suitable methodology, for example whether the use of specific reporter genes (such as lac Z) would be selective resulting in important effects being missed.
18. Regarding ozone, Members considered that additional data from in-vitro studies of mutation signatures could provide valuable information but agreed that it would still be prudent to assume that ozone may have in-vivo genotoxic potential.
ITEM 8: CONDUCT AND INTERPRETATION OF GENOTOXICITY ASSAY 1994-1998 (MUT/99/4)
19. Members noted that this paper outlined some of the general principles for evaluating genotoxicity assays drawn from the Committees discussions 1994-8 and updated the previous paper agreed in 1997. The document was primarily intended to assist Government Departments in the interpretation of mutagenicity data. Members and assessors were asked to comment on the paper by the end of March.
ITEM 9: ANNUAL REPORT 1998 (MUT/99/5)
20. Members were asked to comment on the text by the end of February 1999. It was noted that in future some items would be agreed during the year under the new arrangements for greater openness of Committee business.
ITEM 10: ROLE OF CMO ADVISORY COMMITTEES (MUT/99/6)
21. Members were informed that all advisory committees dealing with food safety issues had been asked to comment on their role with respect to risk assessment and risk communication. MUT/99/6 had been drafted to outline the current practise of the COM and also present a paper on this issue circulated to the COT last autumn.
22. Members agreed that the role of the COM related to providing expert, specialised scientific advice across many chemical sectors and in response to requests from various parts of DH and from other government departments/agencies. The COM did not advise directly on policy or on risk management issues, but the scientific advice provided by COM would be used by DH and other Government Departments in informing policy decisions.
ITEM 11: GUIDANCE DOCUMENT FOR MEMBERS (MUT/99/7)
23. The draft guidance document on procedures and standards was being submitted to COM, COC and COT at their next meetings. It was based on the Cabinet Office model code of practice for board members of advisory non-departmental bodies. The document presented information on areas of committee procedures that had already been agreed with CMO and Ministers (eg the sections on committee openness and the introduction to CMO's advisory committees). Other aspects were new to members, eg appointment procedures but the advice followed the guidelines issued by the Office of the Commissioner for Public Appointments in this regard. There was some flexibility in other aspects with regard to adopting the code to specialist committees such as COM. Members were informed that comments would be considered, together with the comments from the COT and COC before preparing a submission to CMO.
24. Members commented that the requirement to declare direct commercial interests of personal partners and children as currently worded was impracticable and needed to be amended to make it clear that the general principle that Members were not under any obligation to seek out knowledge if they would not normally expect to be informed would apply in this instance. The Committee agreed the document subject to this amendment.
ITEM 12: REVISED GUIDELINES
25. Members submitted a number of draft sections (Implications for carcinogenesis and Monitoring of human populations). These documents would be circulated for comment at the next meeting. The Chairman asked all Members to submit their draft chapters to the secretariat in time for circulation for the May 1999 meeting. The Chairman also requested that members consider the range of available test systems that might be considered in the revised guidelines.
ITEM 13: ANY OTHER BUSINESS
26. There were no other items of business.
ITEM 14: FOR INFORMATION ONLY PAPERS
27. The following 5 papers were circulated for information only.
14.1 Expert Panel Report on Significance of DNA adducts MUT/99/8
14.2 DH paper on risk communication MUT/99/12
14.3 Paper on flawed statistics MUT/99/13
14.4 Improved arrangements for openness MUT/99/14
14.5 Review papers on the Mouse Lymphoma Assay MUT/99/15
ITEM 15: DATE OF NEXT MEETING
28. The next meeting would be held on 20th May 1999. The meeting ended at 3.05 pm
ACTIONS
| Item | Action | Responsibility |
| 4. Malachite Green | Finalise conclusions for February COT | Secretariat |
| 5. TCDD | Draft statement for circulation by post | Secretariat |
| 6. 3-MCPD | Consult COC | Secretariat |
| 8. Interpretation of studies | Amend in light of Members and Assessor comments | Secretariat |
| 9. Annual Report | Amend in light of Members and Assessor comments | Secretariat |
| 11. Guidance document | Collate COM/COC/COT views | Secretariat |
12. Guidelines document (revision) |
Members to draft sections for May meeting | Members |