MUT/MIN/98/3
COMMITTEE ON MUTAGENICITY OF CHEMICALS IN FOOD, CONSUMER PRODUCTS AND THE ENVIRONMENT (COM)
MINUTES - 15th October 1998
Minutes of the meeting held on Thursday 15 October 1998 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:
Dr P E Bryant
Professor C Cooper
Professor D Davies
Professor MHL Green
Professor R Newbold
Dr D Tweats
Dr S Venitt
Secretariat:
Dr R J Fielder (Scientific)
Mr J Battershill (Minutes)
Ms J O'Shea (Minutes)
Mr K N Mistry (Administrative)
Assessors:
Mr A Browning (VMD)
Dr M Costigan (HSE)
Dr R O Shillaker (MAFF-PSD)
In attendance:
Dr J Greig (DH)
Mr D Hewlett (Home Office)
Mr G Jones (DH)
Mr J Sarmotta (DH)
Dr J Tann (Home Office)
ITEM 1: APOLOGIES FOR ABSENCE
1. Apologies for absence were received from Professor J Ashby.
ITEM 2: MINUTES OF MEETING HELD ON 21 MAY 1998- MUT/MIN/98/2
CONCLUSIONS FROM MAY 1998 MEETING
2. The minutes of the meeting held on 21 May 1998 were agreed subject to a number of minor typographical amendments.
Item 5: Ozone. para 13, line 15, "would provide reassurance confirmatory evidence"
DRAFT CONCLUSIONS FROM MEETING HELD ON 21 MAY 1998
Item 5: Ozone (MUT/98/9)
3. Members agreed that the draft conclusions on ozone should be further discussed at the February 1999 meeting before being finalised.
Item 8: Benzene (MUT/98/13)
4. The conclusions were agreed as drafted.
Item 9: 1,3-Butadiene (MUT/98/12)
5. Para i) line 1 "The Committee agreed that the new data demonstrated..."
6. Para ii), line 5 " The Committee questioned whether the re was any value at all in the quantitative risk estimates..."
ITEM 3: MATTERS ARISING NOT COVERED BY LATER AGENDA ITEMS
3.1 Openness
7. Members were told that a submission to Professor Donaldson (the new CMO) and Ministers regarding proposals for greater openness of COT/COC/COM business was currently being drafted. In addition a draft advertisement for a lay member for the COM was also under consideration and it was hoped that this would be placed in the national and ethnic press soon.
8. Members restated previous comments that the Committee might need to respond to external lobbying when items of high public interest were discussed in the future. It would be important to ensure that where necessary members commented by post if they were unable to attend.
ITEM 4: ITEM 4: 2-CHLOROBENZYLIDENE MALONONITRILE (CS) (MUT/98/15)
The minutes of this discussion will be made available upon publication of the COT statement on 2-chlorobenzylidene malononitrile (CS).
ITEM 5: THE COMET ASSAY (MUT/98/16)
10. Members recalled that the Comet (single cell gel electrophoresis) assay had been proposed by several research groups as a rapid in-vivo assay for detecting genotoxicity at multiple sites. In 1995 the Committee assessed all the available published literature on the use of this assay to detect chemical mutagens. The Committee agreed, at that time, that the methods used in the 'Comet assay' represented an interesting research area but further work on the mechanisms of and characterisation of the type of DNA damage observed in the assay, and distinguishing this from cytotoxicity and apoptosis, was required before the significance of results could be interpreted. The Committee agreed that data from 'Comet assays' could not be used for regulatory purposes and further work on optimising test methods and validation of the assay was needed. A considerable amount of additional research on assay development had been published since 1995 and was reviewed in the publications appended as Annexes I and II to MUT/98/16. The committee noted that the status of this assay would need to be considered in the forthcoming update of the COM guidelines.
11. Members considered that there had been advances in the development of this assay which had resolved the issues of distinguishing between cytotoxic and genotoxic effects. The advantages of speed, cost and high flexibility of the assay (ie a wide range of tissues could be studied in-vivo including investigations using non-dividing cells) had resulted in a large research effort regarding the Comet assay. Members noted, however, that the large number of separate methodologies in use made it difficult to validate a standard assay; there were no adequate data on sensitivity and specificity available. At present the assay could be used to confirm an in-vivo genotoxic effect for chemicals supported by an adequate package of in-vitro and in-vivo data but there were insufficient data to justify the use of the Comet assay as a screen for potential genotoxicity. Members commented that the significance of a positive finding in the Comet assay which was not supported by any other positive data was unclear. The Committee agreed that the draft conclusions (paras 12-15 of MUT/98/16) should be circulated for comment with ratification at the next meeting.
ITEM 6: THE IN VITRO MICRONUCLEUS TEST (MUT/98/17)
12. The COM had discussed a validation exercise for the in-vitro micronucleus test in 1996 where it had been agreed that there were sufficient data for the development of an OECD guideline. A draft guideline prepared by a working party of the European Environmental Mutagen Society (EEMS) in 1997 was appended to MUT/98/17. Drafts of this guideline had already been extensively circulated throughout Europe, Japan, Australia and the USA. It was intended to submit a proposal for a guideline to the OECD in January 1999. Members were asked to forward any comments to the Chairman who would liaise with the EEMS.
ITEM 7: UPDATING COM GUIDELINES (MUT/98/18-20 and 22)
13. The Committee reviewed the outlines of the revised chapters which had been tabled. It was acknowledged that the overall size of the guidelines should be roughly comparable to the previously published document (Report on Health and Social Subjects No 35, 1989, published HMSO). Members were encouraged to discuss the revision of the guideline with colleagues and it was considered that there was scope for a draft document to be presented at meetings of appropriate professional bodies. Chapters 1 (Introduction/Background) and 2 (Summary) would be prepared by the secretariat when advanced draft of chapters 3-7 were available.
Chapter 3: DNA genes and chromosomes
14. Members agreed the outline for the amended chapter (MUT/98/20) and agreed that the text of this chapter could be used to highlight the issues for further consideration in other chapters such as an overview of the human genome project and the significance of oxidative DNA damage, DNA methylation and polymorphisms in DNA repair. It was agreed that this chapter would be amended as other chapters were finalised.
Chapter 4: Implications for carcinogenesis
15. A draft outline for this chapter would be presented at the February 1999 meeting. Members agreed that there was a need to clarify the purpose of the chapter; ie that it was restricted to carcinogenesis. There was also a need to balance the information in this chapter in comparison to that which would appear in chapter 5. Information on the genetic susceptibility to cancer would be a key issue for this chapter.
Chapter 5: Genetic diseases in humans
16. Members agreed the outline for the amended chapter (MUT/98/18) and noted that this chapter should provide a succinct review of the available scientific evidence.
Chapter 6: Monitoring of human populations
17. Members agreed the outline for the amended chapter (MUT/98/22) and noted the suggested areas for further literature work. It was agreed that a further draft could be submitted to the February 1999 meeting.
Chapter 7: Recommended test systems
18. Members agreed that the basic testing strategy outlined in the 1989 guidelines was still valid. Updating work would concentrate on the potential value of the proposed in-vivo assays such as in transgenic animals. The main changes to this chapter would concern the relative value of individual mutagenicity and genotoxicity tests and assessment of data. Members noted that an IARC review was currently under preparation which would be a valuable source reference for this chapter. Departmental assessors were asked to send ideas/comments specifically on this chapter to Dr Venitt and Professor Ashby copied to the chairman and secretariat.
19. The chairman asked members to forward contributions for which they were responsible to the secretariat by the second week in January in order that they could be distributed for the February 1999 meeting.
ITEM 8: ANY OTHER BUSINESS
20. Members were told that Professor Donaldson (CMO) had agreed to the publication of the 1997 Annual report. The document would, for the first time, be distributed as a free publication.
ITEM 9: DATE OF NEXT MEETING
21. The meeting ended at 3.02 pm. Members were asked to note the following dates for meetings in 1999: 4th February, 20th May and 7th October.