Minutes of the Meeting of 18th March 1999 COC/MIN/99/1
Minutes of the meeting held at 10.30am on Thursday 18 March 1999 in Room 136/7B, Skipton House, Department of Health, London SE1 6LH.
1. PRESENT
Chairman: Professor P G Blain |
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Members: Professor CD Chilvers |
Assessors: Mr I McManus (PSD) |
Secretariat: Dr R J Fielder (Scientific) |
In Attendance: Item 3.2 Item 4
|
Item 5 Item 6 |
AGENDA
| Item | Subject | Paragraphs |
| 1. | Apologies for absence/Announcements | 2-3 |
| 2. | Minutes of meeting held 19 November 1998 | 4 |
| 3. | Matters arising 3.1 Conclusions from November meeting 3.2 Drinking water and cancer: Conclusions. 3.3 Openness of Committee proceedings |
5 6 7 |
| 4. | Alcohol and Breast Cancer 4.1 Potential mechanisms 4.2 Consideration of Meta-Analysis |
8-14 15 |
| 5. | Organochlorine pesticides and Breast Cancer 5.1 Dieldrin and evidence for synergistic effects. 5.2 Revised Statement (2nd draft) |
16-17 18 |
| 6 | 3-Monochloro propane,1,2-diol (in drinking water) | 19-24 |
7. |
Role of Advisory Committees | 25-26 |
| 8. | Guidance on standards and procedures (draft) | 27-28 |
| 9. | Annual Report (draft) | 29 |
| 10. | For information: 10.1 Alcohol and Breast Cancer: Further analysis |
30 |
| 11. | Any Other Business | 31 |
| 12. | Date of Next Meeting: 24 June 1999 |
ITEM 1: APOLOGIES FOR ABSENCE
2. Apologies were received from Professors Farmer, Newbold, and Purchase, Dr Stemplewski (MCA), Dr Fisher (MAFF), and Mrs Cameron (DETR).
Announcements
3 . Members were reminded of the need to declare all interests before the discussion of each item. Members congratulated Professor Purchase, in his absence, on receiving an honorary chair in Biology at the University of Manchester.
ITEM 2: MINUTES OF MEETING HELD ON 18 NOVEMBER 1998 (CC/MIN/98/3)
4. The minutes were agreed subject to one revision
Para 10 iv), line 7, change .."meaningless..." to "..inadequate..."
ITEM 3: MATTERS ARISING
3.1 Conclusions from November 1998 meeting
5. The Committee was informed that revised draft statements on drinking water and cancer and organochlorine insecticides and breast cancer had been forwarded to members (CC/99/7 and CC/99/12 respectively.). The finalised conclusion on CS had been forwarded to the COT in time for their December 1998 meeting. Members were informed that the draft holding statement for possible inclusion in the White Paper on Health Strategy, regarding the association between alcohol and breast cancer, had been tabled for further discussion under item 4 of the agenda. The Committee was also informed that the draft statement on cancer incidence near to municipal incinerators had not been tabled as further revision was envisaged to take into account some alterations in the SAHSU report. A revised statement on this subject would be circulated for comment at the June 1999 meeting. Members were also told that further consideration of the carcinogenicity data on ozone would take place at the June 1999 meeting.
3.2 Drinking water and cancer: Conclusions (CC/99/7).
6. The statement was agreed subject to a number of alterations to be finalised under Chairman's action.
i) Paragraph 9 : Divide into two paragraphs. Change line 5 as follows " ...., and for which there may theoretically be a higher exposure to agents in the drinking water." Start new paragraph from line 6 and alter as follows " Those animal carcinogenicity studies....."
ii) Paragraph 10. Add new penultimate sentence "The Committee reaffirmed its view that since bottled water products may contain chlorinated water, it was not possible to identify an unexposed control group."
iii) Paragraph 11. Change last line as follows "... arising from several unaccounted for possible confounding factors."
iv) Paragraph 12. Change line 6 as follows; "....studies suffered to some extent in the assessment from the difficulty of assessing..."
v) Paragraph 13, line 13. Substitute the following sentence "In an ecological study 23....." with " Members noted that a new ecological study of chlorination of drinking water and cancer mortality in Taiwan had recently been published but agreed that such studies were only useful in the generation of hypotheses and not in respect of the evaluation of risk."
vi) Paragraph 17 (Conclusion). "Overall, the available epidemiological studies fail to provide persuasive evidence of a consistent relationship between chlorinated drinking-water and cancer. It remains possible that there maybe an association between chlorinated drinking water and cancer which is obscured by problems such as the difficulty of obtaining an adequate estimate of exposure to chlorination byproducts, misclassification of source of drinking water (including the use of bottled water) , failure to take adequate account of confounding factors (such as smoking status), and biases arising from non-participation of subjects."
"We therefore consider that efforts to minimise exposure to chlorination byproducts remain appropriate, providing that they do not compromise the efficiency of disinfection of drinking-water."
3.3 Openness of Committee Procedures
7. Members were informed that the new procedures had been agreed by Professor Liam Donaldson (Chief Medical Officer) and had been introduced on the 26 January 1999. The most evident changes would be the publication of agendas prior to meetings and publication of agreed minutes and conclusions shortly after meetings. Members would note a change in the style of minutes, which reflected the requirement to observe confidentiality of any information submitted to the Committees. Members were also informed that interviews for the Lay Member of the COC and COM were to be held in the near future. It was hoped that the lay Member would be able to attend the June meeting of the COC.
ITEM 4: ALCOHOL AND BREAST CANCER
8. No interests were declared.
4.1 Potential mechanisms (CC/99/8)
9. The review paper drafted by Imperial College of Science, Technology and Medicine (ICSTM) (Annex 1 to CC/99/8) presented an introduction to the main suggestions regarding a potential mechanism by which alcohol could induce breast cancer. This included the potential role of acetaldehyde, the influence of alcohol on hormonal status and effects of alcohol on the metabolism of known carcinogens. A review of the available data from in-vitro tests, animal studies and investigations in humans followed, but most emphasis had been placed on the studies in humans. A copy of the previous ICSTM report, which reviewed the available epidemiology publications, was annexed to the ICSTM report as Appendix 1. A number of the most relevant publications were annexed as Appendix 2. Members were asked if they endorsed the conclusions reached by the ICSTM group.
10. With respect to the ICSTM paper, Members asked that the data on potential effects of alcohol on oestrogens be retabulated to report on individual metabolites in the pathway. Members agreed that the data should be considered by an endocrinologist for a view specifically on what effects alcohol might have on the metabolism of oestrogens in premenopausal and post menopausal women. Members considered that the issue of the potential interaction of Hormone Replacement Therapy (HRT) and consumption of alcoholic beverages in postmenopausal women should be considered as a separate topic.
11. Members queried that if alcohol affected circulating oestrogen levels, then the potential for an association with cancer of the endometrium should be considered and thus asked for a further general review of the relevant epidemiological studies.
12. Members read with interest the additional paper on mechanisms tabled at the meeting (Wright R et al Free Rad Biol and Medicine, 26, No3/4, 348-354, 1999) The Committee agreed to ask the COM to consider the most recent data regarding the suggestion that alcohol might induce DNA damage
13. Members agreed that the evidence that the mechanism of alcohol induced effects on oestrogen levels reported by some authors might be due to the presence of phytoestrogens in alcoholic beverages was not persuasive. The Committee queried whether there were any other foreign language publications, which might be pertinent to the ICSTM report.
14. It was agreed that a final conclusion could not be reached at the present time regarding a mechanism by which the consumption of alcohol could increase the risk of breast cancer. The Committee agreed a revised holding statement for inclusion in the Healthy Nation White Paper or its technical annex as appropriate.
4.2 Consideration of need for Meta-Analysis (CC/99/9)
15. Members agreed, however, that there was now sufficient evidence available to suggest a plausible mechanism whereby the consumption of alcoholic beverages might play a role in breast cancer and thus it was important to draw a conclusion as to whether the observed association in epidemiological studies represent a causal effect. It was agreed that ICSTM should be approached with a view to initiating a meta-analysis. COC epidemiologists would be asked to review the document outlining the proposed approach to be used for this study. Members observed that further consideration needed to be given to the most appropriate method for quality scoring the epidemiology papers and agreed that the method proposed by Margetts et al as used by COMA in the Diet and Cancer report could possibly be adapted for the proposed meta-analysis investigation. Members considered that one particularly useful analysis from this work would be an estimation of the Population Attributable Risk for the UK.
ITEM 5 : ORGANOCHLORINE PESTICIDES AND BREAST CANCER
5.1 Dieldrin and evidence for synergistic effects (CC/99/6)
16. Members considered that the study undertaken by Hoyer et al (The Lancet, 352, 1816-1819, 1998) had been adequately conducted but considered that the results might represent a chance finding as a large number of statistical comparisons had been undertaken in the study (n=46). In addition there was no convincing evidence from animal studies that dieldrin had any oestrogenic activity in-vivo and members questioned the basis of the a priori hypothesis. Members noted that the authors had not obtained blood samples from subjects who had fasted and this might affect the validity of the analyses when expressed in terms of lipid content. The Committee agreed that subject to these points, the draft conclusion in paragraph 19 of the paper could be used as a basis for inclusion in the draft statement.
17. The Committee considered all the available published evidence regarding potential synergism of xenoestrogens and agreed that there was no experimental evidence to support such a claim. Members considered the recent paper by Kortenkamp A and Altenburger R (The Science of the Total Environment, 221, 59-73,1998) where the authors had claimed that potential synergism of xenoestrogens and agreed, although study designs and data analyses were not optimal to reveal slight interactions, any toxiciologically significant synergistic interactions should have been identified in the available published experiments.
5.2 Draft statement (CC/99/12)
18. Members agreed that a further draft statement should be circulated for comment and then agreed under Chairman's action. Members asked that the revised draft statement should present a further consideration of the evidence for oestrogenic effects and in particular a comparison of the potential sources of oestrogenic chemicals. Members asked for further information on the decline of Organochlorine concentration in human fat samples to be included. The Committee also requested that the statement be revised in the light of the conclusions reached in respect of CC/99/6.
ITEM 6: 3-MONOCHLORO PROPANE, 1,2-DIOL (3-MCPD) (CC/99/11)
19. Members heard that extracts from a carcinogenicity study submitted by Nestle UK (part of Nestec Ltd based in Switzerland) had been appended to CC/99/11. These and other relevant studies of 3-MCPD (in particular an in-vivo bone-marrow and colonic micronucleus assay in mice) were jointly owned by Nestec and the European Soup and Gravey Manufacturers Association. No interests were declared.
20. 3-MCPD can arise as a contaminant in food stuffs and may also be present in drinking water from the use of polyamine flocculant containing residual 3-MCPD. This material has been evaluated by the SCF in 1994 who concluded that 3-MCPD should be considered as a genotoxic carcinogen. The SCF reviewed this material again in 1996 when a proposal for the mechanism of carcinogenesis in the rat was provided by industry (CANTOX report see Annex G, published as Lynch BS et al 1998, Intern J Tox, 17, 47-76.) The SCF rejected the arguments advanced by CANTOX on the grounds that no new data had been provided and reaffirmed its previous conclusion. 3-MCPD has been referred to the COM and COC by the Department of Health in respect of the potential for contamination of drinking water following a request for advice from the Committee on Chemicals and Materials of Construction for use in Public Water Supply and Swimming Pools (CCM). This Committee is a statutory body designated to advise the Secretaries of State for the Environment and for Wales.
21. The COM undertook an initial consideration of the available mutagenicity data at its February 1999 meeting and agreed that 3-MCPD should be considered as an in-vitro mutagen, but there were insufficient data to draw any conclusions on in-vivo mutagenicity. The COM asked the secretariat to investigate whether some of the mutagenicity tests reports held by industry could be submitted to the COM. Members were told that the secretariat had initiated discussions with the company using the new guidelines for greater Committee openness as a basis for discussion.
22. The COC concurred with the COM view that there was no evidence of bacterial specific metabolism of 3-MCPD. The Committee agreed that the high dose level used in the carcinogenicity study undertaken by Sunhara et al for Nestec exceeded the Maximum Tolerated Dose (as reported by Lynch BS et al, International Journal of Toxicology, 17, 47-76, 1998). An increased incidence of Leydig cell adenomas was reported in males at the mid and top dose levels and mammary gland fibroadenomas in males at the top dose level. A statistically-non-significant increase in adenoma and carcinoma of the preputial gland was reported in males at the mid and top dose levels. An increase in the number of renal tubular adenomas was reported in females at the top dose (a non-significant increase was seen in males). The authors of the carcinogenicity study and Lynch et al 1998 advanced arguments that all of these tumours were mediated by non-genotoxic mechanisms involving either cytotoxicity (kidney) or hormonal disturbances. Members agreed that the proposed non-genotoxic mechanisms advanced were plausible, but there was no compound specific data to support any of the contentions suggested.
23. The Committee agreed that it would be prudent to consider, on the basis of the available data, that 3-MCPD was a genotoxic carcinogen. Members recognised that such a decision had significant implications for the approach used for risk assessment of the use of polyamine flocculants in water and reaffirmed the COM view that appropriate in-vivo mutagenicity studies should be made available.
24. The Committee agreed to consider draft conclusions on this item at the next meeting on 2th June 1999 where it was hoped that a COM view on the relevant mutagenicity studies would be available.
ITEM 7: ROLE OF ADVISORY COMMITTEES
25. The COC (along with COT and COM) had been asked by DH/MAFF Ministers to consider its role in the context of food safety. A draft paper had been circulated for discussion (CC/99/4) which outlined current practise. A copy of a paper submitted to the COT last autumn had been appended.
26. Members agreed that the role of the COC 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 COC did not advise directly on policy or on risk management issues, but DH and other Government Departments would use the scientific advice provided by COC in informing policy decisions. Members noted that the Royal Commission on Environmental Pollution had recently considered the use of scientific advice to inform policy and asked that a copy of the relevant part of the document be made available for members information.
ITEM 8: GUIDANCE ON PROCEDURES AND STANDARDS (CC/99/3)
27. This draft guidance document on procedures and standards had been previously circulated to COM and COT and had now been submitted for discussion at the COC. It was based on the Cabinet Office model code of practice for board members of advisory non-departmental public bodies (ANDPBs). It included sections that had already been agreed with CMO and Ministers (eg the sections on committee openness and the introduction to CMO's advisory committees) and these were familiar to members. Other aspects are new to members, eg appointment procedures as set out by the guidelines issued by the Office of the Commissioner for Public Appointments. There was some flexibility in other aspects with regard to adapting the code to specialist committees such as COC. Member's comments will be considered, together with the comments from the COT and COM before preparing a submission to CMO and Ministers.
28. The Committee concurred with the views of the COM and COT regarding the need to amend the section on declarations of interest in that the requirement to declare direct commercial interests of personal partners and children as currently worded was impracticable. The amendment should make it clear that the general principle that Members were not under any obligation to seek out knowledge that they would not normally be expected to have would apply in this instance. Members considered that the appointment procedure might dissuade potential members from applying. Members also considered that there was a need for the Department to acknowledge the amount of time required to undertake the reading of papers for the Committee. The Committee asked that these points be raised in any submission to Professor Donaldson (CMO).
ITEM 9: ANNUAL REPORT (DRAFT) (CC/99/5)
29. A draft text for the 1998 Annual Report of the COC had been circulated for comment (by end of March 1999). Members noted changes to style and commented that the format of references needed to be considered further. Additional comments would be considered with reference to any documents on items of business which had already been published.
ITEM 10: FOR INFORMATION:
30. The following papers had been submitted for members information:
10.1 Alcohol and Breast Cancer: Further analysis
of Framingham Study CC/99/13
10.2 Short term tests for carcinogenicity CC/99/14
(Enzmann H et al, Food Chemical Toxicology, 36, 979-995, 1998)
ITEM 11: ANY OTHER BUSINESS
31. Members were informed that Dr Denise Robinson (Scientific Director HESI, USA) had provisionally agreed to attend the 24 June 1999 meeting to give a presentation on the HESI/ILSI planned validation work on short-term tests for carcinogenicity.
ITEM 12:DATE OF NEXT MEETING: 24 June 1999
ACTIONS
| Item | Action | Responsibility |
| 3. Conclusions | Redraft conclusions on drinking water and cancer, ozone, and municipal incinerators | Secretariat |
| 4 . Alcohol | Consult with ICSTM regarding further evaluation work, and COC seek additional expertise with Epidemiologists regard to assessment of intake and endocrinological effects. Discuss proposal for meta-analysis. |
Secretariat |
| 5. OCs and Breast Cancer |
Redraft statement and circulate for submission to ACP on 15/4/99. | Secretariat |
| 6. MCPD | Liaise conclusions with company and draft | Secretariat |
| 7. Role of COC | Convey conclusions to DH/FSP management | Secretariat |
| 8. Guidance | Amend and forward to CMO for his consideration. | Secretariat |
| 9. Annual report | Amend in light of members comments | Secretariat |