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Minutes
ITEM 1: APOLOGIES FOR ABSENCE/ANNOUNCEMENTS 2. Apologies for absence were received from the COC Chairman Professor P Blain, the members Professor P Farmer and Dr P Carthew and the assessors Dr H Stemplewski (MHRA), Mr A Browning (VMD), Mr S Samuels (PSD) and Mr R Alexander (Welsh Assembly). Announcements 3. The Deputy Chairman welcomed Professor Valerie Lund from the Institute of Laryngology and Otolaryngology, Mr B Cockcroft (Deputy Chief Dental Officer), D T England and Dr K Leverton (DH Toxicology unit at Imperial College London). 4. The Deputy Chairman thanked both Dr K Leverton (who would be taking maternity leave) and Dr T England (who would be leaving the DH Toxicology Unit ) for their useful work for the Committee. 5. Members were reminded of the need to make any relevant declaration of interests before the discussion of items. ITEM 2: OLFACTORY NEUROBLASTOMA: EVIDENCE FOR AN ELEVATED INCIDENCE AMONG DENTISTS? AN INITIAL DISCUSSION PAPER (CC/03/37) 6. No interests were declared. 7. The Deputy Chairman noted that the Chief Medical Officer for England (Sir Liam Donaldson) had asked for advice on whether there was any evidence for an elevated incidence of olfactory neuroblastoma (ONB) in dentists and dental nurses. He welcomed Professor Valerie Lund from the Institute of Laryngology and Otology, University College London and invited her to make a short presentation of her research to COC. 8. Professor Lund provided members with a brief overview of the literature pertaining to ONB, including diagnosis, treatment and survival. In recent years, the use of specific immunohistochemistry had increased the number of diagnoses made. A review of 42 cases (from 1978-2001) suggested a bimodal incidence with peaks in the third decade and fifth and sixth decades of life (Lund V et al The Laryngoscope volume 113, 502-507, 2003). Symptoms reported at presentation predominantly included nasal obstruction, epistaxis and rhinorrhea. Professor Lund noted that craniofacial resection had significantly improved 5 and 10 year survival statistics. She informed members that she had documented 52 cases of ONB over a period of approximately 23 years. She had particularly noted the finding of 4 cases of ONB where the patient had worked as a dentist or dental nurse. No case of a dentist or dental nurse with any other malignant tumour in the nose or sinus including adenocarcinoma had been reported to the Institute over the same period. 9. Professor Lund described the available information on these cases regarding chemical exposure and steps taken by individuals to minimise exposure. [This information has been provided to members in confidence. Information that could potentially identify a patient cannot be disclosed in these minutes]. 10. The Deputy Chairman asked members to comment on the human pathology data first, then to consider the epidemiology and exposure information and lastly to comment on the carcinogenicity data summarised in the covering paper. 11. Members heard that the diagnoses of ONB in each case would have been checked independently by two pathologists. It was noted that there had been considerable developments in the use of immunohistochemical stains which were valuable in the diagnosis of ONB and in its differentiation from other nasal tumours. Members felt the diagnosis of ONB for all cases in the literature was almost certain to be accurate. The Committee considered there was little scope to confuse ONB with adenocarcinoma of the nasal epithelium. In answer to a question from a member, Professor Lund confirmed that all four cases in dentists/dental nurses were considered to be the same histological type (according to ICD 0 classification). She also noted that at the present time the Institute had no recorded case of a dentist/dental nurse with any other malignant tumour in the nose and sinuses, including adenocarcinoma. The Committee recalled that nasal adenocarcinoma had been documented in a proportion of woodworkers occupationally exposed to hard wood dust. A cluster had been identified some years ago at High Wycombe. However up to 2003, only one case of a woodworker with ONB had been identified in the published literature. Members considered it very unlikely that the tumour diagnoses in wood workers with nasal adenocarcinoma were incorrect. 12. One member commented that the finding of 4 dentists/dental nurses out of a series of 52 cases of ONB referred to the Institute over a period of 23 years was likely to be a statistically significant association. A brief review of registrations of ONB identifiable through the Office for National Statistics (which covered England and Wales) over the past 10 years found around 120 cases (ie about 12 new registrations/year). Very crude information on occupation could be identified for around half the cases registered with ONS. However no dentists or dental nurses were identified in this limited review. Members considered that there was no evidence of a referral bias to the Institute. Members heard that it was possible that there might be more referrals from the South of England and from consultant pathologists who had been trained at the Institute, but overall there was no reason why there should be selection of dentists or dental nurses in the case series presented by Professor Lund. 13. Members heard that three potential chemical agents had been suggested in the covering discussion paper, namely amalgam (metallic mercury), oil of cloves (principle constituent cited was eugenol) and methylmethacrylate. Members discussed the general hypothesis that nasal irritants such as methylmethacrylate might give rise to nasal tumours. However this was thought to be unlikely since employment in occupational groups such as embalmers was not associated with nasal tumours. In addition the chemical carcinogens identified from the US National Library Chemical Carcinogenesis Research information System (CCRIS) (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?CCRIS) which induced ONB in laboratory animals did not identify any nasal irritants. 14. Members considered the information from the CCRIS and commented that the chemicals identified were either known or potential genotoxic carcinogens. The finding that N-nitrosodimethylamine induced ONB in rats was considered interesting but there was no documented evidence for exposure of dentists and dental nurses to nitrosamines. Members noted that these chemicals induced ONB following a variety of exposures routes. It was suggested that metabolic activation occurred in the nasal epithelium. Members considered that ONB was either not found or its incidence was too low to measure in control animals. 15. Members noted the suggestion of amalgam as a possible etiological agent but considered there was no convincing evidence in the papers provided. The suggestion of eugenol was interesting in that oil of cloves had been widely used by dentists and dental nurses over many years. It was noted that the evaluation of eugenol would be complex. The animal carcinogenicity data on eugenol, an alkenylbenzene derivative, did not suggest any potential to induce ONB but there were some reports in the published literature that this compound might have in-vivo mutagenic potential. One member noted that another alkenylbenzene derivative, 3,4,5-trimethoxycinnamaldehyde (a structural analogue of 3,5-dimethoxy-4-hydroxycinnamaldehyde, which occurs in wood lignin), was tested for carcinogenicity by Schoental and Gibbard (British Journal of Cancer volume 26, 504, 1972). These investigators gave 6 young adult rats two doses, the first by intraperitoneal injection and the second by subcutaneous injection. Of 4 rats that survived >17 mo, 2 had nasal squamous carcinoma. Members agreed this information was interesting but noted that there was no evidence for the presence of this compound in oil of cloves. 16. Members noted the increased incidence of micronuclei in nasal epithelial samples from dental technicians reported in the covering paper. However they agreed this finding was not relevant to dentists and dental nurses since it was noted that dental technicians formed a distinctly different group with regard to chemical exposures compared to dentists and dental nurses. 17. Overall, the Committee agreed that it was premature to discuss potential aetiological agents until some additional epidemiological evidence was available to support this initial observation of ONB in dentists and dental workers from the Institute of Laryngology and Otology. 18. Members discussed what further work could be undertaken. It was suggested that examination of tumour tissue for genetic patterns might be valuable in the future, once a credible hypothesis had been formed. The Committee agreed that the first priority would be to obtain more data on tumour incidence in dentists and dental nurses. This might involve a retrospective cohort study design. One member also commented that it would be useful to review the ONB case series available from the Institute of Laryngology and Otology for residence abroad and in particular for time of residence in warmer climates than that of the UK. This would help to provide information on any other potentially relevant etiological factors such as exposure to fungal microorganisms. Alternatively it might be feasible to collate information on individual cases from centres of excellence and pathology departments from the UK, Europe and elsewhere. Professor Lund offered to provide as much information on this aspect as possible. Members also heard that the European Chief Dentists had been alerted to the COC discussion and might be able to provide additional information. Members were also told that the British Dental Association had indicated a willingness to consider involvement in further research and data collection. 19. The Deputy Chairman thanked Professor Lund for her presentation and her offer to approach recognised centres of excellence outside the UK for relevant information. The secretariat were asked to collate additional information identified during the discussion and to bring back a paper to the next meeting. ITEM 3: MINUTES OF THE MEETING OF 22 SEPTEMBER 2003 20. The minutes were agreed subject to minor editorial changes. ITEM 4: MATTERS ARISING NOT COVERED BY LATER AGENDA ITEMS 21. Members were informed that their comments on the Biobank presentation, made at the last COC meeting, would be summarised in a draft letter. This would be circulated to members for comment before being sent to the Biobank project. 22. The Committee heard that its statement on dibenzo(a,l)pyrene had been finalised and would be placed on the COC website. 23. The COC was told that its statement on alcohol and breast cancer had been finalised and would be sent to the Chief Medical Officer in due course. The secretariat thanked members for their hard work on this issue and also informed members that the analysis on alcohol and breast cancer carried out by Imperial College had been submitted for publication in a peer reviewed journal. ITEM 5: REVIEW OF PROSTATE CANCER (CC/03/35 AND CC/03/36) 24. No interests were declared. 25. Members heard that prostate cancer was now the most commonly diagnosed cancer in men in the UK. The incidence had been steadily increasing since the 1960's. The Committee had reviewed a Small Area Health Statistics Unit (SAHSU) study on geographical variation in the incidence of prostate cancer at the June 2002 meeting (Jarup et al. International Journal of Cancer, 97, 695-699, 2002). The Committee agreed that the study showed no evidence for significant geographical variation in prostate cancer. The Committee had agreed that it was timely to undertake a review with regard to the evidence for chemical induction of prostate cancer. 26. The DH Toxicology Unit had drafted an overview paper for COC to consider. The purpose of the paper was to help members identify areas where further review work might be required. Members were asked for any general comments before considering the questions outlined by the secretariat in the covering paper. 27. Members thought the impact of screening for prostate cancer using Prostate Specific Antigen (PSA) on recording of incidence and to a lesser degree mortality data severely complicated the interpretation of epidemiological studies and in particular time trends for incidence. This was particularly evident in the figures for registration in the USA (figure 5 of the DH Tox Unit paper). 28. The Committee discussed the evidence regarding dietary factors and agreed the results from epidemiology studies published since the COMA report on diet and cancer in 1998 were consistent with the conclusions reached by COMA. The limited data were weakly consistent with the finding that higher total fat intakes are associated with prostate cancer. Members noted there were some studies, which reported a suggested association between consumption of dairy products and increased risk of prostate cancer. It was agreed that this was a difficult subject to evaluate and that the secretariat should contact the secretariat of the Scientific Advisory Committee on Nutrition for further advice. 29. Members noted that occupational exposure to cadmium was associated with an increased incidence of lung cancer and was considered by the World Health Organisation's International Agency for Research on Cancer (IARC) to be carcinogenic to humans (ie Group 1). However the evidence from occupational studies regarding prostate cancer showed no association in the majority of studies including relatively large cohort studies. The finding of increased incidence of prostate cancer in rats given a single subcutaneous injection of cadmium was considered by members to be dependent on functioning of the testes and androgen production. Subcutaneous administration of higher cadmium dose levels, which induced testicular toxicity and thus reduced androgen production, resulted in no evidence for prostate cancer. It was noted that prostate cancer had been induced following direct injection of cadmium into the prostate of rats but members considered that this route of administration was of limited relevance. One member alerted the Committee to a published paper (Martin MB et al Endocrinology, 143, 263-275, 2002) which reported evidence that cadmium activated androgen receptor in both in-vitro studies using human prostate cancer cells and in castrated male Wistar rats. It was agreed that this paper would be presented to the COC at the next meeting. 30. The Committee was asked to comment on the recent paper by Leiztman M et al (Journal of national cancer Institute, 95, 1004-1007, 2003.) Members considered that the study had been adequately undertaken by a well respected group using the Health Professionals cohort established in the USA in 1986. There was a statistically significant increase in relative risk for advanced prostate cancer in men consuming > 100 mg/day supplemental zinc (RR = 2.29, 95% Confidence Interval (CI) 1.06-4.95). There was only limited evidence for a dose-response relationship. There was a statistically significant association with taking supplemental zinc for 10 or more years (RR = 2.37, 95% CI 1.42-3.95), however there were very few cases in each of the groups. Members queried whether individuals who consumed high amounts of supplemental zinc would also seek PSA testing. However it was noted that the authors had considered routine screening for PSA up to 2000 in their evaluation. Members felt that the arguments presented regarding the role of intracellular concentrations of zinc in prostate tissue were inconsistent and it was difficult to derive a biologically plausible hypothesis from the information reported. 31. Overall the Committee considered that the study results could not be dismissed which suggested that further epidemiological studies would be valuable. Members heard that dietary supplements available in the UK provided daily doses of up to 50 mg of zinc, when taken in accordance with the manufacturer's instructions (supplements range from 2 to a maximum of 50 mg). The Expert Group on Vitamins and Minerals had established a Safe Upper level for dietary supplementation of 25 mg/day based on evidence that consumption of 50 mg/day might reduce the absorption of copper across the gastrointestinal tract. It was thought unlikely that there were many individuals in the UK regularly consuming more than 100 mg/day. Members asked whether there would be sufficient numbers of individuals consuming such high levels of dietary supplements containing zinc in the EPIC cohort (European Prospective Investigation of Cancer) and asked the secretariat to respond to this query. 32. Members considered the information presented on pesticides and endocrine disrupting chemicals. Members agreed that any potential androgenic effect in-vivo following environmental exposure to these chemicals would be minimal. The Committee noted that there was some very limited epidemiological evidence suggesting a weak association between herbicide exposure and prostate cancer but agreed that this was not sufficient to indicate any further action was required. Members heard that at a meeting held last year by Sir Richard Doll, invited experts had reviewed the evidence for an association between pesticide use and cancer, and had concluded that there was no convincing evidence with regard to prostate cancer. 33. The Committee noted that there was some evidence for a small but consistent association between occupation as farmer or farm worker and prostate cancer from a number of published meta-analyses. However it was difficult to interpret the significance of this finding. Thus the work activities undertaken and potential occupational exposure to chemicals was likely to be highly variable between different occupational categories within farmers/farm workers. Members heard there was some published information which attempted to correlate estimated exposure of farmers/farm workers to pesticides derived from questionnaires, and biomonitoring data was available; this had not been cited in the DH Toxicology unit report. A copy of this information (available as an abstract only) would be provided to members. Members noted the higher relative risk levels tended to be reported for studies undertaken in the USA compared to Europe. Members heard that HSE had completed a review of occupation and association with prostate cancer in 1998. It was agreed that the section of the HSE review relevant to prostate cancer would be made available to members. Members agreed to review the additional information before finalising their conclusions on the section of the report dealing with farmers/farm workers. The Committee agreed there was no consistent evidence for an association regarding any other occupation. 34. The secretariat was asked to provide the additional information for the next meeting and to begin to draft a statement. ITEM 6: ORGANOCHLORINE INSECTICIDES AND BREAST CANCER 35. No interests were declared.
6.1 Tabulation and graphical presentation of epidemiology (CC/03/41) 36. At the previous COC meeting members had seen paper CC/03/4, which had provided an overview of the epidemiology data on DDT and its isomers/metabolites, hexachlorocyclohexane isomers gamma-HCH (lindane) and beta-HCH, and dieldrin. Members had asked for the data to be re-tabulated to show the results for each chemical entity rather than separated into positive and negative studies. The Committee had also noted that a presentation at a recent symposium held by Sir Richard Doll had included a useful plot of odds ratios with 95% confidence intervals for the associations between breast cancer and DDE for a number of studies. This plot showed that the lower estimate of the 95% confidence intervals in most studies fell below one, suggesting no association. It was suggested that such a plot might be useful for other organochlorine chemicals. 37. Paper CC/03/41 provided the requested re-tabulation and graphical presentation of the epidemiology data for the above compounds. Draft tables were produced, with information subdivided by study design and also by metric of exposure (eg blood or adipose tissue). A graphical summary of the key studies had also been produced. The adopted approach reported odds ratios and the exposure levels from the studies. It was suggested that both the tables and graphs could be appended to the COC statement when finalised. 38. A number of new papers not provided for consideration at the September 2003 meeting were also provided, and these generally gave negative results. As there were a large number of publications on this subject it was agreed that there would have to be cut off date for the inclusion of new studies in the statement. 39. The COC agreed that the re-tabulation and graphical presentation was very helpful and informative, but requested the use of a plot on a logarithmic scale to aid interpretation of the relative risk. Members considered that some of the reported studies provided information on the same series of cases or cohort, thus it would be useful to indicate this fact in the table. It was pointed out that for some of the follow up work on survival by Hoyer et al., (Journal of Clinical Epidemiology, volume 53, 323-330, 2000) it was not clear whether relative risk or the hazard ratio for death/prognosis had been reported. 40. Members agreed that it was generally acceptable to report a comparison of upper and lower tertile or quartile, but noted that a few authors had used different approaches to reporting dose-response. Members felt a caveat regarding the interpretation of data was needed as a footnote to the tables. 41. The Committee agreed that the tabulation of data had offset the need for members to review all negative studies. However members asked the secretariat to ensure that the tables covered all studies including those published prior to the first COC consideration in 1995.
6.2 Additional data on oestrogenicity retrieved since 1999 review (CC/03/38) 42. Paper CC/03/38 gave an update on investigations into the potential oestrogenicity and other proposed mechanisms by which organochlorine compounds (OCIs) might induce breast cancer. This information had been previously reviewed in a section of the 1999 COC statement, which dealt with biological plausibility. The Committee had concluded in 1999 that the OCIs considered, were, at most, very weak in-vivo oestrogens and agreed that there was no evidence of any synergistic effects between these chemicals. The impact of exposure to oestrogenic chemicals would be the product of oestrogenic potency and bioavailability. As OCIs are of low oestrogenic potency and occur at low concentrations, it is most unlikely that the effect of current exposures will represent a significant risk of breast cancer. 43. There was a large amount of new data regarding investigations of the potential oestrogenicity of OCIs published since 1999. Members agreed that the results from the new in-vitro oestrogenicity assays reviewed were consistent with the previous data i.e. OCIs exhibit either weak or no oestrogenic activity in in-vitro assays. 44. There were also new in-vitro studies that investigated the potential for interaction between OCIs with respect to in-vitro oestrogenicity. The results of the studies cited in CC/03/38 were reassuring and showed either no evidence for interaction or at the most an additive effect. Members considered the work of Kortenkamp and colleagues from the Centre for Toxicology, School of Pharmacy, London (Rajapakse N et al Environmental Health Perspectives, 110, 917-921, 2002 and Payne J et al, Environmental health Perspectives, 109, 391-397, 2001). It was agreed that the data from these authors demonstrated concentration additivity with regard to in-vitro oestrogenicity, and that there was no evidence for a synergistic effect. 45. A number of new in-vitro and in-vivo studies had also been identified which examined the effects of some OCIs on oestrogen metabolism. Members agreed that there was some evidence to indicate that OCIs such as dieldrin could induce CYP 1A1, 1A2, 1B1 and arylhydrocarbon hydroxylase (AHH) following oral dosing at very high doses (equivalent to the LD50). However this finding was not considered to be relevant to the induction of breast cancer following exposure to OCIs at environmental levels. 46. Members also considered other suggested mechanisms by which OCIs might induce breast cancer, such as activation of the human pregnane X receptor and down regulation of BRCA1 gene expression. The COC agreed that the conclusions reported by the authors of these studies were speculative and should not be reported in the statement. Members noted the additional data from in-vitro studies in MCF-7 cells treated with ß-HCH and considered the results interesting but felt that no conclusions on mechanism by which ß-HCH induced oestrogenic effects in vivo could be reached from these studies. 47. It was noted that since 1999 no further monitoring studies in the UK had been published on the levels of OCIs in human adipose tissue. A Polish study published in 2002 had reported OCl levels in adipose breast tissue, but no conclusions could be drawn regarding trends in tissue levels of OCIs from this study. 48. Overall the COC concluded that all the available evidence was consistent with the conclusions reached in the 1999 COC statement regarding biological plausibility, namely that it is most unlikely that current exposures to organochlorine compounds would represent a significant risk for breast cancer. It was agreed a first draft of a statement could be produced for the next meeting. ITEM 7: CARCINOGENICITY OF 1,3-DICHLOROPROPAN-2-OL (CC/03/42) 49. No interests were declared. 50. 1,3-dichloropropan-2-ol (1,3-DCP) is a process contaminant that may potentially be found in cooked processed foods where acid-hydrolysed vegetable protein (acid-HVP) has been used as an ingredient, such as soy and similar oriental sauces. 1,3-DCP may also be present as a contaminant in epichlorohydrin/amine copolymers used as flocculants or coagulant aids in water treatment. The COM and COC considered 1,3-DCP in 2001. The COM had concluded that it would be prudent to consider 1,3-DCP as potentially genotoxic in vivo, but agreed that it should be tested for genotoxicity in vivo using the approach set out in the COM guidelines. Subsequently, COC advised that "it was prudent to assume 1,3-DCP is a genotoxic carcinogen and that exposure to 1,3-DCP should be reduced to as low as technologically feasible." 51. In line with COM recommendation the Food Standards Agency commissioned a rat bone marrow erythrocyte micronucleus test and a rat liver unscheduled DNA synthesis (UDS) assay. The COM had considered the new data and concluded that the additional information recommended as being necessary to provide adequate reassurance that the mutagenic activity seen in vitro was not expressed in vivo had been provided. The COM noted uncertainties in relation to routes of metabolic activation of 1,3-DCP and agreed that the new mutagenicity studies supported the view that reactive metabolites if formed, did not produce genotoxicity in vivo in the tissues assessed. Overall COM had concluded that 1,3-DCP could be regarded as having no significant genotoxic potential in vivo. 52. In light of the COM advice the COC was asked to consider whether it should revise its previous opinion. Specifically the COC was asked whether 1,3-DCP could be regarded as a non-genotoxic carcinogen, which would allow a threshold based risk assessment to be adopted. 53. The COC noted its previous opinion that 1,3-DCP induced tumours of the kidney and thyroid could have been secondary to sustained cell proliferation. Members also agreed that there was evidence of a hepatotoxic effect at doses below those producing a significant increase in combined hepatocellular adenoma and carcinoma. The Committee agreed that the evidence of hepatotoxicity, together with negative results from the in vivo rat liver UDS assay, provided evidence of non-genotoxic mode of action in the liver. Members noted the written comments from one member regarding the similarity between pathology observed in the liver of Wistar rats given oral doses of 1,3-DCP and that in Wistar rats dosed with hexachlorobenzene. Members agreed that this information also supported a non-genotoxic mechanism for the 1,3-DCP induced formation of liver tumours. 54. The Committee then considered possible modes of action of 1,3-DCP in inducing tumours of the tongue. Members noted written comments from one member and the exchange of e-mails between members which had identified 2% incidence as an upper bound estimate for the background rate on tumours of the tongue in Wistar rats. Thus the finding of 2% papillary carcinoma in the mid-dose female group might not be treatment related but the incidence of tongue papilloma (14.3%) and carcinoma (8.2%) in high dose females was clearly treatment related. In male rats the incidence of tongue tumours in the high dose group was 12% (for both papilloma and carcinoma). There were no tongue tumours in males at the low and mid dose groups. The high dose level clearly exceeded the Maximum Tolerated Dose level in that there was an increase in treatment related mortality and hepatotoxicity. The Committee agreed that 1,3-DCP was an irritant and had produced irritant effects in gastric mucosa of treated rats, but there were no suitable data on the potential for 1,3-DCP irritation of the tongue. Members noted that at the time of conduct of the bioassay (1986) it was not routine to examine the tongue histologically. It was agreed however, that since the compound had been given in the drinking water in the bioassay, chronic irritation was a plausible hypothesis for the induction of the tumours in the tongue. Members noted that there was evidence suggesting that bacteria metabolised 1,3-DCP to the genotoxic carcinogen epichlorohydrin. It was possible that bacteria present in the oral cavity might produce epichlorohydrin when exposed to 1,3-DCP and it was not known whether this would be rapidly detoxified in the oral cavity or tongue. 55. Members considered that although there was no precedent for site-specific tongue tumours arising from bacterial activation of a compound, the suggestion regarding 1,3 DCP was plausible. It was noted that chemical induction of tumours of the tongue in rats was relatively rare, the only examples that could be recalled readily were a variety of nitrosamine compounds. Members considered the possibility of further work to fully discount a genotoxic mode of action for the tongue tumours in rats. It was agreed that information on contact-irritancy, cell proliferation and formation of adducts using 32P-postlabelling in animals treated with suitably high doses of 1,3-DCP was needed. ITEM 8: OPENNESS OF COMMITTEE PROCEDURES (CC/03/39) 56. The COC currently publishes an agenda and many of its discussion papers before each meeting, whilst minutes of meetings and Committee statements are published when finalised. Members were informed that the COT had agreed in principle, at its December 2002 meeting, to hold future meetings in open session subject to discussion and agreement of a detailed protocol. Following discussions between the secretariats of the three sister Committees (COC, COM, COT) a revised protocol was considered by COT and it was agreed that future COT meetings could move to open session from April 2003. 57. The draft protocol for holding COT meetings in open session was attached at annex A to CC/03/39. It was intended that after discussion by all three Committees had been completed, a finalised document would be agreed and published as part of a revised code of practice for openness. 58. Members heard that since the inception of open COT meetings, only four requests for attendance as observers had been received. These had, with the exception of one member of the press, come from groups who had a financial interest in a particular item under discussion. Advertisements for the open sessions appeared in FSA News and on the FSA website. No applications to attend the COT had so far been received from the general public. 59. The COC agreed that it was important to manage applications for attendance according to the procedures set out in the draft protocol. Of particular importance was the need to seek information from attendees on their declarations of interest prior to the discussion of items. It was noted that observers usually attended for a specific item and it was agreed that, if this were so, then it was appropriate to undertake the proposed question and answer session with the relevant item. 60. The COC expressed concern that observers could attribute comments to individual members and possibly distort members’ contributions. The Committee noted that the draft protocol specified that it was important to clarify with observers at the start of the meeting (or item) what was expected of them, and that comments should only be attributed to the Committee as a whole and not to individuals. It would be for the secretariat to consider any relevant rejoinder of comments attributed to members if these were subsequently published by a third party. 61. Members questioned how in confidence data would be dealt with. It was agreed that if the data holder requested discussion of in confidence data in closed session then this should be accepted. This would inevitably lead to many Committee meetings having both open and closed sessions. 62. Overall members agreed with the proposed protocol for open meetings that had already been used by the COT, although it was noted that some procedural aspects needed to be finalised (eg handling requests from members of the media). It was recognised that this would also have to be discussed with the Chairman. Members were content in principle, for COC meetings to be held in open session. Members were also content for an appendix summarising the protocol, produced in conjunction, when appropriate, with the COM and COT, to be added to the Code of Practice on Openness prior to its publication in the 2004 Annual Report. ITEM 9: PAPERS FOR INFORMATION
9.1 COM statement on 2-phenylphenol (CC/03/40) 63. Members were informed of a revised COM opinion on 2-phenylphenol and its salts. The COM continues to recommend a threshold approach to the risk assessment of 2-phenylphenol. A key piece of information in confirming the COM advice was recent in-vivo studies designed to investigate the potential formation of DNA adducts in the bladder of rats. Single oral doses of 2-phenylphenol were administered over a wide range (from 15-1000 mg/kg bw) using the highly sensitive Accelerator Mass Spectrometry (AMS) as a method for analysing the formation of DNA and protein adducts. A linear dose-response for protein binding in the bladder was reported. No evidence for DNA binding in the bladder was reported. Overall these data were consistent with 2-phenylphenol inducing bladder tumours in the rat via a non-genotoxic mechanism. ITEM 10: ANY OTHER BUSINESS 64. One member offered to provide members with information on Food Awareness meetings, which were initiated to provide information on healthy eating options. Another member raised a concern that recent dietary practices which were becoming increasingly popular to aid in the reduction of weight might be associated with an increased risk and asked the secretariat to raise this with the appropriate colleagues in the Department of Health. ITEM 11: DATE OF NEXT MEETING 65. Date of next meeting 1 April 2004. ACTIONS
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