Detailed record of discussion
Chairman: Professor J G Ayres
Members: Mr J Clark, Dr R Clutterbuck, Prof D Colman, Dr C Elcombe, Dr I Grieve, Prof G Hawksworth, Ms R Howell, Dr A Leake, Prof L Maltby, Dr M McPherson, Dr D Osborn, Dr H Rees, Professor R Smith, Dr R Waring
Assessors: Ms G Asbury (FSA), Mr T Davis (PSD), Dr C Griffiths(SASA)
Advisers: Mr J Battershill (HPA), Mr R Davis (PSD), Dr S Kinghorn-Perry (HSE), Dr D Renshaw (FSA)
Secretariat: Ms J Wilder (PSD) Secretary, Miss S Holiday (PSD) Minutes secretary, Mrs Andrea Parker (PSD) Minutes secretary
Other attendees: Dr Ian Dewhurst (PSD) Mr P Hamey (PSD), Mrs E Jenkins (PSD), Mr S Samuels (PSD)
Observer: Dr M Farrelly (Liverpool University)
1.1 Apologies were received from: Dr J Cherrie, Prof C V Howard, Ms D McCrea, Dr P McElhatton, Dr V K Tohani, Dr M Camlin (DARDNI), Mr S Dyer (DH), Ms L George (NAWAD), Dr J Best (EN), Mrs I O’Neill (HSE), Ms F Holloway (PSD)
2.1 The Chairman reminded Members of the confidentiality of the papers and their discussions. If Members believed that they had a commercial or financial interest in any of the items being discussed, they should declare their interest as soon as the meeting moved on to that agenda item. They would then not take part in the discussion, nor would they be involved in any decision taking, unless invited to do so by the Chairman.
2.2 The Chairman welcomed those attending the ACP for the first time, and introduced Dr Farrelly who was undertaking a Defra funded research project to be discussed later in the meeting.
3 Agenda item 1 :
3.1 a) 319th Meeting: Minutes [ACP 1 (320/2006)]
3.1.1 Agreed as amended.
3.2 b) 319th Meeting: Detailed record of discussion [ACP 2(320/2006]
3.2.1 Agreed as amended.
4. Agenda Item 2: Secretary’s report [ACP 3 (318/2006)]
4.1 The Secretary to the Committee reported on the recommendations made at previous meetings. Members were made aware that ministers have granted emergency approval for the aquatic use of Diquat.
5 Matters arising
5.1 Evaluation of new data in support of an application for first inclusion of Ethaboxam in Annex I of 91/414/EEC and for UK provisional approval under the Plant Protection Products Regulations (PPPR), in the product ‘LGC-30473 10% SC’ formulated as a suspension concentrate containing 100 g/l Ethaboxam [ACP 12 (320/2006)]
5.1.1 Ethaboxam is a new active substance and is intended for use as a fungicide for control of grapevine downy mildew caused by Plasmopara viticola. Provisional approval had been requested in the UK for the product ‘LGC-30473 10% SC’, a suspension concentrate containing 100g/l Ethaboxam, for use on grapevines. At a previous meeting members had identified a possible aneugenic effect and had asked for more information.
5.1.2 The applicant had provided the in vitro micronucleus test in cultured human lymphocytes with chromosome staining that had been requested to clarify the possible aneugenicity of ethaboxam. This test was positive both in presence and absence of S9.
5.1.3 Up to now in vitro results from micronucleus assays had been predictive of an in vivo aneugenic response for all of the benzimidazole and similar tubulin binding substances considered by the Committee on Mutagenicity of Chemicals in Food (COM). Ethaboxam had not shown a clear positive response in the in vivo bone marrow micronucleus study submitted, although taken as a whole the data package had hints of possible activity. This had been the reasoning used to ask for the additional study now submitted. This study indicated that ethaboxam was an aneugen in vitro. The lack of a clear positive response in vivo was suggestive that a possible site of contact effect needed to be studied.
5.1.4 Members agreed that although in the case of the benzimidazole fungicides (also aneugens) it had been possible to identify a clear threshold for the effect and thus regulate them using a threshold approach, at present the estimated exposures for ethaboxam were very close to the apparent effect dose levels. Members heard that there was also some uncertainty at present as to the likely exposure levels as there were assumptions made about the both the site and level of contamination on the skin. For example, by referring back to the operator exposure data base and making slightly different assumptions about the proportion of deposit landing on the face and neck rather than forearms and hands to those presented in the assessment, estimated exposure could be higher than the estimate presented in the papers.
5.1.5 The Health Protection Agency (HPA) advised that COM guidelines for consideration of mutagenicity would suggest that a positive in vitro finding should be followed by an in vivo assessment. It was possible that the No Observed Adverse Effect Level (NOAEL) in vivo could be significantly higher than suggested by in vitro data, for example if the molecule was metabolised. HPA reminded Members that when the gut tissue had been examined at a previous meeting there had been no evidence for an aneugenic effect following oral dosing, which suggested that a further non-standard in vivo study might be able to resolve the concern.
5.1.6 Members agreed that this would be a helpful approach, and HPA indicated that the COM would be willing to provide advice on a suitable protocol if the applicant wished. In addition, Members concluded that the applicant could also consider measuring the concentration of chemical deposited at the possible target sites of concern in order to refine the estimates of exposure. Members concluded that provisional approval could not be recommended at this stage as this issue needed to be clarified by further data from the applicant.
5.2 Draft agenda for ACP open meeting [ACP 16 (320/2006)]
5.2.1 Members agreed that the proposed draft agenda for the next annual open meeting, which will look at uncertainty and dose response, looked appropriate. Following some minor amendments to be notified to the Secretariat, Members confirmed that publicity for the open meeting should start over the Summer.
5.3 Other matters arising [ACP 15 (320/2006)]
5.3.1 Members noted the progress on other matters arising.
5.3.2 Resistance management for high resistance risk grass weed herbicides: Members were advised that PSD had received some late responses to the consultation which are currently being considered.
5.3.3 Funding of Wildlife Incident Investigation Scheme (WIIS) for biocides: PSD advised members that their lawyers had concluded that the arrangements under the Food and Environment Protection Act used to enable charges and levy to be raised under Plant Protection Product Regulations should also be suitable for biocides. PSD were pursuing this further with the Health and Safety Executive (HSE).
5.3.4 The Royal Commission on Environment Pollution (RCEP): The Chairman indicated that he still hoped to arrange a meeting with the RCEP Chairman. However this was clearly going to take time so he had drawn together a draft reply to the RCEP commenting on their draft response to the ACP response to the ‘bystanders’ report. The draft incorporated comments received to date and he asked Members for general comments at the meeting and more specific matters of detail to be sent to the secretariat as soon as possible to enable him to provide a finalised reply to RCEP by Friday 30th June. Members discussed the document and provided comments on its structure and content to be incorporated into the reply. They also asked that the secretariat contact those Members who were absent from the meeting to ensure that they were also aware of the need to provide their comments urgently.
Action: Secretary and Chairman
5.3.5 Pesticides Incidents Appraisal Panel (PIAP): HSE announced that Dill Sen had been appointed as acting head of PIAP. He would consider the suggestions made by the ACP and would reply to the Chairman’s recent letter.
6.Dichlorvos [ACP 14 (320/2006)]
6.1 The Committee considered the recently published ‘Opinion of the Scientific Panel on Plant health, Plant protection products and their Residues Panel (PPR Panel) on dichlorvos in the context of Council Directive 91/414/EEC’.
6.2 Members agreed that there was no scientific basis yet for them to change their previous advice on dichlorvos. It was noted that the PPR Panel opinion presented a rather novel way of thinking about genotoxicity and Members considered that there was no scientific support presented to justify this approach.
6.3 Members advised that the UK approvals should remain suspended pending the submission and evaluation of the further data requested as a result of the UK review
7.Understanding, Assessing, and Applying Non-scientific Expert Contributions to Scientific Advisory Bodies [ACP 18 (320/2006)]
7.1 The views of the Committee were sought on this Defra commissioned research project aiming to understand the role of non-scientific lay members on scientific committees. The ‘lay members’ of the ACP have all been qualified in science to at least degree level, so the suggested appellation ‘non-scientific lay members’ was perhaps not an ideal term. A number of suggestions for alternative names had been made to the research team. Another possibility might be ‘non-expert’ members. The team had already found that the role adopted by these members varied as did the different functions of the committees they had examined. Members pointed out that in a committee with a wide range of expert members, such as the ACP, there was always a balance as many members would also be acting in a ‘lay capacity’ when the specialist discussion was not within their own area of expertise. Outside the committee those members who wished to and felt they had comments to offer agreed to discuss the project with the researcher.
8. European Food Safety Authority (EFSA) PPR Panel Opinion on Acceptable Operator Exposure Level (AOEL) Guidance Document [ACP 13 (320/2006)] Redrafted EC AOEL guidance [ACP 19 (320/2006)]
8.1 Members considered these items in tandem.
8.2 The Committee clarified that the PPR Panel opinion was actually questioning the adequacy of the AOEL guidance note rather than the suitability of the AOEL itself as a reference dose for use in human risk assessment.
8.3 However, Members agreed that it was important to ensure that the reference values selected are appropriate to the range of exposure scenarios considered. Given the information currently available, it was agreed that the AOEL was appropriate for use in bystander risk assessment.
8.4 Members suggested a number of possible changes to the redrafted guidance document. The Committee noted that this document was being prepared for the European Commission and suggested that PSD indicate to them the need to ensure that there was wide consultation on the document.
9. FSA Consultation [ACP 11 (320/2006)]
9.1 Members had been invited to consider this consultation from the Food Standards Agency (FSA.)
9.2 Members heard that the working group had been formed to consider variation and uncertainty in toxicology at the request of the FSA and the Committee on Toxicity of Chemicals in Food (COT). They had produced a draft report which had been made available for comment on the FSA website.
9.3 Members commented that the working group had done a very good job of summarising both current knowledge and possible future developments including the use of genomics and proteomics. They also commended the debate presented about use of benchmark dose and the margins of exposure as alternative approaches to risk assessment. They welcomed the suggestion that systematic reviews should be used. Members noted that point 5 on page 14 of the executive summary was important but it was rather unclear what was intended. This often presented real difficulties in interpretation of a data package. For example if there was a single poor quality study that gave a positive result, but a number of good quality, guideline and Good Laboratory Practice (GLP) compliant studies all giving negative results, could the positive finding be discounted? Members felt that specific interpretation would probably be needed in each such case. Members discussed the possibility that more could be included on metabolomics They concluded that although this area could generate more data it would not necessarily provide more information. The data would need to be used thoughtfully and conservatively and interpretation probably required a second guidance document in itself.
9.4 Members noted that variation and uncertainty is an important topic and also noted that ACP had selected this area of discussion for the next open meeting. Members will provide an overview reply to FSA as a Committee and some Members would probably provide more detailed responses as individuals.
10.Update on operator monitoring [ACP 5 (320/2006)]
10.1 This paper presented further information to support a possible biomonitoring study of UK migrant workers. It was suggested that it was important to monitor cholinesterase over a period of time, as had been the case for the original study conducted in Washington. This would enable the biomonitoring data to be used to check the operation of the exposure control procedures.
10.2 HSE advised that the 5 programmes of work outlined in the paper had now been completed and the conclusions being reached as a result indicated that the risks were actually determined by the activities undertaken rather than the migrant status of the workers involved. HSE reminded the meeting that they had to be careful to ensure that their programme of Research and Development (R&D) was strictly in support of their legal responsibilities. This proposal was interesting but would be at the ‘micro’ level. If it were found that there were problems with exposure of migrant workers in UK this might be indicative that conditions of pesticide approval were not being followed appropriately. The Secretary reminded Members that, when considering the Washington data, they had concluded that migrant workers were unlikely to be involved in spraying activities in the UK because of the associated training requirements, but that they might be involved in other activities involving contact with recently treated items such as planting treated modules. Although estimated exposures were within the AOEL for these activities there was little direct monitoring data.
10.3 Members suggested in the light of this discussion that the suggestion should not focus too much on migrant workers, but should aim to clarify to what extent the actual exposures were related to the predicted exposures from these activities. They added that many of these tasks, such as transplanters, required highly skilled staff capable of working accurately and at speed so there is a tendency for the same people to be involved over considerable periods in some jobs, for example, more or less year round in brassica production.
10.4 Members asked if they could see an ‘executive summary’ of the HSE programme results before reaching a decision on this area of work. HSE agreed to try and produce one for the next meeting
10.5 Members also commented that the practicality of the methods selected for biomonitoring should be considered. For example was the proposal to consider urinary metabolites of organophosphates or plasma cholinesterase levels? If both were suggested it would need to be considered how the different measures might be related. (It was noted that the Health and Safety Laboratory, (HSL) might have some data on this aspect. Plasma cholinesterase & urine metabolites are parameters of organophosphate pesticide exposure, but only a small proportion of the workers monitored might use organophosphates.). The difficulties posed by rather poor response rates from agricultural and migrant workers in studies such as these might cause difficulty. Finally the importance of obtaining valid baseline data was stressed and the need to ensure that the timing of monitoring was appropriately related to the activity.
10.6 Overall, the Committee agreed that this is an important area of work. However, further information would need to be provided before a clear recommendation for research can be made.
11.Any Other Business
11.1 Draft proposal for meeting dates 2007 [ACP 17 (320/2006)]
11.1.1 Members agreed to confirm the proposed dates for 2007 with the Secretariat by Friday 30 June.
11.2 Parkinson’s disease research
11.2.1 Members noted a number of papers that had been tabled for information. These included newspaper reports of research on Parkinson’s Disease and pesticides and the Secretary agreed to circulate a copy of the research paper when it was obtained.
11.3 Position paper- First UK approval for the use of dimethenamid-P [ACP 29 (320/2006)]
11.3.1 Mr Clarke declared a non-personal specific interest in the paper on Dimethenamid-P. One member asked to see the full environmental risk assessment summarised in this paper as, at present, it was internally contradictory with the EU end points requiring a buffer zone of more than 10m to protect the aquatic environment, but the UK evaluation apparently concluding a 5m buffer zone would be adequate. The Secretary noted that some UK specific data had been provided, and this would probably explain the difference, but that she would copy the details to the member concerned.
Post meeting note:
Following consideration of the full environmental risk assessment the ACP member was able to confirm that the risk assessment for the UK was acceptable with a 5m buffer zone.
11.4 For Members Attention
11.4.1 Finally Members’ attention was drawn to a recent research call on Environment and Human Health from Natural Environment Research Council (NERC) for ‘proof of concept’ and ‘workshops’ or networks with an overarching aim of encouraging multidisciplinary collaboration.