Advisory Committee on Pesticides 350th Meeting - Detailed record of discussion
Chairman: Dr A Leake
Members: Prof C Brown; Dr J Cocker; Dr C Harris; Prof G Hawksworth; Mr P Jackson; Dr G M McPherson; Prof P Matthiessen; Prof C Ockleford; Dr W Parker; Dr A Povey; Dr H Rees; Dr S Waring.
Assessors: Dr J Hughes (SASA ); Dr S Jess (AFBINI ); Mr A Spencer (FSA ); Mr D Williams (Defra ).
Advisers: Mr T Davis (CRD ); Dr S Fairhurst (CRD); Dr L Hetherington (HPA); Mr B Maycock (FSA); Miss S Shore (CRD); Dr C Snaith (HSE); Dr M Taylor (SASA ).
Secretariat: Ms J Wilder(CRD ) Secretary; Mr P Fisher (CRD) Secretariat; Mr C Pidgeon (CRD) Secretariat.
Other attendees: Mr M Burns (CRD ); Dr S Butler (CRD); Mrs N Cook (CRD); Mr D Flynn (CRD); Dr H Gustafsson (Kemi); Mr P Hamey (CRD); Miss R Kittoe (CRD); Miss D Liddell (CRD); Mr I McManus (CRD); Dr N Morgan (CRD); Mr P Ridgeway(CRD); Dr L Ross(CRD); Mr M Williams (CRD).
1.1 Apologies were received from: Prof J G Ayres, Ms J Dean, Prof R Smith, Mr D Bench (CRD ), Dr A Davies (Defra ), Mr M Williams (NAWAD), Dr A Burn (NE ), Mr M Camlin (AFBINI ).
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 Jackie Hughes and Mike Taylor from SASA who had taken over from Chris Griffiths, Sarah Shore who had taken over from Richard Davis at CRD, and Hanna Gustafsson from the Swedish Regulatory Authority, currently working at CRD.
2.3 The Chairman noted Prof Ayres had sent apologies due to a recent bereavement and the Committee sent their condolences.The Committee also noted Prof Ayres had received an OBE in the Queen’s Birthday Honours and members sent congratulations on this well-earned honour.
3. Agenda item 1:
3.1 a) 348th Meeting: Minutes [ACP 1 (350/2011)]
3.1.1 Agreed subject to minor amendment.
3.2 b) 348thMeeting: Detailed record of discussion [ACP 2 (350/2011)]
3.2.1 Agreed subject to minor amendment.
4. Agenda item 2: Secretary’s Report [ACP 3 (350/2011)]
4.1 There were no issues to report.
5. Agenda item 3: Matters arising
5.1 a) Penflufen [ACP 5/1 (350/2011)]
5.1.1 Dr McPherson and Dr Harris declared a non-personal non-specific interest but remained for the discussion.
5.1.2 Following ACP 347 and ACP 348, and subsequent discussion with toxicology members, the Committee considered the in vitro rat and human hepatocyte studies submitted by the applicant. Members agreed that these were good studies demonstrating a clear dose response. They confirmed a rodent specific phenobarbital-type response. Members were therefore able to conclude that the mechanism of carcinogenicity was not relevant to humans. The ACP suggested that applicants should be encouraged to provide this type of data in future similar applications.
5.1.3 Members were able to confirm the ADI and AOEL as previously suggested and thus to advise that provisional authorisation be granted.
5.2 b) Outdoor use of rodenticides [ACP 5/3 (350/2011)]
5.2.1 Following discussions at ACP 348, and subsequent correspondence with environmental members, Members considered the updated paper from CRD .
5.2.2 Members were broadly content with this revised draft. They suggested a minor amendment to emphasise that harbourage should be reduced before treatment and maintained post treatment at the minimum possible level. They noted an element of repetition between paragraphs 8 and 9 and suggested these paragraphs be combined to remove this repetition.The HPA requested the requirement to undertake a risk assessment for exposure of unprotected individuals to be included in the approval application. FSA suggested that the warnings outlined in paragraph 7 be extended to include livestock farmers given that incidents involving livestock accessing baits are not unknown.
5.2.3 Members agreed this draft subject to the revisions suggested above and any further comments to be submitted by members unable to attend this meeting.
5.3 c) ACP Recruitment 2011 [ACP 5/2 (350/2011)]
5.3.1 The secretariat recorded their thanks to the appointment panel members in taking forward this programme of appointments. Recommendations to fill some of the posts had now been passed to Ministers. It was hoped that the new members would be in post for the next meeting. Retiring members were thanked for their generosity in continuing beyond their original appointment period in order that the work of the Committee could continue, and were extended a warm welcome to attend the annual open meeting.
5.3.2 Members heard that unfortunately not all posts had been filled by this recruitment and a new recruitment round was planned for the autumn, and members were asked for their help again in drawing these posts to the attention of possible candidates.
5.4 d) Other Matters Arising [ACP 5 (350/2011)]
5.4.1 Members heard an update on various matters arising from previous meetings.
5.4.2 Members heard a short update on the work underway to change the status of the ACP and a number of other Defra sponsored committees to expert scientific committees.The Public Bodies Bill was going through Parliament at present and this provided the enabling powers.Once complete, specific orders would be introduced to complete the changes. Members were advised that Ministers would shortly be consulting on these proposals. For the ACP it was thought that the practical difference in status would be slight.
5.4.3 Members also heard that a new code of conduct had now been agreed and would be passed to them shortly. Again in practical terms for the ACP, it was very similar to the existing code of conduct.
5.4.4 EFSA had now commenced the member states peer review process for a number of applications for Annex I listing of various Trichoderma species.These were being considered together to assist with identification of generic issues. Members attention was also drawn to the tabled reply from EFSA to their letter setting out a number of generic issues associated with the consideration of biological pesticides.
5.4.5 The Committee heard that the regulatory toxicology group of the National Centre of 3Rs (Replacement, Refinement and Reduction of animals in research) were interested in the safety issues associated with biologicals and CRD were asked to provide them with the latest information from EFSA.
6. Application for UK provisional approval (PPPR) for ‘Property 180SC’ containing pyriofenone [ACP 16 (350/2011)]
6.1 Dr Harris declared a non-personal non-specific interest in this item.
6.2 Members considered an application for provisional UK approval of Pyriofenone (IKF-309), a new fungicide formulated as ‘Property 180SC’, a suspension concentrate for use on cereal crops. Members heard that the UK are also the Rapporteur Member State (RMS ) for the Annex I assessment of pyriofenone for which an additional use on grapes had also been evaluated.
6.3 Members agreed the Technical specification had been appropriately derived but there should be a requirement to re-review this once production scale 5 batch analysis data had been provided. This should not delay approval. Members noted that although the pKa was missing from the data package, on a theoretical basis pyriofenone seemed unlikely to ionise and therefore there would be no need for additional clarification of the pKa, or of variation of log Pow or water solubility with pH.
6.4 Members noted that despite considerable work and much very good data, the mechanism of carcinogenicity was still unclear.There was some weak evidence of chromosomal damage and some evidence of enzyme induction, although this did not seem to be Phenobarbital-type. There were good data on haematology and biochemistry and there was evidence of some haemopoietic changes.There was a possibility that the carcinogenicity was caused by some type of high dose inflammatory effect. Members agreed that in order to gain more certainty that a non-genotoxic mechanism was responsible for tumour formation, a COMET assay be requested to provide further evidence whether or not there was a genotoxic mechanism of carcinogenicity.
6.5 Members noted two issues in the developmental toxicology. There was reported to be discontinuous cartilage although it was unclear where this occurred. There was also a dose dependent and statistically significant finding of supernumerary ribs. The concern here was whether in this case this should be considered an adverse finding as it was not clear to what degree the ‘full’ supernumerary ribs are a persistent problem. The staining used was not as good in the rabbit as in the rat, and there was an indication in the evaluation that there might already be some additional data available on this. If so members considered this would be helpful in determining whether or not to consider the supernumerary ribs adverse. This could be relevant to the classification of the substance.
6.6 Members also noted that the ‘historical’ control data on skeletal variations in wistar rats appeared to list data from a study conducted after the date of the study in the package. It was therefore debatable as to whether this should be included in the statistical analysis.
6.7 Members confirmed that if the requested COMET assay was negative, they were content with the reference values proposed in the draft assessment report.
6.8 There were no concerns for operator, worker, bystander, residents or children at the proposed AOEL .
6.9 The Committee heard that the plant metabolism was fairly consistent with differences in residues being observed being related to the PHI and therefore as a function of the speed of metabolism.One plant metabolite occurred in straw just below the threshold that would trigger a feeding study. Members agreed that as this was borderline, the overall metabolism picture was fairly clear, the specific toxicology data on the metabolite were not of concern and the metabolite itself was also a major rat metabolite, overall an additional vertebrate study was not justified to support the current uses. However the applicant should be advised that if future uses of the product resulted in higher residues of this metabolite, they might then need the additional feeding study.
6.10 On the possible need for a rotational crop study, members commented that the radiolabelled study provided would tend to result in higher residues than would occur in practice due to the confined nature of such studies. In the case of a root crop being sown following crop failure members were confident there would be no detectable residue arising from the GAP s under consideration, and therefore the need for additional data on rotational crops could be regarded as a possible confirmatory requirement in the light of any proposed changes to GAP.
6.11 The consumer risk assessment showed good margins on the proposed reference doses, and estimates of exposure for all other groups also fell within the proposed reference doses.
6.12 Members agreed that the environmental fate and behaviour assessment was acceptable.
6.13 On ecotoxicology, members had a question on the assessment of risk from the metabolite 3HDPM. This had been calculated appropriately for the risk from drainflow, but as the metabolite was also formed in sediment /water studies members considered it should be addressed for spray drift also. Calculations suggested that the risk assessment for 3HDPM based on entry via drainflow would cover that from formation in sediment/water, but this point should be made explicit in the document.
6.14 Members confirmed the assessment of efficacy presented. They agreed that the resistance management would need to be harmonised with other compounds in the fungicide resistance group – noting that there were differences in the way the groups were described in the evaluation. Members suggested that this be taken forward as a minor change at the next label printing for existing products in the group to give an example of this active substance (pyriofenone) as being in the same group. As a generic question members asked whether it was an appropriate strategy to allow approval of single active substance products in a relatively high resistance risk area. The secretary explained that whilst the committee usually considered single active substance products, not all of these were commercialised on approval. Many of them were maintained as ‘regulatory tools’ to support approvals for subsequent mixed active substance products.
Post meeting note: Following the meeting it was suggested that, as there appeared to be evidence of cross-resistance between the benzophenones (e.g. metrafenone) and the benzoylpyridines (e.g. pyriofenone), it was appropriate to avoid their repeated use to minimise the risk of resistance development. As the current fungicides of concern are in different sub-groups it would seem most appropriate to reference the parent group i.e. the aryl-phenyl-ketones (FRAC group U8) for clarity as this encompasses both the sub-groups referenced in the draft label amendments. It was suggested that CRD seek further guidance from FRAC in this regard.
6.15 Members noted that the applicant needed to update the documentation to reflect the new global harmonised classification system. They also drew attention to some minor typographical errors in the draft assessment report.
6.16 Overall members agreed that they needed to see the results of the COMET assay before they could make a recommendation on approval for this product.
7. 120 day emergency application for No Scald DPA 31 (contains 319 g / l diphenylamine) for use on stored apples [ACP 6 (350/2011)]
7.1 Dr Harris declared a non-personal specific interest.
7.2 Members considered this application for a 120 day emergency authorisation that would allow for continued use of diphenylamine to treat this season’s apples going into store. Members heard that diphenylamine has been used to prevent scald, a physiological disorder, for many years having been regulated originally under food additives legislation prior to approval under Control of Pesticides Regulations. The EU evaluation for annex I listing had identified a number of data gaps in the supporting package and as a result diphenylamine had not been included in Annex I. Approvals had now expired as a result. The Rapporteur Member State, Ireland, was currently evaluating a resubmission application.
7.3 Members confirmed that the emergency situation primarily concerned Bramley apple growers in Northern Ireland. These growers produce about half of the UK Bramley apple crop. Most of the remaining English growers have now invested in new stores, and these together with the use of an alternative control treatment, 1-MCP, meant reliance on diphenylamine was not as strong in England. Significant investment was necessary to modify existing stores in Northern Ireland, and the time required to develop these stores meant this would not happen quickly.
7.4 The FSA noted that one of the data gaps identified in the EU review was to address the possible formation of nitrosamines.There were a couple of literature studies that suggested this might be a possibility, and if so, clearly they would be concerned about the possible risk particularly as apple purees were widely used in baby foods.
7.5 Members confirmed that this is a data gap rather than evidence of a specific problem. Experience suggested that EFSA identified this gap to be addressed for all substances containing an amine group.Members noted that this was an emergency situation and in practice the risk posed was the same as had been posed over many years. Members suggested that it be made clear to the applicant that the further data identified by EFSA would be required before any future emergency application would be considered.
7.6 Members noted the case made in the Annex I evaluation that this product was used only on apples that were not processed. This was clearly not the case as the proposed use was on Bramley apples and the applicant for Annex I would need to address the data gaps on effects of processing in their re-submission.
7.7 Members heard that, in considering operator exposure, the evaluation for this emergency had used the default value of 100% dermal absorption in the absence of any specific data.Clearly this was an over-estimate, but as a result, estimated exposure exceeded the AOEL . Members heard that there were no specific exposure data available for this drenching procedure.They considered the equipment used and the process of moving the boxes of apples into and out of the treatment vessel. It was clear that there would be some limited handling of wet material in the process and therefore it was not appropriate to assume no exposure other than at mixing and loading stage. CRD had used data available for a similar ‘wet’ process of timber treatment.This involved timber loaded onto a bogie being passed into the treatment vessel and removed and manually handled to move to storage areas.This process was cyclical and exposures measured over a total 180 minute cycle. Exposures in the timber treatment model therefore probably underestimated the ‘handling’ part of the timber treatment cycle, but were considered likely to be an over-estimate of exposures in the apple drenching process as no direct handling of wet treated produce occurred because the boxes were moved by fork lift truck. There was considerable uncertainty about operator exposure, but the values presented were likely to be an over-estimate. A possible risk mitigation factor of reducing the operators exposure periods to 3 hours a day would be expected to reduce the exposure to levels below the AOEL . Members agreed with this approach, and noted that eye protection should be added to the proposed PPE requirements as the product was classified as an eye irritant.
7.8 Members agreed to recommend a 120 day emergency authorisation for this season only. The applicant should be advised that they were not minded to consider a future application, and it should be suggested that they use this opportunity to gather some realistic exposure data to support future use. The applicant should also be asked to widely publicise the additional restriction on exposure periods for this emergency use.
8. Combined Risk Assessment [ACP 13 (350/2011)]
8.1 Members heard that this paper was a report of one of a number of research projects commissioned by the FSA following the publication of the report on ‘Risk Assessment of Mixtures of Pesticides and Similar Substances’ Sept 2002 (the WiGRAMP report).The Committee on Toxicity had reviewed this research at a recent meeting and had passed this report to the ACP to consider whether it raised any regulatory concerns.
8.2 Members noted that the research highlighted a clear need for more detailed information on routes of exposure to pesticides both from dietary and other sources. Members commented that it was particularly important to note the paucity of data in some areas (eg biocidal product and veterinary medicine uses) that means it will be difficult to take this line of research much further.
8.3 Members agreed that the modelling used was an interesting approach, and a good attempt to use all of the available data, but noted that it had not been validated – eg. by comparison with biomonitoring. They suggested one approach might be to estimate exposures in an animal model. An alternative approach to validating the modelling for OPs might be to compare the results with the data held by HSL on measured OP metabolites. These data suggested that di-alkyl phosphate metabolites arising from non-occupational exposures were generally low, suggesting that ‘background’ exposures to OPs were not particularly significant in practice.
8.4 Members heard that this research used a simple pharmaco-kinetic model, but the details of that were not presented in this paper. CRD had assumed that it was probably the same as the pharmacokinetic model used by the same researchers in the Defra commissioned research on biomonitoring that the Committee had seen previously. If so it was known to be a relatively simple approach. Members agreed that it would be helpful if this could be clarified.
8.5 Members found it very surprising that the researchers had modelled exposure to sprays for substances that were only available as granules.They also noted some apparent inaccuracies in the information included on sheep dips and were concerned as to how ‘representative’ the compounds selected and exposures estimated were. Members were interested to note a number of ‘spikes’ in the exposure patterns, and commented that it would be interesting to consider the relevance of current ‘average’ estimates of exposure with these patterns of exposure.
8.6 Members heard that the modelling presented for ‘bystander’ exposure considered exposure to spray drift only, and the ‘spikes’ compared directly with those presented for the operators. It seemed likely therefore that the model used assumed the same bystander was exposed on each occasion that a particular spray was used. Members expressed some concerns about the way in which models were ‘linked’ overall with some of the individual overestimates of exposure then being magnified.
8.7 It was unclear how processing data had been handled in the modelling of consumer exposures. Members commented that significant amounts of data are available and the results suggested that some kind of adjustment had been included, but it was not transparent what had been done. It was also noted that the consumption data for infants were from 1986, and these had not been updated.Exposures via food seemed to be fairly negligible compared to the ADI , suggesting that perhaps dietary exposure was not a major contributor to estimates of combined exposure.
8.8 HPA noted that the estimated exposures for bystanders had been compared to the ADI in this modelling approach, whereas it would be more usual to compare exposures with the AOEL .
8.9 Members asked whether this modelling was restricted to UK pesticides as clearly the UK population was also exposed to residues of pesticides on imported produce.The report had used PRC data which included imported produce. For residues less than the reporting level the model used UK pesticide usage data to proportion these accordingly, but the equivalent process could not be done for imports.It was unclear what adjustments, if any, had been made for these results.
8.10 Members agreed to respond to the CoTthat this research was interesting, but there was a need for clarification of details, and much additional information to fill the current gaps before such an approach might be suitable for regulatory use.
8.11 Members also expressed their concern about the potential for this research to be misinterpreted. They therefore agreed to prepare a statement for the ACP website explaining their consideration of the research.
Action: Secretary to draft based on this discussion and circulate for agreement prior to publication
8.12 CRD explained that since this research had been commissioned, new EU legislation on MRLs and Plant Protection Products required aggregate and cumulative risk assessments to be completed when techniques became available.The European Commission had invested in research and a consortium led by the Netherlands and involving CRD , FSA and Fera from the UK was developing a project called ‘ACROPOLIS’ (Aggregate and Cumulative Risk of Pesticides On-Line Information System).This builds upon the existing dietary consumption model used by the Netherlands and was looking to add in non-dietary routes of exposure.This project was finding the same lack of information on biocides etc., both in terms of exposure and use patterns. EFSA also had a usage project looking at patterns of usage, and Fera were leading this work with contributions from the Netherlands Greece and CRD.This project was also looking at bystander and resident behaviour. Members noted this additional work.
9. Verbal update on the work of the Bystander Risk Assessment Working Group (BRAWG) and the Pesticides Adverse Health Effects Working Group (PAHES)
9.1 The Secretary explained that both working groups had met since the last ACP meeting.Reports were now under construction. Although both reports were running behind their original time-tables it was hoped that work would be completed before the end of the year.
10. Environment Panel Response to ACP comments on Buglife Report [ACP 12 (350/2011)]
10.1 The Chairman of the Environmental Panel introduced this short paper, explaining that the panel had discussed the ‘buglife’ report in detail. They had identified some gaps in the standard ecotoxicology package to address the risk to non-target insects and this was being taken forward in Europe. Members noted that this paper was mainly for their information.
11. The Open Meeting 2011 [ACP 11 (350/2011)]
11.1 Members considered items for possible discussion at the ACP open meeting 2011 to be held on Monday 14 November. Suggestions included the PAHES draft report; the review of respiratory sensitisation; honeybees and colony collapse; definition of endocrine disruptors; new aspects introduced to Plant Protection Regulation by Regulation 1107/2009.T hese will be forwarded to the Chairman for consideration.
11.2 Members agreed to include small groups again, and suggested consideration be given to using group discussion in the morning with plenary sessions in the afternoon.
Action: Secretariat to arrange suitable accommodation
12. FERA Lessons learned correspondence Japanese Knotweed [ACP 22 (350/2011)]
12.1 Members considered the correspondence received from Fera seeking ‘lessons learned’ from the consultation process associated with the release of a non-indigenous insect (Aphalara itadori) for control of Japanese Knotweed. Members commented only that it would be interesting to know how the release was progressing and whether any further evidence on the benefits of the release had been gathered.
Action: Secretary to write to FERA
13. Date of the next meeting:
ACP 351 is to be held on Tuesday 20 September 2011.
14. Any other business
14.1 Mortality and cancer incidence among British agricultural pesticide users, Frost et al, Occupational medicine June 27 2011
14.2 Members heard that this paper had just been published. It was of particular interest because it was the first report on this UK sprayer cohort. Initial findings highlighted that spray operators were overall healthier than the general UK population.There did not seem to be any particular pesticide related aspects to the more general causes of mortality recorded. The report highlighted a possible slight increase in the incidence of three types of cancer. Members agreed to send comments by email.
15. Information Papers
15.1 Members considered a number of information papers.
15.2 First UK Approval for the use of folpet – position paper [ACP 8 (350/2011)]
15.2.1 Dr Harris declared a personal specific interest and left the room during discussion of this item.
15.2.2 Members commented that the lack of specific risk assessments presented with this outline paper made it hard for them to use.They asked that future position papers of this type include more detail. They noted that the endpoints suggested use on grapes exceeded the AOEL and CRD confirmed that this use was not approved in the UK. Members noted that a 5m buffer zone had been required to protect the aquatic environment , and requested that the relevant risk assessment be made available. Members noted that labelling needed to be updated and queried the lack of eye protection when a risk of serious damage to eyes had been identified.
Post meeting note: The active substance is classified risk of serious damage to eyes, but the formulated product is not classified, so there are no requirements for additional protection.
15.3 Residues of OPs and metabolites [ACP 14 (350/2011)]
15.3.1 Members commented that this pilot study, also part of the FSA post-WiGRAMP research programme included 5 pesticides that had not been included in the combined risk assessment project.
15.4 Follow up letter to applicant [ACP 15 (350/2011)]
15.4.1 Members noted this correspondence and sought confirmation that there had been no changes in the agreed technical specification.This was confirmed.
15.5 Revised EU Evaluation Procedures [ACP 19 (350/2011)]
15.5.1 Members welcomed this short outline of current EU procedures and suggested that with some minor editorial work it would be a very helpful document to make available to all on the website.
J G Ayres
Date: 13 November 2011