Chairman: Professor J G Ayres
Members: Ms A Baker, Prof C Brown, Dr J Cherrie, Prof G Hawksworth, Prof C V Howard, Ms R Howell, Dr A Leake, Prof L Maltby, Prof P Matthiessen, Dr M McPherson, Prof C Ockleford, Dr D Osborn, Dr W Parker, Prof J Parry, Dr A Povey, Dr D Ray, Dr H Rees.
Assessors: Mr R Benson (FSA), Dr C Griffiths (SASA), Mr M Ward (PSD ), Mr M Williams (Welsh Assembly Government (WAG) ), Mr G Wilson (HSE ).
Advisers: Dr J Best (NE), Mr R Davis (PSD ), Dr L Hetherington (HPA), Mr B Maycock (FSA), Dr J Osman (HSE ), Dr R Turner (HSE ).
Secretariat: Ms J Wilder (PSD ) Secretary, Mr P Fisher (PSD ) Minutes Secretary, Mrs E Woodfine (PSD ) Secretariat
Visitors: Mr P Jarvis (for agenda item 8)
Other attendees: Dr R Brown (PSD ), Mrs S Burden (PSD ), Dr J Greenwood (PSD ), Mr P Hamey (PSD ), Mrs I Hoy (PSD ), Mrs W Leslie (PSD ), Mr R Mason (PSD ), Dr M Reed (PSD ), Ms T Roberts (PSD ), Mr A Warburton (PSD ).
1.1 Apologies were received from: Ms G Asbury (Food Standards Agency (FSA)) Dr M Camlin (DARDNI), Mr S Dyer (DH) Mr J Battershill (HPA) Dr T Boucard (EA) Dr K Wilson (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 the new members Dr Parker, Prof Parry, Dr Povey and Dr Ray to their first meeting. He also welcomed Mr Jarvis attending to present agenda item 8 and Dr Osman attending to present item 9
3. Agenda item 1:
3.1 a) 328th Meeting: Minutes [ACP 1 (329/2008)]
3.1.1 Agreed as drafted.
3.2 b) 328th Meeting: Detailed record of discussion [ACP 2(329/2008)]
3.2.1 Agreed subject to minor amendments. Members suggested the addition of a glossary to the website would be helpful
3.3 c) Record of the ACP open meeting 12th November 2007 ACP 16 (329/2008)]
3.3.1 Members confirmed that the bullet points already published on the website captured the main points of the meeting. This was therefore accepted as the finalised record of the meeting.
3.3.2 Two additional suggestions were made. It was agreed to suggest to PSD that a consumer/patients representative would be a helpful addition to the proposed human health working group. It was also agreed that Members would have name badges identifying them as ACP members at future open meetings of the Committee.
Action: Secretariat to add footnote to the record and to arrange badges in future
4. Agenda Item 2: Secretary’s report [ACP 3 (329/2008)]
4.1 The Secretary to the Committee reported that Ministers had accepted the advice given at the previous meeting.
5. Matters arising
5.1 a) NEMguard [ACP 26 (329/2008)]
5.1.1 Members heard that the applicant had appealed against the ACP conclusion at the 328th meeting that it was inappropriate to recommend approval of this or any other pesticide product in the absence of clear evidence of its efficacy.
5.1.2 Members considered the written case presented by the applicant and the additional written comments from a nematologist provided at the applicant’s request.
5.1.3 Members agreed that there is a huge amount of spatial and temporal variability in soil pests including nematodes. From the information submitted in the appeal it was very difficult to see whether the variation in pest populations was accounting for the variable results, specifically whether the pattern of plant damage was associated with variable pest population levels. Members felt that such assertions needed to be interpreted with caution. Members were aware of HDC funded data that would counteract the case that the level of damage is related to population levels. (ref HDC Project FV 232 ‘Carrots and parsnips: review and investigation of factors influencing crop damage by plant-parasitic nematodes’)
5.1.4 Overall members concluded that there was nothing in the case presented that would support a change in view from the conclusion reached at the last meeting that further data were required before an approval could be considered.
5.1.5 Members suggested that future trials could take account of populations in individual plots, with counts before and after treatment, and plot these changes against levels of plant damage. As the same plant damage can also be caused by other organisms such as Pythium it was important not to rely solely on impact on plant effects as a means of measuring efficacy. Members offered to provide advice on protocols or sampling procedure if required.
5.1.6 Members then considered the more generic issue of the appropriate level of efficacy for approval of ‘alternative’ products such as this. It was suggested that perhaps a provisional approval could be considered not-withstanding the need for more data and then the market could be allowed to decide whether the product was worthwhile using. Others noted that if an applicant can demonstrate some benefit from the use of an ‘alternative’ product the agricultural industry can make use of this in integrated programmes of control measures. They don’t necessarily need the high levels of efficacy required for more conventional approved products. PSD confirmed that the current standards require a consistent effect in order that an appropriate label recommendation can be formulated, but it was difficult to see how an applicant could be required to demonstrate how their product fitted into an integrated approach. Some members then suggested that perhaps a label warning could be added to the product indicating that there are concerns about the efficacy of the product. Overall members concluded that it was important to give the market clear information on which they could base their decisions. In addition there was a general principle that chemicals should not be released into the environment with no evidence of benefit. This principle underlay much of the legislation on chemicals including the pesticides legislation and REACH. Members concluded that in accordance with these principles they would still need evidence of efficacy as previously advised.
5.2 b) Ipconazole [ACP 18 (329/2008)]
5.2.1 Members noted the progress made during a conference call between certain members on the various toxicology issues and agreed this had been a good way to progress these discussions. Members confirmed that the studies designed to investigate endocrine effects had been based on similar effects of related compounds. They noted that further information was still awaited on the eye effects recorded.
5.2.2 Members also heard that FRAG had recently been consulted about the resistance risk from the use of seed treatment with fungicidal active substance that could persist and have effects on foliar disease organisms. Members agreed they did not need to refer the matter again for further advice.
5.2.3 Finally members had confirmed that there was no concern that there may be disruption of hormones controlling the ‘re-setting’ of the bird breeding cycle in the autumn, and thus restricting use to the autumn would provide an appropriate risk management strategy for the seed treatment.
5.3 c) Amisulbrom [ACP 27 (329/20080]
5.3.1 The Committee heard that following discussion at the 325th Meeting of the ACP, the applicant had provided a confirmatory mouse bone marrow micronucleus study. Members agreed that this study showed a clear negative result, confirming that amisulbrom was not genotoxic. However it was noted that only a single dose and single sample time had been used and with hind sight it might have been more appropriate to test the liver.
5.4 d) Other Matters Arising [ACP 5 (328/2007)]
5.4.1 The Secretary asked Members’ views on the format and content of the 2007 Annual Report, and advised on the minimum requirements that are set out in legislation. In accordance with the ACP ’s wish that a more reader friendly approach is adopted, Members agreed that the Report should include a section on what the ACP is, and what its work involves, and information about the year’s work including three case studies detailing discussions on IPU, Chlorpropham and Candida.
5.4.2 Members noted the progress on other matters arising from previous meetings.
6. Application for Provisional approval of Envidor containing spirodiclofen as a horticultural insecticide and acaricides for use on apples and pears [ACP 10 (329/2008)]
6.1 Dr Ray declared a personal non-specific interest. He had advised this company on a different product. He therefore participated in discussion only in response to questions from the Chairman.
6.2 PSD reminded the Committee that they had based their consideration of this application on the draft assessment report prepared by the EU rapporteur member state. This reduced the cost of the evaluation and thus encouraged earlier application to the UK for approval of products for what were minor uses in the UK . PSD had taken note of the concerns raised at the previous discussion in March 2007 and the applicant had provided some additional information to try and resolve these concerns. PSD had drawn together this new information together with the original assessment, amendments made by the Rapporteur and further clarification by PSD into a single document to make consideration more straightforward. Members commented that PSD had done a good job in drawing together these various sources of information and they were much more reassured about the toxicology.
6.3 The mechanistic data were reassuring, and members confirmed that in addition there was no evidence of redox stress.
6.4 The developmental neurotoxicity study was clearly negative despite the use of an overly sensitive statistical method.
6.5 Members noted that adrenal vacuolation had been identified in dogs in three studies. Taken together the data indicated a possibly steep dose response and they suggested that care may be needed when using the NOAEL of 50ppm. PSD responded that they had considered the raw data taking account of the pathologists’ severity of grading. PSD considered that a comparison of severity of findings and adrenal weight data across the studies provided reassurance that 50ppm was the NOAEL and agreed to provide this fuller analysis of the data to members after the meeting. Members also asked for information to be included as to whether the vacuolation was in the zona fasciculata or the zona glomerulosa of the adrenal.
Action: PSD to send evaluation to toxicology members
6.6 Turning to the genotoxicity data members noted that spirodiclofen had been concluded to be a non-genotoxic compound. Whilst there was a clearly negative in vivo study, this tested a single concentration at three sampling times. There were some reports in the in vitro data indicative of equivocal findings. If this were the case they would usually expect to see a second in vivo study considering the liver. PSD agreed to send the raw data to the relevant member after the meeting for advice as to whether a second in vivo study was required.
Action: PSD to send the raw data
6.7 FSA noted that no NOAEL had been identified in the mouse chronic study, and asked whether members were content there was an adequate margin of safety between the ADI proposed and the LOAEL derived from the mouse study. Members confirmed they were content and there did not seem to be a need to propose an additional safety factor.
6.8 Overall members concluded that, provided toxicologists were reassured by the further data to be considered outside the meeting, a provisional approval could be granted. There was no requirement to reconsider this application at the next meeting if the evaluation was satisfactory.
7. Application for the approval of Emerger containing aclonifen as an agricultural herbicide for use on sunflowers [ACP 11 (329/2008)]
7.1 Members considered an application for the approval of Emerger containing aclonifen as an agricultural herbicide for use on sunflowers. Aclonifen is a herbicide which has never been approved in the UK but is approved in a number of other EU Member States. It is currently under review in the EU with Germany as the lead or ‘rapporteur’ Member State. This application was made for UK approval, prior to an EU decision on Annex I inclusion.
7.2 Members heard that the metabolism studies had only labelled the molecule on one ring and the applicant had provided a case that the metabolites formed by cleavage between the rings would be phenol and /or hydroquinone for which mammalian metabolism was well known. Members were aware that the Committee on Mutagenicity (COM) had considered hydroquinone. Although it is a genotoxic compound, via the oral route it was known to be conjugated and excreted and the COM had concluded that a threshold approach to risk assessment was appropriate. However it was not known whether hydroquinone was formed in the metabolism of aclonifen in the rat and if so whether it conjugated. Members were reassured that it was well known that human metabolism was very good at conjugating these compounds and noted that hydroquinone was known to be nephrotoxic to the rat. The long term rat studies showed no evidence of similar problems after exposure to aclonifen. The in vitro genotoxicity data were negative and the in vivo study was also negative although there was no direct evidence that the bone marrow had been exposed. There was however evidence that aclonifen had been absorbed in this study as it had reached the urine. However members agreed that there was an uncertainty which could be addressed relatively simply with some further in vitro data considering relative production of phenol/hydroquinone in rodent (probably rat) and human hepatocytes. If these data did not indicate a concern for humans this would confirm the risk assessment presented. However if there were a concern identified by this study members suggested expert advice be sought from the COM.
Action: PSD to seek further data
7.3 Members confirmed that the estimate of operator exposure was at the AOEL using POEM and additional reassurance was provided that actual exposure was likely to be lower than this from both a monitoring study and the German model.
7.4 Members heard that the residues assessment was acceptable and the estimated consumer intake would be very low – less than 1% ADI for all consumer groups.
7.5 Members agreed with the assessment of soil dissipation presented and confirmed that the calculation performed to estimate accumulation was acceptable. Members noted that the EU DAR presented estimates for predicted environmental concentrations in surface water (PECsw) using both a buffer zone to reduce spray drift and a vegetated strip to intercept surface run-off. Members sought confirmation as to the basis of the estimate used in the UK specific risk assessment. PSD confirmed that the standard UK approach for first tier and higher tier assessments had been undertaken and agreed to clarify the detailed assumptions made particularly in considering run off by correspondence after the meeting.
Action: PSD to provide the original modelling
7.6 Members then considered the risk assessment for aquatic species. The risk assessment using the endpoint taken from the fish early life stage study was below the EU trigger value of 10 when a 5m buffer zone was assumed. Members noted that PSD had discounted this study and had taken the results of two further chronic fish studies into account as there had been no effect on hatching (the critical stage covered only by the early life stage study). Members considered that contrary to the PSD assessment there was evidence of a dose response on growth in the early life stage study, although they agreed the effects seen were only moderate. If the endpoint of this study were used for risk assessment the TERs are not acceptable. Members also noted that the risk to algae was acceptable only following refinement, but both the median HC5 and 3rd most sensitive species approaches had been used to refine the data and both approaches resulted in an acceptable TER . However, if the lower limit HC5 was used the risk was unacceptable. It could be argued that this was the most appropriate approach to refine the assessment. The risk to aquatic plants had also required a study when sediment was present to refine the risk. Overall members agreed that the aquatic risk assessment was quite marginal and the clarification of the PECsw would be important in resolving the issue.
Action: Further discussion with PSD on the approach adopted to the aquatic risk assessment
7.7 Members noted that a lower dose of this residual pre-emergence herbicide was proposed for use in the UK than had been considered in the EU DAR. They agreed that the efficacy data confirmed activity, but against a reduced spectrum of weed species. It would have a particularly important use in combination with partners to control a range of UK weed species. Members noted the resistance risk assessment and the conclusion that no specific risk management strategy would be required.
7.8 Members noted that other aspects of the application were acceptable. They agreed that if the outstanding points could be clarified quickly, a provisional approval could be considered without the application returning to the next meeting as they were aware that the season of use was close.
8. Draft CIPC Stewardship Plan – Chlorpropham [ACP 14 (329/2008)]
8.1 Prof Parry declared a personal specific interest as he had prepared a review of published literature on this substance for another client. As this had no bearing on this item he was allowed to remain in the meeting, but took no part in the discussion of this item.
8.2 Members heard that, following on from advice given at the 328th Meeting, the industry had responded quickly, and had taken immediate action in forming a stewardship group and amending labels.
8.3 The ACP welcomed this very positive response from the applicants, and were impressed with the detail provided. Members agreed that accurate information as to what dose of CIPC had been applied to potato stores was required and that the recording required in line with assured produce requirements should be appropriate. In response to a question, PSD confirmed they would be sending information to the taskforce on the sampling protocol to be followed by April 2008 and they expected that the resultant residues monitoring data would be made available to the PRC by July 2008.
8.4 Members noted the additional information provided about the cow feeding study considering the use of peel in animal fodder. PSD confirmed that despite the livestock feeding study using rates equivalent to 1555mg/kg CIPC in potato peel, the animal feed did not drive the risk assessment
8.5 Overall members confirmed that approvals could continue subject to the restrictions agreed at the previous meeting.
9. EU Procedures Update [ACP 7 (329/2008)]
9.1 Members received a presentation detailing changes in European procedures for the approval and re-registration of active substances that were designed to ensure completion of the review process by the end of 2008.
9.2 The Committee recognised the challenging nature of the EC proposals, and stressed the need for careful consideration of important gaps in pest control for both major and minor crops that may result from the review process.
9.3 Members also noted that a peak of annex I decisions would inevitably result in a peak of re-registration applications and suggested possible methods of prioritising these. PSD noted that the approach adopted would largely depend on the strategies used by the applicants, and PSD were working with applicants to encourage a planned approach.
9.4 The ACP were appreciative of the presentation and asked to be kept informed of progress.
10. Problems over recycling of pesticides containers [ACP 8 (329/200)]
10.1 The Chairman welcomed Mr P Jarvis who gave a short presentation demonstrating the problems of recycling pesticide containers. Members heard that farmers are no longer allowed to burn containers and that the environment agency had agreed that (following triple rinsing) clean empty containers no longer had to be considered hazardous waste and could be recycled.
10.2 Members noted the practical difficulties encountered in the recycling process some of which could be related to container design. They agreed that there was a need to improve the rate at which containers are recycled, whilst keeping operator exposure to a minimum. It would be important that stakeholders were engaged in any changes proposed and the ACP was pleased to hear that the Pesticides Forum would be receiving a similar presentation. It was also suggested that the Voluntary Initiative would be important in taking forward any change.
10.3 The Committee asked PSD to report back to the next meeting on current guidance on container design, in order to consider amendments to encourage the use of recycling initiatives.
11. Estimating the prevalence and incidence of pesticide-related illness presented to General Practitioners in Great Britain [ACP 17 (329/2008)]
11.1 Members noted that this research report would be published by the HSE in February 2008. [link to report]. The research had been commissioned following cross-departmental consideration of possible sources of information on human health impacts, where it was noted that obtaining information from GPs had not been explored. It was recognised by departments at the outset that that this would present quite a difficult challenge, and indeed the research has proved difficult to do.
11.2 Members heard some of the practical difficulties encountered in undertaking this research and agreed that reports from GPs would not be an appropriate method of routinely monitoring possible ill health associated with pesticide exposure.
11.3 Members observed that there was a possible selection bias both in the GPs participating in the study and in the patients taking part in the interviews. Whilst the GPs surgeries were distributed across the country, it was noted that surgeries in the major agricultural area East Anglia were not well represented, whilst surgeries in Central Wales seemed to be well represented. It was thus possible that GPs with an existing particular interest in this topic (possibly as a result of their involvement with earlier sheep dip studies) might have been more likely to opt to join this research project. It was also not possible to tell from the available data whether the recorded instances of ill-health were clustered in particular surgeries or more widely distributed.
11.4 Members noted that of the 59000 consultations assessed in the project, about 42 patients had visited the GP due to their concerns related to pesticides. About 20 were judged by the GP as having health effects that were likely to be related to pesticide exposure. This information provides confirmation that there is a small proportion of the population that has concerns about the possible impact of pesticides on their health, but the small numbers mean that it is difficult to use the data to draw firm conclusions about the actual incidence of ill health being reported at a National level. Indeed the very low percentages recorded as possibly affected by pesticides could have occurred by chance alone. However Members agreed that it was not appropriate to use the data to conclude that there is no problem of ill health. Rather it was illustrative of the level of uncertainty in the data.
11.5 Members noted that medical students receive virtually no training in toxicology, and indeed most practicing GPs are also unlikely to have received any specific training in this field. The study provides no detail as to the basis for the GPs recorded decisions and thus uncertainty has to remain as to how the GPs attributed a diagnosis or symptom to a putative pesticide exposure. There is no information as to whether any of the patients were subsequently referred to consultants and if so, whether there was any confirmation of the diagnoses. Ethical agreement had not been sought to allow such individual patient follow-up as a part of this study. Members were aware from other studies involving GPs in occupational health issues that it was important to ensure that the GPs participating receive appropriate training in the relevant expertise. It is not possible to determine from this study whether the participating GPs had received adequate training in toxicology in the past and indeed Members noted some differences presented in the data which are indicative of possible behavioural differences between GPs.
11.6 Members noted the use of pesticides in the home or garden was common with about 40% of patients interviewed having used a product during the previous week. Members noted with concern that about 40% of these patients had not used pesticide products in accordance with their labels. This was in line with earlier research and emphasised the importance of particular care being given when considering the approval of pesticides for use in the home and garden.
11.7 The ACP agreed that as the paper was likely to be of wider interest they would publish a response to the research at the time of its publication.
12. IGHRC Draft Guidance Document ‘Chemical Mixtures: A Framework for Assessing Risks’ [ACP 20 (329/2008)]
12.1 Members welcomed this draft guidance document from the Interdepartmental Group on Health Risks from Chemicals.
12.2 Members agreed that this was a scholarly paper and was likely to be very useful in the future. They noted that the potential hazard of low dose disruption of gene expression in the embryo (second messenger disruption) had not been addressed. Furthermore it was possible that the penultimate paragraph of the executive summary might be misunderstood as there was published data (e.g. Brian et al. 2007 Env Sci Technol vol 41, p337-344) showing that exposures at less than the threshold dose could result in an additive effect. Additive effects of low doses were also explored in a paper by Kortenkamp et al (Env Health Perspectives, 2007, 115, 106-114) which was circulated to members for information.
12.3 Members noted that the paper considered the additive effect by mode of action rather than the more restrictive common mechanism approach favoured in the USA .
12.4 Members recalled that PSD was developing methodology to consider the cumulative risk assessment of the organophosphates, and PSD explained that they had been awaiting both the completion of the EU reviews and the UK consumption database which was understood to be available soon from the FSA. It was hoped that this project would therefore soon be able to be progressed further.
12.5 Members agreed to send further written comments to the Secretariat, and these would be co-ordinated into an agreed Committee response.
13. Updated Code of Practice for Scientific Advisory Committees [ACP 20 (329/2008)]
13.1 Members noted a revised version of the Government Office for Science Code of Practice for Scientific Advisory Committees.
14 Date of Next Meeting
14.1 Tuesday 11th March 2008 , commencing 11.00am , at the Monk Bar Hotel, York.
15 Any Other Business
15.1 Members considered the items for information received since the last meeting.
J G Ayres