Conclusion on the peer review of the pesticide risk assessment of the active substance Cydia pomonella granulovirus (CpGV) 1

Transcription

1 EFSA Journal 2012;10(4):2655 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance Cydia pomonella (CpGV) 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Germany, for the pesticide active substance Cydia pomonella are reported. The context of the peer review was that required by Commission Regulation (EC) No 2229/2004, as amended by Commission Regulation (EC) No 1095/2007. The conclusions were reached on the basis of the evaluation of the representative uses of Cydia pomonella as an insectcide on pome fruit and nut trees. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. A concern is identified. European Food Safety Authority, 2012 KEY WORDS Cydia pomonella, Cydia pomonella GV, CpGV, peer review, risk assessment, pesticide, insecticide 1 On request from the European Commission, Question No EFSA-Q , approved on 4 April Correspondence: pesticides.peerreview@efsa.europa.eu Suggested citation: European Food Safety Authority; Conclusion on the peer review of the pesticide risk assessment of the active substance Cydia pomonella. EFSA Journal 2012;10(4):2655. [40 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella SUMMARY Cydia pomonella (GV) is one of the 295 substances of the fourth stage of the review programme covered by Commission Regulation (EC) No 2229/2004 3, as amended by Commission Regulation (EC) No 1095/ Cydia pomonella GV was included in Annex I to Directive 91/414/EEC on 1 May 2009 pursuant to Article 24b of the Regulation (EC) No 2229/2004 (hereinafter referred to as the Regulation ) and has subsequently been deemed to be approved under Regulation (EC) No 1107/2009 5, in accordance with Commission Implementing Regulation (EU) No 540/2011 6, as amended by Commission Implementing Regulation (EU) No 541/ In accordance with Article 25a of the Regulation, as amended by Commission Regulation (EU) No 114/2010 8, the European Food Safety Authority (EFSA) is required to deliver by 31 December 2012 its view on the draft review report submitted by the European Commission in accordance with Article 25(1) of the Regulation. This review report was established as a result of the initial evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Germany being the designated rapporteur Member State submitted the DAR on Cydia pomonella GV in accordance with the provisions of Article 22(1) of the Regulation, which was received by the EFSA on 15 April The peer review was initiated on 24 April 2008 by dispatching the DAR to the notifiers Arysta LifeScience S.A.S., Sipcam S.p.A., and the CpGV Task Force, and on 21 January 2009 to the Member States for consultation and comments. Following consideration of the comments received on the DAR, it was concluded that EFSA should conduct a focused peer review in the area of ecotoxicology and deliver its conclusions on Cydia pomonella GV. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of Cydia pomonella GV as an insecticide on pome fruit and nut trees, as proposed by the notifiers. Full details of the representative uses can be found in Appendix A to this report. In the areas of identity of the microorganism, biological properties, physical and technical properties and methods of analysis, the following data gaps remain: level of contaminating microorganisms, data gap for the relevant impurity in the Arysta source, data gaps for the formulation Carpovirusine and data gaps for the methods of analysis for quantification and identification. In the area of mammalian toxicology, there is no data gap and no critical area of concern. The consumer risk assessment can be finalised and a quantitative assessment is not necessary. The information on fate and behaviour in the environment is sufficient to characterise the competitiveness / persistence of Cydia pomonella GV and its dispersion characteristics in the context of the representative uses assessed. A low risk to birds, mammals, aquatic organisms, non-target arthropods, earthworms and soil microorganisms was concluded. A low risk from direct toxicity to bees was also concluded, however, a data gap for further information to address the risk to bee brood was identified OJ L 379, , p.13 OJ L 246, , p.19 OJ L 309, , p.1 OJ L 153, , p.1 OJ L 153, , p.187 OJ L 37, , p.12 EFSA Journal 2012;10(4):2655 2

3 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background... 4 The identity of the microorganism and the properties of the formulated product... 6 Conclusions of the evaluation Identity of the microorganism/biological properties/physical and technical properties and methods of analysis Mammalian toxicity Residues Environmental fate and behaviour Fate and behaviour in the environment of the microorganism Fate and behaviour in the environment of any relevant metabolite formed by the microorganism under relevant environmental conditions Ecotoxicology Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Soil Ground water Surface water and sediment Air List of studies to be generated, still ongoing or available but not peer reviewed Particular conditions proposed to be taken into account to manage the risk(s) identified Concerns Issues that could not be finalised Critical areas of concern Overview of the concerns identified for each representative use considered References Appendices EFSA Journal 2012;10(4):2655 3

4 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella BACKGROUND Cydia pomonella GV is one of the 295 substances of the fourth stage of the review programme covered by Commission Regulation (EC) No 2229/2004 9, as amended by Commission Regulation (EC) No 1095/ Cydia pomonella GV was included in Annex I to Directive 91/414/EEC on 1 May 2009 pursuant to Article 24b of the Regulation (EC) No 2229/2004 (hereinafter referred to as the Regulation ) and has subsequently been deemed to be approved under Regulation (EC) No 1107/ , in accordance with Commission Implementing Regulation (EU) No 540/ , as amended by Commission Implementing Regulation (EU) No 541/ In accordance with Article 25a of the Regulation, as amended by Commission Regulation (EU) No 114/ the European Food Safety Authority (EFSA) is required to deliver by 31 December 2012 its view on the draft review report submitted by the European Commission in accordance with Article 25(1) of the Regulation (European Commission, 2008). This review report was established as a result of the initial evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Germany being the designated rapporteur Member State submitted the DAR on Cydia pomonella GV in accordance with the provisions of Article 22(1) of the Regulation, which was received by the EFSA on 15 April 2008 (Germany, 2007). The peer review was initiated on 24 April 2008 by dispatching the DAR to the notifiers Arysta LifeScience S.A.S., Sipcam S.p.A., and the CpGV Task Force, and on 21 January 2009 to the Member States for consultation and comments. In addition, the EFSA conducted a public consultation on the DAR. The comments received were collated by the EFSA and forwarded to the RMS for compilation and evaluation in the format of a Reporting Table. The notifiers were invited to respond to the comments in column 3 of the Reporting Table. The comments were evaluated by the RMS in column 3 of the Reporting Table. The scope of the peer review was considered in a telephone conference between the EFSA, the RMS, and the European Commission on 10 October On the basis of the comments received and the RMS evaluation thereof it was concluded that the EFSA should organise a consultation with Member State experts in the area of ecotoxicology. The outcome of the telephone conference, together with EFSA s further consideration of the comments is reflected in the conclusions set out in column 4 of the Reporting Table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in consultation with Member State experts, and additional information to be submitted by the notifiers, were compiled by the EFSA in the format of an Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the Evaluation Table, together with the outcome of the expert discussions where these took place, were reported in the final column of the Evaluation Table. A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in March This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulation evaluated on the basis of the representative uses as an insecticide on pome fruit and nut trees, as proposed by the notifiers. A list of the relevant end points OJ L 379, , p.13 OJ L 246, , p.19 OJ L 309, , p.1 OJ L 153, , p.1 OJ L 153, , p.187 OJ L 37, , p.12 EFSA Journal 2012;10(4):2655 4

5 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella for the active substance as well as the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the Peer Review Report, which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The Peer Review Report (EFSA, 2012) comprises the following documents, in which all views expressed during the course of the peer review, including minority views, can be found: the comments received on the DAR, the Reporting Table (17 October 2011), the Evaluation Table (4 April 2012), the report of the scientific consultation with Member State experts, the comments received on the assessment of the points of clarification (where relevant), the comments received on the draft EFSA conclusion. Given the importance of the DAR including its addendum (compiled version of March 2012 containing all individually submitted addenda (Germany, 2012)) and the Peer Review Report, both documents are considered respectively as background documents A and B to this conclusion. EFSA Journal 2012;10(4):2655 5

6 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella THE IDENTITY OF THE MICROORGANISM AND THE PROPERTIES OF THE FORMULATED PRODUCT The Mexican isolate used in the products Madex (Andermatt Biocontrol) and Granupom (Probis GmbH) is deposited since 2005 at the German Collection of Microorganisms and Cell Cultures (DSMZ), Mascheroder Weg 1b, D Braunschweig, Germany. Virus accession number: GV Sipcam S.p.A. deposited the Cydia pomonella GV Mexican isolate in 2005 at the National Collection of Pathogenic Viruses, Health Protection Agency, Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 0JG, UK. Virus accession number: Arysta LifeScience S.A.S. deposited their Cydia pomonella GV Mexican isolate in 2005 at the German Collection of Microorganisms and Cell Cultures (DSMZ), Mascheroder Weg 1b, D Braunschweig, Germany. Virus accession number: GV The representative formulated products for the evaluation were Madex a suspension concentrate formulation (SC) containing 3 x granules/l, Granupom a SC formulation containing 2.2 x10 13 granules/l, Virgo a SC formulation containing 2x10 13 granules/l and Carpovirusine a SC formulation containing 1x10 13 granules/l. The evaluated use for the formulations Granupom, Virgo and Carpovirusine is as a spray application to pome fruit. The evaluated use for the formulation Madex is as a spray application to pome fruit and nut trees. Full details of the GAP can be found in Appendix A. CONCLUSIONS OF THE EVALUATION 1. Identity of the microorganism/biological properties/physical and technical properties and methods of analysis. The data provided on the microbial contamination of the materials does not show compliance with international standards and a data gap is identified. As viruses cannot produce toxins there is no issue with this. The Arysta source contains the relevant impurity formaldehyde and a data gap has been set for a validated method of analysis and 5 batch analysis data. At this time no maximum level can be proposed. For the formulation Carpovirusine the following data gaps are identified: flash point, autoflammability, viscosity and density. For the identification method data are required to demonstrate the specificity of the method. Validation data are needed for the quantification method for both the technical material and formulated product. Validation data are also needed for the methods used to analyse the contaminating microorganisms. Methods for products of plant or animal origin and the environment are not required as these viruses are not pathogenic and will not produce any toxins. 2. Mammalian toxicity With regard to the batches used in the toxicological studies, no further information is required, provided that adequate quality control is undertaken on the batches produced. Microbial contaminants that are potentially pathogenic for humans have to be kept at levels internationally recognised as acceptable (see data gap in section 1). Formaldehyde has to be considered as a toxicologically relevant impurity. For the viruses, there is no production of antimicrobial substances, toxins or secondary metabolites. Additionally, since viruses are not sensitive to antibiotics or other antimicrobial drugs, they cannot EFSA Journal 2012;10(4):2655 6

7 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella become resistant to these substances or spread resistance. Viruses can only be susceptible to virucidal or virustatic drugs acting mostly by inhibiting certain enzymes. However, there is no evidence that resistance may be transmitted from one virus isolate to another. No adverse effects were shown in people who were involved in research, development, manufacturing and formulation of pest control products containing Cydia pomonella GV. Epidemiological evidence and studies in human volunteers didn t show any increase in disease frequency or adverse effect after exposure to baculoviruses. Several tests were performed with Cydia pomonella GV in order to detect its sensitising potential, with positive results in one of them (Magnusson and Kligman). In the absence of a reliable test for sensitisation, as for other microorganisms, the following warning phrase is applicable, related to the potential to provoke allergic reactions by inhalation as well as by dermal exposure: Microorganisms may have the potential to provoke sensitising reactions. The available acute toxicity data for several baculoviruses confirm that these viruses do not infect vertebrates and can be considered as non-pathogenic and non-toxic. No adverse effect was induced after oral, inhalation (nose-only exposure) or intraperitoneal administration of Cydia pomonella GV. The available information for short-term toxicity was obtained from published studies with Cydia pomonella GV or other baculoviruses in mice, guinea pigs, rats, dogs and rhesus monkeys. These data give no indication of infection with virus replication, and show no adverse effects related to the virus upon repeated exposure irrespective of the application route. Cydia pomonella GV was not clastogenic in vivo after single or repeated dietary exposure of hamsters. Additionally it did not replicate in vitro in human cells and did not damage these cells. Some seroconversion (antibody formation) may occur in different species including man but this is considered a rather unspecific immunological response (not at the usual antigen binding site of the IgG) and not indicative of a productive infection with virus replication. Considering the available information and toxicological data for the different formulations, no further studies are required and results of the studies with Granupom, Virgo and Carpovirusine can be extrapolated to the microorganism. Considering the lack of pathogenicity of the baculoviruses in mammals, it is considered not necessary to derive (and not possible to be derived based on the available data) reference values for Cydia pomonella GV. Therefore, no operator, worker and bystander exposure estimates are needed. 3. Residues As these viruses are not pathogenic to humans and they will not produce any toxins it can be concluded that the consumer risk assessment is finalised. A quantitative risk assessment is not necessary. 4. Environmental fate and behaviour 4.1. Fate and behaviour in the environment of the microorganism No information has been provided in relation to potential interference of Cydia pomonella GV with the analytical systems for the control of the quality of drinking water provided for in Directive 98/83/EC 15 (see specific Annex VI decision making criteria in Directive 2005/25/EC 16 ). However, as a virus, Cydia pomonella GV is unlikely to interfere with the analytical systems. 15 OJ No L 330, , p OJ No L 90, , p.1. EFSA Journal 2012;10(4):2655 7

8 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella No information has been provided on the potential transfer of genetic material from Cydia pomonella GV to other organisms. Replication of baculoviruses in mammalian cells has never been shown (EFSA, 2011). No studies on persistence and multiplication in soil of Cydia pomonella GV are available. The assessment presented in the DAR is based on the scientific publications submitted by the notifiers that included data on baculoviruses in general. Cydia pomonella GV has a high sensitivity to UV light, 98% inactivation in two days. However, further down in the soil layers Cydia pomonella GV can be persistent and accumulative after both natural epizootic events (should these ever occur) and anthropogenic application. In soil es can persist for months or years, respectively, because moisture and temperature changes cause little inactivation under field conditions. Since viruses do not have metabolic activity outside host cells and they are not able to proliferate themselves, the multiplication of Cydia pomonella GV depends on the population density of their host. Mineralisation is not proven. Cydia pomonella GV is to be considered as persistent in soil as other baculoviruses and es have been shown to be persistent in soil for months or years. PEC soil calculations are presented in Appendix A. No studies on persistence and multiplication in water of Cydia pomonella GV are available. Granuloviruses precipitate quickly in aquatic system. An activity in sediment remaining for a length of time comparable to that in soil cannot be excluded. PEC surface water calculations are presented in Appendix A. No studies on mobility in soil of Cydia pomonella GV are available. Baculoviruses including es are able to leach through a column of sieved soil to some degree. Even though es and hence also Cydia pomonella GV display leaching potential in soil, no groundwater risk assessment is necessary since Cydia pomonella GV are neither pathogenic nor toxic to humans. Except at the time of spraying Cydia pomonella GV would not be expected to be present in air. Granuloviruses are sensitive to UV light. Occlusion bodies of es can be considered as suspended solid particles that are non-volatile Fate and behaviour in the environment of any relevant metabolite formed by the microorganism under relevant environmental conditions Virus metabolites can not be formed in environmental matrices. Viruses do not produce metabolites, they can only modify host cell metabolism, as they self-replicate within host organisms. 5. Ecotoxicology Ecotoxicological data presented in the DAR were conducted using Cydia pomonella GV. Information from the literature was also used to address some of the ecotoxicological risk assessments. The issue of using data for other baculoviruses to support the risk assessment for Cydia pomonella GV was discussed at an expert meeting (Pesticides Peer Review Meeting M5). The experts concluded that it was reasonable to extrapolate information on toxicity, infectivity and pathogenicity from other baculoviruses on the basis of the mode of action and information given in the OECD consensus document (OECD, 2002). A 5-day avian infectivity and pathogenicity study with Cydia pomonella GV was available and no indications of infectivity or pathogenicity were observed. Using the NOEL derived from the study, a risk assessment was sufficient to demonstrate a low risk to birds. Further information taken from the literature also confirmed a low risk to birds from the representative uses of Cydia pomonella GV. Information in the mammalian toxicological assessment indicated absence of toxicity, infectivity and pathogenicity. It was therefore possible to conclude a low risk to wild mammals from Cydia pomonella GV. Toxicity data with Cydia pomonella GV were available for fish, aquatic invertebrates, algae and aquatic plants and indicated low direct toxicity. Using the available surface water PEC values a low EFSA Journal 2012;10(4):2655 8

9 Peer Review of the pesticide risk assessment of the active substance Cydia pomonella risk to aquatic organisms from direct toxicity was demonstrated. The risk to aquatic organisms from infectivity and pathogenicity was discussed at an expert meeting (M5). A literature paper, in which the potential for pathogenicity of a nuclear polyhedrosis virus (NPV baculovirus) to fish was investigated, was summarised in the DAR. The study did not indicate any adverse effects. In one of the available acute fish toxicity studies, all the fish in the highest test concentration were observed to have a dark pigmentation at the study termination. No pigmentation effects were reported in the two additional acute fish studies which were available. The experts considered that the pigmentation could be an indication of an effect, but not necessarily a sign of infectivity and pathogenicity. Overall, on the basis of the available literature information a low risk to fish from pathogenicity could be concluded. A literature paper investigating chronic effects in Daphnia magna of a NPV baculovirus was summarised in the DAR. The experts concluded that the information was sufficient to conclude a low risk to aquatic invertebrates from infectivity and pathogenicity. A bee acute oral and contact toxicity study with Cydia pomonella GV was available. On the basis of low toxicity a low risk was concluded for direct toxicity of Cydia pomonella GV to adult bees. According to the mode of action Cydia pomonella GV will infect the larvae stage of the target organism, therefore, the expert meeting considered that a risk assessment for bee brood is necessary. Some information was provided in the DAR, however, as the studies were not summarised in sufficient detail the experts were unable to conclude on the risk assessment. Further details of the literature studies submitted in the original dossier were provided in an addendum. However, it was noted that these data only briefly summarised the results of a literature paper not submitted in the original dossier. It was therefore concluded that the available information in the dossier was not sufficient to conclude a low risk. The RMS also provided an evaluation and summary of the original literature study in which the test methodology and results were described in detail. The RMS concluded that the information in the original literature study was sufficient to indicate a low risk to bee brood. However, in accordance with Regulation EC No. 1095/2007, it is not possible to take account of new data, therefore, a data gap was identified for the notifiers to address the risk to bee brood. Non-target arthropod glass-plate studies with the standard tier I indicator species with Cydia pomonella GV were available. Given that baculoviruses are known to infect the larvae stage of the target organism via oral uptake the relevance of laboratory contact toxicity studies is questionable. Nevertheless, on the basis of low toxicity a low risk to non-target arthropods via contact exposure was concluded. Literature information for the host specificity for a range of baculoviruses, including Cydia pomonella GV, was summarised and generally indicated that the baculoviruses are only able to infect a small number of the tested species. As indicated in the OECD consensus document (OECD, 2002) most of the available cross infectivity information is biased towards Lepidopteran species. However, on the basis of the available data a low risk to non-target arthropods from infectivity and pathogenicity was concluded. A 14-day acute toxicity study on earthworms was available for Cydia pomonella GV where no mortality was observed. Using the available initial soil PEC value a low acute risk to earthworms from direct toxicity was concluded. A 56-day earthworm reproduction study was also available and indicated that exposure to Cydia pomonella GV at the tested concentrations did cause an effect on earthworm reproduction. No mortality or other signs of infectivity and pathogenicity were reported. On the basis of the information available, a low risk to earthworms from infectivity and pathogenicity was concluded. A study with Cydia pomonella GV did not indicate any adverse effects on soil respiration or nitrification and was therefore considered sufficient to demonstrate a low risk to soil microorganisms. A low risk to sewage treatment organisms was concluded for the representative uses. EFSA Journal 2012;10(4):2655 9

10 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments 6.1. Soil Compound (name and/or code) Persistence, viability and dynamics Ecotoxicology Cydia pomonella GV Persistent for months to years A low risk to soil organisms was concluded Ground water Compound (name and/or code) Mobility in soil >0.1 μg/l 1m depth for the representative uses (at least one FOCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicological activity None Surface water and sediment Compound (name and/or code) Cydia pomonella GV Ecotoxicology A low risk to aquatic organisms was concluded Air Compound (name and/or code) Toxicology EFSA Journal 2012;10(4):

11 Cydia pomonella GV Rat LC 50 > 2 x granula of CpGV/L air (4-hr nose-only exposure) EFSA Journal 2012;10(4):

12 7. List of studies to be generated, still ongoing or available but not peer reviewed This is a complete list of the data gaps identified during the peer review process, including those areas where a study may have been made available during the peer review process but not considered for procedural reasons (without prejudice to the provisions of Article 7 of Directive 91/414/EEC concerning information on potentially harmful effects). Demonstrate that the level of microbial contamination complies with international standards. The OECD issues paper (OECD, 2011) should be used as the reference (relevant for all representative uses evaluated; submission date proposed by the notifiers: unknown; see section 1). For the Arysta source a validated method of analysis for the relevant impurity formaldehyde and 5 batch data with analysis of formaldehyde (relevant for the Arysta source; submission date proposed by the notifier: unknown; see section 1). For the formulation Carpovirusine : flash point, auto-flammability, viscosity and density (relevant for the Arysta source; submission date proposed by the notifiers: unknown; see section 1). Data to demonstrate the specificity of the identification method (relevant for all representative uses evaluated; submission date proposed by the notifiers: unknown; see section 1). Validation of the quantitative methods for the technical materials and formulations (relevant for all representative uses evaluated ; submission date proposed by the notifier: unknown; see section 1) Validation data for the methods of analysis for contaminating microorganisms (relevant for all representative uses evaluated; submission date proposed by the notifiers: unknown; see section 1). Data or information to address the risk to bee brood is required (relevant for all representative uses evaluated; submission date proposed by the notifiers: unknown; see section 5). 8. Particular conditions proposed to be taken into account to manage the risk(s) identified none 9. Concerns 9.1. Issues that could not be finalised An issue is listed as an issue that could not be finalised where there is not enough information available to perform an assessment, even at the lowest tier level, for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC and where the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses). 1. Insufficient information was available to finalise the risk assessment for bee brood Critical areas of concern An issue is listed as a critical area of concern where there is enough information available to perform an assessment for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC, and where this assessment does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. EFSA Journal 2012;10(4):

13 An issue is also listed as a critical area of concern where the assessment at a higher tier level could not be finalised due to a lack of information, and where the assessment performed at the lower tier level does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. None EFSA Journal 2012;10(4):

14 9.3. Overview of the concerns identified for each representative use considered (If a particular condition proposed to be taken into account to manage an identified risk, as listed in section 8, has been evaluated as being effective, then risk identified is not indicated in this table.) Representative use Operator risk Worker risk Bystander risk Consumer risk Risk to wild non target terrestrial vertebrates Risk to wild non target terrestrial organisms other than vertebrates Risk to aquatic organisms Groundwater exposure active substance Groundwater exposure metabolites Comments/Remarks Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Legal parametric value breached Assessment not finalised Legal parametric value breached Parametric value of 10µg/L (a) breached Assessment not finalised Pome fruit Nut trees X 1 The superscript numbers in this table relate to the numbered points indicated in sections 9.1 and 9.2. Where there is no superscript number see sections 2 to 6 for further information. (a): Value for non relevant metabolites prescribed in SANCO/221/2000-rev 10-final, European Commission, 2003 EFSA Journal 2012;10(4):

15 REFERENCES EFSA (European Food Safety Authority), Scientific Opinion on the maintenance of the list of QPS biological agents intentionally added to food and feed (2011 update). The EFSA journal 2011;9(12):2497 EFSA (European Food Safety Authority), Peer Review Report to the conclusion regarding the peer review of the pesticide risk assessment of the active substance Cydia pomonella. European Commission, 2002a. Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEC. SANCO/10329/2002 rev.2 final, 17 October European Commission, 2002b. Guidance Document on Aquatic Ecotoxicology Under Council Directive 91/414/EEC. SANCO/3268/2001 rev 4 (final), 17 October European Commission, 2002c. Guidance Document on Risk Assessment for Birds and Mammals Under Council Directive 91/414/EEC. SANCO/4145/2000. European Commission, Guidance Document on Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated under Council Directive 91/414/EEC. SANCO/221/2000- rev final, 25 February European Commission, Review Report for the active substance Cydia pomonella Granulovirus (Mexican isolate) finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 11 July 2008 in view of the inclusion of Cydia pomonella Granulovirus (Mexican isolate) in Annex I of Directive 91/414/EEC.SANCO/1548/08 rev.3, 7 May Germany, Draft Assessment Report (DAR) on the active substance Cydia pomonella prepared by the rapporteur Member State Germany in the framework of Directive 91/414/EEC, December 2007 (rev.1 March 2008). Germany, Final Addendum to Draft Assessment Report on Cydia pomonella, compiled by EFSA, March OECD (Organisation for Economic Co-operation and Development), OECD Consensus Document on Information used in the Assessment of Environmental Applications Involving Baculoviruses, Series on Harmonisation of Regulatory Oversight in Biotechnology, No. 20, ENV/JM/MONO(2002)1. OECD (Organisation for Economic Co-operation and Development), OECD Issue Paper on Microbial Contaminant Limits for Microbial Pest Control Products, ENV/JM/MONO(2011)43. Rautmann, D., Streloke, M. and Winkler, R. (2001): New basic values in the authorisation procedure for plant protection products. In Forster and Streloke. Workshop on Risk assessment and risk mitigation measures in the context of of the authorisation of plant protection products (WORMM). Mitt.Biol.Bundesanst.Land-Forstwirtsch. Berlin-Dahlem, Heft 381 EFSA Journal 2012;10(4):

16 APPENDICES APPENDIX A LIST OF END POINTS FOR THE ACTIVE SUBSTANCE AND THE REPRESENTATIVE FORMULATION Identity, Biological properties, Details of uses, Further information, and Proposed Classification and Labelling Active microorganism: Function (e.g. control of fungi): Cydia pomonella (CpGV) Mexican isolate Insecticide Rapporteur Member State Germany Co-rapporteur Member State (if relevant) - Identity of the Microbial Pest control Agent / Active substance (OECD data point IIM 1) Name of the organism: Taxonomy: Species, subspecies, strain: Identification / detection: Culture collection: Minimum and maximum concentration of the MPCA used for manufacturing of the formulated product (viable granules; g/kg): Cydia pomonella (CpGV) Family: Baculoviridae Genus: Granulovirus C. pomonella Mexican isolate The identity of the virus produce can be bioanalytically checked against the parent strain by - SDS-polyacrylamide-gel electrophoresis of the virus proteins - Restriction endonuclease analysis of viral DNA CpGV task force The isolate used in the products MADEX (Andermatt Biocontrol) and Granupom (Probis GmbH) is deposited at the German Collection of Microorganisms and Cell Cultures (DSMZ). Virus accession number: GV-0001 Sipcam S.p.A. The isolate used in the product Virgo is deposited at the National Collection of Pathogenic Viruses, Health Protection Agency, Centre for Applied Microbiology and Research, UK. Virus accession number: Arysta LifeScience S.A.S. The isolate used in the product CARPOVIRUSINE is deposited at the German Collection of Microorganisms and Cell Cultures (DSMZ), Germany. Virus accession number: GV-0002 Andermatt Biocontrol GmbH The CpGV aqueous virus slurry has a content of the active ingredient CpGV of 6.0 x granules/l. The content of the active ingredient by weight is approximately g/l or 12 g/kg. EFSA Journal 2012;10(4):

17 Probis GmbH The CpGV aqueous virus slurry has a content of the active ingredient CpGV of 1.47 x granules/l. Based on the volume of one virusgranule the calculated amount of the active microorganism in the technical material is approximately 2.8 g granules/l. Sipcam S.p.A. The CpGV aqueous virus slurry has a content of the active ingredient CpGV of 4.0 x granules/l. Based on the volume of one virusgranule the calculated amount of the active microorganism in the technical material is approximately 8 g granules/l. Identity and content of relevant impurities, additives, contaminating organisms in the technical grade of MPCA: Is the MPCA genetically modified; if so provide type of modification Arysta LifeScience S.A.S. The concentration of the active microorganism in the technical concentrate has to be at least 1 x granules/l. Arysta: formaldehyde, no maximum level can be set at this time. Open for contaminating microorganisms Not applicable. Biological properties of the microorganism (OECD data point IIM 2) Origin and natural occurrence, Background level: Target organism(s): Mode of action: Host specificity: Life cycle: The CpGV-isolate was originally isolated in 1963 in nature from diseased insects on apple and pear trees found in Mexico (near Valle de Allende, Chihuahua). Cydia pomonella is naturally present in our environment. The application in pest control means only a fluctuation of the virus titre in the biotope of the pest insect. Codling moth larvae Application of CpGV should be timed at hatching of larvae so that early-instar larvae on the surface of the fruits come in contact with the virus before entering the fruit, as the larval stage of the insect life cycle is the most susceptible to infection with baculoviruses. After oral intake by the codling moth larvae, the granules are dissolved in the midgut and free virions are released which invade the midgut cells by fusion with the microvilli. CpGV is highly specific and only has an effect on very few species of the Tortricidae family (Lepidoptera). The natural route of infection is the peroral ingestion of viral occlusion bodies by larvae. In the alkaline environment of the midgut (ph > 9.5), the occlusion bodies dissolve rapidly and occlusion-derived virions (ODV`s) are released. The ODV`s pass through the peritrophic membrane. After attachment to the microvilli of the midgut epithelium, the nucleocapsids enter the cell lumen either via fusion of the virion envelope with the epithelial membrane or by EFSA Journal 2012;10(4):

18 Infectivity, dispersal and colonisation ability: Relationships to known plant, animal or human pathogens: Genetic stability: Information on the production of relevant metabolites (especially toxins): Resistance/ sensitivity to antibiotics / antimicrobial agents used in human or veterinary medicine: viropexis. The nucleocapsids are transported to the nucleus and become uncoated at the nuclear pore or within the nucleus where the viral DNA is released and DNA expression and replication is initiated. Initial replication produces non-occluded virus particles to hasten the invasion of the host insect. By exocytosis the newly formed virions get to the hemolymph and from there into various tissues of the organism. In the cells of the fat body, hypodermis, Malphigian tubules and tracheal matrix, free virus rods, with and without developmental membrane, partly encapsulated rods and capsules have observed already three days after feeding. After cell lysis a large number of occluded CpGV will be set free which are able to infest new hosts. Sunlight is considered the most important factor contributing to the inactivation of viral inclusion bodies. Viruses may persist in soil for longer periods. The viruses may be distributed by small animals and birds (their faeces are able to contain infective viruses), predators, wind blow of dry soil and rain splash at canopy edges. CpGV is not related to any known plant, animal (other than arthropods) or human pathogens. The used strain of CpGV was isolated in Mexico and propagated for 9 years at the BBA in Darmstadt/Germany and also for 9 years at Berkeley/California. Only one of its enzymatic digests revealed a difference in the DNAs which were subsequently calculated to be % homologous. No differences were found in molecular weights of enveloped virion polypeptides with SDS-polyacryl-amide gel electrophoresis. Also a radioimmune protein blot assay revealed no differences. LD 50 values for first and fifth instar larvae showed both derivatives to have similar virulence. It is concluded that the used CpGV strain is genetically stable and did not change its properties during all the time under test. Baculoviruses do not produce secondary metabolites. Not applicable to viruses. EFSA Journal 2012;10(4):

19 Summary of uses supported by available data Probis GmbH and Andermatt Biocontrol GmbH Kenn-Nr Crop and/ or situation Pome fruit, nut trees Member State or Country Product name F G or I Pests or group of pests controlled Europe MADEX F 1) Cydia pomonella Tractor drawn motor sprayer Before first larvae hatch from eggs 3) max: 6 8 sunny days (2 partially sunny days = 1 sunny day) HG 2) Spraying Knapsack sprayer * MPCA: Microbial Pest Control Agent 1) = Field 2) = Home garden use 3) = First treatment 85 day degrees after the first warm evening with flight activity. Zero point of development of the codling moth is 10 C 4) = normally a max. application of 0.1 L product/ha will be sufficient 400 L/ha and m crown height (0.05 L product/ha and m crown height 4) ) Remarks Formulation Application Application rate per treatment PHI Type Conc. of Method Growth Number Interval MPCA/hL water Granules (days) MPCA* kind stage & between max L/ha MPCA/ha season applications max (min) SC 3 x Spraying x x Not granules granules /hl granules /ha and m relevant /L crown height Spray in the evening EFSA Journal 2012;10(4):

20 Crop and/ or situation Member State or Country Product name F G or I Pests or group of pests controlled Pome fruit Europe Granupom F 1) Cydia pomonella 1) = Field 2) = Home garden use HG 2) Formulation Application Application rate per treatment PHI Type Conc. of Method Growth Number Interval MPCA/hL water Granules (days) MPCA kind stage & between max L/ha MPCA/ha season applications max (min) SC 2.2 x granules /L Tractor drawn motor sprayer Spraying Knapsack sprayer Before first larvae hatch from eggs max: days x granules /hl 500 L/ha and m crown height 0.33 x granules/ha and m crown height (0.15 L product/ha and m crown height) Remarks Not relevant Spray in the evening Remarks: (a) (b) (c) (d) (e) (f) (g) (h) For crops, the EU and Codex classifications (both) should be used; where relevant, the use situation should be described (e.g. fumigation of a structure) Outdoor or field use (F), glasshouse application (G) or indoor application (I) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) GCPF Codes - GIFAP Technical Monograph No 2, 1989 All abbreviations used must be explained Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated (i) (j) (k) (l) (m) g/kg or g/l Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN ), including where relevant, information on season at time of application The minimum and maximum number of application possible under practical conditions of use must be provided PHI - minimum pre-harvest interval Remarks may include: Extent of use/economic importance/restrictions EFSA Journal 2012;10(4):

21 Sipcam Oxon Italia S.A. Kenn-Nr.: Crop and/ or situation Member State or Country Product name F G or I Pests or group of pests controlled Formulation Application Application rate per treatment PHI Type Conc. of Method Growth stage & Number Interval kg water kg (days) MPCA kind season min max between MPCA/hL L/ha MPCA/ha (MPCA/L) applications min max min max min max (min) Remarks Apple Northern and Southern Europe VIRGO F Cydia pomonella SC 2 x GV/L Spray Primarily against first generation of pests / start at the first eggs hatching. Possible against second generation of pests / start at the first eggs hatching days 6-10 x GV/hL* ** 6-15 x GV/ha ( L product/ha) 3 days * Lower concentrations (6 x GV/hL) may be applied against larvae of the first generation, whereas higher concentrations (10 x GV/hL) should be used against larvae of the second generation. ** The lower water volume should be used for lower trees, whereas the highest water amount is recommended for trees with a higher leaf area. In case of very expanded leaf area which requires more than 1500 L water/ha, a higher water volume can be applied, but the maximum rate of 15 x GV/ha must be respected. Remarks: (a) (b) (c) (d) (e) (f) (g) (h) For crops, the EU and Codex classifications (both) should be used; where relevant, the use situation should be described (e.g. fumigation of a structure) Outdoor or field use (F), glasshouse application (G) or indoor application (I) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) GCPF Codes - GIFAP Technical Monograph No 2, 1989 All abbreviations used must be explained Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated (i) (j) (k) (l) (m) g/kg or g/l Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN ), including where relevant, information on season at time of application The minimum and maximum number of application possible under practical conditions of use must be provided PHI - minimum pre-harvest interval Remarks may include: Extent of use/economic importance/restrictions EFSA Journal 2012;10(4):

22 Arysta Lifescience S.A.S. Kenn-Nr Crop and/ or situation (a) Member State or Country Product name F G or I (b) Pests or group of pests controlled Type (d-f) Formulation Application Application rate per treatment PHI Conc. of MPCA Method kind Growth stage (j) Number min max MPCA/hL max water L/ha Granules MPCA/ha (days) (MPCA/L) (f-h) (k) max (l) Interval between applications (min) Remarks Apple Northern and Southern Europe CARPOVI RUSINE F Cydia pomonella SC 1 x GV/L Spray BBCH 71- BBCH days GV/hL* GV/ha 3 days Remarks: (a) (b) (c) (d) (e) (f) (g) (h) For crops, the EU and Codex classifications (both) should be used; where relevant, the use situation should be described (e.g. fumigation of a structure) Outdoor or field use (F), glasshouse application (G) or indoor application (I) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) GCPF Codes - GIFAP Technical Monograph No 2, 1989 All abbreviations used must be explained Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated (i) (j) (k) (l) (m) g/kg or g/l Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN ), including where relevant, information on season at time of application The minimum and maximum number of application possible under practical conditions of use must be provided PHI - minimum pre-harvest interval Remarks may include: Extent of use/economic importance/restrictions EFSA Journal 2012;10(4):

23 Methods of analysis Analytical methods for the microorganism (OECD data point IIM 4.2, 4.3 and IIIM 5.3) manufactured microorganism (principal of method): Impurities and contaminating microorganisms in manufactured material (principal of method): Microscopic counts of the capsules (granula) permit an assessment of the virus concentration. Quantitative bioassays enable calculations on the number of active (infective) viruses in the product. The identity of CpGV, Mexican isolate, can be determined by SDSpolyacrylamide-gel electrophoresis of the virus proteins and by restriction endonuclease analysis of viral DNA. Open for further validation. Andermatt Biocontrol GmbH Determining of aerobic mesophile contaminants, E. coli, Salmonella, Staphylococcus aureus and Bacillus cereus in the final product by plating out on selective media. Probis GmbH Determining of bacteria and fungi, Salmonella, Shigella, Vibrio cholerae and Staphylococcus aureus in the final product by plating out on selective media Sipcam S.p.A. Determining of mesophile contaminants, Salmonella spp., Staphylococcus aureus, Coliforms, E. coli and Bacillus cereus by plating out on selective media. Microbial Pest control product (principle of method): Arysta LifeScience S.A.S. Determining of aerobe mesophilic, Coliform flora, Coliform resistant to heat, Escherichia coli, Staphylococcus, Anaerobes reducing sodium sulfite, Clostridium perfringens, Salmonella, Yeasts, Moulds and Bacillus cereus by plating out on selective media Open for further validation. The granules (occlusion bodies) of the active substance CpGV are counted under the light microscope. The activity (infectivity) of the granules is determined by a quantitative bioassay. Open for further validation. Analytical methods for residues (viable and non-viable) in exposed compartments and organisms (OECD data point IIM 4.5) of the active microorganism (principle of method) Of relevant metabolites (principle of method): Not relevant There are no relevant metabolites EFSA Journal 2012;10(4):