Peer review of the pesticide risk assessment of the active substance Cydia pomonella granulovirus (CpGV)

Abstract

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Germany and co‐rapporteur Member State the Netherlands for the pesticide active substance Cydia pomonella granulovirus (CpGV) and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of CpGV as an insecticide on pome fruit (apple, pear, quince, nashi pears, medlars), stone fruit (peach, apricot, nectarine, almond, plum trees), walnut trees (field foliar spray applications, professional and non‐professional uses). The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed.

Summary

Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659, lays down the procedure for the renewal of the approval of active substances submitted under Article 14 of Regulation (EC) No 1107/2009. The list of those substances is established in Commission Implementing Regulation (EU) No 686/2012 as amended by Commission Implementing Regulation (EU) No 2016/183. Cydia pomonella granulovirus (CpGV) is one of the active substances listed in that Regulation.

In accordance with Article 1 of Regulation (EU) No 844/2012, the rapporteur Member State (RMS), Germany, and co‐rapporteur Member State (co‐RMS), the Netherlands, received an application from CpGV AIR4 Task Force, consisting of Andermatt Biocontrol GmbH, Arysta LifeScience S.A.S and Serbios s.r.l., for the renewal of approval of the active substance CpGV.

An initial evaluation of the dossier on CpGV was provided by the RMS in the renewal assessment report (RAR) and subsequently, a peer review of the pesticide risk assessment on the RMS evaluation was conducted by EFSA in accordance with Article 13 of Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659.The following conclusions are derived.

The uses of CpGV according to the representative professional and non‐professional spray field uses as an insecticide on pome fruits (apple, pear, quince, nashi pears, medlars), stone fruit (peach, apricot, nectarine, plum trees, almond) and walnut trees, as proposed at the European Union (EU) level result in a sufficient insecticidal efficacy against the target pests codling moth (Cydia pomonella) and oriental fruit moth (Grapholita molesta).

The assessment of the data package revealed no issues that need to be included as critical areas of concern with respect to the identity of the microorganism/biological properties/physical and technical properties of the representative formulation.

In the area of mammalian toxicology, there are no data gaps or critical areas of concern. No adverse effects on human health are reported in a broad range of tests performed with different Baculoviruses, which is supported by a long history of safe use and the inclusion of the Baculoviridae family in the EFSA qualified presumption of safety (QPS) list since 2009. In the area of residues, no data gaps were identified. The consumer risk assessment was finalised and did not indicate health risks. CpGV is already included in Annex IV of Regulation (EC) No 396/2005.

The information available on the fate and behaviour of CpGV in the environment was considered sufficient to assess the environmental exposure for the representative uses assessed.

In the area of ecotoxicology, a low risk was concluded for all groups of non‐target organisms for all the reported intended uses of CpGV.

Background

Commission Implementing Regulation (EU) No 844/2012 ¹ , as amended by Commission Implementing Regulation (EU) No 2018/1659 ² , (hereinafter referred to as ‘the Regulation’), lays down the provisions for the procedure of the renewal of the approval of active substances, submitted under Article 14 of Regulation (EC) No 1107/2009 ³ . This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States, the applicant(s) and the public on the initial evaluation provided by the rapporteur Member State (RMS) and/or co‐rapporteur Member State (co‐RMS) in the renewal assessment report (RAR), and the organisation of an expert consultation where appropriate.

In accordance with Article 13 of the Regulation, unless formally informed by the European Commission that a conclusion is not necessary, EFSA is required to adopt a conclusion on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009 within 5 months from the end of the period provided for the submission of written comments, subject to an extension of an additional 3 months where additional information is required to be submitted by the applicant(s) in accordance with Article 13(3).

In accordance with Article 1 of the Regulation, the RMS Germany and co‐RMS the Netherlands received an application from CpGV AIR4 Task Force, consisting of Andermatt Biocontrol GmbH, Arysta LifeScience S.A.S and Serbios s.r.l., for the renewal of approval of the active substance Cydia pomonella granulovirus (CpGV). Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicants, the co‐RMS (the Netherlands), the European Commission and EFSA about the admissibility.

The RMS provided its initial evaluation of the dossier on CpGV in the RAR, which was received by EFSA on 16 October 2020 (Germany, 2020).

In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicants, CpGV AIR4 Task Force, for consultation and comments on 26 February 2021. EFSA also provided comments. In addition, EFSA conducted a public consultation on the RAR. EFSA collated and forwarded all comments received to the European Commission on 30 April 2021. At the same time, the collated comments were forwarded to the RMS for compilation and evaluation in the format of a reporting table. The applicants were invited to respond to the comments in column 3 of the reporting table. The comments and the applicants' response were evaluated by the RMS in column 3.

The need for expert consultation and the necessity for additional information to be submitted by the applicants in accordance with Article 13(3) of the Regulation were considered in a telephone conference between EFSA and the RMS on 25 August 2021. On the basis of the comments received, the applicants' response to the comments and the RMS's evaluation thereof, it was concluded that additional information should be requested from the applicants and that there was no need to conduct an expert consultation.

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 were compiled by EFSA in the format of an evaluation table.

The conclusions arising from the consideration by EFSA, and as appropriate by the RMS, of the points identified in the evaluation table, together with the outcome of the written consultation on the assessment of additional information, where this 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 September 2022.

This conclusion report summarises the outcome of the peer review of the risk assessment of the active substance and the representative formulation, evaluated on the basis of the representative uses of CpGV as an insecticide on pome fruit (apple, pear, quince, nashi pears, medlars), stone fruit (peach, apricot, nectarine, almond, plum trees), walnut trees (field foliar spray applications, professional and non‐professional uses), as proposed by the applicants. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the RAR and considered during the peer review, if any, are presented in the conclusion.

A list of the relevant end points for the active substance and the formulation is provided in Appendix A.

A key supporting document to this conclusion is the peer review report (EFSA, 2022), 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 comprises the following documents, in which all views expressed during the course of the peer review, including minority views, where applicable, can be found:

• the comments received on the RAR;

• the reporting table (25 August 2021);

• the evaluation table (28 September 2022);

• the comments received on the assessment of the additional information (where relevant);

• the comments received on the draft EFSA conclusion.

Given the importance of the RAR, including its revisions (Germany, 2022), and the peer review report, both documents are considered as background documents to this conclusion and thus are made publicly available.

It is recommended that this conclusion and its background documents would not be accepted to support any registration outside the European Union (EU) for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based.

The identity of the microorganism and the properties of the formulated product

CpGV belongs to the genus Betabaculovirus and the family Baculoviridae. CpGV Mexican (CpGV‐M) isolate is the reference isolate of Cydia pomonella granulovirus and was deposited in the German Collection of Microorganisms and Cell Cultures (DSMZ) under the accession number GV‐0001 (by Andermatt Biocontrol GmbH) and under the accession number GV‐0002 (by Arysta Life Science). CpGV‐M is not a mutant or a genetically‐modified virus. It is a wild‐type originally isolated in nature from diseased insects on apple and pear trees near Valle de Allende in Mexico. Identification information on additional CpGV isolates, all of them non‐genetically modified and deposited in the DSMZ, was provided in the dossier. These isolates were CpGV‐V01 (Virus accession number: GV‐0003), CpGV‐V03 (Virus accession number: GV‐0006), CpGV‐V15 (Virus accession number: GV‐0013), CpGV‐V22 (Virus accession number: GV‐0014), CpGV‐V14 (Virus accession number: GV‐0015), CpGV‐V45 (Virus accession number: GV‐0017) and CpGV‐R5 (Virus accession number: GV‐0007). All additional isolates, except the new ones CpGV‐V14 and CpGV‐V45, were previously evaluated according to the Guidance Document SANCO/0253/2008. In this renewal application, microbial pest control agents (MCPA) batch data were provided only for isolates CpGV‐M, CpGV‐V14 and CpGV‐V45.

The representative formulations for the evaluation were ‘Carpovirusine’, a suspension concentrate (SC) containing 1 × 10¹³ CpGV‐M OB/L; ‘Madex’ a SC containing a nominal content of 3 × 10¹³ CpGV‐M OB/L; ‘Madex Twin’ a SC containing a nominal content 3 × 10¹³ CpGV‐V22 OB/L and ‘Virgo’ a SC containing a nominal content of 2 × 10¹³ CpGV‐M OB/L. A data gap was identified for an updated composition of ‘Virgo’ including the range of water and technical material content and a confirmation regarding its minimum and maximum content of CpGV‐M (see Section 9). Data on representative formulations containing CpGV isolates beyond the CpGV‐M and CpGV‐V22 were not provided. Therefore, Good Agricultural Practices (GAPs)/representative use information was not available for the CpGV isolates: CpGV‐V01 (Virus accession number: GV‐0003), CpGV‐V03 (Virus accession number: GV‐0006), CpGV‐V15 (Virus accession number: GV‐0013), CpGV‐V14 (Virus accession number: GV‐0015), CpGV‐V45 (Virus accession number: GV‐0017) and CpGV‐R5 (Virus accession number: GV‐0007). Consequently, assessments/risk characterisation could not be finalised for these CpGV isolates (data gap, see Section 8.1.1).

The representative use evaluated for ‘Carpovirusine’ comprises professional and non‐professional field foliar spray applications on apple, pear, quince, nashi pears, peach, apricot and walnut trees as an insecticide against codling moth (Cydia pomonella) and against Oriental fruit moth (Grapholita molesta). The representative use evaluated for ‘Madex’ comprises professional and non‐professional field foliar spray applications on apple, pear, quince, nashi pears, medlars and walnut trees as an insecticide against codling moth (Cydia pomonella). The representative use evaluated for ‘Virgo’ comprises professional field foliar spray applications on apple, pear, quince, nashi pears and walnut trees as an insecticide against oriental fruit moth (Grapholita molesta). The representative use evaluated for ‘Madex Twin’ comprises professional and non‐professional field foliar spray applications on peach, apricot, nectarine, almond and plum trees as an insecticide against Oriental fruit moth (Grapholita molesta). Full details of the GAP can be found in the list of end points in Appendix A. For the other CpGV isolates not contained in these formulations representative GAPs were not available.

Data were submitted to conclude that the use of CpGV‐M and CpGV‐V22 according to the representative uses proposed at EU level results in a sufficient insecticidal efficacy against the target organisms, following the guidance document SANCO/2012/11251‐rev. 4. (European Commission, 2014).

A data gap was set for a transparent evaluation of the additional studies added to the dossier following the updated literature search for the biological properties of CpGV (see Section 9).

1. Identity of the microorganism/biological properties/physical and technical properties and methods of analysis

The following guidance documents were followed in the production of this conclusion: European Commission, 2012; EFSA FEEDAP Panel, 2012.

The MPCA of the isolates CpGV‐M, CpGV‐V22, CpGV‐V14 and CpGV‐V45 are technical concentrates (TKs) manufactured in commercial plants. The content of the pure microorganism in these technical concentrates is 3.2 × 10¹³ OB/L and 6 × 10¹³ OB/L of CpGV‐M in TKs as manufactured by Arysta Life Science and Andermatt Biocontrol GmbH respectively, and 6 × 10¹³ OB/L of CpGV‐V22, CpGV‐V45 and CpGV‐V14 in the TKs as manufactured by Andermatt Biocontrol GmbH.

Identification and distinction of the of the CpGV isolates can be achieved by using restriction fragment analysis (restriction fragment length polymorphism, RFLP) or single nucleotide polymorphism (SNP) methods. Granules of CpGV isolates can be counted under the microscope, and a standard bioassay using the isolate specific target pest can be applied for the quantification of CpGV in the representative formulations. A data gap was identified for a validated method to determine the content of CpGV‐M isolate in the formulation ‘Virgo’ in terms of OB/L and to provide a description on how the content in terms of OB/L is derived from the bioassay tests (see Section 9). For testing the presence of microbial contaminants according to SANCO/12116/2012‐rev.0 in the MPCA and MPCP, standard microbiological methods (EN ISO) are used and are considered appropriate (European Commission, 2012). Analytical methods of residues for CpGV in food of plant and animal origin, in feed of plant origin, in environmental matrices and in body fluids and tissues are not considered necessary as no residue definitions were set and no MRLs proposed for the representative uses.

CpGV is not pathogenic to humans or animals other than certain insect species. The analysis of contaminating microorganisms in commercially produced batches of the representative formulations ‘Carpovirusine’, ‘Madex’ and ‘Madex Twin’ comply with the requirements of SANCO/12116/2012 rev.0 (European Commission, 2012). Data on microbial contaminants according to SANCO/12116/2012 in only one instead of five commercially produced batches of'Virgo’ were provided (data gap, see Section 9). In addition, a data gap was identified relevant to quantitative data of the contaminating microorganisms following storage of the representative formulations ‘Carpovirusine’, ‘Madex’ and ‘Madex Twin’ at their recommended storage temperatures and storage duration (see Section 9). Finally, a data gap was set for storage stability data (physical and technical properties and growth of contaminating microorganisms) for the representative formulation ‘Virgo’ at the recommended storage conditions of one year at 4°C (see Section 9).

2. Mammalian toxicity

In 2009, the EFSA Panel on Biological Hazard (BIOHAZ Panel) recommended to include plant protection viruses, more specifically baculoviruses (Baculoviridae) as the highest taxonomic unit, in the QPS list (EFSA BIOHAZ Panel, 2009). In the most recent QPS update (EFSA BIOHAZ Panel, 2022), based on an updated extensive literature search, no new safety concern was identified for baculoviruses and therefore, the current QPS status remains unchanged. Baculoviruses are specific for defined target insects and do not infect (cells of) non‐target insects or other organisms including humans and animals.

No adverse effects were observed in individuals involved in the research, development, manufacturing and formulation of pest control products containing CpGV. Published data indicate that oral administration to humans of a baculovirus did not show any increase in disease frequency or adverse effects after repeated exposure (5 days).

With regard to the sensitising potential, a positive result in a Magnusson and Kligman (M&K) test with the representative formulation ‘Carpovirusine’ was observed. Considering also the exceedance of the specific concentrations limits (SCLs) for two sensitising impurities in the technical concentrate from Arysta Life Science, both the concentrate SMT‐M and the formulation ‘Carpovirusine’ may trigger the criteria for classification as skin sensitiser category 1 under CLP Regulation (EC) No 1272/2008. In the absence of a reliable test for CpGV, 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’.

Viruses are obligate intracellular organisms and do not produce toxins, toxic metabolites or degradation products. No adverse effect was induced after oral, inhalation (nose‐only exposure) or intraperitoneal administration of CpGV to rats. Similarly, available acute studies for several baculoviruses confirm that they do not infect vertebrates and can be considered as non‐pathogenic and non‐toxic to humans. Based on the absence of acute effects, available medical data and literature data for repeated exposure to baculoviruses, no short‐term studies are considered necessary. Similarly, no evidence of genotoxicity was observed in literature studies of limited scientific value with CpGV or other baculoviruses. Considering also the general knowledge on baculoviruses, CpGV can be concluded as unlikely to be genotoxic.

In a cell culture study, CpGV was able to penetrate into human cells but did not replicate or damage these cells, and no transcription of viral genes was observed.

Considering the lack of infectivity and pathogenicity of baculoviruses in mammals, it is not necessary to derive reference values for CpGV. Therefore, no operator, worker and bystander exposure estimates are needed. In the absence of a quantitative risk assessment, the use of protective equipment might be considered to reduce the exposure in order to prevent the risk of adverse effects by dermal and/or inhalation exposure for operators and workers (sensitisation potential of the microorganism).

3. Residues

The assessment in the residue section is based on the following guidance document: European Commission, 2015.

Four representative outdoor foliar European uses on (1) pome fruits (apples, pears, quinces), stone fruits (peaches, apricots) and walnut trees; (2) pome fruits (apples, pears, quinces, medlars (Mespilus)) and walnuts; (3) stone fruits (apricots, peaches, nectarines, plums) and almonds; (4) pome fruits (apples, pears, quinches) and walnut trees are provided for CpGV by the applicant. The representative uses 1, 2 and 4 refer also to ‘Nashi’ which is classified as nashi pears (0130020–001) under pears (0130020) according to Commission Regulation (EU) 2018/62 ⁴ .

Treatments are indicated to be started before the first larvae hatch from eggs at BBCH 71–89 of the respective crops, with 3–12 applications at a rate of 0.3 × 10¹³ granulovirus/ha up to 1.5 × 10¹³ granulovirus/ha. For the representative use (1) with a maximum application rate of 1 × 10¹³ granulovirus/ha and the representative use (4) with the highest application rate of 1.5 × 10¹³ granulovirus/ha, plant harvest intervals (PHIs) of 1 and 3 days, respectively, are included, whereby for the other two uses each with application rates of 0.3 × 10¹³ granulovirus/ha no PHI is proposed in addition to the growth stage which defines the time of treatment.

For the family of Baculoviridae which includes CpGV an exhaustive body of knowledge is generated by annual extensive literature reviews performed by the EFSA Panel on Biological Hazard in the context of the QPS assessments since 2009 when a comprehensive assessment of baculoviruses was performed. In 2009, the Panel concluded that ‘on the basis of the available literature and other available sources of information it can be concluded that baculoviruses are safe for animals and human consumption. Baculoviruses are specific for defined target insects and do not infect (cells of) non‐target insects or other organisms including humans and animals. The BIOHAZ Panel therefore recommended to include plant protection viruses, more specifically baculoviruses (Baculoviridae) as the highest taxonomic unit, on the QPS list (EFSA BIOHAZ Panel, 2009)’.

Noting the long history of safe use as a biological pest control agent and related dietary exposure of consumers with remaining residues on agricultural raw commodities, there are no identified reports in the literature which indicate adverse health effects by the oral route. In its most recent QPS update, the BIOHAZ Panel confirmed based on an updated extensive search for papers potentially relevant for the QPS evaluation of Baculoviridae that no new safety concern was identified and that therefore, the current QPS status remains unchanged (EFSA BIOHAZ Panel, 2022). This conclusion is in line with the outcome of the literature search provided for CpGV and its update following the EFSA guidance in the context of this renewal assessment (EFSA, 2011).

With regard to the five assessment criteria according to the Commission guidance (European Commission, 2015) for the potential inclusion of CpGV in Annex IV of Regulation (EC) No 396/2005, three criteria can be considered relevant for viruses and microorganisms. These are: criterion III, referring to the absence of identified hazardous properties; criterion IV: the natural exposure is higher than the one linked to the use as PPP and criterion V: consumer exposure is not expected. In the context of this renewal assessment, criterion III is considered to be fulfilled whereby criteria IV and V are not considered as met for the following reasons:

CpGV has a long‐standing safe history of use based on an extensive body of knowledge and there are no identified hazardous properties reported for dietary consumer exposure. Therefore, criterion III of the guidance is considered as fulfilled.

With regard to the other two criteria IV and V, since it is not demonstrated that natural exposure is higher than the one linked to the use as PPP for the representative uses of CpGV and because consumer exposure to residues of CpGV is expected, these two criteria are not considered to be fulfilled.

Therefore, considering that CpGV was concluded not to have hazardous properties (criterion III laid down in the guidance is fulfilled) and it is included on the QPS list without restrictions, risk managers might consider maintaining CpGV in Annex IV of Regulation (EC) No 396/2005 ⁵ where it is already included according to Commission Regulation (EU) 2016/439 ⁶ .

4. Environmental fate and behaviour

Information regarding the potential interference of CpGV with the analytical systems for the control of the quality of drinking water provided for in Directive 98/83/EC ⁷ was addressed in the applicants' dossier. This is a specific decision‐making criterion for the authorisation of plant protection products containing microorganisms (see uniform principles in Commission Regulation (EU) No 546/2011 ⁸ ). The virus CpGV is unlikely to interfere with the analytical systems used for the control of the quality of drinking water which have bacteria as their target.

Information on the potential transfer of genetic material from CpGV to other organisms was included in the amended assessment report. Infection and replication of CpGV is known to be very specific to insects and has not been reported to occur in other organisms, including humans or animals (EFSA BIOHAZ Panel, 2013, 2022). Transfer of genetic material from CpGV to other organisms except certain insect species is unlikely to be a concern when using CpGV in plant protection. The horizontal transfer of genes and transposable elements occurs frequently within the baculoviruses indicating a role for baculoviruses as vectors of horizontal DNA transfer between insects.

4.1. Fate and behaviour in the environment of the microorganism

Scientific papers from the open literature showed that baculovirus remained in the soil following application and accumulated in soil following repeated applications. The structure of baculovirus occlusion bodies provides for their potential to persist in the environment in a variety of environmental conditions. Therefore, for the representative uses, it cannot be excluded that CpGV may persist and be present above natural background levels in soil, taking into account repeated applications over the years. However, multiplication of the virus outside the host organism will not occur. Consequently, EFSA concluded that the information is sufficient to address the uniform principles criterion associated with persistence and accumulation in the environment regarding soil. Predicted environmental concentrations (PECs) in soil for CpGV were calculated and reported in the RAR and in Appendix A that cover the representative uses for which product information is available.

Scientific papers from the open literature showed that intact occlusion bodies of baculovirus are stable in aqueous suspension. Once introduced into a water body, the viral particles are likely to deposit and absorb to sediments. Therefore, for the representative uses, it cannot be excluded that CpGV may persist and be present above natural background levels in surface water systems, taking into account repeated applications over the years. However, multiplication of the virus outside the host organism will not occur. Consequently, EFSA concluded that the information is sufficient to address the uniform principles criterion associated with persistence and accumulation in the environment regarding surface water. PECs in surface water for CpGV for the representative uses were calculated and reported in the RAR and in Appendix A that cover the representative uses for which product information is available.

For the fate and behaviour in air, scientific papers support that viruses are inactivated by sunlight and multiplication of the virus outside the host organism will not occur.

4.2. Fate and behaviour in the environment of any relevant metabolite formed by the microorganism under relevant environmental conditions

Viruses do not produce metabolites, they can only modify host cell metabolism, as they self‐replicate within host organisms. It is considered that no further information is required at EU level since a qualified presumption of safety has been found to be applicable to the family Baculoviridae such as CpGV (EFSA BIOHAZ Panel, 2013, 2022).

5. Ecotoxicology

Ecotoxicological studies performed with the active substance CpGV were not submitted. However, studies performed with formulated granulovirus were available. Information from the literature was also used to address some of the ecotoxicological risk assessments. As reported in the fate section, CpGV infection and replication is known to be very specific to insects and has not been reported to occur in other organisms, including humans or animals (EFSA BIOHAZ Panel, 2013, 2022).

A 5‐day avian infectivity and pathogenicity study with the formulated CpGV (‘Carpovirusine’) was available and no indications of infectivity or pathogenicity were observed. An acute study with rats reported similar findings for mammals. Further data from the open literature confirmed the lack of toxicity, infectivity or pathogenicity to vertebrates. In fact, none of baculoviruses are known to infect vertebrates. Based on the information reported above and of the outcome of previous risk assessment of CpGV (EFSA, 2012) on similar uses, a low dietary risk to birds and wild mammals was concluded. A quantitative risk assessment was performed for exposure via contaminated water according to the ‘leaf scenario’ reported in EFSA Guidance on risk assessment for birds and mammals (EFSA, 2009). While this scenario is not relevant for the crop included in the GAP, it does represent an absolute worst‐case and was thus accepted. A low risk for both birds and wild mammals was concluded.

Toxicity data with several formulations of CpGV (the representative formulations ‘Carpovirusine’ and ‘Virgo’, plus data with ‘Granupom’, i.e. an older formulation for which a bridging with ‘Madex’ and ‘Madex Twin’ was provided) were available for fish (acute), aquatic invertebrates (acute), algae and aquatic plants (only ‘Granupom’ and ‘Virgo’) and indicated low direct toxicity. Using the available worst‐case surface water PECsw values, a low risk to aquatic organisms from direct toxicity was demonstrated for all intended uses of products for which GAP information was available. Although available studies on aquatic organisms lack information on infectivity and pathogenicity endpoints, detrimental impacts on the non‐target species are not expected due to the very narrow host range of CpGV. As indicated in the fate section, multiplication of the virus outside the host organism is not expected to occur. The available information from the open literature confirmed lack of evidence for pathogenicity and infectivity of baculoviruses to aquatic organisms. Based on the low toxicity and the expected lack of infectivity and pathogenicity, a low risk to aquatic organisms from CpGV was concluded for all representative uses of products for which GAP information was available.

Studies with several formulations of CpGV (‘Carpovirusine’, ‘Virgo’ and ‘Granupom’) were available to assess the acute oral and contact toxicity to honey bees. The available studies demonstrated a low toxicity to adult honey bees. Additionally, a study from the open literature (Mommaerts et al., 2009) confirmed low toxicity (in terms of worker mortality) also towards bumble bee microcolonies. Regarding infectivity, the evidence available in the open literature was considered only supportive and circumstantial. No quantitative risk assessment was carried out, but a low risk to adult honey bees and bumble bees can be concluded based on the available information. No studies were available to assess potential adverse effects of CpGV to solitary bees.

Considering that the primary target of CpGV are insect larvae, attention should particularly be paid to bee larvae. In the former peer‐review on CpGV (EFSA, 2012), a data gap was set to address the risk to bee brood. While in the previous evaluation in 2012 only a brief summary of part of the available literature was provided, a more in‐depth analysis of the available information was performed for the current conclusion. Nonetheless, no targeted studies were performed to address this issue. Most of the available literature studies are rather old (≥ 40 years old), and among the studies carried out with baculoviruses only few were performed with CpGV. While the methods used in these studies are not always fully transparent, they all concur that exposure to these viruses caused no appreciable effects on honey bees, even in experiments with full colonies. Some of them reported targeted assessments on brood and found no adverse effects. In the aforementioned study with bumble bee microcolonies (Mommaerts et al., 2009), exposure to CpGV did not trigger a reduction in the number of produced drones. In conclusion, while the evidence is not fully exhaustive, considering the high specificity of CpGV and its natural occurrence, adverse effects to bee larvae following the intended uses seem unlikely, therefore a low risk can be concluded for all representative uses.

Toxicity laboratory data with different formulations of CpGV (‘Carpovirusine’, ‘Virgo’, and ‘Granupom’) were available for several species of non‐target arthropods. Exposure via contact and via diet to adult and protonymphs did not cause significant mortality or reduction in fecundity for any of the tested species. In addition, effects to larvae of the species Chrysoperla carnea were investigated and no adverse effects were recorded. A quantitative risk assessment for the representative uses was provided comparing the cumulative annual application rate to the available endpoints. Based on this, a low risk could not be demonstrated for any of the intended uses. However, such quantitative risk assessment based on hazard quotient is not considered particularly informative for viruses, because dose–response relationships are rarely observed in cases of pathogenic effects. A considerable amount of literature, albeit rather old, indicates that CpGV and baculoviruses in general exhibit low toxicity to non‐target arthropods when tested under laboratory conditions. Furthermore, a number of field tests from literature – characterised by a wide range of reliability – consistently indicate lack of effects on non‐target arthropods and communities when CpGV is applied to orchards. Multiple studies available from literature confirm that granuloviruses have a very narrow host specificity, and in fact attempts to infect organisms outside of the Totricidae family with CpGV have so far failed. While not fully exhaustive, the evidence from literature indicates that CpGV is unlikely to exert any direct effects (in terms of toxicity, infectivity or pathogenicity) to non‐target arthropods for all representative uses of products for which GAP information was available. Nevertheless, some studies on baculoviruses reported that indirect effects on parasitoids cannot be excluded when the target insect host is killed by the virus before the parasitoid is able to complete its development. This was mainly studied under laboratory conditions and the scale of this issue at the population level is currently not known, as it would depend on the availability of alternative host insects.

Acute and reproductive toxicity studies on earthworms were available for different formulations of CpGV (‘Carpovirusine’, ‘Virgo’, and ‘Granupom’). Using the available PEC in soil, a low risk to earthworms from direct toxicity was concluded for all representative uses of products for which GAP information was available. In addition, no mortality or other signs of infectivity and pathogenicity were reported at any of the tested concentrations. On the basis of the information available, a low risk to earthworms from infectivity and pathogenicity was concluded for all representative uses.

Studies with several formulation of CpGV did not indicate adverse effects on soil microorganisms and were therefore considered sufficient to demonstrate a low risk for all representative uses.

6. Overview of the risk assessment of the organism or metabolite compounds listed in residue definitions triggering assessment of effects data for the environmental compartments (Tables 1, 2, 3, 4–1, 2, 3, 4)

Table 1.

Soil

Compound (name and/or code)	Ecotoxicology
Cydia pomonella granulovirus	Low risk to soil macro‐ and microorganisms from Cydia pomonella granulovirus for all representative uses

Table 2.

Groundwater ^(a)

Compound (name and/or code)	> 0.1 μg/L at 1 m depth for the representative uses (b) Step 2	Biological (pesticidal) activity/relevance Step 3a.	Hazard identified Steps 3b. and 3c.	Consumer RA triggered Steps 4 and 5	Human health relevance
None	–	–	–	–	–

^(a)Assessment according to European Commission guidance of the relevance of groundwater metabolites (2003).

^(b)FOCUS scenarios or a relevant lysimeter.

Table 3.

Surface water and sediment

Compound (name and/or code)	Ecotoxicology
Cydia pomonella granulovirus	Low risk to aquatic organisms from Cydia pomonella granulovirus for all representative uses

Table 4.

Air

Compound (name and/or code)	Toxicology
Cydia pomonella granulovirus	No adverse effects after acute or repeated exposure to baculoviruses by inhalation

7. Particular conditions proposed to be taken into account by risk managers

Risk mitigation measures (RMMs) identified following consideration of Member State (MS) and/or applicant's proposal(s) during the peer review, if any, are presented in this section. These measures applicable for human health and/or the environment leading to a reduction of exposure levels of operators, workers, bystanders/residents, environmental compartments and/or non‐target organisms for the representative uses are listed below. The list may also cover any RMMs as appropriate, leading to an acceptable level of risks for the respective non‐target organisms.

It is noted that final decisions on the need of RMMs to ensure the safe use of the plant protection product containing the concerned active substance will be taken by risk managers during the decision‐making phase. Consideration of the validity and appropriateness of the RMMs remains the responsibility of MSs at product authorisation, taking into account their specific agricultural, plant health and environmental conditions at national level.

No particular conditions to be taken into account by risk managers were identified.

• Use of personal protective equipment (PPE) should be considered for operators handling the representative formulation ‘Carpovirusine’ due to the presence of two sensitising impurities which may trigger the criteria for classification as skin sensitiser category 1 under CLP Regulation (EC) No 1272/2008.

8. Concerns and related data gaps

8.1. Concerns and related data gaps for the representative uses evaluated

8.1.1. Issues that could not be finalised

An issue is listed as ‘could not be finalised’ if there is not enough information available to perform an assessment, even at the lowest tier level, for one or more of the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/2011 ⁹ and if 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).

An issue is also listed as ‘could not be finalised’ if the available information is considered insufficient to conclude on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

The following issues or assessments that could not be finalised have been identified, together with the reasons including the associated data gaps where relevant, which are reported directly under the specific issue to which they are related:

1. Complete risk characterisation of CpGV isolates: CpGV‐V01 (Virus accession number: GV‐0003), CpGV‐V03 (Virus accession number: GV‐0006), CpGV‐V15 (Virus accession number: GV‐0013), CpGV‐V14 (Virus accession number: GV‐0015), CpGV‐V45 (Virus accession number: GV‐0017) and CpGV‐R5 (Virus accession number: GV‐0007) due to there being no GAPs/representative use information for plant protection products containing these isolates (see section ‘The identity of the microorganism and the properties of the formulated product’, relevant for Sections 4 and 5):

   1. GAP/representative use information was not available for the CpGV isolates: CpGV‐V01 (Virus accession number: GV‐0003), CpGV‐V03 (Virus accession number: GV‐0006), CpGV‐V15 (Virus accession number: GV‐0013), CpGV‐V14 (Virus accession number: GV‐0015), CpGV‐V45 (Virus accession number: GV‐0017) and CpGV‐R5 (Virus accession number: GV‐0007). This information was needed to advise the Commission for each isolate, on whether there might be risk of toxic effects to aquatic organisms and earthworms; (see section ‘The identity of the microorganism and the properties of the formulated product’ and Section 5)

8.1.2. Critical areas of concern

An issue is listed as a critical area of concern if there is enough information available to perform an assessment for the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/2011, and if this assessment does not permit the conclusion 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.

An issue is also listed as a critical area of concern if the assessment at a higher tier level could not be finalised due to lack of information, and if the assessment performed at the lower tier level does not permit the conclusion 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.

An issue is also listed as a critical area of concern if, in the light of current scientific and technical knowledge using guidance documents available at the time of application, the active substance is not expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

Critical areas of concern, including associated data gaps, have not been identified.

8.1.3. Overview of the concerns identified for each representative use considered

No concerns have been identified for the representative uses considered.

9. List of other outstanding issues

Remaining data gaps not leading to critical areas of concern or issues not finalised but considered necessary to comply with the data requirements, and which are relevant for some or all of the representative uses assessed at EU level. Although not critical, these data gaps may lead to uncertainties in the assessment and are considered relevant.

These data gaps refer only to the representative uses assessed and are listed in the order of the sections:

• An updated composition of ‘Virgo’ and confirmation regarding its minimum and maximum content of CpGV‐M was not provided by the applicant Serbios s.r.l. (relevant for representative uses evaluated for ‘Virgo’; see Section 1).

• A validated method to determine the content of CpGV isolate in the formulation ‘Virgo’ in terms of OB/L and a description on how the content in terms of OB/L is derived from the bioassay tests have not been provided by the applicant Serbios s.r.l. (relevant for representative uses evaluated for ‘Virgo’; see Section 1).

• A transparent evaluation of the additional studies was not added to the dossier following the updated literature search for the biological properties of CpGV (relevant for all representative uses evaluated; see Section 1).

• Storage stability data (physical and technical properties and content of contaminating microorganisms) for the representative formulation ‘Virgo’ at the recommended storage conditions of one year at 4°C were not provided by the applicant Serbios s.r.l. (relevant for representative uses evaluated for ‘Virgo’; see Section 1).

• Data on microbial contaminants according to SANCO/12116/2012 in five commercially produced batches of'Virgo’ were not provided by the applicant Serbios s.r.l. (relevant for representative uses evaluated for ‘Virgo’; see Section 1).

• Quantitative data of contaminating microorganisms following storage of the representative formulation ‘Carpovirusine’, ‘Madex’ and ‘Madex Twin’ at the recommended storage temperature and information on storage duration were not provided by the applicants Andermatt Biocontrol GmBH and Arysta LifeScience S.A.S (relevant for all representative uses evaluated; see Section 1).

Abbreviations

DSMZ

German Collection of Microorganisms and Cell Cultures

EEC

European Economic Community

FOCUS

Forum for the Co‐ordination of Pesticide Fate Models and their Use

GAP

Good Agricultural Practice

LAGDA

Larval Amphibian Growth and Development Test

MPCA

active agent of the microbial pest control product

MPCP

microbial pest control product

MRL

maximum residue level

OECD

Organisation for Economic Co‐operation and Development

PEC

predicted environmental concentration

PEC_sw

predicted environmental concentration in surface water

PHI

preharvest interval

PPE

personal protective equipment

QPS

Qualified Presumption of Safety

RAR

Renewal Assessment Report

RFLP

restriction fragment length polymorphism

S

svedberg, S (10⁻¹³ s)

SC

Scientific Committee

SNP

single nucleotide polymorphism

TK

technical concentrate

WHO

World Health Organization

Appendix A – List of end points for the active substance and the representative formulation

Appendix A can be found in the online version of this output (‘Supporting information’ section): https://doi.org/10.2903/j.efsa.2022.7630

Supporting information

List of end points for the active substance and the representative formulation

Suggested citation: EFSA (European Food Safety Authority) , Alvarez F, Arena M, Auteri D, Binaglia M, Castoldi AF, Chiusolo A, Colagiorgi A, Colas M, Crivellente F, De Lentdecker C, Egsmose M, Fait G, Ferilli F, Gouliarmou V, Nogareda LH, Ippolito A, Istace F, Jarrah S, Kardassi D, Kienzler A, Lanzoni A, Lava R, Leuschner R, Linguadoca A, Lythgo C, Magrans O, Mangas I, Miron I, Molnar T, Padovani L, Parra Morte JM, Rizzuto S, Serafimova R, Sharp R, Szentes C, Terron A, Theobald A, Tiramani M and Villamar‐Bouza L, 2022. Conclusion on the peer review of the pesticide risk assessment of the active substance Cydia pomonella granulovirus (CpGV). EFSA Journal 2022;20(11):7630, 16 pp. 10.2903/j.efsa.2022.7630