Peer review of the pesticide risk assessment of the active substance Phthorimaea operculella granulovirus (2024)

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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, The Netherlands for the pesticide active substance Phthorimaea operculella granulovirus are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of Phthorimaea operculella granulovirus as an insecticide on tomato (field and greenhouse uses) and on potato (field use) via spraying (tractor drawn or knapsack sprayers) or overhead irrigation. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed.

Keywords: insecticide, peer review, pesticide, Phthorimaea operculella granulovirus, risk assessment

SUMMARY

Phthorimaea operculella granulovirus is a new active substance for which, in accordance with Article 7 of Regulation (EC) No 1107/2009 of the European Parliament and of the Council, the rapporteur Member State (RMS), The Netherlands, received an application from Andermatt Biocontrol Suisse AG on 30 November 2018 for approval. Complying with Article 9 of the Regulation, the completeness of the dossier was checked by the RMS and the date of admissibility of the application was recognised as being 7 June 2019.

An initial evaluation of the dossier on Phthorimaea operculella granulovirus was provided by the RMS in the draft assessment report (DAR) and subsequently, a peer review of the pesticide risk assessment on the RMS evaluation was conducted by EFSA in accordance with Article 12 of Regulation (EC) No 1107/2009. The following conclusions are derived.

The uses of Phthorimaea operculella granulovirus (isolate V65) according to the representative uses as an insecticide applied by spraying or overhead irrigation on tomato (field and permanent and non‐permanent greenhouse) and on potato (field), as proposed at EU level result in a sufficient insecticidal efficacy against the target pests.

The assessment of the data package revealed no issues that could not be finalised or that need to be included as critical areas of concern with respect to identity, biological properties of the microbial active substance and physical and technical properties of the representative formulation and methods of analysis.

In the area of mammalian toxicology, there are no issues that could not be finalised or critical areas of concern. Baculoviruses only infect insect target species, do not show infectivity, pathogenicity and toxicity for mammalians, and do not produce any metabolites or toxins. This is supported by the inclusion of the Baculoviridae family in the EFSA qualified presumption of safety (QPS) list since 2009.

In the area of residues, the consumer dietary exposure did not indicate health risks based on the current body of knowledge for baculoviruses and could therefore be finalised.

The information available on the fate and behaviour of Phthorimaea operculella granulovirus in the environment was considered sufficient to assess the environmental exposure for the representative uses evaluated at EU level.

In the area of ecotoxicology, a low risk was concluded for all groups of non‐target organisms for all the representative uses of Phthorimaea operculella granulovirus.

BACKGROUND

Regulation (EC) No 1107/2009 of the European Parliament and of the Council¹ (hereinafter referred to as ‘the Regulation’) lays down, inter alia, the detailed rules as regards the procedure and conditions for approval of active substances. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicant(s) for comments on the initial evaluation in the draft assessment report (DAR), provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate.

In accordance with Article 12 of the Regulation, EFSA is required to adopt a conclusion on whether an active substance can be expected to meet the approval criteria provided for in Article 4 of the Regulation (also taking into consideration recital (10) of the Regulation) within 120 days from the end of the period provided for the submission of written comments, subject to an extension of 30 days where an expert consultation is necessary, and a further extension of up to 150 days where additional information is required to be submitted by the applicant(s) in accordance with Article 12(3).

Phthorimaea operculella granulovirus is a new active substance for which, in accordance with Article 7 of the Regulation, the RMS, The Netherlands (hereinafter referred to as the ‘RMS’), received an application from Andermatt Biocontrol Suisse AG on 30 November 2018 for approval of the active substance Phthorimaea operculella granulovirus. Complying with Article 9 of the Regulation, the completeness of the dossier was checked by the RMS and the date of admissibility of the application was recognised as being 7 June 2019.

The RMS provided its initial evaluation of the dossier on Phthorimaea operculella granulovirus in the DAR, which was received by EFSA on 25 March 2022 (The Netherlands,2022). The peer review was initiated on 10 November 2022 by dispatching the DAR to the Member States and the applicant, Andermatt Biocontrol Suisse AG, for consultation and comments. EFSA also provided comments. In addition, EFSA conducted a public consultation on the DAR. The comments received were collated by EFSA and forwarded to the RMS for compilation and evaluation in the format of a reporting table. The applicant was invited to respond to the comments in column 3 of the reporting table. The comments and the applicant's 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 applicant in accordance with Article 12(3) of the Regulation were considered in a tele‐conference between EFSA and the RMS on 03 March 2023. On the basis of the comments received, the applicant's response to the comments and the RMS's evaluation thereof, it was concluded that additional information should be requested from the applicant and that EFSA should conduct an expert consultation in the areas of potential effects on human/mammalian health and potential effects on non‐target organisms.

The outcome of the tele‐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 an expert consultation, 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 experts' consultations and the written consultation on the assessment of additional information, where these took place, were reported in the final column of the evaluation table.

In accordance with Article 12 of the Regulation, EFSA should adopt a conclusion on whether Phthorimaea operculella granulovirus can be expected to meet the approval criteria provided for in Article 4 of the Regulation, taking into consideration recital (10) of the Regulation.

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 June – July 2024.

This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the formulation for representative uses evaluated on the basis of the representative uses of Phthorimaea operculella granulovirus as an insecticide on tomato (field and greenhouse uses) and on potato (field use) as proposed by the applicant. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the DAR 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 for representative uses is provided in AppendixA.

A key supporting document to this conclusion is the peer review report (EFSA, 2024), 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 DAR;

• the reporting table (3 March 2023);

• the evaluation table (16 May 2024);

• the reports of the scientific consultation with Member State experts (where relevant);

• 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 DAR, including its revisions (The Netherlands,2024), 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 EU for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based.

THE MICROBIAL ACTIVE SUBSTANCE AND THE FORMULATION FOR REPRESENTATIVE USES

Phthorimaea operculella granulovirus (PhopGV) isolate V65 is deposited at German Collection of Micro‐organisms and Cell Cultures‐Leibniz‐Institute (DSMZ), Germany, under the reference number GV‐0019. PhopGV isolate V65 is produced invivo using Tuta absoluta and P. operculella larvae.

The formulation for the representative uses for the evaluation was ‘TUTAVIR‘, a suspension concentrate (SC) containing 522.96 g/L (2 × 10¹³ OB/L to 1 × 10¹⁴ OB/L) (by bioassay) of aqueous slurry containing PhopGV isolate V65.

The information on the microbial active substance and the formulation for representative uses, including the co‐formulants in this formulation, was considered in the overall assessment during the peer review. None of the co‐formulants is an unacceptable co‐formulant listed in Annex III of Regulation (EC) No 1107/2009, nor considered as an active substance in accordance with Regulation (EC) No 1107/2009. Details on the composition of the formulations cannot be reported in conclusions because of the provisions in Article 63(2)(d) of Regulation (EC) No 1107/2009, however this information was fully available and evaluated during the peer review. A proposal for classification of the formulation(s) according to the Regulation (EC) 1272/2008 was provided by the applicant and assessed by the RMS (please see Volumes 3 CP of the RAR).

The representative uses evaluated were spraying (tractor drawn or knapsack sprayers) or overhead irrigation on tomato (field and permanent and non‐permanent greenhouse) against Tuta absoluta and on potato (field) against P. operculella. Full details of the GAPs can be found in the list of end points in AppendixA.

Data were submitted to conclude that the uses of PhopGV isolate V65 according to the representative uses proposed at EU level results in a sufficient insecticidal efficacy against the target organisms, following the guidance document SANCO/10054/2013 – rev. 3 (European Commission,2013).

GENERAL ASPECTS

With regard to the mammalian toxicity information available for the formulation for representative uses TUTAVIR, studies were performed for acute dermal, skin sensitisation and eye irritation endpoints. With regard to the co‐formulants contained in TUTAVIR, sufficient toxicological data were available for all components. The experts considered that the available toxicological information did sufficiently address the genotoxicity, pathogenicity, infectiveness and repeated dose toxicity potential of TUTAVIR over the short‐ and long‐term and no concern was identified.²

The availability of ecotoxicity data with the formulation for representative uses TUTAVIR was discussed at the experts' meeting.³ Furthermore, the experts also discussed the data retrieval search and the available data for the individual components. Considering the reasoning agreed by the experts, no concerns were identified.

1. SPECIFICATION OF THE MICROORGANISM, PHYSICAL AND TECHNICAL PROPERTIES AND METHODS OF ANALYSIS

The following guidance documents were followed in the production of this conclusion: European Commission(2012).

The microbial pest control agent (MPCA) is not isolated and purified but directly formulated to microbial pest control product (MPCP), therefore the specification was set on the MPCP based on batch data from industrial plant production. However, a justification on their representativeness is missing (data gap, see Section10). The minimum and maximum content of PhopGV isolate V65 in the MPCP proposed by RMS was 2 × 10¹³–1 × 10¹⁴ OB/L. The analysis of contaminating microorganisms in commercially produced batches of MPCP complies with the requirements of SANCO/12116/2012 rev.0 (European Commission,2012).

Whole Genome Sequence (WGS) data of PhopGV isolate V65 was provided and compared with WGS data of other PhopGV isolates. The study confirmed the assignment of PhopGV isolate V65 to Phthorimaea operculella granulovirus species. In addition, it demonstrated that the PhopGV isolates are very similar, some even virtually identical except for marginal variations in the quantitative distribution of single nucleotide polymorphism in few positions. A standard bioassay using specific target pest is used for the quantification of PhopGV isolate V65 in MPCP, however it remains unclear how the target content of 2 × 10¹³ OB/L used to calculate the content of the microorganism (in terms of OB/L [bioassay]) in the individual batches of the product was determined/established (data gap, see Section10). Appropriate methods are available to test the presence of human pathogens in the MPCP.

The product is stable for 24 months in its commercial packaging when stored at 5°C. Data to demonstrate stability of the product upon freezing was not submitted, risk manager could consider the possibility to add the label: ‘Protect the product from frost’.

Residue definitions were not applicable for PhopGV isolate V65; therefore, post‐registration monitoring methods are not required.

2. BIOLOGICAL PROPERTIES OF THE MICROORGANISM

Phthorimaea operculella granulovirus belongs to the genus Betabaculovirus and the family Baculoviridae. PhopGV isolate V65 originates from natural, indigenous wild type virus, isolated from Tuta absoluta individuals descendant from T. absoluta individuals collected in a field in Spain, and is not genetically modified. At species level it is distributed worldwide.

Phthorimaea operculella granulovirus is highly host specific and replicates only in larvae of closely related species of Gelechiidae (such as P. operculella, Tecia solanivora, Tuta/Scrobipalpulpuloides absoluta, Symmetrischema tangolias, Eurysacca quinoae and Paraschema detectendum).

Mode of action of PhopGV is bi‐phasal infection of the larvae of the host. After oral ingestion of viral occlusion bodies, the virus replicates in the midgut cells (primary infection) and then infection is spread via non‐occluded viruses to other body tissues (secondary infection) leading to the insect's death.

As concerns the life cycle, upon ingestion by a host arthropod larva, the virus is replicated in host cells. Upon death of the arthropod host, occlusion bodies containing infectious virions can persist in the environment.

Information on the generation time (infection to infection) is not available in the dossier and identified as a data gap not essential to complete the risk assessment for the representative uses assessed, but information on this may have utility in national efficacy assessments (see Section10).

Phthorimaea operculella granuloviruses are not related to any known plant, animal (other than arthropods) or human pathogen (see Sections6.3 and 6.4).

As regards the genetic stability, information on the potential transfer of genetic material from Phthorimaea operculella granulovirus to other organisms was included in the amended assessment report. Infection and replication of Phthorimaea operculella granulovirus 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, 2024). Transfer of genetic material from Phthorimaea operculella granulovirus to other organisms except certain insect species is unlikely to be a concern when using Phthorimaea operculella granulovirus 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.

3. POTENTIAL EFFECTS ON HUMAN/MAMMALIAN HEALTH

The following guidance document was followed in the production of this conclusion: European Commission(2008).

Based on up‐to‐date information on Baculoviruses (including their biological properties and specificity to target organism, the lack of infectivity, pathogenicity and toxicity for mammalians or the production of any metabolites or toxins) and in line with Commission Regulation (EU) 2022/1438⁴ that refers to Baculoviruses as low risk active substances, there are no safety concerns for humans by P. operculella baculovirus.

4. RESIDUES

The assessment in the residue section is based on the following guidance documents: European Commission(2015).

An extensive body of knowledge is generated for the family of Baculoviridae which includes Phthorimaea operculella granulovirus by the EFSA BIOHAZ Panel in the context of the QPS assessments which performed an extensive literature review in 2009. At the time, 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 in the form of OBs are specific for (certain) insects and do not productively 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). Since then and until 2024 (see Section3.1), Baculoviridae were reviewed periodically in QPS updates upon notification of a new isolate to EFSA by the BIOHAZ Panel. The BIOHAZ Panel also took note of the long history of safe use as a biological pest control agent and related exposure of consumers with potentially remaining residues on agricultural commodities, and that there are no reports in the literature that indicate any adverse health effects following food consumption. This is in line with the outcome of the literature search provided by the applicant and assessed by the RMS for Phthorimaea operculella granulovirus following the EFSA guidance (EFSA,2011). Additional data to investigate residues on crops related to the use of Phthorimaea operculella granulovirus are therefore not necessary.

Contaminating microorganisms in the product comply with the applicable requirements (see Section1). It is noted that also Bacillus cereus is among the contamination in the product at acceptable levels. Consumers may subsequently be exposed to residues thereof. However, a calculation of possible residue levels of B. cereus on edible crops demonstrated that no exceedance of the threshold value of 10⁵ CFU/g on edible commodities at harvest (EFSA BIOHAZ Panel,2016) is to be expected.

With regard to the five assessment criteria according to the Commission guidance SANCO/11188/2013 Rev. 2 (European Commission,2015) for potential inclusion in Annex IV of Regulation (EC) No 396/2005, i.e. approval as basic substance (criterion I), listed in Annex I of Regulation (EC) No 396/2005 (criterion II), having no identified hazardous properties (criterion III), natural exposure is higher than the one linked to the use as a plant protection product (criterion IV), and consumer exposure is not expected considering the representative uses (criterion V), the criterium III was considered to be met for Phthorimaea operculella granulovirus because it did not indicate known health risks for consumers.

5. ENVIRONMENTAL FATE AND BEHAVIOUR

Information regarding the potential interference of Phthorimaea operculella granulovirus with the analytical systems for the control of the quality of drinking water provided for in Directive 98/83/EC⁵ was addressed in the applicant's 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 546/2011⁶). The virus Phthorimaea operculella granulovirus is unlikely to interfere with the analytical systems used for the control of the quality of drinking water which have bacteria as their target.

6. POTENTIAL EFFECTS ON NON‐TARGET ORGANISMS

Viruses do not produce metabolites, they can only modify host cell metabolism, as they self‐replicate within host organisms (see Section3.2). Infection and replication of Phthorimaea operculella granulovirus 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, 2024).

7. OVERVIEW OF THE RISK ASSESSMENT OF THE ORGANISM OR METABOLITES OF (POTENTIAL) CONCERN LISTED IN RESIDUE DEFINITIONS TRIGGERING ASSESSMENT OF EFFECTS DATA FOR THE ENVIRONMENTAL COMPARTMENTS (TABLES1, ​,2,2, ​,33–4)

8. 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.

9. CONCERNS AND RELATED DATA GAPS

10. 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:

• A justification on the representativeness of the batches used for proposing of specification (relevant for the representative uses evaluated; see Section1).

• A clarification on how the target content of 2 × 10¹³ OB/L used to calculate the content of the microorganism (in terms of OB/L [bioassay]) in the individual batches of the product was determined/established (relevant for the representative uses evaluated; see Section1).

• Information on the generation time of the PhopGV V‐65 strain (according to Regulation (EU) 283/2013) either experimentally or by read across from other strains with good argumentation, that may have utility in national efficacy assessments regarding recommendations on application interval was not available (not relevant for the representative uses evaluated; see Section2).

CONFLICT OF INTEREST

If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact ue.aporue.asfe@tnemeganamtseretni.

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2019‐00382

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Supporting information

ACKNOWLEDGEMENTS

EFSA wishes to thank the rapporteur Member State The Netherlands for the preparatory work on this scientific output.

APPENDIX A. List of end points for the active substance and the formulation for representative uses

Notes

EFSA (European Food Safety Authority), Álvarez, F., Arena, M., Auteri, D., Batista Leite, S., Binaglia, M., Castoldi, A. F., Chiusolo, A., Colagiorgi, A., Colas, M., Crivellente, F., De Lentdecker, C., De Magistris, I., Egsmose, M., Fait, G., Ferilli, F., Santonja, G. G., Gouliarmou, V., Halling, K., Nogareda, L. H., … Villamar‐Bouza, L. (2024). Peer review of the pesticide risk assessment of the active substance Phthorimaea operculella granulovirus. EFSA Journal, 22(8), e8976. 10.2903/j.efsa.2024.8976 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Approved: 19 July 2024

Notes

REFERENCES