09-11-2012, 02:15 PM
Guidance Document on the assessment of new isolates of baculovirus species already included in Annex I of Council Directive 91/414/EEC
Guidance Document.pdf (Size: 121.55 KB / Downloads: 134)
Introduction
It is proposed to include Baculoviruses on species level in Annex I, and to add new isolates (after they have been evaluated) in a separate list, to be maintained in the Review Report. This list shall be amended by taking note in the Standing Committee on the Food Chain and Animal Health. New isolates shall be applied for at Member state level. The applicant asks for a national authorisation. The Member State shall assess the properties of the new isolate and compare this with the reference isolate.
Legal basis/Status quo
According to the Sanco document: Guidance developed within the Standing Committee on the Food Chain and Animal Health on the taxonomic level of micro-organisms to be included in Annex I to Directive 91/414/EEC (Sanco/10754/rev. 5) it has been concluded that micro-organisms should be included into Annex I at the strain level. However, the document also contains the following sentence:
General view:
“In other cases in which the species is known to be relatively homogeneous and well studied it may be decided by experts if certain questions may be handled on a species/subspecies rather than on a strain level.”
Background / Justification
Baculoviruses represent a family of double stranded DNA viruses that exclusively infect Arthropoda. The vast majority of the known species are confined to insects, predominantly Lepidoptera, with fewer species in Diptera and Hymenoptera. Some baculoviruses are used in plant protection products for the biological control of insect pests in agriculture, horticulture and forestry. Baculoviruses used as active substances in plant protection products in the EU are regulated as micro-organisms according to Council Directive 91/414/EEC. Data requirements for the registration of baculoviruses as active substances and of products based on baculoviruses are laid down in Council Directive 91/414/EEC, amended by Commission Directive 2001/36/EC. The Uniform Principles for evaluation and authorisation of plant protection products containing micro-organisms are laid down in Council Directive 2005/25/EC.
The OECD Consensus Document (ENV/JM/MONO (2002)1)
In 2002, the OECD released the “Consensus Document on information used in the assessment of environmental applications involving Baculoviruses”. This document reviewed all information publicly available at that time which was considered relevant for safety assessments of baculoviruses. This includes the biology of baculoviruses, infection mechanisms in the host, host range determination, methods for molecular characterisation of isolates, and the history of use in plant protection products. Extensive information was gathered on effects of baculoviruses on human health including infectivity, replication in vertebrate cells, genotoxicity and carcinogenicity. Ecological information summarized in the OECD consensus document includes persistence and dissemination in the environment, host specificity and effects on non-target organisms.
Genetic composition of baculovirus isolates
Micro-organisms are generally registered at strain level. Bacterial and fungal strains used in plant protection products derive from single colonies or spores and are consequently genetically homogenous. Different bacterial and fungal strains from the same species may have significant differences in their biology, especially in the production of secondary metabolites.
Baculoviruses, however, represent a unique case among micro-organisms used in plant protection products in that they consist of a mixture of different, often very similar genotypes. These variations may influence some biological properties, such as the virulence to their specific target host, but they appear to have no consequences on the safety towards non-target organisms or on the environment. The composition of this mixture depends among other factors on the genotype of the host used to multiply the baculovirus. Isolation of a single genotype is extremely difficult if not impossible and even not desired since genetic variation is needed to account for variation in the target organisms. Therefore, the demand to evaluate micro-organisms at strain level is not applicable for baculoviruses.
Potential risks from plant protection products containing baculoviruses
Due to the recorded safety of baculoviruses, potential risks from baculovirus products are minimal and can occur probably rather through product components than the baculovirus itself.
All baculoviruses have to be produced in vivo in order to be infective to larvae. Host insect or media components might be allergenic as any other biological molecule. Hairs from some lepidopteran larvae (caterpillars) are known for their irritating and sensitising potential. Sensitisation through baculovirus-containing products was tested and no effects were found in most cases for products containing CpGV (produced in Cydia pomonella larvae, non-hairy) and SpliNPV (Spodoptera littoralis, non-hairy larvae). However, some test results might indicate a sensitisation potential of viruses of non-hairy larvae which might depend on the virus content of the formulation (CpGV, one formulation).
Conclusion
Based on the conclusions from the OECD consensus document (ENV/JM/MONO (2002)1), the REBECA Proposal on Facilitations in the Regulation of Plant Protection Products containing Baculoviruses (January 2007) and on the first results of the evaluation of dossiers of isolates of Spodoptera exigua NPV, CpGV and AoGV, experts of participating RMSs concluded in the List 4, Part C micro-organisms meeting (30 January – 1 February 2007) that the Baculoviruses themselves can be regarded as harmless concerning effects on human health and the environment.
Therefore it was proposed in that meeting to include Baculoviruses (not genetically modified) on species level in Annex I of Directive 91/414/EEC, and to add the different isolates (after they have been evaluated) to a separate list, to be maintained in the Review Report and to be amended by taking note in the Standing Committee. This approach has been confirmed by a decision in the Standing Committee on May 15, 2007 were Spodoptera exigua NPV was listed at species level in Annex I.