Periodic Reporting for period 1 - RATION (Risk AssessmenT InnOvatioN for low-risk pesticides)
Reporting period: 2022-11-01 to 2024-04-30
Potential low-risk pesticides (LRP) like plant extracts, semiochemicals, pheromones, microbials, and ds-RNA are coming to replace synthetic ones globally. But EU lacks a specific risk assessment scheme for LRPs, hindering their market uptake. RATION aims to develop risk assessment schemes and tools tailored to LRPs, involving stakeholders and fostering innovation. This multi-partner effort targets regulatory barriers and aims to accelerate plant protection innovation.
In the project's initial phase, the Stakeholder Forum (StaFo) was established, now comprising nearly 80 members from regulatory bodies, academia, and industry. Three workshops were organized, focusing on different aspects of LRP risk assessment. Formulated questionnaires probed into the hurdles faced by national authorities in assessing both active substances and products. These inquiries, distributed to EU national authorities, covered a spectrum of LRP, including plant extracts, pheromones, ds-RNA, and microbials. Results from these inquiries were presented at scientific and stakeholder meetings, with a comprehensive paper slated for publication. Highlights of the questionnaires were (a) the understaffing of most MS regulatory bodies (ii) the lack of personnel with specific knowledge to undertake the risk assessment of LRP (iii) the perception of MS regulatory bodies that risk assessment of LRP is more demanding compared to synthetic ones. In parallel, a report was compiled examining current risk assessment procedures per LRP, shedding light on updates, revisions, and ongoing recommendations. The report also undertook a comparative analysis with US market requirements, revealing discrepancies in data requirements and test methodologies. Notably, the EU exhibited a more conservative approach, particularly concerning potential hazards of secondary metabolites. Writing of a scientific paper on this work are currently underway.
The recent implementation of guidance (Nov. 2022) regarding microbial pesticides risk assessment (secondary metabolites and antimicrobial resistance) was reviewed and considered as benchmark for further innovation. In principal, three model microbial substances, that will be used in the proof of concept exercise, were identified, focusing on diverse classes of microbial agents (bacteria, fungi, virus) and their target pests. Efforts were directed towards:
- (i) reviewing and identifying gaps and areas were improvement regarding testing for ecotoxicity of microbial pesticides and formulating testing protocols are needed,
- (ii) improving pathogenicity/infectivity assessment and, microbial secondary metabolites, and antimicrobial resistance traits through whole genome sequencing (WGS) analysis. A development of a novel improved pipeline (vs MoPs EFSA tool) for WGS of microbials is under development,
- (ii) test cases for novel microbiome solutions that are at the doorstep of EU were identified (consortia, phages, and protists), and first thoughts for regulating these solutions were addressed.
Delving into the regulatory landscape of plant extracts and pheromones, thorough reviews and analyses of areas of concern regarding ecotox and exposure assessment were conducted. Model products per group were identified and included in testing. Problem formulation based on these products were established. Experiments with novel and regulatory-approved plant extracts, employing OECD standard test species and innovative techniques such as QSAR and mass spectrometry are on-going. Regulatory new approaches were scrutinised and evaluated within this framework.
Target genes (PSMB5, actin and gfp) were selected for synthesizing dsRNA with the target pest being the Colorado potato beetle. Naked and Chitosan formulated dsRNA were prepared. Bioinformatics analyses using surrogate and non-surrogate NTOs identified species that could be potentially affect by dsRNA, and testing is underway to verify prediction of ecotoxicity. In addition, a bioinformatic tool dedicated to the prediction of potential undesirable effects of dsRNA molecules on NTOs is under development. On going testing develop methods to follow the dynamics of dsRNA in environmental matrices, determine their environmental fate, and the applicability of existing mathematical models for predicting dsRNA e-fate. First tests demonstrated high mortality rates in the beetle population following the application of PSMB5 and Actin dsRNA.
Project partners have participated in several dissemination and networking activities, and four papers have already being published. This will continue to improve communication with relevant parties through the website, the digital channels of the project, alongside the day-to-day coordination and management of the project.
The recent implementation of guidance (Nov. 2022) regarding microbial pesticides risk assessment (secondary metabolites and antimicrobial resistance) was reviewed and considered as benchmark for further innovation. In principal, three model microbial substances, that will be used in the proof of concept exercise, were identified, focusing on diverse classes of microbial agents (bacteria, fungi, virus) and their target pests. Efforts were directed towards:
- (i) reviewing and identifying gaps and areas were improvement regarding testing for ecotoxicity of microbial pesticides and formulating testing protocols are needed,
- (ii) improving pathogenicity/infectivity assessment and, microbial secondary metabolites, and antimicrobial resistance traits through whole genome sequencing (WGS) analysis. A development of a novel improved pipeline (vs MoPs EFSA tool) for WGS of microbials is under development,
- (ii) test cases for novel microbiome solutions that are at the doorstep of EU were identified (consortia, phages, and protists), and first thoughts for regulating these solutions were addressed.
Delving into the regulatory landscape of plant extracts and pheromones, thorough reviews and analyses of areas of concern regarding ecotox and exposure assessment were conducted. Model products per group were identified and included in testing. Problem formulation based on these products were established. Experiments with novel and regulatory-approved plant extracts, employing OECD standard test species and innovative techniques such as QSAR and mass spectrometry are on-going. Regulatory new approaches were scrutinised and evaluated within this framework.
Target genes (PSMB5, actin and gfp) were selected for synthesizing dsRNA with the target pest being the Colorado potato beetle. Naked and Chitosan formulated dsRNA were prepared. Bioinformatics analyses using surrogate and non-surrogate NTOs identified species that could be potentially affect by dsRNA, and testing is underway to verify prediction of ecotoxicity. In addition, a bioinformatic tool dedicated to the prediction of potential undesirable effects of dsRNA molecules on NTOs is under development. On going testing develop methods to follow the dynamics of dsRNA in environmental matrices, determine their environmental fate, and the applicability of existing mathematical models for predicting dsRNA e-fate. First tests demonstrated high mortality rates in the beetle population following the application of PSMB5 and Actin dsRNA.
Project partners have participated in several dissemination and networking activities, and four papers have already being published. This will continue to improve communication with relevant parties through the website, the digital channels of the project, alongside the day-to-day coordination and management of the project.
It is envisaged that StaFo will act as an arena of interaction that brings together all relevant sectors of LRPs. The first EU-wide survey focusing on MS regulatory bodies was undertaken. It highlighted deficiencies at the regulatory process for LPRs and steps that will facilitate innovation in the market uptake of LRPs. A comprehensive summary of the current regulatory status of LRPs along with a comparison with regulatory frameworks in other jurisdictions was prepared gathering fragmented knowledge.
Highlights on microbial pesticides inlcude (i) participation of RATION in OECD action for advancing testing for pathogenicity/infectivity of microbials (ii) on-going development of a WGS analysis tool for decision-making regarding pathogenicity, AMR and secondary metabolites for microbials overcoming deficiencies of MoPS (iii) novel microbial solutions that are under development like consortia, bacteriophages and protists have been identified, and lines for work to support regulatory framework development were identified.
Highlights on botanicals and semiochemicals/pheromones include (a) review of common areas of concern regarding botanical pesticides, ways of addressing including novel ecotoxicological testing approaches are explored (b) current exposure assessment tools for semiochemicals and plant extracts have been scrutinized and advanced methods for exposure assessment of botanicals have been implemented, while efforts for the development of new models for calculation of background levels for semiochemicals are underway.
Highlights on ds-RNA pesticides include (a) development of a novel bioinformatics tool for assessing potential effects of dsRNA molecules on NTOs according to genome availability (b) Ecotoxicity tests under development, adapted to the mode of action of dsRNA (c) nucleic acid detection and quantification methods are being developed to detect and quantify dsRNA in the environment that would be used for exposure assessment.
Several partners have participated in conferences, OECD group meetings, EC WG of biopesticides etc and four benchmarking publications, videos and articles have been produced.
Highlights on microbial pesticides inlcude (i) participation of RATION in OECD action for advancing testing for pathogenicity/infectivity of microbials (ii) on-going development of a WGS analysis tool for decision-making regarding pathogenicity, AMR and secondary metabolites for microbials overcoming deficiencies of MoPS (iii) novel microbial solutions that are under development like consortia, bacteriophages and protists have been identified, and lines for work to support regulatory framework development were identified.
Highlights on botanicals and semiochemicals/pheromones include (a) review of common areas of concern regarding botanical pesticides, ways of addressing including novel ecotoxicological testing approaches are explored (b) current exposure assessment tools for semiochemicals and plant extracts have been scrutinized and advanced methods for exposure assessment of botanicals have been implemented, while efforts for the development of new models for calculation of background levels for semiochemicals are underway.
Highlights on ds-RNA pesticides include (a) development of a novel bioinformatics tool for assessing potential effects of dsRNA molecules on NTOs according to genome availability (b) Ecotoxicity tests under development, adapted to the mode of action of dsRNA (c) nucleic acid detection and quantification methods are being developed to detect and quantify dsRNA in the environment that would be used for exposure assessment.
Several partners have participated in conferences, OECD group meetings, EC WG of biopesticides etc and four benchmarking publications, videos and articles have been produced.