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MetaPath, an internationaldatabase on pesticidemetabolismXavier SardaResidues and Food Safety UnitDirectorate of Regulated Products Assessement"What does the future hold for harmonised human health risk assessment of plant protection products?“Berlin 23-24 November 2017
Evaluation of phytopharmaceutical active substances Regulatory Requirement world wilde Toxicology:– Rat (ADME) Consumer Safety:– Plants– Livestock– Processed commodities Environment:– Soil– Water Metabolism Studies Fate of radiolabelled active substances Identification of relevant metabolites– Toxicological properties– Distribution in different organs /compartments Residue Definition in food and environment compartmentsXavier Sarda, Berlin November 24th 2017
Metabolite management––––494 Active Substances approved in Europe (1359 in total) 3000 studies available (approved AS)Identify easily metabolites that are common to several pesticides.No tool availableMy name isM5 M5M5M3 M3M3M3M3M3M3M5M5M3M3M3M5M5M3M5 M5M5M5M5M3Xavier Sarda, Berlin November 24th 2017
MetaPath ProjectMetabolism Pathways database is a computationtool for reviewing metabolism data.Aim: “to Improve Efficiency In Pesticide Risk Assessments”Robust summaries of metabolism studies for use in regulatory peerreview process: Data evaluation tool;Metabolic profiles;Search and comparison;Project lead by US-EPAXavier Sarda, Berlin November 24th 2017
MetaPath User GroupOECD Project Proposal: MetaPath, a PesticideMetabolite Database with Data Evaluation Tools[ENV/JM/PEST(2010)12],MetaPath User Group: 45 experts fromAUS, AUT, BEL, CAN, DEU, FRA, SVK, UK, USA,EU (ECHA, EFSA),Industry (BIAC), OECD (Secretariat LMCBulgaria as Sofware developer)The MUGXavier Sarda, Berlin November 24th 2017
Metabolism Computational ToolsMetabolism Study Summary (MSS) Composers:data entry software (ready to be used by applicants)– Generate robust summary reports to be included in the Draft AssessmentReports (rat, livestock, plants, rotational crops)– Based on OECD Harmonised Templates (all OHT elements are included).– Generate e-submissions of summaries of metabolism studies by applicants to beincluded in MetaPath for use in regulatory peer review process (XML for dataupload in MetaPath)METAbolism PATHways (METAPATH):database and data evaluation tools– Database of metabolism pathways and metadata– Tool for structure search, map comparisons, identifying common residues, etcXavier Sarda, Berlin November 24th 2017
« MSS Composer »OrganismMaterials et methodsA : materialsChemical-internal drawing tool-Import smiles codesXavier Sarda, Berlin November 24th 2017
« MSS composer »Xavier Sarda, Berlin November 24th 2017
MetaPath databaseXavier Sarda, Berlin November 24th 2017
MetaPath databaseXavier Sarda, Berlin November 24th 2017 10
Identification of Common MetabolitesComparison of 2 metabolic mapsXavier Sarda, Berlin November 24th 2017
Identification of Common MetabolitesIdentify identical or similar molecule: (Search Chemicals)Xavier Sarda, Berlin November 24th 2017 12
Projet Advancement Studies in the base :– 376 active substances– 715 metabolic profiles 65% Rat 19% Livestock 9% Plants 7% Rotational crops– 80% quality assessmentXavier Sarda, Berlin November 24th 2017
OECD QSAR ToolBox new versionXavier Sarda, Berlin November 24th 2017
MetaPath in the OECD QSAR ToolBoxXavier Sarda, Berlin November 24th 2017
MetaPath in the OECD QSAR ToolBoxXavier Sarda, Berlin November 24th 2017
Use of MetaPath in pesticide evaluationMetabolismStudiesMSS tabaseMetabolicsimulation &predictionResidue DefinitionQSARHazardIdentificationRisk AssessmentRegulatory SummaryDocumentsGerrits et al. 2011Xavier Sarda, Berlin November 24th 2017
Conclusion– Identification of common metabolites Chemical Structure Similarity– Facilitate risk assessment Residue definition Aggregate RA––––Improve hazard identification (QSAR complementarity)Reduce animal testingMutualize between regulatory agenciesStreamline information flow between industry and regulatorsXavier Sarda, Berlin November 24th 2017
MetaPath User Group PerspectivesFuture:Increased participation in the MetaPath Users GroupPopulate the databaseElectronic data submission by registrants using MSS ComposersContinue integration with OECD QSAR Toolbox for public releaseof metabolism mapsDevelop MSS Composers for all environmental fate studiesSoil/Water/Air (as resources become available)Xavier Sarda, Berlin November 24th 2017
Thank YouXavier Sarda, Berlin November 24th 2017
database and data evaluation tools - Database of metabolism pathways and metadata - Tool for structure search, map comparisons, identifying common residues, etc . OECD QSAR ToolBox new version. Xavier Sarda, Berlin November 24th 2017 MetaPath in the OECD QSAR ToolBox. Xavier Sarda, Berlin November 24th 2017
