Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8551910 | Regulatory Toxicology and Pharmacology | 2017 | 40 Pages |
Abstract
Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data. The workshop participants confirmed the relevance of these Frameworks to facilitate the regulatory applicability and use of 'omics data, and the workshop discussions provided input for their further elaboration. Additionally, the key objective (iv) to establish approaches to connect 'omics perturbations to phenotypic alterations was addressed. Generally, it was considered promising to strive to link gene expression changes and pathway perturbations to the phenotype by mapping them to specific adverse outcome pathways. While further work is necessary before gene expression changes can be used to establish safe levels of substance exposure, the ECETOC workshop provided important incentives towards achieving this goal.
Keywords
MAQCGHSqRT-PCRPHENCTRLC-MSLRIECETOCIngenuity Pathways AnalysisOECDCLPGLPMIEC&LNOAELBFRMOAPXRLOAELCeficRIVMEPAGlobally harmonised systemFDAWeight-of-evidence (WoE)WOEITSPODTRFAOPRNA-seqSOPEURL ECVAMEuropean Chemical Industry Councilnuclear magnetic resonanceEnvironmental Protection AgencyIntegrated testing strategyPublic Health EnglandGene expressionanalysis of varianceANOVANMRGood Laboratory PracticeRNA-sequencingMode-of-actionstandard operating proceduremolecular initiating eventFood and Drug AdministrationOrganisation for Economic Cooperation and DevelopmentRegulatory toxicologyDEGclassification and labellingClassification, Labelling and PackagingCARMIAMEMetabolomicsTranscriptomicsEuropean Centre for Ecotoxicology and Toxicology of ChemicalsNational Center for Toxicological ResearchAdverse outcome pathway (AOP)adverse outcome pathwayHealth and Environmental Sciences InstitutePoint of departureHESINo observed adverse effect levelquantitative real-time polymerase chain reactionMOEWeight-of-evidenceDifferentially expressed geneDifferentially expressed genesLiquid chromatography – Mass spectrometryLowest observed adverse effect levelquality controlPregnane X receptorIATA
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Authors
Roland Buesen, Brian N. Chorley, Beatriz da Silva Lima, George Daston, Lize Deferme, Timothy Ebbels, Timothy W. Gant, Amber Goetz, John Greally, Laura Gribaldo, Jörg Hackermüller, Bruno Hubesch, Danyel Jennen, Kamin Johnson, Jun Kanno,