| Literature DB >> 28958911 |
Roland Buesen1, Brian N Chorley2, Beatriz da Silva Lima3, George Daston4, Lize Deferme5, Timothy Ebbels6, Timothy W Gant7, Amber Goetz8, John Greally9, Laura Gribaldo10, Jörg Hackermüller11, Bruno Hubesch12, Danyel Jennen13, Kamin Johnson14, Jun Kanno15, Hans-Martin Kauffmann1, Madeleine Laffont16, Patrick McMullen17, Richard Meehan18, Mark Pemberton19, Stefania Perdichizzi20, Aldert H Piersma21, Ursula G Sauer22, Kerstin Schmidt23, Hervé Seitz24, Kayo Sumida25, Knut E Tollefsen26, Weida Tong27, Tewes Tralau28, Ben van Ravenzwaay1, Ralf J M Weber29, Andrew Worth10, Carole Yauk30, Alan Poole31.
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. CrownEntities:
Keywords: Adverse outcome pathway (AOP); Differentially expressed genes; Gene expression; Good laboratory practice (GLP); Metabolomics; Mode-of-action (MoA); Regulatory toxicology; Transcriptomics; Weight-of-evidence (WoE)
Mesh:
Year: 2017 PMID: 28958911 PMCID: PMC6816021 DOI: 10.1016/j.yrtph.2017.09.002
Source DB: PubMed Journal: Regul Toxicol Pharmacol ISSN: 0273-2300 Impact factor: 3.271