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.
Original language | English |
---|---|
Pages (from-to) | S3-S13 |
Journal | Regulatory Toxicology and Pharmacology |
Volume | 91 |
DOIs | |
Publication status | Published - Dec 2017 |
Bibliographical note
Funding Information:The content described in this article has been reviewed by the National Health and Environmental Research Laboratory of the U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The views presented in this article do not necessarily reflect current or future opinion or policy of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification and not intended as an endorsement. LG and AW are staff members of the Commission. The opinions expressed are those of the authors and do not necessarily reflect the official views of the European Commission.
Publisher Copyright:
© 2017
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)