Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop

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: 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).

Figure 1:

Steps of ‘omics studies (taking the example of transcriptomics) and their correspondence to the work streams of the ECETOC workshop GLP: Good Laboratory Practice; WoE: Weight-of-evidence.