Overview

Regulatory agencies increasingly recognise the need for fast and reliable methods to assess the safety of large numbers of chemicals. Omics technologies, such as high-throughput transcriptomics (HTTr) and phenotypic profiling (HTPP), combined with systems toxicology models, offer promising solutions. This project supports the use of these technologies to improve chemical grouping and read-across (RAx ↗), contributing to standardisation, reproducibility, and regulatory acceptance.

The project has three main goals:

• to co-develop with the OECD ↗ a database and interface for the OECD Omics Reporting Framework (OORF) ↗;
• to create an interoperable and toxicologically-oriented pathway and gene set ontology for co-expression models linked to Adverse Outcome Pathways (AOPs ↗);
• to integrate chemical structure similarity with omics and phenotypic mode-of-action data, demonstrated via case studies.

These case studies will use large publicly available datasets from MCF7 and U2OS cell lines, which include data for over 1,500 compounds of concern, such as PFAS, BPAs, and pesticides. This enables a broad exploration of human and environmental toxicological effects.

These cell lines are highly relevant for PARC priority endpoints such as endocrine and metabolic disruption, reproductive toxicity, and non-genotoxic carcinogenicity.

The project directly supports PARC areas focused on replacing animal testing with NAMs and developing read-across case studies. It will also contribute to improving guidance under REACH ↗, particularly ECHA ↗’s recommendations in section 3.7 of the ECHA-13-R-02-EN document ↗.