Computational Strategies for Assessing Adverse Outcome Pathways

Author(s)
Rita Ortega-Vallbona, Martina Palomino-Schätzlein, Laia Tolosa, Emilio Benfenati, Gerhard F. Ecker, Rafael Gozalbes, Eva Serrano-Candelas
Abstract

The evolving landscape of chemical risk assessment is increasingly focused on developing tiered, mechanistically driven approaches that avoid the use of animal experiments. In this context, adverse outcome pathways have gained importance for evaluating various types of chemical-induced toxicity. Using hepatic steatosis as a case study, this review explores the use of diverse computational techniques, such as structure–activity relationship models, quantitative structure–activity relationship models, read-across methods, omics data analysis, and structure-based approaches to fill data gaps within adverse outcome pathway networks. Emphasizing the regulatory acceptance of each technique, we examine how these methodologies can be integrated to provide a comprehensive understanding of chemical toxicity. This review highlights the transformative impact of in silico techniques in toxicology, proposing guidelines for their application in evidence gathering for developing and filling data gaps in adverse outcome pathway networks. These guidelines can be applied to other cases, advancing the field of toxicological risk assessment.

Organisation(s)
Department of Pharmaceutical Sciences
External organisation(s)
ProtoQSAR SL, Instituto de Investigación Sanitaria La Fe, Instituto de Salud Carlos III (ISCIII), Institute for Pharmacological Research Mario Negri, MolDrug AI Systems S.L.
Journal
International Journal of Molecular Sciences
Volume
25
ISSN
1661-6596
DOI
https://doi.org/10.3390/ijms252011154
Publication date
10-2024
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry
Keywords
ASJC Scopus subject areas
Catalysis, Molecular Biology, Spectroscopy, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/b49649a9-6395-4a16-bb7d-dff8d4798448