The use of systems biology in chemical risk assessment

Abstract

Risk assessment of toxicological compounds has traditionally relied upon animal experimentation. Omics technologies, especially genomics and proteomics, generate large amounts of data on genome-wide gene expression profiles, protein expression, and protein interaction with xenobiotics (notably toxic ones), enabling the study of chemical action across multiple scales of complexity from molecular to systems levels. This allows detailed exploration of the mechanisms of toxicity. Although all omics technologies may contribute to better understanding of the toxicological impact of chemicals, their application in chemical risk assessment has not yet been recommended for regulatory purposes. With the recent development of the adverse outcome pathway concept, the combination of the modular framework of adverse outcome pathway, together with the network organisation within systems biology, offers an opportunity to shift the paradigm of chemical risk assessment towards a better understanding of chemical toxicology mechanisms. In this review, we discuss the advantages of the use of systems biology tools in chemical risk assessment, as well as the challenges they present, such as model over-parametrisation in quantitative modelling, data gap management in poorly studied substances and the lack of expertise in bridging the new approaches to regulatory levels.