About

Abstract: A so-called adverse outcome pathway (AOP) is a recent toxicological concept proposed to provide a mechanistic representation of biological perturbation over different layers of biological organization at the molecular, cellular and system levels. The perturbation would lead to an adverse outcome at both the population and individual level. Although the concept is independent from a given chemical, some AOPs have nevertheless been proposed with a specific chemical-induced perturbation defined as a stressor. Many chemicals can putatively interfere with an AOP and such information would be relevant for regulatory decision-making. Therefore, we mapped the bioactivity of the ToxCast HTS assay data to a list of 207 AOPs maintained by OECD. After curation, 6,111 chemicals were identified as active at a non-cytotoxic concentration on 906 bioassays corresponding to molecular initiating events (MIEs) or key events (KEs) in AOPs. With this analysis, we have observed a variety of relevant connections between chemicals and AOP components. Indeed, some chemicals target several MIEs whereas other chemicals are more specific. Furthermore, some MIEs and KEs are involved in several AOPs suggesting potential impact of stressors to several and different adverse outcomes. As an example of this mapping, we investigated endocrine disruptor chemicals (EDCs) tested in ToxCast and their relations to known AOPs through MIEs and KEs. The obtained results may help the prioritization of chemicals to assess risk-based evaluations in the context of human health.

Contact

Alejandro Aguayo-Orozco: alejandro.orozco [at] cpr.ku.dk

Olivier Taboureau: alejandro.orozco [at] cpr.ku.dk

Who are we?

Alejandro Aguayo-Orozco

Ph.D. in Systems Biology

Olivier Taboureau

Professor, Ph.D.

Søren Brunak

Research director, Professor, Ph.D.

Troels Siggaard

Software Developer