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Updated: Oct 3, 2025

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Adverse Outcome Pathways as Versatile Tools in Liver Toxicity Testing.

Emma Arnesdotter¹, Eva Gijbels¹, Bruna Dos Santos Rodrigues¹

¹Department of Pharmaceutical and Pharmacological Sciences, Entity of In Vitro Toxicology, Vrije Universiteit Brussel, Brussels, Belgium.

Methods in Molecular Biology (Clifton, N.J.)

|February 21, 2022

Summary

Adverse outcome pathways (AOPs) visualize toxicological mechanisms. These pathways aid in chemical risk assessment, prioritizing substances, and developing new in vitro toxicity tests.

Keywords:

AOP Cancer Cholestasis Fibrosis Liver toxicity Steatosis

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Area of Science:

Toxicology
Chemical Risk Assessment

Background:

Adverse outcome pathways (AOPs) provide a framework to understand and visualize the mechanistic basis of toxicological effects.
AOPs consist of a molecular initiating event, key events, key event relationships, and an adverse outcome.
Development and evaluation of AOPs should align with Organization for Economic Cooperation and Development guidelines.

Purpose of the Study:

To highlight the utility and applications of Adverse Outcome Pathways (AOPs) in toxicology and chemical risk assessment.
To emphasize the role of AOPs in understanding hepatotoxicity.
To explore the application of AOPs in quantitative structure-activity relationships, prioritization, and in vitro testing.

Main Methods:

Conceptual framework development for Adverse Outcome Pathways.
Review of existing AOPs, particularly those related to hepatotoxicity.
Analysis of proposed applications in risk assessment and testing strategies.

Main Results:

AOPs offer a structured approach to toxicological mechanisms.
The liver is a common target for systemic toxicity, leading to AOP development for hepatotoxicity.
AOPs facilitate quantitative structure-activity relationships, prioritization, and novel in vitro toxicity testing.

Conclusions:

Adverse outcome pathways are valuable tools for understanding and predicting toxicological effects.
AOPs have significant potential to advance chemical risk assessment and the development of predictive toxicology methods.
The structured nature of AOPs supports their integration into regulatory science and testing strategies.