Chemical-induced liver cancer: an adverse outcome pathway perspective

The evaluation of the potential carcinogenicity is a key consideration in the risk assessment of chemicals. Predictive toxicology is currently switching toward non-animal approaches that rely on the mechanistic understanding of toxicity.

Adverse outcome pathways (AOPs) present toxicological processes, including chemical-induced carcinogenicity, in a visual and comprehensive manner, which serve as the conceptual backbone for the development of non-animal approaches eligible for hazard identification. The current review provides an overview of the available AOPs leading to liver cancer and discusses their use in advanced testing of liver carcinogenic chemicals. Moreover, the challenges related to their use in risk assessment are outlined, including the exploitation of available data, the need for semantic ontologies, and the development of quantitative AOPs.

To exploit the potential of liver cancer AOPs in the field of risk assessment, 3 immediate prerequisites need to be fulfilled. These include developing human relevant AOPs for chemical-induced liver cancer, increasing the number of AOPs integrating quantitative toxicodynamic and toxicokinetic data, and developing a liver cancer AOP network. As AOPs and other areas in the field continue to evolve, liver cancer AOPs will progress into a reliable and robust tool serving future risk assessment and management.