Chemical-induced liver cancer: an adverse outcome pathway perspective

ABSTRACT

Introduction

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.

Areas covered

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.

Expert Opinion

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.

KEYWORDS:

• Adverse outcome pathway
• chemical
• carcinogenicity prediction
• liver cancer
• risk assessment

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Conceptualization: J.S.-S. and M.V.; methodology: J.S.-S., E.C., S.D.B. and A.V.; data analysis: J.S.-S., E.C., S.D.B. and A.V.; original draft preparation: J.S.-S. and M.V.; review and editing: J.S.-S., E.C., S.D.B., A.V. and M.V.; supervision: M.V.; project administration: J.S.-S. and M.V.; funding acquisition: J.S.S. and M.V. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This paper was not funded.