Adverse Outcome Pathway-based Screening Strategies for an Animal-free Safety Assessment of Chemicals

Currently the assessment of risk to human health from exposure to manufactured chemicals is mainly based on experiments performed on living animals (in vivo). Substantial efforts are being undertaken to develop alternative solutions to in vivo toxicity testing. Behind these efforts is an emerging paradigm-shift towards systems- and pathway-based approaches that rely on the understanding of biological processes that might be disturbed by the introduction of a chemical into a living organism which may lead to an adverse outcome. This new paradigm based on the Mode-of-Action (MoA) framework postulates that any adverse human health effect caused by exposure to an exogenous substance can be described by a series of causally linked biochemical or biological key events with measurable parameters. The elaboration of mechanistic knowledge through literature research is necessary for a MoA-driven design of integrated testing strategies using in vitro methods for in vivo predictions. The objective of our on-going research is to demonstrate the feasibility of an integrated approach to predict human toxicity following the Adverse Outcome Pathway (AOP) framework. In our publication: ‘Taking a mode-of-action approach to designing a hepatotoxicity screening strategy using the HepaRG cell model and high content imaging’ we reported our experiments related to our design of an in vitro testing strategy to identify chemicals that are potentially hepatotoxic in humans with the purpose of associating them with specific MoA categories and to group them accordingly. This pioneered an innovative way of using data from in vitro experiments to group chemicals based on their MoA, which is likely to be an important step in a toxicity testing strategy. This contribution towards the goal of replacing animals in safety testing was awarded the Lush Science Prize 2012.

LANDESMANN Brigitte;  MENNECOZZI Milena;  BERGGREN Elisabet;  WHELAN Maurice; 

2014-03-24

FUND FOR THE REPLACEMENT OF ANIMALS IN MEDICAL EXPERIMENTS

JRC84925

0306-2465,   

http://www.frame.org.uk/page.php?pg_id=19,    https://publications.jrc.ec.europa.eu/repository/handle/JRC84925,