Using Adverse Outcome Pathways to Group Chemicals into Toxicologically Relevant Categories

Marc Cronin, Liverpool John Moores University, UK

The prediction of chronic toxicity is the real challenge to the assessment of the safety of chemicals. Prolonged exposure to low doses of a chemical may cause non-lethal organ level toxicity. These effects typically arise from numerous mechanisms. Assessing these toxicities in vivo is costly financially and in terms of animal use, as well as the length of time of the tests. It is also difficult for traditional QSAR analysis to capture the mechanistic information i.e. multivariate analysis of lowest observable (adverse) effect levels (LO(A)ELs). Therefore, other suitable alternatives are required. There is increasing interest and regulatory acceptance of read-across predictions following grouping of similar chemicals, or analogues, into categories. The formation of categories for chronic effects can be addressed through the use of adverse outcome pathways (AOPs) to link the chemistry to the downstream effect at the organism and / or ecosystem level. This concept will be illustrated with examples of category formation for organ level toxicity. The funding of the European Union 6th Framework OSIRIS Integrated Project (GOCE-037017-OSIRIS) is gratefully acknowledged.