Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology

To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modelling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organising knowledge about the progression of toxicity events across scales of biological organisation that lead to adverse outcomes relevant for risk assessment. In this study, the authors focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritise higher tier toxicity testing. The authors argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. Information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species we also discussed. Recommendations have been provided for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modelling approaches and with evolutionary life history theory. The authors concluded that the extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models describing species responses to toxicants. This will allow a more efficient application of AOP knowledge for quantitative chemical- and site-specific risk assessment as well as for extrapolation across species in the future.

Authors: Groh KJ, Carvalho RN, Chipman JK, Denslow ND, Halder M, Murphy CA, Roelofs D, Rolaki A, Schirmer K, Watanabe KH. ;Chemosphere. 2015 Feb;120:764-77. doi: 10.1016/j.chemosphere.2014.09.068. Epub 2014 Nov 11. ;