Adverse outcome pathways

Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornimg MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, ViUeneuve DL (2010) Adverse outcome pathways a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29 730-741... 

Extensive reviews concerning the opportunities for the development of in vitro sensitization methods already exist [41-44], These reviews show that essentially all of the methods address one or other of the key mechanistic steps in the induction of skin sensitization—and these are nicely represented in the OECD adverse outcome pathway description [45], From this large body of work, three methods have emerged whose initial promise has been substantiated by demonstration not only of their predictive merits but also by verification of their robustness in terms of inter-laboratory transferability and within and between laboratory reproducibility [46]. The three methods are the direct peptide reactivity assay (DPRA) [47, 48], KeratinoSens [49, 50], and the human Cell Line Activation Test (h-CLAT) [51-53]. The first of these, the DPRA, addresses the question of chemical reactivity, the second investigates an aspect of keratinocyte activation... 

OECD (2012) The adverse outcome pathway for skin sensitization. Organisation for Economic Cooperation and Development, Paris... 

Jennings P (2013) Stress response pathways, toxicity pathways and adverse outcome pathways. Arch Toxicol 87(1) 13-14... 

Several of the validated in vitro methods aim to be validated as full replacement methods to offer an alternative for in vivo test guideline method(s). However, for integrated testing strategies, validated mechanistic tools targeting key events in adverse outcome pathways are necessary to generate state-of-the-art alternative approaches to conventional toxicological test methods based on laboratory animals. 

Schultz, T. W. Adverse outcome pathways a way of linking chemical structure to in vivo toxicological hazards In In Silico Toxicology Principle and Applications, Cronin, M. Madden, J. (Eds.), The Royal Society of Chemistry, London, 2010, pp. 351-376. 

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