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The adverse outcome pathway (AOP) framework has been rightly championed as a powerful tool for this purpose.120,162 An AOP provides a structured linkage from a molecular initiating event (MIE), through a cascade of cellular and physiological key events (KEs), to a final adverse outcome (AO) relevant to risk assessment.120 While this provides an invaluable conceptual roadmap, the classical linear structure of an AOP is a poor fit for the multi-modal nature of ENMs

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