Citation:

Villeneuve, D. AND G. Ankley. Chapter 12 of Toxicology of Fishes, "Adverse Outcome Pathways". Chapter 12, Toxicology of Fishes. CRC Press LLC, Boca Raton, FL, , N/A, (2024).

Impact/Purpose:

Use of data from molecular, cellular, biochemical, and pathway-based assays in chemical safety assessment requires an understanding of the biological and toxicological evidence that links perturbations at those lower levels of organization to adverse effects considered relevant for risk assessment and environmental decision-making. The AOP framework provides a systematic, and transparent method for assembling scientific information in a way that supports the use of these new data streams. The present book chapter provides an introduction to the AOP framework, key principles and AOP development, and the various lines of evidence that are assembled to provide scientific confidence needed to draw qualitative or quantitative inferences based on the pathway outlined. Providing this information in a textbook widely used by current and nascent professionals in aquatic ecotoxicology is expected to help foster greater understanding and engagement in this knowledge synthesis activity, thereby supporting the transition to 21st century toxicity testing.

Description:

Adverse outcome pathways (AOPs) are a framework for organizing scientific information concerning the linkage between biological perturbations measured at low levels of biological organization (e.g., molecular, biochemical, cellular) and adverse effects of concern for risk assessment, regulatory decision-making and/or resource management. While broad in application, efforts to transform toxicity testing from a system based on direct observation of adverse effects in intact animals to a more predictive approach based on in vitro and in silico high throughput screening methods have created the need to develop AOPs to facilitate data translation. AOP development is (1) stressor agnostic, (2) modular in structure, (3) pragmatically simple, but (4) capable of representing biological complexity as networks, and (5) continuously evolving as scientific knowledge expands. The foundation of AOP development is the assembly and evaluation weight of evidence that establishes causal relationships between measurable key events that serve as markers in the progression of toxicity from the initial perturbation of a biological target as a result of interaction with a stressor to and adverse outcome of concern. Where possible, that evidence includes quantitative understanding that can allow for prediction of the magnitude, severity, or probability of the adverse outcome based on upstream measurements. As of fall 2021 there were 33 fish-relevant AOPs out of over 360 AOPs described in the AOP-Wiki. However, there is ample opportunity for experts in fish toxicology, physiology, aquaculture, and other related fields to expand this complement of AOPs through both identifying AOPs with significant orthology to those described for mammals as well as developing AOPs relevant to unique aspects of fish biology. Concerted efforts in fish AOP development can support expanded use of data from new approach methodologies for chemical safety assessment in aquatic toxicology and ecological risk assessment.

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