Chapter 14: Adverse Outcome Pathways: A Way of Linking Chemical Structure to In Vivo Toxicological Hazards Check Access

The concept of adverse outcome pathways is presented here as an organising principle to aid assessment and formation of toxicologically meaningful categories for hazard endpoints, especially chronic health effects where different molecular initiating events and different key biological events lead to the same in vivo outcome. A toxicologically meaningful category can be thought of as a group of chemicals whose human health and/or environmental toxicological properties are likely to be similar or follow a regular pattern for a particular hazard. An adverse outcome pathway is a description of plausible causal linkages, which illustrates how the molecular initiating event, leads to the key biochemical, cellular, physiological, behavioural etc. responses, which characterise the biological cascade across the different levels of biological organisation. The concept of the adverse outcome pathway is discussed in the context of the more stringent mechanism of action approach used in pharmacology. The value of this concept is demonstrated with five examples, each with a different type of molecular initiating event. The pathways concept is also discussed in context of elaborate hazards where the in vivo effects may be cumulative or life stage dependent.