LAUSR

An adverse outcome pathway (AOP) is a description of the sequence of causally linked events, spanning multiple levels of biological organization, required to produce a toxic effect when an organism is exposed to a stressor such as a chemical. In essence, an AOP is a depiction of a complex toxicological process in a simpli fi ed, stepwise, sequential format. An AOP tries to describe the responses of complex biological systems whose behavior is intrinsically dif fi cult to model because of the many relationships and interactions between the various components of the system and because of the emergent properties that often arise as a result of such interactions. An important question, therefore, is whether the AOP framework itself should, by design, also be a complex system to be able to capture the toxicological reality or whether a simpli fi ed repre-sentation of the perturbed biology is indeed suf fi cient. This question has been raised ever since the introduction of the AOP framework in 2010 (Ankley et al., 2010). Some argue that the “ linear ” nature of AOPs is too simple in terms of conceptual model design and data type availability to adequately capture the complexity of any realistic toxicological scenario, even when considering AOP networks that are formed by connecting different linear AOPs. Others feel that the AOP framework is too complex and too overwhelming to be useful. Development of an AOP can be perceived as a daunting task, requiring the knowledge and evidence to connect all the dots between the different events, including establishing causality and essen-tiality, documenting dose and time concordance, and so on. Thus, AOPs are often perceived as being too