Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment

Comparative human and rat neurospheres reveal species differences in chemical effects on neurodevelopmental key events

“…High-content image analysis methods are on the way to further facilitate evaluation of such complex, multi-cellular structures. Data from such testing strategies can then be integrated into the 'Adverse Outcome Pathway' (AOP) framework (Ankley et al 2010;Bal-Price et al 2015b) and will help to develop so called 'Integrated Approaches to Testing Assessment' (IATA), which gather and weigh any existing relevant information-in vivo, in vitro, in silico and in chemico-to support regulatory or safety decisions (Tollefsen et al 2014).…”

An Introduction to the Challenges for Risk Assessment of Endocrine Disrupting Chemicals

“…An AOP provides a conceptual framework that aims to causally link exposure to an EDC with a sequential and/or branching chain of events at different levels of biological organization, leading to an adverse health outcome. Events along the pathway may include molecular actions, cellular effects, whole organ responses, whole body responses, consequences for a whole population, or any combination thereof [29] (Figure 16.3). This provides a model to support risk assessment based on mechanistic reasoning, but identification of the representative end points for predicting adverse outcomes is of central importance, especially if measurements cannot be made at every step of the AOP, if any one EDC does not act at every step in an AOP, or if multiple EDCs act by complementary mechanisms, requiring combined actions to create the adverse outcome.…”

“…The extent to which molecular actions can predict later disease outcomes, or the extent to which early reproductive disturbance can be used as an indicator of later reproductive disorders, remain crucial questions for developing reliable risk assessments. ization (i.e., molecular, cellular, organ, whole body, and population), leading to an adverse health outcome [29]. There may be a molecular initiating event, such as binding of the EDC to a hormone receptor or to an enzyme responsible for endogenous hormone synthesis.…”

“…Construction of adverse outcome pathways (AOPs) [29] provides an approach to enabling assessment of the complexity by which EDCs may influence endocrine health. An AOP provides a conceptual framework that aims to causally link exposure to an EDC with a sequential and/or branching chain of events at different levels of biological organization, leading to an adverse health outcome.…”

Responses to various exposure durations of levonorgestrel during early-life stages of fathead minnows (Pimephales promelas)

“…Adverse outcome pathways (AOP), conceptual frameworks that link direct molecular events to an adverse outcome relevant to risk assessment (Ankley et al, 2010), allow risk assessors to evaluate chemicals using fewer resources and animals. These pathways are valuable in identifying key events in which high-throughput testing methods can be developed and applied (OECD, 2011;Volz et al, 2011).…”