AOP | “An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event (e.g., a molecular interaction between a xeno-biotic and a specific biomolecule) and an adverse outcome at a biological level of organization relevant to risk assessment.”a |
MOA | A “biologically plausible series of key events leading to” an adverse effect.b |
A “sequence of Key Events and processes, starting with interaction of an agent with a cell, proceeding through operational and anatomical changes, and resulting in” an adverse effect. “Mode of action is contrasted with ‘mechanism of action,’ which implies a more detailed understanding and description of events.”c |
KE | “A key event is an empirically observable step or its marker, which is a necessary element of the mode of action critical to the outcome (i.e., necessary, but not necessarily sufficient in its own right); key events are measurable and reproducible.”b |
Measureable/observable biologic changes that are essential to the progression from the molecular interaction of a xenobiotic with the biologic system to an AO considered relevant to regulatory decision making. “KEs are, in essence, measurements of biological state or change in state with regard to a control or reference. Because KEs are measurements or observations of state, the confidence one has in a KE is dictated by the accuracy and precision with which that biological state can be measured.”d |
KER | The predictive and/or causal linkages between a pair of KEs. “KERs, in contrast, are a unit of inference or extrapolation. They are defined by the biological plausibility and evidence that provide a scientifically credible basis for inferring or predicting the state of a downstream KE based on the known state of an upstream KE and the confidence in that inference or prediction is defined by the weight of supporting evidence.”d |
MIE | The first KE within an AOP representing the biologic perturbation resulting from a molecular interaction between a xenobiotic and a specific biomolecule. |
AO | Late stage KE in an AOP representing a biologic perturbation that would be considered adverse in a regulatory context. These typically occur at either the individual (e.g., cancer) or population (e.g., lack of reproductive carrying capacity) levels of organization. |