Session 2: QAOP Pathways

Development of Quantitative AOPs to Extrapolate from Molecular Initiating Events to Adverse Outcomes
Edward J Perkins, ERDC

Edward J. Perkins


Environmental Laboratory, US Army Engineer Research and Development Center


Ed Perkins


Adverse outcome pathways (AOP) are descriptions of the essential, measurable events (KE) linking a molecular initiating event (MIE) to an adverse outcome (AO). AOPs qualitatively describe how perturbation of an MIE causes an AO, but do not provide a quantitative assessment of how likely an AO will occur given perturbation by a toxicant. AOPs can be used in a semi-quantitative or quantitative manner in three general ways:

1. An indexing or scoring weight of evidence approach, where elements of an AOP are given a weighted value based on expert opinion and well-documented criteria;

2. A probabilistic WoE approach, where statistical relationships exist between key events and the AO permitting extrapolation to events of regulatory concern; or

3. A mechanistic approach, where quantitative AOP (QAOP) mathematical models, of dose-response and time course relationships are used to predict the AO of given toxicant.

Examples will be given of each approach demonstrating that each is complementary and supports development of increasingly accurate predictive models to provide support for regulatory decision making.