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A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics
Citation:
Conolly, R., W. Cheng, Dan Villeneuve, G. Ankley, D. Miller, K. Watanabe, AND M. Mayo. A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics. Society of Toxicology, San Diego, CA, March 22 - 27, 2015.
Impact/Purpose:
To be presented at the annual SOT Meeting
Description:
A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). Given an established AOP, identification of a toxicant that participates in an MIE is analogous to hazard identification – the linkage to the adverse outcome is implicit, but the quantitative dose response and time course of the toxicant dose to AO relationship are not characterized. Development of quantitative AOPs (QAOP) is intended to provide this predictive capability. We linked three computational models that represent different levels of biological organization: the hypothalamic-pituitary-gonadal (HPG) axis; oocyte growth dynamics; and a population dynamics model. We simulated aromatase inhibition in fathead minnows exposed to 0, 2, 10, or 50 μg/L fadrozole, a model aromatase inhibitor with an HPG axis model to obtain predictions of plasma vitellogenin concentrations. The time course of predicted plasma vitellogenin concentrations was input into the oocyte growth dynamics model to predict clutch sizes and spawning intervals which were then input to the population dynamics model. Mild to severe reductions in fecundity and associated reductions in population size over an interval of 10 years were predicted, from 80% of normal at 2 μg/L to 0% at 10 μg/L and above. Linking the three models to construct a QAOP creates a structure that can be iteratively refined as new, relevant data are acquired. Thus, prediction accuracy can be expected to increase with time and to provide support for regulatory decision making. This is an abstract or a proposed presentation and does not necessarily reflect EPA policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.