Predicting Early Life Stage Mortality in Birds and Fishes from Exposure to Low-Potency Agonists of the Aryl Hydrocarbon Receptor: A Cross-Species Quantitative Adverse Outcome Pathway Approach.

ABSTRACT

Dioxin-like compounds (DLCs) cause early life stage mortality of vertebrates through activation of the aryl hydrocarbon receptor (AhR). A prior study developed a cross-species quantitative adverse outcome pathway (qAOP) which can predict full dose-response curves of early life stage mortality for any species of bird or fish exposed to DLCs using the species- and chemical-specific 50% effect concentration (EC50) from an in vitro AhR transactivation assay with COS-7 cells. However, calculating a reliable EC50 for input into this qAOP requires the maximal response of the concentration-response curve to be known, which is not always possible for low-potency agonists, such as some polychlorinated biphenyls (PCBs). To enable predictions for these low-potency agonists, the present study revised this qAOP to use the effect concentration threshold (ECThreshold ) from the in vitro AhR transactivation assay as input. Significant linear relationships were demonstrated between ECThreshold and the dose to cause 0, 10, 50, or 100% mortality among early life stages of 3 species of birds and 7 species of fish for 4 DLCs 2,3,7,8-tetrachlorodibenzo-p-dioxin, PCB 126, PCB 77, and PCB 105. These 4 linear relationships were combined to form the revised qAOP. This qAOP using the ECThreshold enables prediction of experimental dose-response curves for lower-potency agonists to within an order of magnitude on average, but the prior qAOP using EC50 predicts experimental dose-response curves for higher-potency agonists with greater accuracy. Environ Toxicol Chem 2020;392055-2064. © 2020 SETAC.