LAUSR

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 three species of birds and seven species of fish for four DLCs, 2,3,7,8-TCDD, PCB 126, PCB 77, and PCB 105. These four linear relationships were combined to form the revised qAOP. This qAOP using 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. This article is protected by copyright. All rights reserved.