A Cross-species Quantitative Adverse Outcome Pathway for Activation of the Aryl Hydrocarbon Receptor Leading to Early Life Stage Mortality in Birds and Fishes

Dioxin-like compounds (DLCs) elicit
adverse effects through activation
of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated
that sensitivity to activation of AHR1 in an in vitro AHR transactivation
assay is predictive of early life stage mortality among birds. The
present study investigated the link between sensitivity to activation
of AHR1s and AHR2s and early life stage mortality among fishes. A
significant, linear relationship was demonstrated between sensitivity
to activation of AHR2 and early life stage mortality among nine fishes,
while no relationship was found for AHR1. The slope and y-intercept for the linear relationship between sensitivity to activation
of AHR1 and early life stage mortality in birds was not statistically
different from the same relationship for AHR2 in fishes. Data for
fishes and birds across DLCs were expanded into four significant,
linear regression models describing the relationship between sensitivity
to activation of AHR and the dose to cause early life stage mortality
of 0%, 10%, 50%, or 100%. These four relationships were combined to
form a quantitative adverse outcome pathway which can predict dose–response
curves of early life stage mortality for DLCs to any bird or fish
from species- and chemical-specific responses in an in vitro AHR transactivation
assay.