Developing tools for risk assessment in protected species: Relative potencies inferred from competitive binding of halogenated aromatic hydrocarbons to aryl hydrocarbon receptors from beluga (Delphinapterus leucas) and mouse

Persistent organic pollutants such as halogenated aromatic hydrocarbons (HAHs) biomagnify in food webs and accumulate to high concentrations in top predators like odontocete cetaceans (toothed whales). The most toxic HAHs are the 2,3,7,8-substituted halogenated dibenzo-p-dioxins and furans, and non-ortho-substituted polychlorinated biphenyls (PCBs), which exert their effects via the aryl hydrocarbon receptor (AHR). Understanding the impact of HAHs in wildlife is limited by the lack of taxon-specific information about the relative potencies of toxicologically important congeners. To assess whether Toxic Equivalency Factors (TEFs) determined in rodents are predictive of HAH relative potencies in a cetacean, we used beluga and mouse AHRs expressed in vitro from cloned cDNAs to measure the relative AHR-binding affinities of ten HAHs from five different structural classes. The rank order of mean IC50s for competitive binding to beluga AHR was: TCDD < TCDF < PCB-126 < PCB-169 < PCB-77 < PCB-81 ⋘ PCB-156 ∼ PCB-128 < PCB-105 < PCB-118. The rank order of mean IC50s for binding to the mouse AHR was TCDD < TCDF < PCB-126 < PCB-169 < PCB-81 < PCB-77 < PCB-156 ≪ PCB-128 ∼ PCB-105 ∼ PCB-118. Ki values for binding of HAHs to beluga and mouse AHRs were highly correlated (r2 = 0.96). Comparison of Ki values suggested that the beluga AHR had a higher affinity than the mouse AHR for most of the HAHs tested, consistent with the ∼2-fold higher [3H]TCDD binding affinity determined previously. These results are consistent with the World Health Organization mammalian TEFs for non- and mono-ortho PCB congeners. The comparatively high HAH binding affinities of the beluga AHR relative to those of an AHR from a dioxin-responsive mouse suggests that beluga, and perhaps cetaceans in general, may be particularly sensitive to the toxic effects of AHR agonists. Further study is warranted in order to more fully address this important question affecting protected and endangered species.