Interactive effects on the EROD inducing potency of polyhalogenated aromatic hydrocarbons in the chicken embryo hepatocyte assay

The chicken embryo hepatocyte-7-ethoxyresorufin O-deethylase (EROD) assay is used as a method to measure the amount of 2,3,7,8- tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) equivalents (TEQs) in environmental samples. A common feature of EROD-induction assays in vertebrates is that they generate biphasic dose response relationships that show dose-related increases of the EROD induction to a maximum activity, followed by a dose related decrease at higher concentrations. In general, the maximum achievable enzyme activity decreases with increasing median effective concentration (EC50). This suggests that aryl hydrocarbon (Ah)-receptor binding affinity is not the only factor determining the enzyme activity. An additional factor can obscure the maximum EROD activity (Y(max)) and EC50 of the enzyme activity. Cytotoxicity and competitive inhibition are ruled out as possible influencing factors. Coadministration of 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153) and 2,3,7,8-TCDD significantly reduces the EC50 value compared to administration of TCDD alone. The dose-related decrease at higher concentrations has been suggested to be induced by mechanisms other than the Ah-receptor-related mechanism responsible for the observed increases at low concentrations. These interactive effects have serious consequences for risk assessment based on bioassay-derived TEQs