Interactive effects on the EROD-inducing potency of polyhalogenated aromatic hydrocarbons in the chicken embryo hepatocyte assay
Journal Article
·
· Environmental Toxicology and Chemistry
- Inst. for Forest and Nature Research/IBN-DLO, Wageningen (Netherlands). Dept. of Ecotoxicology
- Utrecht Univ. (Netherlands). Research Inst. of Toxicology
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{sub max}) and EC50 of the enzyme activity. Cytotoxicity and competitive inhibition are ruled out as possible influencing factors. Coadministration of 2,2{prime},4,4{prime},5,5{prime}-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.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 474327
- Journal Information:
- Environmental Toxicology and Chemistry, Journal Name: Environmental Toxicology and Chemistry Journal Issue: 2 Vol. 16; ISSN 0730-7268; ISSN ETOCDK
- Country of Publication:
- United States
- Language:
- English
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