Responses of mixtures of polyhalogenated aromatic compounds or single compounds in the CALUX-assay a novel species-specific bioassay for Ah-receptor active compounds
- Agricultural Univ. Wageningen (Netherlands). Dept. of Toxicology
- Univ. of Davis, CA (United States). Dept. of Environmental Toxicology
Polyhalogenated aromatic hydrocarbons (PHAHs) elicit a number of common toxic responses, including reproductive toxicity, teratogenicity, impairment of immune responses, alterations in vitamin A and thyroid hormone metabolism and carcinogenesis. The toxic effects however are highly dependent on the animal species used, The most toxic PHAHs are approximate isostereomeres of 2,3,7,8 tetrachlorinated dibenzo-p-dioxin (TCDD) and share a common mechanism of action mediated by the aryl hydrocarbon receptor (AhR). Based on the common receptor mediated mechanism, the toxic equivalency factor concept was developed, in which the potency of each individual congener is expressed relative to TCDD, thus allowing hazard and risk assessment for mixtures of PHAHs. A number of recombinant cell lines were developed, including hepalclc7 mouse and H4IIE rat hepatoma cell lines, with AhR-mediated firefly (Photinus pyralis) luciferase gene expression. The response in this so-called CALUX (chemical activated luciferase expression) assay is additive for polychlorinated dibenzofurans (PCDFs) and PCDDS, but for polychlorinated biphenyls (PCBs) both synergistic and antagonistic interactions have been demonstrated, which are partially species-dependent. Also some structurally related compounds, like polybrominated diphenyl ether, pentachlorinated phenol, benzo(a)pyrene, pyrene, tetrachlorobenzyltoluene (Ugilec 141) and mixtures of polychlorinated terphenyls have been tested in the CALUX assay. The responses of these compounds were sometimes agonistic, but also antagonistic and synergistic effects on the TCDO response were observed.
- OSTI ID:
- 242321
- Report Number(s):
- CONF-9511137-; ISBN 1-880611-03-1; TRN: IM9626%%149
- Resource Relation:
- Conference: 2. Society of Environmental Toxicology and Chemistry (SETAC) world conference, Vancouver (Canada), 5-9 Nov 1995; Other Information: PBD: 1995; Related Information: Is Part Of Second SETAC world congress (16. annual meeting): Abstract book. Global environmental protection: Science, politics, and common sense; PB: 378 p.
- Country of Publication:
- United States
- Language:
- English
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