Subchronic effects of 2,3,7,8-TCDD or PCBs on thyroid hormone metabolism: use in risk assessment
| Autor: | E.A. Smit, Jan H. Koeman, C.N. Groeneveld, A.P.J.M. van Birgelen, M. van den Berg, K.M. Fase, J. H. van der Kolk, I.M. Kampen, Abraham Brouwer, H. Poiger |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
(2 3 7 8-tetrachlorodibenzo-p-dioxin) TCDD Thyroid Hormones Polychlorinated Dibenzodioxins Glucuronidation Toxicology Thyroid hormone metabolism Isozyme Risk Assessment Rats Sprague-Dawley Eating Cytochrome P-450 Enzyme System Internal medicine (2 medicine Cytochrome P-450 CYP1A1 Animals Glucuronosyltransferase Toxicologie reproductive and urinary physiology Pharmacology chemistry.chemical_classification PCB biology food and beverages Cytochrome P450 Pollution Polychlorinated Biphenyls Diet Rats Thyroid hormone stomatognathic diseases Enzyme Endocrinology (polychlorinated biphenyl) chemistry Receptors Aryl Hydrocarbon 8-tetrachlorodibenzo-p-dioxin) Enzyme Induction biology.protein Microsome Female Oxidoreductases |
| Zdroj: | European journal of pharmacology. Environmental toxicology and pharmacology 293 (1995) European journal of pharmacology. Environmental toxicology and pharmacology, 293, 77-85 |
| ISSN: | 0014-2999 0926-6917 |
| Popis: | Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) on thyroid hormone metabolism were studied in 13-week feeding studies in female Sprague-Dawley rats. The diets were supplemented with the compounds tested at concentrations ranging from 0.2 to 20 micrograms/kg diet for TCDD, 7 to 180 micrograms/kg diet for PCB 126, or 1.2 to 12 mg/kg diet for PCB 156, respectively. Significant correlations were found for all three compounds between reductions in plasma total thyroxine (TT4) levels and inductions of the microsomal phase II enzyme UDP-glucuronosyltransferase by using T4 as a substrate (T4UGT). Furthermore, the coinduction of certain phase I and II isozymes, i.c., cytochrome P450 1A1 (CYP1A1) and UGT1A1, by these compounds, clearly suggests the involvement of an Ah receptor-mediated mechanism in the disturbance of thyroid hormone metabolism by these polyhalogenated aromatic compounds. These results provide a mechanistic base for the use of certain effects on thyroid hormone metabolism by polyhalogenated aromatic compounds in risk assessment. By using these effects, potencies of PCB 126 and PCB 156 relative to TCDD ranged from 0.008 to 0.1 for PCB 126, and from 0.00007 to 0.004 for PCB 156, respectively. These values correspond very well with relative potencies of PCB 126 and PCB 156 by using some other well-known Ah receptor-mediated toxic and biochemical parameters. |
| Databáze: | OpenAIRE |
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