Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female rats after a single oral dose
| Autor: | Van Ede, Karin I., Andersson, Patrik L., Gaisch, Konrad P J, Van Den Berg, Martin, Van Duursen, Majorie B M, Sub IRAS Tox CMT/ETX, Department of Chemistry, LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS Tox Algemeen, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1 |
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| Přispěvatelé: | Sub IRAS Tox CMT/ETX, Department of Chemistry, LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS Tox Algemeen, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1 |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Polychlorinated Dibenzodioxins
TEF concept Health Toxicology and Mutagenesis Polychlorinated dibenzodioxins Administration Oral Adipose tissue Aryl hydrocarbon receptor repressor 010501 environmental sciences Pharmacology Dioxins Toxicology 01 natural sciences Rats Sprague-Dawley Single oral dose 03 medical and health sciences chemistry.chemical_compound Oral administration Cytochrome P-450 CYP1A1 Animals Toxicology and Mutagenesis Tissue Distribution Lymphocytes PCBs Toxic equivalency factor Benzofurans 030304 developmental biology 0105 earth and related environmental sciences Systemic REPs 0303 health sciences Dose-Response Relationship Drug Body Weight General Medicine Polychlorinated Biphenyls Peripheral blood Rats 3. Good health Gene Expression Regulation chemistry Health Toxicity Female Dibenzofurans |
| Zdroj: | Archives of Toxicology, 88(3), 637. Springer Verlag Archives of Toxicology |
| ISSN: | 0340-5761 |
| Popis: | Risk assessment for mixtures of dioxin-like compounds uses the toxic equivalency factor (TEF) approach. Although current WHO-TEFs are mostly based on oral administration, they are commonly used to determine toxicity equivalencies (TEQs) in human blood or tissues. However, the use of "intake" TEFs to calculate systemic TEQs in for example human blood, has never been validated. In this study, intake and systemic relative effect potencies (REPs) for 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118) and 2,3,3′,4, 4′,5-hexachlorobiphenyl (PCB-156) were compared in rats. The effect potencies were calculated based on administered dose and liver, adipose or plasma concentrations in female Sprague-Dawley rats 3 days after a single oral dose, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatic ethoxyresorufin-O-deethylase activity and gene expression of Cyp1a1, 1a2, 1b1 and aryl hydrocarbon receptor repressor in liver and peripheral blood lymphocytes were used as endpoints. Results show that plasma-based systemic REPs were generally within a half log range around the intake REPs for all congeners tested, except for 4-PeCDF. Together with our previously reported systemic REPs from a mouse study, these data do not warrant the use of systemic REPs as systemic TEFs for human risk assessment. However, further investigation for plasma-based systemic REPs for 4-PeCDF is desirable. |
| Databáze: | OpenAIRE |
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