title: Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female rats after a single oral dose.
abstract: 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.
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD, Utrecht, The Netherlands, k.i.vanede@uu.nl.
authors.forename: Karin I
authors.initials: KI
authors.lastname: van Ede
authors.forename: Patrik L
authors.initials: PL
authors.lastname: Andersson
authors.forename: Konrad P J
authors.initials: KP
authors.lastname: Gaisch
authors.forename: Martin
authors.initials: M
authors.lastname: van den Berg
authors.forename: Majorie B M
authors.initials: MB
authors.lastname: van Duursen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004147:Dioxins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C070055:2,3',4,4',5-pentachlorobiphenyl; C051452:1,2,3,7,8-pentachlorodibenzo-p-dioxin; C087667:2,3,3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl; C038890:2,3,4,7,8-pentachlorodibenzofuran