title: Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female mice after a single oral dose.
abstract: BACKGROUND
  Risk assessment for mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) is performed using the toxic equivalency factor (TEF) approach. These TEF values are derived mainly from relative effect potencies (REPs) linking an administered dose to an in vivo toxic or biological effect, resulting in "intake" TEFs. At present, there is insufficient data available to conclude that intake TEFs are also applicable for systemic concentrations (e.g., blood and tissues).
  
  
  OBJECTIVE
  We compared intake and systemic REPs of 1,2,3,7,8-pentachlorodibenzodioxin (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) in female C57BL/6 mice 3 days after a single oral dose.
  
  
  METHODS
  We calculated intake REPs and systemic REPs based on administered dose and liver, adipose, or plasma concentrations relative to TCDD. Hepatic cytochrome P450 1A1-associated ethoxyresorufin-O-deethylase (EROD) activity and gene expression of Cyp1a1, 1a2 and 1b1 in the liver and peripheral blood lymphocytes (PBLs) were used as biological end points.
  
  
  RESULTS
  We observed up to one order of magnitude difference between intake REPs and systemic REPs. Two different patterns were discerned. Compared with intake REPs, systemic REPs based on plasma or adipose levels were higher for PeCDD, 4-PeCDF, and PCB-126 but lower for the mono-ortho PCBs 118 and 156.
  
  
  CONCLUSIONS
  Based on these mouse data, the comparison between intake REPs and systemic REPs reveals significant congener-specific differences that warrants the development of systemic TEFs to calculate toxic equivalents (TEQs) in blood and body tissues.
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, 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: D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004147:Dioxins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment
chemical_list: D001572:Benzofurans; D004147:Dioxins; D004785:Environmental Pollutants; D012313:RNA; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1