PMID- 23674508
OWN - NLM
STAT- MEDLINE
DCOM- 20140219
LR  - 20211021
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 121
IP  - 7
DP  - 2013 Jul
TI  - Comparison of intake and systemic relative effect potencies of dioxin-like 
      compounds in female mice after a single oral dose.
PG  - 847-53
LID - 10.1289/ehp.1206336 [doi]
AB  - 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.
FAU - van Ede, Karin I
AU  - van Ede KI
AD  - Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the 
      Netherlands. k.i.vanede@uu.nl
FAU - Andersson, Patrik L
AU  - Andersson PL
FAU - Gaisch, Konrad P J
AU  - Gaisch KP
FAU - van den Berg, Martin
AU  - van den Berg M
FAU - van Duursen, Majorie B M
AU  - van Duursen MB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130503
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Benzofurans)
RN  - 0 (Dioxins)
RN  - 0 (Environmental Pollutants)
RN  - 63231-63-0 (RNA)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Adipose Tissue/*metabolism
MH  - Administration, Oral
MH  - Animals
MH  - Benzofurans/administration & dosage/blood/*metabolism
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Dioxins/administration & dosage/blood/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/administration & dosage/blood/*metabolism
MH  - Female
MH  - Gas Chromatography-Mass Spectrometry
MH  - Gene Expression Regulation/drug effects
MH  - Liver/enzymology/*metabolism
MH  - Lymphocytes/drug effects/enzymology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polychlorinated Biphenyls/administration & dosage/blood/*metabolism
MH  - RNA/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Risk Assessment
PMC - PMC3702004
COIS- The purchase of the compounds was financially made possible by The Dow Chemical 
      Company. However, the authors' freedom to design, conduct, interpret, and publish 
      research was not compromised by The Dow Chemical Company as a condition of review 
      and publication.
EDAT- 2013/05/16 06:00
MHDA- 2014/02/20 06:00
PMCR- 2013/07/01
CRDT- 2013/05/16 06:00
PHST- 2012/11/30 00:00 [received]
PHST- 2013/05/02 00:00 [accepted]
PHST- 2013/05/16 06:00 [entrez]
PHST- 2013/05/16 06:00 [pubmed]
PHST- 2014/02/20 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - ehp.1206336 [pii]
AID - 10.1289/ehp.1206336 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2013 Jul;121(7):847-53. doi: 10.1289/ehp.1206336. Epub 
      2013 May 3.