PMID- 23680695
OWN - NLM
STAT- MEDLINE
DCOM- 20131113
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 220
IP  - 3
DP  - 2013 Jul 18
TI  - Tissue distribution of dioxin-like compounds: potential impacts on systemic 
      relative potency estimates.
PG  - 294-302
LID - S0378-4274(13)00190-2 [pii]
LID - 10.1016/j.toxlet.2013.05.001 [doi]
AB  - Relative effect potencies (REPs) for dioxins and dioxin-like compounds based on 
      tissue concentration or internal dose ((systemic)REPs) can be considered of high 
      relevance for human risk assessment. Within the EU-project SYSTEQ, (systemic)REPs 
      for 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) were calculated based on a plasma, 
      adipose tissue or liver concentration in Sprague Dawley rats and C57bl/6 mice 
      three days after a single oral dose. Compound-specific distribution as well as 
      differences in accumulation and elimination can influence the tissue 
      concentration and thereby the relative potency estimate of a congener. Here, we 
      show that distribution patterns are generally similar for the tested congeners 
      between the SYSTEQ dataset and other studies using either a single dose or 
      subchronic dosing. Furthermore, the responding concentration for TCDD in single 
      dose studies is comparable to the responding concentrations reported in 
      subchronic studies. In contrast with data for laboratory rodents, available 
      distribution data for humans in the general population display little or no 
      hepatic sequestration. Because hepatic sequestration due to CYP1A2 protein 
      binding may affect the amount of congener that is bioavailable for the AhR to 
      produce hepatic responses, estimates of relative potencies between congeners with 
      differing degrees of hepatic sequestration based on hepatic responses may be 
      misleading for application to human risk assessment. Therefore, extra-hepatic 
      concentration in blood serum/plasma or adipose tissue together with a biological 
      extra-hepatic response might give a more accurate prediction of the relative 
      potency of a congener for human responses under environmental conditions.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - van Ede, Karin I
AU  - van Ede KI
AD  - Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, 3584 CM 
      Utrecht, The Netherlands. k.i.vanede@uu.nl
FAU - Aylward, Lesa L
AU  - Aylward LL
FAU - Andersson, Patrik L
AU  - Andersson PL
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 - 20130513
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Benzofurans)
RN  - 0 (Dioxins)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
SB  - IM
MH  - Adipose Tissue/*metabolism
MH  - Animals
MH  - Benzofurans/administration & dosage/blood/*pharmacokinetics
MH  - Dioxins/administration & dosage/blood/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Liver/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polychlorinated Biphenyls/administration & dosage/blood/*pharmacokinetics
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2013/05/18 06:00
MHDA- 2013/11/14 06:00
CRDT- 2013/05/18 06:00
PHST- 2013/03/08 00:00 [received]
PHST- 2013/05/01 00:00 [revised]
PHST- 2013/05/06 00:00 [accepted]
PHST- 2013/05/18 06:00 [entrez]
PHST- 2013/05/18 06:00 [pubmed]
PHST- 2013/11/14 06:00 [medline]
AID - S0378-4274(13)00190-2 [pii]
AID - 10.1016/j.toxlet.2013.05.001 [doi]
PST - ppublish
SO  - Toxicol Lett. 2013 Jul 18;220(3):294-302. doi: 10.1016/j.toxlet.2013.05.001. Epub 
      2013 May 13.