PMID- 18566023
OWN - NLM
STAT- MEDLINE
DCOM- 20081023
LR  - 20121115
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 105
IP  - 1
DP  - 2008 Sep
TI  - Toxicokinetics of 2,3,7,8-TCDF and 2,3,4,7,8-PeCDF in mink (Mustela vison) at 
      ecologically relevant exposures.
PG  - 33-43
LID - 10.1093/toxsci/kfn118 [doi]
AB  - Wild mink (Mustela vison) living along the Tittabawassee River in central 
      Michigan exhibit elevated hepatic and dietary polychlorinated dibenzofuran (PCDF) 
      concentrations exceeding mink-specific, literature-reported toxicity reference 
      values (TRVs) on a toxicity equivalents basis. However, no apparent effects on 
      individuals or population are evident, suggesting that available TRVs may 
      overpredict risk for the site-specific mix of congeners. To investigate this 
      discrepancy, a 180-day spiked feed study was conducted to assess: (1) the dosages 
      of key congeners necessary to achieve liver concentrations bracketing those 
      observed in wild mink, (2) time to achieve steady-state concentrations, and (3) 
      effect of coadministration of 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 
      2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) on the toxicokinetics and 
      distribution of each congener. Adipose and hepatic PCDF concentrations were 
      measured at 0, 90, and 180 days. PCDF concentrations in mink scat were determined 
      at several time points and indicated nearly complete absorption of both TCDF and 
      4-PeCDF from the diet. Elimination half-times of TCDF were < 15 h and were 
      inversely proportional to dose, while those for 4-PeCDF were approximately 7-9 
      days with no clear dose dependency in the tested dose range. Coadministration of 
      4-PeCDF and TCDF accelerated clearance of TCDF compared to administration of TCDF 
      alone. Clearance of 4-PeCDF was not affected by TCDF coadministration. 
      Distribution of 4-PeCDF, but not TCDF, demonstrated increased hepatic 
      sequestration with increasing dose. 4-PeCDF toxicokinetics were described using a 
      previously published two-compartment model. Overall, the toxicokinetic 
      information gathered here illustrates the impact of CYP1A1 induction on 
      bioaccumulation and toxicity potential of TCDF and 4-PeCDF. This information may 
      provide insight into why the current TRVs do not appear to correctly characterize 
      the risk for these two congeners when they are the primary components of an 
      environmental mixture.
FAU - Zwiernik, Matthew J
AU  - Zwiernik MJ
AD  - Aquatic Toxicology Laboratory, National Food Safety and Toxicology Center, 
      Michigan State University, East Lansing, Michigan 48824, USA. zwiernik@msu.edu
FAU - Bursian, Steven
AU  - Bursian S
FAU - Aylward, Lesa L
AU  - Aylward LL
FAU - Kay, Denise P
AU  - Kay DP
FAU - Moore, Jeremy
AU  - Moore J
FAU - Rowlands, Craig
AU  - Rowlands C
FAU - Woodburn, Kent
AU  - Woodburn K
FAU - Shotwell, Melissa
AU  - Shotwell M
FAU - Khim, Jong Seong
AU  - Khim JS
FAU - Giesy, John P
AU  - Giesy JP
FAU - Budinsky, Robert A
AU  - Budinsky RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080619
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Benzofurans)
RN  - U4C2RV3124 (2,3,4,7,8-pentachlorodibenzofuran)
RN  - XZJ41GQI5D (2,3,7,8-tetrachlorodibenzofuran)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Benzofurans/*pharmacokinetics/toxicity
MH  - Ecology
MH  - Female
MH  - Liver/metabolism
MH  - Mink/*metabolism
MH  - Models, Biological
EDAT- 2008/06/21 09:00
MHDA- 2008/10/24 09:00
CRDT- 2008/06/21 09:00
PHST- 2008/06/21 09:00 [pubmed]
PHST- 2008/10/24 09:00 [medline]
PHST- 2008/06/21 09:00 [entrez]
AID - kfn118 [pii]
AID - 10.1093/toxsci/kfn118 [doi]
PST - ppublish
SO  - Toxicol Sci. 2008 Sep;105(1):33-43. doi: 10.1093/toxsci/kfn118. Epub 2008 Jun 19.