ToxSci Advance Access published online on June 19, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn118
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicokinetics of 2,3,7,8-TCDF AND 2,3,4,7,8-PECDF in Mink (Mustela vison) at Ecologically Relevant Exposures
* Michigan State University, National Food Safety & Toxicology Center, Center for Integrative Toxicology, Aquatic Toxicology Lab. East Lansing, Michigan, 48824-1222. moorej42{at}msu.edu, jgiesy{at}aol.com
Michigan State University, Department of Animal Science, Center for Integrative Toxicology, East Lansing, Michigan, 48824. bursian{at}msu.edu
Summit Toxicology, L.L.P., Falls Church, VA 22044. laylward{at}summittoxicology.com
Entrix, Inc., Okemos, MI 48864. dkay{at}entrix.com
|| University of Saskatchewan, Department of Veterinary Biomedical Sciences and Toxicology Centre, Saskatoon, Saskatchewan, S7J 5B3, Canada
¶ The Dow Chemical Company, Midland, Michigan. 48642. JCrowlands{at}dow.com, KBwoodburn{at}dow.com, RABudinsky{at}dow.com
ø Corresponding Author zwiernik{at}msu.edu
Received September 7, 2007; revision received June 5, 2008; accepted June 5, 2008
 |
Abstract |
|---|
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 (TEQ) basis. However, no apparent effects on individuals or population are evident, suggesting that available TRVs may over-predict 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 co-administration 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 d. PCDFs concentrations of 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 to 9 d with no clear dose-dependency in the tested dose range. Co-administration of 4-PeCDF and TCDF accelerated clearance of TCDF compared to administration of TCDF alone. Clearance of 4-PeCDF was not affected by TCDF co-administration. 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.
Key Words: Mink; polychlorinated dibenzodioxins and polychlorinated dibenzofurans (dioxins and furans); toxicokinetics; 2,3,7,8-tetrachlorodibenzofuran; 2,3,4,7,8-pentachlorodibenzofuran.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. D. Burgoon, Q. Ding, A. N'jai, E. Dere, A. R. Burg, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Automated Dose-Response Analysis of the Relative Hepatic Gene Expression Potency of TCDF in C57BL/6 Mice Toxicol. Sci., November 1, 2009; 112(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|