PMID- 16455694
OWN - NLM
STAT- MEDLINE
DCOM- 20060621
LR  - 20121115
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 91
IP  - 1
DP  - 2006 May
TI  - Recommended relative potency factors for 2,3,4,7,8-pentachlorodibenzofuran: the 
      impact of different dose metrics.
PG  - 275-85
AB  - The recent National Toxicology Program (NTP) cancer bioassays for 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran 
      (4-PeCDF) permit a reevaluation of the current TEF value of 4-PeCDF. The data 
      also allow for the derivation of relative potency factors (RPFs) for cancer, 
      which are based not only on administered dose but also on potentially more 
      informative dose metrics, such as liver concentration, area under the liver 
      concentration curve, and lifetime average body burden. Our analyses of these data 
      indicate that chi-squared tests of observed versus predicted liver tumor 
      incidence for 4-PeCDF reject the current TEF value of 0.5 value as too high. 
      4-PeCDF RPFs were derived using estimation methods that either did or did not 
      assume parallelism of the 4-PeCDF and TCDD dose-response curves. The resulting 
      parallelism-based RPFs for administered dose, liver concentration at terminal 
      sacrifice, liver concentration AUC, and lifetime average body burden are 0.26, 
      0.014, 0.021, and 0.036, respectively. The administered dose RPF estimate is 
      approximately one-half the current TEF value of 0.5. However, the use of 
      administered dose fails to take into account pharmacokinetic differences between 
      congeners and the generally acknowledged belief that body burden or some other 
      measure of cumulative dose is more appropriate for estimating the health risk 
      posed by persistent chemicals. The other three dose metrics do account for these 
      important factors, and the corresponding RPFs are at least 10-fold lower than the 
      current TEF for 4-PeCDF. In summary, our analyses support an administered dose 
      TEF no greater than 0.25 and one in the 0.05-0.1 range for internal dose metrics 
      such as lifetime average liver concentration or body burden.
FAU - Budinsky, Robert A
AU  - Budinsky RA
AD  - The Dow Chemical Company, Midland, Michigan 48674, USA. rabudinsky@dow.com
FAU - Paustenbach, Dennis
AU  - Paustenbach D
FAU - Fontaine, Donald
AU  - Fontaine D
FAU - Landenberger, Bryce
AU  - Landenberger B
FAU - Starr, Thomas B
AU  - Starr TB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060202
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)
SB  - IM
MH  - Area Under Curve
MH  - Benzofurans/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Liver Neoplasms/*chemically induced
MH  - Monte Carlo Method
MH  - Tumor Cells, Cultured
EDAT- 2006/02/04 09:00
MHDA- 2006/06/22 09:00
CRDT- 2006/02/04 09:00
PHST- 2006/02/04 09:00 [pubmed]
PHST- 2006/06/22 09:00 [medline]
PHST- 2006/02/04 09:00 [entrez]
AID - kfj125 [pii]
AID - 10.1093/toxsci/kfj125 [doi]
PST - ppublish
SO  - Toxicol Sci. 2006 May;91(1):275-85. doi: 10.1093/toxsci/kfj125. Epub 2006 Feb 2.