PMID- 18723826
OWN - NLM
STAT- MEDLINE
DCOM- 20090122
LR  - 20121115
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 106
IP  - 2
DP  - 2008 Dec
TI  - Estimates of cancer potency of 2,3,4,7,8-pentachlorodibenzofuran using both 
      nonlinear and linear approaches.
PG  - 519-37
LID - 10.1093/toxsci/kfn176 [doi]
AB  - Cancer potency estimates were derived for 2,3,4,7,8-pentachlorodibenzofuran 
      (4-PeCDF) using data collected from the recently published National Toxicology 
      Program bioassay in female Sprague-Dawley rats. By using a toxicokinetic model 
      for 4-PeCDF, the dose-response relationship for combined liver tumors 
      (hepatocellular adenomas and cholangiocarcinomas) in rats was assessed in terms 
      of lifetime average liver concentration and lifetime average adipose 
      concentration with data from both the lifetime and the stop-exposure components 
      of the bioassay. Benchmark dose modeling was performed to estimate tissue 
      concentrations at two points of departure (EC(10) and EC(01) and their 95% upper 
      and lower confidence limits). The same toxicokinetic model with human input 
      values was then used to back-extrapolate human equivalent doses that corresponded 
      to the internal tissue concentration measures at the points of departure. 
      Information regarding the cancer mode of action was used to support the 
      development of several toxicity criterion values based on a nonlinear method, 
      e.g., reference dose or tolerable daily intake. Nonlinear estimates of toxicity 
      criteria based on observed noncancer toxic events as possible precursors to tumor 
      formation were also derived and were similar in value to those based on combined 
      liver tumors. For comparison purposes, linear estimates of cancer potency were 
      also derived.
FAU - Simon, Ted
AU  - Simon T
AD  - Ted Simon, LLC, Winston, Georgia 30187, USA. ted@tedsimon-toxicology.com
FAU - Kirman, Christopher R
AU  - Kirman CR
FAU - Aylward, Lesa L
AU  - Aylward LL
FAU - Budinsky, Robert A
AU  - Budinsky RA
FAU - Rowlands, J Craig
AU  - Rowlands JC
FAU - Long, Tom F
AU  - Long TF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080822
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Benzofurans)
RN  - 0 (Carcinogens)
RN  - U4C2RV3124 (2,3,4,7,8-pentachlorodibenzofuran)
SB  - IM
MH  - Animals
MH  - Benzofurans/pharmacokinetics/*toxicity
MH  - Carcinogens/pharmacokinetics/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Liver Neoplasms, Experimental/*chemically induced
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2008/08/30 09:00
MHDA- 2009/01/23 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2009/01/23 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - kfn176 [pii]
AID - 10.1093/toxsci/kfn176 [doi]
PST - ppublish
SO  - Toxicol Sci. 2008 Dec;106(2):519-37. doi: 10.1093/toxsci/kfn176. Epub 2008 Aug 
      22.