PMID- 9439722
OWN - NLM
STAT- MEDLINE
DCOM- 19980219
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 147
IP  - 2
DP  - 1997 Dec
TI  - Dose-response relationships for polyhalogenated dioxins and dibenzofurans 
      following subchronic treatment in mice. I. CYP1A1 and CYP1A2 enzyme activity in 
      liver, lung, and skin.
PG  - 267-80
AB  - The dose-response relationships for induction of liver, lung, and skin 
      ethoxyresorufin-O-deethylase (EROD) activity and liver acetanilide-4-hydroxylase 
      (ACOH) activity following subchronic exposure to either 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 
      1,2,3,7,8-pentachlorodibenzo-p-dioxin, 2,3,7,8-tetrabromodibenzo-p-dioxin, 
      2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran 
      (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), or octachlorodibenzofuran 
      (OCDF) were determined in female B6C3F1 mice in order to estimate the relative 
      enzyme inducing potency of these chemicals in three different tissues. The 
      relative potencies were calculated based on tissue concentrations as well as 
      administered dose. A dose-dependent induction of EROD activity in liver, lung, 
      and skin and of ACOH activity in liver was found for all seven chemicals. When 
      based on administered dose, the relative potencies for specific congeners did not 
      vary substantially among tissues. The relative potencies for TCDF and 1-PeCDF, 
      congeners which have much shorter half-lives than TCDD, increased for all enzymes 
      when estimated from tissue concentrations. The relative potency of OCDF, which is 
      poorly absorbed, was greater when estimated from tissue concentrations than when 
      estimated from administered dose. 4-PeCDF is highly sequestered in hepatic tissue 
      and when the relative potency was estimated based on tissue concentration, its 
      potency for skin enzyme induction increased. These data indicate that the 
      relative potency of these chemicals is influenced not only by the relative 
      binding affinity to the Ah receptor, but also by differences in pharmacokinetic 
      properties of these chemicals. In addition, it may be useful to derive two sets 
      of toxic equivalency factor values, one used for estimating intake equivalents 
      and the other for estimating tissue equivalents.
FAU - DeVito, M J
AU  - DeVito MJ
AD  - Experimental Toxicology Division, National Health and Environmental Effects 
      Research Laboratory, United States Environmental Protection Agency, Research 
      Triangle Park, North Carolina 27711, USA. devito@epamail.epa.gov
FAU - Diliberto, J J
AU  - Diliberto JJ
FAU - Ross, D G
AU  - Ross DG
FAU - Menache, M G
AU  - Menache MG
FAU - Birnbaum, L S
AU  - Birnbaum LS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Benzofurans)
RN  - 0 (Dioxins)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
SB  - IM
MH  - Animals
MH  - Benzofurans/administration & dosage/*pharmacology
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Cytochrome P-450 CYP1A2/*biosynthesis
MH  - Dioxins/administration & dosage/*pharmacology
MH  - Enzyme Induction
MH  - Female
MH  - Liver/*drug effects/enzymology
MH  - Lung/*drug effects/enzymology
MH  - Mice
MH  - Models, Biological
MH  - Skin/*drug effects/enzymology
MH  - Structure-Activity Relationship
EDAT- 1998/01/24 00:00
MHDA- 1998/01/24 00:01
CRDT- 1998/01/24 00:00
PHST- 1998/01/24 00:00 [pubmed]
PHST- 1998/01/24 00:01 [medline]
PHST- 1998/01/24 00:00 [entrez]
AID - S0041008X97982612 [pii]
AID - 10.1006/taap.1997.8261 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1997 Dec;147(2):267-80. doi: 10.1006/taap.1997.8261.