Document Detail


Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorufin O-deethylase in rats following a single injection.
MedLine Citation:
PMID:  3242446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver and adipose tissue, and hepatic ethoxyresorufin O-deethylase (EROD) activity were studied subsequent to a single subcutaneous injection of TCDD. Two types of experiments were performed to study: (a) time-dependent changes following a single injection of 300 ng TCDD/kg body wt (points 1-4), and (b) dose-dependent changes measurable after 7 days following a single injection (points 5-7). 1. Absorption of TCDD following a single subcutaneous injection was about 90% after 3 days and 98% after 5 days. 2. Following a single dose of 300 ng TCDD/kg body wt peak concentrations were: liver (after 3 days): 4.7 +/- 0.9 ng/g wet wt, and adipose tissue (after 7 days): 0.82 +/- 0.07 ng/g wet wt. 3. T1/2 of TCDD in liver was 13.6 days over the total experimental period (from day 10 to 91 of the study), apparently with an initial faster phase: 11.5 days (from day 10 to 49), and a slower period at the end of the experiment: 16.9 days (from day 49 to 91); in adipose tissue the t1/2 was 24.5 days (from day 14 to 91 of the study). 4. Maximum induction of EROD in the liver was observed (14-fold at 300 ng TCDD/kg body wt) 3-7 days following the injection; the activity was decreased to about one third of the maximum 3 weeks after the injection; increase in total cytochrome P-450 at this dose was only about 1.4-fold at the induction maximum. 5. The ratio of the TCDD concentrations in liver and adipose tissue increased considerably between doses of 3 ng TCDD/kg body wt (ratio: about 0.74) and 3000 ng TCDD/kg body wt (ratio: about 7.7). 6. The extent of EROD induction in the liver increased dose dependently. A significant effect was first observed with a dose of 3 ng TCDD/kg body wt (activity about +32% above control activity). The corresponding tissue concentration was about 10 pg TCDD/g liver wet wt. 7. An almost perfect linear relationship exists (when using a double-log plot) between the hepatic TCDD concentration and the EROD activity for tissue concentrations ranging from 40 to 30,000 pg TCDD/g wet wt.
Authors:
K Abraham; R Krowke; D Neubert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of toxicology     Volume:  62     ISSN:  0340-5761     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  1988  
Date Detail:
Created Date:  1989-05-16     Completed Date:  1989-05-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  359-68     Citation Subset:  IM    
Affiliation:
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / enzymology
Animals
Cytochrome P-450 CYP1A1
Cytochrome P-450 Enzyme System / biosynthesis*
Dioxins / pharmacokinetics*
Dose-Response Relationship, Drug
Enzyme Induction
Female
Half-Life
Injections, Subcutaneous
Liver / enzymology*
Oxidoreductases / biosynthesis*
Rats
Rats, Inbred Strains
Tetrachlorodibenzodioxin / pharmacokinetics*,  toxicity
Tissue Distribution
Chemical
Reg. No./Substance:
0/Dioxins; 1746-01-6/Tetrachlorodibenzodioxin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases; EC 1.14.14.1/Cytochrome P-450 CYP1A1

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