Abstract
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).
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1.
Absorption of TCDD following a single subcutaneous injection was about 90% after 3 days and 98% after 5 days.
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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.
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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).
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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.
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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).
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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.
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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.
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Abbreviations
- TCDD:
-
2,3,7,8-tetrachlorodibenzo-p-dioxin
- EROD:
-
ethoxyresorufin O-deethylase
- AHH:
-
aryl hydrocarbon hydroxylase
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Data presented in this paper are part of the doctoral thesis of Klaus Abraham to be submitted to the Medizinische Fachbereiche, Freie Universität Berlin
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Abraham, K., Krowke, R. & Neubert, D. Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Toxicol 62, 359–368 (1988). https://doi.org/10.1007/BF00293624
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DOI: https://doi.org/10.1007/BF00293624