The pharmacokinetics of hexachlorobenzene in male beagles. Distribution, excretion, and pharmacokinetic model
The distribution of hexachlorobenzene (HCB) was studied in male beagles after a single 1-mg/kg iv dose of either /sup 14/C-HCB or unlabeled HCB. Distribution was also determined in animals after seven daily oral administrations of either 10 mg/kg or 100 mg/kg HCB. Excretion of HCB and metabolites through urinary and fecal routes was studied in all four animals receiving /sup 14/C-HCB. In addition, total bile was collected from one of the animals receiving /sup 14/C-HCB to determine the importance of biliary excretion. Immediately after iv administration, a large proportion of the dose was distributed to the lungs. From the lungs, HCB was rapidly distributed to highly perfused tissues including the visceral organs and brain. Further redistribution of HCB from highly perfused tissues to adipose tissue occurred at a much slower rate. In animals receiving daily oral doses of 10 or 100 mg of HCB per kg, adipose tissue was again found to accumulate the highest concentrations of HCB. Excretion of HCB and metabolites occurred primarily through fecal elimination, with urinary excretion being of less importance. Fecal excretion was found to be composed of two separate processes, biliary excretion and intestinal excretion. Of these two processes, biliary excretion was shown to be the major contributor to fecal excretion. After single 1-mg/kg IV doses of /sup 14/C-HCB in three beagles, blood, urine, and feces were monitored over a 12-week period for /sup 14/C content. Computer-assisted pharmacokinetic models were constructed to characterize these data. A three-compartment mammillary model provided the optimum fit to the observed data. Biological half-life values were projected to range from 6 weeks to 3 years.
- Research Organization:
- Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois
- OSTI ID:
- 6576906
- Journal Information:
- Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 10:4; ISSN DMDSA
- Country of Publication:
- United States
- Language:
- English
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560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADIPOSE TISSUE
ANIMAL TISSUES
ANIMALS
AROMATICS
BEAGLES
BILIARY TRACT
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BODY
BODY FLUIDS
BRAIN
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM
CHLORINATED AROMATIC HYDROCARBONS
CLEARANCE
CONNECTIVE TISSUE
DIGESTIVE SYSTEM
DISTRIBUTION
DOGS
EXCRETION
FECES
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
MATERIALS
NERVOUS SYSTEM
ORAL ADMINISTRATION
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
RESPIRATORY SYSTEM
TISSUE DISTRIBUTION
TISSUES
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES