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 14C-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 14C-HCB. In addition, total bile was collected from one of the animals receiving 14C-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 14C-HCB in three beagles, blood, urine, and feces were monitored over a 12-week period for 14C 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.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D002722:Chlorobenzenes / Q000378:metabolism*; D004285:Dogs; D006581:Hexachlorobenzene / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002722:Chlorobenzenes; D006581:Hexachlorobenzene