Disposition of 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) in rats with decreasing adipose tissue mass. II. Effects of restricting food intake before and after 6-CB administration

Excretion and tissue distribution of the virtually unmetabolizable lipophilic model 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) was studied in rats with decreasing adipose tissue mass imposed by various food intake manipulations. Single doses of 6-CB (0.6 mg/kg iv) were administered to adult male rats. Excretion was followed daily and tissue distribution was determined after 7 weeks. Gradual disappearance of adipose tissue was induced by restricting food intake to 25% of ad libitum consumption. In a first series of experiments, 6-CB was administered simultaneously with the start of food restriction. The fecal excretion rate of 6-CB increased, reached a maximum in the second week, and then leveled off. After 7 weeks, some 50% of the dose was excreted and 26% was located in the skin. Amounts in muscle, liver, lung, kidney, brain, gastrointestinal contents, and residual adipose tissue were between 2.5 and 0.1% of the administered dose. In a second series of experiments, 6-CB was administered 2 weeks after the commencement of food restriction, i.e. when adipose tissue reserves had already largely disappeared. Fecal excretion rate was maximal at the outset and gradually decreased. Cumulative excretion and distribution values for skin and other tissues were not significantly different from the values determined in the above series after 7 weeks. The results, which are discussed in the context of previously published data, demonstrate the profound difference in the pharmacokinetics of 6-CB, depending on whether adipose tissue mass is increasing (as in the ad libitum fed adult rat) or decreasing.