Pharmacokinetics of 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) in rats with decreasing adipose tissue mass. I. Effects of restricting food intake two weeks after administration of 6-CB

Abstract

The tissue distribution and excretion of 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) was studied in rats with decreasing adipose tissue mass. Single doses of 6-CB (0.6 mg/kg, iv) were administered to adult rats on an ad lib. diet, and 2 weeks later their food intake was restricted to 25% of the original daily intake for an additional 6 weeks. Body weights decreased up to the 4th week of fasting by about one half before they became stabilized when adipose tissues had almost disappeared. In liver, lung, brain, skeletal muscle, and blood 6-CB concentrations increased up to the 4th week of fasting and then decreased with half-lives of 8-13 days. In contrast, the concentration did not decrease in skin throughout the fasting period, and the decrease in adipose tissue concentration was not preceded by an increase. During the fasting period cumulative fecal excretion increased tenfold as compared with control animals fed ad lib. Urinary excretion was slightly enhanced but still of the order of only 1% of the dose. Unchanged 6-CB predominated in feces, whereas urine contained polar metabolites only. During the fasting period the 6-CB released from adipose tissue (46 of the 47% of the dose stored at the beginning of the fasting period) appeared in skin (29 up to 55%) and in the fecal excretion (5 up to 36%). It is concluded that the apparently irreversibly stored 6-CB in adipose tissue of normal rats can be released by decreasing this storage or "deep" compartment. In the absence of adipose tissue, skin takes over the characteristics of an alternative storage compartment.