PHARMACOKINETICS OF 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (6-CB) IN RATS WITH DECREASING ADIPOSE-TISSUE MASS .1. EFFECTS OF RESTRICTING FOOD-INTAKE 2 WEEKS AFTER ADMINISTRATION OF 6-CB

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (6) , 657-661
Abstract
Polychlorinated biphenyls (PCB) have become universal environmental contaminants and are also attracting increasing interest for biochemical, pharmacokinetic and toxicological reasons. The tissue distribution and excretion of 2,2'',4,4'',5,5''-hexachlorobiphenyl (6-CB) [a PCB residue] was studied in rats with decreasing adipose tissue mass. Single doses of 6-CB (0.06 mg/kg, i.v.) were administerd to adult rats on an ad lib diet, and 2 wk later their food intake was restricted to 25% of the original daily intake for an additional 6 wk. Body weights decreased up to the 4th wk of fasting by .apprx. 1/2 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 wk of fasting and then decreased with half-lives of 8-13 days. 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 10-fold 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 (29-55%) and in the fecal excretion (5-36%). The apparently irreversibly stored 6-CB in adipose tissue of normal rats can be released by decreasing the storage, or deep, compartment. In the absence of adipose tissue, skin takes over the characteristics of an alternative storage compartment.

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