Distribution and excretion of 2,3,6,2',3',6'- and 2,4,5,2',4',5'-hexachlorobiphenyl in senescent rats

The disposition of two symmetrical [14C]hexachlorobiphenyls (HCBs), 2,3,6,2',3',6'-HCB (236) and 2,4,5,2',4',5'-HCB (245), was studied in 24-month-old male Sprague-Dawley rats after iv treatment. Because body composition changes with age, complete dissections were performed on all rats to determine the size of the skin and adipose tissue depots. More than 50% of 236 was metabolized and excreted via the bile into the feces within 2 days. In contrast, 245 redistributed from the liver, muscle, and skin to adipose tissue where it accumulated without being metabolized. Only 2% of the total dose of 245 was excreted primarily in the feces within 21 days. The data obtained in this study were compared to results previously obtained from 2- to 3-month-old rats in this laboratory (Matthews and Tuey, 1980, Toxicol. Appl. Pharmacol. 53, 377-388). Although the general pattern of HCB disposition did not change with age, i.e., metabolism and excretion of 236 versus persistence of 245, there were differences in the rates of elimination and in the tissue levels. There was enhanced metabolite retention in the muscle, skin, and adipose tissue of older animals which suggested an age-related decrease in tissue clearance. The large volume of adipose tissue in these older Sprague-Dawley rats could in part explain this observation. In general, there were few changes in decay rates from tissues or in biliary excretion. Age had a greater effect on the disposition of the persistent 245 than on the metabolizable 236. Thus, changes in body composition seemed to play a major role in age-related changes in the distribution and excretion of polychlorinated biphenyls.