Effects of polybrominated biphenyls on the concentration and clearance of steroids from blood

Hepatic microsomal mixed-function oxidases have been stimulated when cattle were experimentally fed polybrominated biphenyls (PBB; fireMaster BP-6). These changes provide mechanisms for alteration of the metabolism and clearance of steroid hormones that might then affect reproductive function. This study was conducted to examine the effects of PBB on the clearance of radiolabel from injected estradiol-17 beta and progesterone along with daily determinations of concentrations of endogenous estradiol-17 beta and progestins in blood plasma. Toxicity was induced by dosing two Holstein cows with 25 g of fireMaster BP-6/d for 39 or 50 d. Single iv injections of 35 microCi [4-14C] progesterone and 400 microCi [2,4,6,7-3H] estradiol-17 beta were given on d -5, 10, 30 and 38 or 48 relative to dosing. Last injections were given when severe toxic symptoms were observed in each animal. Clinical signs, blood constituents, and necropsy findings confirmed the toxic syndrome. Clearance of 14C from progesterone was described by a biexponential function of time, while 3H from estradiol was cleared more slowly with a triexponential function. The total clearance rate for radiolabel from progesterone was approximately four times greater than estradiol throughout the experiments. The total clearance rates were similar for both steroids before and 10 d after dosing with PBB. A toxic syndrome was well developed by d 30 of PBB dosing and the total clearance rate of both steroids decreased approximately 50% with precipitous decreases when animals were terminally toxic. Despite the developing toxic syndrome, plasma concentrations of estradiol-17 beta and total progestins were normal and the periodicity of estrous cycles was maintained.