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Effects of Polybrominated Biphenyls on the Concentration and Clearance of Steroids from Blood^1,2,

Ohio Agricultural Research and Development Center, Wooster 44691

⁴ Person to whom correspondence should be directed.

Abstract

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–17β and progesterone along with daily determinations of concentrations of endogenous estradiol–17β and progestins in blood plasma. Toxicity was induced by dosing two Holstein cows with 25 g of fire Master BP-6/d for 39 or 50 d. Single iv injections of 35 µCi [4-¹⁴C] progesterone and 400 βCi [2,4,6,7^-3H] estradiol-17µ 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-17β and total progestins were normal and the periodicity of estrous cycles was maintained.

¹ Salaries and research support provided by State and Federal Funds appropriated to the Ohio Agr. Res. and Develop. Center, The Ohio State Univ. Journal Article No. 83-82.

² This project was supported in part by Contract No. 223-75-7015, Dept. of Health, Education and Welfare, Food and Drug Administration, Bureau of Vet. Med. We acknowledge that portions of this research were conducted by A. L. Sprosty, and the capable technical assistance of B. A. Amiet and C. W. Clark.

³ Dept. of Dairy Sci.