Pathologic Effects of Purified Polybrominated Biphenyl Congeners in Rats

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Abstract
Young male rats were fed diets containing 0, 1, 10, or 100 ppm of Firemaster (FM) BP-6 for 30 days, and the effects were compared with those caused by feeding diets containing identical amounts of either 2, 2', 4, 4', 5, 5-hexabromobiphenyl (HBB) or 2, 3', 4, 4', 5, 5'-HBB, two of the congeners contained in FM BP-6. In addition, rats were fed diets containing 0, 1, or 10 ppm of 3, 3', 4, 4', 5, 5'-HBB, a congener not in FM BP-6 but used because it is strictly a 3-methylcholanthrene (MC)-type inducer of hepatic drug metabolizing enzymes. Feed efficiency and weight gains were reduced only by 3, 3', 4, 4', 5, 5'-HBB at 10 ppm. Hepatomegaly occurred in rats given any of the chemicals. Vacuolation and enlargement of hepatocytes were observed in rats fed diets containing FM BP-6 or any of the congeners but were most prominent with 3, 3', 4, 4', 5, 5-HBB. Proliferation of smooth endoplasmic reticulum (SER), decreased rough endoplasmic reticulum (RER), and increased fat droplets were seen in hepatocytes of rats given FM BP-6. Similar but less severe changes were seen with 2, 3', 4, 4', 5, 5-HBB or 2, 2', 4, 4', 5, 5-HBB. The latter chemical produced the least severe changes. Hepatocytes of rats fed 10 ppm 3, 3', 4, 4', 5, 5'-HBB had extensive proliferation and disorganization of RER, increased fat droplets, and some proliferation of SER. Thymic and splenic atrophy associated with cortical lymphocytic depletion were observed only in rats fed 3, 3', 4, 4', 5, 5-HBB. 3, 3', 4, 4', 5, 5-HBB, which is an MC-type inducer, was the most toxic congener among the congeners studied. Apparently, 2, 2', 4, 4', 5, 5-HBB, which is the major congener in FM BP-6 and a phenobarbital (PB)-type inducer, contributes little to its toxicity. FM BP-6, a mixed (MC and PB)-type inducer, is more toxic than either 2, 2', 4, 4', 5, 5-HBB or 2, 3', 4, 4', 5, 5-HBB. However, 2, 3', 4, 4', 5, 5-HBB, a mixed-type inducer, is more toxic than 2, 2', 4, 4', 5, 5-HBB. Toxicity of FM BP-6 can be mostly attributed to its congeners with MC-type induction capability.