Acute pathologic effects of 3,3',4,4',5,5'-hexabromobiphenyl in rats: comparison of its effects with Firemaster BP-6 and 2,2',4,4',5,5'-hexabromobiphenyl

Male Sprague-Dawley rats were fed diets containing 0, 0.1, 1, 10, or 100 ppm of 3,3′,4,4′,5,5′-hexabromobiphenyl (HBB), 2,2′,4,4′,5,5′-HBB, or Firemaster (FM) BP-6, a commercial mixture of polybrominated biphenyls, for 9 days. Although 3,3′,4,4′,5,5′-HBB is not in FM BP-6, it was used because it is a 3-methylcholanthrene (MC)-type inducer of hepatic drug-metabolizing enzymes. Nearly one-half of FM BP-6 is comprised of 2,2′,4,4′,5,5′-HBB and this congener is strictly a phenobarbital (PB)-type inducer. FM BP-6 has both MC- and PB-type induction capability. Feed consumption and body and organ weights were recorded and histologic and ultrastructural changes were evaluated. Significant effects on feed intake and body weight occurred only at 10 or 100 ppm of 3,3′,4,4′,5,5′-HBB. Therefore, two of six rats given 100 ppm of 3,3′,4,4′,5,5′-HBB were continued on the diet until death occurred at 20 days. Liver weights were increased by each of the three chemicals at 10 and 100 ppm. Hepatocytes were diffusely enlarged and contained lipid vacuoles. The degree of vacuolation was dose related, most prominent in the centrolobular to midzonal area, and most severe in rats given 3,3′,4,4′,5,5′-HBB. Thymic and splenic weights were decreased at 10 and 100 ppm of 3,3′,4,4′,5,5′-HBB and lymphocytic depletion was severe in the thymus. Ultrastructural hepatic lesions were seen with all three chemicals. For 2,2′,4,4′,5,5′-HBB and FM BP-6 at 10 and 100 ppm the changes consisted mainly of increased smooth endoplasmic reticulum and lipid vacuolation. Additional changes seen with 3,3′,4,4′,5,5′-HBB included disorganization of rough endoplasmic reticulum, myelin body formation, and bile ductule hyperplasia. Results indicated that 3,3′,4,4′,5,5′-HBB causes more severe pathologic effects than either FM BP-6 or 2,2′,4,4′,5,5′-HBB.