Polychlorinated biphenyl (PCB) congeners as 2,3,7,8-TCDD antagonists: Teratogenicity studies

Administration of 2,3,7,8-TCDD (20 μg/kg) to female C57BL/6 mice gave >60% cleft palate in the litters. Previous studies have shown that cotreatment of the pregnant mice with 2,3,7,8-TCDD (20 μg/kg) and Aroclor 1254 (750 μmol/kg) resulted in complete protection of the animals from cleft palate. In contrast, a lower dose of Aroclor 1254 (250 μmol/kg) was a less effective 2,3,7,8-TCDD antagonist. Several PCB congeners, including 2,2′,5,5′-tetrachlorobiphenyl and 2,2′,4,4′,5,5′-hexachlorobiphenyl, which exhibit some Ah receptor binding activity were investigated as 2,3,7,8-TCDD antagonists in the in vivo teratogenicity assay system. Both PCB congeners significantly protected the mice from 2,3,7,8-TCDD-mediated cleft palate. The significance of these results and their mechanistic implications will be discussed.