Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-induced fetal cleft palate and immunotoxicity in C57BL/6 mice by 2,2′,4,4′,5,5′-hexachlorobiphenyl

Abstract

3,3′,4,4′,5-Pentachlorobiphenyl (pentaCB) caused a dose-dependent induction of fetal cleft palate in offspring from pregnant C57BL/6 mice exposed to a single dose (783 or 1044 μg/kg) of this compound on gestation and 10. In contrast 2,2′,4,4′,5,5′-hexaCB did not cause cleft palate at a dose 271 mg/kg and, in pregnant mice cotreated with 2,2′,4,4′,5,5′-hexaCB (271 mg/kg) plus 783 or 1044 μg/kg 3,3′,4,4′,5-pentaCB, fetal cleft plane formation was significantly inhibited. 3,3′,4,4′-PentaCB (6 μg/kg) also inhibited the splenic plaque-forming cell (PFC) response and serum IgM levels in C57BL/6 mice treated with the T cell-independent antigen trinitrophenyl-lipopolysaacharide. At doses as high as 72 mg/kg, 2,2′,4,4′,5,5′-hexaCB was not immunotoxic; however, in mice cotreated with a immunotoxic dose of 3,3′,4,4′,5-pentaCB plus different doses of 2,2′,4,4′,5,5′-hexaCB (18, 36 and 72 mg/kg), there was a dose-dependent inhibition of 3,3′,4,4′,5-pentaCB-induced immunotoxicity. These non-additive (antagonistic) interactions of prototypical polychlorinated biphenyl (PCB) congeners may be an important consideration in development of a toxic equivalency factor approach for hazard and risk assessment of PCB mixtures.