INHIBITION OF PENTACHLOROBIPHENYL-INDUCED FETAL CLEFT-PALATE AND IMMUNOTOXICITY IN C57BL 6 MICE BY 2,2',4,4',5,5'-HEXACHLOROBIPHENYL/

3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependent indu ction of fetal cleft palate in offspring from pregnant C57BL/6 mice ex posed to a single dose (783 or 1044 mu g/kg) of this compound on gesta tion day 10. In contrast, 2,2',4,4',5,5'-hexaCB did not cause cleft pa late at a dose of 271 mg/kg and, in pregnant mice cotreated with 2,2', 4,4',5,5'-hexaCB (271 mg/kg) plus 783 or 1044 mu g/kg 3,3',4,4',5-pent aCB, fetal cleft palate formation was significantly inhibited. 3,3',4, 4',5-PentaCB (6 mu g/kg) also inhibited the splenic plaque-forming cel l (PFC) response and serum IgM levels in C57BL/6 mice treated with the T cell-independent antigen trinitrophenyl-lipopolysaccharide. At dose s as high as 72 mg/kg, 2,2',4,4'-5,5'-hexaCB was not immunotoxic; howe ver, 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), t here was a dose-dependent inhibition of 3,3',4,4',5-pentaCB-induced im munotoxicity. These non-additive (antagonistic) interactions of protot ypical polychlorinated biphenyl (PCB) congeners may be an important co nsideration in development of a toxic equivalency factor approach for hazard and risk assessment of PCB mixtures. (C) 1997 Elsevier Science Ltd.