Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin: increased incidence of cleft palate in mice.

The induction of cleft palate in C57BL/6N mice is an extremely reproducible and sensitive indicator of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. This endpoint was used to look for potential interactions between two polychlorinated biphenyl (PCB) congeners and TCDD. Both 2,3,4,5,3',4'-hexachlorobiphenyl (HCB) and 2,4,5,2',4',5'-HCB are of relatively low toxic potency, but their biological properties differ. Pregnant mice were treated with TCDD and either HCB on gestation Days 10 through 13, and the fetuses examined for the presence of cleft palate and renal abnormalities on gestation Day 18. At a dose of TCDD which caused a low level of cleft palate, moderate hydronephrosis was observed. No renal or palatal anomalies were detected after 2,4,5,2',4',5'-HCB treatment, and the combination of this isomer with TCDD had no effect on the incidence of TCDD-induced cleft palate. 2,3,4,5,3',4'-HCB caused mild renal toxicity, but no cleft palate. However, treatment of pregnant mice with a combination of TCDD and 2,3,4,5,3',4'-HCB resulted in a 10-fold increase in the incidence of cleft palate. Thus, the toxicity of compounds such as TCDD may be enhanced by compounds of relatively low acute toxicity such as selected PCBs. The widespread environmental occurrence of such combinations suggests a need for further evaluation of the mechanism of this interaction.