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.