Abstract
The induction of cleft palate by 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) administered with thyroid hormones triiodothyronine (T 3) or thyroxine (T 4) was investigated in C57BL 6N mice. Timed-pregnant mice were treated with vehicle, TCDD, T 3, T 4, TCDD plus T 3, or TCDD plus T 4 on Days 10 to 13 of gestation. No cleft palates were observed in any control fetuses in this study, nor have there been any cleft palates in 1193 fetuses or 154 control litters in the past 24 months. TCDD (3 μg/kg/day) caused about 8% cleft palates per litter, while T 3 (120, 240, 480 μg/kg/day) and T 4 (625, 1250, 2500 μg/kg/day) resulted in no more than 1.2% cleft palates per litter in any of the treatment groups and the incidence was not dose related. The combination of TCDD (3 μg/kg/day) plus T 3 at 120, 240, and 480 μg/kg/day resulted in 15.9, 20.6, and 31.4% cleft palates per litter, respectively. TCDD plus T 4 at 625, 1250 and 2500 μg/kg/day caused 15.1, 22.9, and 27.2% cleft palates per litter. No cleft palates were observed when large doses of T 3 were given in combination with T 4. These data demonstrated that coadministration of T 3 or T 4 with TCDD increased the incidence of cleft palate to incidences greater than expected from the separate administration of the hormones plus TCDD.
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