Teratogenicity of 2,3,7,8-tetrachlorodibenzofuran in the mouse.

Abstract

2,3,7,8-Tetrachlorodibenzofuran (TCDBF) was administered in single doses (0.1-0.8 mg/kg body weight) intraperitoneally to pregnant C57BL mice on d 10, 11, 12, or 13 of gestation. A dose-dependent increase was observed in the frequency of fetal resorptions and fetal death, especially in the earlier stages (d 10-11). Cleft palate and hydronephrosis as well appeared in a dose-dependent manner, with a peak in sensitivity after administration on d 11-12. TCDBF given at a dose level of 0.1 mg/kg body weight on d 12 of gestation (only dose- and stage-tested) produced a marked thymic hypoplasia as well. A few cases of general hydrops occurred. The pattern of malformations and time of sensitivity corresponded well to that observed earlier after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; ED50 approximately equal to 25 micrograms/kg) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB; ED50 approximately equal to 6 mg/kg), two congeners of TCDBF, indicating common mechanisms of action of this family of compounds. Ornithine decarboxylase (ODC) is an important enzyme in cell proliferation and growth with a high activity in embryonic tissues. Liver ODC activity has previously been found to be stimulated by TCDD in weaning mice. However, this enzyme was not found to be stimulated in fetal and placental tissues, but slightly in maternal kidney after treatment with TCDBF in teratogenic doses. It is possible that the ODC activity increases under certain conditions only, on administration of TCDD and its congeners.