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 blood wt) i.p. to pregnant C57BL mice on days 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 (days 10-11). Cleft palate and hydronephrosis appeared in a dose-dependent manner, with a peak in sensitivity after administration on days 11-12. TCDBF given at 0.1 mg/kg body wt on day 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 .apprxeq. 25 .mu.g/kg) and 3,3'',4,4''-tetrachloroazoxybenzene (TCAOB; EC50 .apprxeq. 6 mg/kg), 2 congeners of TCDBF, indicating common mechanisms of action of this family of compounds. Ornithine decarboxylase (ODC) was an important enzyme in cell proliferation and growth with a high activity in embryonic tissues. Liver ODC activity had previously been found to be stimulated by TCDD in weanling mice. This enzyme was not stimulated in fetal and placental tissues, but was slightly stimulated in maternal kidney after treatment with TCDBF at teratogenic doses. The ODC activity possibly increased under certain conditions only, on administration of TCDD and its congeners.