3,3'4,4'-Tetrachlorobiphenyl in pregnant mice: embryotoxicity, teratogenicity, and toxic effects on the cultured embryonic thymus.

3,3',4,4'-Tetrachlorobiphenyl (TCB) is a known ligand of the Ah-receptor. When TCB was given to Ah-responsive C57BL/6 mice at gestation day 11, 12 or 13, a pattern of embryotoxic effects similar to those of TCDD was produced. This pattern included death and resorptions of the conceptus (peak sensitivity at day 11), as well as characteristic malformations such as cleft palate, dilated kidney pelvis (peak sensitivity day 12), and thymus hypoplasia (peak sensitivity day 13). The ED50 for cleft palate induction was found to be about 100 mg/kg, as compared to 30 micrograms/kg for TCDD (earlier results). The binding affinity of TCB for the Ah-receptor has been reported to be two orders of magnitude lower than that of TCDD. When TCB was introduced into a thymus organ culture (thymi taken from day-14 embryos), the lymphoid cell development was inhibited with an approximate EC50 of 5 X 10(-8) M. This is approximately 100 times higher than that of TCDD and in good agreement with the receptor binding affinities of both compounds. The difference in in vivo toxicity between TCB and TCDD can be explained by a more rapid metabolism and excretion of TCB.