Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus.

(1) Following the administration of the highly toxic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant mice, exceedingly low concentrations of this substance were found in the embryo and fetus between gestational days 11 and 18 (between 0.04 and 0.14% of the maternal dose/g tissue). (2) Tissue levels of tCDD in embryos on days 9 and 10 exceeded those of later gestational stages. (3) TCDD levels in fetal livers were 2--4 times higher than those in other fetal organs. (4) Maternal liver contained the highest concentrations of TCDD (4 -10% of the dose/g). A comparison of the results obtained following oral, s.c. and i.p. applications indicated that there was no major first pass effect involved following oral administration. (5) Placenta and other extrahepatic maternal organs exhibited TCDD levels, which were approximately 1, embryos and features 2 orders of magnitude lower than maternal liver concentrations. (6) Good correlation was found between the doses applied (5, 12.5 and 25 microgram/kg) and the tissue levels observed. (7) A single dose of 25 microgram/kg given on day 10 or 5 doses of 5 microgram/kg, 1/day from days 7-11, resulted in higher levels of TCDD in embryos on day 13 than did a singly dose of 25 microgram/kg on day 7; cleft palate was induced at different rates by these treatment schedules.