Rapid distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to embryonic tissues in C57BL/6N mice and correlation with palatal uptake in vitro.
2,3,7,8-Tetracholoridbenzo-p-dioxin (TCDD) is a developmentally toxic environmental contaminant capable of inducing cleft palate and hydronephrosis in embryonic C57BL/6N mice. In this study, the disposition of TCDD was determined in pregnant C57BL/6N mice in the 24 hr immediately following oral administration on Gestation Day (GD) 12. TCDD was detected in maternal blood, liver, and fat and in the placenta, embryonic liver, and palate within 30 min after dosing on GD 12. The levels peaked in blood and placenta at 3 hr and in the other tissues at 8 hr. Levels of TCDD decreased slightly after 8 hr in embryonic liver and palate. In vitro systems were used to study the mechanisms of action of TCDD and in these models exposure is typically reported as concentration of TCDD in the culture medium. The present study is the first to allow a direct comparison of the level of TCDD in embryonic tissue after in vivo and in vitro exposures. Uptake of TCDD was determined in embryonic palatal organ culture and tissue levels were then expressed in comparable units for both in vivo and in vitro exposures. The data provide new information on distribution in the pregnant mouse and the embryo and also show that the palatal organ culture model provides a reasonable dosimetric representation of in utero exposure.
Abbott
B D
BD
Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Birnbaum
L S
LS
Diliberto
J J
JJ
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood / Q000493:pharmacokinetics*; D011247:Pregnancy; D014018:Tissue Distribution
D000072317:Polychlorinated Dibenzodioxins