Distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) in maternal and fetal rabbits

The distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) was examined in maternal and fetal rabbits. Pregnant New Zealand rabbits (28-30 d gestational age) were anesthetized with ketamine/xylazine and the femoral vein and artery were catheterized for compound administration and sampling. Dams received iv [14C]2,4-D (12.5 microCi/kg) with unlabeled sodium 2,4-D (1, 10, or 40 mg/kg) in saline. Blood and tissue were collected up to 2 h after dosing. Fetal to maternal plasma AUC ratios were 0.09, 0.07, and 0.16 after the 1, 10, or 40 mg/kg dose, respectively. Extraplasma AUCs were greatest in maternal kidney and uterus and lowest in maternal and fetal brain. A greater than fourfold elevation in fetal AUC was found when the dose was increased from 10 to 40 mg/kg, suggesting saturation of maternal plasma binding of 2,4-D. Although the in vitro fetal brain tissue to incubation media ratio was unity (1.03 +/- 0.1, mean +/- SD), fetal brain AUCs were 10% or less of the fetal plasma AUCs, indicating the brain barrier system to 2,4-D is functioning in the late-gestation fetal rabbit. However, its development may not be complete due to the higher brain tissue to plasma ratios in the fetus compared to the dam.