title: Distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) in maternal and fetal rabbits.
abstract: 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.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/ FDA, Jefferson, Arkansas 72079, USA. jsandberg@nctr.fda.gov
authors.forename: J A
authors.initials: JA
authors.lastname: Sandberg
authors.forename: H M
authors.initials: HM
authors.lastname: Duhart
authors.forename: G
authors.initials: G
authors.lastname: Lipe
authors.forename: Z
authors.initials: Z
authors.lastname: Binienda
authors.forename: W
authors.initials: W
authors.lastname: Slikker
authors.forename: C S
authors.initials: CS
authors.lastname: Kim
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D014018:Tissue Distribution; D014599:Uterus / Q000737:chemistry / Q000378:metabolism
chemical_list: D015084:2,4-Dichlorophenoxyacetic Acid