title: Toxicokinetic profile of N-(2-aminoethyl)ethanolamine in the female Wistar rat and distribution into the late gestation fetus and milk.
abstract: N-(2-aminoethyl)ethanolamine (AEEA) caused aneurysms of the great vessels in rats exposed in utero and during the first days post partum, exacerbated by postnatal treatment of the lactating dams (Moore et al., 2012). The purpose of this work was to examine the systemic availability of AEEA during gestation and early lactation. The absorption of AEEA was determined following oral administration to nonpregnant and pregnant female Wistar rats. A single dose administered by gavage (0.5 or 50 mg/kg) on gestation day 18 was rapidly and extensively (>90%) absorbed from the gastrointestinal tract (absorption t(1/2)  = 0.1-0.2 hr). Elimination from the plasma followed a biphasic pattern, with a rapid elimination phase (t(1/2 α)  = 1.6-1.8 hr) followed by a slower phase (t(1/2 β)  = 16.7-17.3 hr). Following repeated gavage administration during gestation day 17 to 19, (14) C-AEEA-derived radioactivity readily partitioned into the fetus and was evenly distributed therein, but cleared approximately twofold slower from the fetal blood and tissues than the maternal blood and chorioallantoic placenta. When administered to lactating dams during lactation days 1 to 12, (14) C-AEEA-derived radioactivity preferentially partitioned into the milk reaching levels that were between 1.6- and 2.5-fold higher than the maternal blood. Although the concentration of AEEA equivalents in the maternal blood remained quite consistent, the concentration in the milk fell by almost 40% between lactation days 4 and 12, probably reflecting an increase in milk production over this same period. We confirm exposure of the offspring to AEEA both in utero and during lactation, but that AEEA does not appear to specifically concentrate in the great vessels.
authors.affiliation: Toxicology and Environmental Research and Consulting, Dow Europe GmbH, Horgen, Switzerland. nmoore@dow.com
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Moore
authors.forename: Shakil A
authors.initials: SA
authors.lastname: Saghir
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hansen
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Marshall
authors.forename: Reza J
authors.initials: RJ
authors.lastname: Rasoulpour
authors.forename: Reza
authors.initials: R
authors.lastname: Rasoulpour
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bartels
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007774:Lactation; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000737:chemistry*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004983:Ethanolamines; C035835:N-(2-hydroxyethyl)ethylenediamine