title: Developmental sensitivity to the induction of great vessel malformations by N-(2-aminoethyl)ethanolamine.
abstract: N-(2-Aminoethyl)ethanolamine (AEEA) induced malformations of the great vessels in the offspring of rats treated during gestation and early lactation (Schneider et al., 2012. Birth Defects Res B Dev Reprod Toxicol [in press]). The aim of this study was to determine if in utero exposure alone was sufficient to induce these malformations or whether a peri-postnatal exposure or physiological component was required. Three groups of five time-mated female Wistar Han rats were administered AEEA (250 mg/kg/day) by gavage from gestation day (GD) 6 to GD 19 (groups 1 and 2) or from GD 6 to postnatal day 3 (group 3). Animals were euthanized on GD 21 (group 1) or postnatal day 4 (groups 2 and 3), and the hearts of the offspring were examined for changes to the great vessels. The incidence of malformations in group 1 was 91.1%, and primarily consisted of high aortic arch and abnormal carotid course. One fetus had an aortic aneurysm. All fetuses in groups 2 and 3 were malformed, primarily exhibiting abnormal carotid course and aneurysms, which mainly affected the aorta, ductus arteriosus, and pulmonary trunk. The incidence of high aortic arch was lower relative to group 1. Aneurysms were more prevalent in group 3 compared to group 2. These findings indicate that exposure to AEEA during gestation alone was sufficient to induce malformations of the great vessels and aneurysms, which may be triggered by physiological changes that occur during or after birth, but that the critical period of susceptibility to AEEA-induced aneurysms in the rat extends beyond gestation into the early postnatal period.
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: Belen
authors.initials: B
authors.lastname: Tornesi
authors.forename: Barry L
authors.initials: BL
authors.lastname: Yano
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Nitschke
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
mesh_terms: D000783:Aneurysm / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D004983:Ethanolamines / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D054079:Vascular Malformations / Q000139:chemically induced / Q000473:pathology*
chemical_list: D004983:Ethanolamines; C035835:N-(2-hydroxyethyl)ethylenediamine