Toxicokinetic Profile of N-(2-Aminoethyl)ethanolamine in the Female Wistar Rat and Distribution into the Late Gestation Fetus and Milk
Article first published online: 27 MAR 2012
© 2012 Wiley Periodicals, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Volume 95, Issue 2, pages 107–115, April 2012
How to Cite
Moore, N. P., Saghir, S. A., Clark, A. J., Hansen, S. C., Carney, E. W., Marshall, V. A., Rasoulpour, R. and Bartels, M. J. (2012), Toxicokinetic Profile of N-(2-Aminoethyl)ethanolamine in the Female Wistar Rat and Distribution into the Late Gestation Fetus and Milk. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 95: 107–115. doi: 10.1002/bdrb.21009
- Issue published online: 23 APR 2012
- Article first published online: 27 MAR 2012
- Manuscript Accepted: 3 FEB 2012
- Manuscript Received: 9 DEC 2011
- Dow Chemical Company
- companies of the Ethyleneamines Product Stewardship Discussion Group
Vol. 98, Issue 3, 207, Article first published online: 28 MAY 2013
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. Birth Defects Res B Dev Reprod Toxicol [95:116-122]). 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 t1/2 = 0.1–0.2 hr). Elimination from the plasma followed a biphasic pattern, with a rapid elimination phase (t1/2 α = 1.6–1.8 hr) followed by a slower phase (t1/2 β = 16.7–17.3 hr). Following repeated gavage administration during gestation day 17 to 19, 14C-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, 14C-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.