Malformations of the Great Vessels in the Neonatal Rat Induced by N‐(2‐Aminoethyl)ethanolamine

The reproductive and developmental toxicity of aminoethylethanolamine was evaluated in a standard screening study (OECD, 1995: Organisation for economic co‐operation and development. Paris, France), in which groups of Wistar rats (10/sex/group) were administered the test substance by gavage at dosage levels of 50, 250, or 1000 mg/kg/day (groups 2–4, respectively). A control group received the vehicle, doubly distilled water. No live pups were delivered in group 4, and there was a higher incidence of stillborn offspring and reduced postnatal survival in group 3. Macroscopic changes in groups 2 and 3 were primarily related to the great vessels and characterized by dilations, aneurysms, and altered course of the aorta, pulmonary trunk, carotids, and the ductus arteriosus. A follow‐up study was conducted to characterize the low dose‐response, using dosage levels of 0, 0.2, 1, 5, or 50 mg/kg/day (groups 1–5, respectively). Given the expected scarcity of the lesions in control offspring, each group consisted of 25 animals of each sex. Macroscopic examination revealed a high incidence (18.5%) of aneurysm‐bearing offspring in group 5 litters, and single offspring (0.3–0.4%) with aneurysms in groups 3 and 4. Microscopic examination revealed dissecting aneurysms in offspring from all aminoethylethanolamine treatment groups, without a clear dose‐response between groups 2 and 4 (0.6%, 1.2%, and 0.3%, respectively), and focal hemorrhages in all groups including the control. In comparison, the background incidence of aneurysms in untreated 4‐day old offspring was 0.2% (Treumann et al., 2011: Toxicol Pathol 39:969–974). Consequently, the findings in groups 2–4 cannot be conclusively attributed to treatment.