Disposition and metabolism of 2,2′-dimorpholinodiethyl ether in sprague dawley rats and B6C3F1/N mice after oral, intravenous administration, and dermal application
Creators: name: Suramya Waidyanatha
name: McDonald, Jacob D.
name: J. Michael Sanders
name: Doyle-Eisele, Melanie
name: Moeller, Benjamin C.
name: C. Edwin Garner
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Ecology
subject: Marine Biology

description: The specialty amine catalyst 2,2′-dimorpholinodiethyl ether (DMDEE) is a high-production volume chemical used in the production of flexible foam, high-resilient molded foam, and in coatings and adhesives. The disposition and metabolism of [<sup>14</sup>C]DMDEE (20 or 200 mg/kg) were determined in male ane female rats and mice after oral and intravenous administration and dermal application.In male and female rats, following a single oral administration, [<sup>14</sup>C]DMDEE was well-absorbed and excreted rapidly and extensively via urine (75–93%) and some in feces (∼4–8%). The total radioactivity in tissues at 24 h and 72 h (males only) following oral administration was 8–10% and ∼4%, respectively, suggesting considerable tissue distribution. A moderate amount of the total tissue radioactivity in kidney and liver were unextractable suggesting covalent binding of [<sup>14</sup>C]DMDEE-derived products in tissue macromolecules.Absorption following a single dermal application in rats was significant (∼64%) with a similar disposition pattern to oral.The oral and dermal disposition of [<sup>14</sup>C]DMDEE in male and female mice was similar to rats.Urinary products of DMDEE identified were oxidative metabolism of the morpholine ring.Coadministration of DMDEE with nitrite in rats didn’t produce the rodent carcinogen, <i>N-</i>nitrosomorpholine. The specialty amine catalyst 2,2′-dimorpholinodiethyl ether (DMDEE) is a high-production volume chemical used in the production of flexible foam, high-resilient molded foam, and in coatings and adhesives. The disposition and metabolism of [<sup>14</sup>C]DMDEE (20 or 200 mg/kg) were determined in male ane female rats and mice after oral and intravenous administration and dermal application. In male and female rats, following a single oral administration, [<sup>14</sup>C]DMDEE was well-absorbed and excreted rapidly and extensively via urine (75–93%) and some in feces (∼4–8%). The total radioactivity in tissues at 24 h and 72 h (males only) following oral administration was 8–10% and ∼4%, respectively, suggesting considerable tissue distribution. A moderate amount of the total tissue radioactivity in kidney and liver were unextractable suggesting covalent binding of [<sup>14</sup>C]DMDEE-derived products in tissue macromolecules. Absorption following a single dermal application in rats was significant (∼64%) with a similar disposition pattern to oral. The oral and dermal disposition of [<sup>14</sup>C]DMDEE in male and female mice was similar to rats. Urinary products of DMDEE identified were oxidative metabolism of the morpholine ring. Coadministration of DMDEE with nitrite in rats didn’t produce the rodent carcinogen, <i>N-</i>nitrosomorpholine.