Disposition and metabolism of 2,2′-dimorpholinodiethyl ether in sprague dawley rats and B6C3F1/N mice after oral, intravenous administration, and dermal application

Abstract

1. 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 [¹⁴C]DMDEE (20 or 200 mg/kg) were determined in male ane female rats and mice after oral and intravenous administration and dermal application.

2. In male and female rats, following a single oral administration, [¹⁴C]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 [¹⁴C]DMDEE-derived products in tissue macromolecules.

3. Absorption following a single dermal application in rats was significant (∼64%) with a similar disposition pattern to oral.

4. The oral and dermal disposition of [¹⁴C]DMDEE in male and female mice was similar to rats.

5. Urinary products of DMDEE identified were oxidative metabolism of the morpholine ring.

6. Coadministration of DMDEE with nitrite in rats didn’t produce the rodent carcinogen, N-nitrosomorpholine.

Keywords:

• Absorption
• distribution
• metabolism
• excretion
• 2,2?-Dimorpholinodiethyl Ether

Acknowledgements

The authors are grateful Drs. Esra Mutlu and AtLee Watson for review of this manuscript. This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Intramural Research project ZIA ES103316-04, and performed for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract HHSN291200775562C (Lovelace Respiratory Research Institute, Albuquerque, New Mexico). CEBS Data Link for Reviewers: https://manticore.niehs.nih.gov/cebssearch/paper/14788

Disclosure statement

No potential conflict of interest was reported by the author(s).