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

被引:0
|
作者
Waidyanatha, Suramya [1 ]
McDonald, Jacob D. [2 ]
Sanders, J. Michael [1 ]
Doyle-Eisele, Melanie [2 ]
Moeller, Benjamin C. [2 ]
Garner, C. Edwin [2 ]
机构
[1] NIEHS, Div Natl Toxicol Program, POB 12233,Mail Drop K2-07, Res Triangle Pk, NC 27709 USA
[2] Lovelace Resp Res Inst, Albuquerque, NM USA
基金
美国国家卫生研究院;
关键词
Absorption; distribution; metabolism; excretion; 2; 2?-Dimorpholinodiethyl Ether; IN-VITRO; ADDUCT FORMATION; BIOACTIVATION; MORPHOLINE; CARCINOGENESIS; PHARMACOKINETICS; PATHWAYS;
D O I
10.1080/00498254.2020.1779389
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 [C-14]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, [C-14]DMDEE was well-absorbed and excreted rapidly and extensively via urine (75-93%) and some in feces (similar to 4-8%). The total radioactivity in tissues at 24 h and 72 h (males only) following oral administration was 8-10% and similar to 4%, respectively, suggesting considerable tissue distribution. A moderate amount of the total tissue radioactivity in kidney and liver were unextractable suggesting covalent binding of [C-14]DMDEE-derived products in tissue macromolecules. Absorption following a single dermal application in rats was significant (similar to 64%) with a similar disposition pattern to oral. The oral and dermal disposition of [C-14]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,N-nitrosomorpholine.
引用
收藏
页码:1341 / 1351
页数:11
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