Evaluation of 2,2'-dimorpholinodiethyl ether (DMDEE) in pathology, perinatal, and genotoxicity studies.

2,2'-Dimorpholinodiethyl ether (DMDEE) is a tertiary amine catalyst used in the production of polyurethane foams. Human exposure may occur occupationally through inhalation of DMDEE vapors. B6C3F1/N mice (5-6 weeks old) were exposed to 0-1000 mg DMDEE/kg in water by oral gavage daily for 4 weeks. Time-mated Harlan Sprague Dawley (HSD) rats (12-14 weeks old) were exposed to 0-500 mg DMDEE/kg in water from gestation day (GD) 6 through post-natal day (PND) 27 by oral gavage; their pups were directly dosed from PND12 through PND27. Blood was collected from mice (4-weeks), rat dams (GD18, PND4, PND28) and rat pups (PND 4, PND 28) for hematology, clinical chemistry, and micronucleus evaluation; mouse tissues were analyzed for histopathology. DMDEE (500-6000 μg/plate) was evaluated for mutagenicity using Salmonella typhimurium (TA98, TA100) or Escherichia coli WP2 uvrA pKM101. No DMDEE-related effects were observed on pregnancy or litter parameters in HSD rats. The mouse and rat micronucleus tests and the bacterial reverse mutation tests were negative. At 1000 mg DMDEE/kg, behavioral observations of circling, repetitive head lifting, and abnormal gait were accompanied by cytoplasmic vacuolization in epithelial cells of the brain choroid plexus, and in the renal cortical tubules in male and female mice. Cytoplasmic vacuolization was also observed in the epithelial cells in the coagulating gland, prostate, and epididymis of male mice. These data indicate deficits in the cellular structure and function of neurological and renal tissues in male and female mice, as well as male reproductive tissues at higher doses and suggest caution in the industrial use of DMDEE.