DIFFUSE VACUOLAR EPITHELIAL DEGENERATION IN RATS RECEIVING SUBCHRONICVAPOR EXPOSURE TO BIS[2-(DIMETHYLAMINO)ETHYL] ETHER (DMAEE)

Four groups of Sprague-Dawley rats (15 rats/sex/group) were exposed by whole body to analytically measured concentrations of 0 (control), 0. 23, 1.25, or 5.8 ppm bis[2-(dimethylamino)ethyl] ether (DMAEE) vapor f or 6 h/day, 5 days/wk, for 14 wk. Ten rats/sex/group were euthanized a fter the exposure regimen, and 5 rats/sex/group were euthanized after a 6-wk recovery period. An additional 3 rats/sex exposed to 0 and 5.8 ppm, were sequentially sacrificed following 1, 3, or 5 exposures for e lectron microscopic evaluation. The only systemic toxicity was reduced body weight gain for the 5.8 ppm group throughout the exposure regime n. Clinical signs of ocular and nasal tract irritation (swollen eyelid s and periocular and perinasal encrustation) were observed primarily i n the 5.8 ppm group, during the exposure and recovery periods. An opht halmic examination, following 13 wk of exposure, revealed keratitis in males from the 5.8 ppm group and females from the 1.25 and 5.8 ppm gr oups. At necropsy, diffuse corneal color change and/or swollen eyelids were observed for the 1.25 and/or 5.8 ppm groups. Exposure-related mi croscopic lesions were seen only in tissues having direct contact with DMAEE, including nonhaired skin, eyes, and the upper respiratory trac t. These consisted of necrosis, inflammation, and vacuolar degeneratio n of the nasal cavity mucosa and submucosa, and vacuolar degeneration of the larynx, trachea, bronchial epithelium, corneas, and glabrous or sparsely haired skin (pinna, muzzle, and eyelids). Nasal cavity lesio ns were present in rats from all exposure groups including the recover y period, while lesions in other tissues were observed only in the 5.8 ppm group at the 14-wk sacrifice. Electron microscopy of the nasal mu cosa of rats from the 5.8 ppm group showed the development of intracyt oplasmic membrane-bound vacuoles in the mucosal epithelium after a sin gle exposure, and in the mucosa and submucosa after 3 and 5 exposures. Vacuoles developed from the coalescence of small secretory vesicles b udding from the Golgi apparatus.