Subchronic inhalation toxicity of morpholine in rats*1

The inhalation toxicity of 25-, 100-, and 250-ppm morpholine was investigated by 6 hr/day, 5 day/week exposures to Sprague-Dawley rats for 13 weeks. Irritant effects of morpholine exposures were evident mostly in the high exposure group; a reddish discharge was observed around the nose and mouth in the 250-ppm group rats after the first week; salivation was also observed. Ten rats/sex/dose level were sacrificed after 7 weeks. The high-level (250-ppm) exposure resulted in focal erosion and focal squamous metaplasia of the maxilloturbinates; effects were observed in 6 10 male rats and 2 10 female rats. There was also a sporadic increase of secretions in the Harderian gland sections. Almost all high-level rats sacrificed after 13 weeks demonstrated comparable effects; the lesions, which were increased in incidence and severity, involved the nasal septum and anterior nasal cavities in addition to the nasoturbinates and maxilloturbinates. Lesions of chronic murine pneumonia were increased in severity in the 250-ppm group. The only compound-related histomorphologic alterations observed in the 100-ppm group consisted of focal necrosis and necrotic cell debris in the nasal cavity of two female rats at terminal sacrifice. No exposure related effects were observed in the 25-ppm group. No significant compound-related effects on body weight, clinical chemistry, hematology, or organ weight data were observed.