Chronic morpholine exposure of rats.
The chronic toxicity and carcinogenic potential of morpholine were evaluated in 60 Sprague-Dawley rats/sex/group receiving morpholine at mean inhalation exposure concentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week, for 104 weeks. Survival, body weight gains, organ weights, hematology, and clinical chemistries were normal in exposed groups and comparable to those of the control animals. The incidences of palpable tissue masses and of histologically confirmed neoplasia were comparable among all groups, including the control groups, and were typical of the strain and age of the rats tested. In-life clinical examinations revealed increased incidences of irritation around the eyes and nares, chromadacryorrhea, and urine stains on the fur, predominantly in high-dose animals. Morpholine exposure was associated with corneal irritation seen by ophthalmoscopic examination and confirmed microscopically as keratitis limited to the highest exposure group. Irritation of the maxillary and nasoturbinates as indicated by infiltration of neutrophils, focal squamous metaplasia of the turbinate epithelium, and necrosis of the turbinate bone was observed in high-dose animals. Therefore, chronic exposure of rats to morpholine for 2 years at concentrations of 150 ppm or less revealed no carcinogenic potential or chronic systemic toxicity. Consistent with its known irritating properties, morpholine produced only local irritation, which was limited almost exclusively to high-dose animals.
Harbison
R D
RD
Center for Environmental Toxicology, University of Florida, Alachua 32615.
Marino
D J
DJ
Conaway
C C
CC
Rubin
L F
LF
Gandy
J
J
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D005128:Eye Diseases / Q000139:chemically induced; D005260:Female; D008297:Male; D009025:Morpholines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013997:Time Factors
D002273:Carcinogens; D009025:Morpholines