Propylene oxide is a volatile, colorless liquid used as an intermediate in the production of polyether polyols,
polyurethane foams, and unsaturated
polyester resins and also as a fumigant for sterilizing a variety of materials ranging from
plastic medical instruments to foodstuffs. In the United States,
propylene oxide is registered as a fumigant for packaged dried prunes and glacé fruits such as candied cherries and as an insecticidal and fungicidal fumigant for bulk quantities of cocoa, gums, and processed spices. The 2-year
carcinogenesis studies of
propylene oxide (greater than 99.9% pure) were conducted by exposing groups of 50 F344/N rats and 50 B6C3F1 mice of each sex to air containing
propylene oxide at concentrations of 0 (chamber control), 200, or 400 ppm for 6 hours per day, 5 days per week, for 103 weeks. The survival of rats exposed to
propylene oxide was comparable with that of the controls; terminal
body weights were lower than those of the controls for high dose males (8%) and high dose females (6%). Survival of exposed male and female mice decreased relative to that of the controls (male: control, 42/50; low dose, 34/50; high dose, 29/50; female: 38/50; 29/50; 10/50), but the difference was significant only for animals in the high dose groups. High dose female mice had a mean terminal
body weight 22% below that of the controls. The respiratory epithelium of the nasal turbinates was one of the primary tissues affected in male and female rats; exposure-related increases occurred in the incidences of suppurative
inflammation, epithelial
hyperplasia, and squamous
metaplasia.
Papillary adenomas, involving the respiratory epithelium and underlying submucosal glands of the nasal turbinates, were observed in three female rats and two male rats exposed to
propylene oxide at 400 ppm. The incidence of
adenomas in females was significant by the trend tests. The proportions of high dose female rats with C-cell
adenomas and with C-cell
carcinomas of the thyroid gland were increased, but only the combined incidence of these
tumors was significant (2/45; 2/35; 7/37). These
tumors were not considered to be related to exposure to
propylene oxide because there was no other evidence for C-cells' being a target tissue and because there was no increase in C-cell
hyperplasia. The combined incidences of female rats with endometrial stromal
polyps and
endometrial stromal sarcomas of the uterus were significantly increased in the dosed groups (3/49; 12/50; 10/47). However, the occurrence of these lesions in the dosed groups was similar to the average (306/1,502, 20%) seen in untreated controls in NTP
carcinogenesis studies, and hence this increase was not regarded as being related to exposure to
propylene oxide. The respiratory epithelium of the nasal turbinates was also one of the primary tissues affected in male and female mice; exposure-related increases occurred in the incidences of
inflammation, and squamous
metaplasia was observed in one low dose male and two high dose female mice. One
squamous cell carcinoma and one
papilloma occurred in the nasal cavity of different high dose male mice, and two high dose female mice had
adenocarcinomas of the nasal cavity. The endothelial cells of the submucosal vascular plexus in the nasal turbinates also appeared to be a major site affected in high dose male mice. Three high dose male and three high dose female mice had a saccular dilation (classified as angiectasis) of submucosal turbinate vessels. Further,
hemangiomas were seen in the nasal cavity of 5/50 high dose male mice and 3/50 high dose female mice, and
hemangiosarcomas were found in the nasal cavity of 5/50 high dose male mice and 2/50 high dose female mice. The increased incidences of
hemangiomas in males and females and of
hemangiosarcomas in males were statistically significant. Vascular
tumors were not present in the nasal turbinates of any low dose or control mice. Under the conditions of these studies, there was some evidence of carcinogenicity for F344/N rats, as indicated by increased incidences of papillary adenomasncreased incidences of
papillary adenomas of the nasal turbinates in male and female rats exposed to
propylene oxide at 400 ppm. For male and female B6C3F1 mice, there was clear evidence of carcinogenicity, as indicated by increased incidences of
hemangiomas or
hemangiosarcomas of the nasal turbinates at 400 ppm. In the respiratory epithelium of the nasal turbinates,
propylene oxide also caused suppurative
inflammation,
hyperplasia, and squamous
metaplasia in rats and
inflammation in mice.