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in the induction of injection site sarcomas (8/12 and 3/12 rats receiving propylene oxide in oil and water
vehicle, respectively) (Walpole, 1958). However, the study did not include an appropriate control
group.
F344 rats and B6C3F 1 mice (50/sex/dose) were exposed to 0, 200 or 400 ppm (0, 475 or 950
mg/m 3 ) of propylene oxide for 6 hours/day, 5 days/week for 102 weeks (NTP, 1985; Renne et al.,
1986). In rats, positive trends were demonstrated for papillary adenomas of the nasal turbinate
epithelium (males and females), thyroid gland C-cell adenomas or carcinomas (females) and
keratoacanthomas (males). A significantly increased incidence of endometrial stromal polyps and
sarcomas combined was noted for all doses. However, the NTP decided that only the nasal epithelial
tumors were treatment-related because the other tumors were either relatively common (thyroid) or
were of low incidence relative to historical controls. In mice, the low-dose group was killed due to an
inadvertent overdose 19 weeks after the initial start date. New groups of low-dose mice of both sexes
were started, but additional control groups were not included. Hemangiomas (males) and
hemangiosarcomas (both sexes) were significantly increased at the high dose. One squamous cell
carcinoma and one papilloma were observed in the nasal cavity of 2 high-dose males; nasal cavity
adenocarcinomas were reported in 2 high-dose females. Although not statistically significant, historical
controls have demonstrated an extremely low incidence of these tumor types. A significant dose-related
trend and incidence of mammary gland adenocarcinomas was observed in high-dose females.
Cpb:WU Wistar rats (100/sex/group) were exposed to 0, 30, 100 or 300 ppm (0, 71, 238 or 713
mg/m 3 ) propylene oxide for 6 hours/day, 5 days/week for 123-124 weeks (Reuzel and Kuper, 1983;
Kuper et al. , 1988). No nasal cavity tumors were observed; however, significant increases in
degenerative changes and neoplasia of the olfactory and respiratory epithelium were noted in both sexes
of all exposure groups. Significant increases were also found in mammary gland adenocarcinomas in
high-dose females. Squamous-cell carcinomas of the nose, larynx/pharynx and trachea, and
adenocarcinoma of the larynx/pharynx and lungs were reported in 5 high-dose males. Although not
statistically significant, none of these tumor types were reported in control males.
Male F344 rats exposed to 0, 100 or 300 ppm propylene oxide for 7 hours/day, 5 days/week for 104
weeks displayed a significant increase in nasal epithelium hyperplasia in the high-dose group (Lynch et
al., 1984). The incidence of adrenal pheochromocytomas was also increased.
V. DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Studies by Dunkelberg (1981) and NTP (1985) demonstrated that oral and inhalation exposure,
respectively, to propylene oxide can result in increased animal tumor incidence. In the study by
Dunkelberg (1981), female Sprague-Dawley rats exposed to total average doses of 0, 2714 or 10,798
mg/kg-day propylene oxide for 150 weeks demonstrated a significant increase in forestomach
squamous cell carcinoma tumor incidence (0/100, 2/50 and 19/50 for control, low-dose and high-dose
animals, respectively). These data were used to calculate an oral cancer potency factor for propylene
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