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oxide. In the NTP carcinogenicity study (1985), 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. High-dose rats exhibited an increased incidence of nasal papillary
adenomas (2/50 for males, 3/50 for females), suggesting a carcinogenic response. However, these
increases were not significant when compared to controls (0/50 for both sexes), making them unsuitable
for carcinogenicity risk estimation. The incidence of nasal cavity hemangiomas or hemangiosarcomas in
mice was 10/50 and 5/50 in the high-dose males (p = 0.001) and females (p = 0.028), respectively.
These data, from a study where adequate numbers of animals of both sexes were treated for a lifetime,
demonstrate that inhalation exposure to propylene oxide results in respiratory tract carcinogenicity. The
male rat hemangioma/hemangiosarcoma data was used as the basis for a inhalation unit risk factor.
Methodology
Oral Cancer Potency Factor
Transformed animal doses (0, 2.58 and 10.28 mg/kg/day) and human equivalent doses (0, 0.44 and
1.76 mg/kg-day) were calculated from the administered doses using a rat body weight of 0.35 kg, a
human body weight of 70 kg, 1029 days as the length of the exposure, and 1050 days as the length of
the experiment and animal lifespan. A human oral cancer potency factor of
2.4 E-1 (mg/kg/day) -1 was calculated using the linearized multistage procedure developed by Kenneth
Crump and adopted by US EPA (1980).
Inhalation Unit Risk Factor
Transformed animal doses (0, 55 and 110 mg/kg/day) were calculated from administered doses
assuming 50% pulmonary absorption, 0.03 kg mouse body weight, 0.039 m 3 /day as the daily inhalation
volume for mice and an exposure duration and length of experiment of 103 weeks. The absorption
factor is consistent with that observed for epichlorohydrin in rat respiratory tract (Stott and McKenna,
1984). Human equivalent doses were 0, 4.15 and 8.3 mg/kg/day. The transformed animal dose level
was used to calculate an animal slope factor of 9.3E-4 (mg/kg/day) -1 using the linearized multistage
procedure developed by Kenneth Crump and adopted by US EPA (1980). A human unit risk factor of
3.7 E-6 (µg/m 3 ) -1 was determined using an animal body weight of 0.03 kg, a human body weight of 70
kg and an animal lifetime of 103 weeks. US EPA has stated that the unit risk should not be used if the
air concentration exceeds 3 mg/m 3 , since above this concentration the unit risk may not be appropriate.
V. REFERENCES
Dunkelberg H. 1981. Carcinogenic activity of ethylene oxide and its reaction products 2-chloroethanol,
2-bromoethanol, ethylene glycol and diethylene glycol: 1. Carcinogenicity of ethylene oxide in
comparison with 1,2-propylene oxide after subcutaneous administration in mice. Zentralbl Bakteriol,
Mikrobiol Hyg, Abt 1 Orig. B Hyg Umwelthyg Krankenhaushyg Arbeitshyg Praev Med 174:383-404.
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