For definition of Groups, see Preamble Evaluation.
VOL.: 60 (1994) (p. 181)
CAS No.: 75-56-9
Chem. Abstr. Name: Methyloxirane
Propylene oxide is produced by dehydrochlorination of propylene chlorohydrin or by indirect oxidation of propylene. It is used primarily as a chemical intermediate to produce polyether polyols, propylene glycols and propylene glycol ethers. It is used to a lesser extent in the production of hydroxypropyl starch ethers, as a food additive and as a fumigant for certain dried fruits and nuts.
Occupational exposure occurs during the production of propylene oxide and its derivatives and during production of hydroxypropyl starch ethers.
One case-control study provides information about cancer risk in relation to exposure to propylene oxide specifically but does not allow any firm conclusion regarding carcinogenicity.
Propylene oxide was tested by oral gavage in one study in rats, by inhalation in one study in mice and in three adequate studies in rats and by subcutaneous administration in one study in mice and in one study in rats. Propylene oxide administered by oral gavage to rats produced tumours of the forestomach, which were mainly squamous-cell carcinomas. In mice exposed by inhalation, propylene oxide produced haemangiomas and haemangiosarcomas of the nasal cavity and a few malignant nasal epithelial tumours. In a study in rats of each sex exposed by inhalation, papillary adenomas of the nasal cavity were observed in males and females and thyroid adenomas and carcinomas were found in females; in the second study, in males, papillary adenomas of the nasal cavity and an increased incidence of adrenal phaeochromocytomas were observed; in the third study, in females, increased incidences of mammary fibroadenomas and adenocarcinomas were observed. Subcutaneous administration of propylene oxide to mice produced local sarcomas; the study in rats was inadequate for evaluation.
In rats exposed by inhalation, there is strong uptake of propylene oxide, which is then metabolized extensively and eliminated rapidly. Metabolism occurs predominantly by conjugation with glutathione. Propylene oxide can also be hydrolysed by epoxide hydrolase to 1,2-propanediol, which is subsequently metabolized to lactic and pyruvic acids. Propylene oxide forms adducts with proteins, including haemoglobin, in man, dog, rat and mouse. In mice, the concentration of the N-terminal valine adduct of propylene oxide in haemoglobin is linearly related to the administered dose. The alkylation efficiency in mice exposed by inhalation is about one-half that observed in rats and dogs.
In a seven-week study of rats exposed by inhalation, ataxia in the absence of muscular atrophy was observed, which was due to distal axonopathy in the central and peripheral nervous systems. Chronic and subchronic exposure of rats to propylene oxide by inhalation induced proliferative lesions, irritation and toxicity in the nasal mucosa and respiratory epithelium.
Other than occasional reductions in fetal weight, no adverse effects on reproduction were observed in rats or rabbits exposed to propylene oxide at up to 500 ppm.
DNA adducts of propylene oxide are formed in various organs of mice, rats and dogs. Binding in mouse liver DNA was about one-twentieth that of ethylene oxide.
Dominant lethal mutations were not induced in rats or mice, and sperm abnormalities were not observed in mice exposed to propylene oxide in vivo. Micronuclei and, in single studies, chromosomal aberrations and sister chromatid exchange were induced in mouse bone marrow after intraperitoneal injection of propylene oxide. Neither sister chromatid exchange nor chromosomal aberrations were induced in monkeys exposed by inhalation to 300 ppm. Propylene oxide induced chromosomal aberrations and sister chromatid exchange in human lymphocytes and DNA damage, gene mutation, chromosomal aberrations and sister chromatid exchange in mammalian cells in vitro. It caused dominant lethal mutation in Drosophila and was mutagenic to yeast, fungi and bacteria.
There is inadequate evidence in humans for the carcinogenicity of propylene oxide.
There is sufficient evidence in experimental animals for the carcinogenicity of propylene oxide.
Propylene oxide is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Suppl. 7 (1987) (p. 328)
See Also: Propylene oxide (EHC 56, 1985)