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. 5.3 Animal carcinogenicity data 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 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.