Two-Year Inhalation Studies in Mice and Rats With HFO-1234ze(E), a Near Zero Global Warming Potential Propellant for Use in Pressurized Metered Dose Inhalers.

Abstract

HFO-1234ze(E) is being developed as a next-generation propellant (excipient), with near zero global warming potential, for use in pressurized metered dose inhalers. In accordance with regulatory guidance, an assessment of the carcinogenic potential of HFO-1234ze(E) was required to gain regulatory approval as a new excipient. HFO-1234ze(E) was therefore evaluated in two-year carcinogenicity studies in mice and rats by the inhalation route of administration. Study assessments included in-life observations, organ weights, histopathology, and hematology. Group mean (sex combined) inhaled doses were 2132, 6218, and 21,193 mg/kg/day in mice and 379, 120,8 and 3918 mg/kg/day in rats; in both studies, control animals were exposed to air alone under the same conditions as HFO-1234ze(E)-exposed animals. HFO-1234ze(E) was well tolerated at all doses. There were no HFO-1234ze(E)-related in-life effects and no neoplastic or non-neoplastic findings or effects on hematology in either study. In summary, HFO-1234ze(E) was not carcinogenic in mice or rats. These data support the use of HFO-1234ze(E) as a medical propellant.