The Nonclinical Assessment of Trans-1,3,3,3-tetrafluoropropene (HFO-1234ze (E)), a Near Zero Global Warming Potential Propellant for Use in Metered Dose Inhalation Products.
Paul S GiffenJoanne D KilgourMatthew JacobsenKaren ThackerAnn A HolmbergPublished in: International journal of toxicology (2023)
HFO-1234ze (E) is proposed as a near zero global warming propellant for use in metered dose inhaled (MDI) products. This paper describes the non-clinical safety assessment in mice, rats, and dogs and supplements previously reported data (genetic toxicology, short-term toxicology, and reproductive toxicology). In all species, HFO-1234ze (E) was only detectable in blood for a short period after dosing with no evidence of accumulation. HFO-1234ze (E) was without any toxicological effects at very high doses in subchronic (13-week mouse) and chronic (39-week dog) studies. Chronic (26-week) administration to rats at very high doses was associated with an exacerbation of rodent progressive cardiomyopathy, a well-documented background finding in rodents. In a 2-generation study, extremely high doses were associated with the early euthanasia of some lactating female rats. This finding was considered to be significantly influenced by a state of negative energy balance, reflecting the specific vulnerability of rats during lactation. These findings are considered to not pose a risk to humans with typical MDI use given they occurred at doses which far exceed those expected in patients. Overall, the nonclinical safety data for HFO-1234ze (E) support its further development as an MDI propellant.
Keyphrases
- end stage renal disease
- electronic health record
- newly diagnosed
- ejection fraction
- multiple sclerosis
- chronic kidney disease
- dairy cows
- prognostic factors
- big data
- climate change
- randomized controlled trial
- clinical trial
- gene expression
- genome wide
- placebo controlled
- cystic fibrosis
- type diabetes
- adipose tissue
- metabolic syndrome
- machine learning
- drug induced
- artificial intelligence
- heat stress
- double blind
- data analysis