HFA-134a (1,1,1,2-tetrafluoroethane); lack of oncogenicity in rodents after inhalation.
1. Groups of 60 male and 60 female B6C3F1 mice or HanIbm Wistar rats were exposed to HFA-134a using snout-only inhalation exposure techniques for periods of one hour daily for at least 104 weeks. HFA-134a was delivered directly from cylinders at vapour concentrations of 2500, 15,000 and 75,000ppm for mice and from metered-dose inhalers at vapour concentrations of 2500, 10,000 and 50,000ppm for rats. 2. Intended dosages were achieved. 3. Evidence of absorption was found at each dose level and was dose related. 4. Neither species suffered treatment related effects on survival, clinical signs, body weights, haematology nor on the type, incidence, site or severity of gross lesions. 5. There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats. 6. There were no non-neoplastic findings related to treatment in mice. 7. HFA-134a was considered not to be oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.
Alexander
D J
DJ
Medicines Safety Evaluation Division, Glaxo Research and Development Ltd., Ware, Hertfordshire, UK.
Libretto
S E
SE
Chevalier
H J
HJ
Imamura
T
T
Pappritz
G
G
Wilson
J
J
D000042:Absorption; D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000777:Anesthetics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000777:Anesthetics; D006845:Hydrocarbons, Fluorinated; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons