An overview of the toxicology of HFA-134a (1,1,1,2-tetrafluoroethane)

Abstract

1 This paper reviews the results of preclinical toxicology studies on HFA-134a carried out by Glaxo Research and Development Ltd.

2 A comprehensive range of studies was conducted in ani mal models suitable for the type of investigation.

3 The inhalation route of administration was used in all in vivo studies (with the exception of local tolerance and sensitisation studies) as patients will be exposed only to vapour during actuation of metered-dose inhalers. Cell cultures used for in vitro studies were also exposed to the vapour.

4 There was no mortality of rodents or dogs at extremely high vapour concentrations (81%v/v).

5 HFA-134a was considered not to be toxic or oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.

Keywords

HFA-134a propellent toxicology overview inhalation metered-dose inhalers

Get full access to this article

View all access options for this article.

References

Kontny MJ et al. Issues surrounding MDI formulation development with non-CFC propellants. J Aerosol Med 1991; 4: 181-187.

Programme for Alternative Fluorocarbon Toxicity Testing. HFA-134a Toxicology Summary, PAFT, April 1993.

Graepel P. , Alexander DJ CFC replacements: Safety testing, approval for use in metered dose inhalers . J Aerosol Med 1991; 4: 193-200.

Organisation for Economic Cooperation and Development (OECD) Guidelines for testing of chemicals. Guideline numbers: 401 - Acute inhalation toxicology, 12 May 1981; 412 -Repeated dose inhalation toxicity 28 day or 14 day study, 12 May 1981; 453 - Combined chronic toxicity/carcinogenicity studies, 12 May 1981.

Cannon WC , Blanton EF , McDonald KE The flow-past chamber: An improved nose-only exposure system for rodents . Amer Ind Hyg Assoc J 1983 ; 44: 923-928.

Alexander DJ et al. Microcomputer-based system for administering metered dose aerosol formulations to dogs. Inhalation Toxicol 1993; 5 : 415-425.

Alexander DJ et al. One year study in dogs of the toxicity of HFA-134a by inhalation. Inhalation Toxicol (in press).

Alexander DJ et al. HFA-134a (1,1,1,2-tetrafluoroethane): Lack of oncogenicity in rodents after inhalation. Hum Exp Toxicol (in press).