CFC REPLACEMENTS - SAFETY TESTING, APPROVAL FOR USE IN METERED DOSE INHALERS

被引:13
作者
GRAEPEL, P
ALEXANDER, DJ
机构
[1] CIBA-GEIGY Limited, Basel
来源
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG | 1991年 / 4卷 / 03期
关键词
CFC; HFA-134A; HFA-227; INHALATION TOXICITY;
D O I
10.1089/jam.1991.4.193
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
HFA-134a and HFA-227 (chlorine free hydrofluoro-alkanes) are at present in extensive nonclinical safety testing sponsored by two joint research consortia (IPACT-I, IPACT-II) of companies interested in metered dose inhalers (MDI). The rationale for toxicity testing of these CFC replacements is to predict safety of their use as drug propellants in MDI. Frequency of use, intervals and systemic exposure levels are key parameters. Intact animals and in-vitro systems repeatedly exposed to multiples of patient doses, under conditions comparable to human administration should not show adverse reactions. With an emphasis different from non-U.S. Health Authorities, the U.S. FDA insists on proof of toxic effects which may require excessive doses. This principle is questioned for essentially inert gases such as CFCs and HFA-134a and HFA-227 which only through the effects of oxygen deprivation at unreasonably high concentrations of the inhaled propellant/air mixture indirectly cause mild toxic effects in animals. Provided that no intrinsic toxic effects will be detected, chances are good that these CFC replacements will eventually be approved. In view of the estimated 5-year testing time frame and the risks involved, CFCs should remain available for MDI for some time in the future. © 1991, Mary Ann Liebert, Inc. All rights reserved.
引用
收藏
页码:193 / 200
页数:8
相关论文
共 2 条
[1]  
Altman P.L., Dittmer D.S., Biology Data Handbook, 3, (1974)
[2]  
McMahon T.A., Brain J.D., Lemott S.R., Species Differences in Aerosol Depoostion, Inhaled Particles, 4, pp. 23-32, (1977)