Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts.
Sevoflurane previously has been reported to undergo extensive degradation in the presence of soda lime. To more completely characterize the extent and significnce of this reaction, we studied degradation of sevoflurane with and without soda lime, as well as the toxicity and mutagenicity of the degradation products. Two degradation products detected were CF2 = C(CF3)OCH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B). During circulation of 1%, 2%, and 3% sevoflurance in a closed anesthesia circuit for 8 h, peak concentrations of compound A were 13.3 +/- 0.27, 30.2 +/- 0.10, and 42.1 +/- 1.07 ppm at 2 h, respectively. The concentrations of compound B did not exceed 2 ppm. The temperature of the soda lime was 43.3 +/- 2.8 degrees C at 1 h and increased gradually to 47.9 +/- 1.5 degrees C after 8 h. In closed flasks with soda lime, the magnitude of the decrease in sevoflurance concentrations (3%) and of the increase in compound A concentrations was temperature dependent. The peak concentrations of compound A at 23 degrees C, 37 degrees C, and 54 degrees C were 32.8 +/- 6.8 at 2 h, 46.6 +/- 1.0 at 0.5 h, and 78.5 +/- 2.3 ppm at 0.5 h, respectively. The LC50 (50% lethal concentration) of compound A in Wistar rats was 1,090 ppm in males and 1,050 ppm in females exposed for 1 h. The LC50 was 420 ppm in males and 400 ppm in females exposed for 3 h. The chronic toxicity of compound A in Wistar rats was studied by exposing rats 24 times, for 3 h each, to initial concentrations of 30, 60, or 120 ppm in a ventilated chamber. At all concentrations, there were no apparent effects other than a loss of body weight in females (120 ppm) on the final day (P < 0.01). Compound A did not induce mutation on the reverse (Ames) test at less than 2,500 micrograms/dish (culture medium 2.7 ml) with activation by S-9 mixture, and below 1,250 micrograms/dish (culture medium 2.7 ml) without activation, in four strains of S. typhimurium and in 1 strain of E. coli. Exposure of fibroblasts to 7,500 ppm of compound A for 1 h, compound A did not induce structural change. In a study of acute toxicity of compound B, there was no toxicity in Wistar rats after 3 h of exposure at 2,400 ppm. The reverse (Ames) test for compound B was negative at 625-1,250 micrograms/dish.(ABSTRACT TRUNCATED AT 400 WORDS)
Morio
M
M
Hiroshima University, Japan.
Fujii
K
K
Satoh
N
N
Imai
M
M
Kawakami
U
U
Mizuno
T
T
Kawai
Y
Y
Ogasawara
Y
Y
Tamura
T
T
Negishi
A
A
D000042:Absorption; D000208:Acute Disease; D000777:Anesthetics / Q000737:chemistry*; D000818:Animals; D017610:Calcium Compounds; D002245:Carbon Dioxide / Q000737:chemistry; D002908:Chronic Disease; D004987:Ethers / Q000737:chemistry* / Q000633:toxicity*; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D008297:Male; D008738:Methyl Ethers; D009152:Mutagenicity Tests; D010087:Oxides; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D012972:Sodium Hydroxide / Q000737:chemistry*
D000777:Anesthetics; D017610:Calcium Compounds; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D010087:Oxides; D002245:Carbon Dioxide; D000077149:Sevoflurane; C004569:soda lime; D012972:Sodium Hydroxide; C078745:fluoromethyl 2-methoxy-2,2-difluoro-1-(trifluoromethyl)ethyl ether; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether