Toxicity of compound A in rats. Effect of a 3-hour administration.
BACKGROUND
Soda lime converts sevoflurane to CF2 = C(CF3)OCH2F, an olefin called compound A, whose toxicity raises concerns regarding the safe administration of sevoflurane via rebreathing circuits. The present report extends the findings of a previous investigation by others of the toxicity of this olefin, and establishes concentration-response relationships for such toxicity.


METHODS
Eighteen groups of ten Wistar rats breathed 0, 25, 50, 100, 200, 300, 350, and 400 ppm of the olefin in oxygen for 3 h. The olefin concentrations were developed in a square-wave manner by injection of saturated vapor followed by a continuous delivery of dilute vapor. The lethal concentration in 50% (LC50) of animals was estimated by logistic regression. Rats were killed on day 1 or day 4 after breathing the olefin, and specimens of brain, kidney, lung, liver, and small intestine were obtained from all rats for examination using light microscopy.


RESULTS
The LC50 equaled 331 ppm (95% confidence limits +/- 13 ppm). No injury resulted to lung or small intestine in either the experimental or the control group (those breathing only oxygen for 3 h). Renal injury (necrosis of the outer strip of the outer medulla, defined in this report as corticomedullary tubular necrosis) occurred at 50 ppm and greater; hepatic injury at 350 ppm and greater; and cerebral injury only at 400 ppm.


CONCLUSIONS
The lethal concentration and the threshold for toxicity of the olefin are less than previously reported. The threshold for nephrotoxicity reaches the range of values for the olefin that have been attained in clinical practice. Further studies are required to determine whether these results in rats can be extrapolated to patients.
Gonsowski
C T
CT
Department of Anesthesia, University of California, San Francisco 94143-0464.
Laster
M J
MJ
Eger
E I
EI
Ferrell
L D
LD
Kerschmann
R L
RL
D000777:Anesthetics / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004987:Ethers / Q000378:metabolism* / Q000633:toxicity*; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D008738:Methyl Ethers; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013997:Time Factors
D000777:Anesthetics; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether