TOXICITY OF COMPOUND-A IN RATS - EFFECT OF A 3-HOUR ADMINISTRATION

Background: Soda lime converts sevoflurane to CF2 = C(CF3)OCH2F, an ol efin called compound A, whose toxicity raises concerns regarding the s afe administration of sevoflurane via rebreathing circuits. The presen t report extends the findings of a previous investigation by others of the toxicity of this olefin, and establishes concentration-response r elationships for such toxicity. Methods. Eighteen groups of ten Wistar rats breathed 0, 25, 50, 100, 200, 300, 350, and 400 ppm of the olefi n in oxygen for 3 h. The olefin concentrations were developed in a squ are-wave manner by injection of saturated vapor followed by a continuo us 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 exa mination using light microscopy. Results: The LC50 equaled 331 ppm (95 % confidence limits +/- 13 ppm). No injury resulted to lung or small i ntestine in either the experimental or the control group (those breath ing 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 a nd greater; and cerebral injury only at 400 ppm. Conclusions: The leth al concentration and the threshold for toxicity of the olefin are less than previously reported. The threshold for nephrotoxicity reaches th e range of values for the olefin that have been attained in clinical p ractice. Further studies are required to determine whether these resul ts in rats can be extrapolated to patients.