BACKGROUND: Compound A [CF2 = C(CF3)OCH2F], a degradation product of sevoflurane [(CF3)2CHOCH2F], is a vinyl ether and may be an alkylating agent. Thus it is a potential genotoxin. METHODS: The capacity of compound A to produce sister chromatid exchanges was measured in Chinese hamster ovary cells with and without metabolic activation. Concentrations of 11 to 468 ppm compound A were applied for 2 h, the Chinese hamster ovary cells were incubated for a further 34 h in the presence of bromodeoxyuridine, and then colcemid was added to produce arrest in metaphase. Coded slides of cells were examined blindly, and 50 chromosome spreads were counted for each test concentration. RESULTS: The lowest concentration of compound A applied without metabolic activator (27 ppm) significantly increased (P < 0.001) sister chromatid exchanges, and increasing concentrations of compound A increased the incidence of exchanges. Metabolic activation did not increase the incidence of exchanges. CONCLUSIONS: Compound A increases sister chromatid exchanges at concentrations (27 ppm) obtained in low-flow systems when sevoflurane is used at concentrations approximating minimum alveolar concentration.
BACKGROUND:Compound A [CF2 = C(CF3)OCH2F], a degradation product of sevoflurane [(CF3)2CHOCH2F], is a vinyl ether and may be an alkylating agent. Thus it is a potential genotoxin. METHODS: The capacity of compound A to produce sister chromatid exchanges was measured in Chinese hamster ovary cells with and without metabolic activation. Concentrations of 11 to 468 ppm compound A were applied for 2 h, the Chinese hamster ovary cells were incubated for a further 34 h in the presence of bromodeoxyuridine, and then colcemid was added to produce arrest in metaphase. Coded slides of cells were examined blindly, and 50 chromosome spreads were counted for each test concentration. RESULTS: The lowest concentration of compound A applied without metabolic activator (27 ppm) significantly increased (P < 0.001) sister chromatid exchanges, and increasing concentrations of compound A increased the incidence of exchanges. Metabolic activation did not increase the incidence of exchanges. CONCLUSIONS:Compound A increases sister chromatid exchanges at concentrations (27 ppm) obtained in low-flow systems when sevoflurane is used at concentrations approximating minimum alveolar concentration.