Humoral immune response to a sevoflurane degradation product in the guineapig following inhalation exposure

Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene) is produced by reaction of the inhalation anesthetic, sevoflurane, with CO2 absorbents. C ompound A has been reported to directly react with protein. Since adduction of proteins can transform them into antigenic material, Compound A was ass essed for its ability to produce a humoral immune response. Male outbred Ha rtley guinea pigs (500-600 g, N = 7) were exposed via inhalation for 4 h to a subtoxic level (100 ppm) of Compound A, 3 times, at 42 day intervals. Bl ood samples obtained at 2, 14, 28 and 40 days after each exposure were meas ured for ALT, creatinine, and urea nitrogen and for the presence of antibod ies to trifluoroacetylated guinea pig albumin (TFA-GSA). All indicators of liver and kidney injury remained within normal range throughout the course of the Study. A humoral immune response to TFA-GSA was observed following e ach exposure to Compound A with a titer appearing by day 14 after exposure, peaking near day 28, and resolving to normal levels by day 40. The titer l evels were approximately equivalent after each exposure and about one-third that previously seen in guinea pigs after multiple exposures to halothane. Compound A would appear to have the ability to form antigenic adducts duri ng inhalation exposure. These findings are similar to those observed for ha logenated inhalation anesthetics that have been linked to cases of immune-m edicated idiosyncratic hepatitis and indicate that Compound A exposure may pose the same hazard.