title: Humoral immune response to a sevoflurane degradation product in the guinea pig following inhalation exposure.
abstract: Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene) is produced by reaction of the inhalation anesthetic, sevoflurane, with CO2 absorbents. Compound A has been reported to directly react with protein. Since adduction of proteins can transform them into antigenic material, Compound A was assessed for its ability to produce a humoral immune response. Male outbred Hartley 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. Blood samples obtained at 2, 14, 28 and 40 days after each exposure were measured for ALT, creatinine, and urea nitrogen and for the presence of antibodies 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 each 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 levels 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 during inhalation exposure. These findings are similar to those observed for halogenated inhalation anesthetics that have been linked to cases of immune-medicated idiosyncratic hepatitis and indicate that Compound A exposure may pose the same hazard.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA.
authors.forename: X H
authors.initials: XH
authors.lastname: Zheng
authors.forename: C
authors.initials: C
authors.lastname: Begay
authors.forename: R C
authors.initials: RC
authors.lastname: Lind
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004987:Ethers / Q000737:chemistry / Q000633:toxicity*; D006168:Guinea Pigs; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000737:chemistry / Q000633:toxicity*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D000410:Alanine Transaminase