title: Nephrotoxicity in rats undergoing a one-hour exposure to compound A.
abstract: We previously demonstrated that rats experienced renal injury when exposed for 3-12 h to 50 ppm or more of a vinyl ether called Compound A [CF2 = C(CF3)OCH2F], a compound produced by CO2 absorbents acting on sevoflurane. These durations of exposure exceed the average duration of clinical anesthesia. We now report the effect of a 1-h exposure to 0, 100, 150, 200, 400, 600, or 800 ppm of Compound A in oxygen in 145 Wistar rats. Twenty-four hours after exposure, we obtained kidney and liver specimens for microscopic examination, applying hematoxylin and eosin, and (separately) an immunochemical marker (PCNA) for cell proliferation (regeneration). Compared with results from control rats (those breathing oxygen for 1 h), renal injury (defined as necrosis of the outer strip of the outer medullary layer or "corticomedullary junction necrosis") occurred at and above 200 ppm. Exposure to 150 ppm produced cell regeneration (i.e., stimulated cell proliferation). We conclude that the threshold concentrations for nephrotoxicity (i.e., minimal toxicity) for a 1-h exposure to Compound A exceed the maximum concentrations (particularly those at low inflow rates) reported in clinical practice by a factor of 2-3. If these threshold effects in rats apply to humans, one 1-h exposure to sevoflurane probably would not alter usual measures of renal function.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0464, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kandel
authors.forename: M J
authors.initials: MJ
authors.lastname: Laster
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: R L
authors.initials: RL
authors.lastname: Kerschmann
authors.forename: J
authors.initials: J
authors.lastname: Martin
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics / Q000633:toxicity*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014753:Vinyl Compounds / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D018809:Proliferating Cell Nuclear Antigen; D014753:Vinyl Compounds; C100195:vinyl ether; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether