NEPHROTOXICITY IN RATS UNDERGOING A ONE-HOUR EXPOSURE TO COMPOUND-A

We previously demonstrated that rats experienced renal injury when exp osed 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 se voflurane. 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 Wis tar rats. Twenty-four hours after exposure, we obtained kidney and liv er specimens for microscopic examination, applying hematoxylin and eos in, and (separately) an immunochemical marker (PCNA) for cell prolifer ation (regeneration). Compared with results from control rats (those b reathing oxygen for 1 h), renal injury (defined as necrosis of the out er strip of the outer medullary layer or ''corticomedullary junction n ecrosis'') 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 to xicity) for a 1-h exposure to Compound A exceed the maximum concentrat ions (particularly those at low inflow rates) reported in clinical pra ctice 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.