Chlorotrifluoroethylene Nephrotoxicity in Rats: A Sub-acute Study. Buckley, L.A., Clayton, J.W., Nagle, R.B. and Gandolfi, A.J. (1982). Fundam. Appl. Toxicol. 2:181-186. Male Fischer-344 rats were exposed via inhalation to a sublethal concentration (395 ppm ± 33 ppm; 1882 mg/m3) of the nephrotoxin chlorotrifluoroethylene (CTFE) for 4 h per day for 5 consecutive days. Within 1 day after the first exposure, rats exhibited diuresis, increased water intake, decreased urine osmolality, increased urinary lactic dehydrogenase activity and increased plasma creatinine and urea nitrogen. When animals were exposed repeatedly, values for these parameters declined or returned to control levels during the exposure sequence in a manner comparable to rats receiving the single exposure. By the third day post exposure, coagulative necrosis involving primarily the pars recta, but extending to the pars convoluta, of the proximal tubule was present. Regeneration was apparent by the third day of exposure, and additional necrosis was minimal despite further exposures. Daily levels of urinary inorganic fluoride, an index of CTFE metabolism, were increased to 3-6 μmoles/24 h/rat during the exposure sequence which coincided with a brief elevation in serum fluoride at the end of each exposure. Adaptation to CTFE is evident either through changes in the metabolism or disposition of CTFE or from a refractive property of the regenerating tissue to CTFE.
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