Effects of inhaled chlorotrifluoroethylene and hexafluoropropene on the rat kidney

Abstract

Male Fischer-344 rats were subjected to 4.0 hr inhalation exposure to chlorotrifluoroethylene (CTFE) concentrations ranging from 100 to 540 ppm, or hexafluoropropene (HFP) concentrations ranging from 380 to 1200 ppm. Within 2 days following exposure, the rats exhibited dose-related proximal tubular necrosis, diuresis, increases in urinary fluoride, urinary lactic dehydrogenase (LDH) activity, serum creatinine, and BUN. The toxicities of CTFE and HFP were similar except that (1) CTFE was the more potent renal toxin and (2) HFP produced necrosis of the pars recta and pars convoluta portions of the proximal tubule, while CTFE produced necrosis of only the pars recta. At the lowest exposure concentrations, diuresis was the most sensitive index of toxicity manifesting 50% increases in water intake and 25% decreases in urine osmolality. Increases in urinary LDH activity correlated with the degree of proximal renal tubular necrosis, with greater than 100-fold increases at the highest concentrations of CTFE and HFP. At 100 ppm, CTFE induced renal dysfunction (mild diuresis), but no significant increase in urinary LDH nor necrosis were apparent. All concentrations of HFP studied produced necrosis within 24 hr postexposure, with tubular cell regeneration apparent within 4 days.