Toxicity of tetrafluoroethylene and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine in rats and mice

Groups of 25 female F344 rats and 25 female B6C3F1 mice were exposed to 0, 30, 300, 600, or 1200 ppm tetrafluoroethylene (TFE) by inhalation for up to 12 days. Another set of 25 female rats and 25 female mice of the same stra ins were given 0, 5, 20, or 50 mg/kg of S-(1,1,2,2-tetrafluoroethyl)-L-cyst eine (TFE-CYS) by oral gavage for 12 days. Both 12-day exposure regimens co nsisted of exposures for 5 consecutive days, a weekend with no exposures, a nd 4 consecutive daily exposures following the weekend. Five animals per gr oup were sacrificed after the first exposure, the fifth exposure, and the n inth exposure for evaluation of cell proliferation in the liver and kidney. The remaining animals in each group (up to 10) were sacrificed after the n inth exposure (test day 12) for pathological evaluation of the liver, kidne y, and spleen. Clinical pathology evaluations were performed on test day 11 or 12. Inhalation of TFE by rats and mice caused slight microscopic change s in the kidneys of rats and mice, but no histopathological changes in the liver. In the kidney, administration of TFE-CYS by gavage caused severe mic roscopic changes in rats, moderate-to-severe changes in mice, and no micros copic changes in the liver. Cell proliferation was increased in the kidneys of rats and mice given TFE by inhalation and TFE-CYS by gavage. TFE-CYS al so caused increased liver weights and cell proliferation in the liver of ra ts and mice at the high doses. The cell proliferation response in the kidne y and liver was transient in both species, being most pronounced after 5 da ys of exposure, and less evident or absent after 12 days of exposure. In th e kidney, the cell proliferation and histopathologic response in rats was g enerally more pronounced than in mice. Kidney damage and cell proliferation were confined to the pars recta (P3) of the outer stripe of the outer medu lla and medullary rays. Tubules in mice exposed to TFE and TFE-CYS had most ly regenerating cells by test day 12, while in rats the tubules still showe d marked degeneration along with regeneration by the end of the study. The cortical labyrinth (P1 and P2 segments) was also affected at the 50 mg/kg d ose of TFE-CYS in rats. Rats exposed to 50 mg/kg TFE-CYS had a mild anemia, and rats exposed to 1200 ppm TFE had slight, biologically inconsequential decreases in erythrocyte mass that may have been compound-related. In spite of the rather pronounced histopathologic changes in the kidneys of rats ex posed to TFE-CYS, there was no clinical chemistry evidence for decreased ki dney function. Increased levels of urinary fluoride were present in rats ex posed to 300 ppm and greater of TFE, and in rats exposed to 20 and 50 mg/kg TFE-CYS. The spleen was not affected in this study. Overall, the results o f this study suggest that effects of TFE could be attributed to the toxicit y of TFE-CYS over the course of a 2-week exposure, as all effects that were seen with TFE were also seen with TFE-CYS.