Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague–Dawley rats

Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate, developed for use as a polymerization processing aid in the manufacture of fluoropolymers, was tested for its potential chronic toxicity and carcinogenicity in a 2-year oral dosing study in Sprague-Dawley rats. Male rats were given daily doses of either 0, 0.1, 1 or 50 mg/kg; females were given either 0, 1, 50 or 500 mg/kg. Body weights, food consumption and clinical signs were monitored daily; clinical pathology was conducted at designated intervals and animals were given a complete pathological evaluation after 12 months and 24 months of dosing. Normal survival was seen in all groups, no abnormal clinical signs were seen, and body weight gain was reduced only in female rats at 500 mg/kg. Both sexes at the high dose had mild decreases in red cell mass which were somewhat more pronounced in females. Clinical pathology indicative of liver injury was present in males that received 50 mg/kg and correlated with histomorphological liver changes that included both hypertrophic and degenerative/necrotic lesions. Similar histomorphological lesions were seen in the livers of females at 500 mg/kg. Previous shorter term toxicity studies have identified this chemical as a PPARα agonist and the finding of benign tumors of the liver, pancreas and/or testes in males at 50 mg/kg and females at 500 mg/kg is consistent with the rat response to peroxisome proliferators and is of questionable human relevance. Changes in the kidney, tongue, and stomach were observed only at the highest dose of 500 mg/kg in females. The no-observed-adverse-effect-level in this study lies between 1 and 50 mg/kg for males and between 50 and 500 mg/kg for females.