Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague–Dawley rats
Abstract
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 50mg/kg; females were given either 0, 1, 50 or 500mg/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 500mg/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 50mg/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 500mg/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 50mg/kg and females at 500mg/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 500mg/kg in females. The no-observed-adverse-effect-level in this study lies between 1 and 50mg/kg for males and between 50 and 500mg/kg for females.
- Publication:
-
Toxicology Reports
- Pub Date:
- January 2015
- DOI:
- 10.1016/j.toxrep.2015.06.001
- Bibcode:
- 2015ToxR....2..939C
- Keywords:
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- Fluoropolymers;
- Chronic toxicity and carcinogenicity study;
- Sprague–Dawley rats;
- PPARα agonist