Toxicological evaluation of ammonium perfluorobutyrate in rats: Twenty-eight-day and ninety-day oral gavage studies

Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH4+PFBA) at doses up to 150 and 30 mg/kg-d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30 mg/kg-d in the 28-day study. Female rats were unaffected by NH4+PFBA. Effects in males included: increased liver weight, slight to minimal hepatocellular hypertrophy; decreased serum total cholesterol; and reduced serum thyroxin with no change in serum thyrotropin. During recovery, liver weight, histological, and cholesterol effects were resolved. Results of RT-qPCR were consistent with increased transcriptional expression of the xenosensor nuclear receptors PPARα and CAR as well as the thyroid receptor, and decreased expression of Cyp1A1 (Ah receptor-regulated). No observable adverse effect levels (NOAELs) were 6 and >150 mg/kg-d for male and female rats in the 28-day study and 6 and >30 mg/kg-d in the 90-dat study, respectively.

► The effects of perfluorobutyrate were studied in 28-day and 90-day studies in rats. ► No effects were observed in female rats given up to 150 mg/kg perfluorobutyrate. ► Male effects included reversible hepatocellular hypertrophy and hypolipidemia. ► Effects observed were consistent with hepatic activation of PPARα and CAR. ► NOAEL for male rats was 6 mg/kg in both the 28-day and 90-day studies.