Subchronic toxicity of S-111-S-WB in Sprague Dawley rats

S-111-S-WB, a mixture of perfluoro fatty acid ammonium salts (C(6)-C(13)), was administered orally to Crl:CD (SD)IGS-BR rats. Higher hepatic beta-oxidation and liver weights with hepatocellular hypertrophy were present at the 0.125 and 0.6 mg/kg/d dosage. The 0.6 mg/kg/d males developed hepatocellular degeneration and necrosis. Lower serum protein and higher bilirubin and BUN were seen in the 0.6 mg/kg/d males and lower globulin and higher alkaline phosphatase in the 0.125 mg/kg/d males and 0.6 mg/kg/d animals. After 2 weeks, serum concentrations of pentadecafluorooctanoic acid (C(8)), heptadecafluorononanoic acid (C(9)), perfluoroundecanoic acid (C(11)), and perfluorotridecanoic acid (C(13)) were constant for at least 8 hours. After 90 days, only C(9) in the 0.025 mg/kg/d females had reached steady state. Serum C(8) and C(9) concentrations in the males were 10-fold higher than in the females, whereas C(11) and C(13) were similar for both genders. The main elimination was via the urine for C(8) (males) and C(9) (females), and via the feces for C(11) and C(13). The no-observed-effect level (NOEL) was 0.025 mg/kg/d for the males and 0.125 mg/kg/d for the females.