Subchronic Toxicity of S-111-S-WB in Sprague Dawley Rats

Abstract

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.

Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats

“…PFAAs are known to affect the liver, causing hypertrophy and in some cases necrosis, in rodents (Chengelis et al, 2009;Goldenthal, 1978;Griffith and Long, 1980;Kawashima et al, 1995;Kennedy, 1987;Lieder et al, 2009b;Mertens et al, 2010;van Otterdijk, 2007avan Otterdijk, , 2007bZhang et al, 2008). Hepatocyte hypertrophy was observed at as low as 0.064~0.23 mg/kg/day in a 2-year dietary study of PFOS (Thomford, 2002) and 0.64 mg/kg/day in a 13-week dietary study of PFOA (Perkins et al, 2004) in rats.…”

“…Data on the toxic properties of other PFAAs are limited, but they have been studied in recent years (Chengelis et al, 2009;Das et al, 2008;Fang et al, 2008;Lieder et al, 2009aLieder et al, , 2009bMertens et al, 2010;Shi et al, 2007;Stump et al, 2008;van Otterdijk 2007avan Otterdijk , 2007bZhang et al, 2008). Available data indicate that PFAAs with a longer carbon chain are eliminated more slowly from the body Ohmori et al, 2003), and their toxic potency increases by lengthening the carbon chain (Kudo et al, 2000(Kudo et al, , 2006Permadi et al, 1992).…”

Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins

“…The APFN commercial mixture has its own CAS Registry Number: 72968-38-8. Several publications report toxicological studies on the blend corresponding to this number, but do not provide information on the proportions or linearity of the homologues present (Mundt et al 2007; Stump et al 2008; Mertens et al 2010). …”

NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid, Perfluorooctanoic Acid, Perfluorononanoic Acid, and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

“…PFNA: In a subchronic study, Sprague Dawley rats were administered S-111-S-WB, a mixture of PFAS, once daily for 90 days; the predominant species in the mixture was PFNA 49 . All rats survived to the end of the study, but recorded toxicities included lethargy, decreased body weight, lower serum protein concentrations, higher bilirubin, increased liver weights, and hepatocellular hypertrophy, degeneration, and necrosis.…”