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.

A chronic dietary toxicity study of DAG (diacylglycerol) in Beagle dogs.

The potential chronic toxic effects of DAG (diacylglycerol) when administered orally for 12 months were evaluated in this dietary study in Beagle dogs. DAG is a cooking oil which contains >80% diglycerides, <20% triglycerides and 5% monoglycerides. For this study, a special diet was prepared with no dietary fat so that all of the dietary fat could be provided by DAG, at various concentrations together with a control oil. The control oil, TG (triacylglycerol), was prepared to contain >85% triglycerides, <10% diglycerides and 5% monoglycerides. The fatty acid composition for DAG and TG was closely matched. Dietary concentrations of 0% DAG/9.5% TG (TG control), 1.5% DAG/8.0% TG, 5.5% DAG/4.0% TG, and 9.5% DAG/0% TG were presented daily, seven days per week, for 52 weeks. A second concurrent control group received the standard basal diet (Certified Canine LabDiet 5007, which has a fat content of 9.5%). The basal diet, control article-treated and DAG-treated groups each consisted of four male and four female dogs. Treatment was initiated in prejuvenile (2.5-month-old) dogs. Statistical evaluations compared the DAG-treated groups both to the basal diet and 9.5% TG control groups. The clinical condition of the animals, body weights, body weight gains and food consumption were unaffected by DAG. Hematology and urinalysis parameters were unaffected. No serum chemistry changes indicative of a toxic effect were observed. There were no effects noted on ECG data. No test article-related gross or histopathologic findings or changes in organ weights were observed. While there were no identifiable differences between the effects of TG and DAG, both caused some differences relative to the basal diet (lower food consumption, higher alkaline phosphatase, cholesterol and triglycerides). These differences were not toxicologically significant and were attributed to the differences in the diet rather than the fat source. Thus, DAG at dietary concentrations up to 9.5% for one year had no effect on normal canine growth and development, in comparison to TG.