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1.
Int J Toxicol ; 29(4): 358-71, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20519691

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.


Subject(s)
Fatty Acids/toxicity , Hydrocarbons, Fluorinated/toxicity , Animals , Body Weight/drug effects , Fatty Acids/pharmacokinetics , Feeding Behavior/drug effects , Female , Hydrocarbons, Fluorinated/pharmacokinetics , Lethal Dose 50 , Liver/drug effects , Locomotion/drug effects , Male , Organ Size/drug effects , Rats , Rats, Sprague-Dawley
2.
Reprod Toxicol ; 25(1): 7-20, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18022344

ABSTRACT

S-111-S-WB (CAS No. 72968-38-8), a mixture of perfluoro fatty acid ammonium salts, was administered daily via oral gavage to 30 Crl:CD(SD) rats/sex/group at 0.025, 0.125 and 0.6mg/(kgday) over two generations to assess potential reproductive toxicity. Reproductive performance, mean litter size, pup survival and pup weights were unaffected. Lower mean body weights were observed in 0.6mg/(kgday) group F(0) and F(1) males. Higher liver weights, correlating to hepatocellular hypertrophy in the 0.6mg/kg group, were noted for parental males in the 0.125 and 0.6mg/(kgday) groups, parental females in the 0.6mg/(kgday) group and F(1) pups in the 0.125 and 0.6mg/(kgday) groups. Higher kidney weights, correlating to renal tubule hypertrophy in the 0.6mg/kg group, were observed for parental males and females in the 0.125 and 0.6mg/(kgday) groups. Systemic exposure (measured only in females) to total S-111-S-WB was proportional to dose following 9 weeks of daily administration on the gestation day 19. Total S-111-S-WB concentration in the serum of male and female pups was 1.2-1.4-fold higher than in the dams 2h following administration to the dams on lactation day 13. A dosage level of 0.6mg/(kgday) was considered to be the no-observed-adverse-effect level (NOAEL) for reproductive function. A dosage level of less than 0.025mg/(kgday) was considered to be the NOAEL for F(0) and F(1) parental systemic toxicity based on microscopic hepatic findings in the males of all test article groups, and a dosage level of 0.025mg/(kgday) was considered to be the NOAEL for neonatal toxicity based on higher liver weights in the F(1) and F(2) pups at 0.125mg/(kgday) and higher.


Subject(s)
Fatty Acids/toxicity , Hydrocarbons, Fluorinated/toxicity , Reproduction/drug effects , Surface-Active Agents/toxicity , Administration, Oral , Animals , Animals, Newborn , Birth Weight/drug effects , Body Weight/drug effects , Breeding , Dose-Response Relationship, Drug , Eating/drug effects , Fatty Acids/administration & dosage , Fatty Acids/metabolism , Female , Growth and Development/drug effects , Hydrocarbons, Fluorinated/administration & dosage , Hydrocarbons, Fluorinated/metabolism , Kidney/drug effects , Kidney/pathology , Lactation , Litter Size/drug effects , Liver/drug effects , Liver/pathology , Male , No-Observed-Adverse-Effect Level , Organ Size , Rats , Rats, Sprague-Dawley , Spermatogenesis/drug effects , Surface-Active Agents/administration & dosage , Surface-Active Agents/metabolism , Time Factors , Toxicity Tests, Chronic
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