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-DawleyABSTRACT
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, ChronicABSTRACT
INTRODUCTION: An epidemiological study was conducted of a perfluorononanoic acid (PFNA) surfactant blend, to investigate whether clinical differences were apparent between employees who were potentially exposed to the surfactant and those who were not exposed. The surfactant blend, which is related to other previously studied perfluorinated materials, is used in the production of some high-performance polymers. METHODS: All 630 individuals employed at a polymer production facility using PFNA (CAS No 72968-38-8) at any time between 1 January 1989 and 1 July 2003 were included in the cohort. Plausibly related laboratory test results were abstracted from annual medical examination records, including liver enzyme function and blood lipids. Detailed work histories, available for all employees, provided the basis for determining exposure category. Thirty two clinical parameters were evaluated by exposure level at five points in time, determined to reflect changes in possible exposure intensity, as well as greatest number of records available. Annual cross-sectional analyses and longitudinal analyses that accounted for multiple measurements per person were conducted separately for men and women, by exposure groups. RESULTS: Differences by exposure group for all laboratory measures, adjusted for age and body mass index, were small and not clinically significant. Although some statistically significant pair-wise differences were observed, these observations were not consistent between men and women, or over the five analysis windows. For the seven outcome variables (liver enzymes and blood lipids) examined in separate longitudinal models, no significant increase or decrease was observed by unit increase in cumulative exposure intensity score. CONCLUSION: This is the first epidemiological study investigating the possible health effects in humans associated with exposure to PFNA blend. Based on laboratory measures assessed over more than a decade, no adverse clinical effects were detected from occupational exposure to PFNA blend.
