Effect of perfluorooctane sulfonate (PFOS) on influenza A virus-induced mortality in female B6C3F1 mice

The Journal of Toxicological Sciences (Impact Factor: 1.29). 12/2009; 34(6):687-91. DOI: 10.2131/jts.34.687
Source: PubMed


Recent studies showed that perfluorooctane sulfonate (PFOS) affects the mammalian immune system at levels reportedly found in the general human population. It has been demonstrated that exposure to immunotoxic chemicals may diminish the host resistance of animals to various pathogenic challenges and enhance mortality. Therefore, the current study was carried out to characterize the effect of a 21 day pre-administration of zero, 5, or 25 microg PFOS/kg bw/day in female B6C3F1 mice on host resistance to influenza A virus infection. At the end of PFOS exposure, body/organ weights did not significantly change whereas PFOS distribution in blood plasma, spleen, thymus and lung was dose-dependently increased. PFOS exposure in mice resulted a significant increase in emaciation and mortality in response to influenza A virus. The effective plasma concentrations in female mice were at least several fold lower than reported mean blood PFOS levels from occupationally exposed humans, and fell in the upper range of blood concentrations of PFOS in the normal human population and in a wide range of wild animals. Hence, it should be important to clarify the precise mechanism(s) for excess mortality observed in the high dose group.

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Available from: Dr. Keerthi S. Guruge, Feb 17, 2015
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    • "Peden-Adams et al. (2008) reported that serum concentrations of PFOS associated with the LOEL (lowest observed effect level) for suppression of humoral immunity were 91.5 ng/ml for males and 666 ng/ml for females. Additionally, PFOS exposure (5 or 25 ␮g/kg PFOS/kg/day) suppressed immunity to influenza A infection in mice without altering body or lymphoid organ weights, resulting in significant increases in emaciation and mortality (Guruge et al., 2009). The pesticide sulfluramid, which is rapidly metabolized to PFOS, also has been demonstrated to target T-dependent, IgM antibody production in mice at exposure levels 10-fold lower than overtly toxic doses (Peden-Adams et al., 2007), further confirming the immune system as a sensitive target of PFC toxicity. "
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    ABSTRACT: Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced specific antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans.
    Toxicology Letters 10/2014; 230(2). DOI:10.1016/j.toxlet.2014.01.038 · 3.26 Impact Factor
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    • "PFOS and PFOA exposure have been shown to decrease T-cell-dependent IgM antibody responses in mice (Dewitt et al., 2008, Peden-Adams et al., 2008). PFOS also decreased T-independent IgM production and decreased host resistance to influenza A (Peden-Adams et al., 2008; Guruge et al., 2009). These immune effects have recently been seen in human studies as well. "
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    ABSTRACT: Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in healthy human primary T cells. Jurkat cells were stimulated with phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD-3/anti CD-28, or anti CD-3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 µg ml−1 PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 µg ml−1 PFOA. Jurkat cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production beginning at 50 µg PFOS ml−1 and 5 µg PFOS ml−1 respectively, but stimulation with anti-CD3/anti-CD28 resulted in no changes compared with the control. Addition of the PPAR-alpha antagonist GW6471 to PFOS-dosed cells stimulated with PHA/PMA resulted in decreases in IL-2 production starting at 50 µg PFOS ml−1, which suggests PFOS affected T-cell IL-2 production via PPAR-alpha-independent mechanisms. Exposure to PFOA, PFOA + GW6471, or PFOS + PFOA in Jurkat cells resulted in no significant differences in IL-2 production. In vitro dosing studies using healthy primary human CD4+ T cells were consistent with the Jurkat results. These data demonstrated that PFOA did not impact IL-2 production, but PFOS suppressed IL-2 production in both a human cell line and human primary cells at dose levels within the high end of the human exposure range. A decrease in IL-2 production is characteristic of autoimmune diseases such as systemic lupus erythematosus and should be further investigated. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 07/2014; 35(5). DOI:10.1002/jat.3037 · 2.98 Impact Factor
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    • "For example, in a commonly used mouse model, PFOA effects include decreased spleen and thymus weights, decreased thymocyte and splenocyte counts, decreased immunoglobulin response, and changes in specific populations of lymphocytes in the spleen and thymus. Reduced survival after influenza infection has also been reported as an apparent effect of PFOS exposure in mice [20]. Another study found that the lowest observed effect level (LOEL) for males corresponded to an average serum-PFOS concentration of 92 ng/g (about 94 μg/L), though 7-fold higher in females [21]. "
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    ABSTRACT: Background Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits. Methods Results obtained from follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at age 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children with complete data using linear and logarithmic curves, and sensitivity analyses were included to explore the impact of the low-dose curve shape. Results Under different linear assumptions regarding dose-dependence of the effects, benchmark dose levels were about 1.3 ng/mL serum for perfluorooctane sulfonic acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose–response curves. Assumption of no effect below the lowest observed dose resulted in higher benchmark dose results, as did a benchmark response of 10%. Conclusions The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models. When the results are converted to approximate exposure limits for drinking water, current limits appear to be several hundred fold too high. Current drinking water limits therefore need to be reconsidered.
    Environmental Health 04/2013; 12(1):35. DOI:10.1186/1476-069X-12-35 · 3.37 Impact Factor
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