Effect of perfluorooctane sulfonate (PFOS) on influenza A virus-induced mortality in female B6C3F1 mice.
ABSTRACT 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.
- SourceAvailable from: Tung Viet Nguyen[Show abstract] [Hide abstract]
ABSTRACT: Concerns regarding perfluorinated chemicals (PFCs) have grown significantly in recent years. However, regulations and guidelines regarding the emission and treatment of PFCs are still missing in most parts of the world, mostly due to the lack of PFC toxicity data. In the current study, the genotoxic effects of four common PFCs, named perfluorooctanesulfonate (PFOS), perfluoroocanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were investigated on marine mussels. The effects of exposure time and concentration on the toxic behavior of the compounds were also examined. Genotoxicity of PFCs was assessed in biomarker assays, showing that exposure to the target compounds could damage the organism's genetic material to varying extents, including DNA strand breaks and fragmentation, chromosomal breaks and apoptosis. The adverse effects increased with both exposure concentration and time and were related with the organism burden of PFCs. The integrated biomarker response analysis demonstrated that PFOS exhibited a higher genotoxicity than the other tested compounds. The EC50 values and confidence intervals based on integrative genotoxicity were 33 (29-37), 594 (341-1036), 195 (144-265) and 78 (73-84) μg/L for PFOS, PFOA, PFNA and PFDA respectively, classifying PFOS as a highly genotoxic compound. Although primary DNA damage was shown to be recoverable after exposure ceased, permanent genetic damage caused by elevated PFC concentrations was not restored. This is the first ecotoxicity study of PFCs that focuses on the genotoxic effects of the compounds, clearly indicating the genotoxicity of the tested PFCs and demonstrating that functional groups have a major impact on the compounds' genotoxic behavior.Science of The Total Environment 04/2014; 487C:117-122. · 3.16 Impact Factor
- [Show abstract] [Hide abstract]
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; · 3.17 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Concerns regarding perfluorinated chemicals (PFCs) have risen in recent years due to their ubiquitous presence and high persistency. However, data on the environmental impacts of PFCs on marine organisms is very limited. Oxidative toxicity has been suggested to be one of the major toxic pathways for PFCs to induce adverse effects in organisms. To investigate the PFCs induced oxidative stress and oxidative toxicity, a series of antioxidant enzyme activities and oxidative damage biomarkers were examined to assess the adverse effects of four commonly detected compounds, perfluorooctanesulfonate (PFOS), perfluoroocanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) on green mussel, Perna viridis. Quantitative structure-activity relationship (QSAR) models were also established. The results showed that all the tested PFCs are able to induce antioxidant response and oxidative damage on green mussels in a dose-dependent manner. At low exposure levels (0-100 µg/L), activation of antioxidant enzymes (CAT and SOD) was observed which is an adaptive response to the excessive reactive oxygen species (ROS) induced by PFCs, while at high exposure levels (100-10000 µg/L), PFCs were found to inhibit some enzyme activity (GST and SOD) where the organism's ability to respond in an adaptive manner was compromised. The oxidative stress under high PFC exposure concentration also led to lipid and DNA damage. PFC induced oxidative toxicity was found to be closely correlated with the bioaccumulation potential of PFCs. Based on this relationship, QSAR models were established using the bioaccumulation factor (BAF) as the molecular descriptor for the first time. Compared with previous Kow-dependent QSAR models, the BAF-dependent QSAR model is more suitable for the impact assessment of PFCs and thus provides a more accurate description of the toxic behavior of these compounds. Environ Toxicol Chem © 2014 SETACEnvironmental Toxicology and Chemistry 07/2014; · 2.83 Impact Factor