ABSTRACT
The levels of legacy per- and polyfluoroalkyl substances (PFASs) have been growing in the environmental matrices and blood of residents living around the fluorochemical industrial park (FIP) in Fuxin of China over the past decade. Although some recent studies have reported occurrence of novel PFAS alternatives in biotic and abiotic matrices near fluorochemical facilities worldwide, little is known about novel PFAS congeners in maternal sera, umbilical cord sera, and placentas from the female residents close to the FIP and their related health risks. In this study, 50 paired samples of maternal and cord serum as well as placenta were derived from Fuxin pregnant women at delivery, and 21 target analytes of legacy PFASs in all the samples were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), revealing that PFBS, PFBA, and PFOA were the dominant PFAS contaminants observed in the whole samples. Based upon the suspect screening through high-resolution mass spectrometry (HRMS), 49 novel PFASs assigned to 11 classes were further identified in the Fuxin samples, of which, 20 novel congeners in 4 classes were reported in human blood and placentas for the first time. Moreover, the coefficients for mother-placenta transfer (Rm/p), placenta-newborn transfer (Rp/n), and mother-newborn transfer (Rm/n) of legacy PFASs could be calculated with median values of 1.7, 1.1, and 2.0, respectively, and Rm/p, Rp/n, and Rm/n for each novel PFAS identified were also estimated with the median values of 0.9, 1.2, and 0.8 individually. Accordingly, novel PFASs contributed 90% of all the legacy and novel PFASs in maternal sera and even occupied 96% of the whole PFASs in both placentas and cord sera. In addition, significant associations were determined among the neonate birth outcomes and serum concentrations of thyroid hormone, sex hormone, and glucocorticoid, together with the levels of certain legacy and novel PFASs in cord sera.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Alkanesulfonic Acids/analysis , China , Female , Fluorocarbons/analysis , Glucocorticoids , Humans , Infant, Newborn , Placenta/chemistry , Pregnancy , Tandem Mass Spectrometry , Umbilical CordABSTRACT
The levels of perfluoroalkyl substances (PFASs) have been growing progressively in the groundwater beneath a fluorochemical industrial park (FIP) in Fuxin of China recently, however, little information is available about whether long-term irrigation with local groundwater could have a potential effect on the bioaccumulation of PFASs in greenhouse vegetables near the FIP. In the present study, groundwater, soil, and vegetable samples were collected from Fuxin with five sampling campaigns during a period of 40 days, and ten target analytes of PFASs in all the samples were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAS contaminants, perfluorooctanoic acid (PFOA) and perfluorobutane sulfonate (PFBS) in groundwater samples were determined with the maximum levels of 2.47 and 32.4 µg L-1, respectively. Furthermore, perfluorobutanoic acid (PFBA), PFOA, and PFBS were the major PFASs in greenhouse samples of soil (up to 6.1, 6.8, and 46 ng g dry weight (dw)-1), tomato (up to 87, 1.7, and 13 ng g dw-1), and cucumber (up to 63, 2.6, and 15 ng g dw-1), which were significantly correlated with those in groundwater samples, indicating PFAS contaminations could be introduced into soil and vegetables in the greenhouse through long-term groundwater irrigation. In addition, all the levels of three main PFAS analytes in soil and vegetables presented an overall increasing trend over the period of vegetable growth. The bioaccumulation efficiencies for PFAS contaminants from soil to vegetables were negatively associated with the carbon chain length in PFASs. According to the reference dose (RfD) for PFBA, PFOA, and PFBS from the Minnesota Department of Health (MDH), daily intakes of those three analytes by rural residents in Fuxin were lower than the respective RfD via consumption of greenhouse tomatoes and cucumbers so far. However, long-term surveillance would be focused on greenhouse vegetables near the Fuxin FIP to prevent potential health risks of local residents from increasing PFAS contaminations.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Groundwater , Water Pollutants, Chemical , Bioaccumulation , China , Environmental Monitoring , Fluorocarbons/analysis , Minnesota , Tandem Mass Spectrometry , Vegetables , Water Pollutants, Chemical/analysisABSTRACT
High-level contaminations of perfluoroalkyl substances (PFASs) were determined in both surface water and groundwater around a fluorochemical industrial park (FIP) in Fuxin, China, over the past few years. Yet little is known about whether groundwater PFAS contaminations in Fuxin could be introduced into home-produced vegetables and eggs in local residences via the application of groundwater for the irrigation or feeding purposes. In the present study, ten PFAS analytes were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to investigate the extent of PFAS contaminations in the groundwater, soil, and home-produced vegetable and egg samples derived from Fuxin. As the predominant PFAS contaminants, perfluorobutane sulfonate (PFBS) and perfluorooctanoic acid (PFOA) were observed in groundwater beneath the Fuxin FIP with the maximum concentrations of 21.2 and 2.51⯵g/L, respectively, which were 24-fold and 5-fold higher individually compared to those reported previously. Both of them were also higher than the updated health advisories for PFBS and PFOA in drinking water issued by the Minnesota Department of Health and the US Environmental Protection Agency. In addition, short-chain PFASs involving perfluorobutanoic acid (PFBA) and PFBS were found to be the major contaminants in both home-produced vegetables and eggs from the residential gardens around the FIP. Statistically significant relationships were determined between the levels of PFBA, PFOA, and PFBS in local groundwater and those observed in home-produced vegetables (pâ¯=â¯0.003, pâ¯=â¯0.025, and pâ¯<â¯0.001), suggesting potential entry of those PFAS contaminants into home-produced vegetables via irrigation with groundwater beneath the FIP.
Subject(s)
Eggs/analysis , Environmental Monitoring/methods , Fluorocarbons/analysis , Groundwater/chemistry , Vegetables/chemistry , Water Pollutants, Chemical/analysis , China , IndustryABSTRACT
Severe perfluoroalkyl substance (PFAS) contaminations have been observed in both surface water and groundwater in the vicinity of Fuxin, China, over the past years, attributing to the fast-growing fluorochemical industries locally. However, little is known about the overall daily intake of PFAS contaminations by Fuxin residents recently. In the present study, ten target PFAS analytes in the blood serum samples collected from 100 non-occupationally exposed healthy residents in Fuxin, with an average age of 47.6 years, together with 14 drinking water samples obtained from the public water system (PWS) of Fuxin were analyzed via high-performance liquid chromotography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAS contaminant, the serum concentrations of perfluorooctanoic acid (PFOA) in Fuxin residents ranged between <0.05 and 160 ng/mL, with a median concentration of 9.4 ng/mL, which was higher than those reported previously for Fuxin and other areas worldwide. In drinking water samples, PFOA had a median value of 8.5 ng/L, ranging from 7.7 to 8.8 ng/L. Based upon the simplified one-compartment pharmacokinetic model, the total daily intake of PFOA for individuals residing in Fuxin ranged from 0.30 to 1.76 ng/kg bw/day, with a median of 0.79 ng/kg bw/day; furthermore, daily consumption of drinking water from the PWS in Fuxin appeared to contribute 35% of overall PFOA burden in local residents, which was approximately 3-fold higher compared to that estimated for Fuxin residents in 2009.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Caprylates , China , Drinking Water/chemistry , Humans , Tandem Mass Spectrometry , Water Pollutants, ChemicalABSTRACT
In 2011, Taiwan authorities reported that two phthalates, including di-(2-ethylhexyl) phthalate and di-iso-nonyl phthalate, were intentionally introduced into a variety of foods and beverages during the course of 15 years. However, little is known about body burdens of phthalate contaminations in local residents, especially children recently living in Taiwan. In the present study, five target phthalate metabolite analytes-including mono-methyl phthalate, mono-ethyl phthalate, mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP)-in spot urine samples were analyzed by way of high performance liquid chromatography-tandem mass spectrometry-mass spectrometry. All of the urine samples were collected from 225 healthy school children between 12 and 15 years of age (average 13.6) in the Taipei area, Taiwan, between 2009 and 2010. As the dominant urinary phthalate metabolites in Taiwanese school children, MEHP and MBP contributed 61 and 29 % of all of the target analytes, respectively. MEHP had the highest median of 29.8 µg/g creatinine (range of 13.1-72.8), which was greater than those reported for school children in the other countries during the same period, whereas MBP had a median of 14.3 µg/g creatinine (range 7.91-27.8). Statistically, urinary concentrations of MBP, MBzP, and MEHP were determined to have significantly positive correlations with the ages of Taiwanese school children (p < 0.05). Furthermore, urinary levels of MBzP in male children were considerably greater than those in female children (p = 0.006).
Subject(s)
Environmental Exposure/analysis , Environmental Pollutants/urine , Phthalic Acids/urine , Adolescent , Child , Environmental Exposure/statistics & numerical data , Female , Humans , Male , TaiwanABSTRACT
Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), are a family of commonly used industrial chemicals whose persistence and ubiquity in blood samples of humans and wildlife have become a growing concern. Despite PFOS and PFOA having been found in human blood and tissue samples from occupationally exposed workers and the general worldwide population, little systematic knowledge has accrued with respect to exposure levels in Uyghurs in the Sinkiang-Uighur Autonomous Region of China, which is predominantly agricultural and pastoral. Our goal was to provide background data for biological monitoring in the general population of this region. In this study, 110 self-reported healthy human serum samples were collected from nonoccupationally exposed Uyghurs volunteers and analyzed by microbore HPLC-electrospray tandem mass spectrometry. Among the 110 blood specimens, PFOS was detected in 102 samples (93%) and ranged from the lower limit of quantification of 0.01 to 22.63 µg/L with a median of 1.93 µg/L (interquartile range 1.00-3.43 µg/L). The median was higher among males (2.39 µg/L; interquartile range 1.23-4.40 µg/L) than that among females (1.20 µg/L; interquartile range 0.83-2.77 µg/L). No significant difference was observed with respect to age. The concentration of PFOA was lower than that of PFOS and was found only in seven samples (6%) at concentrations above the limit of quantification. This study is the first investigation to reveal serum PFOS and PFOA levels in the general population of Uyghurs. PFOS and PFOA concentrations found in the present investigation were lower than those found in recent studies consisting of subjects from different geographic locations (PFOS 5.0-44.7 µg/L, PFOA 1.5-10 µg/L).
Subject(s)
Alkanesulfonic Acids/blood , Caprylates/blood , Environmental Exposure , Fluorocarbons/blood , Adult , Agriculture , China , Chromatography, High Pressure Liquid , Environmental Monitoring , Female , Humans , Male , Middle Aged , Occupational Exposure/analysis , Tandem Mass SpectrometryABSTRACT
Severe perfluoroalkyl acid (PFAA) contamination resulting from the fast-growing semiconductor, electrochemical, and optoelectronic industries has been determined in the river water in the vicinity of the Taipei area, Taiwan, during recent years. However, little is known about body burdens of the PFAA contaminations in local residents, especially children living in the Taipei area recently. In this study, ten target PFAA analytes consisted of three perfluorosulfonates (PFSAs) and seven perfluorocarboxylates (PFCAs) in the blood serum samples, collected from 225 healthy children with an average age of 13.6 years in the Taipei area from 2009 to 2010, were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAA contaminant in the blood serum samples from Taiwanese children, perfluorooctane sulfonate (PFOS) contributed 86% of all the target PFAA analytes, while the other nine analytes contributed less than 5% individually. PFOS showed the highest median up to 29 ng/mL, ranging from 0.03 to 148 ng/mL, which was higher than that observed in the serum samples collected from Taiwanese children between 2006 and 2008. Statistically, serum concentrations of perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA) had significantly positive correlations with ages of children (p < 0.05). Furthermore, serum PFBS, PFHxS, and PFOA concentrations in the male children were considerably higher than those in the female children (p = 0.049, p = 0.000, p = 0.000).
Subject(s)
Fluorocarbons/blood , Water Pollutants, Chemical/blood , Adolescent , Alkanesulfonic Acids/blood , Caprylates/blood , Child , Chromatography, High Pressure Liquid , Female , Humans , Male , Rivers , Taiwan , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Perï¬uorinated compounds (PFCs) are ubiquitous pollutants. Experimental data suggest that they may be associated with adverse health outcomes, including asthma. However, there is little supporting epidemiological evidence. METHODS: A total of 231 asthmatic children and 225 nonasthmatic controls, all from northern Taiwan, were recruited in the Genetic and Biomarkers study for Childhood Asthma. Structure questionnaires were administered by face-to-face interview. Serum concentrations of 11 PFCs and levels of immunological markers were also measured. Associations of PFC quartiles with concentrations of immunological markers and asthma outcomes were estimated using multivariable regression models. RESULTS: Nine PFCs were detectable in most children (≥ 84.4%), of which perfluorooctane sulfonate (PFOS) was the most abundant (median serum concentrations of 33.9 ng/mL in asthmatics and 28.9 ng/mL in controls). Adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFC exposure ranged from 1.81 (95% CI: 1.02, 3.23) for the perfluorododecanoic acid (PFDoA) to 4.05 (95% CI: 2.21, 7.42) for perfluorooctanic acid (PFOA). PFOS, PFOA, and subsets of the other PFCs were positively associated with serum IgE concentrations, absolute eosinophil counts (AEC), eosinophilic cationic protein (ECP) concentrations, and asthma severity scores among asthmatics. CONCLUSIONS: This study suggests an association between PFC exposure and juvenile asthma. Because of widespread exposure to these chemicals, these findings may be of potential public health concern.
Subject(s)
Asthma/epidemiology , Environmental Pollutants/blood , Fluorocarbons/blood , Adolescent , Asthma/chemically induced , Biomarkers/blood , Case-Control Studies , Child , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Eosinophil Cationic Protein/blood , Eosinophils/cytology , Female , Humans , Immunoglobulin E/blood , Leukocyte Count , Logistic Models , Male , Odds Ratio , Surveys and Questionnaires , Taiwan , Tandem Mass SpectrometryABSTRACT
As a new type of persistent organic pollutant, perfluorooctane sulfonate (PFOS) has raised great concern in recent years due to its ubiquitous distribution in the general environment and its long elimination half-life in humans. PFOS has toxic and carcinogenic effects in animals and humans, but the effects of PFOS on apoptosis are still not clear. The present study aimed to determine the mode of cell death and its mechanism in splenocytes and thymocytes from adult male C57BL/6 mice administered 0, 1, 5, or 10 mg PFOS/kg/day by gavage daily for 7 days. The results showed that more apoptotic cells were present in PFOS-treated mice than in control mice. PFOS induced production of reactive oxygen species (ROS), dissipation of mitochondria membrane potential, and apoptosis of splenocytes and thymocytes. Moreover, activities of superoxide dismutase, catalase, and glutathione reductase were increased, whereas activities of glutathione-S-transferase and glutathione peroxidase were decreased, in splenocytes. Glutathione contents were reduced as well. Differential expressions of proteins such as p53, Bax, caspase-3, and caspase-9 were significantly up-regulated in PFOS-exposed hosts, whereas Bcl-2 expression was significantly down-regulated. One possible mechanism for the findings here was that PFOS could overwhelm homeostasis of anti-oxidative systems, boost ROS generation, impact on mitochondria, and affect protein expression of apoptotic regulators, the latter of which resulted in initiation of the apoptosis program. Results from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans, at the cellular level.
Subject(s)
Alkanesulfonic Acids/toxicity , Apoptosis , Environmental Pollutants/toxicity , Fluorocarbons/toxicity , Spleen/drug effects , Thymus Gland/drug effects , Alkanesulfonic Acids/administration & dosage , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Cells, Cultured , Environmental Pollutants/administration & dosage , Female , Fluorocarbons/administration & dosage , Gene Expression Regulation/drug effects , Humans , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/immunology , Mice , Mice, Inbred C57BL , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Spleen/pathology , Thymus Gland/pathology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50mg PFOS/kg, respectively, over 60days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host.
Subject(s)
Alkanesulfonic Acids/toxicity , Apoptosis/drug effects , Fluorocarbons/toxicity , Immunosuppressive Agents/toxicity , Spleen/cytology , Thymocytes/drug effects , Tumor Suppressor Protein p53/physiology , Alkanesulfonic Acids/blood , Animals , Apoptosis Inducing Factor/metabolism , Caspase 3/biosynthesis , Cell Count , Cell Cycle/drug effects , Cell Separation , Cell Survival/drug effects , Cytochromes c/biosynthesis , Flow Cytometry , Fluorocarbons/blood , Immunosuppressive Agents/blood , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Necrosis , Organ Size/drug effects , Spleen/drug effects , Spleen/metabolism , Thymocytes/metabolism , bcl-2-Associated X Protein/biosynthesis , bcl-X Protein/biosynthesis , bcl-X Protein/geneticsABSTRACT
Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60-day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin-1 ß (IL-1ß), and interleukin-6 (IL-6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations ≥ 1 mg PFOS/kg TAD in a dose-dependent manner. Ex vivo IL-1ß production by peritoneal macrophages was elevated substantially at concentrations of ≥ 5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF-α, IL-1ß and IL-6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and proto-oncogene, c-myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action.
Subject(s)
Alkanesulfonic Acids/toxicity , Fluorocarbons/toxicity , Animals , Cytokines/blood , Cytokines/metabolism , Dose-Response Relationship, Drug , Inflammation/blood , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-1beta/blood , Interleukin-1beta/metabolism , Interleukin-6/blood , Interleukin-6/metabolism , Macrophages, Peritoneal/drug effects , Male , Mice , Mice, Inbred C57BL , Spleen/drug effects , Spleen/metabolism , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Extensive human exposure to perfluoroalkyl compounds (PFAA) together with their persistence and various toxicities have arisen increasing concern. A noninvasive method would improve exposure assessment for large population, especially the children susceptible to contaminants. The aim of the study was to assess the use of PFAA measurements in human nails as a biomarker of exposure to PFAAs. Fingernail, toenail, and blood samples were collected from 28 volunteers. The PFAA concentrations were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Six PFAA were detected in nails, with perfluorooctane sulfonate (PFOS) being the compound with the highest median concentration (33.5 and 26.1 ng/g in fingernail and toenail, respectively). Followed was perfluorononanoate (PFNA), with the median concentrations of 20.4 and 16.8 ng/g, respectively, in fingernail and toenail. Other PFAA detected were perfluorooctanoate (PFOA), perfluorodecanoate (PFDA), perfluorododecanoate (PFDoA), and perfluorotetradecanoate (PFTA), with median levels ranging between 0.19 and 8.94 ng/g. PFOS and PFNA concentrations in fingernail significantly correlated with those in serum. Fingernail PFOS and PFNA levels were 2.8 and 24.4 times, respectively, higher than the serum levels. The accumulation of PFAA in nails, together with its advantages in noninvasive sampling and ability of reflecting long-term exposure, made nails PFAA an attractive biomarker of exposure.
Subject(s)
Environmental Monitoring , Fluorocarbons/metabolism , Nails/metabolism , Adult , Biomarkers/metabolism , Female , Fluorocarbons/blood , Humans , Limit of Detection , Male , Middle Aged , Quality Assurance, Health Care , Quality Control , Time Factors , Young AdultABSTRACT
As a ubiquitous and highly persistent environmental contaminant, the clear mechanisms to explain any perfluorooctanesulfonate (PFOS)-induced immunotoxicity are still unknown. This study here sought to examine the ability of PFOS to potentially perturb T-helper (T(H))-1 and T(H)-2 cell cytokine secreting activities, as well as to cause shifts in antibody isotype levels, and possible mechanisms involved in PFOS-induced immunotoxicity. Adult male C57BL/6 mice were exposed to PFOS daily via gavage for 60 days [0, 0.5, 1, 5, 25, or 50 mg/kg total administered dose (TAD)]. One day after the final exposure, the ex vivo production of the T(H)1-type cytokines (IL-2 and IFN-γ), T(H)2-type (IL-4), and IL-10 cytokines by isolated splenocytes, serum levels of immunoglobulin (Ig) were assessed via ELISA or ELISPOT. The results showed that IL-4 secretion was increased at exposure ≥5 mg PFOS/kg TAD in a dose-dependent manner. PFOS exposure increased IL-10 but decreased IL-2 and IFN-γ formation markedly at 50 mg PFOS/kg TAD. Serum levels of sheep red blood cells (SRBC)-specific IgM synthesis decreased significantly with PFOS exposure in a dose-related manner; serum SRBC-specific IgG, IgG1, and IgE levels increased with 50 mg PFOS/kg TAD regimens. These results indicated that, after a long-term exposure to PFOS, a host's immune state is likely to be characterized by a shift toward a more T(H)2-like state that, in turn, may lead to enhancement of their humoral response and suppression of their cellular response at levels of upper range for occupationally exposed workers or approximately 150-fold for general human population.
Subject(s)
Alkanesulfonic Acids/adverse effects , Cytokines/metabolism , Fluorocarbons/adverse effects , Toxicity Tests, Subchronic , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Eating/drug effects , Environmental Pollutants/adverse effects , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Immunoglobulin M/blood , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-2/metabolism , Interleukin-4/metabolism , Male , Mice , Mice, Inbred C57BL , Sheep , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/metabolismABSTRACT
Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant induces immunotoxicity in mice. However, clear mechanisms to explain any PFOS-induced immunotoxicity are still unknown. The study here sought to examine the ability of PFOS to potentially perturb T-helper (T(H))-1 and -2 cell cytokine secreting activities, as well as to cause shifts in antibody isotype levels, as possible mechanisms involved in PFOS-induced immunotoxicity. Adult male C57BL/6 mice were given by gavage 0, 5, or 20 mg PFOS/kg/d for 7 days. One day after the final exposure, spleens from these hosts were isolated and used for analyses of the ex vivo production of T(H)1-type (interleukin-2 (IL-2), interferon-γ (IFNγ), T(H)2-type (IL-4), and IL-10 cytokines by isolated splenocytes. In addition, serum was isolated from these mice in order to assess their levels of immunoglobulin M (IgM) and IgG antibodies. In all studies, levels of the cytokines of the antibodies were quantified via enzyme-linked immunosorbent assay or enzyme-linked immunosorbent spot. The results here showed that IL-2 and IFNγ formation was reduced, but that IL-4 production increased by the 5 and 20 mg PFOS/kg/d treatments. Serum IgM levels decreased significantly (in dose-related manner) as a result of the PFOS exposures; serum IgG levels increased markedly with 5 mg PFOS/kg/d, but decreased slightly with the 20 mg PFOS/kg/d regimens PFOS exposure increased serum corticosterone levels in a dose-dependent manner. These results indicated that, after a high-dose short-term exposure to PFOS, a host's immune state is likely to be characterized by a shift toward a more T(H)2-like state that, in turn, may lead to suppression of their cellular response and enhancement of their humoral response.
Subject(s)
Alkanesulfonic Acids/toxicity , Cytokines/immunology , Environmental Pollutants/toxicity , Fluorocarbons/toxicity , Th1 Cells/drug effects , Th2 Cells/drug effects , Administration, Oral , Animals , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Spleen/cytology , Spleen/drug effects , Spleen/immunology , Th1 Cells/immunology , Th2 Cells/immunologyABSTRACT
The toxicity of perfluorooctane sulfonate (PFOS), a persistent organic compound, is of great concern. Several studies have reported that PFOS decreases circulating thyroid hormone (TH) concentrations. However, the mechanisms involved remain to be determined. Female rats were exposed to (1) vehicle; (2) PFOS (0.2, 1.0, and 3.0 mg/kg); (3) propylthiouracil (PTU, 10 mg/kg); or (4) PTU (10 mg/kg) + PFOS (3.0 mg/kg) by gavage once a day for 5 consecutive days. Parameters including contents of total T4 (TT4) and total T3 (TT3) in both serum and bile, serum concentrations of transthyretin and thyroglobulin, as well as transcripts of transporters involved in hepatic uptake and efflux of T4 were determined in control and PFOS-exposed groups. TT4 and TT3 were also analyzed in PTU and PTU + PFOS groups in order to reflect the different hormone effects between PFOS, PTU, and PFOS + PTU. Results showed that serum TT4 and TT3 decreased, while bile TT4 and TT3 remained stable following PFOS exposure. Exposure to 3.0 mg/kg of PFOS significantly enhanced hepatic organic anion transporter OATP2 mRNA expression (1.43 times of control). Treatment with PFOS increased hepatic expression of multidrug resistance--associated protein MRP2, approximately 1.80 and 1.69 times of control in 1.0 and 3.0 mg/kg groups, respectively. Spearman's correlation coefficients revealed that MRP2 mRNA expression correlated well with serum TT4 level (r = -0.528, P = 0.012). Serum thyroglobulin and transthyretin levels remained stable. Serum TT3, bile TT4, and bile TT3 were significantly different between PFOS and PTU groups. No significant differences of TT4 and TT3 in both serum and bile were observed between PTU and PTU + PFOS (P > 0.05). In conclusion, PFOS increased hepatic expression of OAPT2, which could possibly enhance hepatic uptake and metabolism of T4 in rats. PFOS-induced TT4 deficiency is mainly due to the extrathyroidal metabolism of T4, which is probably different from the classic goitrogen, PTU.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Alkanesulfonic Acids/toxicity , Antithyroid Agents/toxicity , Environmental Pollutants/toxicity , Fluorocarbons/toxicity , Liver/drug effects , Organic Anion Transporters/metabolism , Up-Regulation/drug effects , ATP-Binding Cassette Transporters/genetics , Alkanesulfonic Acids/administration & dosage , Animals , Antithyroid Agents/administration & dosage , Bile/metabolism , Dose-Response Relationship, Drug , Environmental Pollutants/administration & dosage , Female , Fluorocarbons/administration & dosage , Hypothyroidism/chemically induced , Liver/metabolism , Organic Anion Transporters/genetics , Propylthiouracil/toxicity , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Wistar , Thyroxine/blood , Thyroxine/metabolism , Triiodothyronine/blood , Triiodothyronine/metabolismABSTRACT
OBJECTIVE: To study the effects of prenatal and postnatal perfluorooctane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippocampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. METHODS: Twenty-eight pregnant rats were randomly divided into three groups in proportion of 3:2:2, including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0, 7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day (PND) 30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and temporal cortex) and hippocampus (CA1, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. RESULTS: The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99.83 +/- 25.77) s, (111.30 +/- 17.82) s, (106.40 +/- 18.71) s, (107.70 +/- 16.85) s, and longer as compared with CC group [(54.90 +/- 26.69) s] (q value were 4.349, 4.773, 6.026 and 5.641, respectively, P <0.01). The number of errors of HH group rat pups entering dead end was (22.30 +/- 7.56) at the training day 4, and it was significantly higher than that of CC group (9.80 +/- 4.64) (q = 5.173, P < 0.01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1, and LC group, HC group and HH group at PND14 were (0.167 +/- 0.008), (0.364 +/- 0.035), (0.341 +/- 0.030) and (0.328 +/- 0.045) respectively,which were significantly lower than CC group (0.271 +/- 0.060) and (0.465 +/- 0.067) (q values were 3.547, 3.739, 4.597 and 5.006, respectively, P< 0.05 ). The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091 +/- 0.005), and showed significant lower than CC group which was (0.123 +/- 0.009) at PND1 (q = 5.209, P <0.05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. CONCLUSION: Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebral cortex and hippocampal formation regions.
Subject(s)
Alkanesulfonic Acids/toxicity , Fluorocarbons/toxicity , Hippocampus/drug effects , Learning/drug effects , Memory/drug effects , Animals , Female , Male , Pregnancy , Rats , Rats, WistarABSTRACT
Perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, has been reported to be transferred to the developing organisms via both placenta and breast milk. A cross-foster model was used to determine whether prenatal or postnatal exposure to PFOS alone can disturb the TH homeostasis in rat pups, and if so, which kind of exposure is a major cause of TH level alteration. Pregnant rats were fed standard laboratory rodent diet containing 0 (control) or 3.2 mg PFOS/kg throughout gestation and lactation period. On the day of birth, litters born to treated and control dams were cross-fostered, resulting in the following groups: unexposed control (CC), pups exposed only prenatally (TC), only postnatally (CT) or both prenatally and postnatally (TT). Serum and liver PFOS concentrations, serum total thyroxine (T4), total triiodothyronine (T3), reverse T3 (rT3) levels, and hepatic expression of genes involved in TH transport, metabolism, and receptors were evaluated in pups at the age of postnatal days (PNDs) 0, 7, 14, 21, or 35. PFOS body burden level in pups in group CT increased, while those in group TC dropped as they aged. Neither total T3 nor rT3 in pups was affected by PFOS exposure. Gestational exposure to PFOS alone (TC) significantly (p < 0.05) decreased T4 level in pups on PNDs 21 and 35, 20.3 and 19.4% lower than the control on the same PND, respectively. Postnatal exposure to PFOS alone (CT) also induced T4 depression on PNDs 21 and 35, 28.6 and 35.9% lower than controls, respectively. No significant difference in T4 level (p > 0.05) was observed between TC and CT on these two time points. None of the selected TH related transcripts was affected by PFOS in pups on PND 0. Only transcript level of transthyretin, TH binding protein, in group TT significantly increased to 150% of the control on PND 21. The results showed that prenatal PFOS exposure and postnatal PFOS exposure induced hypothyroxinemia in rat pups to a similar extent, which suggested that in utero PFOS exposure and postnatal PFOS accumulation, especially though maternal milk, are matters of great concern.
Subject(s)
Alkanesulfonic Acids/chemistry , Alkanesulfonic Acids/toxicity , Embryonic Development/drug effects , Fluorocarbons/chemistry , Fluorocarbons/toxicity , Prenatal Exposure Delayed Effects/pathology , Thyroid Hormones/metabolism , Alkanesulfonic Acids/blood , Animals , Animals, Newborn , Body Weight/drug effects , Embryonic Development/genetics , Female , Fluorocarbons/blood , Gene Expression Regulation, Developmental/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Organ Size/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Hormones/blood , Thyroid Hormones/geneticsABSTRACT
There is a great concern about global contamination with persistent fluoroorganic compounds including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), however, few data are available on the environmental levels of these chemicals in China. In the present study, therefore, environmental or tap water samples collected from various regions of China were assayed for PFOS and PFOA by solid phase extraction and liquid chromatography-mass spectrometry technique. Median concentrations (maximum concentration) of PFOS and PFOA in environmental water were 0.4 (2.4) and 0.1 (1.3) ngL(-1) for the remote area (n=13), 4.0 (14.1) and 3.9 (30.8) ngL(-1) for the urban area (n=22), respectively. Systematic survey was also conducted in the Hun River (n=11) and the Yangtze River (n=34). In the Hun River, the median of PFOS concentration was 4.9ngL(-1), while PFOA was below the limit of quantitation (0.1ngL(-1)) at many of the sampling sites. The Yangtze River was moderately contaminated with both chemicals: median concentration was 4.2ngL(-1) for PFOS and 5.4ngL(-1) for PFOA. Remarkably high concentration of PFOA was found at 2 sampling sites of the Yangtze River (110.6 and 297.5ngL(-1)), but the concentration had declined to the average level at the next sampling site in both cases. Many cities provided tap water with low levels of PFOS and PFOA, however, tap water in Guangzhou and Shenzhen exceeded 10ngL(-1) for both chemicals. This study revealed obvious presence of perfluorinated compounds spread out the entire territory of China, and the levels in urban area of China were almost comparable to those in the US, Europe and Japan.
Subject(s)
Alkanesulfonic Acids/analysis , Caprylates/analysis , Fluorocarbons/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis , Water Supply/analysis , China , Cities , Environmental MonitoringABSTRACT
A paucity of data exists to corroborate the few studies that report immune suppression after exposure to perfluorooctanesulfonate (PFOS). In this study, adult male C57BL/6 mice were exposed to PFOS daily via gavage for 60 days [0, 0.5, 5, 25, 50, or 125 mg/kg total administered dose (TAD)]. The results showed that liver mass was significantly increased at > or =5 mg PFOS/kg TAD and in a dose-dependent manner. Lymphocyte proliferation and natural killer cell activity were altered in male mice. Plaque forming cell (PFC) response was suppressed beginning at 5 mg/kg TAD. Based on the liver mass and PFC response, the no observed adverse effect level and lowest observed adverse effect level for male mice exposed PFOS for 60 days was 0.5 and 5 mg/kg TAD, respectively. Measured PFOS serum concentrations at these dose levels were 0.674 +/- 0.166 and 7.132 +/- 1.039 mg/l, respectively. These results indicate that PFOS exposure can affect the immunity function in mice at levels approximately 50-fold for highly exposed human populations.
Subject(s)
Alkanesulfonic Acids/toxicity , Fluorocarbons/toxicity , Immune System/drug effects , Administration, Oral , Alkanesulfonic Acids/blood , Animals , Body Weight/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Administration Schedule , Fluorocarbons/blood , Formazans/metabolism , Hemolytic Plaque Technique , Kidney/drug effects , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Liver/drug effects , Liver/immunology , Lymphocyte Subsets/drug effects , Lymphocytes/drug effects , Lymphocytes/immunology , Male , Mice , Mice, Inbred C57BL , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Organ Size/immunology , Random Allocation , Spleen/cytology , Spleen/drug effects , Spleen/growth & development , Spleen/immunology , Tetrazolium Salts/metabolism , Thymus Gland/cytology , Thymus Gland/drug effects , Time FactorsABSTRACT
Perfluorooctane sulfonate (PFOS) was evaluated alone and in binary mixtures with pentachlorophenol, atrazine and diuron, respectively to investigate the effects of interactions between PFOS and other compounds on the growth rate in Scenedesmus obliquus. Single application of PFOS showed no inhibition on the growth of S. obliquus below 40 mg L(-1), whereas PFOS acting with pentachlorophenol resulted in higher algal growth inhibition in comparison with pentachlorophenol alone. A maximum increase of 45% in the growth inhibition was observed at a pentachlorophenol concentration of 2.56 mg L(-1) together with a PFOS concentration of 40 mg L(-1). On the contrary, the algal growth inhibition of atrazine and diuron was depressed by PFOS. Furthermore, cell uptake was examined to gain some insights into the mechanisms of the effects of PFOS on the toxicity of the other compounds. Cell uptake of pentachlorophenol increased while that of atrazine and diuron was reduced in cells that have been exposed to PFOS. The effects of PFOS on the toxicity of pentachlorophenol, atrazine and diuron were possibly related to the influence of PFOS on the cell uptake of these hydrophobic compounds. Results suggested that PFOS influenced the cell uptake and toxicity of structurally different compounds in dissimilar manners and potentially increased the accessibility and toxicity of more hydrophobic compounds to algal cells.