Associations of per- and poly-fluoroalkyl substances exposure with blood lipids in middle-aged and elderly women / 环境与职业医学

Background Per- and poly-fluoroalkyl substances (PFAS) are a class of emerging persistent organic pollutants, and their negative health impacts have been widely concerned. There is a lack of epidemiological studies on the associations of PFAS exposure with lipid homeostasis. Objective To investigate the associations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure with blood lipid levels and dyslipidemia in middle-aged and elderly women. Methods This study was based on 795 middle-aged and elderly women from a female sub-cohort of the Dongfeng-Tongji cohort study, excluding the participants without blood lipid measurements and/or reported use of lipid-lowering drugs at baseline. The concentrations of plasma PFOS and PFOA were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured using an automatic analyzer. The normally distributed continuous variables were presented as mean ± standard deviation (\begin{document}$ \bar{x}\pm s) $\end{document}, while the skewedly distributed continuous variables were presented as median (M) and the 25th and 75th percentiles (P25, P75). Generalized linear models (GLM), generalized additive models (GAM), and logistic regression models were applied to evaluate the associations of PFOS and PFOA exposure with blood lipid levels and the risk of dyslipidemia. Stratified analyses were also implemented to explore potential modification effects of sociodemographic characteristics, lifestyles, and menopause on associations of PFOS and PFOA exposure and blood lipids. Results The \begin{document}$ \bar{x}\pm s $\end{document} of baseline age for the study participants was (59.4±8.6) years old, and their baseline body mass index (BMI) was (24.3±3.4) kg·m−2. The M (P25, P75) of baseline plasma concentrations for PFOS and PFOA were 9.96 (6.24, 15.09) μg·L−1 and 1.20 (0.84, 1.80) μg·L−1 respectively. The GLM analysis showed that plasma concentration of PFOS was positively associated with serum HDL-C [b (95%CI): 0.04 (0.01, 0.07)]. The plasma concentration of PFOA was also positively associated with serum TC [b (95%CI): 0.05 (0.02, 0.08)] and serum LDL-C [b (95%CI): 0.05 (0.01, 0.09)]. No significant association was observed between plasma PFOS and serum TC, TG, or LDL-C, nor between plasma PFOA and serum TG or HDL-C. The stratified analyses showed that the association between PFOA and LDL-C was significant among the participants aged <60 years old [b (95%CI): 0.06 (0.01, 0.11), P=0.014]. A modification effect was observed for age on the association of plasma PFOA with serum LDL-C, with Pinteraction=0.046. The analysis of the associations between PFOS/PFOA exposure and the risk of dyslipidemia showed that an increased plasma PFOA was significantly associated with an increased risk of hypercholesterolemia, with an OR (95%CI) of 1.69 (1.23, 2.15). No association was observed between PFOS exposure and the risk of dyslipidemia. Conclusion This cross-sectional study reveals that common PFAS exposure could affect the homeostasis of blood lipids based on the female sub-cohort of the Dongfeng-Tongji cohort, which provides new evidence for the negative health impact of PFAS.

Perfluorooctanoic acid-induced lipid metabolism disorder in SD rat liver and its effect on the expression of fatty acid metabolism-related proteins / 中南大学学报(医学版)

OBJECTIVES@#Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR.@*METHODS@#A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting.@*RESULTS@#After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.

Effects of PFOA exposure on inflammatory mediators IL-4, IFN-γand glucocorticoid receptor in asthmatic mice / 中国病理生理杂志

AIM:To investigate the effects of perfluorooctanoic acid(PFOA)exposure on the changes of asth-matic mouse airway inflammation,inflammatory mediators interleukin-4(IL-4)and interferon-γ(IFN-γ)in serum, and glucocorticoid receptor(GR)expression in the lung tissue.METHODS:BALB/c mice(n=30)were randomly divided into 5 groups:normal control(C)group,asthma(A)group,asthma+low-dose PFOA(AP10)group,asthma+mode-rate-dose PFOA(AP50)group and asthma+high-dose PFOA(AP100)group.Asthma model and PFOA exposure model of mice were established according to the grouping.The animals were sacrificed and their lungs were collected for HE stai-ning,transmission electron microscopy,Western blot and immunohistochemical staining.ELISA was applied to detect the levels of IL-4 and IFN-γin the serum.RESULTS: HE staining of the lungs showed that the asthmatic mice, compared with the normal control mice,had obvious mucus secretion around the airways and infiltration of inflammatory cells around airways and blood vessels,and the effects were much more marked in AP groups.Ultrastructural alteration of the lung tis-sues in the asthmatic mice were indicated by transmission electron microscopy.Compared with C group, the results of ELISA in A group and AP groups proved that IL-4 in the serum was increased and IFN-γwas decreased significantly(P<0.05).Compare with A group,IL-4 was significantly increased and IFN-γwas decreased in AP100 group(P<0.05), and no difference of those between AP 10 group and AP50 group was found.The results of Western blot indicated that GR protein expression in the asthmatic mice were decreased compare with the normal mice(P<0.05), and no difference of that among A group and AP groups was observed.Immunohistochemical staining manifested that GR protein was mainly lo-cated in the cytoplasm of bronchial columnar epithelial cells,airway smooth muscle cells and vascular smooth muscle cells. CONCLUSION:Acute airway PFOA exposure in asthmatic mice dose-dependently exacebates lung inflammation by indu-cing Th2 type immune responses, promotes infiltration of inflammatory cells and mucus secretion around the airways and blood vessels,and destroys the ultrastructure of the lung tissues.

Elimination of Perfluorooctanoic Acid Interference from Liquid Chromatography System by Impurity Delay / 分析化学

A high performance liquid chromatography tandem mass spectrometric ( HPLC-MS/MS ) method was developed for the determination of seven perfluorinated alkyl acidin ( C4-C10 ) and perfluorooctane sulfonate in water. After the particulate was removed by leaching, surrogate standard was added, then the sample was loading to a pre-conditioned WAX cartridge for purification, and then the eluent was concentrated and analyzed by HPLC-MS/MS. Due to the situation that the fluoride polymer was unavoidable to be used in the LC system, a delay column was employed and the perfluorooctanoic acid ( PFOA ) of interference was departed from the PFOA in sample. The method detection limit ( MDL) of PFOA was 0. 8 ng/L, and the lowest quantitative concentration (LQC) was 3. 2 ng/L. For other compounds, the MDL was ranged from 0. 2 to 1. 2 ng/L, and the LQC was 0. 8-4. 8 ng/L. This method also had good reproducibility, for six duplicated samples, the relative standard deviations ( RSD ) of all target compounds were less than 16%. And the recoveries of target compounds at six spiked matrix samples ranged from 87% to 129%, and the RSD were less than 15%. Because of the connection of delay column, the background was well controlled, and a relatively lower MDL were obtained.

Assessing the Spatial Distribution of Perfluorooctanoic Acid Exposure via Public Drinking Water Pipes Using Geographic Information Systems

OBJECTIVES: Geographic Information Systems (GIS) is a powerful tool for assessing exposure in epidemiologic studies. We used GIS to determine the geographic extent of contamination by perfluorooctanoic acid, C8 (PFOA) that was released into the environment from the DuPont Washington Works Facility located in Parkersburg, West Virginia. METHODS: Paper maps of pipe distribution networks were provided by six local public water districts participating in the community cross-sectional survey, the C8 Health Project. Residential histories were also collected in the survey and geocoded. We integrated the pipe networks and geocoded addresses to determine which addresses were serviced by one of the participating water districts. The GIS-based water district assignment was then compared to the participants' self-reported source of public drinking water. RESULTS: There were a total of 151,871 addresses provided by the 48,800 participants of the C8 Health Project that consented to geocoding. We were able to successfully geocode 139,067 (91.6%) addresses, and of these, 118,209 (85.0%) self-reported water sources were confirmed using the GIS-based method of water district assignment. Furthermore, the GIS-based method corrected 20,858 (15.0%) self-reported public drinking water sources. Over half (54%) the participants in the lowest GIS-based exposure group self-reported being in a higher exposed water district. CONCLUSIONS: Not only were we able to correct erroneous self-reported water sources, we were also able to assign water districts to participants with unknown sources. Without the GIS-based method, the reliance on only self-reported data would have resulted in exposure misclassification.

Negative results ofumu genotoxicity test of fluorotelomer alcohols and perfluorinated alkyl acids

<p><b>OBJECTIVES</b>Recently, perfluorooctanoate (PFOA) has been ubiquitously detected in the environment as well as in human serum. Fluorotelomer alcohols (FTOHs), a precursor of PFOA, undergo biodegradation via several metabolic routes which leads to formation of various biodegradation products. The degradation of FTOHs produces an α,β-unsaturated aldehyde that seems possibly to be electrophilic and may react with cellular macromolecules including DNA.</p><p><b>METHODS</b>We investigated the genotoxicity of three FTOHs (6∶2 FTOH, 8∶2 FTOH and 10∶2 FTOH), PFOA and perfluorooctane sulfonate (PFOS) using theumu test.</p><p><b>RESULTS</b>The FTOHs, PFOA and PFOS showed no significant increases in β-galactosidase activity at 0-1000 μM in the absence of S9 mix. The results were unchanged by the metabolic activation with S9 mix.</p><p><b>CONCLUSION</b>The genotoxicities of FTOHs, PFOA or PFOS are not detectable using the present method, suggesting that they are unlikely mutagens.</p>

Negative Results of \it{umu} Genotoxicity Test of Fluorotelomer Alcohols and Perfluorinated Alkyl Acids

Objectives: Recently, perfluorooctanoate (PFOA) has been ubiquitously detected in the environment as well as in human serum. Fluorotelomer alcohols (FTOHs), a precursor of PFOA, undergo biodegradation via several metabolic routes which leads to formation of various biodegradation products. The degradation of FTOHs produces an α,β-unsaturated aldehyde that seems possibly to be electrophilic and may react with cellular macromolecules including DNA. Methods: We investigated the genotoxicity of three FTOHs (6:2 FTOH, 8:2 FTOH and 10:2 FTOH), PFOA and perfluorooctane sulfonate (PFOS) using the umu test. Results: The FTOHs, PFOA and PFOS showed no significant increases in β-galactosidase activity at 0−1000 μM in the absence of S9 mix. The results were unchanged by the metabolic activation with S9 mix. Conclusion: The genotoxicities of FTOHs, PFOA or PFOS are not detectable using the present method, suggesting that they are unlikely mutagens.