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  • 1.
    Ax, Erika
    et al.
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Lampa, Erik
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology. MTM Research Centre, Örebro University, Örebro, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Sjögren, Per
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Circulating levels of environmental contaminants are associated with dietary patterns in older adults2015In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 75, p. 93-102Article in journal (Refereed)
    Abstract [en]

    Background: Food intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability.

    Objective: The aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population.

    Methods: Dietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate-high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models.

    Results: A Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate-high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p'-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor.

    Conclusion: Dietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants.

  • 2.
    Ax, Erika
    et al.
    Uppsala Univeristy, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupational & Environmental Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Acute & Internal Medicine, Uppsala University, Uppsala, Sweden.
    Lampa, Erik
    Occupational & Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Sjögren, Per
    Clinical Nutrition & Metabolism, Uppsala University, Uppsala, Sweden.
    Circulating levels of environmental contaminants are associated with dietary pattern2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S101-S101Article in journal (Refereed)
  • 3. Ax, Erika
    et al.
    Sjögren, Per
    Lind, P. Monica
    Lampa, Erik
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Dietary pattern affects blood levels of environmental pollutants in elderly Swedish men and women2011In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 58, no Suppl. 3, p. 59-60Article in journal (Refereed)
  • 4.
    Geng, Dawei
    et al.
    Örebro University, School of Science and Technology.
    Ericson Jogsten, Ingrid
    Örebro University, School of Science and Technology.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Dunstan, J.
    Ruzzin, J.
    Rémi, RL.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Atmospheric pressure gas chromatography (APGC) coupled to triple quadrupole mass spectrometry (MS/MS) for the quantitative analysis of pesticides and PCBs regulated by the Stockholm Convention2013In: Organohalogen Compounds, ISSN 1026-4892, Vol. 75Article in journal (Refereed)
  • 5.
    Haug, Line Smastuen
    et al.
    Div Environm Med, Norwegian Inst Publ Hlth, Oslo, Norway.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Ericson Jogsten, Ingrid
    Örebro University, School of Science and Technology.
    Thomsen, Cathrine
    Div Environm Med, Norwegian Inst Publ Hlth, Oslo, Norway.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lindström, Gunilla
    Örebro University, School of Science and Technology.
    Becher, Georg
    Div Environm Med, Norwegian Inst Publ Hlth, Oslo, Norway; Dept Chem, Univ Oslo, Oslo, Norway.
    Levels in food and beverages and daily intake of perfluorinated compounds in Norway2010In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 80, no 10, p. 1137-1143Article in journal (Refereed)
    Abstract [en]

    Perfluorinated compounds (PFCs) have been determined in 21 samples of selected food and beverages such as meat, fish, bread, vegetables, milk, drinking water and tea from the Norwegian marked. Up to 12 different PFCs were detected in the samples. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were found in concentrations similar to or lower than what has been observed in other studies world-wide. Differences in the relative proportion of PFOA and PFOS between samples of animal origin and samples of non-animal origin were observed and support findings that PFOS has a higher bio-accumulation potential in animals than PFOA. Based on these 21 measurements and consumption data for the general Norwegian population, a rough estimate of the total dietary intake of PFCs was found to be around 100 ng d(-1). PFOA and PFOS contributed to about 50% of the total intake. When dividing the population in gender and age groups, estimated intakes were decreasing with increasing age and were higher in males than females. The estimated intakes of PFOS and PFOA in the present study are lower than what has been reported in studies from Spain, Germany, United Kingdom, Canada and Japan. This study illustrates that by improving the analytical methods for determination of PFC in food samples, a broad range of compounds can be detected, which is important when assessing dietary exposure. (C) 2010 Elsevier Ltd. All rights reserved.

  • 6.
    Helmfrid, Ingela
    et al.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Occupational and Environmental Medicine, County Council of Östergötland, Linköping, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Wingren, Gun
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Berglund, Marika
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Exposure and body burden of polychlorinated biphenyls (PCB) and metals in a historically contaminated community2015In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 76, p. 41-48Article in journal (Refereed)
    Abstract [en]

    There are many small villages where environmental contamination is substantial due to historical industrial activities. The aim of the present study was to investigate if long-term or current consumption of local foods, as reported in food frequency questionnaires, co-vary with measured concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides ( OCPs), lead (Pb), cadmium (Cd) and mercury (Hg) in blood, urine and hair from a population living in a historically contaminated village.

    Blood, urine and hair were provided by men (n = 38) and women (n = 57), who had participated in a previous case-control study in the contaminated area, and were analyzed for PCB, OCPs, Pb, Cd and Hg. A detailed food frequency questionnaire, used in the previous epidemiological study, was repeated, and up-dated information of life-style, exposure factors and other covariates was collected. Associations between reported consumption of local foods and exposure biomarkers were explored in relation to age, gender, life-style factors and other covariates. A large part of the population in the area reported consumption of local food, and thus, was potentially exposed to the contaminants. Despite the limited number of participants and other weaknesses described, it was possible to link reported consumption of different foods to biomarker concentrations.

    Reported consumption of local vegetables, forest berries and mushrooms co-varied with urinary Cd, indicating an influence from the contaminated area on the Cd exposure. We found no associations between PCB plasma concentrations with reported consumption of local fish, but with consumption of herring (non-local sea fish) which is typically high in PCB. Pesticide (HCB, p,p'-DDE, trans-nonachlor) exposure was mainly associated with agricultural work and having a private well the first five years of life, but we found no associations between pesticide concentrations in plasma and consumption of local vegetables or fish. Exposure to Hg was associated with consumption of fish, both local and non-local, and Pb exposure was associated with the consumption of game.

    Overall, the contaminant concentrations measured in blood, urine and hair varied substantially among study participants, but on average, the concentrations were similar to concentrations measured in other groups of the general Swedish population in the same age range. Larger studies are needed to evaluate health risks (and causality) associated with historical environmental contamination.

  • 7.
    Jayasinghe, Saroj
    et al.
    Faculty of Medicine, University of Colombo, Sri Lanka.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    DDT and its metabolites could contribute to the aetiology of chronic kidney disease of unknown aetiology (CKDu) and more studies are a priority2019In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 649, p. 1638-1639Article in journal (Other academic)
  • 8.
    Jayasinghe, Saroj
    et al.
    Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    High serum levels of p,p'-DDE are associated with an accelerated decline in GFR during 10 years follow-up2018In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 644, p. 371-374, article id S0048-9697(18)32495-1Article in journal (Refereed)
    Abstract [en]

    Over the past 20 years, the global incidence of chronic kidney disease (CKD) has been increasing and organochlorine pesticides (such as DDT) is a suspected etiological factor. The present study examines the associations between low level background exposure to p,p'-DDE (1-dichloro-2,2-bis (p-chlorophenyl) ethylene), the main DDT metabolite, and kidney function during a 10-year follow-up. Data was analysed from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1016, 50% women, all aged 70 years). Serum levels of p,p'-DDE was measured by gas chromatography coupled to high-resolution mass spectrometry (GC/HRMS) at baseline (i.e. age of 70 years). Glomerular filtration rate (GFR) was estimated using serum creatinine and cystatin C at 70, 75 and 80 years of age. A significant decline in GFR was seen during the 10-year follow-up (-24 ml/min/1.73 m2, p < 0.0001). A significant negative interaction was seen between baseline p,p'-DDE levels and change in GFR over time (p < 0.0001) following adjustment for sex, systolic blood pressure, diabetes, BMI, smoking and education level at age 70. Subjects with the lowest levels of p,p'-DDE levels at age 70 showed the lowest decline in GFR over 10 years, while subjects with the highest p,p'-DDE levels showed the greatest decline.

    Baseline levels of p,p'-DDE were related to an accelerated reduction in GFR over 10 years suggesting a nephrotoxic effect of DDT/p,p'-DDE. These findings support a potential role for DDT in the epidemic of CKD of unknown etiology (CKDu) in agricultural communities of Sri Lanka and Central America where DDT was previously used.

  • 9.
    Kumar, Jitender
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden.
    Persistent organic pollutants and liver dysfunction biomarkers in a population-based human sample of men and women2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 134, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Background and objective: Persistent organic pollutants (POPs) are stable organic compounds generated through different industrial activities. Liver is involved in the metabolism of POPs, and hence exposure to POPs may interfere with liver function. Although a few studies have shown adverse effects of POPs on liver function, large-scale studies involving humans are lacking. We performed this large population-based cross-sectional study to assess the associations between different POPs and liver dysfunction biomarkers.

    Methods: A total of 992 individuals (all aged 70 years, 50% males) were recruited as part of Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The total toxic equivalency (TEQ) value was calculated for seven mono-ortho and two non-ortho substituted polychlorinated biphenyls (PCBs) and octachloro-p-dibenzodioxin (OCDD) to assess their toxicological effects. The association of TEQ values, summary measures of 16 PCBs (sum of PCBs) and three organochlorine pesticides (sum of OC pesticides) with liver dysfunction biomarkers (bilirubin; alkaline phosphatase, ALP; alanine amino-transferase, ALT; and gamma-glutamyltransferase, GGT) was analyzed utilizing linear regression analysis.

    Results: The mono-ortho PCB TEQ values were found to be significantly positively associated with bilirubin (beta=0.71, P=0.008), while sum of OC pesticide concentrations was negatively associated with ALP (beta= -0.02, P=0.002) after adjusting for various potential confounders. When analyzed individually, a number of different POPs were associated with ALP, ALT and bilirubin. No such association with GGT was observed.

    Conclusion: Various POPs including PCBs, OCDD and pesticides were associated with the liver dysfunction biomarkers bilirubin, ALT and ALP, suggesting adverse effects on liver function from these environmental pollutants. (C) 2014 Elsevier Inc. All rights reserved.

  • 10.
    Kumar, Jitender
    et al.
    Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, Monica
    Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ingelsson, Erik
    Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Persistent Organic Pollutants and Inflammatory Markers in a Cross-Sectional Study of Elderly Swedish People: The PIVUS Cohort2014In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, no 9, p. 977-983Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Persistent organic pollutants (POPs) are compounds that are generated through various industrial activities and released in the surrounding environment. Different animal studies have shown effects of different POPs on various inflammatory markers.

    OBJECTIVE: Because very few studies have been conducted in humans, we assessed the associations between different POPs and inflammatory markers in a large population-based sample of elderly men and women (all 70 years of age) from Sweden.

    METHODS: This cross-sectional study investigated the concentrations of several polychlorinated biphenyls (PCBs), organochlorine pesticides, polychlorinated dibenzo-p-dioxin, and brominated diphenyl ether congeners and their association with a number of inflammatory markers [vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, C-reactive protein (CRP), total leucocyte count, tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), and interleukin 6 (IL-6)] in 992 individuals. These individuals were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. We used a total toxic equivalency (TEQ) value that measures toxicological effects with the relative potencies of various POPs.

    RESULTS: Following adjustment for potential confounders, the TEQ value (driven mainly by PCB-126) was significantly associated with levels of ICAM-1 (p < 10(-5)). A similar trend was also observed between sum of PCBs and VCAM-1 (p < 0.001). No significant associations were observed between levels of POPs and other inflammatory markers.

    CONCLUSIONS: TEQ values were associated with levels of ICAM-1, to a lesser degree also with VCAM-1, but not with CRP and several other inflammatory markers. These findings suggest an activation of vascular adhesion molecules by POPs, and particularly by PCB-126.

  • 11.
    Kumar, Jitender
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ekdahl, Kristina N.
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden .
    Nilsson, Bo
    Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Influence of persistent organic pollutants on the complement system in a population-based human sample2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 71, p. 94-100Article in journal (Refereed)
    Abstract [en]

    Background: Persistent organic pollutants (POPS) are toxic compounds generated through various industrial activities and have adverse effects on human health. Studies performed in cell cultures and animals have revealed that POPs can alter immune-system functioning. The complement system is part of innate immune system that helps to clear pathogens from the body. We performed a large-scale population-based study to find out associations between summary measures of different POPs and different complement system markers.

    Methods: In this cross-sectional study, 16 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, octachloro-p-dibenzodioxin, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were analyzed for their association with levels of protein complement 3 (C3), 3a (C3a), 4 (C4) and C3a/C3 ratio. A total of 992 individuals (all aged 70 years, 50% females) were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. Regression analysis adjusting for a variety of confounders was performed to study the associations of different POP exposures (total toxic equivalency value or TEQ and sum of 16 PCBs) with protein complements.

    Results: The TEQ values were found to be positively associated with C3a (beta = 0.07, 95% CI = 0.017-0.131, p = 0.01) and C3a/C3 ratio (beta = 0.07, 95% Cl = 0.015-0.126, p = 0.01) taking possible confounders into account. The association observed was mainly driven by PCB-126.

    Conclusion: In this study involving 992 elderly individuals from the general population, we showed that POPs, mainly PCB-126, were associated with levels of complement system markers indicating that the association of these toxic compounds with downstream disease could be mediated by activation of immune system. (C) 2014 Elsevier Ltd. All rights reserved.

  • 12.
    Kumar, Jitender
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Influence of persistent organic pollutants on oxidative stress in population-based samples2014In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 114, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Persistent organic pollutants (POPs) are a large group of chemicals widely used and produced in various industrial applications. Many cell culture/animal studies have shown that POPs can induce oxidative stress. Since such data is lacking in humans, we conducted a large population-based study to analyze associations between POPs and oxidative stress markers. We measured following POPs; 16 polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides, octachlorinated dibenzo-p-dioxin, and polybrominated diphenyl ether 47, and oxidative stress markers; homocysteine, reduced [GSH] and oxidized glutathione [GSSG], glutathione ratio [GSSG/GSH], total glutathione, oxidized low-density lipoprotein [ox-LDL], ox-LDL antibodies, conjugated dienes, baseline conjugated dienes of LDL, and total anti-oxidative capacity in plasma samples collected from 992 70-year old individuals (50% women) from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Linear regression analyses were performed to study the associations between oxidative stress markers and summary measures of POPs including the total toxic equivalence (TEQ), sums of PCBs and BC pesticides (main exposures) while adjusting for potential confounders. In multivariable-adjusted analyses, sum of PCBs showed strong associations with ox-LDL (beta = 0.94; P = 2.9 * 10(-6)). Further, sum of PCBs showed association with glutathione-related markers (GSSG: beta = 0.01; P = 6.0 *10(-7); GSSG/GSH: beta = 0.002; P = 9.7 * 10(-10)), although in reverse direction. Other summary measures did not show any significant association with these markers. In our study of elderly individuals from the general population, we show that plasma levels of POPs are associated with markers of increased oxidative stress thereby suggesting that even low dose background exposure to POPs may be involved in oxidative stress. (C) 2014 Elsevier Ltd. All rights reserved.

  • 13.
    La Merrill, Michele A.
    et al.
    Department of Environmental Toxicology, University of California, Davis CA, USA.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Norwegian Institute for Water Research (NIVA), Oslo, Norway.
    van Bavel, Bert
    Örebro University, School of Science and Technology. Norwegian Institute for Water Research (NIVA), Oslo, Norway.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity2018In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 160, p. 541-546Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: The pesticide metabolite p,p'-DDE has been associated with left ventricular (LV) mass and known risk factors for LV hypertrophy in humans and in experimental models. We hypothesized that the associations of p,p'-DDE with LV hypertrophy risk factors, namely elevated glucose, adiposity and hypertension, mediate the association of p,p'-DDE with LV mass.

    METHODS: p,p'-DDE was measured in plasma from 70-year-old subjects (n = 988) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). When these subjects were 70-, 75- and 80- years old, LV characteristics were measured by echocardiography, while fasting glucose, body mass index (BMI) and blood pressure were assessed with standard clinical techniques.

    RESULTS: We found that p,p'-DDE levels were associated with increased fasting glucose, BMI, hypertension and LV mass in separate models adjusted for sex. Structural equation modeling revealed that the association between p,p'-DDE and LV mass was almost entirely mediated by BMI (70%), and also by hypertension (19%).

    CONCLUSION: The obesogenic effect of p,p'-DDE is a major determinant responsible for the association of p,p'-DDE with LV mass.

  • 14.
    Lampa, Erik
    et al.
    Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medicine, Uppsala University, University Hospital, Uppsala, Sweden.
    Hermansson, Anna Bornefalk
    Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    An investigation of the co-variation in circulating levels of a large number of environmental contaminants2012In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 22, no 5, p. 476-482Article in journal (Refereed)
    Abstract [en]

    We are daily exposed to many different environmental contaminants. Mixtures of these contaminants could act together to induce more pronounced effects than the sum of the individual contaminants. To evaluate the effects of such mixtures, it is of importance to assess the co-variance amongst the contaminants. Thirty-seven environmental contaminants representing different classes were measured in blood samples from 1016 individuals aged 70 years. Hierarchical cluster analysis and principal component analysis were used to assess the co-variation among the contaminants. Within each identified cluster, possible marker contaminants were sought for. We validated our findings using data from the National Health and Nutrition Examination Survey (NHANES) 2003--2004 study. Two large clusters could be identified, one representing low/medium chlorinated polychlorinated biphenyls (PCBs) (<= 6 chlorine atoms), as well as two pesticides and one representing medium/high chlorinated PCBs (>= 6 chlorine atoms). PCBs 118 and 153 could be used as markers for the low/medium chlorinated cluster and PCBs 170 and 209 could be used as markers for the medium/high chlorinated cluster. This pattern was similar to data from the NHANES study. Apart from the PCBs, little co-variation was seen among the contaminants. Thus, a large number of chemicals have to be measured to adequately identify mixtures of environmental contaminants.

  • 15.
    Lampa, Erik
    et al.
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Dept. of Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupt and Environ Med, Uppsala University, Uppsala, Sweden.
    Mixtures of environmental contaminants and the metabolic syndrome2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S35-, article id OS1-2Article in journal (Refereed)
  • 16.
    Lee, Duk-Hee
    et al.
    Kyungpook National University, Daegu, Republic of Korea.
    Lind, Lars
    Uppsala University Hospital, Uppsala, Sweden.
    Jacobs, David R., Jr.
    University of Minnesota, Minneapolis MN, United States; University of Oslo, Oslo, Norway .
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Uppsala University, Uppsala, Sweden.
    Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2012In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 40, p. 170-178Article in journal (Refereed)
    Abstract [en]

    Objectives: In animal experiments, persistent organic pollutants (POPs) have induced visceral obesity. To address this possibility in humans, we evaluated associations between POPs and abdominal obesity both cross-sectionally and prospectively.

    Methods: Twenty-one plasma POPs (16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured at baseline in 970 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), with prospective analyses in 511 participants re-examined after 5 years. Abdominal obesity was defined by an increased waist circumference.

    Results: In the cross-sectional analyses, concentrations of the less chlorinated PCBs, OC pesticides such as p,p'-DDE and dioxin had adjusted odds ratios of 2 to 3 for abdominal obesity. Many relations had inverted U-shapes rather than being linear, particularly in women. In contrast, concentrations of highly chlorinated PCBs were strongly inversely associated with abdominal obesity. In a single model including summary measures of the less chlorinated PCBs, highly chlorinated PCBs, and OC pesticides, both the positive associations and inverse associations strengthened. Similar but somewhat weaker associations were seen between POPs and risk of development of abdominal obesity in the prospective analyses.

    Conclusion: Using both a cross-sectional and a prospective design, low-dose exposure to less chlorinated PCBs, p,p'-DDE, and dioxin, were associated with existence or development of abdominal obesity, while highly chlorinated PCBs had an opposite association in an elderly population, despite the previous observation of higher incident diabetes associated with these same PCBs.

  • 17.
    Lee, Duk-Hee
    et al.
    Sch Med, Dept Prevent Med, Kyungpook Natl Univ, Taegu, South Korea; Dept Biomed Sci, Plus KNU Biomed Convergence Program BK21, Kyungpook Natl Univ, Taegu, South Korea.
    Lind, Lars
    Dept Med Sci, Univ Uppsala Hosp, Uppsala, Sweden.
    Jacobs, David R., Jr.
    Sch Publ Hlth, Div Epidemiol & Community Hlth, Univ Minnesota, Minneapolis MN, USA; Dept Nutr, Univ Oslo, Oslo, Norway.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Does Mortality Risk of Cigarette Smoking Depend on Serum Concentrations of Persistent Organic Pollutants?: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e95937-Article in journal (Refereed)
    Abstract [en]

    Cigarette smoking is an important cause of preventable death globally, but associations between smoking and mortality vary substantially across country and calendar time. Although methodological biases have been discussed, it is biologically plausible that persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides can affect this association. This study was performed to evaluate if associations of cigarette smoking with mortality were modified by serum concentrations of PCBs and OC pesticides. We evaluated cigarette smoking in 111 total deaths among 986 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) with mean follow-up for 7.7 years. The association between cigarette smoking and total mortality depended on serum concentration of PCBs and OC pesticides (P value for interaction = 0.02). Among participants in the highest tertile of the serum POPs summary score, former and current smokers had 3.7 (95% CI, 1.5-9.3) and 6.4 (95% CI, 2.3-17.7) times higher mortality hazard, respectively, than never smokers. In contrast, the association between cigarette smoking and total mortality among participants in the lowest tertile of the serum POPs summary score was much weaker and statistically nonsignificant. The strong smoking-mortality association observed among elderly people with high POPs was mainly driven by low risk of mortality among never smokers with high POPs. As smoking is increasing in many low-income and middle-income countries and POPs contamination is a continuing problem in these areas, the interactions between these two important health-related issues should be considered in future research.

  • 18. Lee, Duk-Hee
    et al.
    Lind, P. Monica
    Jacobs, David R., Jr.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Background exposure to persistent organic pollutants predicts stroke in the elderly2012In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 47, p. 115-120Article in journal (Refereed)
    Abstract [en]

    Background exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that accumulate mainly in adipose tissue, has recently emerged as a new risk factor for cardiovascular diseases. This prospective study was performed to evaluate if plasma concentrations of selected POPs predict incident stroke among the elderly. Twenty-one POPs (including 16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured in plasma collected at baseline in 898 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Stroke diagnosis was validated by hospital records. During the five year follow-up, 35 subjects developed hospital-treated stroke. After adjusting for known stroke risk factors, most PCBs with 4, 5, or 6 chlorine atoms, p,p'-DDE, trans-nonachlor, and octachlorodibenzo-p-dioxin significantly predicted the risk of stroke. Across quartiles of summary measures of PCBs and OC pesticides, the adjusted ORs were 1.0, 0.8 (95% confidence interval: 0.2-2.5), 1.2 (0.4-3.4), and 2.1 (0.7-6.2) for PCBs and 1.0, 1.2 (0.3-4.2), 2.3 (0.7-6.9), and 3.0 (1.0-9.4) for OC pesticides (P for trend = 0.11 and 0.03, respectively). The adjusted ORs among participants >= 90th percentile of the summary measures were 5.5 (1.7-18.1) for PCBs and 4.0 (1.1-14.6) for OC pesticides; corresponding ORs for those >= 95th percentile were 7.8 (2.1-29.6) and 9.5 (2.3-38.9). Background exposure to POPs may play an important role in development or progression of stroke in the elderly. 

  • 19. Lee, Duk-Hee
    et al.
    Lind, P. Monica
    Jacobs, David R., Jr.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Polychlorinated Biphenyls and Organochlorine Pesticides in Plasma Predict Development of Type 2 Diabetes in the Elderly2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 8, p. 1778-1784Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly. RESEARCH DESIGN AND METHODS-Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). RESULTS-After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8-42.7), and 7.5 (1.4-38.8) (P(trend) <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that P(trend) = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (P(trend) = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes. CONCLUSIONS-Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.

  • 20.
    Lee, Duk-Hee
    et al.
    Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Jacobs, David R.
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis MN, United States.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change2016In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 89-90, p. 179-184Article in journal (Refereed)
    Abstract [en]

    Background: Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change.

    Methods: Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases.

    Results: The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and ≥75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (Ptrend=0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and ≥75th percentiles compared to <25th percentile (Ptrend<0.01).

    Conclusions: This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations.

  • 21.
    Lind, L.
    et al.
    Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Uppsala University, Uppsala, Sweden.
    Van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, M.
    Uppsala University, Uppsala, Sweden.
    Circulating levels of perfluorinated compounds and left ventricular geometry2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S93-S93Article in journal (Other academic)
  • 22.
    Lind, Lars
    et al.
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Ng, Esther
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford CA, USA.
    Lindgren, Cecilia
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Broad Institute of the Massachusetts Institute of Technology, Cambridge, USA; Broad Institute of Harvard University, Cambridge, USA.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Mahajan, Anubha
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
    Lampa, Erik
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Morris, Andrew P.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample2017In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 98, p. 212-218Article in journal (Refereed)
    Abstract [en]

    Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.

    Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.

    Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.

    Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.

  • 23.
    Lind, Lars
    et al.
    Uppsala University, Uppsala, Sweden.
    Nordfors, Louise
    Karolinska Institutet, Stockholm, Sweden.
    Luttrop, Karin
    Karolinska Institutet, Stockholm, Sweden.
    Syvänen, Ann-Christine
    Dep of Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occup and Environ Medicine, Uppsala University, Uppsala, Sweden.
    DNA methylation and persistent organic pollutants2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S82-Article in journal (Refereed)
  • 24.
    Lind, Lars
    et al.
    Uppsala University, Uppsala, Sweden.
    Penell, Johanna
    Uppsala University, Uppsala, Sweden.
    Luttropp, Karin
    Karolinska Institutet, Stockholm, Sweden.
    Nordfors, Louise
    Karolinska Institutet, Stockholm, Sweden.
    Syvänen, Anne-Christine
    Uppsala University, Uppsala, Sweden.
    Axelsson, Tomas
    Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Fall, Tove
    Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Uppsala University, Uppsala, Sweden.
    Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population2013In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 59, p. 456-461Article in journal (Refereed)
    Abstract [en]

    Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p = 0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p = 0.009) only in subjects with one G-allele (n = 103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p = 0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis. (C) 2013 Elsevier Ltd. All rights reserved.

  • 25.
    Lind, Lars
    et al.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Penell, Johanna
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Syvänen, Anne-Christine
    Dept Med Sci, Mol Med & Sci Life Lab, Uppsala Univ, Uppsala, Sweden.
    Axelsson, Tomas
    Dept Med Sci, Mol Med & Sci Life Lab, Uppsala Univ, Uppsala, Sweden.
    Ingelsson, Erik
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden; Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Morris, Andrew P.
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Lindgren, Cecilia
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 133, p. 135-140Article in journal (Refereed)
    Abstract [en]

    Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures > 80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p < 0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.

  • 26. Lind, Lars
    et al.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Riserius, Ulf
    Lind, P. Monica
    An environmental and life-style wide association study (ELWAS) approach2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S81-S81Article in journal (Refereed)
  • 27.
    Lind, Lars
    et al.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Zethelius, Björn
    Dept Publ Hlth Geriatr, Uppsala Univ, Uppsala, Sweden; Med Prod Agcy, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 3, p. 473-479Article in journal (Refereed)
    Abstract [en]

    Several environmental contaminants, such as polychlorinated biphenyls, dioxins, bisphenol A and phthalates, have been linked to diabetes. We therefore investigated whether other kinds of contaminants, perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), are also associated with diabetes.

    The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study investigated 1,016 men and women aged 70 years. Seven PFAS were detected in almost all participant sera by ultra-high performance liquid chromatograph/tandem mass spectrometry. Diabetes was defined as use of hypoglycaemic agents or fasting glucose > 7.0 mmol/l.

    114 people had diabetes. In the linear analysis, no significant relationships were seen between the seven PFAS and prevalent diabetes. However, inclusion of the quadratic terms of the PFAS revealed a significant non-linear relationship between perfluorononanoic acid (PFNA) and diabetes, even after adjusting for multiple confounders (OR 1.96, 95% CI 1.19, 3.22, p = 0.008 for the linear term and OR 1.25, 95% CI 1.08, 1.44, p = 0.002 for the quadratic term). Perfluorooctanoic acid (PFOA) also showed such a relationship (p = 0.01). PFOA was related to the proinsulin/insulin ratio (a marker of insulin secretion), but none of the PFAS was related to the HOMA-IR (a marker of insulin resistance) following adjustment for multiple confounders.

    PFNA was related to prevalent diabetes in a non-monotonic fashion in this cross-sectional study, supporting the view that this perfluoroalkyl substance might influence glucose metabolism in humans at the level of exposure seen in the general elderly population.

  • 28.
    Lind, M.
    et al.
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medicine, Uppsala University, Uppsala, Sweden.
    Larsson, A.
    Department of Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, L.
    Department of Medicine, Uppsala University, Uppsala, Sweden.
    Circulating levels of perfluoroalkyl substances and biomarkers of liver function in a large population based sample of elderly men and women from Sweden2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S91-S91Article in journal (Other academic)
    Abstract [en]

    Objective: Since perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), have been shown to accumulate in the liver in experimental studies, we investigated the relationships between PFAS and biomarkers of liver function in the general population.

    Methods: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFAS were detected in almost all participants era by liquid chromatograph/tandem mass spectrometry. Several biomarkers of liver function were measured in parallel.

    Results: Bilirubin levels were significantly related to several of the PFAS, like perfluoroheptanoic acid (PFHpA), perfluorooctanoicacid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA). Of those, PFHpA, PFOA, PFDA, and PFNA were also related to Alanine Aminotransferase (ALT) levels. PFNA and PFUnDA were inversely related to alkaline phosphatases, while only PFHpA levels were significantly related to gamma-glutamyl transferase (GGT) levels. All associations were adjusted for life-style factors, like smoking, education, exercise habits, energy and alcohol intake.

    Conclusion: Circulating level of PFAS were related to biomarkers of liver function in this population-based sample, suggesting that PFAS could have a negative effect on liver function also in humans.

  • 29.
    Lind, Monica
    et al.
    Uppsala University, Uppsala, Sweden.
    Roos, Vendela
    Occ and Env Med, Uppsala University, Uppsala, Sweden.
    Rönn, Monika
    Occ and Env Med, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ahlström, Håkan
    Department of Radiolog, Uppsala University, Uppsala, Sweden.
    Johansson, Lars
    Department of Radiolog, Uppsala University, Uppsala, Sweden.
    Kullberg, Joel
    Department of Radiolog, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medicine, Uppsala University, Uppsala, Sweden.
    Persistent organic pollutants and adipose tissue distribution2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S82-, article id P11-09Article in journal (Refereed)
  • 30.
    Lind, Monica
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Stubleski, Jordan
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, p. E18-E18Article in journal (Other academic)
    Abstract [en]

    Aim: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, we here analyzed if the longitudinal changes in PFASs during a 10 years follow-up were related to the change in intima-media thickness (IMT) during the same period.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study,1,016 individuals were investigated at age 70. 826 of those were reinvestigated at age 75 and 606 at age 80 years. Eight different PFASs and carotid artery intima-media thickness (IMT, ultrasound) were measured at the three time-points.

    Results: IMT increased 0.058 mm during the 10-year period (p<0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period (p<0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional CV risk factors (HDL and LDL-cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) did only affect these relationships marginally.

    Conclusions: The change in plasma levels of several PFASs during 10 years was related the increase in IMT seen during the same period, giving further evidence that PFASs might interfere with the atherosclerotic process.

  • 31.
    Lind, P. M.
    et al.
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lee, Duk-Hee
    Department of Preventative Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
    Jacobs, David R.
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis MN, USA; Department of Nutrition, School of Medicine, University of Oslo, Oslo, Norway.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Wolff, Mary S.
    Department of Preventive Medicine, Mount Sinai School of Medicine, New York NY, USA.
    Lind, Lars
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Circulating levels of persistent organic pollutants are related to retrospective assessment of life-time weight change2013In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, no 3, p. 998-1004Article in journal (Refereed)
    Abstract [en]

    Background: Persistent organic pollutants (POPs) have been suggested to be linked to obesity. We have previously shown that less-chlorinated PCBs were positively related to fat mass, while highly-chlorinated PCBs were inversely related to obesity.

    Objective: The aim of the present evaluation is to investigate the relationship between retrospective assessed life-time change in body weight (20-70 years) with circulating POP levels measured at age 70 years.

    Methods: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUSs) study. 16 PCBs and 3 OC pesticides were analyzed using HRGC/HRMS. Current body weight was measured and participants self-reported their weight at age 20.

    Results: The average estimated weight change over 50 years was 14.4 kg. Both the sum of OC pesticide concentrations (4.3 kg more weight gain in quintile 5 vs. quintile 1, p < 0.0001) and the sum of the less-chlorinated PCBs were positively related to the estimated weight change (3.7 kg more weight gain in quintile 2 vs. quintile 1, non-linear relationship p = 0.0015). In contrast, the sum of concentrations of highly-chlorinated PCBs were inversely related to estimated weight change (8.4 kg less weight gain in quintile 5 vs. quintile 1, p < 0.0001).

    Conclusion: High levels of OC pesticides and the less-chlorinated PCBs at age 70 were associated with a pronounced estimated weight change over the previous 50 years. However, the opposite was seen for highly-chlorinated PCBs. Differences in mode of action, toxicokinetics, non-linear relationships and reverse causation might explain these discrepancies.

  • 32.
    Lind, P. Monica
    et al.
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Penell, Johanna
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Circulating levels of p,p '-DDE are related to prevalent hypertension in the elderly2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 129, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women.

    Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure >= 140 mmHg or a diastolic blood pressure >= 90 mmHg, and/or use of antihypertensive medication.

    Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 135 for a 1 SD change, 95% CI 1.17-1.56, p < 0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06-1.43, p=0.006).

    Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure. (C) 2013 Elsevier Inc. All rights reserved.

  • 33. Lind, P. Monica
    et al.
    Riserus, Ulf
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    An environmental wide association study (EWAS) approach to the metabolic syndrome2013In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 55, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Background

    Environmental contaminants have previously been linked to components of the Metabolic Syndrome (MetS). However, exposure to environmental contaminants is in part determined by various lifestyle factors.

    Objective

    Using an "Environmental Wide Association Study" (ELWAS) integrating environmental contaminants and lifestyle factors, we aimed to evaluate a possible additive role of both contaminants and lifestyle factors regarding MetS.

    Methods

    1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. 43 environmental contaminants were measured in the circulation. Dietary records were used to evaluate 21 nutrients and the proportions of 13 fatty acids were determined in serum cholesterol esters to further quantify fat quality intake. Adding 5 other important lifestyle factors yielded together 76 environmental and lifestyle factors. MetS was defined by the NCEP/ATPIII-criteria.

    Results

    23% had MetS. Using cross-validation within the sample, fourteen environmental contaminants or lifestyle factors consistently showed a false discovery rate <0.05. When the major variables entered a multiple model, only p,p'-DDE levels (positive), PCB209 (inverse) and exercise habits (inverse) were together with a fatty acid pattern, with high levels of palmitic acid and oleic acid and low levels of linoleic acid, related to MetS (p<0.002 for all variables).

    Conclusion

    Using a cross-sectional EWAS approach, certain environmental contaminants and lifestyle factors were found to be associated with prevalent metabolic syndrome in an additive fashion in an elderly population.

  • 34.
    Lind, P. Monica
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

    OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

    RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

    CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

  • 35.
    Lind, P. Monica
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Stubleski, Jordan
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study2018In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, article id 59Article in journal (Refereed)
    Abstract [en]

    Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

    Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

    Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

  • 36.
    Lind, P. Monica
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 152, p. 157-164Article in journal (Refereed)
    Abstract [en]

    Background and objective: During recent years, some persistent organic pollutants (POPs) have been linked to atherosclerosis. One group of POPs, the poly- and perfluoroalkyl substances (PFASs) have not been investigated with regard to atherosclerotic plaques.

    Methods: Carotid artery atherosclerosis was assessed by ultrasound in 1016 subjects aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants' plasma by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    Results: No significant linear associations were observed between the PFASs and intima-media thickness (IMT), or the echogenicity in the intima-media complex (IM-GSM, a marker of lipid infiltration in the artery) when men and women were analyzed together. Neither was occurrence of carotid plaques related to PFASs levels. However, highly significant interactions were observed between some PFASs and sex regarding both IM-GSM and plaque prevalence. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were all related to IM-GSM in a positive fashion in women (p=0.002-0.003), while these relationships were negative in men. The levels of PFUnDA were significantly related to carotid plaque in women (OR 1.59, 95%CI 1.03-2.43, p=0.03), but not in men (OR 0.93, 95%CI 0.62-1.42, p=0.75).

    Conclusions: In this cross-sectional study, a pronounced gender difference was observed regarding associations between some PFASs, especially the long-chain PFUnDA, and markers of atherosclerosis, with more pronounced relationships found in women. These findings suggest a sex-specific role for PFASs in atherosclerosis.

  • 37.
    Lind, P. Monica
    et al.
    Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medicine, Uppsala University, Uppsala, Sweden.
    Circulating levels of pp-DDE and hypertension2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no Supplement, p. S83-, article id P11-12Article in journal (Refereed)
  • 38.
    Lind, P. Monica
    et al.
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medicine, Uppsala University, Uppsala, Sweden.
    Circulating Levels of Persistent Organic Pollutants (POPs) and Carotid Atherosclerosis in the Elderly2012In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 120, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Increased circulating levels of persistent organic pollutants (POPs) have been associated with myocardial infarction. Because myocardial infarction is an atherosclerotic disease, we investigated, in a cross-sectional study, whether POP levels are related to atherosclerosis.

    METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1,016 participants 70 years of age), the prevalence of carotid artery plaques was determined by ultrasound. The number of carotid arteries with plaques (0, 1, or 2) was recorded. Also, the intima-media thickness (IMT) and gray scale median of the intima-media complex (IM-GSM) were measured. Twenty-three POPs, comprising 16 polychlorinated biphenyls (PCBs), 5 pesticides, 1 dioxin, and 1 brominated compound (brominated diphenyl ether congener BDE-47), were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry.

    RESULTS: Seven of the POPs (PCB congeners 153, 156, 157, 170, 180, 206, and 209) were significantly associated with the number of carotid arteries with plaques even after adjusting for multiple risk factors (sex, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, high-density lipoprotein and low-density lipoprotein cholesterol, serum triglycerides, smoking, antihypertensive treatment, and statin use; p = 0.002-0.0001). Highly chlorinated PCBs (congeners 194, 206, and 209) were associated with an echolucent IM-GSM (p < 0.0001 after adjustment), whereas associations between POPs and IMT were modest.

    CONCLUSIONS: Circulating levels of PCBs were associated with atherosclerotic plaques and echogenicity of the intima-media complex independent of cardiovascular risk factors, including lipids. This suggests that POPs may be a risk factor for myocardial infarction, but associations need to be confirmed in prospective studies.

  • 39.
    Lind, Ylva Sjöberg
    et al.
    Dept Emergency Med, Linköping University Hospital, Linköping, Sweden.
    Lind, Lars
    Dept Med, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Uppsala University, Uppsala, Sweden.
    Persistent organic pollutants and abnormal geometry of the left ventricle in the elderly2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 8, p. 1547-1553Article in journal (Refereed)
    Abstract [en]

    Background:Established risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes, and obesity. However, as these risk factors explain only part of the variation in left ventricular mass, we investigated whether persistent organic pollutants (POPs) might also play a role in LVH, because exposure to polychlorinated biphenyl 126 induced cardiac growth in rats.

    Methods:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), left ventricular mass index (LVMI), relative wall thickness (RWT), and geometric groups of LVH, were determined by echocardiography and 21 POPs were measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 1016 individuals aged 70 years. All individuals with a history of myocardial infarction were excluded from analysis (n=72).

    Results:Several of the POPs were related to abnormal left ventricular geometry before adjustment for established risk factors, but lost in significance following adjustment. However, the pesticide hexachlorobenzene (HCB) levels were significantly related to RWT, and concentric left ventricular remodeling, also following adjustment for sex, blood pressure, antihypertensive treatment, diabetes, and BMI (P<0.0001).

    Conclusion:In this cross-sectional study, circulating levels of HCB were related to increased wall thickness of the left ventricle and concentric left ventricular remodeling, independently of LVH risk factors, suggesting a role of this environmental contaminant in abnormal growth of the left ventricle.

  • 40.
    Ljunggren, Stefan A.
    et al.
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Helmfrid, Ingela
    Linköping Univ Hosp, Cty Council Östergötland, Linköping, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Wingren, Gun
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Lindahl, Mats
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Karlsson, Helen
    Cty Council Östergötland, Linköping Univ Hosp, Linköping, Sweden.
    Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 65, p. 93-99Article in journal (Refereed)
    Abstract [en]

    Persistent organic pollutants (POPS) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation. (C) 2014 Elsevier Ltd. All rights reserved.

  • 41.
    Park, Wook Ha
    et al.
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
    Kang, Sora
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
    Lee, Hong Kyu
    Department of Internal Medicine, College of Medicine, Eulji University, Seoul, South Korea.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Pak, Youngmi Kim
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, South Korea.
    Lind, Lars
    Department of Medicine, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs)2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9383Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum samples obtained from 911 elderly subjects in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Plasma concentrations of 30 POPs and plastic chemicals have previously been determined in the same PIVUS subjects. Linear regression analysis demonstrated that total toxic equivalence (TEQ) values and polychlorinated biphenyls (PCBs) were significantly correlated with AhR bioactivity (positively) and ATP concentration (negatively). Serum AhR bioactivities were positively associated with some PCBs, regardless of their dioxin-like properties, but only dioxin-like PCBs stimulated AhR bioactivity. By contrast, PCBs mediated a reduction in ATP content independently of their dioxin-like properties. This study suggests that AhR bioactivity and ATP concentrations in serum-treated cells may be valuable surrogate biomarkers of POP exposure and could be useful for the estimation of the effects of POPs on human health.

  • 42.
    Penell, Johanna
    et al.
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Lind, Lars
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Fall, Tove
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Syvanen, Anne-Christine
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Axelsson, Tomas
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Lundmark, Per
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Morris, Andrew P.
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Lindgren, Cecilia
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ingelsson, Erik
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden; Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Lind, P. Monica
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Genetic variation in the CYP2B6 Gene is related to circulating 2,2 ',4,4 '-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study2014In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, p. 34-Article in journal (Refereed)
    Abstract [en]

    Background: Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample.

    Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS).

    Results: Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10(- 4) to 10(-9)). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals.

    Conclusion: Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.

  • 43.
    Penell, Johanna
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, R. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Persistent organic pollutants are related to the change in circulating lipid levels during a 5 year follow-up2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 134, p. 190-197Article in journal (Refereed)
    Abstract [en]

    When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data indicate that exposure to POPs may change lipid values. The aim of the present study is to investigate if POP levels can predict future changes in levels of circulating lipids. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-three different POPs, including 16 polychlorinated biphenyls (PCBs), five organochlorine pesticides, one dioxin (OCDD) and one flame retardant brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) at age 70. Strong relationships were seen among the baseline levels of the non-dioxin-like PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipidnormalized levels were used compared to wet-weight based levels. On the contrary, for two of the pesticides, hexachlorobenzene and trans-nonachlordane, levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol, in particular for wet-weight based levels. However, these relationships were only significant for wet-weight PCB 194 following adjustment for multiple testing. None of the POPs was related to the change in serum triglycerides. When investigating the association between the change in total serum cholesterol and LDL-cholesterol across different categories of change in BMI, we noted robust results especially in the group with stable BMI, suggesting that the observed relationships were not due to fluctuations in BMI over time. In conclusion, POPs are related to the change in lipids over time, especially LDL-cholesterol. This may explain why POP exposure previously has been linked to atherosclerosis and cardiovascular disease.

  • 44.
    Roos, Vendela
    et al.
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Rönn, Monika
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Kullberg, Joel
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Johansson, Lars
    Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden; Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Ahlström, Håkan
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Circulating Levels of Persistent Organic Pollutants in Relation to Visceral and Subcutaneous Adipose Tissue by Abdominal MRI2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 2, p. 413-418Article in journal (Refereed)
    Abstract [en]

    Objective: We and others have shown relationships between circulating levels of persistent organic pollutants (POPs) and different measures of obesity in both cross-sectional and prospective studies. Since viscerally located fat seems to be the most harmful type, we investigated whether plasma POP levels were more closely related to visceral adipose tissue (VAT) than to subcutaneous adipose tissue (SAT).

    Design and Methods: Thousand hundred and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high-resolution gas chromatography/ high-resolution mass spectrometry. Abdominal magnetic resonance imaging, measuring VAT and SAT, respectively, was performed in a representative subsample of 287 subjects.

    Results: The less chlorinated polychlorinated biphenyl (PCB) congeners (105 and 118), and the pesticides dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans-nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in an inverted U-shaped manner (P = 0.0008).

    Conclusions: In conclusion, the results were in accordance with our previous studies using waist circumference and fat mass as obesity measure. However, the novel finding that PCB189 was related to the VAT/SAT ratio deserves further investigation since exposure to this PCB congener, which has previously been linked to diabetes development, might thereby play a role in the distribution of abdominal adipose tissue.

  • 45. Rönn, Monika
    et al.
    Lind, Lars
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Salihovic, Samira
    Michaelsson, Karl
    Lind, Pia Monica
    Circulating levels of persistent organic pollutants associate in divergent ways to fat mass measured by DXA in humans2011In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 85, no 3, p. 335-343Article in journal (Refereed)
    Abstract [en]

    Background: Environmental contaminants have recently been implicated in the pathogenesis of obesity. Objective: To explore relations between persistent organic pollutants (POPS) and fat mass independently of body stature, using a cross-sectional design. Methods: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), fat mass was determined in 70-year-old subjects (n = 890) by dual-energy X-ray absorptiometry (DXA). The plasma levels of 21 POPs (including 16 PCB congeners, 3 OC pesticides, 1 BDE47, and 1 dioxin) were measured by high resolution chromatography coupled with high resolution mass spectrometry (HRGC/HRMS). Results: Lipid-standardized plasma concentrations of octachlorodibenzo-p-dioxin (OCDD), the PCBs 74, 99, 105 and 118, and the pesticides HCB. TNK, and DDE were all positively related to fat mass (p = 0.03-0.0001). Subjects in the fifth quintile for PCB 105 showed a mean fat mass that was 4.8 kg more than subjects in the first quintile. On the other hand, the PCBs 156, 157, 169, 170, 180, 189, 194, 206, and 209 were negatively related to fat mass (p = 0.0001). For PCB 194, subjects in the fifth quintile showed a mean fat mass that was 10.8 kg less than subjects in the first quintile. Following adjustment for smoking, physical activity, education level, height, lean mass, and gender, these results remained significant (p = 0.01-0.0001) except for the PCBs 74 and 99. For some PCBs, the associations vs. fat mass were more pronounced in women than in men. Conclusion: Plasma concentrations of some pesticides are positively related to fat mass, while divergent associations are seen for the PCBs. These results implicate a complex role of POPs in obesity. (C) 2011 Elsevier Ltd. All rights reserved.

  • 46.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    Development and application of high-throughput methods for analysis of persistent organic pollutants in human blood2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The general public is continuously exposed to a wide range of environmental pollutants. This thesis focuses on a group of anthropogenic chemicals referred to as persistent organic pollutants (POPs) that have been linked to various adverse health effects in humans.

    The main objective of this thesis was focused on the development and application of high-throughput methods for analysis of a broad range of chlorinated, brominated, and fluorinated POPs in human blood.

    After establishing that the methods were effective, the two methods were applied to human plasma samples to examine the background levels of a broad range of POPs in human plasma samples among elderly men and women from Sweden and to assess the influence of gender. Levels of a wide range of chlorinated, brominated, and fluorinated compounds were determined in plasma samples collected during 2001-2004 from 1, 016 (50.2% women) 70 year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). The POPs studied were 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), 1 dioxin, 1 brominated flame retardant as well as 14 perfluoroalkyl substances (PFAS) including structural perfluorooctane sulfonic acid (PFOS) isomers. The majority of the studied compounds were detected in the 70-100% of the participants. The structural PFOS isomers were successfully quantified in a sub-sample of 25 men and women. Furthermore, gender differences in the concentrations of the POPs studied showed that the majority of chlorinated and brominated compounds were significantly different when comparing men and women in the study, while the concentrations of the fluorinated compounds were found to be less influenced by gender.

    This thesis has, by using the developed high-throughput methods requiring only small amounts of human blood, provided background exposure information of a broad range of POPs for an epidemiological study.

    List of papers
    1. Trends in the analysis of persistent organic pollutants (POPs) in human blood
    Open this publication in new window or tab >>Trends in the analysis of persistent organic pollutants (POPs) in human blood
    2013 (English)In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 46, p. 129-138Article in journal (Refereed) Published
    Abstract [en]

    The general demands on analytical practices in laboratories involved in monitoring concentrations of persistent organic pollutants (POPs) in human blood in the context of the Stockholm Convention are met by the validated analytical procedures applied in most laboratories today. At the same time, as the concentrations of many of the legacy POPs are decreasing in the general populations, more specific, sensitive, and accurate analytical techniques are required. Thus, a challenge for the Stockholm Convention is the analytical capacity, in terms of quality and availability worldwide, to monitor declining concentrations of POPs in human blood. However, other POP issues (e.g., those targeted by epidemiological studies) might require different information and therefore more specialized analytical procedures having greater instrumental sensitivity.

    We review current and emerging analytical procedures used for analysis of the chlorinated, brominated, and fluorinated classes of POPs in human blood with a focus on the compounds included in the Stockholm Convention. In general, analytical trends in sample clean-up, separation, detection techniques and quality protocols provide a tool for POP laboratories to measure POPs in human blood. Techniques based on established mass-selective instruments are most commonly employed but declining concentrations in humans in the future might require more selective, more sensitive techniques.

    Place, publisher, year, edition, pages
    Oxon, UK: Elsevier, 2013
    Keywords
    Gas chromatography (GC), High-resolution mass spectrometry (HRMS), Human blood, Liquid chromatography (LC), Organochlorine (OC) pesticide, Perfluoroalkylated substance (PFAS), Polychlorinated biphenyl (PCB), Polychlorinated dibenzo-p-dioxin (PCDD), Polychlorinated diphenyl ether (PBDE), Stockholm Convention
    National Category
    Chemical Sciences Analytical Chemistry
    Research subject
    Chemistry
    Identifiers
    urn:nbn:se:oru:diva-29858 (URN)10.1016/j.trac.2012.06.009 (DOI)000319087800027 ()2-s2.0-84876816513 (Scopus ID)
    Available from: 2013-06-28 Created: 2013-06-28 Last updated: 2017-12-06Bibliographically approved
    2. A rapid method for screening of the Stockholm Convention POPs in small amounts of human plasma using SPE and HRGC/HRMS
    Open this publication in new window or tab >>A rapid method for screening of the Stockholm Convention POPs in small amounts of human plasma using SPE and HRGC/HRMS
    Show others...
    2012 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 86, no 7, p. 747-753Article in journal (Refereed) Published
    Abstract [en]

    A rapid analytical screening method allowing simultaneous analysis of 23 persistent organic pollutants (POPs) in human plasma was developed. Sample preparation based on solid-phase extraction (SPE) with additional clean-up using small multilayer silica gel columns. SPE was performed using a custom made polystyrene-divinylbenzene sorbent for the extraction of chlorinated and brominated POPs. Special efforts to reduce sample volume and improve speed and efficiency of the analytical procedure were made. Determination of 16 polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides, octachlorinated dibenzo-p-dioxin (OCDD) and polybrominated diphenyl ether (BDE #47) in 0.5 mL human plasma was performed by using high resolution gas chromatography coupled to high resolution mass spectrometry (HRGC/HRMS). Recovery of POPs ranged between 46% and 110%, and reproducibility was below 25% relative standard deviation (RSD) for all target compounds, except for trans-nonachlor and OCDD, which were present only at low levels. Limits of detection (LOD) were for the PCBs between 0.8 and 117.7 pg mL(-1) plasma and for the OC pesticides between 5.9 and 89.1 pg mL(-1) plasma. The LOD for OCDD and BDE #47 were 1.4 pg mL(-1) plasma, and 9.2 pg mL(-1) plasma, respectively. The presented method was successfully applied to 1016 human plasma samples from an epidemiological study on cardiovascular disease. (C) 2011 Elsevier Ltd. All rights reserved.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Persistent organic pollutants, Sample extraction, Human plasma, HRGC/HRMS, Polychlorinated biphenyls, Organochlorine pesticides
    National Category
    Chemical Sciences
    Research subject
    Environmental Chemistry
    Identifiers
    urn:nbn:se:oru:diva-22315 (URN)10.1016/j.chemosphere.2011.11.006 (DOI)000301166700008 ()22153485 (PubMedID)2-s2.0-84856031844 (Scopus ID)
    Available from: 2012-04-02 Created: 2012-04-02 Last updated: 2017-12-07Bibliographically approved
    3. A rapid method for analysis of PFAS including structural PFOS isomers in human serum using 96-well plate column-switching UPLC-S/MS
    Open this publication in new window or tab >>A rapid method for analysis of PFAS including structural PFOS isomers in human serum using 96-well plate column-switching UPLC-S/MS
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    To facilitate high-throughput analysis suitable for large epidemiological studies we developed an automated column-switching ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of perfluorocarboxylates (PFCAs; C5, C6, C7, C8, C9, C10, C11, C12, and C13), perfluoroalkyl sulfonic acids (PFSAs; C4, C6, C8, and C10), perfluorooctane sulfonamide (PFOSA), and five groups of structural perfluorooctane sulfonic acids (PFOS) isomers in human serum or plasma. The analytical procedure involves rapid protein precipitation using 96-well plates followed by a fully automated sample clean-up using an on-line trap column removing many potentially interfering sample components while through the mobile phase gradient the target analytes are eluted onto the analytical column for further separation and subsequent mass detection. The method showed good linearity (R2 < 0.995) at concentrations ranging from 0.01 to 60 ngmL-1 and low method detection limits (MDLs) ranging between 0.01-0.17 ngmL-1 depending on the analyte. The precision of the developed method was good, with within-run (n=7) and between-run (n=103) coefficients of variation between 2% and 20% for most compounds including PFOS (2%, 8%) and its structural isomers (2-6% and 4-8%). The method showed good conformity with a standard reference material (n=56). The columnswitching UPLC method has been successfully applied for the determination of perflourinated alkyl acids (PFAAs), including structural PFOS isomers, and PFOSA in human plasma from an epidemiological study.

    Keywords
    human blood, perfluoroalkylated substances, structural isomers, perfluorooctane sulfonamide, sample preparation, column-switch, pfos, pfoa
    National Category
    Chemical Sciences
    Research subject
    Chemistry
    Identifiers
    urn:nbn:se:oru:diva-30109 (URN)
    Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2017-10-17Bibliographically approved
    4. Circulating levels of Persistent Organic Pollutants (POPs) among elderly men and women from Sweden: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)
    Open this publication in new window or tab >>Circulating levels of Persistent Organic Pollutants (POPs) among elderly men and women from Sweden: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)
    Show others...
    2012 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 44, p. 59-67Article in journal (Refereed) Published
    Abstract [en]

    Persistent Organic Pollutants (POPs) are a huge group of chemicals that have been linked to various adverse health effects in humans. Large epidemiological studies investigating gender differences in levels of POPs in the elderly are limited and the results from these are not always consistent. The present study was undertaken to examine the background levels of a broad range of POPs in human plasma samples among elderly men and women from Sweden and to assess the influence of gender. Levels of 23 POPs were determined in plasma samples collected during 2001-2004 from 1016 (50.2% women) 70year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). Measurements were performed using high resolution gas chromatography with high resolution mass spectrometry (HRGC-HRMS) and the POPs studied were 16 polychlorinated biphenyls (PCBs), five organochlorine (OC) pesticides, one dioxin, and one brominated flame retardant. The concentrations of the selected POPs were found similar, or comparable, to other studies of non-occupationally exposed populations from Sweden and Europe. Differences in levels of POPs between men and women were assessed by using Wilcoxon rank-sum (Mann-Whitney) test. Significant (p<0.0001) gender differences in levels of specific POPs were observed and a number of POP concentrations were found to differ between men and women. More specifically, levels of HCB, OCDD, and PCB congeners #74, #105, and #118 were found to be higher in women, while the rest of the majority of POPs were higher in men.

    National Category
    Natural Sciences Chemical Sciences
    Research subject
    Chemistry
    Identifiers
    urn:nbn:se:oru:diva-23923 (URN)10.1016/j.envint.2012.01.011 (DOI)000304745900008 ()
    Available from: 2012-07-05 Created: 2012-07-05 Last updated: 2017-12-07Bibliographically approved
  • 47.
    Salihovic, Samira
    et al.
    Örebro University, School of Science and Technology. Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
    Fall, Tove
    Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
    Ganna, Andrea
    Massachusetts General Hospital, Harvard Medical School and Broad Institute, Boston, MA, USA.
    Broeckling, Corey D.
    Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
    Prenni, Jessica E.
    Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances2018In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064XArticle in journal (Refereed)
    Abstract [en]

    Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.

  • 48.
    Salihovic, Samira
    et al.
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ganna, Andrea
    Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge Center, Cambridge, USA.
    Fall, Tove
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Broeckling, Corey D.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, USA.
    Prenni, Jessica E.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, USA.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, USA.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    The metabolic fingerprint of p,p'-DDE and HCB exposure in humans2016In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 88, p. 60-66Article in journal (Refereed)
    Abstract [en]

    Background: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown.

    Objectives: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    Methods: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression.

    Results: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides.

    Conclusions: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.

  • 49.
    Salihovic, Samira
    et al.
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Lindström, Gunilla
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Perfluoroalkyl substances (PFAS) including structural PFOS isomers in plasma from elderly men and women from Sweden: Results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)2015In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 82, no Sept 2015, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Per- and polyfluoroalkyl substances (PFASs) are a class of compounds with unique chemical properties that have been shown useful in a wide variety of applications because they provide materials with reduced surface tension and exceptional non-stick properties. PFASs are commonly found in impregnation materials, coatings of papers and textiles, fire-fighting foams, pesticides, and cleaning agents. The potential for human exposure to PFASs is high because of their widespread distribution. The aim of this study was to investigate levels of PFASs in men and women from Sweden and to assess the influence of gender and parity among women. Levels of 13 PFASs were determined in plasma samples collected during 2001–2004 from 1016 (507 women) 70 year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). The PFASs studied were nine perfluorinated carboxylic acids (PFCAs), four perfluorinated sulfonic acids (PFSAs) and perfluorooctane sulfonamide (PFOSA). In addition, structural isomers of perfluorooctane sulfonic acid (PFOS) were determined in a subset of 398 individuals. The detection rates were high and the majority of the studied compounds were detected in more than 75% of the participants. Levels of the selected analytes were found to be similar to other studies of non-occupationally exposed populations. Gender differences were observed in levels of PFHpA which was higher in men, while PFHxS was higher in women. Parity among women was shown to have a minor effect on PFAS concentrations and we found primi- and multiparous women to have slightly lower levels of PFUnDA when compared to nulliparous women.

  • 50.
    Salihovic, Samira
    et al.
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Lindström, Gunilla
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    2Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    3Acute and Internal Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    A rapid method for analysis of PFAS including structural PFOS isomers in human serum using 96-well plate column-switching UPLC-S/MSManuscript (preprint) (Other academic)
    Abstract [en]

    To facilitate high-throughput analysis suitable for large epidemiological studies we developed an automated column-switching ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of perfluorocarboxylates (PFCAs; C5, C6, C7, C8, C9, C10, C11, C12, and C13), perfluoroalkyl sulfonic acids (PFSAs; C4, C6, C8, and C10), perfluorooctane sulfonamide (PFOSA), and five groups of structural perfluorooctane sulfonic acids (PFOS) isomers in human serum or plasma. The analytical procedure involves rapid protein precipitation using 96-well plates followed by a fully automated sample clean-up using an on-line trap column removing many potentially interfering sample components while through the mobile phase gradient the target analytes are eluted onto the analytical column for further separation and subsequent mass detection. The method showed good linearity (R2 < 0.995) at concentrations ranging from 0.01 to 60 ngmL-1 and low method detection limits (MDLs) ranging between 0.01-0.17 ngmL-1 depending on the analyte. The precision of the developed method was good, with within-run (n=7) and between-run (n=103) coefficients of variation between 2% and 20% for most compounds including PFOS (2%, 8%) and its structural isomers (2-6% and 4-8%). The method showed good conformity with a standard reference material (n=56). The columnswitching UPLC method has been successfully applied for the determination of perflourinated alkyl acids (PFAAs), including structural PFOS isomers, and PFOSA in human plasma from an epidemiological study.

12 1 - 50 of 63
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