| 1. |
- Alijagic, Andi, 1992-, et al.
(författare)
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Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.
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| 2. |
- Ax, Erika, et al.
(författare)
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Circulating levels of environmental contaminants are associated with dietary patterns in older adults
- 2015
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 75, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Dunder, Linda, et al.
(författare)
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Plasma levels of per- and polyfluoroalkyl substances (PFAS) and cardiovascular disease - Results from two independent population-based cohorts and a meta-analysis
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- Background: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD).Objectives: To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies.Methods: In 2,278 subjects aged 45-75 years from the EpiHealth study, the risk of incident CVD in relation to relative plasma levels of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) was investigated. Associations between plasma levels of six PFAS and incident CVD were also examined in the PIVUS-study (n = 1,016, all aged 70 years). In addition, a meta-analysis was performed including three previous prospective studies, together with the results from the present study.Results: There were no overall statistically significant associations between levels of the different PFAS and incident CVD, neither in EpiHealth nor in PIVUS. However, there was a significant sex interaction for PFOS in EpiHealth (p = 0.008), and an inverse association could be seen only in men (Men, HR: 0.68, 95 % CI: 0.52, 0.89) (Women, HR: 1.13, 95 % CI: 0.82, 1.55). A meta-analysis of five independent studies regarding PFOA and incident CVD showed a risk ratio (RR) of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels.Conclusions: This longitudinal study using data from two population-based cohort studies in Sweden did not indicate any increased risk of incident CVD for moderately elevated PFAS levels. A meta-analysis of five independent cohort studies rather indicated a modest inverse association between PFOA levels and incident CVD, further supporting that increasing PFAS levels are not linked to an increased risk of CVD.
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| 4. |
- Dunder, Linda, et al.
(författare)
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Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results.AIM: The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease.METHODS: Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45-75 years old, 50.6 % men).RESULTS: After adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS.CONCLUSIONS: Our findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.
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| 5. |
- Helmfrid, Ingela, et al.
(författare)
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Exposure and body burden of polychlorinated biphenyls (PCB) and metals in a historically contaminated community
- 2015
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 76, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Kumar, Jitender, et al.
(författare)
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Influence of persistent organic pollutants on the complement system in a population-based human sample
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 71, s. 94-100
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Lee, Duk-Hee, et al.
(författare)
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Association between background exposure to organochlorine pesticides and the risk of cognitive impairment : A prospective study that accounts for weight change
- 2016
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 89-90, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Lee, Duk-Hee, et al.
(författare)
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Associations of persistent organic pollutants with abdominal obesity in the elderly : The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2012
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 40, s. 170-178
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Lee, Duk-Hee, et al.
(författare)
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Background exposure to persistent organic pollutants predicts stroke in the elderly
- 2012
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 47, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Lind, Lars, et al.
(författare)
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Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
- 2017
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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