| 1. |
- Balidemaj, Festina, et al.
(författare)
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Prenatal Exposure to Locally Emitted Air Pollutants Is Associated with Birth Weight : An Administrative Cohort Study from Southern Sweden
- 2022
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- While prenatal exposure to ambient air pollution has been shown to be associated with reduced birth weight, there is substantial heterogeneity across studies, and few epidemiological studies have utilized source-specific exposure data. The aim of the present study was, therefore, to investigate the associations between local, source-specific exposure to fine particulate matter (PM2.5) during pregnancy and birth weight. An administrative cohort comprising 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on relevant covariates. Investigated sources of PM2.5 included all local sources together as well as tailpipe exhaust, vehicle wear-and-tear, and small-scale residential heating separately. The relationships between these exposures, rep-resented as interquartile range (IQR) increases, and birth weight (continuous) and low birth weight (LBW; <2500 g) were analyzed in crude and adjusted models. Each local PM2.5 source investigated was associated with reduced birth weight; average decreases varied by source (12–34 g). Only small-scale residential heating was clearly associated with LBW (adjusted odds ratio: 1.14 (95% confidence interval: 1.04–1.26) per IQR increase). These results add to existing evidence that prenatal exposure to ambient air pollution disrupts fetal growth and suggest that PM2.5 from both vehicles and small-scale residential heating may reduce birth weight.
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| 2. |
- Aasa, Jenny, et al.
(författare)
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Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk
- 2019
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 mu g/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/10(5)) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels.
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| 3. |
- Al Naggar, Yahya, et al.
(författare)
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Are Honey Bees at Risk from Microplastics?
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Microplastics (MPs) are ubiquitous and persistent pollutants, and have been detected in a wide variety of media, from soils to aquatic systems. MPs, consisting primarily of polyethylene, polypropylene, and polyacrylamide polymers, have recently been found in 12% of samples of honey collected in Ecuador. Recently, MPs have also been identified in honey bees collected from apiaries in Copenhagen, Denmark, as well as nearby semiurban and rural areas. Given these documented exposures, assessment of their effects is critical for understanding the risks of MP exposure to honey bees. Exposure to polystyrene (PS)-MPs decreased diversity of the honey bee gut microbiota, followed by changes in gene expression related to oxidative damage, detoxification, and immunity. As a result, the aim of this perspective was to investigate whether wide-spread prevalence of MPs might have unintended negative effects on health and fitness of honey bees, as well as to draw the scientific community's attention to the possible risks of MPs to the fitness of honey bees. Several research questions must be answered before MPs can be considered a potential threat to bees.
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| 4. |
- Anand, MP, et al.
(författare)
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Clinical, Epidemiological and Experimental Approaches to Assess Adverse Health Outcomes of Indoor Biomass Smoke Exposure: Conclusions from An Indo-Swedish Workshop in Mysuru, January 2020
- 2020
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 8:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This report summarizes the outcome of a workshop held in Mysuru, India in January 2020 addressing the adverse health effects of exposure to biomass smoke (BMS). The aim of the workshop was to identify uncertainties and gaps in knowledge and possible methods to address them in the Mysuru study on Determinants of Health in Rural Adults (MUDHRA) cohort. Specific aims were to discuss the possibility to improve and introduce new screening methods for exposure and effect, logistic limitations and other potential obstacles, and plausible strategies to overcome these in future studies. Field visits were included in the workshop prior to discussing these issues. The workshop concluded that multi-disciplinary approaches to perform: (a) indoor and personalized exposure assessment; (b) clinical and epidemiological field studies among children, adolescents, and adults; (c) controlled exposure experiments using physiologically relevant in vitro and in vivo models to understand molecular patho-mechanisms are warranted to dissect BMS-induced adverse health effects. It was perceived that assessment of dietary exposure (like phytochemical index) may serve as an important indicator for understanding potential protective mechanisms. Well trained field teams and close collaboration with the participating hospital were identified as the key requirements to successfully carry out the study objectives.
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| 5. |
- Engström, Karin, et al.
(författare)
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Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:12, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants’ residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.
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| 6. |
- Hedgespeth, Melanie, et al.
(författare)
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Assessing potential vulnerability and response of fish to simulated avian predation after exposure to psychotropic pharmaceuticals
- 2016
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Psychotropic pharmaceuticals present in the environment may impact organisms both directly and via interaction strengths with other organisms, including predators; therefore, this study examined the potential effects of pharmaceuticals on behavioral responses of fish to avian predators. Wild-caught juvenile perch (Perca fluviatilis) were assayed using a striking bird model after a seven-day exposure to psychotropic pharmaceuticals (the antidepressants fluoxetine or sertraline, or the -blocker propranolol) under the hypotheses that exposure would increase vulnerability to avian predation via increasing the probability of predator encounter as well as degrading evasive behaviors upon encounter. None of the substances significantly affected swimming activity of the fish, nor did they increase vulnerability by affecting encounter probability or evasive endpoints compared to control treatments. Counter to our expectations, fish exposed to 100 g/L fluoxetine (but no other concentrations or pharmaceuticals) were less likely to enter the open area of the arena, i.e., less likely to engage in risky behavior that could lead to predator encounters. Additionally, all fish exposed to environmentally relevant, low concentrations of sertraline (0.12 g/L) and propranolol (0.1 g/L) sought refuge after the simulated attack. Our unexpected results warrant further research as they have interesting implications on how these psychotropic pharmaceuticals may affect predator-prey interactions spanning the terrestrial-aquatic interface.
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| 7. |
- Muindi, Kanyiva, et al.
(författare)
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Household Air Pollution : Sources and Exposure Levels to Fine Particulate Matter in Nairobi Slums
- 2016
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- With 2.8 billion biomass users globally, household air pollution remains a public health threat in many low- and middle-income countries. However, little evidence on pollution levels and health effects exists in low-income settings, especially slums. This study assesses the levels and sources of household air pollution in the urban slums of Nairobi. This cross-sectional study was embedded in a prospective cohort of pregnant women living in two slum areasKorogocho and Viwandaniin Nairobi. Data on fuel and stove types and ventilation use come from 1058 households, while air quality data based on the particulate matters (PM2.5) level were collected in a sub-sample of 72 households using the DustTrak II Model 8532 monitor. We measured PM2.5 levels mainly during daytime and using sources of indoor air pollutions. The majority of the households used kerosene (69.7%) as a cooking fuel. In households where air quality was monitored, the mean PM2.5 levels were high and varied widely, especially during the evenings (124.6 mu g/m(3) SD: 372.7 in Korogocho and 82.2 mu g/m(3) SD: 249.9 in Viwandani), and in households using charcoal (126.5 mu g/m(3) SD: 434.7 in Korogocho and 75.7 mu g/m(3) SD: 323.0 in Viwandani). Overall, the mean PM2.5 levels measured within homes at both sites (Korogocho = 108.9 mu g/m(3) SD: 371.2; Viwandani = 59.3 mu g/m(3) SD: 234.1) were high. Residents of the two slums are exposed to high levels of PM2.5 in their homes. We recommend interventions, especially those focusing on clean cookstoves and lighting fuels to mitigate indoor levels of fine particles.
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| 8. |
- Reyes-Goya, C, et al.
(författare)
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Mechanism of Vascular Toxicity in Rats Subjected to Treatment with a Tyrosine Kinase Inhibitor
- 2020
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Sunitinib (Su) is a tyrosine kinase inhibitor with antiangiogenic and antineoplastic effects that is recommended therapy for renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. Arterial hypertension is one of the adverse effects observed in the treatment with Su. The aim of this work was to deepen our understanding of the underlying mechanisms involved in the development of this side effect. Studies on endothelial function, vascular remodeling and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) system were carried out in thoracic aortas from rats treated with Su for three weeks. Animals subjected to Su treatment presented with increased blood pressure and reduced endothelium-dependent vasodilation, the latter being reverted by NADPH oxidase blockade. Furthermore, vascular remodeling and stronger Masson trichrome staining, together with enhanced immunofluorescence signal for collagen 1 alpha 1 (Col1α1), were observed in aortas from treated animals. These results were accompanied by a significant elevation in superoxide anion production and the activity/protein/gene expression of NADPH oxidase isoforms (NOX1, NOX2, and NOX4), which was also prevented by NOX inhibition. Furthermore, a decrease in nitric oxide (NO) levels and endothelial nitric oxide synthase (eNOS) activation was observed in aortas from Su-treated animals. All these results indicate that endothelial dysfunction secondary to changes in vascular remodeling and oxidative stress might be responsible for the typical arterial hypertension that develops following treatment with Su.
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| 9. |
- Rylander, L, et al.
(författare)
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Per- and Polyfluoroalkyl Substances in Early Pregnancy and Risk for Preeclampsia: A Case-Control Study in Southern Sweden
- 2020
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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| 10. |
- Shetty, BSP, et al.
(författare)
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Inflammatory Biomarkers Interleukin 1 Beta (IL-1β) and Tumour Necrosis Factor Alpha (TNF-α) Are Differentially Elevated in Tobacco Smoke Associated COPD and Biomass Smoke Associated COPD
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD), the leading cause of mortality and morbidity worldwide, is characterized by abnormal activation of inflammatory cells. The increased pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), further amplify the inflammation. We evaluated the dose response relationship of IL-1β and TNF-α levels and severity of airflow limitation, and differential responses in IL-1β and TNF-α between biomass COPD (BMS-COPD) and tobacco smoke COPD (TS-COPD) using a case control design in 160 subjects. Patients with COPD had higher serum levels of both IL-1β and TNF-α compared to healthy controls. A large difference in TNF-α was observed between TS-COPD and BMS-COPD, where TS-COPD patients had much higher levels. Serum IL-1β levels were higher in BMS-COPD. Levels of IL-1β correlated better with severity of airflow limitation than TNF-α levels. Both TNF-α and IL-1β levels had a negative linear relationship with Forced Expiratory Volume in 1st second (FEV1) and six-minute walk distance. The correlations were stronger with FEV1 than six-minute walk distance. The correlations of TNF-α and IL-1β with St George Respiratory Questionnaire (SGRQ) scores and body mass index (BMI) were not significant. In conclusion, the levels of pro-inflammatory cytokines TNF-α and IL-1β are differently elevated in TS-COPD and BMS-COPD, respectively.
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| 11. |
- Sousa, Pedro F.M. 1977-, et al.
(författare)
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nLossFinder—A Graphical User Interface Program for the Nontargeted Detection of DNA Adducts
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- DNA adductomics is a relatively new omics approach aiming to measure known and unknown DNA modifications, called DNA adducts. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) has become the most common method for analyzing DNA adducts. Recent advances in the field of mass spectrometry have allowed the possibility to perform a comprehensive analysis of adducts, for instance, by using a nontargeted data-independent acquisition method, with multiple precursor m/z windows as an inclusion list. However, the generated data are large and complex, and there is a need to develop algorithms to simplify and automate the time-consuming manual analysis that has hitherto been used. Here, a graphical user interface (GUI) program was developed, with the purpose of tracking a characteristic neutral loss reaction from tandem mass spectrometry of the nucleoside adducts. This program, called nLossFinder, was developed in the MATLAB platform, available as open-source code. Calf thymus DNA was used as a model for method optimization, and the overall adductomics approach was applied to DNA from amphipods (Monoporeia affinis) collected within the Swedish National Marine Monitoring Program. In the amphipod DNA, over 150 putative adducts were found in comparison to 18 using a manual approach in a previous study. The developed program can improve the processing time for large MS data, as it processes each sample in a few seconds, and hence can be applicable for high-throughput screening of adducts.
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| 12. |
- Timmermann, Clara Amalie Gade, et al.
(författare)
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A Review of Dietary Intake of Acrylamide in Humans
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:7
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Forskningsöversikt (refereegranskat)abstract
- The dietary intake of acrylamide (AA) is a health concern, and food is being monitored worldwide, but the extent of AA exposure from the diet is uncertain. The aim of this review was to provide an overview of estimated dietary intake. We performed a PubMed search identifying studies that used dietary questionnaires and recalls to estimate total dietary AA intake. A total of 101 studies were included, corresponding to 68 original study populations from 26 countries. Questionnaires were used in 57 studies, dietary recalls were used in 33 studies, and 11 studies used both methods. The estimated median AA intake ranged from 0.02 to 1.53 mu g/kg body weight/day between studies. Children were represented in 25 studies, and the body-weight-adjusted estimated AA intake was up to three times higher for children than adults. The majority of studies were from Europe (n = 65), Asia (n = 17), and the USA (n = 12). Studies from Asia generally estimated lower intakes than studies from Europe and the USA. Differences in methods undermine direct comparison across studies. The assessment of AA intake through dietary questionnaires and recalls has limitations. The integration of these methods with the analysis of validated biomarkers of exposure/internal dose would improve the accuracy of dietary AA intake exposure estimation. This overview shows that AA exposure is widespread and the large variation across and within populations shows a potential for reduced intake among those with the highest exposure.
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| 13. |
- Uddin, S., et al.
(författare)
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A Preliminary Assessment of Size-Fractionated Microplastics in Indoor Aerosol—Kuwait’s Baseline
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- The omnipresence of microplastic (MP) in various environmental samples, including aer-osols, has raised public health concerns; however, there is presently very limited information on MPs in indoor aerosol. This paper presents a unique dataset where smaller MPs have been sampled using a six-stage cascade impactor from indoor environments in Kuwait. The MP concentration in the indoor air varied between 3.2 and 27.1 particles m−3, and the relative MP concentration decreased linearly from the lowest to the highest size fraction. A significant effect of location was observed for the total number of MPs (F2,14 = 5.80, p = 0.02) and the inhalable fraction (F2,14 = 8.38, p = 0.005), while location had no effect on the respirable fraction (F2,14 = 0.54, p = 0.60). A significant effect of the type of air conditioning used was also observed for the total number of MPs (F2,19 = 5.58, p = 0.01) and the inhalable fraction (F2,19 = 6.45, p = 0.008), while location had no effect on the respirable fraction (F2,19 = 1.30, p = 0.30). For the total number of MPs and the inhalable fraction, the concentration was sig-nificantly higher for the split unit air-conditioning as compared to the central air-conditioning plants. The presence/absence of carpets had no significant effect on the MP concentrations (total: F1,19 = 4.08, p = 0.06; inhalable: F1,19 = 3.03, p = 0.10; respirable: F1,19 = 4.27, p = 0.05). The shape was dominantly fibers, with few fragments in lower size fractions. These datasets represent the first baseline information for Kuwait, and the smaller MPs in all the samples further underscore the need to develop standardized protocols of MP collection in the ≤2.5 µm fraction that can have more con-spicuous health implications. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 14. |
- Veerapaneni, VV, et al.
(författare)
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Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease
- 2021
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study (n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air–liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly (p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3–2.4) and TS-COPD (1.8; 1.4–2.5) subjects compared to TS-CONTROL (3.3; 2.9–3.5) and healthy controls (5.1; 4.5–7.2). The levels of SCGB1A1 were positively correlated (r = 0.7–0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly (p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly (p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.
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| 15. |
- Zeiner, Michaela, 1973-, et al.
(författare)
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Harmful Elements (Al, Cd, Cr, Ni, and Pb) in Wild Berries and Fruits Collected in Croatia
- 2018
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Fruits and vegetables are considered a beneficial contribution to the human diet. Especially, berries contain a great deal of bioactive compounds, such as anthocyanins, organic acids, tannins, phenols, and antioxidants. Apart from organic substances, inorganic nutrients are also present in fruits. Some metals and metalloids are essential for humans, whilst others may exhibit harmful effects. Wild grown berries, collected in so-called unpolluted areas, are considered to be free of any potentially toxic ingredients. However, due to transmission processes pollutants can also reach remote areas and, furthermore, metal uptake from the soil via roots has to be taken into account. Thus, the presented study focused on the determination of Al, Cd, Cr, Ni, and Pb in lingonberries, blueberries, and rose hips collected in a non-polluted area in Croatia. Neither Cd nor Cr could be found in any sample. Ni levels were mainly up to 25 mg/kg, in a comparable range to the literature data. No health threat is to be expected by eating these fruits and berries regarding Cd, Cr, and Ni. Rose hips, however, contain Pb beyond the stipulated limit in fruits, and also Al is present at a high level (8 mg/g).
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| 16. |
- Zurita, Javier, et al.
(författare)
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Detection of Benzo[a]pyrene Diol Epoxide Adducts to Histidine and Lysine in Serum Albumin In Vivo by High-Resolution-Tandem Mass Spectrometry
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons (PAHs). The exposure of humans to this PAH can be assessed by measuring stable blood protein adducts, such as to histidine and lysine in serum albumin, from their reactive metabolites. In this respect, measurement of the adducts originating from the genotoxic (+)-anti-benzo[a]pyrene diol epoxide is of interest. However, these are difficult to measure at such low levels as are expected in humans generally exposed to benzo[a]pyrene from air pollution and the diet. The analytical methods detecting PAH-biomarkers still suffer from low selectivity and/or detectability to enable generation of data for calculation of in vivo doses of specific stereoisomers, for evaluation of risk factors and assessing risk from exposures to PAH. Here, we suggest an analytical methodology based on high-pressure liquid chromatography (HPLC) coupled to high-resolution tandem mass spectrometry (MS) to lower the detection limits as well as to increase the selectivity with improvements in both chromatographic separation and mass determination. Method development was performed using serum albumin alkylated in vitro by benzo[a]pyrene diol epoxide isomers. The (+)-anti-benzo[a]pyrene diol epoxide adducts could be chromatographically resolved by using an HPLC column with a pentafluorophenyl stationary phase. Interferences were further diminished by the high mass accuracy and resolving power of Orbitrap MS. The achieved method detection limit for the (+)-anti-benzo[a]pyrene diol epoxide adduct to histidine was approximately 4 amol/mg serum albumin. This adduct as well as the adducts to histidine from (−)-anti- and (+/−)-syn-benzo[a]pyrene diol epoxide were quantified in the samples from benzo[a]pyrene-exposed mice. Corresponding adducts to lysine were also quantified. In human serum albumin, the anti-benzo[a]pyrene diol epoxide adducts to histidine were detected in only two out of twelve samples and at a level of approximately 0.1 fmol/mg.
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| 17. |
- Al Naggar, Yahya, et al.
(författare)
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Chronic Exposure to Polystyrene Microplastic Fragments Has No Effect on Honey Bee Survival, but Reduces Feeding Rate and Body Weight
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Microplastics (MPs), in the form of fragments and fibers, were recently found in honey samples collected in Ecuador as well as in honey bees collected from Denmark and China. However, little is known about how MPs impact bee health. To fill this knowledge gap, we investigated the potential toxicity of irregularly shaped polystyrene (PS)-MP fragments on honey bee health. In the first experiment of its kind with honey bees, we chronically exposed bees with a well-established gut microbiome to small (27 ± 17 µm) or large (93 ± 25 µm) PS-MP fragments at varying concentrations (1, 10, 100 µg mL−1) for 14 days. Bee mortality, food consumption, and body weight were all studied. We found that chronic exposure to PS-MP fragments has no effect on honey bee survival, but reduced the feeding rate and body weight, particularly at 10 µg PS-MP fragments per mL, which may have long-term consequences for honey bee health. The findings of this study could assist in the risk assessment of MPs on pollinator health.
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| 18. |
- Behbehani, M., et al.
(författare)
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Ocean Acidification-Mediated Food Chain Transfer of Polonium between Primary Producers and Consumers
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Phytoplankton and zooplankton are key marine components that play an important role in metal distribution through a food web transfer. An increased phytoplankton concentration as a result of ocean acidification and warming are well-established, along with the fact that phytoplankton biomagnify Po-210 by 3-4 orders of magnitude compared to the seawater concentration. This experimental study is carried out to better understand the transfer of polonium between primary producers and consumers. The experimental produced data highlight the complex interaction between the polonium concentration in zooplankton food, i.e. phytoplankton, its excretion via defecated fecal pellets, and its bioaccumulation at ambient seawater pH and a lower pH of 7.7, typical of ocean acidification scenarios in the open ocean. The mass of copepods recovered was 11% less: 7.7 pH compared to 8.2. The effects of copepod species (n = 3), microalgae species (n = 3), pH (n = 2), and time (n = 4) on the polonium activity in the fecal pellets (expressed as % of the total activity introduced through feeding) was tested using an ANOVA 4. With the exception of time (model: F-20,F- 215 = 176.84, p < 0.001; time: F-3 = 1.76, p = 0.16), all tested parameters had an impact on the polonium activity (copepod species: F-2 = 169.15, p < 0.0001; algae species: F-2 = 10.21, p < 0.0001; pH: F-1 = 9.85, p = 0.002) with complex interactions (copepod x algae: F-2 = 19.48, p < 0.0001; copepod x pH: F-2 = 10.54, p < 0.0001; algae x pH: F-2 = 4.87, p = 0.009). The experimental data underpin the hypothesis that metal bioavailability and bioaccumulation will be enhanced in secondary consumers such as crustacean zooplankton due to ocean acidification.
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| 19. |
- Branco, V, et al.
(författare)
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N-Acetylcysteine or Sodium Selenite Prevent the p38-Mediated Production of Proinflammatory Cytokines by Microglia during Exposure to Mercury (II)
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is known for its neurotoxicity and is reported to activate microglia cells at low exposure levels. Since mercury decreases the activity of the glutathione and thioredoxin systems, we hypothesize that Hg would, in turn, disrupt microglia homeostasis by interfering with redox regulation of signaling pathways. Thus, in this work, we analyzed the effect of exposure to Hg2+ on nuclear translocation and activation of NF-kB (p50) and p38 and pro-inflammatory gene transcription (IL-1ß; iNOS, TNF-alpha) considering the interaction of Hg with the glutathione system and thioredoxin systems in microglial cells. N9 (mouse) microglia cells were exposed to different concentrations of Hg2+ and the 24 h EC50 for a reduction in viability was 42.1 ± 3.7 μM. Subsequent experiments showed that at sub-cytotoxic levels of Hg2+, there was a general increase in ROS (≈40%) accompanied by a significant depletion (60–90%) of glutathione (GSH) and thioredoxin reductase (TrxR) activity. Upon 6 h of exposure to Hg2+, p38 (but not p50) accumulated in the nucleus (50% higher than in control), which was accompanied by an increase in its phosphorylation. Transcript levels of both IL1-ß and iNOS were increased over two-fold relative to the control. Furthermore, pre-exposure of cells to the p38 inhibitor SB 239063 hindered the activation of cytokine transcription by Hg2+. These results show that disruption of redox systems by Hg2+ prompts the activation of p38 leading to transcription of pro-inflammatory genes in microglia cells. Treatment of N9 cells with NAC or sodium selenite—which caused an increase in basal GSH and TrxR levels, respectively, prevented the activation of p38 and the transcription of pro-inflammatory cytokines. This result demonstrates the importance of an adequate nutritional status to minimize the toxicity resulting from Hg exposure in human populations at risk.
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| 20. |
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| 21. |
- Erdei, Anna Laura
(författare)
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The Comparative Toxicity, Biochemical and Physiological Impacts of Chlorantraniliprole and Indoxacarb on Mamestra brassicae (Lepidoptera: Noctuidae)
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The cabbage moth, Mamestra brassicae, is a polyphagous pest that attacks several crops. Here, the sublethal and lethal effects of chlorantraniliprole and indoxacarb were investigated on the developmental stages, detoxification enzymes, reproductive activity, calling behavior, peripheral physiology, and pheromone titer of M. brasssicae. Methods: To assess pesticide effects, the second instar larvae were maintained for 24 h on a semi-artificial diet containing insecticides at their LC10, LC30, and LC50 concentrations. Results: M. brassicae was more susceptible to chlorantraniliprole (LC50 = 0.35 mg/L) than indoxacarb (LC50 = 1.71 mg/L). A significantly increased developmental time was observed with both insecticides at all tested concentrations but decreases in pupation rate, pupal weight, and emergence were limited to the LC50 concentration. Reductions in both the total number of eggs laid per female and the egg viability were observed with both insecticides at their LC30 and LC50 concentrations. Both female calling activity and the sex pheromone (Z11-hexadecenyl acetate and hexadecenyl acetate) titer were significantly reduced by chlorantraniliprole in LC50 concentration. Antennal responses of female antennae to benzaldehyde and 3-octanone were significantly weaker than controls after exposure to the indoxocarb LC50 concentration. Significant reductions in the enzymatic activity of glutathione S-transferases, mixed-function oxidases, and carboxylesterases were observed in response to both insecticides.
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| 22. |
- Lagerlöf, Jan
(författare)
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Commercial Fungicide Toxic Effects on Terrestrial Non-Target Species Might Be Underestimated When Based Solely on Active Ingredient Toxicity and Standard Earthworm Tests
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The ecosystem services provided by earthworms are lost when land management reduces their populations, hence, the importance of thorough assessments of management effects on this group. The present study aimed to: (1) review the possible influence of other ingredients within the formulations of two commercial fungicides; (2) assess the sublethal effects of these commercial fungicides on Eisenia fetida; and (3) assess the acute lethal effects of one commercial fungicide on both Glossoscolex none and E. fetida. Examining all components of the studied commercial formulations revealed that alongside the toxic active ingredients are other ingredients that are equally as or more toxic than the former and may even be in higher concentrations. The inhibition concentration of 10% of E. fetida's progeny (IC10) was estimated at 133 mg kg(-1) for PROSARO (R) and 1544 mg kg(-1) for SWING PLUS (R). Both fungicides showed an effect of hormesis on the progeny. In this first toxicity study with G. nione, it was found that this species is more sensitive to PROSARO (R) than E. fetida, with preliminary 14 day-lethal concentrations of 285 mg kg(-1) for the former and >1000 mg kg(-1) for the latter.
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| 23. |
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| 24. |
- Lizano Fallas, Veronica, et al.
(författare)
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Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- The impact of exposure to multiple chemicals raises concerns for human and environmental health. The adverse outcome pathway method offers a framework to support mechanism-based assessment in environmental health starting by describing which mechanisms are triggered upon interaction with different stressors. The identification of the molecular initiating event and the molecular interaction between a chemical and a protein target is still a challenge for the development of adverse outcome pathways. The cellular response to chemical exposure studied with omics could not directly identify the protein targets. However, recent mass spectrometry-based methods are offering a proteome-wide identification of protein targets interacting with s but unrevealing a molecular initiating event from a set of targets is still dependent on available knowledge. Here, we directly coupled the target identification findings from the proteome integral solubility alteration assay with an analytical hierarchy process for the prediction of a prioritized molecular initiating event. We demonstrate the applicability of this combination of methodologies with a test compound (TCDD), and it could be further studied and integrated into AOPs. From the eight protein targets identified by the proteome integral solubility alteration assay after analyzing 2824 human hepatic proteins, the analytical hierarchy process can select the most suitable protein for an AOP. Our combined method solves the missing links between high-throughput target identification and prediction of the molecular initiating event. We anticipate its utility to decipher new molecular initiating events and support more sustainable methodologies to gain time and resources in chemical assessment.
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| 25. |
- Malm, Ellen, et al.
(författare)
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Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden
- 2023
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Ingår i: Toxics. - 2305-6304. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Small for gestational age (SGA) is considered an adverse birth outcome. Per- and polyfluoralkyl substances (PFAS) have become increasingly investigated as contributing environmental factors, thus far with inconclusive results. The current study aimed to investigate the hypothesized association between increased maternal PFAS levels in early pregnancy and an increased risk for SGA birth. This population-based study used data from a sample of children born in Scania, Southern Sweden, between 1995 and 2009. Two groups were compared: cases born with SGA (n = 298) and non-SGA controls (n = 580). The cases consisted of two subgroups: one included women whose children’s growth in late pregnancy was in the lowest quartile, and another included women from the remaining growth quartiles. Corresponding maternal serum samples were collected from a biobank and analyzed for concentrations of four types of PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) using liquid chromatography–tandem mass spectrometry (LC/MS/MS). The results were combined with information from birth registers and analyzed using Mann–Whitney U-tests and logistic regression—unadjusted as well as adjusted for potential confounders. In conclusion, elevated maternal concentrations of PFAS were not associated with an increased risk of SGA birth. However, significant ORs were observed in a subgroup analysis restricted to women of Nordic origin (unadjusted OR 3.2 and adjusted OR 2.4) for PFHxS.
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| 26. |
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| 27. |
- Olstrup, Henrik, et al.
(författare)
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The Long-Term Mortality Effects Associated with Exposure to Particles and NOx in the Malmö Diet and Cancer Cohort
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the long-term mortality effects associated with exposure to PM10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NOx (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM10, PM2.5, BC, and NOx at the cohort participants’ home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM10, PM2.5, BC, and NOx and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1–5 years (lag1–5), and 6–10 years (lag6–10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM10, PM2.5, BC, and NOx in the single-pollutant models at lag1–5 were 1.06 (95% CI: 1.02–1.11), 1.01 (95% CI: 0.95–1.08), 1.07 (95% CI: 1.04–1.11), and 1.11 (95% CI: 1.07–1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NOx, with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.
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| 28. |
- Pennoyer, Emily H., et al.
(författare)
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Unknown Organofluorine Mixtures in U.S. Adult Serum : Contribution from Pharmaceuticals?
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: -1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.
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| 29. |
- Poteser, M, et al.
(författare)
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Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies
- 2022
-
Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.
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| 30. |
- Poteser, M, et al.
(författare)
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Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000-2021)
- 2022
-
Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.
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| 31. |
- Rahman, Mizanur, et al.
(författare)
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Comparable response following exposure to biodiesel and diesel exhaust particles in advanced multicellular human lung models
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air–liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects.
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| 32. |
- Rylander, Lars, et al.
(författare)
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Per-and polyfluoroalkyl substances in early pregnancy and risk for preeclampsia : A case-control study in southern Sweden
- 2020
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Ingår i: Toxics. - 2305-6304. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most common causes of perinatal and maternal morbidity/ mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per-and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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| 33. |
- Sapounidou, Maria, et al.
(författare)
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From Cohort to Cohort : A Similar Mixture Approach (SMACH) to Evaluate Exposures to a Mixture Leading to Thyroid-Mediated Neurodevelopmental Effects Using NHANES Data
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:4
-
Tidskriftsartikel (refereegranskat)abstract
- Prenatal exposure to a mixture (MIX N) of eight endocrine-disrupting chemicals has been associated with language delay in children in a Swedish pregnancy cohort. A novel approach was proposed linking this epidemiological association with experimental evidence, where the effect of MIX N on thyroid hormone signaling was assessed using the Xenopus eleuthero-embryonic thyroid assay (XETA OECD TG248). From this experimental data, a point of departure (PoD) was derived based on OECD guidance. Our aim in the current study was to use updated toxicokinetic models to compare exposures of women of reproductive age in the US population to MIX N using a Similar Mixture Approach (SMACH). Based on our findings, 66% of women of reproductive age in the US (roughly 38 million women) had exposures sufficiently similar to MIX N. For this subset, a Similar Mixture Risk Index (SMRIHI) was calculated comparing their exposures to the PoD. Women with SMRIHI > 1 represent 1.1 million women of reproductive age. Older women, Mexican American and other/multi race women were less likely to have high SMRIHI values compared to Non-Hispanic White women. These findings indicate that a reference mixture of chemicals identified in a Swedish cohort—and tested in an experimental model for establishment of (PoDs)—is also of health relevance in a US population.
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| 34. |
- Sherif, Moustafa, et al.
(författare)
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Genotoxicity of Occupational Pesticide Exposures among Agricultural Workers in Arab Countries : A Systematic Review and Meta-Analysis
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:8
-
Forskningsöversikt (refereegranskat)abstract
- Exposure to pesticides in Arab countries is a significant public health concern due to extensive agricultural activity and pesticide use. This systematic review aimed to evaluate the genotoxic effects of agricultural pesticide exposure in the region, identify research gaps, and assess methodological limitations. Following the PRISMA guidelines, a comprehensive search yielded five relevant studies conducted in Egypt, Syria, and Jordan. Various genotoxicity assays were employed, revealing a higher level of DNA damage in exposed compared to non-exposed individuals. Farmers exposed to pesticides exhibited a significantly higher occurrence of chromosomal translocation (t(14;18)), micronuclei, and chromosomal aberrations. However, only two studies assessed cytotoxicity indirectly. The studies predominantly focused on male participants, with variations in sample size and pesticide types. The lack of detailed exposure data necessitates cautious interpretation. This review underscores the need for further research on the genotoxicity of occupational pesticide exposure in the Middle East. Future studies should adopt robust study designs, collect biological and environmental samples, conduct repeated sampling, analyze seasonal variations, and encompass diverse study sites associated with specific crop groups.
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| 35. |
- Spörndly-Nees, Ellinor, et al.
(författare)
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Basic Exploratory Study of Bisphenol A (BPA) Dietary Administration to Istrian Pramenka Rams and Male Toxicity Investigation
- 2022
-
Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA), an endocrine-disrupting chemical and environmental pollutant, has been reported by many researchers to induce male reproductive toxicity in different experimental models. In this study, we investigated whether long-term exposure for two months to 25 mu g/kg body weight (low dose) of BPA affects spermatogenesis or sperm quality in young Istrian Pramenka rams exposed via diet. We evaluated body and testicular weights, histopathology of testes and epididymides, and sperm analyses, and compared these parameters between the group of treated rams and the control group of rams. Although there were some differences between the two groups, these differences were not large or statistically significant. The only statistically significant difference was the lower epithelial height of seminiferous tubules in treated rams, compared to control rams. In addition to assessing toxicity, BPA concentrations in the blood plasma of treated rams were determined after the first administration, and the toxicokinetic parameters of total BPA were calculated. In this study, no major signs of altered reproduction in rams were detected.
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| 36. |
- Tarazona, Jose V., et al.
(författare)
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Improving the Risk Assessment of Pesticides through the Integration of Human Biomonitoring and Food Monitoring Data : A Case Study for Chlorpyrifos
- 2022
-
Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food con-sumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers’ exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer’s internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.
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| 37. |
- Tornevi, Andreas, et al.
(författare)
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Short-Term Associations between PM10 and Respiratory Health Effects in Visby, Sweden
- 2022
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- The old Swedish city Visby, located on the island Gotland, has, for several years, reported higher PM10 concentrations than any other city in Sweden. In Visby, local limestone is used, both in road paving and as sand used for anti-slip measures, resulting in a clear annual pattern of PM10 with the highest concentrations during winter/spring when studded tires are allowed. This study analyzes the short-term associations between PM10 and daily number of patients with acute respiratory problems (ICD-10 diagnoses: J00-J99) seeking care at the hospital or primary healthcare units in Visby during the period of 2013-2019. The daily mean of PM10 was on average 45 µg m-3 during winter/spring and 18 µg m-3 during summer/autumn. Four outcome categories were analyzed using quasi-Poisson regression models, stratifying for period and adjusting for calendar variables and weather. An increase in respiratory visits was associated with increasing concentrations in PM10 during the summer/autumn period, most prominent among children, where asthma visits increased by 5% (95% CI: 2-9%) per 10 µg m-3 increase in PM10. For the winter/spring period, no significant effects were observed, except for the diagnose group 'upper airways' in adults, where respiratory visits increased by 1% (95% CI: 0.1-1.9%) per 10 µg m-3 increase. According to the results, limestone in particles seem to be relatively harmless at the exposure concentrations observed in Visby, and this is in line with the results from a few experimental and occupational studies.
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| 38. |
- Turkez, Hasan, et al.
(författare)
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Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity : In Vitro and In Vivo Study
- 2022
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.
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| 39. |
- Ullah, MK, et al.
(författare)
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Impact of Acute Exacerbation and Its Phenotypes on the Clinical Outcomes of Chronic Obstructive Pulmonary Disease in Hospitalized Patients: A Cross-Sectional Study
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Acute exacerbations of COPD (AECOPD) are clinically significant events having therapeutic and prognostic consequences. However, there is a lot of variation in its clinical manifestations described by phenotypes. The phenotypes of AECOPD were categorized in this study based on pathology and exposure. In our cross-sectional study, conducted between 1 January 2016 to 31 December 2020, the patients were categorized into six groups based on pathology: non-bacterial and non-eosinophilic; bacterial; eosinophilic; bacterial infection with eosinophilia; pneumonia; and bronchiectasis. Further, four groups were classified based on exposure to tobacco smoke (TS), biomass smoke (BMS), both, or no exposure. Cox proportional-hazards regression analyses were performed to assess hazard ratios, and Kaplan–Meier analysis was performed to assess survival, which was then compared using the log-rank test. The odds ratio (OR) and independent predictors of ward admission type and length of hospital stay were assessed using binomial logistic regression analyses. Of the 2236 subjects, 2194 were selected. The median age of the cohort was 67.0 (60.0 to 74.0) and 75.2% were males. Mortality rates were higher in females than in males (6.2% vs. 2.3%). AECOPD-B (bacterial infection) subjects [HR 95% CI 6.42 (3.06–13.46)], followed by AECOPD-P (pneumonia) subjects [HR (95% CI: 4.33 (2.01–9.30)], were at higher mortality risk and had a more extended hospital stay (6.0 (4.0 to 9.5) days; 6.0 (4.0 to 10.0). Subjects with TS and BMS-AECOPD [HR 95% CI 7.24 (1.53–34.29)], followed by BMS-AECOPD [HR 95% CI 5.28 (2.46–11.35)], had higher mortality risk. Different phenotypes have different impacts on AECOPD clinical outcomes. A better understanding of AECOPD phenotypes could contribute to developing an algorithm for the precise management of different phenotypes.
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| 40. |
- Upadhyay, S, et al.
(författare)
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Establishment of Repeated In Vitro Exposure System for Evaluating Pulmonary Toxicity of Representative Criteria Air Pollutants Using Advanced Bronchial Mucosa Models
- 2022
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- There is mounting evidence that shows the association between chronic exposure to air pollutants (particulate matter and gaseous) and onset of various respiratory impairments. However, the corresponding toxicological mechanisms of mixed exposure are poorly understood. Therefore, in this study, we aimed to establish a repeated exposure setting for evaluating the pulmonary toxicological effects of diesel exhaust particles (DEP), nitrogen dioxide (NO2), and sulfur dioxide (SO2) as representative criterial air pollutants. Single, combined (DEP with NO2 and SO2), and repeated exposures were performed using physiologically relevant human bronchial mucosa models developed at the air–liquid interface (bro-ALI). The bro-ALI models were generated using human primary bronchial epithelial cells (3–4 donors; 2 replicates per donor). The exposure regime included the following: 1. DEP (12.5 µg/cm2; 3 min/day, 3 days); 2. low gaseous (NO2: 0.1 ppm + SO2: 0.2 ppm); (30 min/day, 3 days); 3. high gaseous (NO2: 0.2 ppm + SO2: 0.4 ppm) (30 min/day, 3 days); and 4. single combined (DEP + low gaseous for 1 day). The markers for pro-inflammatory (IL8, IL6, NFKB, TNF), oxidative stress (HMOX1, GSTA1, SOD3,) and tissue injury/repair (MMP9, TIMP1) responses were assessed at transcriptional and/ or secreted protein levels following exposure. The corresponding sham-exposed samples under identical conditions served as the control. A non-parametric statistical analysis was performed and p < 0.05 was considered as significant. Repeated exposure to DEP and single combined (DEP + low gaseous) exposure showed significant alteration in the pro-inflammatory, oxidative stress and tissue injury responses compared to repeated exposures to gaseous air pollutants. The study demonstrates that it is feasible to predict the long-term effects of air pollutants using the above explained exposure system.
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| 41. |
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| 42. |
- Vogel, N, et al.
(författare)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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| 43. |
- Vogel, N, et al.
(författare)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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