| 1. |
- Arlt, Volker M., et al.
(författare)
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Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone
- 2017
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 91:4, s. 1957-1975
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1-SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1(−/−) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3-nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AAI-/AAII-DNA adduct formation in Sult1a1(−/−) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2, Sult1a1(−/−) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation.
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| 2. |
- Bondarenko, Olesja M., et al.
(författare)
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Current challenges and coming opportunities in nanoparticle risk assessment
- 2020
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Ingår i: Colloids for Nanobiotechnology : Synthesis, Characterization and Potential Applications - Synthesis, Characterization and Potential Applications. - 1876-276X .- 1876-2778. - 9780081028285 ; 16, s. 353-371
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Bokkapitel (refereegranskat)abstract
- This chapter discusses the key aspects of engineered nanomaterial (ENM) toxicity. The individual properties of ENMs affecting their toxic potential are described, with a special focus on size, shape, and surface charge and functionalization. We present empirical evidence from a range of in vitro and in vivo studies showing potential adverse effects induced via inhalation, ingestion, or skin contact with ENMs, as well as a brief overview of human studies and nanoecotoxicology. Finally, a summary of current guidelines and frameworks is provided, together with a collection of the most prominent nanosafety projects and resources available for the assessment of nanotoxicity. This literature review demonstrates that there is a need for the collection of standardized data from human studies to inform epidemiological studies. Moreover, despite the wide usage of ENMs and reported toxic potentials, there is a shortage of policies regulating the exposure and usage of ENMs to protect both the environment and human health.
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| 3. |
- Gorrochategui, Eva, et al.
(författare)
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High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring
- 2023
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Ingår i: Environment International. - 0160-4120. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.
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| 4. |
- Gren, Louise, et al.
(författare)
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Effect of renewable fuels and intake O2 concentration on diesel engine emission characteristics and reactive oxygen species (ROS) formation
- 2020
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Ingår i: Atmosphere. - : MDPI AG. - 2073-4433. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Renewable diesel fuels have the potential to reduce net CO2 emissions, and simultaneously decrease particulate matter (PM) emissions. This study characterized engine-out PM emissions and PM-induced reactive oxygen species (ROS) formation potential. Emissions from a modern heavy-duty diesel engine without external aftertreatment devices, and fueled with petroleum diesel, hydrotreated vegetable oil (HVO) or rapeseed methyl ester (RME) biodiesel were studied. Exhaust gas recirculation (EGR) allowed us to probe the effect of air intake O2 concentration, and thereby combustion temperature, on emissions and ROS formation potential. An increasing level of EGR (decreasing O2 concentration) resulted in a general increase of equivalent black carbon (eBC) emissions and decrease of NOx emissions. At a medium level of EGR (13% intake O2), eBC emissions were reduced for HVO and RME by 30 and 54% respectively compared to petroleum diesel. In general, substantially lower emissions of polycyclic aromatic hydrocarbons (PAHs), including nitro and oxy-PAHs, were observed for RME compared to both HVO and diesel. At low-temperature combustion (LTC, O2 < 10%), CO and hydrocarbon gas emissions increased and an increased fraction of refractory organic carbon and PAHs were found in the particle phase. These altered soot properties have implications for the design of aftertreatment systems and diesel PM measurements with optical techniques. The ROS formation potential per mass of particles increased with increasing engine O2 concentration intake. We hypothesize that this is because soot surface properties evolve with the combustion temperature and become more active as the soot matures into refractory BC, and secondly as the soot surface becomes altered by surface oxidation. At 13% intake O2, the ROS-producing ability was high and of similar magnitude per mass for all fuels. When normalizing by energy output, the lowered emissions for the renewable fuels led to a reduced ROS formation potential.
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| 5. |
- Krais, Annette M., et al.
(författare)
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Carcinogen-DNA Adducts
- 2019. - Third Edition
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Ingår i: Encyclopedia of Cancer. - 9780128124857 ; , s. 282-295
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Bokkapitel (refereegranskat)abstract
- Carcinogen-DNA adducts result from the covalent interaction of electrophilic chemical carcinogens with nucleophilic sites in DNA. Some highly reactive genotoxic carcinogens are capable of directly binding to DNA but most carcinogens require metabolic activation. DNA adducts, if not repaired, can lead to mutations, and mutations in critical genes are a characteristic feature of tumors. Thus DNA adduct formation is considered a critical step in the initiation of carcinogenesis. DNA adducts formed in human tissues can be detected by a variety of sensitive techniques including 32P-postlabeling, mass spectrometry, accelerator mass spectrometry, and immunoassays. Their detection and characterization in human tissues can provide clues on the etiology of human cancer.
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| 6. |
- Krais, Annette, et al.
(författare)
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Metabolic activation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and DNA adduct formation depends on p53: Studies in Trp53(+/+),Trp53(+/-) and Trp53(-/-) mice.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136.
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Tidskriftsartikel (refereegranskat)abstract
- The expression of the tumor suppressor p53 can influence the bioactivation of, and DNA damage induced by, the environmental carcinogen benzo[a]pyrene, indicating a role for p53 in its cytochrome P450 (CYP)-mediated biotransformation. The carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is formed during the cooking of food, is also metabolically activated by CYP enzymes, particularly CYP1A2. We investigated the potential role of p53 in PhIP metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with a single oral dose of 50 mg/kg body weight PhIP. N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP-C8-dG) levels in DNA, measured by liquid chromatography-tandem mass spectrometry, were significantly lower in liver, colon, forestomach and glandular stomach of Trp53(-/-) mice compared to Trp53(+/+) mice. Lower PhIP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with lower Cyp1a2 enzyme activity (measured by methoxyresorufin-O-demethylase activity) in these animals. Interestingly, PhIP-DNA adduct levels were significantly higher in kidney and bladder of Trp53(-/-) mice compared to Trp53(+/+) mice, which was accompanied by higher sulfotransferase (Sult) 1a1 protein levels and increased Sult1a1 enzyme activity (measured by 2-naphthylsulfate formation from 2-naphthol) in kidneys of these animals. Our study demonstrates a role for p53 in the metabolism of PhIP in vivo, extending previous results on a novel role for p53 in xenobiotic metabolism. Our results also indicate that the impact of p53 on PhIP biotransformation is tissue-dependent and that in addition to Cyp1a enzymes, Sult1a1 can contribute to PhIP-DNA adduct formation.
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| 7. |
- Li, Li, et al.
(författare)
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Characterization of residential household dust from Shanghai by particle size and analysis of organophosphorus flame retardants and metals
- 2019
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Physical and biological properties of dust particles might affect the availability and distribution of chemicals associated to indoor dust; however it has not been adequately examined. In this study, household dust from Shanghai was fractionated into five particle sizes and size distribution, morphology, surface area, organic matter, microorganisms, elemental composition, metals and organophosphorus flame retardants (OPFRs) compositions were characterized. Also, household dust samples from Stockholm that has previously been characterized were included in the analysis of OPFRs for comparison.Results: The respirable fraction had a yield of 3.3% in mass percentage, with a particle size of 2.22 +/- 2.04 mu m. As expected, both metals and OPFRs concentrations increased with decreased particle size. Al and Fe dominated (66-87%) followed by the concentrations of Zn (5-14%) and Ga (1.8-5%) of the sum of 16 metals in the dust. The concentrations of OPFRs in Shanghai dust ranged from 5.34 to 13.7 mu g/g (median: 7.21 mu g/g), compared to household dust from Stockholm that ranged from 16.0 to 28.3 mu g/g (median: 26.6 mu g/g). Tris(2-chloroisopropyl) phosphate (TCIPP) and tris(2-chloroethyl) phosphate (TCEP) dominated in Shanghai dust samples while tris(2-butoxyethyl) phosphate (TBOEP) dominated in dust from Stockholm homes.Conclusion: The results showed that mass percentage for each particle size fraction was not evenly distributed. Furthermore, the particle-bound microorganisms and OPFRs increased with decreased particle size, whereas metals had the highest concentrations at specific dust sizes. Therefore, it is essential to select the proper particle size in order to assess any specific human exposure study to indoor pollutants.
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| 8. |
- McCarrick, Sarah, et al.
(författare)
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Toxicity of particles derived from combustion of Ethiopian traditional biomass fuels in human bronchial and macrophage-like cells
- 2024
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Ingår i: Archives of Toxicology. - 0340-5761. ; 98:5, s. 1515-1532
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Tidskriftsartikel (refereegranskat)abstract
- The combustion of traditional fuels in low-income countries, including those in sub-Saharan Africa, leads to extensive indoor particle exposure. Yet, the related health consequences in this context are understudied. This study aimed to evaluate the in vitro toxicity of combustion-derived particles relevant for Sub-Saharan household environments. Particles (< 2.5 µm) were collected using a high-volume sampler during combustion of traditional Ethiopian biomass fuels: cow dung, eucalyptus wood and eucalyptus charcoal. Diesel exhaust particles (DEP, NIST 2975) served as reference particles. The highest levels of particle-bound polycyclic aromatic hydrocarbons (PAHs) were found in wood (3219 ng/mg), followed by dung (618 ng/mg), charcoal (136 ng/mg) and DEP (118 ng/mg) (GC–MS). BEAS-2B bronchial epithelial cells and THP-1 derived macrophages were exposed to particle suspensions (1–150 µg/mL) for 24 h. All particles induced concentration-dependent genotoxicity (comet assay) but no pro-inflammatory cytokine release in epithelial cells, whereas dung and wood particles also induced concentration-dependent cytotoxicity (Alamar Blue). Only wood particles induced concentration-dependent cytotoxicity and genotoxicity in macrophage-like cells, while dung particles were unique at increasing secretion of pro-inflammatory cytokines (IL-6, IL-8, TNF-α). In summary, particles derived from combustion of less energy dense fuels like dung and wood had a higher PAH content and were more cytotoxic in epithelial cells. In addition, the least energy dense and cheapest fuel, dung, also induced pro-inflammatory effects in macrophage-like cells. These findings highlight the influence of fuel type on the toxic profile of the emitted particles and warrant further research to understand and mitigate health effects of indoor air pollution.
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| 9. |
- Weiss, Jana M., et al.
(författare)
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Daily intake of phthalates, MEHP, and DINCH by ingestion and inhalation
- 2018
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 208, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters, suspected endocrine disrupting chemicals, are used in a wide range of applications. Because phthalate esters are not covalently bound, they can easily leach into the indoor environment and associate to dust particles. Thus, exposure may occur through inhalation, ingestion, or contact with the skin. However, it is unclear to what degree indoor dust contributes to the daily intake of phthalate esters.This study investigates household dust as an exposure pathway for seven phthalate esters, the monoester MEHP, and the plasticizer DINCH. Household dust collected from children's sleeping rooms and from living rooms were analysed using gas and liquid chromatography tandem mass spectrometry. To compare two exposure pathways, different dust particle sizes were generated: a respirable fraction (<5 mu m) and an ingested particle fraction in the anticipated size range of skin adherence (<75 mu m). Modelling of dust inhalation and ingestion showed that the daily intake of dust-bound phthalate esters was likely to be 2 times (inhalation) to 12 times (ingestion) higher for 21-month-old children than for adults. These children's daily uptake of phthalate esters was 40-140 times higher through ingestion than inhalation. Furthermore, dust may be an exposure pathway for phthalate esters as well as for MEHP. Therefore, phthalate monoesters could be environmental contaminants of their own and need to be considered in health risk assessments. (C) 2018 Elsevier Ltd. All rights reserved.
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| 10. |
- Alhamdow, Ayman, et al.
(författare)
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DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
- 2018
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 39:7, s. 869-878
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Tidskriftsartikel (refereegranskat)abstract
- Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.
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| 11. |
- Alhamdow, Ayman, et al.
(författare)
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Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
- 2020
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2. Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
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| 12. |
- Alhamdow, Ayman, et al.
(författare)
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Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
- 2021
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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| 13. |
- Andersen, Christina, et al.
(författare)
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Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
- 2018
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Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
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Konferensbidrag (refereegranskat)abstract
- We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
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| 14. |
- Bendtsen, Katja Maria, et al.
(författare)
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Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
- 2020
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Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black. RESULTS: Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m2/g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 μg/mg) and acid-extractable metal content (0.9-16 μg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS. CONCLUSIONS: We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.
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| 15. |
- De Loma, Jessica, et al.
(författare)
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Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia
- 2022
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women living in the Bolivian Andes are environmentally exposed to arsenic, yet there is scarce information about arsenic-related effects in this region. Several biomarkers for telomere length and oxidative stress (mitochondrial DNA copy number, mtDNAcn; 8-Oxo-2'-deoxyguanosine, 8-oxo-dG; and 4-hydroxy nonenal mercapturic acid, 4-HNE-MA) have been previously linked to arsenic, and some of which are prospective biomarkers for cancer risk.OBJECTIVE AND HYPOTHESIS: To evaluate associations between arsenic exposure and telomere length, mtDNAcn, 8-oxo-dG, and 4-HNE-MA in Bolivians. Arsenic exposure was hypothesized to be positively associated with all four toxicity biomarkers, particularly in individuals with a less efficient arsenic metabolism.METHODS: The study encompassed 193 indigenous women. Arsenic exposure was assessed in urine as the sum of inorganic arsenic metabolite concentrations (U-As) measured by HPLC-HG-ICP-MS, and in whole blood as total arsenic (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated by a polymorphism (rs3740393) in the main arsenic methylating gene AS3MT measured by TaqMan allelic discrimination, and by the relative fractions of urinary inorganic arsenic metabolites. Telomere length and mtDNAcn were determined in peripheral blood leukocytes by quantitative PCR, and urinary 8-oxo-dG and 4-HNE-MA by LC-MS/MS.RESULTS: U-As and B-As were associated with longer telomeres and higher mtDNAcn, particularly in women with a less efficient arsenic metabolism. Urinary 8-oxo-dG and 4-HNE-MA were positively associated with U-As, but only 4-HNE-MA was associated with B-As. Arsenic metabolism efficiency did not have a clear effect on the concentrations of either of these biomarkers.CONCLUSION: Bolivian women showed indications of arsenic toxicity, measured by four different biomarkers. Telomere length, mtDNAcn, and 4-HNE-MA were positively associated with both U-As and B-As. The association of arsenic exposure with telomere length and mtDNAcn was only present in Bolivian women with a less efficient metabolism. These findings call for additional efforts to evaluate and reduce arsenic exposure in Bolivia.
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| 16. |
- Diaz, Oscar E., et al.
(författare)
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Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation
- 2021
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Ingår i: DMM Disease Models and Mechanisms. - : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 14:12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors, we used zebrafish reporters of intestinal inflammation. Using zebrafish, we interrogated the immunomodulatory effects of polyfluoroalkyl substances, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. This was associated with a neutrophil-dependent expansion of systemic CD4+ T cells. Thus, our results indicate that PFOS worsens inflammation-induced intestinal damage with disruption of T-cell homeostasis beyond the gut and provides a novel in vivo toolbox to screen for pollutants affecting intestinal homeostasis.
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| 17. |
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| 18. |
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| 19. |
- Eriksson, Axel C., et al.
(författare)
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The role of organic fraction of aerosol particles in uptake of indoor SVOC investigated with real time aerosol mass spectrometry
- 2018
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Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
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Konferensbidrag (refereegranskat)abstract
- We investigate the uptake of the Di(2-ethylhexyl) phthalate (DEHP) by laboratory generated and ambient aerosol particles passing through a 1.2 liter chamber covered with vinyl flooring on its internal surfaces. We found approximately five times more efficient DEHP uptake on a mass basis by organic particles (ambient particles) compared to laboratory generated salt particles. The increased uptake is likely due to increased adsorption by pre-existing organic aerosol, which is abundant in the ambient aerosol particles. This implies that compounds with adverse health outcomes are added to particles in indoor air after infiltration into buildings via gas-to-particle conversion of indoor generated SVOCs. We show that aerosol mass spectrometry is a suitable tool for highly time-resolved investigations of this process.
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| 20. |
- Erlandsson, Lena, et al.
(författare)
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Exposure to wood smoke particles leads to inflammation, disrupted proliferation and damage to cellular structures in a human first trimester trophoblast cell line
- 2020
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 264
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Tidskriftsartikel (refereegranskat)abstract
- The ongoing transition to renewable fuel sources has led to increased use of wood and other biomass fuels. The physiochemical characteristics of biomass combustion derived aerosols depends on appliances, fuel and operation procedures, and particles generated during incomplete combustion are linked to toxicity. Frequent indoor wood burning is related to severe health problems such as negative effects on airways and inflammation, as well as chronic hypoxia and pathological changes in placentas, adverse pregnancy outcome, preterm delivery and increased risk of preeclampsia. The presence of combustion-derived black carbon particles at both the maternal and fetal side of placentas suggests that particles can reach the fetus. Air pollution particles have also been shown to inhibit trophoblast migration and invasion, which are vital functions for the development of the placenta during the first trimester. In this study we exposed a placental first trimester trophoblast cell line to wood smoke particles emitted under Nominal Burn rate (NB) or High Burn rate (HB). The particles were visible inside exposed cells and localized to the mitochondria, causing ultrastructural changes in mitochondria and endoplasmic reticulum. Exposed cells showed decreased secretion of the pregnancy marker human chorionic gonadotropin, increased secretion of IL-6, disrupted membrane integrity, disrupted proliferation and contained specific polycyclic aromatic hydrocarbons (PAHs) from the particles. Taken together, these results suggest that wood smoke particles can enter trophoblasts and have detrimental effects early in pregnancy by disrupting critical trophoblast functions needed for normal placenta development and function. This could contribute to the underlying mechanisms leading to pregnancy complications such as miscarriage, premature birth, preeclampsia and/or fetal growth restriction. This study support the general recommendation that more efficient combustion technologies and burning practices should be adopted to reduce some of the toxicity generated during wood burning.
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| 21. |
- Gren, Louise, et al.
(författare)
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Underground emissions and miners' personal exposure to diesel and renewable diesel exhaust in a Swedish iron ore mine
- 2022
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Underground diesel exhaust exposure is an occupational health risk. It is not known how recent intensified emission legislation and use of renewable fuels have reduced or altered occupational exposures. We characterized these effects on multipollutant personal exposure to diesel exhaust and underground ambient air concentrations in an underground iron ore mine.METHODS: Full-shift personal sampling (12 workers) of elemental carbon (EC), nitrogen dioxide (NO2), polycyclic aromatic hydrocarbons (PAHs), and equivalent black carbon (eBC) was performed. The study used and validated eBC as an online proxy for occupational exposure to EC. Ambient air sampling of these pollutants and particle number size distribution and concentration were performed in the vicinity of the workers. Urine samples (27 workers) were collected after 8 h exposure and analyzed for PAH metabolites and effect biomarkers (8-oxodG for DNA oxidative damage, 4-HNE-MA for lipid peroxidation, 3-HPMA for acrolein).RESULTS: The personal exposures (geometric mean; GM) of the participating miners were 7 µg EC m-3 and 153 µg NO2 m-3, which are below the EU occupational exposure limits. However, exposures up to 94 µg EC m-3 and 1200 µg NO2 m-3 were observed. There was a tendency that the operators of vehicles complying with sharpened emission legislation had lower exposure of EC. eBC and NO2 correlated with EC, R = 0.94 and R = 0.66, respectively. No correlation was found between EC and the sum of 16 priority PAHs (GM 1790 ng m-3). Ratios between personal exposures and ambient concentrations were similar and close to 1 for EC and NO2, but significantly higher for PAHs. Semi-volatile PAHs may not be effectively reduced by the aftertreatment systems, and ambient area sampling did not predict the personal airborne PAHs exposure well, neither did the slightly elevated concentration of urinary PAH metabolites correlate with airborne PAH exposure.CONCLUSION: Miners' exposures to EC and NO2 were lower than those in older studies indicating the effect of sharpened emission legislation and new technologies. Using modern vehicles with diesel particulate filter (DPF) may have contributed to the lower ambient underground PM concentration and exposures. The semi-volatile behavior of the PAHs might have led to inefficient removal in the engines aftertreatment systems and delayed removal by the workplace ventilation system due to partitioning to indoor surfaces. The results indicate that secondary emissions can be an important source of gaseous PAH exposure in the mine.
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| 22. |
- Gustafsson, Asa, et al.
(författare)
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Isolation and characterization of a respirable particle fraction from residential house-dust
- 2018
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Ingår i: Environmental Research. - : Academic Press Inc Elsevier Science. - 0013-9351 .- 1096-0953. ; 161, s. 284-290
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Tidskriftsartikel (refereegranskat)abstract
- Indoor air pollution has caused increasing concern in recent years. As we spend most of our lives indoors, it is crucial to understand the health effects caused by indoor air pollution. Household dust serve as good proxy for accessing indoor air pollution, especially smaller dust particles that can pass into the lungs are of interest. In this study we present an efficient method for the isolation of dust particles in the respirable size range. The respirable fraction was recovered from vacuum cleaner bags, separated by stepwise sieving, followed by characterization for size, morphology, surface area, organic content and elemental composition. The respirable fraction was obtained in a yield of 0.6% with a specific surface area of 2.5 m(2)/g and a Mass Median Aerodynamic Diameter of 3.73 +/- 0.15 mu m. Aluminum and zink were the dominating metals measured in the dust, whereas the major mineral components were found to be silicon dioxide and calcium carbonate. The fraction of organic matter in the dust was measured to be 69 +/- 1%. The organic matrix contained bacterial and fungi and a presence of skin fragments. We present here an efficient and fast method for the isolation of dust particles in the respirable size range. That is of considerable value due to the need for large quantities of respirable particle fractions to conduct toxicological studies and risk assessment work.
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| 23. |
- Igra, Annachiara Malin, et al.
(författare)
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Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy and timing of pubertal onset in a longitudinal mother-child cohort in rural Bangladesh
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- Background: In experimental studies, several polycyclic aromatic hydrocarbons (PAHs) have shown endocrine disrupting properties, but very few epidemiological studies have examined their impact on pubertal development and results have been heterogenous. Objective: To explore if maternal PAH exposure during pregnancy was associated with the offspring's timing of pubertal onset. Methods: We studied 582 mother-daughter dyads originating from a population-based cohort in a rural setting in Bangladesh. Maternal urinary samples, collected in early pregnancy (on average, gestational week 8), were analyzed for monohydroxylated metabolites of phenanthrene (1-OH-Phe, E2-,3-OH-Phe, and 4-OH-Phe), fluorene (E2-,3-OH-Flu), and pyrene (1-OH-Pyr) using liquid chromatography with tandem mass spectrometry (LCMS/MS). The girls were interviewed on two separate occasions concerning date of menarche, as well as breast and pubic hair development according to Tanner. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox proportional hazards regression or ordered logistic regression. Results: In early pregnancy, the mothers' median urinary concentrations of E1-,2-,3-,4-OH-Phe, E2-,3-OH-Flu, and 1-OH-Pyr were 3.25 ng/mL, 2.0 ng/mL, and 2.3 ng/mL respectively. At the second follow-up, 78 % of the girls had reached menarche, and the median age of menarche was 12.7 +/- 0.81 years. Girls whose mothers belonged to the second and third quintiles of EOH-Phe metabolites had a higher rate of menarche, indicating a younger menarcheal age (HR 1.39; 95 % CI 1.04, 1.86, and HR 1.41; 95 % CI 1.05, 1.88, respectively), than girls of mothers in the lowest quintile. This trend was not observed in relation to either breast or pubic hair development. None of the other maternal urinary PAH metabolites or the sum of all thereof in early pregnancy were associated with age at menarche or pubertal stage. Conclusions: Indications of non-monotonic associations of prenatal phenanthrene exposure with the daughters' age of menarche were found, warranting further investigation.
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| 24. |
- Jiang, Zheshun, et al.
(författare)
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Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium : A cross-sectional study within the SafeChrom project
- 2024
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 190
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hexavalent chromium (Cr(Ⅵ)) is classified as a group 1 human carcinogen and increases the risk of lung cancer. Non-coding RNAs (ncRNAs) have key regulatory roles in lung cancer, but less is known about their relation to Cr(Ⅵ) exposure.OBJECTIVES: We aimed to 1) measure the expression of lung cancer-related circulating ncRNAs in exposed workers and controls; 2) assess associations between ncRNAs expression and Cr concentrations in red blood cells (RBC) and urine; and 3) evaluate correlations between the ncRNAs.METHODS: The study included 111 Cr(VI) exposed workers and 72 controls recruited from the SafeChrom project. Cr concentrations were measured in RBC (biomarker of long-term exposure) and urine (biomarker of short-term exposure) samples. Long ncRNA (lncRNA) and microRNA (miRNA) were extracted from plasma followed by deoxyribonuclease treatment, complementary DNA synthesis, and quantitative real-time polymerase chain reaction using target-specific assays for three lncRNAs (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a).RESULTS: Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = -0.16 to -0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR-142-3p (rS = -0.33) and miR-15b-5p (rS = -0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations.CONCLUSIONS: Cr(VI) exposure was inversely and in a dose-response manner associated with the expression of circulating non-coding RNA, which suggests ncRNAs as potential biomarkers for Cr(VI)-induced toxicity. Correlations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-messenger RNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.
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| 25. |
- Jiang, Zheshun, et al.
(författare)
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Hexavalent chromium still a concern in Sweden : Evidence from a cross-sectional study within the SafeChrom project
- 2024
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Ingår i: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 256
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesHexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown.MethodsThis cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance.ResultsThe exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 μg/m3 (95% confidence interval: 0.11–0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 μg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 μg/L, 5th-95th percentile 0.10–3.20) and RBC concentrations (0.73 μg/L, 0.51–2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 μg/L, 0.06–0.56 and RBC 0.53 μg/L, 0.42–0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today.ConclusionsOur study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.
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| 26. |
- Krais, Annette M., et al.
(författare)
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Biomarkers after Controlled Inhalation Exposure to Exhaust from Hydrogenated Vegetable Oil (HVO)
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogenated vegetable oil (HVO) is a renewable diesel fuel used to replace petroleum diesel. The organic compounds in HVO are poorly characterized; therefore, toxicological properties could be different from petroleum diesel exhaust. The aim of this study was to evaluate the exposure and effective biomarkers in 18 individuals after short-term (3 h) exposure to HVO exhaust and petroleum diesel exhaust fumes. Liquid chromatography tandem mass spectrometry was used to analyze urinary biomarkers. A proximity extension assay was used for the measurement of inflammatory proteins in plasma samples. Short-term (3 h) exposure to HVO exhaust (PM1 ~1 µg/m3 and ~90 µg/m3 for vehicles with and without exhaust aftertreatment systems, respectively) did not increase any exposure biomarker, whereas petroleum diesel exhaust (PM1 ~300 µg/m3 ) increased urinary 4-MHA, a biomarker for p-xylene. HVO exhaust from the vehicle without exhaust aftertreatment system increased urinary 4-HNE-MA, a biomarker for lipid peroxidation, from 64 ng/mL urine (before exposure) to 141 ng/mL (24 h after exposure, p < 0.001). There was no differential expression of plasma inflammatory proteins between the HVO exhaust and control exposure group. In conclusion, short-term exposure to low concentrations of HVO exhaust did not increase urinary exposure biomarkers, but caused a slight increase in lipid peroxidation associated with the particle fraction.
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| 27. |
- Krais, Annette M, et al.
(författare)
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Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica
- 2024
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Ingår i: Journal of Exposure Science & Environmental Epidemiology. - 1559-064X. ; 34:2, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil.OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica.METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations.RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed.IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.
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| 28. |
- Krais, Annette M., et al.
(författare)
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Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure
- 2018
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100⁻300 µg/m³ of deuterium-labelled diethyl phthalate (D₄-DEP) and bis(2-ethylhexyl) phthalate (D₄-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D₄-DEP and D₄-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D₄-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m³ (nmol of urinary metabolites per phthalates air concentration in (nmol/m³)). After dermal exposure to D₄-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m³. After combined inhalation and dermal exposure to D₄-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m³ between participants. No dermal uptake of particle phase D₄-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D₄-DEP was three times higher than after combined exposure to D₄-DEHP; and nine times higher than after dermal exposure of D₄-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.
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| 29. |
- Krais, Annette, et al.
(författare)
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Sensitive detection of hydroxymethylcytosine levels in normal and neoplastic cells and tissues.
- 2019
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 40:9, s. 1293-1297
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Tidskriftsartikel (refereegranskat)abstract
- A new sensitive analytical method using capillary electrophoresis with laser induced fluorescence (CE-LIF) was applied for the simultaneous detection of DNA methylation and hydroxymethylation levels in human cancers of different origin. DNA hydroxymethylation, measured as 5-hydroxymethylcytosine (5hmC) levels, was decreased in gliomas with mutation in the isocitrate dehydrogenase 1 (IDH1) gene when compared to IDH1-wildtype gliomas. Independent from IDH1 mutation, 5hmC levels were decreased in lung carcinomas when compared to normal lung tissue. Reduced DNA hydroxymethylation was also observed upon dedifferentiation in cultured murine embryonic fibroblasts. Our data show that reduced DNA hydroxymethylation is related to cellular dedifferentiation and can be detected in various types of cancers, independent from the IDH1 mutation status. Quantitative determination of altered 5hmC levels may therefore have potential as a biomarker linked to cellular differentiation and tumorigenesis.
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| 30. |
- Moshfiqur Rahman, Syed, et al.
(författare)
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Polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy and child anthropometry from birth to 10 years of age : Sex-specific evidence from a cohort study in rural Bangladesh
- 2023
-
Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 227
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons (PAHs) have endocrine disrupting properties and they cross the placental barrier, but studies on gestational exposure and child anthropometry are inconclusive. We aimed to elucidate the impact of early gestational PAH exposure on anthropometry from birth to 10 years of age in 1295 mother-child pairs from a nested sub-cohort of the MINIMat trial in Bangladesh. Several PAH metabolites [1-hydroxyphenanthrene (1-OH-Phe), Σ2-,3-hydroxyphenanthrene (Σ2-,3-OH-Phe), 4-hydroxyphenanthrene (4-OH-Phe), 1-hydroxypyrene (1-OH-Pyr), Σ2-,3-hydroxyfluorene (Σ2-,3-OH-Flu)] were quantified in spot urine collected around gestational week 8 using LC-MS/MS. Child weight and height were measured at 19 occasions from birth to 10 years. Multivariable-adjusted regression models were used to assess associations of maternal PAH metabolites (log 2-transformed) with child anthropometry. The median concentration of 1-OH-Phe, Σ2-,3-OH-Phe, 4-OH-Phe, 1-OH-Pyr and Σ2-,3-OH-Flu was 1.5, 1.9, 0.14, 2.5, and 2.0 ng/mL, respectively. All maternal urinary PAH metabolites were positively associated with newborn weight and length and all associations were more pronounced in boys than in girls (p interaction for all <0.14). In boys, the strongest associations were observed with Σ2-,3-OH-Phe and Σ2-,3-OH-Flu for which each doubling increased mean birth weight by 41 g (95% CI: 13; 69 and 12; 70) and length by 0.23 cm (0.075; 0.39) and 0.21 cm (0.045; 0.37), respectively. Maternal urinary PAH metabolites were not associated with child anthropometry at 10 years. In longitudinal analysis, however, maternal urinary PAH metabolites were positively associated with boys' weight-for-age (WAZ) and height-for-age Z-scores (HAZ) from birth to 10 years, but only the association of 4-OH-Phe with HAZ was significant (B: 0.080 Z-scores; 95% CI 0.013, 0.15). No associations were observed with girls' WAZ or HAZ. In conclusion, gestational PAH exposure was positively associated with fetal and early childhood growth, especially in boys. Further studies are needed to confirm causality and to explore long-term health effects.
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| 31. |
- Møller, Peter, et al.
(författare)
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Inflammation, oxidative stress and genotoxicity responses to biodiesel emissions in cultured mammalian cells and animals
- 2020
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Ingår i: Critical Reviews in Toxicology. - : Informa UK Limited. - 1040-8444 .- 1547-6898. ; 50:5, s. 383-401
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Forskningsöversikt (refereegranskat)abstract
- Biodiesel fuels are alternatives to petrodiesel, especially in the transport sector where they have lower carbon footprint. Notwithstanding the environmental benefit, biodiesel fuels may have other toxicological properties than petrodiesel. Particulate matter (PM) from petrodiesel causes cancer in the lung as a consequence of delivery of genotoxic polycyclic aromatic hydrocarbons, oxidative stress and inflammation. We have reviewed articles from 2002 to 2019 (50% of the articles since 2015) that have described toxicological effects in terms of genotoxicity, oxidative stress and inflammation of biodiesel exhaust exposure in humans, animals and cell cultures. The studies have assessed first generation biodiesel from different feedstock (e.g. rapeseed and soy), certain second generation fuels (e.g. waste oil), and hydrogenated vegetable oil. It is not possible to rank the potency of toxicological effects of specific biodiesel fuels. However, exposure to biodiesel exhaust causes oxidative stress, inflammation and genotoxicity in cell cultures. Three studies in animals have not indicated genotoxicity in lung tissue. The database on oxidative stress and inflammation in animal studies is larger (13 studies); ten studies have reported increased levels of oxidative stress biomarkers or inflammation, although the effects have been modest in most studies. The cell culture and animal studies have not consistently shown a different potency in effect between biodiesel and petrodiesel exhausts. Both increased and decreased potency have been reported, which might be due to differences in feedstock or combustion conditions. In conclusion, combustion products from biodiesel and petrodiesel fuel may evoke similar toxicological effects on genotoxicity, oxidative stress and inflammation.
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| 32. |
- Preece, Anna-Sofia, et al.
(författare)
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Indoor phthalate exposure and contributions to total intake among pregnant women in the SELMA study
- 2021
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Ingår i: Indoor Air. - : WILEY. - 0905-6947 .- 1600-0668. ; 31:5, s. 1495-1508
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are widely used in consumer products. Exposure to phthalates can lead to adverse health effects in humans, with early-life exposure being of particular concern. Phthalate exposure occurs mainly through ingestion, inhalation, and dermal absorption. However, our understanding of the relative importance of different exposure routes is incomplete. This study estimated the intake of five phthalates from the residential indoor environment for 455 Swedish pregnant women in the SELMA study using phthalate mass fraction in indoor dust and compares these to total daily phthalate intakes back-calculated from phthalate metabolite concentrations in the women's urine. Steady-state models were used to estimate indoor air phthalate concentrations from dust measurements. Intakes from residential dust and air made meaningful contributions to total daily intakes of more volatile di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), and di-iso-butyl phthalate (DiBP) (11% of total DEP intake and 28% of total DnBP and DiBP intake combined). Dermal absorption from air was the dominant pathway contributing to the indoor environmental exposure. Residential exposure to less volatile phthalates made minor contributions to total intake. These results suggest that reducing the presence of low molecular weight phthalates in the residential indoor environment can meaningfully reduce phthalate intake among pregnant women.
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| 33. |
- Preece, Anna-Sofia, et al.
(författare)
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Phthalate levels in indoor dust and associations to croup in the SELMA study
- 2021
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Nature Publishing Group. - 1559-0631 .- 1559-064X. ; 30, s. 257-265
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are ubiquitous indoor pollutants which have been associated with child airway disease although results are inconclusive. This study examined associations between phthalate levels in residential indoor dust and croup during infancy. Settled indoor dust was collected in 482 homes of 6-month-old infants in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study and analysed for seven phthalates and one phthalate replacement using gas chromatography tandem mass spectrometry. The incidence of parental reported croup at 12 months was 6.4% for girls and 13.4% for boys. Associations between phthalate dust levels and croup were analysed by logistic regression adjusted for potential confounders. We found significant associations between di-ethyl phthalate (DEP) and di-ethyl-hexyl phthalate (DEHP) in residential dust and parental reported croup (adjusted odds ratio (aOR) = 1.71; 95% CI: 1.08-2.73 and 2.07; 1.00-4.30, respectively). Stratified results for boys showed significant associations between DEP and butyl-benzyl phthalate (BBzP) in dust and infant croup (aOR = 1.86; 95% CI: 1.04-3.34 and 2.02; 1.04-3.90, respectively). Results for girls had questionable statistical power due to few cases. Our results suggest that exposure to phthalates in dust is a risk factor for airway inflammatory responses in infant children.
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| 34. |
- Preece, Anna-Sofia, et al.
(författare)
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Phthalate levels in prenatal and postnatal bedroom dust in the SELMA study
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 212
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates are common in polyvinyl chloride (PVC) plastics and numerous consumer goods in our homes from which they can migrate and adhere to indoor dust particles. It is known that indoor dust exposure contribute to human phthalate intake; however, there is a lack of large studies with a repeated-measure design investigating how phthalate levels in indoor dust may vary over time in people's homes.This study investigated levels of seven phthalates and one alternative plasticiser di-iso-nonyl-cyclohexane-di-carboxylate (DiNCH) in bedroom dust collected prenatally around week 25 during pregnancy and postnatally at six months after birth, from 496 Swedish homes. Prenatal and postnatal phthalate levels were compared using correlation and season-adjusted general linear regression models.Over the nine-month period, levels of six out of seven phthalates were associated as indicated by a positive Pearson correlation (0.18 < r < 0.50, P < .001) and Lin's concordance correlation between matched prenatal and postnatal dust samples. Compared to prenatal levels, the season-adjusted postnatal levels decreased for five phthalates, whilst di-ethyl-hexyl phthalate (DEHP), di-2-propylheptyl phthalate (DPHP) and DiNCH increased.The results suggest that families with higher phthalate levels in bedroom dust during pregnancy are likely to remain among those with higher levels in the infancy period. However, all average phthalate levels changed over this specific nine-month period suggesting that available phthalate sources or their use were altered between the dust collections. Changes in home characteristics, family lifestyle, and phthalate replacement trends may contribute to explain the differences.
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| 35. |
- Quintana-Belmares, Raúl Omar, et al.
(författare)
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Phthalate esters on urban airborne particles : Levels in PM10 and PM2.5 from Mexico City and theoretical assessment of lung exposure
- 2018
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 161, s. 439-445
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Tidskriftsartikel (refereegranskat)abstract
- Endocrine disrupting chemicals (EDCs) from the environment are associated with reproductive abnormalities (i.e. decreased sperm concentration; increased endometriosis) and alterations of the cardiovascular system (i.e. increased blood pressure and risk of coronary disease). Some phthalates esters have been identified as EDCs, for which inhalation is considered as one of the routes of exposure. However, only little is known regarding inhalational exposure to EDCs via urban airborne particles. In the present study, we report the monthly concentration of 8 phthalate esters measured in PM10 and PM2.5 collected and recovered during 7 months in a highly populated area of Mexico City. Using the levels of PM10 and PM2.5 reported by the automatized network of environmental monitoring of Mexico City for the sampling site, we estimated exposure levels for people of different ages and gender. Two endocrine disrupting compounds, the phthalate esters DEHP and DnBP, were found on the particles in higher concentrations during the warmer months of the year. The highest concentration was reported for DEHP (229.7 mu g/g of particles) in PM2.5 collected in May 2013. After calculations of the DEHP concentration in the atmosphere, and using the respiratory flow rate, we determined males were potentially exposed to larger quantities of DEHP, reaching up to 18 ng/8 h in April 2013. Despite the concentrations of phthalates seem to be rather small, a comprehensive characterization of its presence is necessary in order to evaluate the overall exposure to these compounds, providing a clear view of exposure on children, adolescents and pregnant women.
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| 36. |
- Rothmann, Monika Hezareh, et al.
(författare)
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Genotoxicity by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells
- 2023
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Ingår i: Mutagenesis. - 0267-8357. ; 38:4, s. 238-249
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Tidskriftsartikel (refereegranskat)abstract
- Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. The present study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from combustion of petrodiesel, RME and hydrogenated vegetable oil (HVO) in lung epithelial (A549) cells. Genotoxicity was assessed as DNA strand breaks by the alkaline comet assay. EOM from combustion of petrodiesel and RME generated the same level of DNA strand breaks based on equal concentration of total PAH (i.e. net increases of 0.13 [95% confidence interval (CI): 0.002, 0.259 and 0.12 [95% CI: 0.01, 0.24] lesions per million base pairs, respectively). In comparison, the positive control (etoposide) generated much higher level of DNA strand breaks (i.e. 0.84, 95% CI: 0.72, 0.97) lesions per million base pairs). Relatively low concentrations of EOM from RME and HVO combustion particles (<116 ng/ml total PAH) did not cause DNA strand breaks in A549 cells, whereas benzo[a]pyrene and PAH-rich EOM from petrodiesel combusted using low oxygen inlet concentration were genotoxic. The genotoxicity was attributed to high molecular weight PAH isomers with 5-6 rings. In summary, the results show that EOM from combustion of petrodiesel and RME generate the same level of DNA strand breaks on equal total PAH basis. However, the genotoxic hazard of engine exhaust from on-road vehicles is lower for RME than petrodiesel because of lower PAH emission per fuel energy content.
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| 37. |
- Scholten, Rebecca Harnung, et al.
(författare)
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Inhalation of hydrogenated vegetable oil combustion exhaust and genotoxicity responses in humans
- 2021
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 95:10, s. 3407-3416
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Tidskriftsartikel (refereegranskat)abstract
- Biofuels from vegetable oils or animal fats are considered to be more sustainable than petroleum-derived diesel fuel. In this study, we have assessed the effect of hydrogenated vegetable oil (HVO) exhaust on levels of DNA damage in peripheral blood mononuclear cells (PBMCs) as primary outcome, and oxidative stress and inflammation as mediators of genotoxicity. In a randomized cross-over study, healthy humans were exposed to filtered air, inorganic salt particles, exhausts from combustion of HVO in engines with aftertreatment [i.e. emission with nitrogen oxides and low amounts of particulate matter less than 2.5 µm (approximately 1 µg/m3)], or without aftertreatment (i.e. emission with nitrogen oxides and 93 ± 13 µg/m3 of PM2.5). The subjects were exposed for 3 h and blood samples were collected before, within 1 h after the exposure and 24 h after. None of the exposures caused generation of DNA strand breaks and oxidatively damaged DNA, or affected gene expression of factors related to DNA repair (Ogg1), antioxidant defense (Hmox1) or pro-inflammatory cytokines (Ccl2, Il8 and Tnfa) in PBMCs. The results from this study indicate that short-term HVO exhaust exposure is not associated with genotoxic hazard in humans.
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| 38. |
- Strandberg, Bo, et al.
(författare)
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Particulate-Bound Polycyclic Aromatic Hydrocarbons (PAHs) and their Nitro- and Oxy-Derivative Compounds Collected Inside and Outside Occupied Homes in Southern Sweden
- 2023
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Ingår i: Polycyclic Aromatic Compounds. - : Informa UK Limited. - 1040-6638 .- 1563-5333. ; 43:8, s. 7399-7415
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Tidskriftsartikel (refereegranskat)abstract
- This study presents indoor and outdoor levels of airborne fine particles (PM2.5), particle bound polycyclic aromatic compounds (PACs) including parent-, alkylated-, nitro-, and oxy-PAHs. Week-long simultaneous measurements were conducted inside and outside 15 occupied homes in southern Sweden during wintertime. The homes were single-family houses or apartments located in urban, semi-urban, and rural areas. The PM2.5 and PACs levels were low compared to studies worldwide. There was great variation in concentrations between sites, which likely is due to proximity to road and traffic intensity. The lower concentrations of nitro and oxy-PAHs compared to parent PAHs in this study, compared to other studies, could possibly be due to lower atmospheric photochemical formation outdoors because the cold climate. This assumption could not be confirmed and need to be further tested. The results point to that particle PAC levels found inside arise primarily from outdoor. This correlation was not as clear for PM2.5. The results of a comparison between residences before and after energy renovation did not indicate an improvement in indoor air regarding PACs. To understand exposure and assess risks it is important to measure wide range of PACs both in gas and particle phase.
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