| 61. |
- Carnerup, Martin, et al.
(författare)
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Levels of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine from volunteers after experimental exposure to NMP in dry and humid air.
- 2006
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Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 162:2-3, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden. The aim of this study was to investigate if the uptake of N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical, increases after exposure to NMP in humid air compared to dry air. NMP has been described to be an airway irritant and a developmentally toxic compound. Six male volunteers were exposed to NMP, three at the time, for 8h in an exposure chamber. They were each exposed on four different occasions to air levels of 0 and 20mg NMP/m(3) in dry and humid air. Blood and urine were sampled before, during and up to 5 days after the end of the 8-h exposure. Plasma and urine were analysed for NMP and its metabolites, using liquid chromatography-tandem mass spectrometry. There was no statistically significant increase in the total cumulated excretion of NMP and its metabolites in urine after exposure in humid air as compared to dry air. Furthermore, there were no differences in the levels of peak concentrations in either plasma or urine. Also, no differences were found in AUC between the exposures. However, there were large individual differences, especially for the exposure in humid air. A not previously identified metabolite in human, 2-pyrrolidone (2-P), was identified. The results do not support a significantly higher absorption of NMP at exposure in humid air as compared to dry air. However, the large individual differences support the use of biological monitoring for assessment of NMP exposure. In addition, 2-P was confirmed to be an NMP metabolite in humans. This may be of importance for the developmental toxicity of NMP since 2-P have been described to be a reproductively toxic substance.
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| 62. |
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| 63. |
- Cohen, Arieh, et al.
(författare)
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Automated solid-phase extraction and liquid chromatography tandem mass spectrometry determination of N-methyl-2-pyrrolidone and its metabolites in urine and plasma
- 2007
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Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 65:7-8, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- A method for the simultaneous determination of N-methyl-2-pyrrolidone (NMP) and its metabolites 5-hydroxyl-N-pyrrolidone (5HNMP), N-methylsuccinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2HMSI) in plasma and urine has been developed. Samples were purified by SPE using an ASPEC XL4. Analysis was performed using LC-MS equipped with an APCI interface. The analysis provided linear responses in the range of 0.125-12 mu g mL(-1) for all of the analytes and up to 150 mu g mL(-1) for 5HNMP and 2HMS1. The within day precision was in the range of 0.9-19.1% for plasma samples and 1.9-10.4% for urine samples whereas the between day precisions were 4.5-11.9% and 1.2-17.5%, respectively. The method was deemed to be suitable for monitoring the levels of NMP and its metabolites in the plasma and urine of occupationally exposed persons.
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| 64. |
- Consales, Claudia, et al.
(författare)
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Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.
- 2016
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 57:3, s. 200-209
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
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| 65. |
- Drexler, H, et al.
(författare)
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Exposure assessment and sensitisation in workers exposed to organic acid anhydrides
- 2000
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 73:4, s. 228-234
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To clarify whether the intensity of exposure to organic acid anhydrides (OAAs) is associated with the risk of sensitisation to these allergens. METHODS: The investigations were carried out in three different manufacturing plants (A, B, and C) where OAAs were used in the production of epoxy resins. Methyltetrahydrophthalic acid anhydride (MTHPA) was used in all three plants. The exposure assessment included stationary and ambient air monitoring (OAAs in the air) and biological monitoring (metabolites in urine). In plant A 20, in plant B 86 and in plant C 113 employees were examined by a physician (anamnesis, skin-prick test, specific IgE, spirometry). In plants B and C, the exposure areas were classified as high, medium, and low, without the results of the exposure assessment being known. RESULTS: The ambient air concentrations (in microg/m3) of MTHPA were 37.2 and 58.5 in plant A (number of samples n = 2), ranged from <0.5-26.2 in plant B (n = 5) and from 2.1-57.9 in plant C (n = 3) with stationary air collecting, and from 8-45 (n = 6), from < 4.7-35.7 (n = 3) and from 2-37.8 (n = 3) with personal air collection. The metabolites of OAAs in urine (in nmol/mmol creatinine) ranged from 5.7-645 (median of MTHPA: 346) in plant A, from < 1-213 (median of MTHPA: 10.1) in plant B and from 0.1-830 (median of the sum of the OOA metabolites: 108.6) in plant C. The prevalence of sensitisation was 35% in plant A, 21% in plant B and 29% in plant C. A higher prevalence in the highly exposed areas, however, could not be seen. Levels of IgE specific for conjugates of MTHPA were not associated with the metabolites in the end of shift urine. Levels of IgG specific for conjugates of MTHPA, however, were associated with the metabolites in the end of shift urine. CONCLUSIONS: The data showed that biological monitoring is a useful tool in the exposure assessment of OAAs. Comparing the prevalence of sensitisation and the results of biological monitoring, between the three plants, we found that sensitisation increased with increasing exposure. Within a plant a higher risk of sensitisation in persons working in highly exposed areas at the time of the examination could not be seen, possibly due to frequent job rotation.
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| 66. |
- Duan, Rui-Dong, et al.
(författare)
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Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites.
- 2007
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 61:1, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may catalyze the hydrolysis of endogenous sphin-gomyelin (SM) and milk SM in human-milk fed infants. The enzymes generate sphingolipid metabolites that may influence gut maturation. Alk-SMase also inactivates platelet-activating factor (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We examined whether the two enzymes are expressed in both preterm and term infants and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and 38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C-14-choline-labeled SM and for neutral ceramidase using C-14-octanoyl-sphingosine as substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by high-performance liquid chromatography mass spectroscopy. Meconium contained significant levels of Alk-SMase and ceramidase at all gestational ages. It also contained 16-24 carbon molecular species of SM, palmitoyl-and stearoyl-sphingosine, and sphingosine. There were positive correlations between levels of SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk-SMase and ceramidase are expressed in the gut of both preterm and term newborn infants and may generate bioactive sphingolipid messengers.
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| 67. |
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| 68. |
- Ekman, Eva, et al.
(författare)
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Determination of 5-hydroxythiabendazole in human urine as a biomarker of exposure to thiabendazole using LC/MS/MS.
- 2014
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 973, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Thiabendazole (TBZ) is widely used as a pre-planting and post-harvest agricultural fungicide and as an anthelminthic in humans and animals. TBZ is of toxicological concern, since adverse effects including nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals. Occupational exposure can occur among agricultural workers and the general public may be environmentally exposed to TBZ through the diet. The metabolite 5-hydroxythiabendazole (5-OH-TBZ) was chosen as biomarker of exposure to TBZ and a LC/MS/MS method for the quantification of 5-OH-TBZ in human urine was developed. The method includes enzyme hydrolysis, as 5-OH-TBZ is conjugated to glucuronide and sulphate in urine. Sample through put was optimised using 96-well plates for sample handling as well as for solid phase extraction (SPE). The method has excellent, within-run, between-run and between-batch precision between 4 and 9%. The limit of detection (LOD) of 0.05 and a limit of quantification (LOQ) of 0.13ng 5-OH-TBZ/mL urine enable detection in environmentally exposed populations. When applying the method in a general Swedish population, 52% had levels above LOD. The method was also applied in one oral and one dermal human experimental exposure study in two individuals. After oral exposure, the excretion of 5-OH-TBZ in urine was described by a two-compartment model and both the first rapid and the second slower elimination phase followed first-order kinetics, with estimated elimination half-life of 2h and 9-12h. The recoveries in urine were between 21 and 24% of the dose. Dermal exposure was described by a one compartment model and followed first order kinetics, with estimated elimination half-life of 9-18h. The recovery in urine was 1% of the administrated dose of TBZ. Although these studies are limited to two individuals, the data provide new basic information regarding the toxicokinetics of TBZ after oral and dermal exposure.
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| 69. |
- Ekman, Eva, et al.
(författare)
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High-throughput method for the analysis of ethylenethiourea with direct injection of hydrolysed urine using online on-column extraction liquid chromatography and triple quadrupole mass spectrometry.
- 2013
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 934:Jul,5, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Ethylenethiourea (ETU) is of major toxicological concern, since in experimental animal studies, ETU has shown a large spectrum of adverse effects. High occupational exposure can be found among agricultural workers or during manufacturing of ethylenbisdithiocarbamates (EBDC). For the general public, sources of environmental exposure may be residues of ETU in commercial products, food and beverages. For the determination of ETU in human urine we present a high-throughput online on-column extraction liquid chromatography triple quadrupole mass spectrometry method using direct injection of hydrolysed urine samples. This method is simple, user- and environmentally friendly and all sample preparation is performed in 96-well plates. A labelled ETU internal standard was used for quantification. The method showed a good sensitivity with a limit of quantification (LOQ) of 0.5ng ETU/mL urine and the calibration curve was linear in the range 0.25-200ng ETU/mL urine. The within-run, between-run and between-batch precision was between 6% and 13%. Alkaline hydrolysis considerably increased the levels of ETU indicating a potential conjugate. The method was applied in an experimental dermal exposure study in humans, with sample concentrations ranging from 0.4 to 5.0ng ETU/mL urine. The excretion in urine was 10% of the applied dose. The elimination profile seemed to differ between the two individuals. The results show an estimated half-life of ETU between 34 and 72h. Although the experiment is limited to two individuals, the data provide valuable and new information regarding the toxicokinetics of ETU after dermal exposure.
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| 70. |
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