| 1. |
- Jönsson, Lena S, et al.
(författare)
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Influence of glutathione-related genes on symptoms and immunologic markers among vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 81:7, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to elucidate the role of genetic variants on symptoms of the eyes and airways, headache and nausea, as well as on immunologic markers, among vulcanization workers in the contemporary Swedish rubber industry. Polymorphisms in genes, which are involved in the defense against reactive oxygen species and metabolism of toxic substances present in the vulcanization fumes, were analyzed. METHODS: One hundred and forty-five exposed and 117 unexposed workers were included in the study. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded and immunologic markers analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105, GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and ordinary PCR. RESULTS: A protective effect of GSTA1-52 (G/A + A/A) genotype on symptoms and immunologic cells, in particular among exposed workers, was suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val + val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased levels of immunologic cells among exposed workers, although statistical significance was not reached. CONCLUSION: Our data indicate that hereditary factors influence the susceptibility to symptoms and the immunologic response of workers in the rubber industry.
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| 2. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 1-hydroxypyrene, symptoms and immunologic markers in vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 82, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to determine urinary 1-hydroxypyrene (1-HP) levels in contemporary Swedish vulcanization workers and in controls. These levels were used as an index substance for vulcanization fumes, as well as a biomarker for polycyclic aromatic hydrocarbons (PAHs). The risk of symptoms and changed levels of immunologic markers were investigated in relation to the 1-HP levels. METHODS: Included in the study were 163 exposed workers and 106 controls. Medical and occupational histories were obtained by structured interviews. Symptoms were recorded and immunologic markers analysed in blood by routine analysis methods. Levels of 1-HP were determined by liquid chromatography and fluorescence detection. RESULTS: The highest levels of 1-HP were found among exposed workers using injection and compression vulcanization and lower levels were found among exposed workers vulcanizing with salt bath, hot air, microwaves or fluid-bed. Compared to controls, exposed workers had increased risks of eye symptoms, nosebleeds, burning and dry throat, hoarseness, severe dry cough, nausea and headache. Furthermore, exposed workers had elevated levels of neutrophils and total IgG (immunoglobulin subclass G). However, only for severe dry cough an evident exposure-response relationship with urinary 1-HP levels was found. CONCLUSIONS: This work clearly shows increased levels of urinary 1-HP in Swedish vulcanization workers. Furthermore, it demonstrates an increased risk of several symptoms and elevated levels of some immunologic markers in these workers. However, no obvious exposure-response relationships were found.
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| 3. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries.
- 2007
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 80:7, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS2), which is biotransformed to 2-thiothiazolidine- 4carboxylic acid (TTCA). TTCA is used as a biomarker of CS2 exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or Xuid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.
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| 4. |
- Jönsson, Lena S, et al.
(författare)
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Lung function in relation to 2-thiothiazolidine-4-carboxylic Acid and genetic effect modification among rubber workers in sweden.
- 2008
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Ingår i: Journal of Occupational and Environmental Medicine. - 1536-5948. ; 50:9, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: What is the risk of impaired lung function in contemporary Swedish rubber workers and are there modifying effects of genetic variants? METHODS:: Included in the study were 159 rubber exposed and 118 not-rubber exposed workers. Lung function was analyzed as forced vital capacity percent of predicted and forced expiratory volume in 1 second percent of predicted. Levels of 2-thiothiazolidine-4-carboxylic acid (a marker of carbon disulfide and vulcanization fumes) was assessed with liquid chromatography tandem mass spectrometry. Polymorphisms in glutathione-related genes were analyzed by Taqman-based allelic discrimination and ordinary polymerase chain reaction. RESULTS:: There was an association between increasing levels of 2-thiothiazolidine-4-carboxylic acid and impaired lung function among exposed workers. The association was modified by glutathione S-transferase alpha 1 (GSTA1)-52 and GSTP1-114. GSTM1 had an influence on lung function among unexposed workers. CONCLUSIONS:: There may be a risk of impaired lung function in contemporary rubber workers. Gene-modifying effects may be considered in risk assessments.
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| 5. |
- Jönsson, Lena S, et al.
(författare)
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N-nitrosamines in the southern Swedish rubber industries - exposure, health effects, and immunologic markers
- 2009
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 35:3, s. 11-203
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was twofold: (i) to evaluate the air levels of N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of symptoms and changed levels of immunologic markers in relation to these levels.METHODS: Using adsorption tubes, we collected samples of N-nitrosamines in the breathing zone of 96 rubber workers and analyzed them with liquid chromatography tandem mass spectrometry. Of these 96 workers, 66 were included in a medical examination and blood analysis together with an additional 106 rubber workers and 118 unexposed subjects. Medical and occupational histories were obtained in structured interviews, symptoms were recorded and immunologic markers analyzed in blood.RESULTS: The sum of N-nitrosamines ranged from less than the limit of detection to 36 microg/m (3)and differed with the vulcanization (ie, curing process) method used. Workers vulcanizing with a salt bath had the highest levels (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and changed levels of eosinophils and total immunoglobulin G (IgG). However, we found no clear exposure-response relationship with the symptoms or the immunologic markers studied.CONCLUSIONS: High levels of N-nitrosamines were found and must be lowered considerably in order to decrease the risk of cancer. There is a need for an occupational exposure limit for N-nitrosamines in Sweden. The lack of exposure-response relationships with the subacute symptoms examined in this study may be due to a healthy-worker selection or to the possibility that the symptoms are caused by an exposure not co-varying with N-nitrosamines.
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| 6. |
- Jönsson, Lena S, et al.
(författare)
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Symptoms and immunologic markers among vulcanization workers in rubber industries in southern Sweden
- 2007
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 33:4, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to estimate the risk of symptoms and the possible derangement of levels of immunologic markers for contemporary Swedish rubber workers. Furthermore, the relation between exposure and these biomarkers of response was examined using urinary levels of 2-thiothiazolidine-4-carboxylic acid (TTCA), which reflect the exposure. Methods Included in the study were 166 exposed workers and 117 controls. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded, and immunologic markers were analyzed in blood. Urinary levels of TTCA were determined by liquid chromatography tandem mass spectrometry. Results Compared with the controls, the exposed workers had increased risks of eye symptoms [odds ratio (OR) 3.0], nose bleeds (OR 4.0), burning and dry throat (OR 3.0), hoarseness (OR 2.4), severe dry cough (OR 3.8), nausea (OR 4.3), and headache (OR 2.5). When the exposed workers were divided into three groups according to the TTCA levels, the highest risks were observed among the exposed workers with intermediate TTCA levels. Furthermore, the exposed workers in all of the TTCA subgroups had elevated concentrations of total immunoglobulin G when compared with the controls. Elevated concentrations of leukocytes, neutrophils, and eosinophils were observed in the group with high TTCA levels. Conclusions This work shows an increased risk of several symptoms and elevated levels of some immunologic markers among exposed workers in Swedish rubber industries. In addition, relationships between urinary levels of TTCA and some biomarkers of response were reported.
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| 7. |
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| 8. |
- Broberg Palmgren, Karin, et al.
(författare)
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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 20:2, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.
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| 9. |
- Broström, Julia, et al.
(författare)
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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
- 2015
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
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Tidskriftsartikel (refereegranskat)abstract
- Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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| 10. |
- 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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