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OBJECTIVE@#To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice.@*METHODS@#Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated.@*RESULTS@#TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05).@*CONCLUSION@#Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.
Subject(s)
Animals , Mice , Asthma/chemically induced , Inflammation , Macrophages , Receptor-Interacting Protein Serine-Threonine Kinases , Respiratory System , Toluene 2,4-Diisocyanate/adverse effectsABSTRACT
OBJECTIVE: To investigate the role of high mobility group protein 1(HMGB1) in toluene diisocyanate(TDI) induced nucleotide-binding oligomerization domain like receptor family pyrin domain-containing 3(NLRP3) inflammasome activation in human bronchial epithelial cells(HBECs). METHODS: i) The TDI-human serum albumin(HSA) stimulation experiment: the HBECs in logarithmic growth phase were randomly divided into control group, low-, medium-and high-dose groups that were pretreated with TDI-HSA with the final concentration of 0.00, 40.00, 80.00 and 120.00 mg/L for 12 hours. ii) The HMGB1 expression inhibition experiment: the HBECs in logarithmic growth phase were divided into control group, TDI-HSA group, TDI-HAS+negative-siRNA group, and TDI-HAS+HMGB1-siRNA group. The cells in TDI-HAS+negative-siRNA group and TDI-HAS+HMGB1-siRNA group were infected with HBECs with negative-siRNA lentivirus and HMGB1-siRNA lentivirus, respectively. Cells in these two groups and the TDI-HSA group were treated with 120.00 mg/L of TDI-HSA for 12 hours. The cells in the control group were not treated with TDI-HAS. iii) The expression of HMGB1, NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), pro-caspase-1 and caspase-1 p20 proteins in all groups were detected by Western blot. The number of NLRP3 and caspase-1 inflammasome in TDI-HSA stimulation experiment was observed by immunofluorescence method. RESULTS: i) TDI-HSA stimulation experiment: the relative protein expression of HMGB1 and ASC was higher in HBECs of medium-and high-dose groups than that of control group(all P values were <0.01). The relative protein expression of NLRP3 and casepase-1 p20 and the number of NLRP3-caspase-1 inflammasome were higher in HBECs of 3 dose groups than that of control group(all P values were <0.01). The number of NLRP3-caspase-1 inflammasome in HBECs increased obviously in low-, medium-and high-dose groups as compared to the control group(all P values were <0.05). The number of NLRP3-caspase-1 inflammasome in HBECs increased with the increase of TDI-HSA dose(all P values were <0.01). ii) The HMGB1 expression inhibition experiment: the relative protein expression of HMGB1, NLRP3, ASC, pro caspase-1 and caspase-1 p20 in HBECs were higher in the TDI-HSA group and TDI-HSA + negative-siRNA group than those of the control group(all P values were <0.01). The above indexes of HBECs were lower in the TDI-HAS + HMGB1-siRNA group than those in the TDI-HSA group and TDI-HSA + negative-siRNA group(all P values were <0.01).CONCLUSION: TDI treatment in HBECS can induce the increase of HMGB1 protein expression and activate NLPR3 inflammasome. Inhibition of HMGB1 expression can down-regulate the expression of NLPR3 and its related proteins.
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OBJECTIVE: To investigate the effect of toluene diisocyanate(TDI) on the activation of autophagy and expression of inflammatory cytokines interleukin(IL)-4 and IL-6 in normal human bronchial epithelial cells(16 HBE). METHODS: i) We prepared TDI-human serum albumin(HSA) and determined the mass concentration of TDI in TDI-HSA. ii) The cells were treated with TDI-HSA and HSA at concentrations of 0.00-400.00 mg/L for 12 hours. CCK-8 assay was used to determinate the cell viability, and TDI-HSA and HSA doses were selected for subsequent experiments. iii) The cells were treated with TDI-HSA and HSA at doses of 0.00-120.00 mg/L for 12 hours, and the levels of reactive oxygen species(ROS) in the cells were detected by flow cytometry. The levels of IL-4 and IL-6 in the cell supernatant were measured by enzyme-linked immunosorbent assay. iv) The cells were treated with TDI-HSA at doses of 0.00-120.00 mg/L for 12 hours, and the autophagy activity was observed under transmission electron microscope. Western blot was utilized to detect the expression of Beclin1, microtubule-associated protein 1 light chain(LC3β) and P62. RESULTS: i) The mass concentrations of TDI in 40.00, 80.00 and 120.00 mg/L TDI-HSA groups were 0.44, 0.89 and 1.33 mg/L respectively. ii) The results of CCK-8 showed that TDI-HSA and HSA at doses below 120.00 mg/L did not affect cell viability, and 0.00-120.00 mg/L was selected as the TDI-HSA and HSA treatment doses for subsequent experiments. iii) The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells in the TDI-HSA group at 40.00, 80.00, and 120.00 mg/L were higher than that in HSA group at the same dose(P<0.01). The level of ROS in cells and the levels of IL-4 and IL-6 in the supernatant of 16 HBE cells increased with the increase of TDI-HSA doses(P<0.01). iv) Transmission electron microscopy showed that the number of autophagic lysosomes in 16 HBE cells increased significantly, and the number of mitochondrial vacuoles increased in 40.00, 80.00, 120.00 mg/L TDI-HSA group compared with 0.00 mg/L group. With the increase of TDI-HSA dose, the relative expression of Beclin1 protein and LC3β-Ⅱ/Ⅰ ratio in 16 HBE cell supernatant increased(P<0.05), and the relative expression of P62 protein decreased(P<0.05). CONCLUSION: TDI-HSA induces increased expression of ROS and inflammatory factors and induces autophagy activation in 16 HBE cells. Autophagy may be an important factor for the development of airway inflammation in TDI-induced occupational asthma.
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OBJECTIVE: To explore the changes of retinoic acid related orphan receptor-γt( ROR-γt),interleukin( IL)-17 A and forkhead / winged helix protein 3( Foxp3) mRNA expression and promoter methylation in the process of asthma induced by toluene-diisocyanate( TDI). METHODS: Specific pathogens free grade healthy male BALB / c mice were randomly assigned into asthma group and control group with 18 animals in each group. In the asthma group,the mice were sensitized with 0. 30% TDI( mass-volume concentration) dropped on the dorsum of both ears( 20 μL / ear) on day 1 and day 8. On day 15,the mice were challenged with 20 μL 0. 01% TDI( mass-volume concentration) by the trachea. The control group mice were sensitized and challenged by the same procedures with the same amount of solvent( acetone / olive oil). The mice were challenged 24 hours,the pathological changes of trachea and lung tissues were observed. The bronchoalveolar lavage fluid( BALF) from each group was collected,and the inflammatory cells in BALF were counted and classified. IL-4and Interferon-γ( IFN-γ) levels in BALF supernatant were measured by enzyme-linked immunosorbent assay. ROR-γt,IL-17 A and Foxp3 mRNA expression in the lung tissue were measured by real-time fluorescent quantitative polymease chain reaction. The degree of ROR-γt,IL-17 A and Foxp3 promoter methylation in lung issue were detected by Mass Array system.RESULTS: The asthmatic group demonstrated the symptoms of acute asthma,such as breathing deeply and fastly,bowing the back,lifting the forelimbs,et al. But the control group had no such symptoms in mice. Hematoxylin-Eosin staining showed obvious inflammatory lesions in the trachea and lung tissue of asthmatic mice. Compared with the control group,the white blood cell count,the neutrophil and eosinophil percentages in BALF,the IL-4,IFN-γ levels in BALF supernatant in asthma group were all significantly increased( P < 0. 01),meanwhile the lymphocyte and monocyte percentages in BALF were reduced( P < 0. 01); ROR-γt mRNA expression was significantly increased( P < 0. 01),and the degree of promoter methylation from sites 3,4,5,6,8,11 and 12 was significantly reduced( P < 0. 05); IL-17 A mRNA expression was significantly increased( P < 0. 01),and the degree of promoter methylation from sites 6 and 7 was significantly reduced( P < 0. 01); Foxp3 mRNA expression was significantly reduced( P < 0. 01),and the degree of promoter methylation from sites 1 and 10 was significantly increased( P < 0. 01). CONCLUSION: Th17 / Treg cell immune imbalance occurs in asthma induced by TDI. ROR-γt,IL-17 A and Foxp3 gene promoter methylation abnormalities may be involved in Th17 / Treg cell immune imbalance.
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AIM@#To investigate the active chloroform fraction of the ethanol extract of Ipomoea carnea flowers on hematological changes in toluene diisocyanate-induced inflammation in Wistar rats.@*METHOD@#Except for the control group, all of the rats were sensitized with intranasal application of 5 μL of 10% toluene diisocyanate (TDI) for 7 days. One week after second sensitization, all of the rats were provoked with 5 μL of 5% TDI to induce airway hypersensitivity. After the last challenge, blood and bronchoalvelor lavage (BAL) fluid were collected and subjected to total and differential leucocytes count. Flash chromatography was performed on the most active chloroform fraction to isolate an individual component.@*RESULTS@#Treatment with the ethanolic extract and its chloroform fraction at an oral dose of 200 mg·kg⁻¹ showed a significant decrease in circulating neutrophil and eosinophil in blood and BAL as compared with standard dexamethasone (DEXA). The structure of the compound obtained from chloroform fraction of Ipomea carnea was elucidated as stigmast-5, 22-dien-3β-ol on the basis of spectral data analysis.@*CONCLUSION@#The chloroform fraction was found to be more effective to suppress airway hyper reactivity symptoms, and decreased count of both total and differential inflammatory cells.
Subject(s)
Animals , Female , Male , Rats , Asthma , Blood , Drug Therapy , Metabolism , Bronchoalveolar Lavage Fluid , Eosinophils , Metabolism , Flowers , Chemistry , Hematology , Inflammation , Blood , Drug Therapy , Metabolism , Ipomoea , Chemistry , Leukocyte Count , Molecular Structure , Neutrophils , Metabolism , Phytotherapy , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Rats, Wistar , Stigmasterol , Chemistry , Pharmacology , Therapeutic Uses , Toluene 2,4-DiisocyanateABSTRACT
Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 microg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA.
Subject(s)
Humans , Antibodies , Asthma , Asthma, Occupational , Biomarkers , Cyanates , Ferritins , Genetic Markers , Genotype , GTP-Binding Proteins , Haplotypes , Immunoglobulin E , Immunoglobulin G , Isocyanates , Keratins , Leukocytes , Matrix Metalloproteinase 9 , Polymorphism, Genetic , Prevalence , Proteins , Receptors, Neurokinin-2 , Serologic Tests , Toluene 2,4-Diisocyanate , Transferrin , Transglutaminases , Vascular Endothelial Growth Factor AABSTRACT
Antiallergic activity of Aristolochia bracteolata was evaluated by using compound 48/80 induced anaphylaxis, dermatitis rhinitis and pruritis, as a preclinical model for acute phase of hypersensitivity reactions. The late phase hypersensitivity was evidenced by considering toluidine diisocyanate induced volume of bronchoalveolar fluid secretion and its inhibition. The possible antiallergic mechanism was evaluated by using compound 48/80 induced mast cell activation and estimated serum nitric oxide (NO), rat peritoneal fluid NO, bronchoalveolar fluid NO and blood histamine levels. The present study implied that the chloroform extract of Aristolochia bracteolata had potent and significant inhibitory effect on compound 48/80 induced pruritis and dermatitis activity in Swiss albino mice. It showed significant effect in toluidine diisocyanate induced rhinitis in swiss albino mice. Mast cell membrane stabilization activity was also observed in compound 48/80 induced mast cell activation. A significant reduction was observed in serum nitrate levels, rat peritoneal fluid nitrate levels and BAL nitrate levels. The extract was also found to possess significant inhibitory effect on blood histamine levels. It could be concluded that chloroform extract of A. bracteata possess potent antiallergic activity, possibly through mast cell membrane stabilization, inhibiting NO and histamine pathway.
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BACKGROUND: Toluene diisocyanate (TDI) can cause contact allergy and occupational asthma, but the mechanism underlying sensitization to this chemical compound remains controversal. Also the correlation of mast cell with contact hypersensitivity (CHS) and the role of mast cell in the TDI-induced CHS is unknown. This issue was investigated by administrating TDI on the skin of genetically mast cell-deficient WBB6F1/J-Kit(W)/ Kit(W-v) (W/W(V)) and congenic normal WBB6F1/J-Kit +/+ (+/+) mice. METHODS: To development of animal model of TDI-induced CHS and to investigate the correlation of mast cell with CHS and the role of mast cell in the TDI-induced CHS, W/W(V) and +/+ mice were sensitized with TDI on the back skin at day 1 and day 8, and then challenged with 1% TDI on the ear at day 15. At 1, 2, 4, 8, and 24 hours after 1% TDI challenge, the ear thicknesses were measured. It was investigated the histologic changes of dermis in the ear of W/W(V) and +/+ mice at 24 hours after 1% TDI challenge. RESULTS: TDI induced a significant ear swelling response in W/W(V) and +/+ mice. TDI induced the significant infiltrations of polymorphonuclear leukocytes and eosinophils in W/W(V) and +/+ mice, but not of mast cells in normal mice. And TDI increased a characteristic extent of mast cell degranulation in normal mice. There were no significant differences in the ear swelling and the infiltrations of polymorphonuclear leukocytes and eosinophils of normal versus W/W(V) mice, either at baseline or after TDI-induced CHS. CONCLUSION: From the above results, TDI can be used as a murine CHS model, and the mast cells may not be essential in TDI-induced CHS.
Subject(s)
Animals , Mice , Asthma, Occupational , Dermatitis, Contact , Dermis , Ear , Eosinophils , Hypersensitivity , Mast Cells , Models, Animal , Neutrophils , Skin , Toluene 2,4-Diisocyanate , TolueneABSTRACT
BACKGROUND: Toluene diisocyanate (TDI) can cause contact allergy and occupational asthma, but the mechanism underlying sensitization to this chemical compound remains controversal. Also the correlation of mast cell with contact hypersensitivity (CHS) and the role of mast cell in the TDI-induced CHS is unknown. This issue was investigated by administrating TDI on the skin of genetically mast cell-deficient WBB6F1/J-Kit(W)/ Kit(W-v) (W/W(V)) and congenic normal WBB6F1/J-Kit +/+ (+/+) mice. METHODS: To development of animal model of TDI-induced CHS and to investigate the correlation of mast cell with CHS and the role of mast cell in the TDI-induced CHS, W/W(V) and +/+ mice were sensitized with TDI on the back skin at day 1 and day 8, and then challenged with 1% TDI on the ear at day 15. At 1, 2, 4, 8, and 24 hours after 1% TDI challenge, the ear thicknesses were measured. It was investigated the histologic changes of dermis in the ear of W/W(V) and +/+ mice at 24 hours after 1% TDI challenge. RESULTS: TDI induced a significant ear swelling response in W/W(V) and +/+ mice. TDI induced the significant infiltrations of polymorphonuclear leukocytes and eosinophils in W/W(V) and +/+ mice, but not of mast cells in normal mice. And TDI increased a characteristic extent of mast cell degranulation in normal mice. There were no significant differences in the ear swelling and the infiltrations of polymorphonuclear leukocytes and eosinophils of normal versus W/W(V) mice, either at baseline or after TDI-induced CHS. CONCLUSION: From the above results, TDI can be used as a murine CHS model, and the mast cells may not be essential in TDI-induced CHS.
Subject(s)
Animals , Mice , Asthma, Occupational , Dermatitis, Contact , Dermis , Ear , Eosinophils , Hypersensitivity , Mast Cells , Models, Animal , Neutrophils , Skin , Toluene 2,4-Diisocyanate , TolueneABSTRACT
BACKGROUND AND OBJECTIVES: Nitric oxide (NO) in exhaled air is elevated in allergy. Topical corticosteroid therapy which has been shown to reduce airway inflammation is associated with reduction in exhaled levels of NO in allergy. The aim of this study is to investigate the induction of inducible nitric oxide synthase (iNOS) and the effect of steroid on the expression of iNOS in the nasal mucosa of TDI (toluene diisecyanate)-induced nasal hyperreactive guinea pig. MATERIALS AND METHODS: We developed an allergy model in guinea pigs using the intranasal application of TDI, We evaluated the iNOS expression and in vivo effects of triamcinolone on the expression of iNOS and infiltration of eosinophil in TDI-sensitized guinea pigs by immunohistochemical stain. RESULTS: Nasal symptoms were significantly suppressed and the number of eosinophils in the nasal mucosa were significantly inhibited by the treatment of triamcinolone. Immunoreactivity to iNOS was localized to ciliated cells of epithelium, vascular endothelial cells, secretory cells of nasal glands and some inflammatory cells in the mucosa of the control group. High expression of iNOS in the nasal mucosa of the TDI-sensitized group was demonstrated, and it was suppressed by triamcinolone therapy. CONCLUSION: These results show that increased expression of iNOS may contribute to allergic inflammation and the antiinflammatory effect of steroid in allergy is partly mediated by the reduction of iNOS expression.
Subject(s)
Animals , Endothelial Cells , Eosinophils , Epithelium , Guinea Pigs , Guinea , Hypersensitivity , Inflammation , Mucous Membrane , Nasal Mucosa , Nitric Oxide , Nitric Oxide Synthase , Nitric Oxide Synthase Type II , Steroids , Toluene 2,4-Diisocyanate , TriamcinoloneABSTRACT
Following recent advanced industrialization. the amount of polyurethane to use as thermal insulating materials, upholstery mattresses and packing materials in automotive and furniture industry is increasing world-widely, and the number of polyurethane-producing worker will be increased. Because the numerous organic solvents are used in polyurethane-producing factory, the workers in this work site is exposed to many organic solvents. Of the organic solvents. Toluene Diisocyanate(TDI) has many hazardous effects to human. The effects of TDI on human are the irritation to respiratory mucosa and gastrointestinal symptoms. Conjunctival irritation, dermal inflammation (redness, pain, vesicular formation) and gastrointestinal symptom(nausea, vomiting, abdominal pain) are reported just after short-term exposure of TDI. TDI is known to give rise to bronchial asthma, as the immune disorder. And because of strongly volatile characteristics of TDI, it is suggested as a more injurious material to human health, especially human immune system, than other organic solvents. Bronchial asthma inducing mechanism of TDI is not clearly known, but on the analogy of TDI-induced symptoms and recent studies, early-onset asthma is type I hypersensitivity reaction mediated by immunoglobulin E(IgE), and late-onset asthma is maybe type III hypersensitivity reaction by circulating IgG. And we know that the complicated human immune function is likely to move in such that mechanisms, there are not studies on immune indices evaluating the bronchial asthma-related immune function. The evaluation of change patterns of humoral immunity including IgE and IgG and cellular immunity including T-helper cell, T-suppressor cell and T-cytotoxic cell will be helpful to evaluate exposure degrees and prognosis in TDI-exposed workers. Because TDA(toluene diamine) as a biological exposure index of TDI becomes the focus of interest, we know that a study on the correlation between urinary TDA and air TDI and immunological indices will make a contribution to biological effect monitoring indicies. We examined human immunity indicators such as WBC. %Lymph (percentile of Lymphocyte in WBC). %T-cell(percentile of T-lymphocyte in total lymphocyte). CD4, CD8, C3, C4, IgA, IgG, IgM, IgE in peripheral blood to evaluate the health hazard of the TDI-exposed workers. And we examined TDA to evaluate correlation between exposure and effect. Total 90 subjects was selected, 45 workers who worked in the polyurethane-producing factories as an exposed group, and 45 cases who were office workers(10 cases), other blue collors(27 cases), and medical college students(8 cases) as a control group. And the results were as follows ; 1. The logarithm of IgE -Log10(IgE)+/-SD- in peripheral blood of a exposed group was significantly higher than a control group, 2 22+/-.62 in case group compared with 1.98+/-.53 in control group.(p0.05). 3. WBC, %Lymph, %T-cell, C3, C4, CD4, CD8, CD4/CDB ratio and IgG in case group were 6,391.1 ea/ml, 37.53%, 59.54%, 76.68 mg/dl, 30.54 mg/dl, 0.76x10(9) ea/L, 0.63x10(9) ea/L, 1.39, and 1606.29 mg/dl, respectively, and 6,974.7 ea/ml, 35.12%, 59.64%, 71.95 mg/dl, 33.94 mg/dl, 0.80x109 ea/L, 0.61x10(9) ea/L, 1.39, and 1581.51 mg/dl in control group. There was no statistical sinificance between two groups. (p>0.05) 4. In the comparison of each other companies, average of individual urinary TDA in polyurethane paint manufacturing companies is higher than that of polyurethane sponge foaming companies. And, the concentration of 2,6-TDA which is a metabolite of well-vaporized 2,6-TDI is higher than that of 2,4-TDA in the polyurethane sponge foaming companies. But, the concentration of 2,4-TDA which is a metabolite of illvaporized but well skin-absorbed 2,4-TDI is higher in polyurethane paint manufactures. 5. There were no statistical significance in the correlations between individual urinary TDA and immunologic indices.
Subject(s)
Humans , Asthma , Beds , Hypersensitivity, Immediate , Immune Complex Diseases , Immune System , Immune System Diseases , Immunity, Cellular , Immunity, Humoral , Immunoglobulin A , Immunoglobulin E , Immunoglobulin G , Immunoglobulin M , Immunoglobulins , Inflammation , Interior Design and Furnishings , Lymphocytes , Paint , Polyurethanes , Porifera , Prognosis , Respiratory Mucosa , Solvents , T-Lymphocytes , Toluene , Vomiting , WorkplaceABSTRACT
Objective To establish a rapid,accurate and sensitive method for the determination of toluene diisocyanate(TDI) in plastic playground.Methods The samples were distilled continuously for 12 hours by acetone at 80-85 ℃ in water bath,and after centrifuged,precipitated and filtered,separated by using GC1490,7% SE-30 column,the contents of TDI in the samples were determined by gas chromatography.The qualitative and quantitative analyses were carried out by the retention time and peak area respectively.Results The linear range of the method was 0.001 30-0.043 80 mmol/L.Regression equation was y=28 612x-29.336,with r=0.999,and the limit of detection was 0.001 30 mmol/L.The rates of recovery ranged 100.8%-103.6%,with RSD of 5.7%.Conclusion The developed method was rapid,accurate,sensitive and is applicable to the determination of TDI inplastic playground.
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Objective To study the effect of toluene diisocyanate (TDI) on cell multiplication and DNA damage. The present paper also aims to provide the proof for the potential biological effect. Methods The cell growth inhibition rate of toluene diisocyanate (0.04,0.08,0.16 ?mol/ml)was determined with MTT method,the DNA damage of TDI(0.01,0.02,0.04,0.08,0.16 ?mol/ml) was detected by the single cell gel electrophoresis technique (SCGE). Results Toluene diisocyanate caused morphological change of the cells. It could inhibit CHL cells growth with a dose-time-reaction relationship. The cell growth inhibition rate in 0.16 ?mol/ml group was 88.6%. Toluene diisocyanate could induce DNA breakage. The rate of comet tail,DNA content of comet tail and comet tail length in experiment group were higher and showed a dose-response relationship compared with the negative group. The rate of comet tail,DNA content of comet tail and comet tail length in 0.16 ?mol/ml group were 86.30%,34.54% and 7.18 ?m. Conclusion TDI can inhibit the growth of the cells and induce DNA damage.
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Current asthma is often diagnostically excluded by the presence of normal bronchial responsiveness. We report on a TDI-induced occupational asthma patient with normal bronchial responsiveness. He had suffered from shortness of breath during and after TDI exposure for several months. His initial methacholine bronchial challenge test showed a negative response. The bronchoprovacation test with TDI showed an isolated immediate bronchoconstriction. The following methacholine bronchial challenge tests revealed that the bronchial hyperresponsiveness developed seven hours after the TDI challenge (methacholine PC20:5.1 mg/ml), progressed up until 24 hours, and returned to normal on the seventh day. This case provides evidence that the response of the airway to TDI may not always be accompanied by bronchial hyperresponsiveness to methacholine. Screening programs utilizing methacholine challenges may not always identify TDI-sensitized asthmatic workers.
Subject(s)
Adult , Humans , Male , Asthma/chemically induced , Bronchial Provocation Tests , Bronchoconstriction/drug effects , Methacholine Chloride , Occupational Diseases/chemically induced , Skin Tests , Time Factors , Toluene 2,4-Diisocyanate/adverse effectsABSTRACT
Objective To establish a simple,rapid,accurate and sensitive method for determination of free toluene diisocyanate in paint.Method The samples were diluted by acetone and separated using GC,25%SE-30column.The contents of free toluene diisocyanate in the samples of paint were analysed by gas chromatography.The qualitative and the quantitative analyses were carried out based on the retention time and peak height or peak area respectively.Re -sults The linear range of the method was0.000～0.025%with r=0.9997.The RSD was in the range of0.08～0.75%and the recovery rates ranged95.0～106.7%.Conclusion The method was simple,rapid and accurate,which was suit-able for the determination of free toluene diisocyanate in paint.