Tag: diisocyanate

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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.

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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.

Toxicol Appl Pharmacol. 2015 Jun 11;

Authors: Broström JM, Ye ZW, Axmon A, Littorin M, Tinnerberg H, Lindh CH, Zheng H, Ghalali A, Stenius U, Jönsson BA, Högberg J

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 TDI on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of toluene diisocyanate (TDI) exposure in urine collected from workers exposed to<5p.p.b.(parts per billion). Information on workers’ symptoms was collected through interviews. One nM 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 a 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.

PMID: 26072274 [PubMed – as supplied by publisher]

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Toluene diisocyanate emission to air and migration to a surface from a flexible polyurethane foam.

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Toluene diisocyanate emission to air and migration to a surface from a flexible polyurethane foam.

Ann Occup Hyg. 2013 Jun;57(5):650-61

Authors: Vangronsveld E, Berckmans S, Spence M

Abstract
Flexible polyurethane foam (FPF) is produced from the reaction of toluene diisocyanate (TDI) and polyols. Because of the potential for respiratory sensitization following exposure to TDI, concerns have been raised about potential consumer exposure to TDI from residual ‘free TDI’ in FPF products. Limited and conflicting results exist in the literature concerning the presence of unreacted TDI remaining in FPF as determined by various solvent extraction and analysis techniques. Because residual TDI results are most often intended for application in assessment of potential human exposure to TDI from FPF products, testing techniques that more accurately simulated human contact with foam were designed. To represent inhalation exposure to TDI from polyurethane foam, a test that measured the emission of TDI to air was conducted. For simulation of human dermal exposure to TDI from polyurethane foam, a migration test technique was designed. Emission of TDI to air was determined for a representative FPF using three different emission test cells. Two were commercially available cells that employ air flow over the surface of the foam [the Field and Laboratory Emission Cell (FLEC®) and the Micro-Chamber/Thermal Extraction™ cell]. The third emission test cell was of a custom design and features air flow through the foam sample rather than over the foam surface. Emitted TDI in the air of the test cells was trapped using glass fiber filters coated with 1-(2-methoxyphenyl)-piperazine (MP), a commonly used derivatizing agent for diisocyanates. The filters were subsequently desorbed and analyzed by liquid chromatography/mass spectrometry. Measurement of TDI migration from representative foam was accomplished by placing glass fiber filters coated with MP on the outer surfaces of a foam disk and then compressing the filters against the disk using a clamping apparatus for periods of 8 and 24 h. The sample filters were subsequently desorbed and analyzed in the same manner as for the emission tests. Although the foam tested had detectable levels of solvent-extractable TDI (56ng TDI g(-1) foam for the foam used in emissions tests; 240-2800ng TDI g(-1) foam for the foam used in migration tests), no TDI was detected in any of the emission or migration tests. Method detection limits (MDLs) for the emissions tests ranged from 0.03 to 0.5ng TDI g(-1) foam (0.002-0.04ng TDI cm(-2) of foam surface), whereas those for the migration tests were 0.73ng TDI g(-1) foam (0.16ng TDI cm(-2) of foam surface). Of the three emission test methods used, the FLEC® had the lowest relative MDLs (by a factor of 3-10) by virtue of its high chamber loading factor. In addition, the FLEC® cell offers well-established conformity with emission testing standard methods.

PMID: 23680588 [PubMed – indexed for MEDLINE]

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Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice.

Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice.

Proteomics. 2012 Oct 4;

Authors: Haenen S, Clynen E, De Vooght V, Schoofs L, Nemery B, Hoet PH, Vanoirbeek JA

Abstract
Some reactive chemicals, such as diisocyanates, are capable of initiating an allergic response, which can lead to occupational asthma after a latency period. Clinical symptoms such as cough, wheezing and dyspnea occur only late, making it difficult to intervene at an early stage. So far, most studies using proteomics in lung research have focused on comparisons of healthy vs. diseased subjects. Here, using two-dimensional difference gel electrophoresis (2D-DIGE), we explored proteome changes in the local draining lymph nodes and serum of mice dermally sensitized once or twice with TDI before asthma is induced. In the lymph nodes, we found 38 and 58 differentially expressed proteins after one and two treatments, respectively, between toluene diisocyanate-treated and vehicle-treated mice. In serum, 7 and 16 differentially expressed proteins were detected after one and two treatments, respectively. We identified 80-85% of the differentially expressed proteins by mass spectrometry. Among them, lymphocyte specific protein-1, coronin 1a and hemopexin were verified by Western blotting or ELISA in an independent group of mice. This study revealed alterations in the proteomes early during sensitization in a mouse model before the onset of chemical-induced asthma. If validated in humans, these changes could lead to earlier diagnosis of TDI-exposed workers.

PMID: 23038679 [PubMed – as supplied by publisher]

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