Isotriamine, a Biomarker of Isocyanurate Exposure in Automotive Spray Painters
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2013/04/03
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Description:Purpose: We have measured high levels of inhalation and dermal exposure to isocyanurate (the cyclic trimer of 1,6-hexamethylene diisocyanate; HDI) in automotive spray-painters. Biological monitoring of HDI exposure has been limited to the hydrolysis product of HDI monomer, 1,6-hexamethylene diamine (HDA). Determination of isotriamine as a metabolite of isocyanurate will contribute to the realistic exposure assessment in automotive spray painters. Relevance: Over 200,000 automotive spray painters in the U.S. are exposed annually to HDI-containing spray paints in the work environment. Isocyanurate represents the vast majority of isocyanate exposure in automotive spray painting. Exposure to HDI monomer and its oligomers is associated with a high risk for contact dermatitis and asthma in the automotive repair industry. Isocyanurate sensitization has been observed to be stronger than that of HDI monomer in both humans and animals. In addition, the risk for occupational asthma from exposure to isocyanurate has been observed to be greater than from exposure to HDI monomer. Participants: Urine samples were collected and analyzed from 6 spray painters during 2-4 repeated independent exposure assessment surveys in North Carolina and Washington. Skin and respiratory exposure to isocyanurate were previously assessed using samples collected from the workers' breathing-zone and skin. Methods: Urine (1 mL) from 6 exposed spray painters (n=24) was treated with sulfuric acid and heated for 24 h and then extracted with methanol:formic acid using solid-phase extraction with Phenomenex Strata-X reversed-phase columns. The extract was concentrated by vacuum centrifugation drying and analyzed with ultra-performance liquid chromatography/ tandem-mass spectrometry (UPLC-MS/MS). Analysis: UPLC-MS/MS analysis was performed with a nanoAcquity UPLC system (Waters Corp., Milford, MA) coupled to a TSQ Quantum Ultra triple-quadrupole MS (Thermo Fisher Scientific, Waltham, MA). Reversed-phase separation was carried out using an Atlantis dC18 analytical column, 3 um, 100 um x 100 mm (Waters Corp). Analytes were ionized by nano-electrospray ionization in the positive-ion mode and detected using selected reaction monitoring. Calibration curves were obtained using spiked control urine samples from non-exposed persons. Results: The calibration curve treated with weighted linear regression (1/x2) had a concentration range 0.4-4.0 ug/L (LOQ=0.4; LOD=0.2 ug/L). Isotriamine was detected in 5 of 6 painters and in 10 of 24 urine samples. The isotriamine concentration in the workers' urine ranged from 0.34-0.72 ug/L. Conclusions: The triamine metabolite of isocyanurate in urine can be quantitated in the exposed workers using this extraction procedure and UPLC-MS/MS analysis. This method will be modified for detection of isotriamine in the plasma of exposed workers. Implications: Triamine metabolite of isocyanurate in the urine of workers exposed to HDI-containing spray paints has not been previously reported to our knowledge. Historically, HDI monomer metabolites have been analyzed using derivatization and GCMS analysis. The new UPLC-MS/MS method requires less preparation time, no derivatization, and detects large HDI oligomer metabolites that the GC-MS method cannot detect. This research provides evidence that biological monitoring of HDI oligomer exposure in the workplace can be performed and that assessment of exposure-dose relationship and assessment of adverse health risks due to isocyanurate exposure are warranted in future studies. [Description provided by NIOSH]
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Pages in Document:74
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NIOSHTIC Number:nn:20054289
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Citation:Isocyanates & Health: Past, Present and Future, April 3-4, 2013, Potomac, Maryland. Vancouver, BC, Canada: Work Wellness and Disability Prevention Institute (WWDPI), 2013 Apr; :74
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Email:zgr322@gmail.com
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CAS Registry Number:
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Federal Fiscal Year:2013
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Performing Organization:University of North Carolina, Chapel Hill
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Peer Reviewed:False
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Start Date:20050701
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Source Full Name:Isocyanates & Health: Past, Present and Future, April 3-4, 2013, Potomac, Maryland
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End Date:20270630
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Main Document Checksum:urn:sha-512:eb7f9c8dc8f6e7833dba389d9ebd096d064222960896bb0ecc00e3ea22d57efd0eb3a78182d52b3e2e628aebb4b36c744c9fc9352e60de205e9f248f702df531
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