Vapor conjugation of toluene diisocyanate to specific lysines of human albumin

Details

• Personal Author:
  Green, Brett J. ; Hettick JM ; Liu J ; Siegel, Paul D. ; Wisnewski AV
• Description:
  Exposure to toluene diisocyanate (TDI), an industrially important crosslinking agent used in the production of polyurethane products, can cause asthma in sensitive workers. Albumin has been identified as a major reaction target for TDI in vivo, and TDI-albumin reaction products have been proposed to serve as exposure biomarkers and to act as asthmagens, yet they remain incompletely characterized. In the current study, we used a multiplexed tandem mass spectrometry (MS/MS) approach to identify the sites of albumin conjugation by TDI vapors, modeling the air/liquid interface of the lung. Vapor phase TDI was found to react with human albumin in a dose-dependent manner, with up to 18 potential sites of conjugation, the most susceptible being Lys351 and the dilysine site Lys413-414. Sites of vapor TDI conjugation to albumin were quantitatively limited compared with those recently described for liquid phase TDI, especially in domains IIA and IIIB of albumin. We hypothesize that the orientation of albumin at the air/liquid interface plays an important role in vapor TDI conjugation and, thus, could influence biological responses to exposure and the development of in vitro assays for exposure and immune sensitivity. [Description provided by NIOSH]
• Subjects:
  Biomarkers Chemistry Immune System Lung Lung Diseases Mass Spectrometry Men Occupational Health Polyurethanes Respiratory System Safety Solvents Toluene Women

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• Keywords:
  Allergy Author Keywords: Toluene Diisocyanate Chemical-composition Chemical-reactions Exposure-levels Exposure-limits Humans Human Serum Albumin Immune-reaction Immune-system Immune-system-disorders Immunologic-disorders Lung-disorders Lung-function Lung-tissue Mass-spectrometry Models Polyurethane-foams Tandem Mass Spectrometry Toluenes Vapors

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• ISSN:
  0003-2697
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; OSHA Region 1 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  421
• Issue:
  2
• NIOSHTIC Number:
  nn:20040181
• Citation:
  Anal Biochem 2012 Feb; 421(2):706-711
• Contact Point Address:
  Justin M. Hettick, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505
• Email:
  jhettick@cdc.gov
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Analytical Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:df28ce2e629f0721ac0612368812dee4dcdec8bf25b4af528d043a85cc08db3277245a03629824a30999a19251239725d6fd254e65795f542b61fcd27d99ae91
• Download URL:
  https://stacks.cdc.gov/view/cdc/193132/cdc_193132_DS1.pdf
• File Type:
  [PDF - 816.82 KB ]