Comparative analysis of aromatic diisocyanate conjugation to human albumin utilizing multiplexed tandem mass spectrometry

Details

• Personal Author:
  Hettick JM ; Siegel, Paul D.
• Description:
  Diisocyanates are industrially important chemicals that serve as polymerizing agents in a variety of polyurethane products. In addition to their many industrial uses, diisocyanates have been implicated as causative agents of occupational allergic respiratory disease, although the specific mechanism(s) by which these diseases occur remains unknown. In this study the sites of conjugation of the two most industrially important monomeric diisocyanates, methylene diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI) on human serum albumin are identified utilizing multiplexed tandem mass spectrometry on a quadrupole time-of-flight mass spectrometer. Analysis of human albumin reacted with MDI and TDI over the range of 1:1-40:1 (isocyanate:protein) mol ratio reveals that MDI and TDI react with a maximum of 20 and 37 residues, respectively. Conjugation of diisocyanates to albumin proceeds in a concentrationdependant manner with MDI and TDI reacting at a preferred subset of 5 and 10 residues, respectively, in the limiting case of a 1:1 mol ratio. MDI reacts at fewer residues than does TDI, and is not observed to react with any residues exclusive of TDI. These results cannot be explained on the basis of simple sterics or hydrophobicity, but rather on the basis of increased reactivity of one TDI isocyanate moiety due to electron withdrawing character of the second isocyanate moiety. Furthermore, reaction of diisocyanates with albumin in a phosphate buffered saline (PBS) solution provides three additional reactive sites that are not observed in ammonium bicarbonate buffer. Two lysine residues, Lys199 and Lys525, are observed to be reactive to both diisocyanates at all concentrations and in all solvent systems employed in this study. This study presents a comprehensive conjugation map of MDI and TDI on human albumin. The results suggest that several albumin residues are reactive toward both MDI and TDI and may be useful for biomonitoring of diisocyanate exposures. [Description provided by NIOSH]
• Subjects:
  Chemistry Lung Lung Diseases Mass Spectrometry Occupational Health Polymers Polyurethanes Respiratory System Respiratory Tract Diseases Safety Toluene

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• Keywords:
  Allergy Author Keywords: Diisocyanates Chemical-composition Mass-spectrometry Polymerization Polyurethane-foams Protein Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-system-disorders Tandem Mass Spectrometry Toluenes

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• ISSN:
  1387-3806
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  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
• Pages in Document:
  168-175
• Volume:
  309
• Issue:
  1
• NIOSHTIC Number:
  nn:20040165
• Citation:
  Int J Mass Spectrom 2012 Jan; 309(1):168-175
• Contact Point Address:
  Justin M. Hettick, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  jhettick@cdc.gov
• CAS Registry Number:
  Toluene (CAS RN 108-88-3)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  International Journal of Mass Spectrometry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:aeba61078ee8804dd6315305d9cfbedc741aa8b6b44110981418849cd9273622ef4a56bad0cb9a09957f81b6f78f657809ba9619dbd017a8c8c717052c6c72c9
• Download URL:
  https://stacks.cdc.gov/view/cdc/193120/cdc_193120_DS1.pdf
• File Type:
  [PDF - 718.50 KB ]