Polymerization of Hexamethylene Diisocyanate in Solution and a 260.23 m/Z [M+H]+ Ion in Exposed Human Cells

Details

• Personal Author:
  Liu J ; Nassar AF ; Redlich CA ; Wisnewski AV
• Description:
  Hexamethylene diisocyanate (HDI) is an important industrial chemical that can cause asthma, however pathogenic mechanisms remain unclear. Upon entry into the respiratory tract, HDI's N=C=O groups may undergo nucleophilic addition (conjugate) to host molecules (e.g. proteins), or instead react with water (hydrolyze), releasing CO2 and leaving a primary amine in place of the original N=C=O. We hypothesized that (primary amine groups present on) hydrolyzed or partially hydrolyzed HDI may compete with proteins and water as a reaction target for HDI in solution, resulting in polymers that could be identified and characterized using LC-MS and LC-MS/MS. Analysis of the reaction products formed when HDI was mixed with a pH buffered, isotonic, protein containing solution identified multiple [M+H]+ ions with m/z's and collision-induced dissociation (CID) fragmentation patterns consistent with those expected for dimers (259.25/285.23 m/z), and trimers (401.36/427.35 m/z) of partially hydrolyzed HDI (e.g. ureas/oligoureas). Human peripheral blood mononuclear cells (PBMCs) and monocyte-like U937, but not airway epithelial NCI-H292 cell lines cultured with these HDI ureas contained a novel 260.23 m/z [M+H]+ ion. LC-MS/MS analysis of the 260.23 m/z [M+H]+ ion suggest the formula C13H29N3O2 and a structure containing partially hydrolyzed HDI, however definitive characterization will require further orthogonal analyses. [Description provided by NIOSH]
• Subjects:
  Asthma, Occupational Biomarkers Isocyanates Occupational Exposure Occupational Health Polymers Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Hexamethylene Diamine Diisocyanate Hexamethylene Diisocyanate Hydrolyze Industrial Exposures Occupational Asthma Polymerize Respiratory Diseases Respiratory Function
• ISSN:
  0003-2697
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  21-29
• Volume:
  543
• NIOSHTIC Number:
  nn:20054085
• Citation:
  Anal Biochem 2018 Feb; 543:21-29
• Contact Point Address:
  Adam V. Wisnewski, Department Internal Medicine/Section General Medicine, Program in Occupational & Environmental Medicine, Yale School of Medicine, 300 Cedar Street/PO Box 208057, Building: TACS420, New Haven, CT 06520-8057, United States
• Email:
  adam.wisnewski@yale.edu
• CAS Registry Number:
  Hexamethylene diisocyanate (CAS RN 822-06-0)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing ; Construction
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  True
• Start Date:
  20130901
• Source Full Name:
  Analytical Biochemistry
• End Date:
  20160831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c4484245d9c4e98842130b591f8182b1b55f8383be00fc79de8c7030b9484db69afd939350e5af18d30366c86d49d8c0b67c111814af1655f4930cb2f5613bbf
• Download URL:
  https://stacks.cdc.gov/view/cdc/216722/cdc_216722_DS1.pdf
• File Type:
  [PDF - 1.22 MB ]