Monoclonal Antibodies (mAbs) to Methylene Diphenyl Diisocyanate (MDI) and Toluene Diisocyanate (TDI) Conjugated Protein: Research and Potential Biomonitoring Applications

Details

• Personal Author:
  Anderson S ; Beezhold, Donald H. ; Green B ; Hettick J ; Johnson V ; Nayak A ; Ruwona T ; Siegel P ; Wisnewski A
• Description:
  Diisocyanates are known immunological sensitizers through both dermal and pulmonary routes of exposure. Research into specific pathophysiological mechanisms and immunologically relevant biomarkers of disease have been hampered by the lack of diisocyanate (dNCO)-specific immunochemical reagents. We have previously reported the production of IgG mAbs that recognize TDI conjugated proteins independent of the specific protein. A hybridoma that produces MDI-protein specific IgM mAbs, which also has good cross-reactivity to hexamethylene diisocyanate conjugated protein, has recently been isolated and cloned. Effort's to create a hybridoma that produces an anti- MDI-protein IgG are ongoing. The dNCO mAbs have proven useful for several research applications including Western Blotting of diisocyanate conjugated proteins and conjugated proteins from TDI exposed cells; immunochemical staining of dermal tissue and enzyme-linked immunoassays (ELISA). Affinity constants for the TDI mAb are very high (108-1010 M-1) suggesting greater utility for immunoassay and immunohistochemistry, but limited use for immunoprecipitation/protein isolation. TDI conjugated human albumin (TDI-HSA) could only be dissociated from a mAb-TDI-HSA complex under harsh denaturing conditions. Preliminary data suggest that both the MDI and TDI mAb may have utility in ELISAs for measurement of dNCO conjugated proteins in sera. Immunohistochemical dermal exposure studies where 4% TDI was applied to mouse ears have also been conducted. These studies demonstrated that TDI-conjugated proteins were located mainly in the stratum cornum and in the epidermis particularly in hair follicles and associated sebaceous glands in the dermis. These preliminary studies suggest potential use of dNCO mAb for assessment systemic and dermal exposure biomarkers and also for research. [Description provided by NIOSH]
• Subjects:
  Antibodies Biomarkers Isocyanates Occupational Health Safety Skin
• Keywords:
  4,4'methylenebisphenyl Isocyanate Biological Effects Dermal Exposures Diisocyanates Immunoassays MDI Proteins
• Publisher:
  Work Wellness and Disability Prevention Institute (WWDPI)
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Connecticut ; Maryland ; North Carolina ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; 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:
  65
• NIOSHTIC Number:
  nn:20054294
• 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; :65
• Contact Point Address:
  Paul Siegel, Team Leader, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  psiegel@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Toluene diisocyanate (CAS RN 26471-62-5)
• Federal Fiscal Year:
  2013
• Peer Reviewed:
  False
• Source Full Name:
  Isocyanates & Health: Past, Present and Future, April 3-4, 2013, Potomac, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:94d367562726d0d82d4923b2835a7b98e66722397fd98610f1632aef621cfa8027918d09fdf566bf2b99e4b540f468353eea017de004f3560769f4da93f54953
• Download URL:
  https://stacks.cdc.gov/view/cdc/216888/cdc_216888_DS1.pdf
• File Type:
  [PDF - 705.52 KB ]