Quantitation of 4,4'-methylene diphenyl diisocyanate human serum albumin adducts

Details

• Personal Author:
  Arnold SM ; Bartels MJ ; Green, Brett J. ; Luna LG ; Siegel, Paul D. ; Zhang F
• Description:
  4,4'-Methylene diphenyl diisocyanate (herein 4,4'-MDI) is used in the production of polyurethane foams, elastomers, coatings, adhesives and the like for a wide range of commercial products. Occupational exposure to MDI levels above current airborne exposure limits can elicit immune mediated hypersensitivity reactions such as occupational asthma in sensitive individuals. To accurately determine exposure, there has been increasing interest in developing analytical methods to measure internal biomarkers of exposure to MDI. Previous investigators have reported methodologies for measuring MDI diamine metabolites and MDI-Lysine (4,4'-MDI-Lys) adducts. The purpose of this study was to develop and validate an ultra performance liquid chromatography isotope dilution tandem mass spectrometry (UPLC-ID/MS/MS) quantitation method via a signature peptide approach to enable biomonitoring of 4,4'-MDI adducted to human serum albumin (HSA) in plasma. Amurine, anti-4,4'-MDI monoclonal IgM antibody was bound to magnetic beads and utilized for enrichment of the MDI adducted HSA. Following enrichment, trypsin digestion was performed to generate the expected 414 site (primary site of adduction) 4,4'-MDI-adducted HSA signature peptide that was quantified by UPLC-ID/MS/MS. An Agilent 6530UPLC/quadrupole time of flight MS (QTOF) system was utilized for intact adducted protein analysis and an Agilent 6490 UPLC/MS/MS system operated in multiple reaction monitoring (MRM) mode was utilized for quantification of the adducted signature peptidebiomarker both for in chemico and worker serum samples. Worker serum samples were initially screened utilizing the previously developed 4,4'-MDI-Lys amino acid method andresults showed that 12 samples were identified as quantifiable for 4,4'-MDI-Lys adducts.The signature peptide adduct approach was applied to the 12 worker samples identified asquantifiable for 4,4-MDI-Lys adducts. Results indicated no positive results were obtainedabove the quantification limit by the signature peptide approach. If the 414 site of lysineadduction accounted for 100% of the 4,4'-MDI adductions in the signature peptide adductapproach, the three highest quantifiable samples by the 4,4'-MDI-Lys method should haveat least been detectable by the signature peptide method. Results show that although the4,4'-MDI signature peptide approach is more selective, it is 18 times less sensitive thanthe 4,4'-MDI-Lys method, thus limiting the ability to detect adduct levels relative to the4,4'-MDI-Lys amino acid method. [Description provided by NIOSH]
• Subjects:
  Adhesives Air Pollutants, Occupational Asthma Asthma, Occupational Biomarkers Energy Metabolism Isocyanates Mass Spectrometry Occupational Health Particulate Matter Polyurethanes Safety

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• Keywords:
  Adduct Airborne-particles Analytical-processes Author Keywords: MDI Bronchial-asthma Coatings Diisocyanates Liquid-chromatography Mass-spectrometry Mass Spectrometry Metabolites Methyl-compounds Polyurethane-foams

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• ISSN:
  2214-7500
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 3 ; OSHA Region 4 ; 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:
  1
• NIOSHTIC Number:
  nn:20045533
• Citation:
  Toxicol Rep 2014 Oct; 1:743-751
• Email:
  Luna@dow.com
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  False
• Source Full Name:
  Toxicology Reports
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b43375b3c103c27f88a785561e66e69c0173c3321ed70d6e39bccb00b6c1f7e6a7723b7619847a65993df86d9b2c982c21eda283f8cd513fccc8cb569d61d765
• Download URL:
  https://stacks.cdc.gov/view/cdc/200924/cdc_200924_DS1.pdf
• File Type:
  [PDF - 551.69 KB ]