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i

Population-Based Genetic Model for Diisocyanate-Induced Asthma



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  • Description:
    Our main goal in this research study was to deduce the genetic and mechanistic basis for susceptibility to diisocyanate-induced asthma (DA) caused by exposure to the components of polyurethane-based products. Clearcoats used for painting automobiles are one example of polyurethane-based products that consist of 1,6-hexamethylene diisocyanate (HDI) prepolymers. We studied the two most common forms, the monomer of HDI (HDI-M) and the trimer, HDI isocyanurate (HDIIC). Occupational exposure to these compounds during automobile spray-painting puts workers at risk for DA even when skin is the only exposure route (i.e., a respirator is worn by a worker). About 15% of spray-painters will be diagnosed with DA suggesting that a worker's genetics plays a role in the disease development. Because it is unethical to expose humans to induce DA, we postulated that the use of a genetically diverse mouse model, the Collaborative-Cross (CCRIL), compared to an inbred mouse, BALB/cJ, will demonstrate how each reacts to low, medium, and high levels of HDI-IC to aid in the understanding of the cause of and susceptibility to DA in humans. We also hypothesized that one form of HDI (HDI-IC) is more allergenic than the other (HDI-M) after skin and lung exposure. We were unable to accomplish some of our goals due to isolation and facility closings during the COVID-19 pandemic. We had to limit our testing to the trimer HDI-IC based on its known rapid absorption into the skin and stronger allergenicity as compared to the HDI-M. Therefore, we were unable to test the difference between the two commonly used diisocyanates. However, we were able to detect low levels of sensitization using biomarkers of allergy and asthma in lung fluid and plasma of the exposed CCRILs and inbred mice and to demonstrate inter-strain differences after exposure to HDI-IC. We also observed different forms of asthma in response to HDI-IC treatment between the mouse models. In conclusion, this study provides critical insight into how genetically different mice react to different levels of HDI-IC exposure and further shows that the use of the genetically diverse mouse model is required to investigate the mechanism and risk of skin sensitization and development of DA due to diisocyanate exposure. [Description provided by NIOSH]
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  • Pages in Document:
    1-12
  • NIOSHTIC Number:
    nn:20066304
  • Citation:
    Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R21-OH-011562, 2022 Jan; :1-12
  • Contact Point Address:
    Leena A. Nylander-French, University of North Carolina Chapel Hill, University of North Carolina Chapel Hill, Office of sponsored Research, Chapel Hill, NC 27599-5023
  • Email:
    leena_french@unc.edu
  • CAS Registry Number:
  • Federal Fiscal Year:
    2022
  • NORA Priority Area:
  • Performing Organization:
    University of North Carolina Chapel Hill
  • Peer Reviewed:
    False
  • Start Date:
    20180930
  • Source Full Name:
    National Institute for Occupational Safety and Health
  • End Date:
    20200929
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:cfc58e91fcebf21a55d6e4946824740beeb908b2cd104a57ef7621d5e600cc5a4fd8e2984411570402e2337531867c4f0d55544167aab9705bdd3fc571a6e12f
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  • File Type:
    Filetype[PDF - 159.95 KB ]
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