Disposition of toluene diisocyanate (TDI) following dermal exposure

Details

• Personal Author:
  Anderson S ; Beezhold, Donald H. ; Green B ; Nayak A ; Siegel P
• Description:
  RATIONALE: Diisocyanates are highly potent allergens that cause work-related asthma and allergic disease. We describe a model for dermal exposure to diisocyantates using toluene diisocyanate (TDI) as a prototypic hapten that covalently modifies proteins to characterize the dermal exposure route. METHODS: Ears of BALB/c mice were dosed a single time with TDI (0.1%, 4% and 15%) in acetone. Vehicle exposed mice served as controls. Ears and draining lymph nodes were collected at various time points between 1 hour and 15 days post-exposure and were processed for histology and immunochemical assessment. Monoclonal anti-TDI-haptenated protein (TDI-hp, mAb) and anti-langerin (CD207+) were used to examine antigen localization and processing using immunohistochemical confocal microscopy. RESULTS: Hematoxylin and eosin stained sections of mouse ears exhibited edema, followed by infiltration of immune cells, epidermal sheading, hyperplasia, and remodeling. At early time points staining for TDI-hp was found localized to the stratum corneum and in hair follicles and sebaceous glands. Immunostaining for TDI-hp was observed between 1 hour to 4 days post exposure, but could no longer be detected at later time points. Immunohistochemistry showed co-localization of CD207+ positive Langerhans cells and TDI-hp in the hair follicles. Co-localization of antigen and dendritic cells was observed in the lymph nodes by 48 hrs. CONCLUSIONS: TDI-hp were located mainly in the stratum corneum but the hair follicles and associated sebaceous glands appeared to be the hapten route of entry with subsequent migration of TDI-hp to the lymph nodes. These studies showthe utility of TDImAb for characterizing dermal and systemic exposures. [Description provided by NIOSH]
• Subjects:
  Animals Hypersensitivity Immune System Irritants Laboratories Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety Skin Toluene

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• Keywords:
  Allergens Allergic-disorders Exposure-levels Immunology Laboratory-animals Models Proteins Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-irritants Respiratory-system-disorders Skin-exposure Toluenes

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• ISSN:
  0091-6749
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  131
• Issue:
  2
• NIOSHTIC Number:
  nn:20042451
• Citation:
  J Allergy Clin Immunol 2013 Feb; 131(2)(Suppl):AB14
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9) ; Toluene diisocyanate (CAS RN 26471-62-5)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  False
• Source Full Name:
  Journal of Allergy and Clinical Immunology
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:14e2e3c5372428ec6a9b64c20c50900f33b7e24caf3b8bfe34dcf1c0c6d615b345f267200dabf47281580f1983d141e48ce66c821317c4dd0dc961ab6e8e4805
• Download URL:
  https://stacks.cdc.gov/view/cdc/194674/cdc_194674_DS1.pdf
• File Type:
  [PDF - 37.41 KB ]