Development of a combined irritancy/phenotypic assay for the identification and differentiation of chemicals known to elicit irritation, type I, or type IV hypersensitivity responses.

Details

• Personal Author:
  Manetz TS ; Meade BJ
• Description:
  There remains a need for a rapid, cost effective, reproducible method to identify chemicals with the capacity to elicit irritation, Type I, or Type IV hypersensitivity responses in man. Previous studies in our lab established the use of a phenotypic analysis method that identifies potential Type I allergens by their ability to modulate the level IgE+B220+ draining lymph node cells. Prior observations in our lab and others also suggested that measurement of the percent of draining lymph node B220+ cells by flow cytometry may allow for differentiation of irritants from sensitizers. Therefore, the phenotypic analysis method was incorporated into the protocol of an existing irritancy assay which was investigated for its capacity to identify and differentiate chemicals capable of eliciting irritation, Type I, or Type IV hypersensitivity responses. B6C3Fl female mice were dermally exposed once daily for four consecutive days with concentrations ofTDI (Toluene 2,4-Diisocyanate), TMA (Trimellitic Anhydride) (Type I sensitizers), Dinitrofluorobenzene (DNFB), Oxaz (Oxazolone), and BkCl (Benzalkonium Chloride) (Type IV sensitizers), Tet (Tetradecane) and SLS (Sodium Lauryl Sulfate) (Irritants). Ear swelling was assessed five days and the draining lymph nodes were removed for analysis ten days following initial dermal chemical exposure. The development of the IgE+B220+ population was correlated with the animals' total serum IgE levels. In these studies chemicals known to be irritants but not sensitizers were expected to show an increase in percent ear swelling with no significant increase in the percent of either B220+ or IgE+B220+ cells, which occurred with Tet and SLS exposed animals. Type I sensitizers (TMA, TDI) showed an elevation in the percentage ofB220+ and IgE+B220+ cells. All known Type IV sensitizers tested showed an elevation in B220+ cells with animals exposed to chemicals known to induce slight elevations in the percent oflgE+B220+ cells, although to (Oxaz, BkCl) showing moderate increases in the percent oflgE+B220+ cells. For the sensitizers, the percent increase in ear swelling correlated with their ability to induce irritation. These preliminary studies indicate that _the combined irritancy/ phenotyping assay may be a useful screening tool for identifying and differentiating irritants, Type I and Type IV sensitizers. These studies were in part supported by the NIEHS Contract ES 55387.
• Subjects:
  Accidents, Occupational Air Pollutants, Occupational Air Pollution, Indoor Asbestos Automobiles Dust Occupational Health Particulate Matter Preceptorship Safety
• Keywords:
  Allergens Animals Chemical Composition Chemical Hazards Chemical Properties Chemical Reactions Chemicals Dermal Exposures Diisocyanates Ears Exposure Levels Humans Hypersensitivity Irritants Laboratory Animals Lymph Nodes Men Risk Factors Toluenes Trimellitic Anhydride Women

  More +
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Genre:
  Abstract
• 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:
  16
• NIOSHTIC Number:
  nn:20047942
• Citation:
  Proceedings of the 7th Joint Science Symposium on Occupational Safety and Health, October 26-27 1998, Hidden Valley, Pennsylvania. Cincinnati, OH: National Institute for Occupational Safety and Health,1998 Oct; :16
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9) ; Trimellitic anhydride (CAS RN 552-30-7) ; Quaternary ammonium compounds, alkylbenzyldimethyl, chlorides (CAS RN 8001-54-5) ; Sodium dodecyl sulfate (CAS RN 151-21-3)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the 7th Joint Science Symposium on Occupational Safety and Health, October 26-27 1998, Hidden Valley, Pennsylvania
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:623d93cf61273fe2edeaffc90a2399a502e1b490d9d8800a37e7467d7a240e52e5f8a5094724436a6b031d773a573f16c3c447cf7a756901691141250a5196b2
• Download URL:
  https://stacks.cdc.gov/view/cdc/181682/cdc_181682_DS1.pdf
• File Type:
  [PDF - 46.12 KB ]