Genotoxicity and Immunological Changes in Isocyanate Exposed Brown Norway Rats

Details

• Personal Author:
  Lawerence TE ; Lewis, Daniel M. ; Siegel, Paul D. ; Zhong BZ
• Description:
  Methylene di-phenyl diisocyanate (MDI) is an important chemical used to make many polyurethane products such as foams and wood binders. The predominant occupational disease attributed to isocyanates including MDl is asthma, however, the potential for genotoxicity has also been of concern. Diisocyanates are very reactive. MDI can be hydrolyzed to methylene dianiline (MDA), and/or react with primary amines and thiols under physiological conditions. MDA is a carcinogen in animals and is a suspected carcinogen in humans. Brown Norway rats (BNR) were exposed to either 7 (LOW) or 113 mglm3 (HIGH) MDI aerosol for 1 hr, 1x/week for 3 weeks with sacrifice 1 week later. A third, acute 135 mg/m3 (ACUTE) MDI aerosolt 1 hr exposure group was sacrificed within 1 hr of exposure to assess acute eosinophilic inflammation. Bone marrow was recovered from HIGH and LOW groups to assess micronuclei formation in polychromatic erythrocytes (PCE) and peripheral blood for measurement of specific antibodies. Trachea and bronchial alveolar lavage were assessed for inflammatory changes. Dose dependent formation of PCE micronuclei formation was noted in MDI exposed BNR. Preliminary in vitro evidence suggest that the genotoxicity may have been mediated through the formation of MDA and/or thioester MDT conjugates. Eosinophilic inflammation measured by histochemical diaaminobertzidine staining of tracheal sections was present only in the acute inflammatory response. T -cells were slightly elevated in the BAL of half of the HIGH MDl exposed BNR and the cd4/cd8 ratio was normal. MDI-specitic IgE was detected in 5/6 and 4/6 of the rats from the LOW and HIGH groups, respectively. MDI-specific IgG was detected in all rats from both groups. These data demonstrates the genotoxic potential along with the allergenic effects of MDl aerosol exposure in the BNR model. [Description provided by NIOSH]
• Subjects:
  Aerosols Air Pollutants, Occupational Amines Animals Carcinogens Chemistry Chemistry, Analytic Environmental Monitoring Hazardous Substances Isocyanates Laboratories Neoplasms Occupational Health Particulate Matter Safety Sulfhydryl Compounds Toxicology

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• Keywords:
  Aerosol-particles Airborne-particles Analytical-chemistry Analytical-methods Animal-studies Cancer Chemical-analysis Chemical-properties Exposure-assessment Laboratory-animals Particulates Statistical-analysis Thiols Toxic-materials Toxins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; 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:
  48
• NIOSHTIC Number:
  nn:20028006
• Citation:
  Toxicologist 1999 Mar; 48(1-S):130
• CAS Registry Number:
  4,4'-Diaminodiphenylmethane (CAS RN 101-77-9) ; Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0094ab0fa505360b3d12228459c8fdc384abff07f7933cb19cd5b7bafe256c453ffb526d106559a2d9ab7534294da3aa1d6589c5ab1d34c4f990d40f633e63bb
• Download URL:
  https://stacks.cdc.gov/view/cdc/189724/cdc_189724_DS1.pdf
• File Type:
  [PDF - 318.47 KB ]