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Genotoxicity and immunological changes in isocyanate exposed Brown Norway rats.
Siegel-PD; Zhong-BZ; Lawerence-TE; Lewis-DM
Toxicologist 1999 Mar; 48(1-S):130
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.
Toxicology; Toxins; Toxic-materials; Statistical-analysis; Analytical-methods; Analytical-chemistry; Chemical-analysis; Chemical-properties; Animal-studies; Laboratory-animals; Exposure-assessment; Aerosol-particles; Aerosols; Airborne-particles; Particulates; Carcinogens; Cancer; Amines; Thiols; Isocyanates
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana