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© 1991 Oxford University Press

research-article

Prechronic Inhalation Toxicity Studies of 2-Mercaptobenzimidazole (2-MBI)in F344/N Rats

CHARLES L. GAWORSKI*,2, CATHERINE ARANYI*,3, STANLEY VANA*, NARAYANAN RAJENDRAN*, KAMAL ABDO{dagger}, BARRY S. LEVINE{ddagger} and ALAN HALL, III§

*IIT Research Institute 10 West 35th Street, Chicago, Illinois 60616 {dagger}National Institute of Environmental Health Sciences, National Toxicology Program Research Triangle Park, North Carolina 27709 {ddagger}University of Illinois at Chicago Chicago, Illinois 60612 §Pathology Associates, Inc. Chicago, Illinois 60616

Received April 30, 1990; accepted August 15, 1990

2-Mercaptobenzimidazole (2-MBI), used in rubber processing, is a suspect carcinogen structurally related to ethylene thiourea. The inhalation toxicity of 2-MBI was evaluated in male and female F344/N rats exposed 6 hr/day, 5 days/week to respirable aerosols generated by spray atomization of aqueous suspensions of the 2-MBI powder and subsequent drying of the resulting aerosols. Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0, 50.0, or 100 mg/m3 of 2-MBI produced a dose-related reduction in body weight gains, thyroid follicular cell hyperplasia, adrenal cortex fatty change, and pituitary atrophy. Sub-chronic exposures were conducted at target concentrations of 0, 3.1, 6.2, 12.5, 25.0, and 50.0 mg/m3 of 2-MBI. Rats at ≥25 mg/m3 displayed hunched posture, hypoactivity, and reduced body weight gain, with compound related mortality at the highest exposure level. Anemia; increased SGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN, and cholesterol; and reduced free fatty acid were seen in rats at ≥25 mg/m3. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at ≥6.2 mg/m3, with reduced triiodothyronine and thyroxine levels in both sexes at > 12.5 mg/m3. Thyroid follicular cell hyperplasia was also seen in rats at 3.1 mg/m3. Thymus weights were significantly reduced in both sexes at all exposure levels with liver weight increases at ≥6.2 mg/m3. Exposure-related histopathologic changes included pituitary cytoplasmic vacuolization, adrenal cortex necrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy, renal mineralization and tubular atrophy, and hypocellularity of the bone marrow.


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