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

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 femaleF344/N rats exposed 6 hr/day, 5 days/week to respirable aerosolsgenerated by spray atomization of aqueous suspensions of the2-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 reductionin body weight gains, thyroid follicular cell hyperplasia, adrenalcortex fatty change, and pituitary atrophy. Sub-chronic exposureswere 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 hunchedposture, hypoactivity, and reduced body weight gain, with compoundrelated mortality at the highest exposure level. Anemia; increasedSGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN,and cholesterol; and reduced free fatty acid were seen in ratsat 25 mg/m³. Increased thyroid weight and thyroid follicularcell hyperplasia were noted in both sexes at 6.2 mg/m³, withreduced triiodothyronine and thyroxine levels in both sexesat > 12.5 mg/m³. Thyroid follicular cell hyperplasia wasalso seen in rats at 3.1 mg/m³. Thymus weights were significantlyreduced in both sexes at all exposure levels with liver weightincreases at 6.2 mg/m³. Exposure-related histopathologic changesincluded pituitary cytoplasmic vacuolization, adrenal cortexnecrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy,renal mineralization and tubular atrophy, and hypocellularityof the bone marrow.