Prechronic inhalation toxicity studies of 2-mercaptobenzimidazole (2-MBI) in F344/N rats

Fundam Appl Toxicol. 1991 Jan;16(1):161-71. doi: 10.1016/0272-0590(91)90144-s.

Abstract

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 greater than or equal to 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 greater than or equal to 25 mg/m3. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at greater than or equal to 6.2 mg/m3, with reduced triiodothyronine and thyroxine levels in both sexes at greater than or equal to 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 greater than or equal to 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Antimetabolites / administration & dosage
  • Antimetabolites / toxicity*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / analysis
  • Benzimidazoles / toxicity*
  • Body Weight / drug effects
  • Enzymes / blood
  • Male
  • Organ Size / drug effects
  • Particle Size
  • Radioimmunoassay
  • Rats
  • Rats, Inbred F344
  • Sex Factors
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Aerosols
  • Antimetabolites
  • Benzimidazoles
  • Enzymes
  • Triiodothyronine
  • 2-mercaptobenzimidazole
  • Thyroxine