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 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.
Gaworski
C L
CL
IIT Research Institute, Chicago, Illinois 60616.
Aranyi
C
C
Vana
S
S
Rajendran
N
N
Abdo
K
K
Levine
B S
BS
Hall
A
A
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000633:toxicity*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004798:Enzymes / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000336:Aerosols; D000963:Antimetabolites; D001562:Benzimidazoles; D004798:Enzymes; D014284:Triiodothyronine; C030698:2-mercaptobenzimidazole; D013974:Thyroxine