Toxicity study of a rubber antioxidant, 2-mercaptobenzimidazole, by repeated oral administration to rats.
The chemical structure of 2-mercaptobenzimidazole (2-MBI), which is widely used as a rubber antioxidant, is partially similar to those of thiourea (TU) and ethylenethiourea (ETU), both potent thyrotoxic compounds. In order to determine the oral toxicity of 2-MBI, a 28-day repeated dose toxicity study in Wistar rats followed by observation over a 14-day recovery period was conducted at dose levels of 2, 10 and 50 mg/kg 2-MBI administered by gavage. No toxic deaths occurred due to 2-MBI treatment. Decreases of body weight gain and food consumption in the 50 mg/kg dose group were observed during the second half of the treatment period. In addition, hematological examination and serum biochemical tests revealed decreased white blood cells and hemoglobin and increased serum urea nitrogen, cholesterol, phospholipid, gamma-glutamyl transpeptidase and the Na+/K+ ratio in the 50 mg/kg dose group. Marked thyroid enlargement (to 10 fold the control weight), histopathologically associated with diffuse hyperplasia of follicles with decreased colloid and thickening of the fibrous capsule, was found. Reduction in thymus weight was also observed in a dose-dependent manner, without significant histopathological alteration. The non-observed effect level (NOEL) of 2-MBI in this gavage study was found to be less than 2 mg/kg/day based on the significant decrease in thymus weight in the 2 mg/kg 2-MBI treatment group. In an ancillary study, measurement of serum levels of T3, T4 and TSH, and thyroid weight after gavage treatment with 0.15 and 0.3 mmol/kg of three antithyroid compounds for 14 days revealed a more potent antithyroid effect for 2-MBI than for TU or ETU.
Kawasaki
Y
Y
Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Umemura
T
T
Saito
M
M
Momma
J
J
Matsushima
Y
Y
Sekiguchi
H
H
Matsumoto
M
M
Sakemi
K
K
Isama
K
K
Inoue
T
T
Kurokawa
Y
Y
Tsuda
M
M
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D001562:Benzimidazoles / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004435:Eating / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006965:Hyperplasia; D007958:Leukocyte Count; D008297:Male; D009929:Organ Size; D010743:Phospholipids / Q000097:blood; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012408:Rubber; D012964:Sodium / Q000097:blood; D013950:Thymus Gland / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
D000975:Antioxidants; D001562:Benzimidazoles; D006454:Hemoglobins; D010743:Phospholipids; D013963:Thyroid Hormones; C030698:2-mercaptobenzimidazole; D012408:Rubber; D002784:Cholesterol; D012964:Sodium; D005723:gamma-Glutamyltransferase; D011188:Potassium