TOXICITY STUDY OF A RUBBER ANTIOXIDANT, 2-MERCAPTOBENZIMIDAZOLE, BY REPEATED ORAL ADMINISTRATION TO RATS

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概要

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• 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, γ-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 T_3, T_4 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.

• 日本トキシコロジー学会の論文
• 1998-02-13

著者

• Umemura T

  Division Of Pathology National Institute Of Health Sciences

• UMEMURA Takashi

  Division of Pathology, National Institute of Health Sciences

• INOUE Tohru

  Safety and Research Center of National Institute of Health Sciences

• Kitajima Satoshi

  Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health

• KAWASAKI Yasushi

  Div of Cellular and Molecular Toxicology

• INOUE Tohru

  Division of Toxicology

• KUROKAWA Yuji

  Division of Toxicology

• Saito Minoru

  Division of Toxicology, National Institute of Health Sciences

• SAKEMI Kazue

  Division of Pharmacology, National Institute of Health Sciences

• TSUDA Mitsuhiro

  Division of Pharmacology, National Institute of Health Sciences

• INOUE Tohru

  Center for Biological Safety and Research

• Kitamura Y

  Division Of Pathology National Institute Of Health Sciences

• Kurokawa Y

  Division Of Toxicology National Institute Of Health Sciences

• Sakemi Kazue

  Division Of Pharmacology National Institute Of Health Sciences

• Saito Minoru

  Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences

• Saito Masako

  Department Of Applied Physics University Of Tokyo:(present Address)institute For Solid State Physics

• Inoue Tohru

  Division Of Toxicol. Mutagen. Nihs

• Tsuda Mitsuhiro

  Division Of Pharmacology National Institute Of Health Sciences

• Sakemi K

  Division Of Pharmacology National Institute Of Health Sciences

• Sakemi Kazue

  Division Of Pharmacology And Biological Safety Research Center National Institute Of Health Sciences

• Sakemi Kazue

  Division Of Pharmacology National Institute Of Hygienic Sciences

• KAWASAKI Yasushi

  Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences

• MOMMA Junko

  Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences

• MATSUSHIMA Yuko

  Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences

• SEKIGUCHI Hiromi

  Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences

• MATSUMOTO Mami

  Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences

• ISAMA Kazuo

  Division ofMedical Devices, Biological Safety Research Center, National Institute of Health Sciences

• SATO Michio

  Div. of Medical Devices National Institute of Hygienic Sciences

• Matsushima Yuko

  国立医薬品食品衛生研究所

• Tsuda Mitsuhiro

  Div.of Toxicology

• Tsuda Mitsuhiro

  Divisions Of Toxicology And Pharmacology National Institute Of Health Sciences

• Unno Takashi

  Division Of Pathology National Institute Of Health Sciences

• Umemura T

  Hokkaido Univ. Sapporo Jpn

• Umemura Takashi

  Division Of Pathology National Institute Of Health Science

• Mathushima Yuko

  Cellular & Molecular Toxicology Division Biological Safety Research Center National Institute Of

• Tsuda Mitsuhiro

  Division Of Pharmacology And Biological Safety Research Center National Institute Of Health Sciences

• Sugi M

  Toin Univ. Yokohama Yokohama Jpn

• Isama Kazuo

  Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences

• Momma Junko

  Division Of Toxicology Biological Safety Research Center National Institute Of Health Sciences

• Momma Junko

  Division Of Toxicol. Mutagen. Nihs

• Unno Takashi

  Japan Pharmaceutical Manufactures Association (jpma):kanebo Ltd

• Matsumoto Masahiro

  Division Of Toxicology Biological Safety Research Center National Institute Of Health Sciences

• Kuroiwa Yuichi

  Division Of Pathology National Institute Of Health Sciences

• Matsushima Yuko

  Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences

• Sekiguchi Hiromi

  Division Of Toxicology Biological Safety Research Center National Institute Of Health Sciences

• Shigeno M

  Sii Nanotechnology Inc.

• Sakemi Kazue

  国立医薬品食品衛生研究所

• Kawasaki Yasushi

  Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences

• Matsushima Yuko

  Division Of Celluar A Molecular Toxicology Center For Biological Safety Research National Institute

• Matsushima Yuko

  Division Of Cellular And Molecular Toxicology National Institute Of Health Sciences

• Momma Junko

  Compliance Review Department The Organization For Drug Adr Relief R&d Promotion And Product Revi

• Umemura Takashi

  Laboratory Of Comparative Pathology Graduate School Of Veterinary Medicine Hokkaido University

• Inoue Tohru

  Division Of Cellular And Molecular Toxicology Center For Biological Safety And Research National Ins

• Inoue Tohru

  Division Of Cellular & Molecular Toxicology Center For Biological Safety Research National Insti

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