Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800ppm by inhalation, 6h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800ppm. Body weight gains were decreased in male rats at 900 and 1800ppm and in female mice at 1800ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through alpha2micro-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800ppm, indicating that CPN was increased by mechanisms in addition to those related to alpha2micro-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800ppm. The relationship of these tumors to exposure to MIBK was uncertain. Hepatocellular adenomas, and adenoma or carcinoma (combined) were increased in male and female mice exposed to 1800ppm. There were also treatment-related increases in multiple adenomas in both sexes.

中文翻译：

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F344N 大鼠和 B6C3F1 小鼠吸入暴露 2 年后甲基异丁基酮的毒性和致癌性。

甲基异丁基酮 (MIBK) 主要用作外用酒精的变性剂、溶剂以及甲基戊醇的制造。吸入蒸气是工作场所最可能的暴露途径。为了评估长期暴露后 MIBK 诱导毒性和致癌作用的潜力，将 50 只雄性 F344/N 大鼠和 50 只雌性 F344/N 大鼠和 B6C3F1 小鼠组成的组通过吸入方式暴露于浓度为 0、450、900 或 1800 ppm 的 MIBK，每天 6 小时，每周 5 天，持续 2 年。雄性大鼠的存活率在 1800ppm 时降低。雄性大鼠的体重增加在 900 和 1800 ppm 时有所下降，雌性小鼠的体重增长在 1800 ppm 时有所下降。MIBK 毒性和致癌性的主要目标是大鼠的肾脏和小鼠的肝脏。在雄性大鼠中，所有暴露浓度下肾乳头的矿化均增加。慢性进行性肾病（CPN）的发病率在 1800ppm 时增加，并且所有暴露组的严重程度均增加。在所有暴露浓度下，肾小管增生均有所增加，在 1800ppm 时，腺瘤和腺瘤或癌（合并）也有所增加；这些病变被认为代表肾小管上皮增殖性病变进展的连续体。这些增加可能是由于 CPN 严重程度增加所致，无论是通过 α2 微球蛋白依赖性还是非依赖性机制。单核细胞白血病在 1800ppm 时增加是一个不确定的发现。1800ppm时肾上腺​​髓质增生增加，良性或恶性嗜铬细胞瘤（合并）有增加的正趋势。在雌性大鼠中，所有暴露浓度下 CPN 的发生率均有所增加，且在 1800ppm 时严重程度均有所增加，这表明除了与 α2 微球蛋白相关的机制之外，CPN 的增加还受到其他机制的影响。在 1800ppm 浓度下，两只雌性大鼠出现肾间质肿瘤，这在历史对照动物中未观察到。这些肿瘤与 MIBK 暴露的关系尚不确定。暴露于 1800ppm 的雄性和雌性小鼠的肝细胞腺瘤、腺瘤或癌（合并）均增加。两性的多发性腺瘤也出现了与治疗相关的增加。