Ryu J C, Ohtsubo K, Izumiyama N, Nakamura K, Tanaka T, Yamamura H, Ueno Y
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Fundam Appl Toxicol. 1988 Jul;11(1):38-47. doi: 10.1016/0272-0590(88)90268-0.
In an attempt to ascertain precisely the toxic effects of nivalenol (NIV), we conducted the determination of LD50 values, and interim kills during the carcinogenic study in mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY mice were determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv). Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessed for effects on body weight gain, feed efficiency, terminal organ weights, hematology, and histopathology. The rates of body weight gain and feed efficiency showed a good dose-dependent correlation in all experimental periods. Gross and histopathological evaluation of the liver, thymus, spleen, kidneys, stomach, adrenal glands, pituitary gland, ovaries, sternum, bone marrow, lymph node, brain, and small intestines with or without Peyer's patch portion from control and all NIV-exposed mice revealed that these tissues were normal in appearance and in histopathological structure. Also, no changes were observed in the ultrastructural studies on the bone marrow. Dietary NIV did, however, cause dose-dependent decreases of absolute organ weights (mg) and increases of relative organ weights (mg/g body weight) in the terminal organ weights recorded. A significant leukopenia was observed in the 30 ppm group at 6 months and in all NIV-treated groups at 1 year. No marked changes were observed in the other hematological parameters. These results indicated that 6 ppm or more of dietary NIV for 1 year showed a characteristic toxic effect of trichothecene mycotoxins in mice.
为了精确确定雪腐镰刀菌烯醇（NIV）的毒性作用，我们在小鼠致癌性研究中进行了半数致死剂量（LD50）值的测定以及中期处死实验。6周龄雄性ddY小鼠的NIV LD50值（mg/kg）经测定分别为：经口38.9、腹腔注射7.4、皮下注射7.2和静脉注射7.3。将7周龄雌性C57BL/6CrSlc无特定病原体（SPF）小鼠喂食含0、6、12和30 ppm（mg/kg）NIV的饲料，持续1年，并评估其对体重增加、饲料效率、终末器官重量、血液学和组织病理学的影响。在所有实验阶段，体重增加率和饲料效率均呈现出良好的剂量依赖性相关性。对对照组和所有接触NIV小鼠的肝脏、胸腺、脾脏、肾脏、胃、肾上腺、垂体、卵巢、胸骨、骨髓、淋巴结、脑以及有无派伊尔氏淋巴集结部分的小肠进行大体和组织病理学评估，结果显示这些组织外观和组织病理学结构均正常。此外，骨髓的超微结构研究未观察到变化。然而，在记录的终末器官重量中，饲料中的NIV确实导致了绝对器官重量（mg）的剂量依赖性降低以及相对器官重量（mg/g体重）的增加。在6个月时，30 ppm组观察到明显的白细胞减少，在1年时，所有NIV处理组均观察到明显的白细胞减少。其他血液学参数未观察到明显变化。这些结果表明，1年中饲料中NIV含量达到6 ppm或更高时，在小鼠中表现出了单端孢霉烯族霉菌毒素的特征性毒性作用。
