Chan Po C, Haseman Joseph K, Prejean J D, Nyska Abraham
Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-9998, USA.
Toxicol Lett. 2003 Oct 15;144(3):295-311. doi: 10.1016/s0378-4274(03)00240-6.
These investigations of riddelliine analyzed potential carcinogenesis and the utility of the female-rat/male-mouse design in bioassays and dose-response. Groups of 50 Fischer rats and B6C3F1 mice were gavage-administered riddelliine 5 days per week for 105 weeks. The dose levels for male rats were 0 or 1.0 mg/kg body weight; female rats 0, 0.01, 0.033, 0.1, 0.33, or 1.0 mg/kg; male mice 0, 0.1, 0.3, or 1.0, 3.0 mg/kg; and female mice 0 or 3.0 mg/kg. The dose groups were purposely designed to evaluate the dose-response relationship only in female rats and male mice. In rats, liver hemangiosarcoma, hepatocellular adenoma, and mononuclear cell leukemia were significantly increased in the 1.0 mg/kg male and female dose groups. Non-neoplastic lesions occurred in the liver and kidney of male and female rats. In mice, hemangiosarcomas increased significantly in the liver of males in the 3.0 mg/kg dose group. Alveolar/bronchiolar neoplasms in the 3.0 mg/kg dose group of female mice were significantly increased. Hepatocellular neoplasms were significantly decreased in the 1.0 mg/kg dose group of male and 3.0 mg/kg dose groups of male and female mice. Non-neoplastic lesions occurred in the liver and kidney of male and female, and lung and arteries of female mice. These studies demonstrate toxicity and carcinogenicity of riddelliine in rats and mice, and a dose-response relationship in female rats and male mice under the experimental conditions employed.
这些对瑞得灵的研究分析了潜在致癌作用以及雌性大鼠/雄性小鼠设计在生物测定和剂量反应中的效用。每组50只Fischer大鼠和B6C3F1小鼠，每周5天经口灌胃给予瑞得灵，持续105周。雄性大鼠的剂量水平为0或1.0毫克/千克体重；雌性大鼠为0、0.01、0.033、0.1、0.33或1.0毫克/千克；雄性小鼠为0、0.1、0.3或1.0、3.0毫克/千克；雌性小鼠为0或3.0毫克/千克。剂量组特意设计用于仅评估雌性大鼠和雄性小鼠中的剂量反应关系。在大鼠中，1.0毫克/千克的雄性和雌性剂量组中肝血管肉瘤、肝细胞腺瘤和单核细胞白血病显著增加。雄性和雌性大鼠的肝脏和肾脏出现非肿瘤性病变。在小鼠中，3.0毫克/千克剂量组的雄性小鼠肝脏中血管肉瘤显著增加。3.0毫克/千克剂量组的雌性小鼠肺泡/细支气管肿瘤显著增加。1.0毫克/千克剂量组的雄性小鼠以及3.0毫克/千克剂量组的雄性和雌性小鼠中肝细胞肿瘤显著减少。雄性和雌性小鼠的肝脏和肾脏以及雌性小鼠的肺和动脉出现非肿瘤性病变。这些研究证明了瑞得灵在大鼠和小鼠中的毒性和致癌性，以及在所采用的实验条件下雌性大鼠和雄性小鼠中的剂量反应关系。
