Chan P C, Mahler J, Bucher J R, Travlos G S, Reid J B
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Toxicon. 1994 Aug;32(8):891-908. doi: 10.1016/0041-0101(94)90368-9.
Toxicity studies of riddelliine, a member of a class of pyrrolizidine alkaloids, were conducted because riddelliine has been found to contaminate human food sources. Groups of male and female Fischer rats were administered riddelliine by gavage in phosphate buffer at doses up to 10 mg/kg, and B6C3F1 mice at doses up to 25 mg/kg, five times a week. The animals were necropsied after 13 weeks of treatment or after a 7 or 14 week recovery period. Body weight gains were inversely related to dose in both rats and mice. Body weight of the 1.0 and 3.3 mg/kg female rats and 10.0 and 25.0 mg/kg mice remained depressed during the 14 week recovery period. At 13 weeks, significant findings included dose-related hepatopathy and intravascular macrophage accumulation in rats and hepatocytomegaly in mice. During the 14 week recovery period these lesions persisted and hepatic foci of cellular alteration in male rats and bile duct proliferation in female rats and male and female mice increased in severity. In the 10 mg/kg group of female rats adenomas of the liver occurred in two of ten at 13 weeks and in one of five at the 14 week recovery period. In separate studies, the frequency of micronucleated erythrocytes in peripheral blood was increased in male mice administered a single dose (150 mg/kg) of riddelliine. Increases in unscheduled DNA and S-phase syntheses were detected in primary hepatocytes from rats and mice treated with riddelliine at doses up to 25.0 mg/kg for 5 or 30 days. In mating trials in rats and mice, pup weights from treated dams at birth and during suckling were lower than controls. Thus, riddelliine is genotoxic and carcinogenic and may cross the placenta and/or be found in milk, causing developmental toxicity in rodents.
对千里光裂碱（一种吡咯里西啶生物碱类成员）进行了毒性研究，因为已发现千里光裂碱会污染人类食物来源。将雄性和雌性Fischer大鼠分组，以高达10mg/kg的剂量通过灌胃给予磷酸盐缓冲液中的千里光裂碱，将B6C3F1小鼠以高达25mg/kg的剂量，每周五次。在治疗13周后或7或14周的恢复期后对动物进行尸检。大鼠和小鼠的体重增加均与剂量呈负相关。在14周的恢复期内，1.0和3.3mg/kg雌性大鼠以及10.0和25.0mg/kg小鼠的体重仍然较低。在13周时，显著的发现包括大鼠中与剂量相关的肝病和血管内巨噬细胞积聚以及小鼠中的肝细胞肿大。在14周的恢复期内，这些病变持续存在，雄性大鼠的细胞改变肝灶以及雌性大鼠和雄性及雌性小鼠的胆管增生严重程度增加。在10mg/kg雌性大鼠组中，13周时十只中有两只出现肝腺瘤，在14周恢复期时五只中有一只出现肝腺瘤。在单独的研究中，给予单剂量（150mg/kg）千里光裂碱的雄性小鼠外周血中微核红细胞的频率增加。在用高达25.0mg/kg的剂量处理5或30天的大鼠和小鼠的原代肝细胞中检测到非计划DNA和S期合成增加。在大鼠和小鼠的交配试验中，经处理的母鼠所产幼崽在出生时和哺乳期间的体重低于对照组。因此，千里光裂碱具有遗传毒性和致癌性，可能会穿过胎盘和/或存在于乳汁中，对啮齿动物造成发育毒性。
