Collins T F, Sprando R L, Black T N, Shackelford M E, Laborde J B, Hansen D K, Eppley R M, Trucksess M W, Howard P C, Bryant M A, Ruggles D I, Olejnik N, Rorie J I
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, MD 20708, USA.
Food Chem Toxicol. 1998 Aug;36(8):673-85. doi: 10.1016/s0278-6915(98)00036-2.
The developmental toxicity of purified fumonisin B1 (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats. Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FB1 does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity.
对常见玉米真菌串珠镰刀菌产生的霉菌毒素——纯化伏马毒素B1（FB1）的发育毒性，在查尔斯河大鼠中进行了研究。妊娠大鼠在妊娠第3至16天经口给予0、6.25、12.5、25或50毫克FB1/千克体重/天的剂量。在所测试的剂量下，FB1没有致畸性。在50毫克/千克时，观察到母体毒性（食欲不振、消瘦、嗜睡、死亡、整窝吸收）和胎儿毒性（晚期死亡数量增加、胎儿体重下降、顶臀长度减少、脑积水发生率增加、骨骼异常发生率增加）。在50毫克/千克时观察到的胎儿毒性可能与母体毒性有关。对对照组和所有处理组母鼠的组织进行组织病理学评估，发现肾脏和肝脏组织出现与剂量相关的毒性变化。在所有处理组的肾脏中都观察到急性毒性肾小管坏死。在两个高剂量组中，肝脏出现肝细胞胞质改变和个别细胞坏死。在第17天的成年和胎儿组织中测量了鞘氨醇（Sa）和鞘氨醇（So）。在母体肝脏、肾脏、血清和大脑中观察到Sa/So比值与剂量相关的增加，但对胎儿肝脏、肾脏和大脑没有影响。这些数据表明FB1不会穿过胎盘，进一步表明观察到的胎儿毒性是对母体毒性的继发反应。
