(2S)-2-[2-[(5R,6R,7S,9S,11R,16R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2-[2-[(5R,6R,7S,9S,11R,16R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid
• 化学式: C₃₄H₅₉NO₁₅
• 分子量: 721.8
• InChiKey: UVBUBMSSQKOIBE-UWCNXKJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  50
• 可旋转键数：
  31
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  289
• 氢给体数：
  8
• 氢受体数：
  16

ADMET

毒理性

• 致癌性证据

评估：对于来自串珠镰刀菌的毒素在人类中的致癌性，证据不足。对于含有大量伏马毒素的串珠镰刀菌培养物在实验动物中的致癌性，有充分的证据。对于伏马毒素B1在实验动物中的致癌性，有有限的证据。总体评估：来自串珠镰刀菌的毒素可能对人类具有致癌性（2B组）。/来自串珠镰刀菌的毒素/

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium moniliforme. There is sufficient evidence in experimental animals for the carcinogenicity of cultures of Fusarium moniliforme that contain significant amounts of fumonisins. There is limited evidence in experimental animals for the carcinogenicity of fumonisin B1. Overall evaluation: Toxins derived from Fusarium moniliforme are possibly carcinogenic to humans (Group 2B). /Toxins derived from Fusarium moniliforme/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别：伏马毒素B1是伏马毒素中最普遍的一种，由真菌串珠镰刀菌和其他镰刀菌属产生。纯净物质是一种白色吸湿性粉末，可溶于水、乙腈-水和甲醇。该物质在食品加工温度和光照下稳定。伏马毒素B1是与玉米相关的最常见的真菌代谢物。当天气条件有利于玉米穗腐时，玉米中会显著积累。人类暴露：没有与这种化合物相关的急性毒性的确认记录。可用的相关性研究表明，饮食暴露与食管癌之间存在关联。其他研究对于伏马毒素B1的潜在致癌性尚无定论。动物/植物研究：伏马毒素B1对所有测试的动物物种（包括小鼠、大鼠、马科动物、猪、兔子和非人灵长类动物）都具有肝脏毒性。除了叙利亚仓鼠外，只有在母体毒性同时或之后才会观察到胚胎毒性或致畸性。伏马毒素对猪、大鼠、羊、小鼠和兔子具有肾脏毒性。在大鼠和兔子中，肾脏毒性发生在低于肝脏毒性的剂量下。伏马毒素已知会导致马脑白质病和猪肺水肿综合征。对某一品系的大鼠具有肝脏致癌性，对另一品系具有肾脏致癌性。伏马毒素B1是新型鞘脂代谢的特异性抑制剂。这种化合物抑制细胞生长，并在动物、植物和一些酵母（如酿酒酵母）中导致自由鞘脂基的积累和脂质代谢的改变。它没有在大肠杆菌中诱导基因突变，也没有在原代大鼠肝细胞中诱导非计划性DNA合成，但在低浓度下诱导了剂量依赖性的染色体畸变增加。这种化合物具有植物毒性，损害细胞膜并减少叶绿素合成。根据使用猪、产蛋鸡和狒狒的研究，当口服给药时，这种化合物吸收不良，并且迅速从血浆或循环中消除并在粪便中回收；胆汁排泄很重要；在一些动物中，肠肝循环很重要。少量通过尿液排出，有些保留在肝脏和肾脏中。

IDENTIFICATION: Fumonisin B1 is the most prevalent of the fumonisins and produced by the fungus Fusarium moniliforme and other F. species. The pure substance is a white hygroscopic powder and is soluble in water, acetonitrile-water and methanol. The material is stable at food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with maize. Significant accumulation in maize occurs when weather conditions favor kernel rot. HUMAN EXPOSURE: There are no confirmed records of acute toxicity associated with this compound. Available correlation studies suggest a link between dietary exposure and esophageal cancer. Other studies are inconclusive as to the potential carcinogenicity of Fumonisin B1. ANIMAL/PLANT STUDIES: Fumonisin B1 is hepatotoxic in all animal species tested including mice, rats, equids, pigs, rabbits and non-human primates. With the exception of Syrian hamsters, embryotoxicity or teratogenicity is only observed concurrent with or subsequent to maternal toxicity. Fumonisins are nephrotoxic in pigs, rats, sheep, mice and rabbits. In rats and rabbits, renal toxicity occurs at lower doses than hepatotoxicity. The fumonisins are known to cause equine leukoencephalomalacia and porcine pulmonary edema syndrome. It is hepatocarcinogenic to male rats in one strain and nephrocarcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid metabolism. This compound inhibits cell growth and causes accumulation of free sphingoid bases and alteration of lipid metabolism in animals, plants and in some yeasts such as Saccharomyces cerevisae. It did not induce gene mutations in bacteria or unscheduled DNA synthesis in primary rat hepatocytes, but induced a dose dependent increase in chromosomal aberrations at low concentrations. This compound is phytotoxic, damages cell membranes and reduces chlorophyll synthesis. This compound is poorly absorbed when dosed orally based on studies using pigs, laying hens and Vervet monkeys and it is rapidly eliminated from the plasma or circulation and recovered in the feces; biliary excretion is important; enterohepatic cycling is important in some animals. Small amounts are excreted in the urine, and some is retained in the liver and kidney.[

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。开始静脉输液，使用D5W /SRP: "保持开放"，最低流速。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……监测休克，如有必要，进行治疗……预计可能出现癫痫，如有必要，进行治疗……对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用生理盐水连续冲洗每只眼睛……不要使用催吐剂。对于摄入，如果患者能够吞咽，有强烈的干呕反射，并且不流口水，用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……在去污后，用干无菌敷料覆盖皮肤烧伤……/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 医疗监测

对于"致癌物"的预防措施：每当需要进行医疗监测时，尤其是在暴露于致癌物的情况下，应就.../细胞遗传学和其他/可能变得有用或必须进行的测试做出特别决定。/化学致癌物/

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Fumonisin B1（FB1）是 Sheldon 镰刀菌产生的镰刀菌素类次级代谢物中的主要化合物，与一些人类和动物疾病有关。在大鼠腹膜内给药（7.5 mg/kg）后，FB1 被迅速吸收，并在注射后20分钟内达到血浆中的最高浓度。此后，它从血浆中迅速清除，表现出符合单室模型的单指数消除阶段，半衰期为18分钟。收集24小时和48小时的尿液样本表明，只有16%的给药剂量未在尿液中代谢排出，且全部在给药后第一个24小时内排出。与此相反，通过灌胃给予相似剂量的FB1，在尿液中仅回收了0.4%的FB1。

Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Fumonisin B1 (FB1)，是真菌Fusarium moniliforme Sheldon的一种有毒和致癌的次级代谢产物，可以通过静脉注射或灌胃的方式给予食蟹猴（Cercopithecus aethiops）。通过静脉注射FB1给两只雌性食蟹猴，FB1从血浆中迅速消除，消除阶段的平均半衰期为40分钟。在给药后5天内对尿液和粪便的分析显示，平均47%的剂量以FB1及其水解类似物的形式回收。给两只雌性食蟹猴单次灌胃14C标记的FB1。在随后的3天内，放射性物质通过粪便排出的平均量为给药剂量的61%，通过尿液排出的量为1.2%。在骨骼肌（1%）、肝脏（0.4%）、大脑（0.2%）、肾脏、心脏、血浆、红细胞和胆汁（每个0.1%）中以低水平回收残留放射性物质，而肠道内容物占放射性剂量的另外12%。总的来说，76%的给药放射性物质被回收。对粪便、肠道内容和尿液的 分析表明，这些样本中超过90%的放射性物质是由FB1及其水解产物引起的。

Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一种用于测定非人灵长类（长尾猴）粪便中伏马菌素B1（FB1）的方法已经开发出来。动物被喂食了标记有14C的FB1，通过用0.1 M乙二胺四乙酸反复提取，回收粪便中的放射性化合物。提取物在反相（C18）固相萃取柱上进行净化，然后通过o-苯基甲醛衍生化和反相高效液相色谱法测定FB1。粪便提取物中FB1的测定方法具有可重复性[2.6%相对标准偏差（RSD）]和准确性（从加标空白提取物中的回收率为93 +/- 2.9% RSD）。通过高效液相色谱和薄层色谱确认了粪便中FB1的鉴定，表明提取的放射性主要对应于FB1和一个具有与霉菌毒素相似色谱性质的新代谢物。通过质谱和核磁共振光谱鉴定出新代谢物是部分水解FB1的两个结构异构体的平衡混合物，这些异构体是通过霉菌毒素的一个酯基的水解形成的。

A method has been developed for the determination of fumonisin B1 (FB1) in the feces of non-human primates (vervet monkeys). The animals were dosed with 14C-labelled FB1, and the radioactive compounds in faeces were recovered by repeated extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned-up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The analytical method for the determination of FB1 in the fecal extracts was reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed that the radioactivity extracted corresponded mainly to FB1 and a new metabolite with chromatographic properties similar to those of the mycotoxin. The new metabolite was identified by mass spectrometry and nuclear magnetic resonance spectroscopy to be an equilibrium mixture of the two structural isomers of partially hydrolysed FB1, which are formed by hydrolysis of one of the ester groups of the mycotoxin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

真菌毒素伏马毒素B1（FB1）会引起动物的各种健康问题，而流行病学证据表明它与人类食管癌有关。我们使用隔离灌注的牛乳腺研究了FB1进入牛乳的情况。将2毫克FB1注入3个乳腺的灌注血液中，并在150分钟内测定乳汁和灌注血清中的水平。FB1穿过了乳腺屏障进入乳汁，但浓度如此之低，对消费者来说风险可以忽略不计。

The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals, while epidemiological evidence suggests it is linked to human esophageal cancer. We investigated the carry-over of FB1 into bovine milk using the isolated perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3 udders, and milk and perfused serum levels were determined for 150 min. FB1 passed through the mammary barrier into the milk, but in such low concentrations as to present a negligible risk for consumers.

来源:Hazardous Substances Data Bank (HSDB)