[(1R,2S,7S,9R,10S,11R,12R)-3,10-dihydroxy-2-(hydroxymethyl)-1,5-dimethyl-4-oxospiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-11-yl] acetate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1R,2S,7S,9R,10S,11R,12R)-3,10-dihydroxy-2-(hydroxymethyl)-1,5-dimethyl-4-oxospiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-11-yl] acetate
• 化学式: C₁₇H₂₂O₈
• 分子量: 354.4
• InChiKey: XGCUCFKWVIWWNW-ZMXHXVLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  8

ADMET

代谢

气相色谱-质谱分析显示，在肉鸡和鸭子服用FX后，大部分FX以NIV/脱氧雪腐镰刀菌烯醇/的形式恢复。在体外，将FX与肝脏微粒体和细胞质部分一起培养，证明肝脏和肾脏能够进行FX到NIV的转化...

The gas chromatography-mass spectrometry profile in plasma showed that a large proportion of FX was recovered as NIV /nivalenol/ after administration of FX in both broilers and ducks. In vitro incubation of liver microsomal and cytosolic fractions with FX demonstrated that the liver and kidney are capable of the FX-to-NIV conversion...

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠肝亚组分实验中发现，fusarenon-X和T-2毒素通过微粒体酯酶在C-4（R2）位置脱乙酰化，分别产生了nivalenol和HT-2毒素。这些结果表明，给小鼠和大鼠施用的三线镰刀菌素通过肝脏酶转化为脱乙酰化产物，然后通过粪便和尿液排出体外。

Experiments with subfractions of rat liver revealed that fusarenon-X & T-2 toxin were deacetylated at C-4 (R2) by microsomal esterase & yielded nivalenol & HT-2 toxin, respectively. These findings indicate that the trichothecenes admin to mice & rats are metabolized by liver enzyme(s) into deacetylated products, which are then eliminated in the feces & urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

高效液相色谱法检测尿和粪便中乙腈提取物的放射性剖面图显示，FX在从胃肠道吸收后迅速代谢为NIV。组织匀浆与(3)H-FX的体外孵化实验表明，肝脏和肾脏是将FX转化为NIV的主要器官。

The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with (3)H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion...

来源:Hazardous Substances Data Bank (HSDB)

代谢

...霉菌毒素的植物代谢物，也称为隐蔽霉菌毒素。霉菌毒素是真菌的次级代谢物，对人类和动物有毒。产毒真菌通常在可食用植物上生长，从而污染食品和饲料。作为活生生的生物，植物可以改变霉菌毒素的化学结构，作为它们对抗外来化合物的防御的一部分。形成的可提取结合或不可提取结合的霉菌毒素仍然存在于植物组织中，但目前既没有在食品中常规筛查，也没有通过立法进行规定，因此它们可能被认为是隐蔽的。镰刀菌霉菌毒素（脱氧雪腐镰刀菌烯醇、玉米赤霉烯酮、伏马毒素、雪腐镰刀菌烯醇、镰刀菌烯-X、T-2毒素、HT-2毒素、镰刀菌酸）容易通过植物的代谢或结合，但植物对其他霉菌毒素（赭曲霉毒素A、棒曲霉毒素、破坏菌素）的转化也已经有过描述。毒理学数据很少，但有几项研究表明这些物质对消费者安全构成了潜在威胁。特别是，隐蔽霉菌毒素在哺乳动物消化过程中可能水解回其有毒的母体，这引起了人们的关注。

...plant metabolites of mycotoxins, also called masked mycotoxins. Mycotoxins are secondary fungal metabolites, toxic to human and animals. Toxigenic fungi often grow on edible plants, thus contaminating food and feed. Plants, as living organisms, can alter the chemical structure of mycotoxins as part of their defence against xenobiotics. The extractable conjugated or non-extractable bound mycotoxins formed remain present in the plant tissue but are currently neither routinely screened for in food nor regulated by legislation, thus they may be considered masked. Fusarium mycotoxins (deoxynivalenol, zearalenone, fumonisins, nivalenol, fusarenon-X, T-2 toxin, HT-2 toxin, fusaric acid) are prone to metabolism or binding by plants, but transformation of other mycotoxins by plants (ochratoxin A, patulin, destruxins) has also been described. Toxicological data are scarce, but several studies highlight the potential threat to consumer safety from these substances. In particular, the possible hydrolysis of masked mycotoxins back to their toxic parents during mammalian digestion raises concerns.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Trichothecenes是一组主要由Fusarium属真菌产生的霉菌毒素。消费者特别关注来自食用动物的食物安全和T-2毒素、脱氧雪腐镰刀菌烯醇（DON）、雪腐镰刀菌烯醇（NIV）、镰刀菌烯-X（FX）、二乙酰氧基香豆素（DAS）、3-乙酰脱氧雪腐镰刀菌烯醇（3-aDON）和15-乙酰脱氧雪腐镰刀菌烯醇（15-aDON）及其代谢物在啮齿类动物、猪、反刍动物、家禽和人体内的代谢情况。这些霉菌毒素的代谢途径非常不同。T-2毒素在动物体内的主要代谢途径是水解、羟基化、脱环氧化和结合。转化为HT-2毒素后，它在C-3'位置进一步羟基化，生成3'-羟基-HT-2毒素，这被认为是一种活化途径，而T-2毒素转化为T-2四醇是一种动物体内的失活途径。T-2毒素在动物体内的典型代谢物是HT-2毒素、T-2三醇、T-2四醇、新鞘氨醇（NEO）、3'-羟基-HT-2和3'-羟基-T-2，而在人体内HT-2毒素是主要的代谢物。脱环氧化是动物体内解毒的重要途径。脱环氧产物DOM-1和脱环氧-NIV分别是DON和NIV在大多数动物体内的主要代谢物。然而，这两种代谢物在人体内并未发现。乙酰衍生物3-aDON、15-aDON和FX上的脱乙酰作用可以迅速发生。DAS在动物体内代谢为15-单乙酰氧基香豆素（15-MAS）通过C-4脱乙酰化，然后转化为香豆三醇（SCP）通过C-15脱乙酰化。最后，环氧基团丢失，生成脱环氧-SCP。脱环氧-15-MAS也是DAS的主要代谢物。15-MAS是人类皮肤中的主要代谢物。这篇关于Trichothecenes代谢的综述将帮助人们更好地理解这些毒素在动物和人体内的命运，并为食品安全的风险评估提供基本信息。

Trichothecenes are a group of mycotoxins mainly produced by the fungi of Fusarium genus. Consumers are particularly concerned over the toxicity and food safety of trichothecenes and their metabolites from food-producing animals. The metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), fusarenon-X (FX), diacetoxyscirpenol (DAS), 3-acetyldeoxy-nivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, swine, ruminants, poultry, and humans are reviewed in this article. Metabolic pathways of these mycotoxins are very different. The major metabolic pathways of T-2 toxin in animals are hydrolysis, hydroxylation, de-epoxidation, and conjugation. After being transformed to HT-2 toxin, it undergoes further hydroxylation at C-3' to yield 3'-hydroxy-HT-2 toxin, which is considered as an activation pathway, whereas transformation from T-2 to T-2 tetraol is an inactivation pathway in animals. The typical metabolites of T-2 toxin in animals are HT-2 toxin, T-2 triol, T-2 tetraol, neosolaniol (NEO), 3'-hydroxy-HT-2, and 3'-hydroxy-T-2, whereas HT-2 toxin is the main metabolite in humans. De-epoxidation is an important pathway for detoxification in animals. De-epoxy products, DOM-1, and de-epoxy-NIV are the main metabolites of DON and NIV in most animals, respectively. However, the two metabolites are not found in humans. Deacetyl can occur rapidly on the acetyl derivatives, 3-aDON, 15-aDON, and FX. DAS is metabolized in animals to 15-monoacetoxyscirpenol (15-MAS) via C-4 deacetylation and then transformed to scirpentriol (SCP) via C-15 deacetylation. Finally, the epoxy is lost, yielding de-epoxy-SCP. De-epoxy-15-MAS is also the main metabolite of DAS. 15-MAS is the main metabolite in human skin. The review on the metabolism of trichothecenes will help one to well understand the fate of these toxins' future in animals and humans, as well as provide basic information for the risk assessment of them for food safety.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于禾谷镰刀菌产生的毒素在人类中的致癌性，目前证据不足。关于从F. crookwellense和F. culmorum产生的毒素对人类致癌性的数据并不存在。... 对于fusarenone X在实验动物中的致癌性，证据也不足。... 总体评估：来自禾谷镰刀菌、F. culmorum和F. crookwellense的毒素对人类的致癌性无法分类（第3组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium graminearum. No data were available on the carcinogenicity to humans of toxins derived from F. crookwellense and F. culmorum. ... There is inadequate evidence in experimental animals for the carcinogenicity of fusarenone X. ... Overall evaluation: Toxins derived from Fusarium graminearum, F. culmorum and F. crookwellense are not classifiable as to their carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

脱氧雪腐镰刀菌烯醇（DON）是欧洲和北美作物中最普遍的镰刀菌毒素。DON经常与其他B型镰刀菌毒素如3-乙酰脱氧雪腐镰刀菌烯醇（3-ADON）、15-乙酰脱氧雪腐镰刀菌烯醇（15-ADON）、雪腐镰刀菌烯醇（NIV）和镰刀菌素-X（FX）一起存在。尽管单个真菌毒素的细胞毒性已经被广泛研究，但关于真菌毒素混合物毒性的数据有限。这项研究的目的是评估B型镰刀菌毒素共同暴露对肠道上皮细胞的影响。将增殖的Caco-2细胞暴露于不断增加剂量的B型镰刀菌毒素，单独使用或以二种或三种混合物形式使用。使用与线粒体和溶酶体功能相关的MTT试验和中性红摄取来测量肠道上皮细胞毒性。五种测试的真菌毒素对增殖的肠细胞有剂量依赖性影响，并且可以按照毒性增加的顺序分类：3-ADON<15-ADON约等于DON<NIV远小于FX。二种或三种混合物也显示出剂量依赖性效应。在低浓度下（细胞毒性效应在10%到30-40%之间），真菌毒素组合表现出协同作用；然而，DON-NIV-FX混合物表现出拮抗作用。在高浓度下（细胞毒性效应约为50%），组合物具有相加或几乎相加的效果。这些结果表明，食品商品和饮食中同时存在低剂量的真菌毒素可能比单独的真菌毒素预测的毒性更大。考虑到饮食中镰刀菌毒素的频繁共存以及消费者接触到的毒素浓度，应该考虑这种协同作用。

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON equal approx. DON<NIV much less FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40%), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons 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（如有需要，使用口咽或鼻咽气道）。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……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons A and B/

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、严重肺水肿或严重呼吸困难的病人，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。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。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……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /毒物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 severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在小鼠中进行ip注射后，大部分剂量的(3)H-伏沙雷诺-X迅速通过尿液排出；3小时后，组织中几乎没有放射性残留。

Following... ip injection in mice, most of a dose of (3)H-fusarenon-X was rapidly excreted in the urine; almost no radioactivity remained in the tissues after 3 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(3) H-fusarenon-X sc注射到小鼠体内后，从注射部位迅速吸收并分布到肝脏、肾脏、肠道和其他器官。大约25%的总放射性在24小时内通过尿液排出。

(3)H-fusarenon-X sc injected in mice was rapidly absorbed from the injection site & distributed to the liver, kidneys, intestines, & other organs. About 25% of the total radioactivity was eliminated in the urine within 24 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

皮下给药后30分钟，在肝脏、肾脏、肠道、胃、脾脏、胆汁和血浆中发现了活性，心脏、大脑或睾丸中未检测到活性。活性最高的是肝脏，占给药剂量的3%。给药12小时后，器官中无放射性标记，25%的剂量以呋喃内酯X的代谢形式在尿液中回收。

Thirty minutes after subcutaneous administration of uniformly labeled (3)H-fusarenone X at 4 mg/kg body weight to mice, activity was found in liver, kidneys, intestines, stomach, spleen, bile and plasma; none was detected in heart, brain or testis. The highest activity, corresponding to 3% of the dose, was observed in the liver. Twelve hours after administration, no label was present in the organs, and 25% of the dose was recovered as metabolized forms of fusarenone X in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了研究呋喃菌素-X（FX）在肉鸡和鸭子体内的比较命运和处置，FX通过静脉注射（i.v.）或口服（p.o.）给药给肉鸡和鸭子。使用气相色谱-质谱法测定血浆和排泄物中的FX及其代谢物（尼瓦伦醇，NIV）。在静脉注射和口服给药后，肉鸡和鸭子分别在180分钟和120分钟内测定了FX的血浆浓度。NIV的消除速度比其母体化合物慢...因此，本研究表明FX在鸭子中的吸收效率高于肉鸡，而在鸭子中的消除速度慢于肉鸡。

In order to investigate the comparative fates and dispositions of fusarenon-X (FX) in broilers and ducks, FX was administered i.v. or orally (p.o.) to broilers and ducks. The FX and its metabolite (nivalenol, NIV) were determined in plasma and excreta using gas chromatography-mass spectrometry. The plasma concentrations of FX were determined up to 180 and 120 min in broilers and ducks, respectively, after i.v. and p.o. administration. The NIV was eliminated more slowly than its parent compound... Thus, this study demonstrated that FX is absorbed more efficiently in ducks than in broilers, whereas it is eliminated more slowly in ducks than in broiler chickens.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了研究nivalenol（NIV）及其4-乙酰衍生物（fusarenon-X，FX）在小鼠体内的比较命运，将(3)H-FX或(3)H-NIV口服给小鼠。给予(3)H-FX的小鼠主要通过尿液排出放射性，而给予(3)H-NIV的小鼠则主要通过粪便排出。给予(3)H-FX或(3)H-NIV后，血浆放射性在30或60分钟达到峰值。血浆峰值水平在(3)H-FX给药的小鼠中比(3)H-NIV给药的小鼠高5倍，曲线下面积（AUC）高10倍。这些发现清楚地表明，FX比NIV更快速、更有效地从胃肠道吸收...因此，本研究表明，在小鼠和大鼠中观察到的FX比NIV的口服毒性更高，是因为FX比NIV更有效地从胃肠道吸收，随后被肝脏和肾脏迅速转化为NIV。

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, (3)H-FX or (3)H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given (3)H-FX, but mainly via the feces in mice given (3)H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of (3)H-FX or (3)H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in (3)H-FX-administered than (3)H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV... Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.

来源:Hazardous Substances Data Bank (HSDB)