[(1R,2S,9S,10R,11R,12R)-11-acetyloxy-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-2-yl]methyl acetate | 2270-40-8

• 物质功能分类: 分析化学 - 标准品 - 食品和化妆品标准品
• 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,9S,10R,11R,12R)-11-acetyloxy-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-2-yl]methyl acetate
• CAS: 2270-40-8
• 化学式: C₁₉H₂₆O₇
• 分子量: 366.4
• InChiKey: AUGQEEXBDZWUJY-NXHGFVQPSA-N

物化性质

• 熔点：
  162-164℃
• 沸点：
  407.62°C (rough estimate)
• 密度：
  1.1821 (rough estimate)
• 闪点：
  2 °C
• 溶解度：
  DMF：30mg/mL； DMF:PBS (pH 7.2) (1:4)：0.2 mg/mL； DMSO：30mg/mL；乙醇：20mg/mL
• 颜色/状态：
  Solid
• 蒸汽压力：
  3.8X10-9 mm Hg at 25 °C (est)
• 亨利常数：
  Henry's Law constant = 9.8X10-17 atm-cu m/mole at 25 °C (est)
• 稳定性/保质期：
  These toxins are heat and uv light stable... and capable of long-term storage... . /Trichothecenes/
• 旋光度：
  Specific optical rotation = -27 deg at 20 °C/D
• 分解：
  Hazardous decomposition products formed under fire conditions. - Carbon oxides

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  94.6
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

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毒素是主要代谢物。脱环氧化是动物体内解毒的重要途径。DON和NIV在大多数动物体内的主要代谢物分别是DOM-1和脱环氧化-NIV。然而，这两种代谢物在人体内并未发现。3-aDON、15-aDON和FX的乙酰衍生物可以迅速发生脱乙酰作用。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，然后转化为香豆素三醇（SCP）通过C-15脱乙酰化。最后，环氧化消失，产生脱环氧化-SCP。脱环氧化-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未来命运，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)

代谢

三环烯类化合物，如T-2毒素、二乙酰氧基雪腐烯醇和脱氧雪腐镰刀菌烯醇，在饲料中存在，它们主要通过两相代谢途径进行代谢。在第一阶段进行氧化和水解，而第二阶段则将转化产物与葡萄糖醛酸结合；此外，环氧环会被肠道微生物群裂解。T-2毒素的代谢物包括HT-2毒素、3'-羟基-T-2毒素、3'-羟基-HT-2毒素、新茄三醇、4-去乙酰新茄三醇、T-2三醇、T-2四醇和去环氧T-2四醇。二乙酰氧基雪腐烯醇转化为15-单乙酰氧基雪腐烯醇、雪腐三醇、去环氧15-单乙酰氧基雪腐烯醇和去环氧雪腐三醇。脱氧雪腐镰刀菌烯醇没有广泛的代谢；仅假定产生脱氧雪腐镰刀菌烯醇葡萄糖苷酸和去环氧脱氧雪腐镰刀菌烯醇。由于三环烯类化合物迅速代谢，通过分析猪源样本诊断中毒几乎是不可能的；同样地，三环烯类代谢物在食用组织中富集的可能性被认为是低的。

Trichothecenes like T-2 toxin, diacetoxyscirpenol, and deoxynivalenol, which occur in feed, are metabolized preponderant in a biphasic way. Oxidation and hydrolysis are carried out in phase 1, while the transformation products are conjugated with glucuronic acid in phase 2; in addition, the epoxide ring is cleaved by the gut microflora. Metabolites of T-2 toxin are HT-2 toxin, 3'-hydroxy-T-2 toxin, 3'-hydroxy-HT-2 toxin, neosolaniol, 4-deacetylneosolaniol, T-2 triol, T-2 tetraol, and de-epoxide T-2 tetraol. Diacetoxyscirpenol is transformed to 15-monoacetoxyscirpenol, scirpenetriol, de-epoxide 15-moneacetoxyscirpenol, and de-epoxide scirpenetriol. Deoxynivalenol undergoes no extensive metabolism; only the production of deoxynivalenol glucuronide and de-epoxide deoxynivalenol is assumed. As trichothecenes are rapid metabolized, the diagnosis of an intoxication by the analysis of samples of pig origin should be hardly possible; for the same reason, the possibility of an enrichment of trichothecene metabolites in edible tissues is graded as low.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

The possible protective effect of a feed additive (Mycofix) against the toxic effects of 4,15-diacetoxiscirpenol (DAS) in growing broiler chickens was investigated in a 21-d fully randomized trial consisting of seven dietary treatments (control with no DAS or Mycofix added, 1 ppm DAS alone, 1 ppm DAS supplemented with 0.75 g/kg Mycofix, 1 ppm DAS supplemented with 1.5 g/kg Mycofix, 2 ppm DAS alone, 2 ppm DAS supplemented with 0.75 g/kg Mycofix, and 2 ppm DAS supplemented with 1.5 g/kg Mycofix). When no feed additive was included, both levels of dietary DAS significantly decreased BW and feed intake and caused oral lesions, with the effect of 2 ppm DAS being more severe. When 1 ppm DAS was added to the diet, supplementation of Mycofix protected against the adverse effects of DAS on feed intake and BW at both levels of inclusion (0.75 and 1.5 g/kg); however, no protection against oral lesions was obtained by Mycofix supplementation. This finding suggests that the adverse effect of DAS on performance is not due to the oral lesions per se but it is likely the result of the systemic absorption of the mycotoxin. When 2 ppm dietary DAS was present in the diet, only partial protection on BW and feed intake was obtained by Mycofix supplementation. 调查了一种饲料添加剂（Mycofix）对生长肉鸡中4,15-二乙酰氧基螺旋醇（DAS）毒性效应的可能保护作用。在一项为期21天的完全随机试验中，包括了七种不同的饮食处理（对照组不加DAS或Mycofix，单独使用1 ppm DAS，1 ppm DAS配合0.75 g/kg Mycofix，1 ppm DAS配合1.5 g/kg Mycofix，单独使用2 ppm DAS，2 ppm DAS配合0.75 g/kg Mycofix，以及2 ppm DAS配合1.5 g/kg Mycofix）。当饮食中不包含饲料添加剂时，两种水平的DAS饮食都显著降低了体重（BW）和饲料摄入量，并引起了口腔病变，其中2 ppm DAS的效果更为严重。当饮食中添加了1 ppm DAS时，Mycofix的补充在两种添加水平（0.75和1.5 g/kg）下都能防止DAS对饲料摄入量和体重的不利影响；然而，Mycofix的补充并没有提供对口腔病变的保护。这一发现表明，DAS对性能的不利影响并非由于口腔病变本身，而是可能由于霉菌毒素的系统吸收。当饮食中存在2 ppm DAS时，Mycofix的补充只能部分保护体重和饲料摄入量。

The possible protective effect of a feed additive (Mycofix) against the toxic effects of 4,15-diacetoxiscirpenol (DAS) in growing broiler chickens was investigated in a 21-d fully randomized trial consisting of seven dietary treatments (control with no DAS or Mycofix added, 1 ppm DAS alone, 1 ppm DAS supplemented with 0.75 g/kg Mycofix, 1 ppm DAS supplemented with 1.5 g/kg Mycofix, 2 ppm DAS alone, 2 ppm DAS supplemented with 0.75 g/kg Mycofix, and 2 ppm DAS supplemented with 1.5 g/kg Mycofix). When no feed additive was included, both levels of dietary DAS significantly decreased BW and feed intake and caused oral lesions, with the effect of 2 ppm DAS being more severe. When 1 ppm DAS was added to the diet, supplementation of Mycofix protected against the adverse effects of DAS on feed intake and BW at both levels of inclusion (0.75 and 1.5 g/kg); however, no protection against oral lesions was obtained by Mycofix supplementation. This finding suggests that the adverse effect of DAS on performance is not due to the oral lesions per se but it is likely the result of the systemic absorption of the mycotoxin. When 2 ppm dietary DAS was present in the diet, only partial protection on BW and feed intake was obtained by Mycofix supplementation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

/nivalenol/（NIV）与T2 /toxin/、/diacetoxyscirpenol/（DAS）或/deoxynivalenol/（DON）的组合在淋巴细胞增殖试验中显示出加性毒性，而DON与T2或DAS的组合所产生的抑制作用略低于预期。总之，测试的曲霉毒素以剂量依赖性方式抑制人淋巴细胞的增殖和Ig生产，个体间的敏感性变化有限。在接触较低剂量毒素的细胞培养中观察到Ig生产的增强。两种毒素的联合暴露主要产生加性或拮抗作用，尽管不能排除协同作用，且应进一步研究。

Combinations of /nivalenol/ (NIV) with T2 /toxin/, /diacetoxyscirpenol/ (DAS) or /deoxynivalenol/ (DON) resulted in additive toxicity in the lymphocyte proliferation test, while combinations of DON with T2 or DAS resulted in an inhibition that was slightly lower than what could have been expected from the inhibition produced by the individual toxins. In conclusion, the tested trichothecenes inhibited both proliferation and Ig production in human lymphocytes in a dose-dependent manner with limited variation in sensitivity between individuals. Enhanced Ig production was observed in cell cultures exposed to the lower doses of the toxins. Combined exposure to two of the toxins resulted mainly in additive or antagonistic effects, although synergistic effects cannot be excluded and should be further investigated.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

实验评估了两种处理对母火鸡苗（尼古拉斯大白）从孵化到3周龄的影响：一种是含有300毫克伏马菌素B1（FB1）的饲料，另一种是含有4毫克二乙酰氧基角鲨烯（DAS）或3毫克赭曲霉毒素A（OA）的饲料。与对照组相比，FB1使体重增长减少了30%（实验1）和24%（实验2），DAS使体重增长减少了30%，OA使体重增长减少了8%，FB1和DAS组合使体重增长减少了46%，FB1和OA组合使体重增长减少了37%。除了实验2中的FB1处理外，所有处理都降低了饲料的利用效率。除了DAS处理外，所有处理都显著增加了肝脏的相对重量。单独喂食FB1以及与DAS或OA组合喂食的火鸡苗，其血清胆固醇浓度降低，天冬氨酸转氨酶和乳酸脱氢酶活性增加，并且几种血液学值发生了改变。结果表明，当火鸡苗喂食含有300毫克FB1、4毫克DAS或3毫克OA/千克饲料时，毒性呈现相加或小于相加，但不存在毒性协同作用。

The individual and combined effects of feeding diets containing 300 mg fumonisin B1 (FB1), and 4 mg diacetoxyscirpenol (DAS) or 3 mg ochratoxin A (OA) were evaluated in two experiments using female turkey poults (Nicholas Large Whites) from day of hatch to 3 wk of age. When compared with controls, body weight gains were reduced 30% (Study 1) and 24% (Study 2) by FB1, 30% by DAS, 8% by OA, 46% by the FB1 and DAS combination, and 37% by the FB1 and OA combination. The efficiency of feed utilization was adversely affected by all treatments except FB1 in Experiment 2. Relative weights of the liver were significantly increased by all treatments except the DAS treatment. Serum concentrations of cholesterol were decreased and activities of aspartate aminotransferase and lactate dehydrogenase were increased and several hematological values were altered in poults fed FB1 alone and in combination with either DAS or OA. Results indicate additive or less than additive toxicity, but not toxic synergy, when poults are fed diets containing 300 mg FB1, and 4 mg DAS or 3 mg OA/kg of diet.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

支持性护理，特别是维持电解质平衡，是唯一的治疗方法。没有解毒剂，所以避免接触是唯一的预防措施。外用皮肤抗生素软膏可能有助于预防皮肤疼痛和继发感染。/三环孢菌素/

Supportive care, especially maintenance of electrolyte balance, is the only treatment. There are no antidotes, so avoidance of contact is the only preventive measure. Topical dermal antibiotic creams may be of help to prevent dermal pain and secondary infection. /Trichothecenes/

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，开始进行人工呼吸，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，让患者前倾或将其置于左侧（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)

吸收、分配和排泄

在大鼠和小鼠局部应用单一剂量的/(3)H-二乙酰氧基二烯醇/([(3)H]DAS)后的90分钟内，大鼠吸收并保留的[(3)H]DAS比小鼠多，通过尿液和粪便排出的放射性活性较少。治疗后24小时内，大鼠吸收、排出并保留的[(3)H]DAS大约是小鼠的两倍（p < 0.05或< 0.005）。治疗7天后，大鼠吸收的[(3)H]DAS量比小鼠多出四倍以上（13.1% 对 57.5%；p < 0.005）。然而，小鼠组织保留的放射性活性的比例（4.1%）高于大鼠（1.0%；p < 0.05）。大鼠的总放射性标记排泄量大约是小鼠的六倍（56% 对 9%；p < 0.005）。大鼠尿液中排泄的比例是粪便中的大约2比1（37% 对 18%），而小鼠的比例大约是3.5比1（7% 对 2%）。当数据以组织中吸收剂量的百分比或每克组织的特定放射性活性（dpm）表示时，发现大鼠和小鼠的[(3)H]DAS组织分布的时间过程有显著差异。这些结果表明，局部给药的[(3)H]DAS在大鼠和小鼠中的吸收、排泄和组织分布模式不同。

During the 90-min period after topical application of a single dose of /(3)H-diacetoxyscirpenol/ ([(3)H]DAS), the rat absorbed and retained more [(3)H]DAS and excreted less radioactivity through urine and feces than the mouse. By 24 hr after treatment, the rat had absorbed, excreted, and retained about twice as much [(3)H]DAS as had the mouse (p < 0.05 or < 0.005). At 7 days posttreatment, the rat had absorbed more than four times the amount of [(3)H]DAS than had the mouse (13.1 vs 57.5%; p < 0.005). However, tissues of the mouse retained a higher proportion of administered radioactivity (4.1%) than those of the rat (1.0%; p < 0.05). Total excretion of radiolabel by the rat was approximately sixfold higher than that of the mouse (56 vs 9%; p < 0.005). The ratio of excretion in urine to that in feces in the rat was about 2 to 1 (37 vs 18%) and in the mouse was about 3.5 to 1 (7 vs 2%). Significant differences in the time course of tissue distribution of [(3)H]DAS in the rat and mouse were found when data were expressed as the percentage of absorbed dose present in tissues or as specific radioactivity (dpm) per gram tissue. These results demonstrated a different pattern of absorption, excretion, and tissue distribution of topically administered [(3)H]DAS in rats and mice.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  Xn,T+,F,T
• 安全说明：
  S16,S36/37,S45,S53
• 危险类别码：
  R20/21/22,R36/38,R36,R26/27/28,R11
• WGK Germany：
  3
• 海关编码：
  29329990
• 危险品运输编号：
  UN 3462 6.1/PG 2
• RTECS号：
  YD0112000
• 包装等级：
  II
• 危险类别：
  6.1(a)

制备方法与用途

生物活性

Diacetoxyscirpenol (DAS) 是一种单端孢霉烯真菌毒素，由真菌产生。摄入 DAS 可引起人类和动物血液病（如中性粒细胞减少、再生障碍性贫血）。

类别

有毒物品

毒性分级

剧毒

急性毒性

• 口服 - 大鼠 LD50: 7 毫克/公斤
• 口服 - 小鼠 LD50: 7.3 毫克/公斤

刺激数据

• 皮肤 - 豚鼠：0.284 毫克，轻度刺激

可燃性危险特性

可燃；燃烧时产生刺激烟雾

储运特性

库房需通风干燥低温存放；与食品原料分开存储

灭火剂

干粉、泡沫、沙土、二氧化碳、雾状水