二乙酰镳草镰刀菌烯醇 | 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
• 中文名称: 二乙酰镳草镰刀菌烯醇
• 中文别名: 蛇形菌素
• 英文名称: [(2R,7R,9R,10R,11S)-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-WGTJCWDGSA-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)
• 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

脱氧雪腐镰刀菌烯是一组主要由镰刀菌属真菌产生的真菌毒素。消费者特别关注脱氧雪腐镰刀菌烯及其代谢物对食品生产动物的中毒性和食品安全问题。本文综述了T-2毒素、脱氧雪腐镰刀菌烯（DON）、雪腐镰刀菌烯（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（3-aDON）和15-乙酰脱氧雪腐镰刀菌烯（15-aDON）在家鼠、猪、反刍动物、家禽和人体内的代谢情况。这些真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，这被认为是一种激活途径，而T-2毒素转化为T-2四醇是一种在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、新香豆素（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分别是大多数动物体内DON和NIV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。对脱氧雪腐镰刀菌烯代谢的综述将有助于人们深入了解这些毒素在动物和人体内的命运，并为这些毒素的食品安全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、新雪腐醇、4-去乙酰新雪腐醇、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

• 副作用

Dermatotoxin - 皮肤烧伤。

Dermatotoxin - Skin burns.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 毒性数据

LC50（小鼠）= 11.3毫克/千克

LC50 (mice) = 11.3 mg/kg

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

研究了饲料添加剂（Mycofix）对生长肉鸡中4,15-二乙酰氧基西松醇（DAS）毒性效应的可能保护作用。这是一项为期21天的完全随机试验，包括七种饮食处理（对照组不加DAS或Mycofix，单独使用1 ppm DAS，1 ppm DAS补充0.75 g/kg Mycofix，1 ppm DAS补充1.5 g/kg Mycofix，单独使用2 ppm DAS，2 ppm DAS补充0.75 g/kg Mycofix，以及2 ppm DAS补充1.5 g/kg Mycofix）。当不包含饲料添加剂时，两种饮食DAS水平都显著降低了体重和饲料摄入量，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的补充在两个添加水平（0.75和1.5 g/kg）上均能防止DAS对饲料摄入量和体重的负面影响；然而，Mycofix的补充并没有获得对口腔病变的保护作用。这一发现表明，DAS对性能的负面影响并非由于口腔病变本身，而可能是由于霉菌毒素的系统吸收。当饮食中存在2 ppm DAS时，Mycofix的补充仅对体重和饲料摄入量提供了部分保护作用。

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.

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效果略低于单独毒素所引起的预期抑制效果。总之，测试的曲霉毒素以剂量依赖性方式抑制了人淋巴细胞的增殖和Ig产生，且个体间的敏感性变化有限。在暴露于较低剂量毒素的细胞培养中观察到了增强的Ig产生。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

在两个实验中，评估了从孵化当天到3周龄期间，给雌性火鸡苗（尼古拉斯大白）喂食含有300毫克伏马菌素B1（FB1）和4毫克二乙酰氧基柄菌素（DAS）或3毫克赭曲霉毒素A（OA）的饮食的单独和联合效果。与对照组相比，FB1使体重增重减少了30%（实验1）和24%（实验2），DAS减少了30%，OA减少了8%，FB1和DAS组合减少了46%，FB1和OA组合减少了37%。除了实验2中的FB1处理外，所有处理都降低了饲料利用效率。除DAS处理外，所有处理都显著增加了肝脏的相对重量。血清胆固醇浓度降低，天门冬氨酸转移酶和乳酸脱氢酶活性增加，并且FB1单独喂养以及与DAS或OA联合喂养的火鸡苗的几种血液学值发生了改变。结果表明，当火鸡苗喂食含有300 mg FB1和4 mg DAS或3 mg OA/千克饮食时，毒性为加性或小于加性，但不是毒性协同。

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)

吸收、分配和排泄

在大鼠和小鼠局部应用单一剂量的/(3)H-二乙酰氧基甲酸酯/([(3)H]DAS)后90分钟内，大鼠吸收并保留了更多的[(3)H]DAS，并通过尿液和粪便排出了更少的放射性物质，而小鼠则相反。在处理24小时后，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）。在处理后7天，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，小鼠的组织保留的放射性物质比例（4.1%）高于大鼠（1.0%; p < 0.05）。大鼠的总放射性标记排出量大约是小鼠的六倍（56% 对 9%; p < 0.005）。在大鼠中，尿液排出量与粪便排出量的比例大约是2比1（37% 对 18%），而在小鼠中大约是3.5比1（7% 对 2%）。当数据以组织中的吸收剂量百分比或每克组织的特定放射性（dpm）表示时，大鼠和小鼠的[(3)H]DAS组织分布的时间过程存在显著差异。这些结果表明，局部应用的[(3)H]DAS在大鼠和小鼠中的吸收、排出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