[(1S,2R,4S)-11-acetyloxy-2-(acetyloxymethyl)-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-4-yl] 3-methylbutanoate

• 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: [(1S,2R,4S)-11-acetyloxy-2-(acetyloxymethyl)-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-4-yl] 3-methylbutanoate
• 化学式: C₂₄H₃₄O₉
• 分子量: 466.5
• InChiKey: BXFOFFBJRFZBQZ-DDWKCWKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

ADMET

代谢

给一头哺乳期母牛口服180毫克T-2毒素后，从其尿液中获得了两种主要代谢物。它们是3'-羟基-HT 2毒素和3'-羟基T 2毒素。

Two major metabolites were obtained from the urine of a lactating cow given 180 mg of T-2 toxin orally. They were 3'-hydroxy-HT 2 toxin & 3'-hydroxy T 2 toxin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类肝脏酶将T2-三线镰刀菌毒素脱乙酰化成HT2-三线镰刀菌毒素。

Human liver enzymes deacetylate T2-trichothecene to HT2-trichothecene in vitro.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给予小鼠和大鼠(3)H-T2-三线霉素(1 mg/kg体重)的放射性，在72小时内以粪便(55%)和尿液(15%)的形式回收。 ... 分析大鼠粪便中回收的放射性，发现剂量的2.7%以未改变的T2-三线霉素形式排出，7.5%以4-O-脱乙酰化T2-三线霉素(HT2-三线霉素)形式排出...其余的粪便排泄产物未鉴定。 在尿液中，鉴定出代表总剂量1.4%的HT2-三线霉素和8-羟基二乙酰氧基斯卡波醇(1.8%)；还分离出3种未鉴定的代谢物。 环氧化合物基团...似乎是其毒理学活性的关键；肝脏通过环氧化物水解酶来解毒T2-三线霉素。 在体外，大鼠肝脏匀浆将T2-三线霉素代谢为HT2-三线霉素，T2-三线霉素四醇，4-脱乙酰新茄病醇...和新茄病醇... 从HT2-三线霉素中也获得了相同的代谢物，这表明T2-三线霉素优先在C-4位置水解，生成NT2-三线霉素。

The radioactivity of orally admin (3)H-T2-trichothecene (1 mg/kg body wt) to mice & rats was recovered in feces (55%) & urine (15%) within 72 hr. ... Analysis of the radioactivity recovered in feces of rats revealed that 2.7% of the dose was excreted as unchanged T2-trichothecene & 7.5% as 4-O-deacetylated T2-trichothecene (HT2-trichothecene)...the remaining fecal excretion products were not identified. In urine, HT2-trichothecene, representing 1.4% of the total dose & 8-hydroxydiacetoxyscirpenol (1.8%) were identified; 3 unidentified metabolites...were also isolated. The epoxide moeity...seems to be essential for its toxicological activity; the liver detoxifies T2-trichothecene, probably through epoxide hydrolase. In vitro, rat liver homogenate metabolizes T2-trichothecene to HT2-trichothecene, T2-trichothecene tetraol, 4-deacetylneosolaniol...& neosolaniol... The same metabolites were obtained from HT2-trichothecene, indicating that T2-trichothecene was preferentially hydrolyzed at the C-4 position to give NT2-trichothecene.

来源:Hazardous Substances Data Bank (HSDB)

代谢

曲霉菌属产生的三环烯类是倍半萜类毒素。由于这些霉菌毒素非常稳定，因此对微生物转化产生了兴趣，这些转化能够去除被污染的谷物或谷物产品中的毒素。对23种属于毛霉科（子囊菌门，子囊菌亚门）的酵母菌种进行了测试，包括四种毛霉科物种和19种目前归类于芽枝霉属的无性物种，以检测它们将三环烯T-2毒素转化为毒性较低产品的能力。这些物种产生了三种生物转化类型：乙酰化形成3-乙酰T-2毒素，糖基化形成T-2毒素3-葡萄糖苷，以及去除异戊酰基团形成新茄尼醇。一些物种产生了多种生物转化类型。三种芽枝霉属物种将T-2毒素转化为T-2毒素3-葡萄糖苷，这种化合物已被识别为在曲霉感染的谷物中的一种隐蔽霉菌毒素。这是首次报告微生物全细胞方法生产三环烯糖苷，T-2毒素3-葡萄糖苷的大量可用性将促进毒性测试和开发检测农业和其他产品中这种化合物的方法。

Trichothecenes are sesquiterpenoid toxins produced by Fusarium species. Since these mycotoxins are very stable, there is interest in microbial transformations that can remove toxins from contaminated grain or cereal products. Twenty-three yeast species assigned to the Trichomonascus clade (Saccharomycotina, Ascomycota), including four Trichomonascus species and 19 anamorphic species presently classified in Blastobotrys, were tested for their ability to convert the trichothecene T-2 toxin to less-toxic products. These species gave three types of biotransformations: acetylation to 3-acetyl T-2 toxin, glycosylation to T-2 toxin 3-glucoside, and removal of the isovaleryl group to form neosolaniol. Some species gave more than one type of biotransformation. Three Blastobotrys species converted T-2 toxin into T-2 toxin 3-glucoside, a compound that has been identified as a masked mycotoxin in Fusarium-infected grain. This is the first report of a microbial whole-cell method for producing trichothecene glycosides, and the potential large-scale availability of T-2 toxin 3-glucoside will facilitate toxicity testing and development of methods for detection of this compound in agricultural and other products.

来源:Hazardous Substances Data Bank (HSDB)

代谢

T-2毒素是一种由多种镰刀菌产生的真菌毒素，是谷物及其产品中广泛存在的污染物。了解其对人体毒性和代谢情况对于任何风险评估都至关重要，因为T-2毒素可以在加工和未加工的食物样本中被检测到。使用来自人体细胞的细胞培养研究代表了一个强大的模型系统，用于研究T-2毒素的代谢命运以及体外细胞毒性。在这项研究中，使用高效液相色谱与傅里叶变换质谱（HPLC-FTMS）联用的方法分析了T-2毒素在来自人结肠癌细胞（HT-29）和原代人肾近端小管上皮细胞（RPTEC）的细胞系中的代谢情况。两种细胞类型都将T-2毒素代谢为多种化合物。此外，RPTEC的细胞周期分析证明了T-2毒素及其代谢物HT-2毒素和新镰刀菌醇在微摩尔浓度下的凋亡作用。

The mycotoxin T-2 toxin, produced by various Fusarium species, is a widespread contaminant of grain and grain products. Knowledge about its toxicity and metabolism in the human body is crucial for any risk assessment as T-2 toxin can be detected in processed and unprocessed food samples. Cell culture studies using cells of human origin represent a potent model system to study the metabolic fate of T-2 toxin as well as the cytotoxicity in vitro. In this study the metabolism of T-2 toxin was analyzed in a cell line derived from human colon carcinoma cells (HT-29) and primary human renal proximal tubule epithelial cells (RPTEC) using high-performance liquid chromatography coupled with Fourier transformation mass spectrometry (HPLC-FTMS). Both cell types metabolized T-2 toxin to a variety of compounds. Furthermore, cell cycle analysis in RPTEC proved the apoptotic effect of T-2 toxin and its metabolites HT-2 toxin and neosolaniol in micromolar concentrations.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有关于来自串珠镰刀菌的毒素对人类致癌性的数据。T-2毒素在实验动物中的致癌性有有限证据。总体评估：来自串珠镰刀菌的毒素对人类的致癌性无法分类（第3组）。

Evaluation: No data were available on the carcinogenicity to humans of toxins derived from Fusarium sporotrichioides. There is limited evidence in experimental animals for the carcinogenicity of T-2 toxin. Overall evaluation: Toxins derived from Fusarium sporotrichiodes are not classifiable as to their carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：T2-三线镰孢霉毒素

IARC Carcinogenic Agent:T2-Trichothecene

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第31卷：（1983年）某些食品添加剂、饲料添加剂和天然存在物质

IARC Monographs:Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 相互作用

进行了实验以确定饮食纤维对大鼠T-2毒素中毒的影响。断奶的大鼠被喂以不同水平的纤维素、半纤维素、木质素和果胶，以及含有或不含有T-2毒素（3微克/克饲料）的饲料，持续2周。只有木质素显示出有望克服因喂食T-2毒素而导致的饲料拒绝和生长抑制。进一步的实验表明，喂食苜蓿粉（0%，5%，10%，15%，20%或25%）以及含有或不含有T-2毒素的饲料，这种富含木质素的饲料原料可以很大程度上克服由毒素引起的饲料拒绝和生长抑制。然而，饮食对肝酯酶的活性没有影响，这种酶被认为是分解T-2毒素的酶。大鼠被喂食含有0%，5%，12.5%或20%苜蓿的饲料2周，然后口服给予[(3)H]T-2毒素。饮食中的苜蓿增加了3H的粪便排泄，而尿液排泄不受影响。当口服给予[(3)H]T-2毒素时，苜蓿饲料减少了肾脏和肌肉中的残留(3)H。肠道腔内消化物中的残留(3)H增加。发现苜蓿饲料减少了肠道转运时间。结论是，苜蓿饲料通过在大肠腔内结合毒素，从而促进粪便排泄，减少了大鼠的T-2毒素中毒。

Experiments were conducted to determine the effect of dietary fibers on T-2 toxicosis in rats. Weanling rats were fed varying levels of cellulose, hemicellulose, lignin and pectin with and without T-2 toxin (3 ug/g feed) for 2 weeks. Only lignin showed promise of overcoming feed refusal and growth depression in animals fed T-2 toxin. Further experiments feeding alfalfa meal (0, 5, 10, 15, 20 or 25%) with and without T-2 toxin indicated that this lignin-rich feedstuff could largely overcome feed refusal and growth depression caused by the toxin. There was no effect of diet, however, on the activity of hepatic esterase, the enzyme believed to catabolize T-2 toxin. Rats were fed diets containing 0, 5, 12.5 or 20% alfalfa for 2 weeks and then dosed orally with [(3)H]T-2 toxin. Dietary alfalfa increased fecal excretion of 3H, whereas urinary excretion was unaffected. Residual (3)H in kidney and muscle was reduced with alfalfa feeding when [(3)H]T-2 toxin was administered orally. Residual (3)H in the digesta in the intestinal lumen increased. Alfalfa feeding was found to reduce intestinal transit time. It was concluded that the feeding of alfalfa reduced T-2 toxicosis in rats by binding the toxin in the intestinal lumen thereby promoting fecal excretion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

T2-三唑仑可以通过猪和鼠的皮肤和肠道轻易吸收。

T2-Trichothecene is readily absorbed through skin & the gut in pigs & rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

T-2毒素会通过哺乳期牛和猪的乳汁传播。

T-2 toxin is transmitted in the milk in lactating cattle & pigs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

估计那些每天口服1毫克/千克体重的T-2毒素，连续8天的鸡所产的蛋，相当于饮食中含有的1.6毫克/千克的T-2毒素，含有0.9微克的这种物质。

Estimated that the eggs from chickens treated orally with 1 mg T-2 toxin/kg body weight daily for 8 consecutive days, which is equivalent to 1.6 mg/kg dietary T-2, contain 0.9 ug of this material.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给予小鼠和大鼠(3)H-T2-三线霉素(1 mg/kg体重)后，72小时内通过粪便(55%)和尿液(15%)排出。它分布在肝脏、肾脏和其他器官中，没有特定的积累。

The radioactivity of orally admin (3)H-T2-trichothecene (1 mg/kg body wt) to mice & rats was recovered in feces (55%) & urine (15%) within 72 hr. It was distributed in the liver, kidneys & other organs, without specific accumulation.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(3)H-T-2毒素口服给予小鼠和大鼠后，迅速分布到组织中，并通过粪便和尿液排出。口服给药后，小鼠血浆中放射性标记物含量在30分钟内达到最大值……，而豚鼠在肌肉注射后……也达到最大值。在通过饲料给予(3)H-T-2毒素的雏鸡中，血液、血浆、腹脂、心脏、肾脏、肌胃、肝脏和剩余胴体中的最大水平在4小时内达到，而肌肉、皮肤、胆汁和胆囊中的最大水平在12小时内达到……。T-2毒素在猪组织中的分布与鸡相似……。

(3)H-T-2 Toxin given orally to mice and rats was distributed rapidly to tissues and eliminated in feces and urine. Maximal levels of radiolabel were found after 30 min in plasma of mice after oral administration ... and of guinea pigs after intramuscular injection ... . In chicks administered (3)H-T-2 toxin in the diet, maximal levels were reached by 4 hr in blood, plasma, abdominal fat, heart, kidneys, gizzard, liver and the remainder of the carcass and by 12 hr in muscle, skin, bile and gall bladder ... . The distribution of T-2 toxin in tissues of swine was similar to that in chickens ... .

来源:Hazardous Substances Data Bank (HSDB)