二次乙基氨荒酸 | 111-54-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 二硫代氨基甲酸及其衍生物
• 中文名称: 二次乙基氨荒酸
• 英文名称: N,N'-ethylenebis(dithiocarbamate)
• 英文别名: Ethylen-bis-dithiocarbaminsaeure；2-(dithiocarboxyamino)ethylcarbamodithioic acid
• CAS: 111-54-6
• 化学式: C₄H₈N₂S₄
• 分子量: 212.385
• InChiKey: AWYFNIZYMPNGAI-UHFFFAOYSA-N

物化性质

• 沸点：
  308.2±52.0 °C(Predicted)
• 密度：
  1.413±0.06 g/cm3(Predicted)
• 物理描述：
  Ethylenebisdithiocarbamic acid, salts and esters is a solid. Very unstable material, used as a pesticide and fungicide.
• 颜色/状态：
  Unstable liquid
• 溶解度：
  In water, 1.14X10+5 mg/L at 25 °C (est)
• 蒸汽压力：
  7.50X10-8 mm Hg at 20 °C
• 稳定性/保质期：
  Ethylene bisdithiocarbamates (EBDCs) are generally unstable in the presence of moisture, oxygen, or biological systems, and decompose rapidly in water.
• 分解：
  The ethylene(bis)dithiocarbamates decompose rather rapidly in water. /Ethylene(bis)dithiocarbamates/
• 解离常数：
  pKa = 5.11 (thiol) (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.2
• 氢给体数：
  4
• 氢受体数：
  4

ADMET

代谢

ETU和DIDT（5,6-二氢-3 H-咪唑（2,1-C）-1,2,4-二噻唑-3-硫酮）是处理了锌EB的大鼠尿液中发现的主要代谢物，并且在呼出的空气中检测到了二硫化碳。

ETU and DIDT /(5,6-dihydro-3 H-imidazo(2,1-C)-1,2,4-dithiazole-3-thione)/ were the major metabolites found in the urine of rats treated with zineb, and carbon disulfide was detected in the expired air.

来源:Hazardous Substances Data Bank (HSDB)

代谢

杀真菌剂代森锌（锌乙撑双硫代氨基甲酸酯）在大鼠和卷尾猴体内的代谢已经进行了研究。在两种物种中，相对较大比例（21-22%）的原始给药代森锌可以在排泄物中检测为乙撑硫脲（ETU）……进一步的比例（2-5%）被确定为乙烯脲，这是ETU的代谢物。在卷尾猴中进行的比较实验结果显示，ETU在排泄物存在的情况下对光敏感，因此突显了在黑暗中进行研究的重要性。

The metabolism of the fungicide zineb, (zinc ethylenebisdithiocarbamate), has been studied in the rat and the marmoset. In both species a relatively large proportion (21-22%) of the original zineb administered was detectable in the excreta as ethylenethiourea (ETU) ... A further proportion (2-5%) was determined to be ethyleneurea which is a metabolite of ETU. Results of comparative experiments in marmosets revealed that ETU was photolabile in the presence of excreta, thus showing the importance of conducting the studies in the dark.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Zineb ... 在大鼠体内代谢为碳二硫化物，通过呼吸排出，以及代谢为乙撑亚硫脲 ... 和乙烯双(异硫氰酸酯)硫化物（ebis）... 这些物质通过尿液排出。

Zineb ... Is metabolized in rats to carbon disulfide, which is expired, and to ethylenethiourea ... and ethylenebis(isothiocyanate)sulfide (ebis) ... which are excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

乙烯硫脲是植物中的主要代谢物。乙烯硫脲单磺酸盐以及可能形成的乙烯硫脲双磺酸盐和硫磺也被形成。

Ethylenethiourea is the major metabolite in plants. Ethylenethiuram monosulfide and presumably ethylenethiuram disulfide and sulfur are also formed.

来源:Hazardous Substances Data Bank (HSDB)

代谢

二硫代氨基甲酸盐在某些情况下可能会分解成多种化合物，如硫、5,6-二氢-3 H-咪唑[2,1-C]-1,2,4-二噻唑-3-硫酮、乙撑硫脲（ETU）和乙二胺（EDA）。ETU相对稳定，具有很高的水溶性，并且因其特定的毒性而特别重要。/二硫代氨基甲酸盐/

Dithiocarbamates may decompose under certain circumstances into a number of compounds, such as sulfur, 5,6-dihydro-3 H-imidazol [2,1-C]-1,2,4-dithiazole-3-thione, ethylenethiourea (ETU), and ethylenediamine (EDA). ETU is fairly stable, has a high water solubility, and is of particular importance because of its specific toxicity. /Dithiocarbamates/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：代森锌是一种灰黄色的自由流动粉末。它用于控制多种作物、水果、坚果、蔬菜和观赏植物中的许多真菌病。它还用作种子处理/保护剂。人类暴露和毒性：暴露可能导致毒性表皮坏死松解症（TEN），这是一种具有高死亡率的生命威胁性粘膜炎性疾病。曾有一名花商出现手足湿疹和对代森锌的敏感。一名女性报告说，在车库里储存代森锌粉末后出现了广泛的皮炎。一项流行病学研究表明，居住在用代森锌空中喷洒的香蕉种植园附近的孕妇可能会环境暴露于锰，高浓度的锰是一种神经毒素。另一项研究表明，接触代森锌的受试者患皮肤黑色素瘤的风险增加，特别是在职业阳光下暴露的受试者中。代森锌暴露与外周血淋巴细胞中结构染色体畸变细胞频率的显著增加和每细胞姐妹染色单体交换数量的增加之间存在关联。在低水平、长期职业暴露条件下，观察到代森锌的轻微免疫调节作用。动物研究：这类化合物的急性毒性通常较低。动物研究显示，接触后可能会出现接触性皮炎和甲状腺增生。代森锌在豚鼠中是一种强烈的皮肤致敏剂。在代森锌、锌硝和代森间观察到了交叉致敏作用。在大鼠中，100 ppm及以上剂量的甲状腺滤泡细胞增生。代森锌对大鼠的性腺产生剂量依赖性的损害作用。剂量水平为每千克体重140-1400毫克代森锌，每周两次，持续4.5个月。在所有剂量水平上，生殖和内分泌结构都受到影响，导致生育力下降。在大鼠发育研究中，观察到了吸收胎的数量增加、外出血和波状肋骨；在没有母体毒性的情况下没有观察到胚胎毒性。接受代森锌处理的大鼠表现出剂量依赖性的抑郁、动力不足、肌张力下降、协调障碍、麻痹和四肢无力，以及食欲不振和虚脱。致突变性：细菌和体外哺乳动物细胞系统的致突变性、体内的染色体损伤和哺乳动物细胞转化试验均为阴性。体外中国仓鼠卵巢细胞姐妹染色单体交换为阳性。代森锌可诱导雄性小鼠骨髓细胞在不同测试剂量下发生多种类型的染色体畸变。使用Salmonella typhimurium测试菌株TA97a、TA98、TA100和TA102对代森锌可能的致突变活性进行了检测，结果为阴性。在体内接受代森锌处理的大鼠中，它通过彗星试验诱导了DNA损伤，并增加了微核的频率。代森锌的急性治疗抑制了细胞色素P450介导的代谢。代森锌代谢为乙烯硫脲（ETU）。基于大鼠的甲状腺和其他癌症，ETU是一种致癌物，ETU还已知会在大鼠中引起甲状腺素（T4）的减少和甲状腺刺激激素（TSH）的增加。生态毒性研究：在一项季节性繁殖的野生动物鸟类，红 Munia (Amandava amandava) 的研究中，代森锌显著降低了血浆T4、T3和TSH。在鸟类和哺乳动物中观察到的代森锌毒性效应可能是由于可能的激素干扰。在鸟类繁殖研究中，注意到生殖效应，如：产蛋量减少；早期和晚期胚胎存活率；孵化率；孵化后和14天龄的幼鸟体重；以及14天龄幸存者的数量减少。暴露于代森锌的蝌蚪的生长速度降低。在淡水生物的慢性测试中，观察到不动性、长度和Daphnia首次产卵的时间以及减少脂肪头鱼的存活和生长效果。在淡水物种中观察到的这些效应可能是由于可能的激素干扰。生菜暴露于代森锌对植物代谢产生了显著影响，成熟叶片往往比幼嫩叶片受到更广泛的影响。

IDENTIFICATION AND USE: Mancozeb is a greyish-yellow free-flowing powder. It is used for control of many fungal diseases in a wide range of field crops, fruits, nuts, vegetables, and ornamentals. It is also used as seed treatment/protectant. HUMAN EXPOSURE AND TOXICITY: Exposure could lead to toxic epidermal necrolysis (TEN), which is a life-threatening mucocutaneous disease with high mortality. There has been a case of dyshidrotic eczema and sensitization to mancozeb in a florist. A widespread dermatitis was reported by a woman following storage of mancozeb powder in a garage. An epidemiological study suggests that pregnant women living near banana plantations aerially sprayed with mancozeb may be environmentally exposed to Mn, which is a neurotoxicant at high concentrations. Another study demonstrated an augmented risk of cutaneous melanoma among subjects with exposure to mancozeb, in particular among those with occupational sun exposure. There appeared to be an association between mancozeb exposure and a significant increase in the frequencies of cells with structural chromosome aberrations and the number of sister chromatid exchanges per cell in peripheral blood lymphocytes. Slight immunomodulator effect of mancozeb in conditions of low-level, prolonged occupational exposure was observed. ANIMAL STUDIES: Compounds of this class usually have low acute toxicity. Studies in animals suggest that contact dermatitis and thyroid hyperplasia may occur after exposure. Mancozeb was a potent dermal sensitizer in the guinea pig. Cross-sensitization was observed between mancozeb, zineb and maneb. In rats, thyroid follicular cell hyperplasia was seen at 100 ppm and higher doses. Mancozeb exerts dose-dependent damaging effects on the gonads of rats of both sexes. The dose level was 140-1400 mg mancozeb/kg body weight, given twice a week for 4.5 months. Both reproductive and endocrine structures were affected at all dose levels, leading to decreased fertility. In developmental studies in rats, increase in resorbed litters, external hemorrhage and wavy ribs have been observed; no embryotoxicity in absence of maternal toxicity. Rats treated with mancozeb showed dose-dependent signs of depression, adynamia, decreased tonus, disturbances in coordination, paresis, and paralysis of extremities combined with general weakness, lack of appetite, and prostration. Mutagenicity: Bacterial and in vitro mammalian cell systems, chromosome damage in vivo and in mammalian cell transformation tests were negative. Sister chromatid exchanges in Chinese hamster ovary cells in vitro was positive. Mancozeb induces a number of different types of chromosomal aberrations in the bone marrow cells of male mice at various test doses. Mancozeb was examined for its possible mutagenic activity using Salmonella typhimurium tester strains TA97a, TA98, TA100, and TA102 with negative results. In rats treated with mancozeb in vivo, it induced DNA damage as detected by the comet assay and increased the frequency of micronuclei. Acute treatments with mancozeb inhibit cytochrome P450 mediated metabolism. Mancozeb is metabolized to ethylene thiourea (ETU). ETU is a carcinogen, based on thyroid and other cancers in rodents, ETU is also known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. ECOTOXICITY STUDIES: In a seasonally breeding wildlife bird, Red Munia (Amandava amandava) plasma T4, T3 and TSH were significantly decreased in response to mancozeb. Mancozeb toxicity effects noted in both birds and mammals could be a result of possible hormonal disruptions. The avian reproductive studies noted reproductive effects such as reductions in: egg production; early and late embryo viability; hatchability; offspring weight at hatch and 14-days of age; and the number of 14-day old survivors. Reduced growth rates were noted in tadpoles exposed to mancozeb. Chronic testing in freshwater organisms showed immobility, length and time until first brood in Daphnia and reduced survival and lack of growth effects in fathead minnow. These effects noted in freshwater species could be a result of possible hormonal disruptions. Lettuce exposure to mancozeb was shown to have a significant impact on plant metabolism, with mature leaves tending to be more extensively affected than younger leaves.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据不足。总体评估：第3组：该物质对人类致癌性无法分类。

No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：B2组可能的人类致癌物

Cancer Classification: Group B2 Probable Human Carcinogen

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：福美锌

IARC Carcinogenic Agent:Zineb

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)

吸收、分配和排泄

摄入的代森锌大约有70-75%通过大鼠的消化道，并在24-72小时内出现在粪便中。

... Approx 70-75% of ingested zineb passed through the gastrointestinal tract of rats and appeared in the feces within 24-72 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

只有11%到17%的辛内布剂量从大鼠的消化道被吸收。一些额外的物质可能在肠道分解后被吸收。在不同膳食水平下，68.5%到74.9%的摄入物质在粪便中未改变地被回收。

... Only 11 to 17% of an oral dose of zineb is absorbed from the gastrointestinal tract of the rat. Some additional material may be absorbed following breakdown in the intestine. At different dietary levels 68.5 to 74.9% of the ingested material was recovered unchanged in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在短期静态生物积累实验中，使用(14)C标记的亚乙基双硫代氨基甲酸锌（乙撑双）和甲基双硫代氨基甲酸锌（齐拉姆），两种化合物都迅速通过组织传播。整体身体消除是迅速的，16天净化期结束时，齐拉姆和乙撑双的初始放射性分别保留了45%和25%。色素组织似乎也是主要的分布位点。这可能与化合物及其降解产物对黑色素或与酪氨酸酶（一种参与黑色素合成的含铜酶）的亲和力有关。放射自显影还揭示了甲状腺滤泡的高度标记。结果表明，二硫代氨基甲酸盐在各种组织中具有选择性定位，据报道这些组织是其毒性作用的目标器官。

In short-term static bioaccumulation experiments with (14)C-labeled zinc ethylenebisidithiocarbamate (zineb) and zinc dimethyldithiocarbamate (ziram) both compounds were rapidly disseminated through the tissues. Whole body elimination was rapid with 45% and 25% of the initial radioactivity from ziram, and zineb, respectively, being retained by the end of the 16 day depuration period. Pigmented tissues appeared to be major distribution sites as well. This may be related to the affinity of the compounds and/or their degradation products to melanin or to complexion with phenoloxidase, a copper containing enzyme involved in melanin synthesis. Autoradiography also revealed a high labeling of thyroid follicles. The results show that dithiocarbamates are selectively localized in various tissues, reported to be the target organs for their toxic actions.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

乙烯硫脲是乙烯基双二硫代氨基甲酸/酸/杀菌剂的代谢物，在大鼠单次口服锌巴后16天内监测其尿液和粪便中的排泄情况。48小时后，排泄出的乙烯硫脲中有86%在尿液中，14%在粪便中。尿液排泄在摄入后24小时达到峰值，此时已排泄出总尿液乙烯硫脲的52%。在整个研究期间，尿液中持续排泄低水平的乙烯硫脲，到研究结束时，口服锌巴剂量的5.1%作为尿液中的乙烯硫脲被排泄。乙烯硫脲的粪便排泄在3天内完成。

Urinary and fecal excretion of ethylene thiourea, a metabolite of ethylene-bis-dithiocarbamic /acid/ fungicides, was monitored in rats for 16 days after they were administered a single oral dose of zineb. After 48 hr, 86% of the excreted ethylene thiourea was in the urine, 14% in the feces. Urinary excretion peaked at 24 hr after ingestion, at which time 52% of the total urinary ethylene thiourea had been excreted. Low levels of ethylene thiourea excretion continued in urine for the length of the study, by which time 5.1% of the zineb /oral dose/ was excreted as urinary ethylene thiourea. Fecal excretion of ethylene thiourea was complete after 3 days.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一般来说，二硫代氨基甲酸盐可以通过皮肤、粘膜以及呼吸和消化系统被生物体吸收。/二硫代氨基甲酸盐/

As a general rule, dithiocarbamates can be absorbed by the organism via the skin, mucous membranes, and the respiratory and gastrointestinal tracts. /Dithiocarbamates/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  二次乙基氨荒酸 在 水 作用下， 生成 亚乙基硫脲
  参考文献：
  名称：

  Jakubowitsch; Klimowa, Zhurnal Obshchei Khimii, 1939, vol. 9, p. 1782

  摘要：

  DOI：
• 作为产物：
  描述：

  乙二胺 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 生成 二次乙基氨荒酸
  参考文献：
  名称：

  Jakubowitsch; Klimowa, Zhurnal Obshchei Khimii, 1939, vol. 9, p. 1782

  摘要：

  DOI：

文献信息

• Mechanisms of Acid Decomposition of Dithiocarbamates. 2. Efficiency of the Intramolecular General Acid Catalysis
  作者：Eduardo Humeres、Nito A. Debacher、M. Marta de S. Sierra

  DOI：10.1021/jo981382i

  日期：1999.3.1

  M. The acid decomposition of the dithiocarbamic conjugate acid of EbisDTC anion proceeds through a fast N-protonation and a slower C-N breakdown. The intramolecular general acid catalysis rate constant is (8.2 +/- 2.8) x 10(6) s(-)(1), but the efficiency of this fast proton transfer is only (14.3 +/- 4.9) M. The intramolecular general acid catalysis of the free acid forms of the carboxylic and dithiocarbamic

  研究了乙二（二硫代氨基甲酸酯）（EbisDTC）和甘氨酸二硫代羧酸酯（glyDTC）在25°C的水中H（o）-5至pH 5的酸分解作用。根据LFER计算出所有相关物种的酸解离常数以及pH值曲线。根据反应性物种的母体胺的pK（a），两种化合物都通过二硫代氨基甲酸酯阴离子和两性离子中间体分解。glyDTC阴离子的羧酸共轭酸的分子间N质子化速率常数为12.6 M（-）（1）s（-）（1），比CN分解慢。该物质还通过分子内一般酸催化的机理裂解，其中N质子化的速率常数为（7.1 +/- 4.2）x 10（3）s（-）（1），质子转移步骤的效率通过有效摩尔比测量为（5.6 +/- 3。3）x 10（2）M。EbisDTC阴离子的二硫代氨基甲酸共轭酸的酸分解通过快速的N质子化和较慢的CN分解而进行。分子内一般酸的催​​化速率常数为（8.2 +/- 2.8）x 10（6）s（-）（1），但是这种快速质子转移的效率仅为（14
• Fungicides and fungicidal compositions
  申请人：UNION CARBIDE CORP

  公开号：US02843518A1

  公开（公告）日：1958-07-15
• Barnes; Fatome; Esslemont, European Journal of Medicinal Chemistry, 1975, vol. 10, # 6, p. 619 - 622
  作者：Barnes、Fatome、Esslemont、et al.

  DOI：——

  日期：——
• Melendez, E.; Merchan, F. L.; Tejero, T., Anales de Quimica, 1994, vol. 90, # 7-8, p. 487 - 490
  作者：Melendez, E.、Merchan, F. L.、Tejero, T.、Merino, P.、Garcia, M.

  DOI：——

  日期：——
• Kloepping; van der Kerk, Recueil des Travaux Chimiques des Pays-Bas, 1951, vol. 70, p. 949,959
  作者：Kloepping、van der Kerk

  DOI：——

  日期：——