涕灭威 | 116-06-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 甲亚胺酸及其衍生物
• 中文名称: 涕灭威
• 中文别名: 铁灭克；丁醛肟威；2-甲基-2-(甲硫基)丙醛-O-[(甲基氨基)羰基]肟；涕灭威(铁灭克)；2-甲基-2-(甲硫基)丙醛-O-[(甲基氨基)甲酰基]肟
• 英文名称: temik
• 英文别名: Aldicarb；[(2-methyl-2-methylsulfanylpropylidene)amino] N-methylcarbamate
• CAS: 116-06-3
• 化学式: C₇H₁₄N₂O₂S
• 分子量: 190.266
• InChiKey: QGLZXHRNAYXIBU-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  常温常压下不会分解，应避免与强氧化剂和强碱接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  76
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

在给予碳基-(14)C标记的丁硫克百威后48小时内，大鼠通过呼出超过60%的(14)C作为二氧化碳，尿液中发现的不到30%。在其他(14)C研究中，大鼠通过尿液排出了超过80%的降解产物，通过粪便排出的不到10%（这种排泄模式有利于葡萄糖苷酸的内脏-肝脏循环，这也可以帮助延长有毒代谢物的系统活性）。主要的尿液代谢物是丁硫克百威亚砜（剂量的40%），其肟和腈形式（超过30%）；亚砜和相关的肟和腈；以及，醛和酸类似物。丁硫克百威在排泄物中不常见。摄入植物组织的结合残留物未被吸收，因此可以在粪便中找到。在单次剂量和短期饮食研究中，哺乳期奶牛以与大鼠相同的速度并以相同的代谢物阵列排出了丁硫克百威代谢物。大约1%的剂量通过牛奶排出，亚砜和亚砜分别是总牛奶残留含量的15%和4%的主要代谢物。

Within 48 hours of administration of carbonyl-(14)C labelled aldicarb rats eliminated over 60% of the (14)C as carbon dioxide, less than 30% was found in the urine. In other (14)C-studies rats excreted more than 80% of the degradation products in urine and less than 10% in faeces (an excretion pattern favoured by enterohepatic cycling of glucuronides which may also serve to extend the systemic activity of the toxic metabolites). The major urinary metabolites were aldicarb sulfoxide (40% of the dose), its oxime and nitrile forms (over 30%); the sulfone and related oxime and nitrile; and, the aldehyde and acid analogues. Aldicarb is not commonly found in the excreta. Bound residues of ingested plant tissues are not absorbed and therefore are found in the faeces. In single dose and short-term diet studies, lactating cows eliminated aldicarb metabolites as rapidly as rats and in the same array of metabolites. Approximately 1% of the dose was excreted in the milk, sulfone and sulfoxide were the major metabolites at 15 and 4% of the total milk residue content respectively.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... Aldicarb 通过氧化途径和水解过程进行代谢。氧化产生具有活性的胆碱酯酶抑制剂的化合物，而水解则产生几乎没有杀虫活性或对其他生物有毒性的化合物。

... Aldicarb is metabolized by both oxidative pathways and hydrolytic processes. Oxidation results in cmpd which are also active cholinesterase inhibitors, while hydrolysis produces cmpd of little or no insecticidal activity or toxicity to other organisms.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Temik-(35)S/aldicarb/的主要消除途径是通过尿液。在牛奶中提取并初步鉴定出11种化合物，包括Temik亚砜和砜、氧亚砜和砜、腈亚砜和砜、Temik氧肟酸以及4种未识别的化合物。尿液中鉴定的代谢物在性质上相同，但在数量上有所不同。粪便中仅鉴定出5种代谢物：Temik氧肟酸、氧亚砜、Temik亚砜、Temik砜和腈砜。

The major route of elimination of Temik-(35)S /aldicarb/ ... admin to lactating cow was by way of urine. Extracted and tentatively identified in milk were 11 compounds, incl temik sulfoxide and sulfone, oxime sulfoxide and sulfone, nitrile sulfoxide & sulfone, temik oxime, and 4 unidentified compounds. Metabolites identified in urine were qualitatively identical but differed quantitatively. Only 5 metabolites were identified in feces: temik oxime, oxime sulfoxide, temik sulfoxide, temik sulfone and nitrile sulfone.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠中，亚砜占剂量的40%，磺酰酮占1%；这两种代谢物都比涕灭威更强的抗胆碱酯酶。牛乳和尿中的代谢物是磺酰酮的羟甲基类似物；另外两种牛代谢物是2-甲基-2-(甲硫亚基)丙醇和2-甲基-2-(甲硫基)丙醇。

In rats, sulfoxide accounted for 40% of dose /of aldicarb/ and sulfone for 1%; both ... are more potent anticholinesterases than aldicarb. Metabolite in cow's milk and urine was hydroxymethyl analogue of sulfone; two other bovine metabolites were 2-methyl-2-(methylsulfinyl)propanol and 2-methyl-2-(methylsulfonyl)propanol.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别： Aldicarb 是一种氨基甲酸酯类杀虫剂。它是一种白色结晶固体，水中溶解度适中，容易发生氧化和水解反应。人类暴露：一般人群对 Aldicarb 及其有毒代谢物（亚砜和砜）的暴露主要通过食物。摄入受污染的食物已导致 Aldicarb 及其有毒代谢物（亚砜和砜）的中毒事件。由于 Aldicarb 具有高度的急性毒性，职业暴露条件下通过吸入和皮肤接触可能对工人造成危险，如果预防措施不足。由于使用不当或缺乏保护措施，工人发生了几起意外暴露事件。Aldicarb 可从胃肠道有效地吸收，并通过皮肤吸收较少。如果有尘埃存在，它可能会被呼吸道轻易吸收。它通过代谢转化为亚砜和砜（两者均有毒），并通过水解转化为羟肟酸和腈以解毒。Aldicarb 及其代谢物的排泄迅速，主要通过尿液进行。还有一小部分会通过胆汁排出，并因此进行肠肝循环。由于长期暴露，Aldicarb 不会在体内积累。Aldicarb 对乙酰胆碱酯酶活性的抑制作用在体外是可逆的，半衰期为 30-40 分钟。Aldicarb 在人类中唯一公认的效果是在神经突触和神经肌肉接头处抑制乙酰胆碱酯酶，这与有机磷的作用相似。碳酰胺化酶不稳定，与磷酸化酶相比，自发性再活化相对较快。人类的非致命性中毒是迅速可逆的。恢复可由阿托品给药辅助。动物研究：Aldicarb 是一种强效的胆碱酯酶抑制剂，具有高度的急性毒性。从中枢神经系统的影响中恢复是自发的，除非死亡，否则在 6 小时内完全恢复。没有充分的证据表明 Aldicarb 具有致畸性、致突变性、致癌性或免疫毒性。由于摄入未完全按推荐方式掺入土壤的 Aldicarb 颗粒，鸟类和小型哺乳动物已被杀死。在实验室测试中，Aldicarb 对水生生物具有急性毒性。

IDENTIFICATION: Aldicarb is a carbamate ester pesticide. It is a white crystalline solid, moderately soluble in water, and susceptible to oxidation and hydrolytic reactions. HUMAN EXPOSURE: Exposure of the general population to aldicarb and its toxic metabolites (the sulfoxide and sulfone) occurs mainly through food. The ingestion of contaminated food has led to poisoning incidents from aldicarb and its toxic metabolites (the sulfoxide and sulfone). Due to the high acute toxicity of aldicarb, both inhalation and skin contact under occupational exposure conditions may be dangerous for workers if preventive measures are inadequate. There have been a few incidents of accidental exposure of workers due to improper use or lack of protective measures. Aldicarb is efficiently absorbed from the gastrointestinal tract and, to a lesser extent, through the skin. It could be readily absorbed by the respiratory tract if dust were present. It is metabolically transformed to the sulfoxide and the sulfone (both of which are toxic), and is detoxified by hydrolysis to oximes and nitriles. The excretion of aldicarb and its metabolites is rapid and primarily via the urine. A minor part is also subject to biliary elimination and, consequently, to enterohepatic recycling. Aldicarb does not accumulate in the body as a result of long-term exposure. The inhibition of cholinesterase activity in vitro by aldicarb is spontaneously reversible, the half-life being 30-40 min. The inhibition of acetylcholinesterase at the nervous synapse and myoneural junction is the only recognized effect of aldicarb in humans and is similar to the action of organophosphates. The carbamyolated enzyme is unstable, and spontaneous reactivation is relatively rapid compared with that of a phosphorylated enzyme. Non-fatal poisoning in man is rapidly reversible. Recovery is aided by the administration of atropine. ANIMAL STUDIES: Aldicarb is a potent inhibitor of cholinesterases and has a high acute toxicity. Recovery from its cholinergic effects is spontaneous and complete within 6 hr, unless death results. There is no substantial evidence to indicate that aldicarb is teratogenic, mutagenic, carcinogenic, or immunotoxic. Birds and small mammals have been killed as a result of ingesting aldicarb granules not fully incorporated into the soil as recommended. In laboratory tests, aldicarb is acutely toxic to aquatic organisms.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有来自人类研究的资料。实验动物中关于涕灭威致癌性的证据不足。总体评估：涕灭威的致癌性无法分类为对人类的影响（第3组）。

Evaluation: No data were available from studies in humans. There is inadequate evidence for the carcinogenicity of aldicarb in experimental animals. Overall evaluation: Aldicarb is not classifiable as to its carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：人类非致癌性证据E组

Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

分类：D；无法归类为人类致癌性。分类依据：在喂养研究中，没有发现aldoarb在大小鼠中诱导统计学上显著增加肿瘤发生率，在小鼠的皮肤涂抹研究中也未发现。然而，在喂养研究中，雌性大鼠的垂体肿瘤和雄性小鼠的纤维肉瘤有显著的趋势。这一证据，加上使用的剂量低于最大耐受剂量的事实，表明现有的检测方法不足以评估aldoarb的致癌潜力。人类致癌性数据：无。动物致癌性数据：不充分。/基于先前的分类系统/

CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Aldicarb was not found to induce statistically significant increases in tumor incidence in mice or rats in feeding studies or mice in a skin painting study. In the feeding studies there were, however, significant trends in pituitary tumors in female rats and fibrosarcomas in the male mouse. This evidence, together with the fact that less than maximum tolerated doses were used, indictes that the available assays are inadequate to assess the carcinogenic potential of aldicarb. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. /Based on former classification system/

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：阿德卡宾

IARC Carcinogenic Agent:Aldicarb

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

雄性大鼠（Carworth Farms-Elias Stock）通过口服或腹腔注射方式接受了标记的Temik乙醇溶液或Temik亚砜水溶液的处理。S-甲基-(14)C和叔丁基-(14)C Temik的排泄在4天内基本完成。N-甲基-(14)C则通过尿液和粪便排泄，持续高达11天。

Male rats (Carworth Farms-Elias Stock) were treated orally or ip with labeled Temik in ethanol or Temik sulfoxide in water. Excretion of s-methyl-(14)C & tert-butyl-(14)C temik was completed, essentially, in 4 days. N-methyl-(14)C was excreted in urine & feces up to 11 days.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿德卡普从处理过的动物的胃肠道被迅速吸收。放射性标记的化合物给大鼠排泄主要是通过尿液，大约80%在24小时内出现，另外1%在粪便中。在排泄物中只发现了微量的未改变的母体化合物。当阿德卡普在N-甲基碳或羰基碳上标记时，很大一部分放射性活性在呼出的空气中以(14)CO2的形式被发现。在处理过的动物的组织或尸体中只发现了很少的阿德卡普残留物。

Aldicarb is readily absorbed from GI tract of treated animals. Excretion of radiolabeled cmpd admin to rats is primarily in urine, as approx 80% appears within 24 hr, with additional 1% in feces. Only traces of unchanged parent cmpd were found in excreta. When aldicarb is labeled on n-methyl carbon or carbonyl carbon large portion of radioactivity is found in expired air as (14)CO2. Very little aldicarb residues are found in tissues or carcasses of treated animals.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了测量aldicarb的排泄量，实验犬在给药前20天和给药后10天分别维持摄入0.75毫克/犬/日的饮食，并给予单次(14)C标记的aldicarb剂量。在尿液中回收的放射性物质中，有90%在给药放射性标记aldicarb后24小时内发现。

To measure the excretion of aldicarb admin repeatedly, dogs were maintained on diets determining an intake of 0.75 mg/dog/day for 20 days before & 10 days after being given a single (14)C-labeled dose. Of the radioactivity recovered in the urine, 90% was found within 24 hr after admin of the radiolabeled aldicarb.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Aldicarb在大鼠和牛中通过肠道容易吸收，在大鼠和兔中通过皮肤吸收。它被迅速代谢并在接触后24小时内排出体外，几乎所有有毒和无毒的代谢物都通过尿液排出。

Aldicarb is readily absorbed through the gut in rats and cows and through the skin in rats and rabbits. It is rapidly metabolized and excreted within 24 hours of exposure, almost all of the toxic and nontoxic metabolites being excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法：将异丁烯、亚硝酸钠和盐酸进行二聚反应，生成2-氯-2-甲基-1-亚硝基丙烷二聚物。随后，该二聚物与甲硫醇钠反应，生成2-甲基-2-(甲硫基)丙醛肟。最终，肟与异氰酸甲酯反应制得涕灭威。

合成制备方法：同样地，将异丁烯、亚硝酸钠和盐酸进行二聚反应，生成2-氯-2-甲基-1-亚硝基丙烷二聚物。接着，该二聚物与甲硫醇钠作用，得到2-甲基-2-(甲硫基)丙醛肟。最后一步，肟与异氰酸甲酯反应制得涕灭威。

用途简介：涕灭威用作农用杀虫剂。

用途：涕灭威用于农业中作为杀虫剂使用。

反应信息

• 作为反应物：
  描述：

  涕灭威 在 氢化铝 作用下， 以 水 、 乙腈 为溶剂， 生成 甲胺
  参考文献：
  名称：

  高效液相色谱法对农药进行柱后光解，用于荧光测定。

  摘要：

  DOI：

  10.1021/ac00154a007
• 作为产物：
  描述：

  2-甲基-2-(甲硫基)丙醛肟 以 氯仿 为溶剂， 反应 3.0h， 生成 涕灭威
  参考文献：
  名称：

  2,2'-羰基-双（3,5-二氧代-4-甲基-1,2,4-恶二唑烷）：一种用于制备氨基甲酸酯和酰胺的新型试剂，用于合成二肽。

  摘要：

  制备了2,2'-羰基双（3,5-二氧-4-甲基-1,2,4-氧二唑烷）并将其用于合成各种氨基甲酸酯和二肽。

  DOI：

  10.1016/s0040-4039(01)81064-9

文献信息

• Alkyl 1-Chloroalkyl Carbonates: Reagents for the Synthesis of Carbamates and Protection of Amino Groups
  作者：Gérard Barcelo、Jean-Pierre Senet、Gérard Sennyey、Jean Bensoam、Albert Loffet

  DOI：10.1055/s-1986-31724

  日期：——

  The synthesis of 1-chloroalkyl carbonates and their reaction with various type of amines are described. This reaction is useful for the synthesis of carbamate pesticides and for the protection of various amino groups, including amino acids.

  描述了1-氯代烷基碳酸酯的合成及其与各种类型胺的反应。这一反应对于合成氨基甲酸酯类农药和保护包括氨基酸在内的各种氨基团具有重要作用。
• Genetic toxicity of <i>N</i>-methylcarbamate insecticides and their <i>N</i>-nitroso derivatives
  作者：T. C. Wang、C. M. Chiou、Y. L. Chang

  DOI：10.1093/mutage/13.4.405

  日期：——

  N-Methylcarbamate esters are an important group of insecticides. They have lower acute toxicity to vertebrates than organophosphates, although their genotoxicity has not been adequately studied. Here we investigate the cytotoxicity and genotoxicity of N-methylcarbamate insecticides and their N-nitroso derivatives in Chinese hamster V79 cells, using the hprt locus as a marker, and also assess inhibition

  N-甲基氨基甲酸酯是重要的一组杀虫剂。尽管对它们的遗传毒性尚未进行充分研究，但它们对脊椎动物的急性毒性比有机磷酸盐低。在这里，我们使用hprt基因座作为标记，研究N-甲基氨基甲酸酯杀虫剂及其N-亚硝基衍生物在中国仓鼠V79细胞中的细胞毒性和遗传毒性，并评估对间隙连接细胞间通讯的抑制作用。将N-甲基氨基甲酸酯杀虫剂化学N-亚硝化以获得N-亚硝基衍生物。N-亚硝基化大大增加了中国仓鼠V79细胞hprt位点的N-甲基氨基甲酸酯的细胞毒性和致突变性。N-亚硝基-N-甲基氨基甲酸酯的诱变潜力远高于许多其他已知的诱变亚硝基化合物，以及一些非亚硝基诱变的烷基化剂。亲本N-甲基氨基甲酸酯本身没有致突变性，但是，它们抑制间隙连接的细胞间通讯的效率是经过充分研究的肿瘤启动子12-O-十四烷酰phorbol-13-乙酸酯的一半。研究结果表明，N-甲基氨基甲酸酯杀虫剂及其N-亚硝基衍生物具有在化学致癌作用的多个阶
• A Fluorescence Detection Scheme for Capillary Electrophoresis of <i>N</i>-Methylcarbamates with On-Column Thermal Decomposition and Derivatization
  作者：Yuan Sheng Wu、Hian Kee Lee、Sam F. Y. Li

  DOI：10.1021/ac990928d

  日期：2000.4.1

  conditions, fluorescence detection of 10 NMC compounds was achieved, with column efficiencies typically higher than 50,000 and detection limits better than 0.5 ppm. The present work represents an unprecedented effort in capillary electrophoresis (CE), in which an intact capillary was consecutively utilized as chambers for separation, decomposition, derivatization, and detection, without involving any

  本文介绍了胶束电动色谱（MEKC）分离中N-甲基氨基甲酸酯（NMC）农药的荧光检测方法。荧光检测的实现取决于发现季铵盐表面活性剂（尤其是十六烷基三甲基溴化铵，CTAB），除了在MEKC中用作疏水假相外，还能够催化NMC的热分解以释放甲胺。因此，配制了由硼酸盐缓冲液，CTAB和衍生化成分（邻苯二甲醛/ 2-巯基乙醇）组成的多功能MEKC介质，该介质可首先进行常规的MEKC分离，随后进行热分解，最后进行NMC的原位衍生化。通过精心优化操作条件，实现了10种NMC化合物的荧光检测，色谱柱效率通常高于50,000，检测限优于0.5 ppm。本工作代表了毛细管电泳（CE）方面的空前努力，其中完整的毛细管被连续用作分离，分解，衍生和检测的腔室，而没有涉及任何接口功能。与通过反相HPLC进行NMC的传统柱后荧光测定相比，这种检测系统的成功实施使仪器非常简单。在确定CE格式的多种农药和药物时，类似的方案也
• Determination of the rate of aldicarb sulphoxidation in rat liver, kidney and lung microsomes
  作者：M. PELEKIS、K. KRISHNAN

  DOI：10.1080/004982597239877

  日期：1997.1

  sulphoxidation of aldicarb (2-methyl-2-(methylthio) propanal O-[(methylamino) carbonyl oxime], Temik) in rat hepatic, renal and pulmonary microsomes was determined by quantitating the levels of aldicarb sulphoxide and aldicarb sulphone produced during incubations. Under in vitro experimental conditions used in the present study, aldicarb sulphoxide was the only metabolite produced, and further metabolism of aldicarb

  1.通过定量涕灭威亚砜和涕灭威的含量，确定涕灭威（2-甲基-2-（甲硫基）丙醛O-[（甲基氨基）羰基肟]，Temik）在大鼠肝，肾和肺微粒体中的硫氧化速度。孵育过程中产生的砜。在本研究中使用的体外实验条件下，涕灭威亚砜是唯一产生的代谢产物，而涕灭威亚砜进一步代谢为涕灭威砜的作用可忽略不计。2.基于产物形成的测量，在肝脏，肾脏和肺微粒体中，涕灭威硫氧化的平均最大速度（mumol / min / mg蛋白质）分别为5.41、39.51和2.45。米氏常数（microM）的相应值分别为184、1050和188。3。
• The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells
  作者：Chih-Min Lin、L.Y. Wei、Tsing-Cheng Wang

  DOI：10.1016/j.fct.2006.11.015

  日期：2007.6

  N-nitroso derivative of an extensively used insecticide, propoxur, consistently induced dose-responsive chromosome aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations indicated that post-treatment incubation with a regular 1.5-cell-cycle period did not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate insecticides. The scale

  广泛使用的杀虫剂丙氧磷的N-亚硝基衍生物在中国仓鼠卵巢（CHO-W8）细胞中持续诱导剂量反应性染色体畸变和姐妹染色单体交换（SCE）。进一步的研究表明，在规则的1.5个细胞周期内进行后处理孵育不会对N-亚硝基氨基甲酸酯类杀虫剂的遗传毒性提供公正的估计。染色体畸变诱导的规模随着治疗后潜伏期的延长而增加。在熟练O（6）-甲基鸟嘌呤-DNA-甲基转移酶的CHO-AGT细胞中未发现可比的现象。在CHO-W8细胞中，在第一个复制周期中对杀虫剂进行脉冲处理显示出比第二个周期中更高的SCE诱导率。在其他氨基甲酸酯类杀虫剂（包括涕灭威，呋喃丹和灭多威）的N-亚硝基衍生物诱导的SCE中也发现了类似现象。处理的细胞直到去除处理后12小时才显示出明显的扰动的细胞周期进程。基于上述观察结果，O（6）-甲基鸟嘌呤-DNA加合物被认为是由N-甲基氨基甲酸酯杀虫剂的延迟遗传毒性作用引起的主要病变，如本报告所述。

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