甲拌磷 | 298-02-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机二硫代磷酸及其衍生物
• 中文名称: 甲拌磷
• 中文别名: 三九一一；甲拌磷原油；O,O-二乙基-S-乙硫基甲基-二硫代磷酸酯；西梅脱；伏螟
• 英文名称: Phorate
• 英文别名: diethoxy-(ethylsulfanylmethylsulfanyl)-sulfanylidene-λ5-phosphane
• CAS: 298-02-2
• 化学式: C₇H₁₇O₂PS₃
• mdl: MFCD00036348
• 分子量: 260.383
• InChiKey: BULVZWIRKLYCBC-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  1. 稳定性^[14]：稳定。 2. 禁配物^[15]：强氧化剂和碱类。 3. 避免接触的条件^[16]：避免受热。 4. 聚合危害^[17]：不聚合。 5. 分解产物^[18]：氧化磷、硫化物。

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  13
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

Thimet (32)P in oil was administered orally to male albino rats. ...Hydrolysis products appearing in urine of rats within 2 days were found to consist of o,o-diethyl phosphoric acid (17%); o,o-diethyl phosphorothioic acid (80%); and o,o-diethyl phosphorodithioic acid (3%). Using rat liver preparation, phosphorodithioate sulfoxides and sulfones and phosphorothiolate sulfoxides and sulfones were formed ...<1% of radioactive metabolites appeared as hydrolysis products or unextractable residue from proteins... . After thimet was applied to plants ...four non-hydrolyzed metabolites were identified as phosphorodithioate sulfoxide and sulfone, phoratoxon, phosphorothiolate sulfoxide and sulfone. o,o-Diethyl phosphorothioic and o,o-diethyl phosphoric acid were also found.

Thimet (32)P in oil was administered orally to male albino rats. ...Hydrolysis products appearing in urine of rats within 2 days were found to consist of o,o-diethyl phosphoric acid (17%); o,o-diethyl phosphorothioic acid (80%); and o,o-diethyl phosphorodithioic acid (3%). Using rat liver preparation, phosphorodithioate sulfoxides and sulfones and phosphorothiolate sulfoxides and sulfones were formed ...<1% of radioactive metabolites appeared as hydrolysis products or unextractable residue from proteins... . After thimet was applied to plants ...four non-hydrolyzed metabolites were identified as phosphorodithioate sulfoxide and sulfone, phoratoxon, phosphorothiolate sulfoxide and sulfone. o,o-Diethyl phosphorothioic and o,o-diethyl phosphoric acid were also found.

来源:Hazardous Substances Data Bank (HSDB)

代谢

该化合物被植物代谢成非常强的抗胆碱酯酶剂，其中已经确定了磷精和其氧类似物的亚砜和磺酰亚胺。这些化合物的抗胆碱酯酶活性，以pI 50值表示，如下：磷精，3.17；P-亚砜，3.35；磷精-磺酰亚胺，5.00；氧类似物（PO）5.87；PO-亚砜，6.76；PO-磺酰亚胺，7.02。由于植物的这种氧化作用，尽管总残留量不可避免地会有所损失，但施用过磷精的植物上的残留物在几天内会增加抗胆碱酯酶活性，然后才会逐渐失去活性。虽然在从处理过的种子生长的7.4周大的棉花叶片中可以检测到磷精代谢物，但在植物长到16周时收集的种子中未发现代谢物（<0.03 ppm）。

The compound is metabolized by plants to very potent anticholinesterase agents, of which both the sulfoxide and the sulfone of both phorate and its oxygen analog have been identified. The anticholinesterase activity of the compounds expressed as pI 50 values are as follows: phorate, 3.17; P-sulfoxide, 3.35; phorate-sulfone, 5.00; oxygen analog (PO) 5.87; PO-sulfoxide, 6.76; PO-sulfone, 7.02. Because of this oxidation by plants and in spite of some inevitable loss of total residue, residues on plants to which phorate had been applied increase in anticholinesterase activity for several days and only then gradually lose activity. Although phorate metabolites could be detected in foliage of 7.4 week old cotton plants grown from treated seed, no metabolites (<0.03 ppm) could be found in the seeds gathered when the plants were 16 weeks old.

来源:Hazardous Substances Data Bank (HSDB)

代谢

老鼠和牛不仅形成与植物相同的代谢物，而且还能裂解P-S键，形成O,O-二乙基硫代磷酰氧和随后的O,O-二乙基磷酸，这些物质通过尿液排出体外。

Rats and cows not only form the same metabolites as plants but, in addition cleave the P-S bond to form O,O-diethylphosphorothiolic and later O,O-diethyl-phosphoric acid, which are excreted in the urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了细胞色素P450依赖的单加氧酶系统和含黄素的单加氧酶在小鼠微粒体中氧化对硫磷（O,O-二乙基S-((乙基硫代)甲基)亚磷酸酯）的相对贡献，小鼠分别接受了苯巴比妥、对溴苯氧基丁烷、丙酮或氢化可的松的处理。对溴苯氧基丁烷处理对几种肝脏酶活性产生了明显的双向效应（初始抑制随后诱导），包括对硫磷亚砜氧化。细胞色素P450依赖的单加氧酶系统在对硫磷亚砜氧化中的相对贡献从对照组的76%降至处理2小时后的58%，并在12小时后增加到89%。氢化可的松处理增加了肝脏微粒体中含黄素的单加氧酶活性，但肺微粒体中未见增加。丙酮给药导致肝脏中苯甲他明N-去甲基化和对硝基酚羟基化增加，但未观察到对硫磷亚砜氧化酶活性的变化，细胞色素P450依赖的单加氧酶系统和含黄素的单加氧酶的相对贡献也没有改变。苯巴比妥处理大大增加了肝脏微粒体中苯甲他明N-去甲基化和对硫磷亚砜氧化酶活性，细胞色素P450依赖的单加氧酶系统在对硫磷亚砜氧化酶活性中的比例从对照组肝脏的76%增加到处理组肝脏的85%。

The relative contributions of the cytochrome p450 dependent monooxygenase system and the flavin containing monooxygenase in the microsomal oxidation of phorate, O,O-diethyl S-((ethylthio)methyl)phosphorodithioate, were investigated in mice following treatment with phenobarbital, piperonyl butoxide, acetone, or hydrocortisone. Piperonyl butoxide treatment produced a distinct biphasic effect (initial inhibition and subsequent induction) on several hepatic enzyme activities, including phorate sulfoxidation. The relative contribution by the cytochrome p450 dependent monooxygenase system to phorate sulfoxidation decreased from 76% in control to 58% at 2 hr after treatment and increased to 89% at 12 hr. Hydrocortisone treatment caused an increase in flavin containing monooxygenase activity in liver microsomes, but not in lung microsomes. Administration of acetone caused an increase in benzphetamine N-demethylation and p-nitrophenol hydroxylation in the liver, but no change in phorate sulfoxidase activity was observed, nor was the relative contributions due to the cytochrome p450 dependent monooxygenase system and flavin containing monooxygenase altered. Treatment with phenobarbital produced a large increase in both benzephetamine N-demethylase and phorate sulfoxidase activity in liver microsomes, with the percentage of phorate sulfoxidase activity due to the cytochrome p450 dependent monooxygenase system being increased from 76% in the control livers to 85% in the treated livers.

来源:Hazardous Substances Data Bank (HSDB)

代谢

从一家农药制剂厂的员工每日尿样中定量了磷酰的代谢物。尿液中发现的 主要烷基磷酸酯是二乙基磷酸、二乙基硫代磷酰和二乙基硫代磷酸。

Metabolites of phorate were quantified in daily urine specimens obtained from employees of a pesticide formulating plant. The predominant alkyl phosphates found in urine were diethyl phosphate, diethyl phosphorothiolate, and diethyl thiophosphate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

Phorate是一种胆碱酯酶或乙酰胆碱酯酶（AChE）抑制剂。胆碱酯酶抑制剂（或“抗胆碱酯酶”）抑制乙酰胆碱酯酶的作用。由于其基本功能，干扰乙酰胆碱酯酶作用的化学物质是强大的神经毒素，在低剂量时会导致过度流涎和眼泪，随后是肌肉痉挛，最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸，完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱，该递质在神经和肌肉接头处释放，以使肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用，使得任何神经冲动不断传递，肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于磷的化合物，它们被设计用来结合到酶的活性位点上。结构要求是一个带有两个亲脂性基团的磷原子，一个离去基团（如卤素或硫氰酸盐）以及一个末端的氧。

Phorate is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

来源:Toxin and Toxin Target Database (T3DB)

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

A4：不能归类为人类致癌物。

A4: Not classifiable as a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

急性接触胆碱酯酶抑制剂可能会导致胆碱能危象，表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、晕厥和抽搐。肌肉无力可能性增加，如果呼吸肌受累，可能会导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处烟碱受体的过度刺激。当这种情况发生时，可能会看到肌肉无力、疲劳、肌肉痉挛、肌束震颤和麻痹的症状。当自主神经节积累乙酰胆碱时，这会导致交感系统中烟碱受体的过度刺激。与此相关的症状是高血压和低血糖。由于乙酰胆碱积累而在中枢神经系统中过度刺激烟碱乙酰胆碱受体，会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力，甚至可能昏迷。当由于副交感乙酰胆碱受体上乙酰胆碱过多而导致毒蕈碱过度刺激时，可能会出现视力障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、肠蠕动和排尿的症状。对于男性和女性的生育、生长和发育，已经特别将与有机磷农药暴露联系起来。关于生殖影响的大多数研究都是在农村地区使用杀虫剂和杀虫剂的农民进行的。在女性中，月经周期紊乱、怀孕时间延长、自然流产、死产以及后代的一些发育效应与有机磷农药暴露有关。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与人因接触有机磷农药而中毒引起的四种神经毒性效应有关：胆碱能综合症、中间综合症、有机磷诱导的迟发性多发性神经病（OPIDP）和慢性有机磷诱导的神经精神障碍（COPIND）。这些综合症在急性接触和慢性接触有机磷农药后出现。

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

(32)P标记的thimet通过口服给药给哺乳期荷斯坦牛。尿液中仅存在水解产物。...总组织残留量最高出现在肝脏、肾脏、肺、消化道和腺体组织中。脂肪样本中的thimet代谢物含量非常低。

(32)P-labeled thimet was orally admin to lactating Holstein cow. Only hydrolysis products present in urine. ...Highest total tissue residues appeared in liver, kidney, lung, alimentary canal, and glandular tissues. Fat samples ...very low in thimet metabolites.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它可以通过所有途径被吸收，包括口服、呼吸道和皮肤。

It is absorbed by all routes, oral, respiratory, and dermal.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠体内，口服剂量的约77%在24小时内通过尿液排出，12%通过粪便排出。给予大鼠口服磷精酸2毫克/千克或每天6次剂量，每次1毫克/千克的情况下，6天内尿液排出剂量高达35%，粪便排出高达6%。以每天1毫克/千克的剂量连续治疗6天的大鼠，在7天内仅通过尿液排出12%，通过粪便排出6%。

About 77% of an oral dose was excreted in the urine of rats within 24 hr, and 12% was excreted in the feces. Rats given oral phorate at 2 mg/kg or 6 daily doses at 1 mg/kg/day eliminated up to 35% of the dose in urine and up to 6% in feces in 6 days. Rats treated at the rate of 1 mg/kg/day for 6 days excreted only 12% in the urine and 6% in the feces within 7 days.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一头接受了3.04毫克/千克剂量的牛在72小时内通过尿液排出了59%，仅有0.8%通过粪便排出。在牛和老鼠体内，当动物被宰杀时，大部分剩余的放射性物质以未识别的形式（可能是二乙基磷酸化蛋白）与组织结合，尤其是肝脏和肾脏，这种形式无法用氯仿或丙酮提取。

A cow that received a dosage of 3.04 mg/kg excreted 59% in the urine within 72 hr and only 0.8% in the feces. In both /cows and rats/ most of the radioactivity remaining in the body when the animals were killed was bound to the tissues, especially liver and kidney, in an unidentified form (perhaps diethyl phosphorylated protein) that could not be extracted with either chloroform or acetones.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

似乎主要是与蛋白质结合，其转化似乎与这些蛋白质的半衰期有关。有限的数据表明，残基并入DNA仅在微量发生，并非通过直接烷基化，例如可能被认为与遗传损伤有关的。/有机磷农药/

Binding seems to be to proteins, principally, and the turnover appears to be related to the half-life of these proteins. There are limited data showing that incorporation of residues into DNA occurs only in trace amounts and not by direct alkylation, such as might be believed to be associated with genetic damage. /Organophosphorus Pesticides/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

将O，O-二乙基二硫代磷酸酯和乙硫醇在甲醛水溶液存在下反应而得。具体操作为：将约23%的二乙基二硫代磷酸酯与36%的甲醛水溶液及乙硫醇按照摩尔比1:1.1:1.16的比例配合，连续加入串联的两个反应缸中。温度分别控制在50℃和70℃，缩合成甲拌磷，经连续分液得到含量为85-90%的甲拌磷原油，收率为85-92%。加工剂型为60%乳油。原料消耗定额：二乙基二硫代磷酸酯900kg/t、乙硫醇350kg/t、甲醛（36%）530kg/t。

合成制备方法

同样地，将O，O-二乙基二硫代磷酸酯和乙硫醇在甲醛水溶液存在下反应而得。具体的步骤是：将约23%的二乙基二硫代磷酸酯与36%的甲醛水溶液及乙硫醇按照摩尔比1:1.1:1.16的比例配合，连续加入串联的两个反应缸中。温度分别控制在50℃和70℃，缩合成甲拌磷，经连续分液得到含量为85-90%的甲拌磷原油，收率为85-92%。加工剂型为60%乳油。原料消耗定额：二乙基二硫代磷酸酯900kg/t、乙硫醇350kg/t、甲醛（36%）530kg/t。

用途简介

该品具有内吸和熏蒸作用，主要用于棉籽拌种、浸种或土壤处理，防治棉花早期蚜虫、红蜘蛛、蓟马等，并可兼治地老虎、蝼蛄、金针虫等地下害虫。它是剧毒且高效的广谱性杀虫剂。

用途

1. 该品具有内吸和熏蒸作用，主要用于棉籽拌种、浸种或土壤处理，防治棉花早期蚜虫、红蜘蛛、蓟马等，并可兼治地老虎、蝼蛄、金针虫等地下害虫。
2. 作为剧毒且高效的广谱性杀虫剂，它同样具备内吸和熏蒸作用，主要用于棉籽拌种、浸种或土壤处理，防治棉花早期蚜虫、红蜘蛛、蓟马等，并可兼治地老虎、蝼蛄、金针虫等地下害虫。
3. 在农业上，该品可用于棉花、甜菜、萝卜等作物的浸种和拌种，但不可用于喷洒。 [20]

反应信息

• 作为反应物：
  描述：

  甲拌磷 在 双氧水 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 生成 甲拌磷砜
  参考文献：
  名称：

  有机磷杀虫剂“甲拌磷”的光降解

  摘要：

  甲拌磷 (I)（0,0-二乙基 S-乙基硫代甲基二硫代磷酸酯）的光解已被研究为玻璃表面和甲醇-水（60:40）溶液中的薄膜，通过紫外光（λ > 290纳米）。甲拌磷在溶液中的消失速率为一级动力学，速率常数为 4.9 × 10–5 S –1。发现（I）暴露在玻璃表面上的半衰期为 5 小时。主要光产物的结构通过 1 H NMR 和质谱进行表征。

  DOI：

  10.1080/02772249409357980
• 作为产物：
  描述：

  chloromethyl ethyl sulfide 、 二硫代磷酸二乙酯 在 1,2-二氯乙烷 作用下， 生成 甲拌磷
  参考文献：
  名称：

  DE917668

  摘要：

  公开号：

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
  申请人：BASF SE

  公开号：WO2014206910A1

  公开（公告）日：2014-12-31

  The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式（I）中变量如索权和说明中所定义的自行车基取代异噻唑啉化合物。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种通过使用这些化合物来控制无脊椎动物害虫的方法，以及包含所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] AZOLINE COMPOUNDS<br/>[FR] COMPOSÉS AZOLINE
  申请人：BASF SE

  公开号：WO2015128358A1

  公开（公告）日：2015-09-03

  The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及式（I）的噁唑啉化合物，其中A、B1、B2、B3、G1、G2、X1、R1、R3a、R3b、Rg1和Rg2如权利要求和描述中所定义。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种利用这些化合物控制无脊椎动物害虫的方法，以及包括所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。

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