毒杀芬 | 8001-35-2

• 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: 毒杀芬
• 中文别名: 氯化莰、氯化茨烯、八氯茨烯、氯代莰烯、3956、多氯莰烯；氯化茨烯；八氯莰烯；八氯茨烯；多氯莰烯；多氯化莰烯；氯代莰烯；氯化莰
• 英文名称: 1,4,5,6,7,7-Hexachloro-2,2-bis(chloromethyl)-3-methylidenebicyclo[2.2.1]heptane
• CAS: 8001-35-2
• 化学式: C₁₀H₈Cl₈
• 分子量: 411.8
• InChiKey: OEJNXTAZZBRGDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

使用生物测定方法发现，抗性苍蝇能够从吸收的5.4微克剂量中代谢掉4.0微克的毒杀芬。没有发现代谢物。在研究棉铃虫时，发现了脱氢氯化酶的存在，并且毒杀芬被分解。通过纸层析法分离出了3个组分，但未鉴定出这些组分。

USING BIOASSAY METHODS, IT WAS FOUND THAT RESISTANT FLIES COULD METABOLIZE 4.0 UG OF TOXAPHENE FROM AN ABSORBED DOSE OF 5.4 UG. NO METABOLITES WERE IDENTIFIED. ... IN STUDIES WITH THE COTTON LEAFWORM, THE PRESENCE OF A DEHYDROCHLORINASE & THE BREAKDOWN OF TOXAPHENE WAS DEMONSTRATED. 3 COMPONENTS WERE SEPARATED BY PAPER CHROMATOGRAPHY BUT WERE NOT IDENTIFIED.

来源:Hazardous Substances Data Bank (HSDB)

代谢

老鼠在代谢过程中会去氯化毒杀酚。在多种生物体中，这一反应是还原性脱氯，有时是脱氢氯化。部分毒杀酚也会通过大鼠肝微粒体酶制剂中的还原型烟酰胺腺嘌呤二核苷酸依赖性混合功能氧化酶进行代谢。

Rats metabolically dechlorinate toxaphene. In several organisms ... this reaction is a reductive dechlorination, sometimes a dehydrochlorination. In part toxaphene is also metabolized by reduced nicotinamide adenine dinucleotide dependent mixed function oxidase in rat hepatic microsomal enzyme preparations. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠肝脏微粒体制备物中进行了体外研究。通过添加还原型谷胱甘肽和烟酸腺嘌呤二核苷酸磷酸，增加了毒杀酚的代谢。除了脱氯作用外，还发生了一些氧化反应，生成了羟基化合物和酸性化合物。进一步的研究表明，通过β-葡萄糖醛酸酶和β-磺酸酯酶的作用释放了苷元，表明在体外存在水释放的共轭物。

In vitro studies were conducted with rat liver microsomal preparations. Metabolism of toxaphene was increased by addition of reduced glutathione & nicotinamide-adenine dinucleotide phosphate. In addition to dechlorination, some oxidation to hydroxyl and acidic cmpd occurred. Further study showed that aglycones were released by action of beta-glucuronidase and beta-sulfatase, indicating the presence of water releasing conjugates in vitro.

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了 toxaphene 在灌流牛肝脏中的代谢。从两头肉牛和一头奶牛的颈静脉采血，然后取出肝脏。血液去纤颤并过滤；加入100毫克土霉素，然后用作灌流液。肝脏被清洗和排干，然后连接到灌流室的动脉侧。加入乙醇溶液的 toxaphene，使血液中的浓度为每克20微克。在实验结束时，每隔15分钟取一次灌流液的样本，此时称重肝脏并取样。通过循环给药血液而不经过肝脏，确定 toxaphene 的回收率和血液对 toxaphene 的影响。血液样本用于分析 toxaphene，并通过气液色谱分析去氯代谢物。在给药后15分钟，大约75%的 toxaphene 被肝脏吸收；给药后105分钟，又额外吸收了15%。toxaphene 从灌流液中早期快速下降和后期下降的半衰期分别为7分钟和86分钟。气相色谱图显示，toxaphene 成分产生了部分去氯的衍生物，这些衍生物随着时间的推移进一步降解。灌流液与肝脏和不含肝脏的循环血液之间的响应比表明，肝脏对 toxaphene 的代谢在给药后15分钟内发生。

The metabolism of toxaphene in perfused bovine liver was studied. Two beef cows and one dairy calf had blood collected from the jugular vein and the liver was then removed. The blood was defibrinated and filtered; 100 milligrams oxytetracycline was added and then used as perfusate. The liver was cleaned and drained, then attached to the arterial side of a perfusion chamber. An ethanolic solution of toxaphene was added to give a concentration of 20 micrograms per gram in the blood. Samples of the perfusate were taken every 15 minutes until the end of the experiment when the liver was weighed and a sample taken. Recovery of toxaphene and the effect of blood on toxaphene were determined by circulating dosed blood without the liver. Blood samples were analyzed for toxaphene and dechlorinated metabolites were analyzed by gas liquid chromatography. By 15 minutes after dosing, approximately 75% of the toxaphene was taken up by the liver; 105 minutes after dosing, an additional 15% was taken up. The half-life of early rapid rate of decline and later rate of decline of toxaphene from the perfusate was 7 minutes and 86 minutes, respectively. The gas chromatographs showed that toxaphene components produced partially dechlorinated derivatives that degraded further with time. The response ratio between perfusate with liver and circulating blood without liver showed that toxaphene metabolism by the liver occurred by 15 minutes after dosing.

来源:Hazardous Substances Data Bank (HSDB)

代谢

杀螟松通过肠道和肺被吸收，然后主要分布到脂肪组织中。由于杀螟松的复杂组成，它需要通过多种代谢途径来降解，包括脱氯、脱氢脱氯和氧化。代谢主要通过肝脏的混合功能氧化酶进行，代谢物通过尿液和粪便排出体外。

Toxaphene is absorbed through the intestines and lungs, then distributed mainly to fat tissues. Due to the complex composition of toxaphene, it requires various metabolic pathways to degrade, which involve dechlorination, dehydrodechlorination, and oxidation. Metabolism occurs primarily by hepatic mixed-function oxidases, and metabolites are excreted in the urine and faeces. (L107)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Toxaphene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效的神经毒素，在低剂量时会导致过度流涎和流泪，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，后者在神经和肌肉接头处释放，以允许肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积累并继续发挥作用，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，它们被设计成与酶的活性位点结合。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。

Toxaphene 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

评估：对于毒杀芬对人类致癌性的证据不足。对于毒杀芬对实验动物致癌性的证据是充分的。总体评估：毒杀芬可能对人类具有致癌性（2B组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxaphene. There is sufficient evidence in experimental animals for the carcinogenicity of toxaphene. Overall evaluation: Toxaphene is possibly carcinogenic to humans (Group 2B).

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

• 致癌性证据

分类：B2；可能的人类致癌物。分类依据：基于小鼠肝细胞肿瘤增加和大鼠甲状腺肿瘤增加的情况，并且通过沙门氏菌的致突变性得到支持。人类致癌性数据：无。动物致癌性数据：充分。

CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: The classification is based on increased incidence of hepatocellular tumors in mice and thyroid tumors in rats and is supported by mutagenicity in Salmonella. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Sufficient.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3：已确认的动物致癌物，对人类的相关性未知。

A3: Confirmed animal carcinogen with unknown relevance to humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中，(36)氯-莰烯口服剂量的52.6%在9天内被排出。大约37%随粪便排出，15%随尿液排出。在提取过程中，大部分放射性物质出现在尿液和粪便的水分中，以离子态氯化物形式存在。在第9天给予第二次剂量的动物以类似方式排出莰烯，只是粪便中的(36)氯排出量减少了。在处理后的第1天，选定的组织和器官中发现的剂量少于10%。

IN RAT, 52.6% OF ORAL DOSE OF (36)CL-TOXAPHENE WAS EXCRETED WITHIN 9 DAYS. APPROX 37% ... IN FECES, & 15% IN URINE. ON EXTRACTION, MOST OF RADIOACTIVITY OCCURRED IN WATER FRACTIONS OF URINE & FECES AS IONIC CHLORIDE. ANIMALS GIVEN 2ND DOSE ON 9TH DAY EXCRETED TOXAPHENE IN SIMILAR MANNER, EXCEPT THAT (36)CHLORINE EXCRETION IN FECES WAS REDUCED. LESS THAN 10% OF DOSE WAS FOUND IN SELECTED TISSUES & ORGANS 1 DAY AFTER TREATMENT.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它通过完整的皮肤、呼吸系统和胃肠系统被吸收。可消化的油类和液体制剂（油性溶剂）的存在增加了肠道的吸收，它们比粉尘或粉末更容易渗透皮肤。

/IT IS/ ... ABSORBED THROUGH INTACT SKIN, RESP TRACT & GI TRACT. ... INTESTINAL ABSORPTION IS INCR BY PRESENCE OF DIGESTIBLE OILS, & LIQ PREPN (OIL SOLVENTS) PENETRATE THE SKIN FAR MORE READILY THAN DO DUSTS OR POWDERS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

给大鼠口服(14)C-毒杀芬3%的剂量在粪便中未改变地排出。超过5%的给药剂量以完全脱氯代谢物的形式在尿液和粪便中排出，27%以部分脱氯代谢物的形式排出；20%的活性在呼出的空气中找到。

3% OF AN ORAL DOSE OF (14)C-TOXAPHENE WAS EXCRETED UNCHANGED IN THE FECES OF RATS. MORE THAN 5% OF THE ADMINISTERED DOSE WAS EXCRETED IN THE URINE AND FECES AS COMPLETELY DECHLORINATED METABOLITES, AND 27% AS PARTIALLY DECHLORINATED METABOLITES; 20% OF THE ACTIVITY WAS FOUND IN EXPIRED AIR.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当白来航鸡在饲料中摄入5、50或100 ppm的毒杀芬时，可以在蛋中检测到残留物。... 8周大的 Hubbard-Hubbard 肉鸡的脂肪组织中毒杀芬的浓度随着饲料摄入量的增加而增加。生物富集因子大约为5。

When white leghorn chickens are fed 5, 50, or 100 ppm toxaphene in the diet, residues are detected in eggs. ... The concn of toxaphene in adipose tissue of 8 wk old Hubbard-Hubbard broiler chickens increases with increasing dietary intake. Bioaccumulation factor is about 5.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

莰烯与氯反应可得毒杀芬。松节油经减压蒸馏提取α-蒎烯，再在水合氧化钛存在下进行异构化，异构液通过减压蒸馏得到纯度约90%以上的莰稀。将莰烯溶于2.5倍体积的四氯化碳中进行通氯反应。氯化过程可采用间歇法或连续法：先使莰烯四氯化碳溶液与氯化反应尾气中的氯气反应，再加入新鲜氯气。在光照条件下进行氯化反应，温度控制在40-60℃之间。氯气经过串联反应后，尾气含有少量余氯和大量氯化氢，压力约为10.7kPa，可用液碱吸收综合利用。当氯化液的含氯量达到66.5-68.5%时，在光照下放料至水蒸气蒸馏锅中，于110℃条件下蒸馏得到毒杀芬。工业品为莰烯氯化异构反应的混合物，含氯量在66.5-68.5%，每吨消耗松节油约700kPa左右和氯气约1350kPa。商品有40%或50%的乳油。

合成制备方法

同样由莰烯与氯反应得到毒杀芬。松节油经减压蒸馏提取α-蒎烯，再在水合氧化钛存在下进行异构化，异构液通过减压蒸馏得到纯度约90%以上的莰稀。将莰烯溶于2.5倍体积的四氯化碳中进行通氯反应。氯化过程可采用间歇法或连续法：先使莰烯四氯化碳溶液与氯化反应尾气中的氯气反应，再加入新鲜氯气。在光照条件下进行氯化反应，温度控制在40-60℃之间。氯气经过串联反应后，尾气含有少量余氯和大量氯化氢，压力约为10.7kPa左右，可用液碱吸收综合利用。当氯化液的含氯量达到66.5-68.5%时，在光照下放料至水蒸气蒸馏锅中，于110℃条件下蒸馏得到毒杀芬。工业品为莰烯氯化异构反应的混合物，含氯量在66.5-68.5%，每吨消耗松节油约700kPa左右和氯气约1350kPa。商品有40%或50%的乳油。

用途简介

毒杀芬是一种非内吸性的持久性接触和胃毒杀虫剂，同时也具有一定的杀螨作用。主要用于防治棉花铃期害虫如棉铃象鼻虫、棉红铃虫、棉蚜虫等，也适用于玉米、水稻、蔬菜、苎麻、果树、森林等方面的多种害虫，包括水稻螟虫、稻苞虫、稻蓟马、稻尽虱、浮尘子、稻螟、松毛虫、松毒蛾、柠檬恶性叶虫、柑桔凤蝶、苎麻黄夹蝶等。此外，还能够杀灭牲畜和家禽体外寄生虫，并可用于拌种以防治地下害虫。

用途

作为非内吸性的持久性接触和胃毒杀虫剂，毒杀芬具有一定的杀螨作用。主要用于防治棉花铃期的棉铃象鼻虫、棉红铃虫、棉蚜虫等害虫；也可用于玉米、水稻、蔬菜、苎麻、果树、森林等方面的多种害虫，包括水稻螟虫、稻苞虫、稻蓟马、稻尽虱、浮尘子、稻螟、松毛虫、松毒蛾、柠檬恶性叶虫、柑桔凤蝶、苎麻黄夹蝶等。此外，还能够杀灭牲畜和家禽体外寄生虫，并可用于拌种以防治地下害虫。

文献信息

• Methods and compositions for increasing the efficacy of biologically-active ingredients
  申请人：Windsor Brian J.

  公开号：US20060276339A1

  公开（公告）日：2006-12-07

  The invention provides methods and compositions for modulating the sensitivity of cells to cytotoxic compounds and other active agents. In accordance with the invention, compositions are provided comprising combinations of ectophosphatase inhibitors and active agents. Active agents include antibiotics, fungicides, herbicides, insecticides, chemotherapeutic agents, and plant growth regulators. By increasing the efficacy of active agents, the invention allows use of compositions with lowered concentrations of active ingredients.
• US6818692B2
  申请人：——

  公开号：US6818692B2

  公开（公告）日：2004-11-16
• [EN] HIGH STRENGTH NON-HAP RUBBER CEMENT COMPOSITION<br/>[FR] COMPOSITION DE COLLE DE CAOUTCHOUC HAUTE RESISTANCE NE CONSTITUANT PAS UN POLLUANT ATMOSPHERIQUE DANGEREUX
  申请人：TEXAS RES INTERNATIONAL INC

  公开号：WO2003020811A1

  公开（公告）日：2003-03-13

  This invention pertains to rubber cement compositions containing a rubber elastomer, a tackifier, and an organic solvent that is not a hazardous air pollutant (HAP). This invention also includes the method of making this rubber cement composition and of using this adhesive to bond to surfaces together.