methyl (1E)-N-[methyl-[methyl-[(Z)-1-methylsulfanylethylideneamino]oxycarbonylamino]sulfanylcarbamoyl]oxyethanimidothioate | 59669-26-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫基化合物
• 英文名称: methyl (1E)-N-[methyl-[methyl-[(Z)-1-methylsulfanylethylideneamino]oxycarbonylamino]sulfanylcarbamoyl]oxyethanimidothioate
• CAS: 59669-26-0
• 化学式: C₁₀H₁₈N₄O₄S₃
• 分子量: 354.5
• InChiKey: XDOTVMNBCQVZKG-NTLHZVPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  0
• 氢受体数：
  9

ADMET

代谢

代谢研究在大鼠中使用单次低剂量和单次高剂量的放射性标记的硫代 dicarb 进行。主要消除途径是呼出（二氧化碳和丙酮）和排尿。在给药后 7 天，组织残留物中含有剂量的 7-9%，这可能反映了 (14)C-丙酮代谢进入体内的 C-2 和 C-1 池，随后与天然产物相互作用或结合。大鼠中硫代 dicarb 的主要终末代谢物是 CO2 和丙酮。主要的尿代谢物是一种不稳定的未知物质，占尿中放射性标记的 50%。在任何组织中都没有检测到乙酰胺。红细胞中只含有不能被有机溶剂或水提取的残留物，这表明存在放射性标记结合到天然产物中或物质紧密结合到血红蛋白上。

Metabolic studies were performed in rats using single low and single high doses of radiolabeled thiodicarb. The major routes of elimination were expiration (CO2 and acetonitrile) and urination. Tissue residues contained 7-9% of the dose at 7 days post dose and may reflect the metabolism of (14)C-acetonitrile into the body's C-2 and C-1 pools and subsequent interaction with, or incorporation into natural products. The major terminal metabolites of thiodicarb in the rat are CO2 and acetonitrile. The major urinary metabolite is a labile unknown that represents 50% of the urinary radiolabel. No acetamide was detected in any of the tissues. The RBCs contained only residue that cannot be extracted by organic solvents or water, indicating the presence of radiolabel incorporated into natural products or of material tightly bound to hemoglobin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项猴子代谢研究中，一些含有放射性同位素标记的thiodicarb（顺式，顺式-异构体）通过体内代谢转化为顺式-甲基异柳磷，随后异构化为反式-甲基异柳磷，大约有0.8-1.0%（下限）到2.6-3.3%（上限）的thiodicarb按重量转化为乙酰胺并通过尿液排出。

In a metabolism study in monkeys, some thiodicarb (syn, syn-isomer) radiolabel was converted via in vivo metabolism to syn-methomyl and subsequently isomerized to anti-methomyl, with ~0.8-1.0% (lower limit) to 2.6-3.3% (upper limit) by weight of thiodicarb being converted to acetamide and excreted in the urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：硫代卡巴是固体。它被用作杀虫剂，以及种子处理/保护剂。人类暴露和毒性：它可能是人类致癌物。动物研究：在兔眼内滴入后导致轻微刺激。硫代卡巴在兔子的初级皮肤刺激性研究中未产生刺激。硫代卡巴在豚鼠中诱导了弱的皮肤致敏反应。大鼠接触硫代卡巴后，观察到明显的系统性器官毒性。在大鼠中，它降低了红细胞胆碱酯酶活性，并降低了血红蛋白。在狗中，它降低了红细胞压积和血红蛋白。兔子的皮肤应用导致巨幼细胞性贫血、红斑和水肿。兔子其他皮肤研究描述了红细胞减少、血红蛋白减少和体重减轻。接受硫代卡巴处理的雄性大鼠与同期对照雄性相比，睾丸间质细胞肿瘤的发生率增加，且高于历史对照。在雌雄小鼠中，它产生了肝细胞肿瘤发生率的增加。大鼠发育研究表明，胎儿体重减轻，以及发育异常的窝数和胎儿数增加。硫代卡巴在Ames试验中，无论是否经过代谢激活，均未诱导突变反应。硫代卡巴在小鼠淋巴瘤TK +/-细胞中诱导了与剂量相关的突变频率增加，无论是否经过代谢激活，在小鼠淋巴瘤正向突变试验中被认为是具有不确定的弱效应。硫代卡巴，无论是否经过代谢激活，均未在中国仓鼠卵巢细胞的染色体上引起断裂反应。硫代卡巴在初级大鼠肝细胞非计划DNA合成试验中被认为是无活性的。生态毒性研究：硫代卡巴对蜜蜂直接处理具有中等毒性，但在喷洒残留物干燥后不具有毒性。

IDENTIFICATION AND USE: Thiodicarb is a solid. It is used as insecticide, and as a seed treatment/protectant. HUMAN EXPOSURE AND TOXICITY: It is a probable human carcinogen. ANIMAL STUDIES: Instillation in rabbit eyes resulted in slight irritation. Thiodicarb produced no irritation during the primary dermal irritation study in rabbits. Thiodicarb induced a weak dermal sensitization reaction in guinea pigs. Marked systemic organ toxicity was noted in rats after exposure to thiodicarb. In rats it decreased red blood cell cholinesterase activity, and decreased hemoglobin. In dogs it decreased hematocrit and hemoglobin. Skin application in rabbits caused macrocytic anemia, erythema, and edema. Other dermal study in rabbits described decreased erythrocytes, decreased hemoglobin, and decreased body weight. Male rats treated with thiodicarb displayed an increased incidence of interstitial cell tumors in the testes compared to the concurrent control males, and the incidence was also greater than the historical control. In mice it produced increased incidences of hepatocellular tumors in both sexes. Developmental studies in rats demonstrated decreased fetal body weight and an increase in the number of litters and fetuses with developmental variations. Thiodicarb did not induce a mutagenic response in the Ames assay, with or without metabolic activation. Thiodicarb induced dose-related increased mutant frequencies in mouse lymphoma TK+/- cells, with and without metabolic activation and is considered to have an equivocal weak effect in the mouse lymphoma forward mutation assay. Thiodicarb, with or without metabolic activation, did not cause a clastogenic response in the chromosomes of Chinese hamster ovary cells. Thiodicarb is considered inactive in the primary rat hepatocyte unscheduled DNA synthesis assay. ECOTOXICITY STUDIES: Thiodicarb is moderately toxic to bees as direct treatment, but is not toxic after spray residues have dried.

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

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。 其他毒物 - 肥酸酯 皮肤致敏剂 - 可以诱导皮肤过敏反应的制剂。 ACGIH致癌物 - 动物确认致癌。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation. Other Poison - Carbamate Skin Sensitizer - An agent that can induce an allergic reaction in the skin. ACGIH Carcinogen - Confirmed Animal.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 毒性数据

大鼠LC50 = 220毫克/立方米/4小时

LC50 (rat) = 220 mg/m3/4h

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 解毒与急救

确保呼吸道通畅。如有必要，对患者进行气管插管，并使用大口径吸引设备抽吸分泌物。如果呼吸受到抑制，通过机械辅助肺通气给予氧气。在给予阿托品之前，尽可能改善组织氧合，以最小化心室颤动的风险。在严重中毒的情况下，可能需要机械支持肺通气数日。/N-甲基碳酰胺类杀虫剂/

Ensure that a clear airway exists. Intubate the patient and aspirate the secretions with a large bore suction device if necessary. Administer oxygen by mechanically assisted pulmonary ventilation if respiration is depressed. Improve tissue oxygenation as much as possible before administering atropine, so as to minimize the risk of ventricular fibrillation. In severe poisonings, it may be necessary to support pulmonary ventilation mechanically for several days. /N-methyl carbamate insecticides/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

代谢研究在大鼠中使用单次低剂量和单次高剂量的放射性标记硫代碳酸进行。主要消除途径是呼出（二氧化碳和丙酮）和排尿。在给药后7天，组织残留物中含有7-9%的剂量，这可能反映了(14)C-丙酮转化为体内的C-2和C-1库，并随后与天然产物相互作用或结合。

Metabolic studies were performed in rats using single low and single high doses of radiolabeled thiodicarb. The major routes of elimination were expiration (CO2 and acetonitrile) and urination. Tissue residues contained 7-9% of the dose at 7 days post dose and may reflect the metabolism of (14)C-acetonitrile into the body's C-2 and C-1 pools and subsequent interaction with, or incorporation into natural products.

来源:Hazardous Substances Data Bank (HSDB)