Metofluthrin | 240494-70-6

• 物质功能分类: 化学农药原药 - 杀虫剂 - 拟除虫菊脂杀虫剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Metofluthrin
• 英文别名: [2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2-dimethyl-3-[(E)-prop-1-enyl]cyclopropane-1-carboxylate
• CAS: 240494-70-6
• 化学式: C₁₈H₂₀F₄O₃
• 分子量: 360.3
• InChiKey: KVIZNNVXXNFLMU-AATRIKPKSA-N

物化性质

• 沸点：
  336.3±42.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)
• 颜色/状态：
  Pale yellow liquid
• 溶解度：
  Solvent solubility (20 to 25 °C; g/L): acetone 303.4; methanol 312.2; ethyl acetate 307.6; toluene 326.9; n-hexanes 328.7; dichloromethane 318.9; n-octanol 325.1; isopropyl alcohol 313.2
• 蒸汽压力：
  1.47X10-5 Torr /SRC: 1.47X10-5 mm Hg / at 25 °C
• 旋光度：
  Specific optical rotation: -23.7 deg at 20 °C/D (c = 0.02, ethanol)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

代谢

雄性Sprague-Dawley大鼠接受1 mg/kg/天的(Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ（批号RIS2001-003，比放射性：6.19 Mbq/mg；放射化学纯度：(12/00) 99.4%；研究期间重新纯化两次，(5/7/02) 99.2%，(5/17/02) 99.1%）的处理。给药准备中补充了未标记的S-1264RTZ（/甲氧氟氰/批号010621G，纯度：99.3%）。在排泄研究中，三只动物每天通过灌胃给药21天测试材料，并每天收集尿液和粪便样本，直至21天，并在最后一次给药后的24、48和72小时以及5、7、10和14天收集样本。在组织分布研究中，12只动物通过灌胃给药测试材料，并在给药10、16和21次以及最后一次给药后7天，每次三个动物的时间点处死。在排泄研究中，总给药量的75%通过尿液排出，22%通过粪便排出。...根据分离的代谢物，主要的代谢途径是酯键的断裂，分子中苄基上的甲基氧化形成醇、醛和羧酸代谢物，分子中酸部分的双键还原，以及形成谷胱甘肽和硫酸酯加成物。/Z-异构体/

Male Sprague-Dawley rats were treated with 1 mg/kg/day of (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ (lot no. RIS2001-003, specific radioactivity: 6.19 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 2 times during study, (5/7/02) 99.2%, (5/17/02) 99.1%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin/ lot no. 010621G, purity: 99.3%). In the Excretion Study, three animals were dosed orally by gavage daily for 21 days with the test material and urine and fecal samples were collected up daily through 21 days and at 24, 48, and 72 hours and 5, 7, 10 and 14 days post-final dose. In the Tissue Distribution Study, 12 animals were dosed orally by gavage with the test material and 3 animals/time point were euthanized after 10, 16, and 21 doses and 7 days post-final dose. In the Excretion Study, 75% of the total administered dose was excreted in the urine and 22% in the feces. ... Based upon the isolated metabolites, the major pathways of metabolism were cleavage of the ester linkage, oxidation of methyl groups on the benzyl moiety of the molecule to form alcohol, aldehyde and carboxylic acid metabolites, reduction of the double bond in the acid moiety of the molecule, and the formation of glutathione and sulfate adducts. /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

代谢

雄性Sprague-Dawley大鼠以1 mg/kg/天的剂量给予(Carbonyl-(14)C) S-1264RTZ (又名甲氧氟虫腈，批号RIS2000-019，比放射性：6.50 Mbq/mg；放射化学纯度：(12/00) 99.4%；研究期间重新纯化两次；(5/8/02) 98.6%，(5/16/02) 99.7%)。给药准备中补充了未标记的S-1264RTZ (批号010621G，纯度：99.3%)。在排泄研究中，三只动物每天通过灌胃给予实验材料，连续21天，收集尿液和粪便样本，直至21天，并在最后一次给药后24、48和72小时以及5、7、10和14天收集。在组织分布研究中，12只动物通过灌胃给予实验材料，并在给予10、16和21次剂量后以及最后一次给药后7天，每个时间点处死3只动物。在排泄研究中，总给药量的57%通过尿液排出，38%通过粪便排出。根据分离的代谢物，主要的代谢途径包括酯键的断裂，分子中酸部分甲基基团的氧化形成醇、醛和羧酸代谢物，酸部分双键的还原，以及形成谷胱甘肽、硫酸酯和葡萄糖醛酸加合物。/Z-异构体/

Male Sprague-Dawley rats were treated with 1 mg/kg/day of (Carbonyl-(14)C) S-1264RTZ (/metofluthrin/ lot no. RIS2000-019, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 2 times during study;(5/8/02) 98.6%, (5/16/02) 99.7%),. Dosing preparations were supplemented with unlabeled S-1264RTZ (lot no. 010621G, purity: 99.3%). In the Excretion Study, three animals were dosed orally by gavage daily for 21 days with the test material and urine and fecal samples were collected up daily through 21 days and at 24, 48, and 72 hours and 5, 7, 10 and 14 days post-final dose. In the Tissue Distribution Study, 12 animals were dosed orally by gavage with the test material and 3 animals/time point were euthanized after 10, 16, and 21 doses and 7 days post-final dose. In the Excretion Study, 57% of the total administered dose was excreted in the urine and 38% in the feces. ... Based upon the isolated metabolites, the major pathways of metabolism were cleavage of the ester linkage, oxidation of methyl groups in the acid moiety of the molecule to form alcohol, aldehyde and carboxylic acid metabolites, reduction of the double bond in the acid moiety of the molecule, and the formation of glutathione, sulfate and glucuronide adducts. /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

代谢

Sprague-Dawley 大鼠，无论雌雄，被用 1 或 20 毫克/千克剂量的 (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ（/甲氧氟菊酯 Z-异构体/ 批号 RIS2001-003，比放射性：6.19 Mbq/毫克；放射化学纯度：(12/00) 99.4%；在研究中重新精制 4 次，(10/22/01) 99.1%，(10/31/01) 98.6%，(11/19/01) 99.1%，(11/26/01) 99.5%）进行处理。给药准备中补充了未标记的 S-1264RTZ（/甲氧氟菊酯 Z-异构体/ 批号 010621G，纯度：99.3%）。在排泄研究中，每个性别/组各四只动物通过灌胃口服给予 1 或 20 毫克/千克的试验材料，并在给药后长达 7 天内收集尿液和粪便样本。空气样本在 72 小时内收集。在药代动力学研究中，每个性别/组各三只动物被给予 1 或 20 毫克/千克的试验材料，并在给药后指定的时间间隔内抽取血液样本，直至 7 天。在组织分布研究中，每个性别/组各 12 只动物被给予 1 或 20 毫克/千克的试验材料，并在给药后指定的时间间隔处死每组各 3 只动物，并测定特定组织中放射性标记的浓度。在排泄研究中，给予剂量的 60 至 71% 通过尿液排出，25 至 36% 通过粪便排出，两个剂量水平之间几乎没有差异。... 根据分离出的代谢物，主要的代谢途径包括酯键的断裂，分子中酸部分甲基氧化形成醇、醛和羧酸代谢物，酸部分双键的还原，以及谷胱甘肽、硫酸盐和葡萄糖苷酸加合物的形成。/Z-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ (/metofluthrin z-isomer/ lot no. RIS2001-003, specific radioactivity: 6.19 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 4 times during study, (10/22/01) 99.1%, (10/31/01) 98.6%, (11/19/01) 99.1%, (11/26/01) 99.5%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin z-isomer/ lot no. 010621G, purity: 99.3%). In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 60 to 71% of the administered dose was excreted in the urine and 25 to 36% in the feces with little difference demonstrated between the two dosing levels. ... Based upon the isolated metabolites, the major pathways of metabolism were cleavage of the ester linkage, oxidation of methyl groups in the acid moiety of the molecule to form alcohol, aldehyde and carboxylic acid metabolites, reduction of the double bond in the acid moiety of the molecule, and the formation of glutathione, sulfate and glucuronide adducts. /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

代谢

Sprague-Dawley 大鼠，无论雌雄，被用 1 或 20 毫克/千克剂量的 (Carbonyl-(14)C) S-1264RTE（/甲氟菊酯 e-异构体/ 批号 RIS2000-020，比放射性：6.50 Mbq/mg；放射化学纯度：(12/00) 99.2%；在研究中复纯化 4 次，(3/18/02) 99.0%，(3/26/02) 98.1%，(4/15/02) 99.4%，(4/22/02) 99.2%；）进行处理。给药准备中加入未标记的 S-1264RTE（/甲氟菊酯 e-异构体/ 批号 010831G，纯度：96.9%）。 在排泄研究中，每组每性别四只动物通过灌胃给予 1 或 20 毫克/千克的试验物质，并在给药后长达 7 天内收集尿液和粪便样本。空气样本在 72 小时内收集。在胆汁排泄研究中，四只胆管已插管的雄性大鼠被给予 1 毫克/千克的试验物质。在给药后 72 小时内收集胆汁、尿液和粪便样本。在药代动力学研究中，每组每性别三只动物被给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔内抽取血液样本，直至 7 天。在组织分布研究中，每组每性别 12 只动物被给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔处死每性别每组的 3 只动物，并测定特定组织中放射性标记的浓度。 在排泄研究中，29 至 45% 的给药剂量通过尿液排出，50 至 66% 通过粪便排出，两种剂量水平之间几乎没有差异。...根据分离出的代谢物，主要的代谢途径是酯键的断裂，分子中酸部分甲基基团的氧化形成醇、醛和羧酸代谢物，酸部分双键的还原，以及硫酸盐加合物的形成。/E-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Carbonyl-(14)C) S-1264RTE (/metofluthrin e-isomer/ lot no. RIS2000-020, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.2%; repurified 4 times during study, (3/18/02) 99.0%, (3/26/02) 98.1%, (4/15/02) 99.4%, (4/22/02) 99.2%;). Dosing preparations were supplemented with unlabeled S-1264RTE (/metofluthrin e-isomer/ lot no. 010831G, purity: 96.9%) . In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Biliary Excretion Study, four male rats, whose bile ducts had been cannulated, were dosed with 1 mg/kg of the test material. Bile, urine and fecal samples were collected through 72 hours post-dose. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 29 to 45% of the administered dose was excreted in the urine and 50 to 66% in the feces with little difference demonstrated between the two dosing levels. ... Based upon the isolated metabolites, the major pathways of metabolism were cleavage of the ester linkage, oxidation of methyl groups in the acid moiety of the molecule to form alcohol, aldehyde and carboxylic acid metabolites, reduction of the double bond in the acid moiety of the molecule, and the formation of a sulfate adduct. /E-isomer/

来源:Hazardous Substances Data Bank (HSDB)

代谢

斯普拉格-道利雄性和雌性大鼠被给予1或20毫克/千克的(Carbonyl-(14)C) S-1264RTZ（/甲氧氟氰菊酯Z-异构体/批号RIS2000-019，比活度：6.50 Mbq/mg；放射化学纯度：(12/00) 99.4%；研究期间重新纯化4次，(12/3/01) 99.6%，(12/19/1) 98.2%，(2/18/02) 98.6%，(2/25/02) 98.9%）。给药准备中补充了未标记的S-1264RTZ（/甲氧氟氰菊酯Z-异构体/批号010621G，纯度：99.3%）。在排泄研究中，每组每性别四只动物通过灌胃给予1或20毫克/千克的试验材料，并在给药后7天内收集尿液和粪便样本。空气样本收集了72小时。在胆汁排泄研究中，四只雄性大鼠的胆管被插管后，给予1毫克/千克的试验材料。在给药后72小时内收集胆汁、尿液和粪便样本。在药代动力学研究中，每组每性别三只动物给予1或20毫克/千克的试验材料，并在给药后指定的时间间隔内抽取血液样本，直至7天。在组织分布研究中，每组每性别12只动物给予1或20毫克/千克的试验材料，并在给药后指定的时间间隔处死每组每性别三只动物，并测定特定组织中放射性标记的浓度。在排泄研究中，给予剂量的44至57%通过尿液排出，38至52%通过粪便排出，两个给药水平之间差异不大。空气采样回收了0.7至1.4%的给予剂量。在给药后第一个24小时内回收了74至83%的给予剂量。在胆汁排泄研究中，30至40%的剂量在胆汁中回收，25至26%在尿液中回收，30至39%在粪便中回收。...根据分离的代谢物，主要的代谢途径是酯键的断裂，分子中酸部分的甲基氧化形成醇、醛和羧酸代谢物，酸部分中双键的还原，以及形成谷胱甘肽、硫酸酯和葡萄糖醛酸加成物。/Z-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Carbonyl-(14)C) S-1264RTZ (/metofluthrin z-isomer/ lot no. RIS2000-019, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 4 times during study, (12/3/01) 99.6%, (12/19/1) 98.2%, (2/18/02) 98.6%, (2/25/02) 98.9%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin z-isomer/ lot no. 010621G, purity: 99.3%). In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Biliary Excretion Study, four male rats, whose bile ducts had been cannulated, were dosed with 1 mg/kg of the test material. Bile, urine and fecal samples were collected through 72 hours post-dose. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 44 to 57% of the administered dose was excreted in the urine and 38 to 52% in the feces with little difference demonstrated between the two dosing levels. Air sampling recovered from 0.7 to 1.4% of the administered dose. Seventy four to 83% of the administered dose was recovered in the 1st 24 hours post-dose. In the Bile Excretion Study, 30 to 40% of the dose was recovered in the bile, 25 to 26% in the urine and 30 to 39% in the feces. ... Based upon the isolated metabolites, the major pathways of metabolism were cleavage of the ester linkage, oxidation of methyl groups in the acid moiety of the molecule to form alcohol, aldehyde and carboxylic acid metabolites, reduction of the double bond in the acid moiety of the molecule, and the formation of glutathione, sulfate and glucuronide adducts. /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 紧急急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /拟除虫菊酯、拟除虫菊酯类和相关化合物/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Pyrethrins, pyrethroids, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立通畅气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有必要，进行辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。预防并治疗癫痫发作，如有必要……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于误食，如果患者能够吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……。/天然除虫菊酯、拟除虫菊酯及相关化合物/

/SRP:/ Basic treatment: . Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Pyrethrins, pyrethroids, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。考虑给予β受体激动剂如沙丁胺醇治疗严重支气管痉挛...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最低流速/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。注意观察液体过载的迹象...。用地西泮或劳拉西泮治疗癫痫发作...。使用丙美卡因氢氯化物协助眼部冲洗...。/拟除虫菊酯、拟除虫菊酯类和相关化合物/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for air way control in the patient who is unconscious or is in severe respiratory distress. Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Pyrethrins, pyrethroids, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

皮肤去污。立即用肥皂和水清洗皮肤……。如果出现刺激或感觉异常效果，请由医生进行治疗。由于拟除虫菊酯的挥发显然是导致面部感觉异常的原因，应采取强烈措施（通风、保护面罩和头罩）以避免蒸汽接触面部和眼睛。维生素E油制剂（dL-α-生育酚醋酸酯）在预防和停止感觉异常反应方面具有独特效果。它们适用于现场条件下的皮肤应用。玉米油也有一定效果，但可能的副作用使得长期使用不太合适。凡士林的效果不如玉米油。氧化锌实际上会加剧反应。/拟除虫菊酯/

Skin decontamination. Wash skin promptly with soap and water ... . If irritant or paresthetic effects occur, obtain treatment by a physician. Because volatilization of pyrethroids apparently accounts for paresthesia affecting the face, strenuous measures should be taken (ventilation, protective face mask and hood) to avoid vapor contact with the face and eyes. Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely effective in preventing and stopping the paresthetic reaction. They are safe for application to the skin under field conditions. Corn oil is somewhat effective, but possible side effects with continuing use make it less suitable. Vaseline is less effective than corn oil. Zinc oxide actually worsens the reaction. /Pyrethroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/遗传毒性/ 使用新鲜女性人类肝细胞进行原代肝细胞培养，暴露于50微摩尔S-1264（/甲氟菊酯/ 纯度未报告）或50微摩尔苯巴比妥3天。在培养期结束时，测定了肝细胞中7-戊氧基芪-O-脱戊基酶的活性和CYP2B mRNA的含量。S-1264的处理导致7-戊氧基芪-O-脱戊基酶活性增加，CYP2B mRNA含量比对照组的人类肝细胞培养物高出2到3倍。苯巴比妥在所有肝细胞培养物中增加了酶活性和mRNA水平。

/GENOTOXICITY/ Primary hepatocyte cultures of ... fresh female human hepatocytes were exposed to 50 uM of S-1264 (/metofluthrin/ purity not reported) or 50 uM of phenobarbital for 3 days. The activity of 7-pentoxyresorufin O-depentylase and the CYP2B mRNA content in the hepatocytes were assayed at the conclusion of the incubation period. Treatment with S-1264 resulted in an increase in 7-pentoxyresorufin O-depentylase activity and a 2 to 3 fold increase in the CYP2B mRNA content above that of the control levels for the ... human hepatocyte cultures. ... Phenobarbital increased the enzyme activity and the mRNA levels in all of the hepatocyte cultures.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雄性Sprague-Dawley大鼠以1 mg/kg/天的剂量给予(Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ（批号：RIS2001-003，比放射性：6.19 Mbq/mg；放射化学纯度：(12/00) 99.4%；在研究中重新纯化2次，(5/7/02) 99.2%，(5/17/02) 99.1%）。给药准备中补充了未标记的S-1264RTZ（/甲氧氟氰/ 批号：010621G，纯度：99.3%）。在排泄研究中，三只动物每天通过灌胃口服给药21天，收集尿液和粪便样本，持续21天，并在最后一次给药后24、48和72小时以及5、7、10和14天收集。在组织分布研究中，12只动物通过灌胃口服给药，并在给药10、16和21次以及最后一次给药后7天，每次三个动物的时间点处死。在排泄研究中，总给药剂量的75%通过尿液排出，22%通过粪便排出。肝脏和肾脏是整个给药期间放射性标记物回收的主要部位，放射性水平在给药期间稳定。在最后一次给药后14天，肝脏、红细胞和毛发是放射性标记物回收的主要位置。胃、小肠、盲肠和大肠中回收的放射性水平在给药期间稳定或略有增加。毛发中回收的放射性标记物在第16次给药时达到峰值。放射性标记物未在脂肪中蓄积，也没有显著的一部分给药剂量通过血脑屏障。... /Z-异构体/

Male Sprague-Dawley rats were treated with 1 mg/kg/day of (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ (lot no. RIS2001-003, specific radioactivity: 6.19 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 2 times during study, (5/7/02) 99.2%, (5/17/02) 99.1%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin/ lot no. 010621G, purity: 99.3%). In the Excretion Study, three animals were dosed orally by gavage daily for 21 days with the test material and urine and fecal samples were collected up daily through 21 days and at 24, 48, and 72 hours and 5, 7, 10 and 14 days post-final dose. In the Tissue Distribution Study, 12 animals were dosed orally by gavage with the test material and 3 animals/time point were euthanized after 10, 16, and 21 doses and 7 days post-final dose. In the Excretion Study, 75% of the total administered dose was excreted in the urine and 22% in the feces. The liver and kidneys were the primary sites of radiolabel recovery over the course of the dosing period with the level of radioactivity stabilizing over the dosing period. At 14 days post-final dose, the liver, red blood cell and hair were the primary locations where the radiolabel was recovered. The level of radioactivity recovered from the stomach, small intestine, cecum and large intestine was stabilized or slightly increased over the course of the dosing period. Radiolabel recovered in the hair peaked at the time of the 16th dose. The radiolabel was not sequestered in the fat nor did a significant fraction of the administered dose pass across the blood:brain barrier. ... /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雄性Sprague-Dawley大鼠接受1 mg/kg/天的(Carbonyl-(14)C) S-1264RTZ（批号RIS2000-019，比放射性：6.50 Mbq/mg；放射化学纯度：(12/00) 99.4%；研究期间重新纯化两次；(5/8/02) 98.6%，(5/16/02) 99.7%）治疗。给药准备中补充了未标记的S-1264RTZ（/甲氧氟菊酯/批号010621G，纯度：99.3%）。在排泄研究中，三只动物每天通过灌胃给药21天，收集尿液和粪便样本，持续21天，并在最后一次给药后的24、48和72小时以及5、7、10和14天收集。在组织分布研究中，12只动物通过灌胃给药，每个时间点有三只动物在给药10、16和21次以及最后一次给药后7天处死。在排泄研究中，总给药剂量的57%通过尿液排出，38%通过粪便排出。肝脏和肾脏是整个给药期间放射性同位素回收的主要部位，放射性水平在给药期间稳定。然而，在最后一次给药后14天，红细胞和毛发成为放射性同位素回收的主要位置。胃、小肠、盲肠和大肠中回收的放射性水平在给药期间稳定。毛发中回收的放射性同位素在第21次给药时达到峰值。放射性同位素没有在脂肪中隔离，也没有显著部分的治疗剂量通过血脑屏障。... /Z-异构体/

Male Sprague-Dawley rats were treated with 1 mg/kg/day of (Carbonyl-(14)C) S-1264RTZ (lot no. RIS2000-019, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 2 times during study;(5/8/02) 98.6%, (5/16/02) 99.7%),. Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin/ lot no. 010621G, purity: 99.3%). In the Excretion Study, three animals were dosed orally by gavage daily for 21 days with the test material and urine and fecal samples were collected up daily through 21 days and at 24, 48, and 72 hours and 5, 7, 10 and 14 days post-final dose. In the Tissue Distribution Study, 12 animals were dosed orally by gavage with the test material and 3 animals/time point were euthanized after 10, 16, and 21 doses and 7 days post-final dose. In the Excretion Study, 57% of the total administered dose was excreted in the urine and 38% in the feces. The liver and kidneys were the primary sites of radiolabel recovery over the course of the dosing period with the level of radioactivity stabilizing over the dosing period. However, at 14 days post-final dose, the red blood cell and hair were the primary locations where the radiolabel was recovered. The level of radioactivity recovered from the stomach, small intestine, cecum and large intestine was stabilized over the course of the dosing period. Radiolabel recovered in the hair peaked at the time of the 21st dose. The radiolabel was not sequestered in the fat nor did a significant fraction of the administered dose pass across the blood:brain barrier. ... /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Sprague-Dawley 大鼠，无论雌雄，都用1或20毫克/千克剂量的 (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ (/metofluthrin z-异构体/ 批号 RIS2001-003，比放射性：6.19 Mbq/mg；放射化学纯度：(12/00) 99.4%；在研究中复纯化4次，(10/22/01) 99.1%，(10/31/01) 98.6%，(11/19/01) 99.1%，(11/26/01) 99.5%) 进行处理。给药制剂中补充了未标记的 S-1264RTZ (/metofluthrin z-异构体/ 批号 010621G，纯度：99.3%)。在排泄研究中，每组每性别四只动物通过灌胃口服1或20毫克/千克的试验物质，并在给药后7天内收集尿液和粪便样本。空气样本在72小时内收集。在药代动力学研究中，每组每性别三只动物用1或20毫克/千克的试验物质进行处理，并在给药后7天内指定的时间间隔抽取血液样本。在组织分布研究中，每组每性别12只动物用1或20毫克/千克的试验物质进行处理，并在给药后指定的时间间隔处死每组每性别三只动物，并测定特定组织中放射性标记的浓度。在排泄研究中，60至71%的给药剂量通过尿液排出，25至36%通过粪便排出，两个给药水平之间差异不大。空气采样中没有检测到放射性标记。在给药后24小时内回收了68至84%的给药剂量。达到最大血液浓度的时间范围是给药后4.0至8.0小时。在7天的收集期间，肝脏和肾脏是放射性标记回收的主要部位。对胃、小肠、盲肠和大肠的放射性分析表明，放射性标记化合物通过胃肠道的传递有时间过程。毛发中的放射性标记回收峰值较系统性循环中观察到的峰值晚。放射性标记没有在脂肪中隔离，也没有显著部分通过血液：大脑屏障。... /Z-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Methoxymethylbenzyl-alpha -(14)C) S-1264RTZ (/metofluthrin z-isomer/ lot no. RIS2001-003, specific radioactivity: 6.19 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 4 times during study, (10/22/01) 99.1%, (10/31/01) 98.6%, (11/19/01) 99.1%, (11/26/01) 99.5%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin z-isomer/ lot no. 010621G, purity: 99.3%). In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 60 to 71% of the administered dose was excreted in the urine and 25 to 36% in the feces with little difference demonstrated between the two dosing levels. No radiolabel was recovered in the air sampling. Sixty eight to 84% of the administered dose was recovered in the 1st 24 hours post-dose. The time to maximal blood concentrations ranged from 4.0 to 8.0 hours post-dose. The liver and kidneys were the primary sites of radiolabel recovery over the course of the 7 day collection period. Radioassay of the stomach, small intestine, cecum and large intestine demonstrated a time-course of passage for the radiolabeled compound through the gastrointestinal tract. Radiolabel recovery in the hair peaked later than that observed in the systemic circulation. The radiolabel was not sequestered in the fat nor did a significant fraction of the administered dose pass across the blood:brain barrier. ... /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Sprague-Dawley 大鼠，无论雌雄，都被用 1 或 20 毫克/千克剂量的 (Carbonyl-(14)C) S-1264RTE（/甲氟菊酯 e-异构体/ 批号 RIS2000-020，比放射性：6.50 Mbq/mg；放射化学纯度：(12/00) 99.2%；在研究中重新精制 4 次，(3/18/02) 99.0%，(3/26/02) 98.1%，(4/15/02) 99.4%，(4/22/02) 99.2%；）进行处理。给药准备中加入未标记的 S-1264RTE（/甲氟菊酯 e-异构体/ 批号 010831G，纯度：96.9%）。在排泄研究中，每组每性别四只动物通过灌胃口服给予 1 或 20 毫克/千克的试验物质，并在给药后长达 7 天内收集尿液和粪便样本。空气样本在 72 小时内收集。在胆汁排泄研究中，四只雄性大鼠，其胆管已被插管，被给予 1 毫克/千克的试验物质。在给药后 72 小时内收集胆汁、尿液和粪便样本。在药代动力学研究中，每组每性别三只动物被给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔内抽取血液样本，直至 7 天。在组织分布研究中，每组每性别十二只动物被给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔内，每性别每组每个时间点三只动物被安乐死，并测定特定组织中放射性标记的浓度。在排泄研究中，29 至 45% 的给药剂量通过尿液排出，50 至 66% 通过粪便排出，两个给药水平之间差异很小。空气采样回收了 0.4 至 0.6% 的给药剂量。在给药后前 24 小时内回收了 65 至 78% 的给药剂量。在胆汁排泄研究中，雄性和雌性动物胆汁中分别回收了 27% 和 55% 的剂量。雌性动物胆汁中放射性标记回收量增加，导致尿液和粪便中放射性活性的回收量减少（尿液：45.1 至 20.4%，粪便：50.2 至 19.6%）。对于雄性动物，只有尿液中的放射性标记回收量减少（37.1 至 9.6%）。与雌性动物的 77% 相比，雄性动物只吸收了 40% 的给药剂量。无论给药水平如何，达到最大血药浓度的时间范围是 4.7 至 6.7 小时。在 7 天的收集期间，肝脏是放射性标记回收的主要部位。对胃、小肠、盲肠和大肠的放射性分析表明，放射性标记化合物通过胃肠道的传递有时间过程。头发中放射性标记的回收峰值比在全身循环中观察到的峰值晚。放射性标记没有在脂肪中隔离，也没有显著的部分给药剂量通过血脑屏障。... /E-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Carbonyl-(14)C) S-1264RTE (/metofluthrin e-isomer/ lot no. RIS2000-020, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.2%; repurified 4 times during study, (3/18/02) 99.0%, (3/26/02) 98.1%, (4/15/02) 99.4%, (4/22/02) 99.2%;). Dosing preparations were supplemented with unlabeled S-1264RTE (/metofluthrin e-isomer/ lot no. 010831G, purity: 96.9%) . In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Biliary Excretion Study, four male rats, whose bile ducts had been cannulated, were dosed with 1 mg/kg of the test material. Bile, urine and fecal samples were collected through 72 hours post-dose. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 29 to 45% of the administered dose was excreted in the urine and 50 to 66% in the feces with little difference demonstrated between the two dosing levels. Air sampling recovered 0.4 to 0.6% of the administered dose. Sixty five to 78% of the administered dose was recovered in the 1st 24 hours post-dose. In the Bile Excretion Study, 27 and 55% of the dose was recovered in the bile of the males and females, respectively. The greater recovery of the radiolabel in the bile of the females resulted in a decrease of radioactivity recovered from the urine and the feces (urine: 45.1 to 20.4%, feces: 50.2 to 19.6%), For the males, only the urinary recovery of the radiolabel was decreased (37.1 to 9.6%). The males absorbed only 40% of the administered dose in contrast to the 77% demonstrated by the females. The time to maximal blood concentrations ranged from 4.7 to 6.7 hours post-dose, irrespective of the dosing level. The liver was the primary site of radiolabel recovery over the course of the 7 day collection period. Radioassay of the stomach, small intestine, cecum and large intestine demonstrated a time-course of passage for the radiolabeled compound through the gastrointestinal tract. Radiolabel recovery in the hair peaked later than that observed in the systemic circulation. The radiolabel was not sequestered in the fat nor did a significant fraction of the administered dose pass across the blood:brain barrier. ... /E-isomer/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Sprague-Dawley 大鼠，无论雌雄，被用 1 或 20 毫克/千克剂量的 (Carbonyl-(14)C) S-1264RTZ (/metofluthrin z-异构体/ 批号 RIS2000-019，比放射性：6.50 Mbq/mg；放射化学纯度：(12/00) 99.4%；在研究中再精制 4 次，(12/3/01) 99.6%，(12/19/1) 98.2%，(2/18/02) 98.6%，(2/25/02) 98.9%) 进行处理。给药准备中加入未标记的 S-1264RTZ (/metofluthrin z-异构体/ 批号 010621G，纯度：99.3%)。在排泄研究中，每组性别各四只动物口服给予 1 或 20 毫克/千克的试验物质，并在给药后长达 7 天内收集尿液和粪便样本。空气样本收集持续 72 小时。在胆汁排泄研究中，四只雄性大鼠，其胆管已被插管，给予 1 毫克/千克的试验物质。在给药后 72 小时内收集胆汁、尿液和粪便样本。在药代动力学研究中，每组性别各三只动物给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔内抽取血液样本，最长可达 7 天。在组织分布研究中，每组性别各 12 只动物给予 1 或 20 毫克/千克的试验物质，并在给药后指定的时间间隔处死每组性别各三只动物，并测定特定组织中放射性标记的浓度。在排泄研究中，44 至 57% 的给药剂量通过尿液排出，38 至 52% 通过粪便排出，两种给药水平之间几乎没有差异。空气采样回收了 0.7 至 1.4% 的给药剂量。在给药后前 24 小时内回收了 74 至 83% 的给药剂量。在胆汁排泄研究中，30 至 40% 的剂量在胆汁中回收，25 至 26% 在尿液中，30 至 39% 在粪便中。雄性和雌性分别吸收了 58% 和 68% 的给药剂量。达到最大血药浓度的时间范围是 3.3 至 6.7 小时。在 7 天的收集期间，肝脏和肾脏是放射性标记回收的主要部位。对胃、小肠、盲肠和大肠的放射性分析表明，放射性标记化合物通过胃肠道的通过有时间过程。毛发中的放射性标记回收峰值比在全身循环中观察到的峰值晚。放射性标记没有在脂肪中隔离，也没有显著部分通过血脑屏障。... /Z-异构体/

Sprague-Dawley rats of both sexes were treated with 1 or 20 mg/kg of (Carbonyl-(14)C) S-1264RTZ (/metofluthrin z-isomer/ lot no. RIS2000-019, specific radioactivity: 6.50 Mbq/mg; radiochemical purity: (12/00) 99.4%; repurified 4 times during study, (12/3/01) 99.6%, (12/19/1) 98.2%, (2/18/02) 98.6%, (2/25/02) 98.9%). Dosing preparations were supplemented with unlabeled S-1264RTZ (/metofluthrin z-isomer/ lot no. 010621G, purity: 99.3%). In the Excretion Study, four animals/sex/group were dosed orally by gavage with 1 or 20 mg/kg of the test material and urine and fecal samples were collected up to 7 days post-dose. Air samples were collected through 72 hours. In the Biliary Excretion Study, four male rats, whose bile ducts had been cannulated, were dosed with 1 mg/kg of the test material. Bile, urine and fecal samples were collected through 72 hours post-dose. In the Pharmacokinetics Study, 3 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and blood samples were drawn at specified time intervals up to 7 days post-dose. In the Tissue Distribution Study, 12 animals/sex/group were dosed with 1 or 20 mg/kg of the test material and 3 animals/sex/group/time point were euthanized at specified time intervals post-dose and the concentration of radiolabel in particular tissues was determined. In the Excretion Study, 44 to 57% of the administered dose was excreted in the urine and 38 to 52% in the feces with little difference demonstrated between the two dosing levels. Air sampling recovered from 0.7 to 1.4% of the administered dose. Seventy four to 83% of the administered dose was recovered in the 1st 24 hours post-dose. In the Bile Excretion Study, 30 to 40% of the dose was recovered in the bile, 25 to 26% in the urine and 30 to 39% in the feces. The males and females demonstrated 58 and 68% absorption of the administered dose. The time to maximal blood concentrations ranged from 3.3 to 6.7 hours post-dose. The liver and kidneys were the primary sites of radiolabel recovery over the course of the 7 day collection period. Radioassay of the stomach, small intestine, cecum and large intestine demonstrated a time-course of passage for the radiolabeled compound through the gastrointestinal tract. Radiolabel recovery in the hair peaked later than that observed in the systemic circulation. The radiolabel was not sequestered in the fat nor did a significant fraction of the administered dose pass across the blood:brain barrier. ... /Z-isomer/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

化学性质

甲氧苄氟菊酯原药为浅黄色透明油状液体，沸点达到334℃，25℃下的饱和蒸气压为1.96mPa。其分配系数Kow lgP值为5.0（25℃），相对密度在20℃时为1.21。该物质在pH 7的水中溶解度为0.73mg/L（20℃）。甲氧苄氟菊酯能在乙腈、二甲基亚砜、甲醇、乙醇、丙酮和正己烷中迅速溶解，在紫外线照射下分解，且在碱性溶液中水解。比旋光度[α]D₂₀为-23.7℃（c=0.02，乙醇），闪点不低于110℃。

毒性

雄(雌)性大鼠急性经口LD50大于200mg/kg，急性经皮LD50大于2000mg/kg。该物质无刺激性和过敏性。吸入毒性方面，雄(雌)性大鼠的LD₅₀范围为1000~2000mg/m3。

作用机理

甲氧苄氟菊酯是钠通道抑制剂，通过与神经细胞中的钠离子通道结合，导致靶标害虫神经功能丧失而死亡。它对媒介昆虫有扰乱神经系统的作用，并表现出快速击倒的特性，主要以接触毒性方式进行杀虫。

用途

甲氧苄氟菊酯是一种拟除虫菊酯类（pyrethroids）杀虫剂。

残留量与安全施药

含有甲氧苄氟菊酯的树脂制剂至少能在8周内保持稳定的有效性。

合成方法

甲氧苄氟菊酯可通过以下三种途径合成：第一种路线是通过Witting反应得到；第二种路线为常规的酯化反应；第三种则是通过酯交换反应来制备。

文献信息

• METHODS AND COMPOSITIONS FOR IMPROVED INSECT REPELLENCY
  申请人：Board of Trustees of Michigan State University

  公开号：US20210392882A1

  公开（公告）日：2021-12-23

  Described herein are compositions and methods useful for isolating compositions that repel insects, including mosquitoes.