氟菌唑 | 149465-52-1

• 物质功能分类: 化学农药原药 - 杀菌剂 - 其他杀菌剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 氟菌唑
• 中文别名: 1-[(1E)-1-[[4-氯-2-(三氟甲基)苯基]亚氨基]-2-丙氧基乙基]-(1H-咪唑)；(E)-4-氯-Α,Α,Α-三氟-N-(1-咪唑-1-基-2-丙氧亚乙基)-邻甲苯胺；三氟啶磺隆钠盐；4-氯-Α,Α,Α-三氟-N-(1-咪唑-1-基-2-丙氧亚乙基)邻甲苯胺；特富灵
• 英文名称: Triflumizole
• 英文别名: N-[4-chloro-2-(trifluoromethyl)phenyl]-1-imidazol-1-yl-2-propoxyethanimine
• CAS: 149465-52-1；68694-11-1；99387-89-0
• 化学式: C₁₅H₁₅ClF₃N₃O
• 分子量: 345.75
• InChiKey: HSMVPDGQOIQYSR-UHFFFAOYSA-N

物化性质

• 熔点：
  63.5°C
• 沸点：
  421.2±55.0 °C(Predicted)
• 密度：
  1.3288 (estimate)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）
• 物理描述：
  COLOURLESS CRYSTALS.
• 颜色/状态：
  Colorless crystals
• 蒸汽压力：
  1.4X10-6 mm Hg at 25 °C
• 稳定性/保质期：
  纯品为白色结晶，无味。熔点为63.5℃，25℃时的蒸气压为1.4×10^-6 Pa。在不同溶剂中的溶解度分别为：二甲苯639g/L、氯仿2.22kg/L、丙酮1.44kg/L、乙腈1.03kg/L、己烷17g/L，水中溶解度为12.5mg/L。 对兔皮肤无刺激作用，但对眼睛黏膜有轻微刺激。动物试验未发现致癌、致畸或致突变的作用。
• 分解：
  Decomposes on burning. This produces toxic and corrosive fumes including nitrogen oxides, hydrogen fluoride, and hydrogen chloride.
• 解离常数：
  pKa = 3.70 at 25 °C
• 碰撞截面：
  177.09 Ų [M+H]+
• 保留指数：
  2057

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

代谢

三氟米唑的代谢通过分析保留自之前研究的粪便和尿液样本进行了调查：单次口服给药10或300毫克/千克体重，以及连续14次口服给药，每次10毫克/千克体重。三氟米唑被广泛代谢：从尿液或粪便中回收的放射性标记中，不到2%被确认为母化合物。在重复低剂量和单次高剂量后，雄性和雌性在代谢物模式上有一些差异，但在单次低剂量后没有差异。主要的尿液代谢物是FM-8-1和FA-1-5的硫酸结合物，每个约占单次低剂量从该基质中回收的放射性标记的约20%，在高剂量后分别约占11%和20%。在粪便中，FD-2-1是所有剂量方案中的主要代谢物（约6-10%的回收放射性标记）。在其它主要代谢物方面，不同剂量方案之间存在显著差异。FM-2-1是在单次口服低剂量后的主要代谢物（约9%的粪便中回收的放射性标记），但在其它剂量方案中占比不到2%。FA-1-1在单次和重复低剂量后是主要代谢物（约5-10%），但在单次口服高剂量后不是（<3%），而FD-1-1在单次口服高剂量后是主要代谢物（约16%），在单次和重复低剂量后是次要代谢物（<2%）。代谢物FM-6-1通过薄层色谱共色谱法初步鉴定，由于放射性活性低，与真实FM-6-1对应的放射性条带模糊不清。

The metabolism of triflumizole was investigated by analyzing fecal and urine samples retained from ... previous studies: single oral administration of 10 or 300 mg/kg bw and 14 consecutive oral doses of 10 mg/kg bw per day. ... Triflumizole is extensively metabolized: less than 2% of the radiolabel recovered from urine or feces was identified as parent compound. A few differences in metabolite pattern were observed between males and females after repeated low and single high doses, but not after a single low dose. The major urinary metabolites are the sulfate conjugates of FM-8-1 and FA-1-5, each representing approximately 20% of the radiolabel recovered after the single low dose from that matrix and, respectively, approximately 11% and 20% after the high dose. In feces, FD-2-1 is a major metabolite in all dose regimens (~6-10% of the recovered radiolabel). Considerable differences between dose regimens exist with respect to other major metabolites. FM-2-1 is the major metabolite after a single oral low dose (~9% of radiolabel recovered in feces), but represents less than 2% for the other dose regimens. FA-1-1 is a major metabolite after single and repeated low dosing (~5-10%), but not after single oral high dosing (<3%), whereas FD-1-1 is the major metabolite after a single oral high dose (~16%) and a minor metabolite after single and repeated low doses (<2%). The metabolite FM-6-1 was tentatively identified by TLC co-chromatography, and the radioactive band corresponding to the authentic FM-6-1 was obscure, because of its low radioactivity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

三氟米唑是一种用于控制如Sphaerotheca fuliginea、Sphaerotheca pannosa、Erysiphe cichoracearum等粉霉病的杀菌剂。在1996年5月至2002年5月期间，对日本高冈工厂生产三氟米唑的员工进行了年度健康检查，并发表了相关报告。报告显示，没有观察到与化学暴露相关的有害健康影响。此外，报告还指出，在此期间内，没有观察到因暴露导致的急性中毒事件或皮肤和/或眼睛刺激。反复或长期接触可能会导致皮肤敏感。该物质可能对肝脏和血液有影响，可能导致肝功能损害和血红蛋白减少。在豚鼠身上的研究表明，三氟米唑对豚鼠皮肤有致敏作用。在兔眼中有轻微刺激性。在大鼠中进行了三氟米唑的急性吸入毒性测试。毒性症状包括大多数动物出现弓背姿势、乏力、鼻涕流泪（头部和/或鼻部）。在大鼠中观察到的三氟米唑口服毒性迹象包括共济失调、低张力、腹部朝下、流泪、尿失禁、体温降低、心率和呼吸率下降以及眼睑下垂。在大鼠连续治疗104周后，三氟米唑没有产生肿瘤。在大鼠的发育研究中，没有观察到与治疗相关的显著外部、内脏或骨骼畸形或变异。在一项小鼠研究中，产前接触三氟米唑会增加脂肪库重量，并将间充质干细胞命运转向脂肪细胞系。在没有代谢激活的情况下，三氟米唑在Ames试验中不具有致突变性。在生态毒性研究中，使用稀有鮈鱼（Gobiocypris rarus）早期生活阶段，评估了包括三氟米唑在内的五种广泛使用的三唑类杀菌剂的发育毒性，被评为高度有毒。

IDENTIFICATION AND USE: Triflumizole is a fungicide used for the control of powdery mildew, such as Sphaerotheca fuliginea, Sphaerotheca pannosa, Erysiphe cichoracearum, and others. HUMAN EXPOSURE AND TOXICITY: A report on the results of its yearly health examination of the personnel involved in the production of triflumizole at the Takaoka plant (Japan) during the period May 1996 to May 2002 was published. No adverse health effects attributable to chemical exposure were observed. In addition, it was reported that in the period covered, no events of acute poisoning by exposure or skin and/or eye irritation were observed. Repeated or prolonged contact may cause skin sensitization. The substance may have effects on the liver and blood. This may result in liver impairment and a decrease in hemoglobin. ANIMAL STUDIES: Triflumizole is sensitizing to the skin of guinea pigs. It is mildly irritating to the eye of rabbits. An acute inhalation toxicity test for triflumizole was conducted in rats. Symptoms of toxicity included hunched posture, lethargy and chromodacryorrhoea (head and/or snout) among the majority of the animals. Signs of oral toxicity from triflumizole observed in rats included ataxia, hypotonia, ventral position, lacrimation, urinary incontinence, decreased body temperature, decreased heart rate and respiration rate, and ptosis. Triflumizole did not produce tumors in rats after 104 weeks of treatment. In developmental studies in rats no statistically significant treatment-related external, visceral, or skeletal malformations or variations were noted. In a mouse study, prenatal triflumizole exposure increases adipose depot weight and diverts mesenchymal stromal stem cells fate toward the adipocyte lineage. Triflumizole was not mutagenic in the Ames test with or without metabolic activation. ECOTOXICITY STUDIES: Using rare minnow (Gobiocypris rarus) at early-life stages, the developmental toxicity of five widely used triazole fungicides including triflumizole was rated as highly toxic.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

三氟米唑被归类为对人类不太可能具有致癌性，这是基于在大鼠和小鼠研究中未发现致癌性的证据，并且没有突变性的担忧。

Triflumizole is classified as not likely to be carcinogenic to humans, based on the lack of evidence of carcinogenicity in studies in rats and mice and the absence of a mutagenicity concern.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

未列在IARC（国际癌症研究机构）的名单上。

Not listed by IARC.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

在人类中，观察到在单次暴露于100 mg/kg/天后，出现了神经肌肉损伤和运动活动减少。在大鼠、小鼠和狗中，肝脏是三氟米唑的主要靶器官。它增加了肝脏重量，肝细胞脂肪空泡化，细胞肥大，炎症，脂肪变性，并导致坏死。三氟米唑的慢性影响包括肝细胞脂肪空泡化，肝细胞肥大，局部炎症和坏死；脂肪变性，肝细胞改变的嗜酸性灶，肝结节，胆管增生，以及胆管玻璃样变性/纤维化。在大鼠和小鼠的亚慢性、慢性/致癌性研究中观察到了肝脏效应。在大鼠中也观察到了胎儿效应。三氟米唑也具有生殖毒性，接受高剂量三氟米唑的大鼠的妊娠期延长。

In human, a neuromuscular impairment and decreased locomotor activity were observed following a single exposure of 100 mg/kg/day. The liver is the primary target organ of triflumizole in the rat, mouse, and dog. It increased liver weight, hepatocyte fatty vacuolization, hypertrophy, inflammation, fatty degeneration, and caused necrosis. Chronic effects of triflumizole included hepatocyte fatty vacuolization, hepatocyte hypertrophy, focal inflammation, and necrosi,; fatty degeneration, eosinophilic foci of hepatocyte alteration, hepatic nodules, bile duct hyperplasia, and hyaline degeneration/fibrosis of the bile duct. Liver effects were seen in rat and mouse subchronic and chronic/carcinogenicity studies. The fetal effects were also seen in rats. Triflumizole has a reproductive toxicity as well, the gestation length was increased in rats receiving high dose of triflumizole.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

该物质可以通过吸入灰尘和摄入的方式被身体吸收。

The substance can be absorbed into the body by inhalation of dust and by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

吸收、分配和排泄

在大鼠口服单一剂量10 mg/kg的[phenyl-U-(14)C]-NF-114后，未观察到性别在吸收、代谢、分布或排泄方面的差异。在给药后1小时内，两性动物的血浆中达到放射性活性的最高浓度。所有组织、器官和血液样本中都能检测到低水平的放射性活性。尿液中放射性活性占剂量的69.5-74.4%，粪便中占21.7-21.9%。

Following oral treatment of rats with /a single oral dose of 10 mg/kg/ [phenyl- U-(14)C]-NF-114, no sex-related differences were observed in absorption, metabolism, distribution or excretion. Maximum concentrations of radioactivity in plasma were attained within 1 hour of dosing in both sexes. Low levels of radioactivity were detectable in all tissue, organ, and blood samples. Radioactivity in urine accounted for 69.5-74.4% of the dose and feces accounted for 21.7-21.9% of the dose. /From table/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

M&F: 10或300毫克/千克单次口服剂量：在大鼠口服给予[phenyl-U-(14)C]-NF-114后，大约93.8-100.6%的给药剂量被回收。尿液是主要的排泄途径。在所有收集的组织、器官和血液样本中都可以检测到低水平的放射性，这些样本是在给药后2天（10毫克/千克组）或4天（300毫克/千克组）收集的，通常雄性动物的组织浓度高于雌性。排泄物中的代谢物轮廓在性别和剂量组之间在数量和质量上是相似的。/来自表格/

M&F: 10 or 300 mg/kg as single oral dose: Following oral treatment of rats with [phenyl- U-(14)C]-NF-114, approximately 93.8-100.6% of the administered dose was recovered. Urine was the major route of excretion. Low levels of radioactivity were detectable in all tissue, organ, and blood samples collected 2 days (10 mg/kg group) or 4 days (300 mg/kg group) post-dose with tissue concentrations generally higher in males than females. The metabolite profile in the excreta was quantitatively and qualitatively similar between the sexes and dose groups. /From table/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

毒性

• 雄性大鼠急性经口 LD50 >715 mg/kg，雌性为695 mg/kg；
• 雄性小鼠急性经口 LD50 560 mg/kg，雌性为510 mg/kg；
• 雄性大鼠腹腔注射 LD50 895 mg/kg，雌性为710 mg/kg；
• 雄性小鼠腹腔注射 LD50 710 mg/kg，雌性为530 mg/kg；
• 大鼠、小鼠皮下注射 LD50 >5000 mg/kg；
• 大、小鼠急性经皮 LD50 >5000 mg/kg；
• 大鼠急性吸入 LC50 >3.2 mg/L。

对兔皮肤无刺激作用，但对眼睛黏膜有轻度刺激。大鼠慢性饲喂试验无作用剂量为3.7 mg/kg饲料。动物试验未见致癌、致畸、致突变作用。

生物活性

• Triflumizole是一种咪唑类杀真菌剂，通过抑制麦角甾醇的生物合成，广泛用于控制各种水果和作物上的白粉病和疮痂。

化学性质

• 纯品为白色结晶，无味。熔点63.5℃，蒸气压1.4×10^-6 Pa (25℃)。
• 25℃时溶解度：二甲苯639 g/L，氯仿2.22 kg/L，丙酮1.44 kg/L，乙腈1.03 kg/L，己烷17 g/L，水中溶解度为12.5 mg/L。

用途

• 广谱性杀菌剂，甾醇脱甲基化抑制剂，具有内吸、保护、治疗和铲除作用。
• 主要用于禾谷类、蔬菜、果树等作物防治白粉病、锈病等。如每100 kg种子用30%可湿性粉剂500 g拌种，可防治麦类条纹病和黑穗病；用30%可湿性粉剂20～30倍液浸种10 min，可防治水稻恶苗病、稻瘟病、胡麻叶枯病；此外，还可防治茶树炭疽病、桃褐腐病以及瓜类和蔬菜的立枯病、炭疽病等。

生产方法

• 在PCl5存在下，4-氯-α，α，α-三氟甲苯胺与N-正丙氧基乙酸反应生成N-（正丙氧基甲基甲酰基）-4-氯-α，α，α-三氟甲苯胺。生成的酰胺化合物在三乙胺存在下与光气作用，最后与咪唑缩合，合成氟菌唑。

类别

• 农药

毒性分级

• 中毒

急性毒性

• 口服 - 大鼠 LD50: 715 毫克/公斤；
• 口服 - 小鼠 LD50: 510 毫克/ 公斤。

可燃性危险特性

• 燃烧时产生有毒氮氧化物、氯化物和氟化物气体。

储运特性

• 库房需通风低温干燥；与食品原料分开储存运输。

灭火剂

• 干粉、泡沫、砂土。

文献信息

• N-ARYLAMIDINE-SUBSTITUTED TRIFLUOROETHYL SULFIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
  申请人：BAYER CROPSCIENCE AG

  公开号：US20140315898A1

  公开（公告）日：2014-10-23

  The present invention relates to novel N-arylamide-substituted trifluoroethyl sulfide derivatives of the formula (I) in which X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , n have the meanings given in the description—to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation

  本发明涉及公式（I）中的新型N-芳酰胺取代三氟乙基硫醚衍生物，其中X1、X2、X3、X4、R1、R2、R3、n的含义如描述所示—它们作为杀螨剂和杀虫剂用于控制动物害虫，并涉及其制备的过程和中间体。
• MICROBIOCIDAL PYRAZOLE DERIVATIVES
  申请人：Syngenta Participations AG

  公开号：US20150031541A1

  公开（公告）日：2015-01-29

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

  公式（I）中的化合物，其中取代基如权利要求1中所定义，可用作农药。
• [EN] MICROBIOCIDAL PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLE MICROBICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013127808A1

  公开（公告）日：2013-09-06

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

  公式（I）中的化合物，其中取代基如权利要求1中定义，可用作杀虫剂。
• [EN] MICROBICIDAL HETEROCYCLES<br/>[FR] HÉTÉROCYCLES MICROBICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2012069633A1

  公开（公告）日：2012-05-31

  Compounds of the formula I Formula (I) wherein the substituents are as defined in claim 1, are useful as active ingredients, which have microbiocidal activity, in particular fungicidal activity.

  式I的化合物，其中取代基如权利要求1所定义的那样，作为活性成分是有用的，具有微生物杀灭活性，特别是真菌杀灭活性。
• ARYL SULFIDE DERIVATIVES AND ARYL SULFOXIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
  申请人：BAYER CROPSCIENCE AKTIENGESELLSCHAFT

  公开号：US20160145235A1

  公开（公告）日：2016-05-26

  The present invention relates to aryl sulphide and aryl sulphoxide derivatives, to the use thereof as acaricides and insecticides for controlling animal pests and to processes and intermediates for preparation thereof. The aryl sulphide and aryl sulphoxide derivatives have the general structure (I) in which the respective radicals are as defined in the description.

  本发明涉及芳基硫醚和芳基亚砜衍生物，其用作杀螨剂和杀虫剂，用于控制动物害虫，并涉及其制备的过程和中间体。芳基硫醚和芳基亚砜衍生物具有一般结构（I），其中各自的基团如描述中所定义。

表征谱图