Pyrasulfotole | 365400-11-9

• 物质功能分类: 分析化学 - 标准品 - 农残、兽药及化肥类
• 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: Pyrasulfotole
• 英文别名: 2,5-dimethyl-4-[2-methylsulfonyl-4-(trifluoromethyl)benzoyl]-1H-pyrazol-3-one
• CAS: 365400-11-9
• 化学式: C₁₄H₁₃F₃N₂O₄S
• 分子量: 362.33
• InChiKey: CZRVDACSCJKRFL-UHFFFAOYSA-N

物化性质

• 沸点：
  515℃
• 密度：
  1.49
• 闪点：
  265℃
• 溶解度：
  可溶于氯仿（少许）、二氯甲烷（少许）
• LogP：
  -1.58-0.276 at 23℃ and pH4-9
• 表面张力：
  61.95mN/m at 1g/L and 20℃
• 解离常数：
  3.97-4.25 at 23℃
• 颜色/状态：
  Beige powder
• 气味：
  No characteristic odor
• 熔点：
  201 °C
• 蒸汽压力：
  2.7X10-4 mPa at 20 °C /SRC: 2.0X10-9 mm Hg at 20 °C/

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  91.9
• 氢给体数：
  1
• 氢受体数：
  8

ADMET

代谢

在一个代谢研究中，AE 0317309（/pyrasulfotole/ 97.6-100% ai，小瓶编号C-938, C-939, C-938B, C-1024A, K-1196, K-1267），雄性Wistar Hanover大鼠（每种放射性标记五只大鼠）分别口服单一剂量的（苯基-UL-(14)C）AE 0317309或吡唑-3-(14)C AE 0317309，剂量分别为10.0和9.88 mg/kg bw。在两个单独的实验中，有颈静脉插管的雄性Wistar Hanover大鼠（四只大鼠）静脉注射（苯基-UL-(14)C）AE 0317309，剂量为9.81 mg/kg bw，或者（吡唑-3-(14)C）AE 0317309（五只大鼠），剂量为9.60 mg/kg bw。...口服和静脉给药后，大部分剂量以未改变的AE 0317309形式排出。尿和粪便中观察到少量的羟基甲基AE 0317309、去甲基AE 0317309和AE B197555作为代谢物。口服给药后，大约70%的放射性在48或52小时内通过尿液排出，30%通过粪便排出。

In a metabolism study, AE 0317309 (/pyrasulfotole/ 97.6-100% ai, Vial #s C-938, C-939, C- 938B, C-1024A, K-1196, K-1267), male Wistar Hanover rats (five rats for each radiolabel) were given single oral doses of (phenyl-UL-(14)C) AE 0317309 or pyrazole-3-(14)C AE 0317309 at dose rates of 10.0 and 9.88 mg/kg bw, respectively. In two separate experiments, male Wistar Hanover rats with surgically implanted jugular cannula were dosed intravenously with (phenyl-UL-(14)C) AE 0317309 (four rats) or (pyrazole-3-(14)C) AE 0317309 (five rats) at dose rates of 9.81 and 9.60 mg/kg bw, respectively. ... Following both oral and intravenous administration, most of the dose was excreted unchanged as AE 0317309. Hydroxymethyl AE 0317309, desmethyl AE 0317309, and AE B197555 were observed as minor metabolites in the urine and feces. Following oral dosing, approximately 70% of the radioactivity was excreted in the urine and 30% in the feces by 48 or 52 hr.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：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、球囊阀面罩设备或口袋面罩，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。如果患者呕吐，让患者向前倾或将其置于左侧（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。寻求医疗救助。 /毒物A和B/

/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 if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the 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. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，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。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/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 needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

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、严重肺水肿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。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's 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 ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/研究类型：原发性眼刺激 - 兔子；结果：该配方对眼睛有中等刺激性。/来自表格/

/LABORATORY ANIMALS: Acute Exposure/ Study type: Primary Eye Irritation - rabbit; Results: Formulation is moderately irritating to the eye. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：亚慢性或前慢性暴露/ 在一项28天的皮肤毒性研究中，AE 0317309（/pyrasulfotole/ 96.3% w/w ai，批次Op:1-4）被涂抹在10只Wistar HsdCpb:WU大鼠/性别/剂量的剃毛皮肤上，剂量水平为0、10、100或1000 mg/kg bw/天，每天6小时，每周5天，持续28天。在研究中没有观察到与化合物相关的死亡、临床体征（包括眼科检查）、体重、食物和水的消耗、血液学或大体病理学的影响。在1000 mg/kg bw/天的剂量下，雄性大鼠的胆固醇（27%）、甘油三酯（46%）和蛋白质（4%）以及雌性大鼠的总胆红素（17%）统计学上显著增加。由于观察到的变化是轻微的，并且在提交的历史对照数据范围内，因此它们不被认为是毒理学上显著的。在1000 mg/kg bw/天的剂量下，雄性（13.9%）和雌性（11.3%）的绝对肝脏重量统计学上显著增加。在1000 mg/kg bw/天的雄性大鼠中观察到肝细胞肥大和垂体前叶肥大。在100 mg/kg bw/天的2/10雄性和1/10雌性以及1000 mg/kg bw/天的8/10雄性和8/10雌性中观察到胰腺局灶性变性。在高剂量雄性大鼠中观察到甲状腺滤泡细胞肥大的发生率增加。在雄性大鼠中，大于或等于10 mg/kg bw/天时，甲状腺胶质的改变发生率和严重程度增加。然而，由于在10 mg/kg时这种改变主要是最小的，因此在这个剂量下它不被认为是毒理学上相关的。基于胰腺局灶性变性和甲状腺胶质的改变（雄性），LOAEL为100 mg/kg/天。NOAEL为10 mg/kg/天。

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 28-day dermal toxicity study, AE 0317309 (/pyrasulfotole/ 96.3% w/w ai, batch Op:1-4) was applied to the shaved skin of 10 Wistar HsdCpb:WU rats/sex/dose at dose levels of 0, 10, 100, or 1000 mg/kg bw/day, 6 hours/day for 5 days/week during a 28-day period. There were no compound-related effects on mortality, clinical signs (including ophthalmology), body weight, food and water consumption, hematology, or gross pathology. Statistically significant increases in cholesterol (27%), triglycerides (46%), and protein (4%) were observed in males, and total bilirubin (17%) in females at 1000 mg/kg bw/day. Since the observed changes were minor and within the limits of the submitted historical control data, they were not considered toxicologically significant. Absolute liver weights were statistically significantly increased in males (13.9%) and females (11.3%) at 1000 mg/kg bw/day. Hepatocellular hypertrophy and hypertrophy of the pars distalis of the pituitary gland were observed in males at 1000 mg/kg bw/day. Focal degeneration of the pancreas was observed in 2/10 males and 1/10 females at 100 mg/kg bw/day and in 8/10 males and 8/10 females at 1000 mg/kg bw/day. An increased incidence of thyroid follicular cell hypertrophy was seen in high-dose males. Alteration of thyroid colloid was seen with increasing incidence and severity at greater than or equal to 10 mg/kg bw/day in males. However, since the alteration was predominantly minimal at 10 mg/kg, it was not considered toxicologically relevant at this dose. The LOAEL is 100 mg/kg/day, based on focal degeneration of the pancreas (both sexes) and alteration of thyroid colloid (males). The NOAEL was 10 mg/kg/day.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在口服10毫克/千克的苯基或吡唑环标记的吡唑硫代醇后，大约60%的放射性标记化合物在6小时后通过尿液排出，而大约73%的给药剂量在牺牲时（52小时）通过尿液回收。因此，大约60%的化合物在暴露后6小时内被吸收。在牺牲时，剩余尸体和组织中残留的给药剂量不到2%，且在肝脏和肾脏中发现的残留物最高。在大约52小时后，大约35%的标记化合物通过粪便排出，其中大约25%为母体。

Following oral administration of 10 mg/kg phenyl or pyrazole ring-labeled pyrasulfotole, approximately 60% of radiolabeled compound was excreted in the urine after 6 hours, while approximately 73% of the administered dose was recovered in the urine by the time of sacrifice (52 hours). Therefore, approximately 60% of the compound was absorbed within 6 hours of exposure. Less than 2% of the administered dose remained in the residual carcass and tissues at sacrifice, and the highest residues were found in the liver and kidney. Approximately 35% of labeled compound was excreted in the feces 52 hr after dosing, approximately 25% of was parent.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在代谢研究中，AE 0317309（/pyrasulfotole/ 97.6-100% ai，样品编号C-938，C-939，C-938B，C-1024A，K-1196，K-1267）给雄性Wistar Hanover大鼠（每种放射性标记5只大鼠）单次口服（phenyl-UL-(14)C）AE 0317309或pyrazole-3-(14)C AE 0317309，剂量分别为10.0和9.88 mg/kg bw。在两个单独的实验中，雄性Wistar Hanover大鼠通过手术植入颈静脉插管，静脉注射（phenyl-UL-(14)C）AE 0317309（4只大鼠）或（pyrazole-3-(14)C）AE 0317309（5只大鼠），剂量分别为9.81和9.60 mg/kg bw。口服给药后，（phenyl-UL-(14)C）AE 0317309被迅速吸收，大约62%的给药放射性剂量在给药后6小时内通过尿液回收。在处死时（52小时），总共大约73%的给药放射性剂量通过尿液回收。单次口服给药后，（pyrazole-3-(14)C）AE 0317309被迅速吸收，大约57%的给药放射性剂量在给药后6小时内通过尿液回收。在处死时（48小时），总共大约75%的剂量通过尿液回收。静脉给药的情况下，大约90%的放射性物质通过尿液排出，大约10%通过粪便排出，在48小时内。大多数（超过80%）的静脉注射剂量在6小时内通过尿液排出。在所有实验中，处死时剩余尸体和组织中残留的给药剂量小于2%。在所有实验中，肝脏和肾脏中的残留物最高。在静脉给药后，组织中的等量分布方面，phenyl-UL-(14)C标记和pyrazole-3-(14)C标记之间没有明显差异。然而，在口服给药后，pyrazole-3-(14)C标记的组织浓度始终高于phenyl-UL-(14)C标记。口服和静脉给药后，组织中的放射性分布没有太大差异，除了后者剩余尸体中的浓度略高。口服和静脉给药后，大部分剂量以AE 0317309的形式未改变排出。...

In a metabolism study, AE 0317309 (/pyrasulfotole/ 97.6-100% ai, Vial #s C-938, C-939, C- 938B, C-1024A, K-1196, K-1267), male Wistar Hanover rats (five rats for each radiolabel) were given single oral doses of (phenyl-UL-(14)C) AE 0317309 or pyrazole-3-(14)C AE 0317309 at dose rates of 10.0 and 9.88 mg/kg bw, respectively. In two separate experiments, male Wistar Hanover rats with surgically implanted jugular cannula were dosed intravenously with (phenyl-UL-(14)C) AE 0317309 (four rats) or (pyrazole-3-(14)C) AE 0317309 (five rats) at dose rates of 9.81 and 9.60 mg/kg bw, respectively. The (phenyl-UL-(14)C) AE 0317309 was readily absorbed following oral dosing, with approximately 62% of the administered radioactivity dose being recovered in the urine within 6 h post dose. A total of approximately 73% of the administered radioactivity dose was recovered in the urine by the time of sacrifice (52 hr). The (pyrazole-3-(14)C) AE 0317309 was readily absorbed following a single oral dose, with approximately 57% of the administered radioactivity dose being recovered in the urine within 6 h post dose. A total of approximately 75% of the dose was recovered in the urine by the time of sacrifice (48 hr). In the case of intravenous administration, approximately 90% of the radioactivity was excreted in the urine and approximately 10% in the feces by 48 h. Most (over 80%) of the intravenous dose was excreted in the urine within 6 h. In all experiments, <2% of the administered dose remained in the residual carcass and tissues at sacrifice. In all experiments, the highest residues were found in the liver and kidney. There was no apparent difference between the phenyl-UL-(14)C label and the pyrazole-3-(14)C label in the distribution of equivalents in the tissues following intravenous dosing. However, concentrations in the tissues were consistently higher in the case of the pyrazole-3-(14)C label than in the case of the phenyl-UL-(14)C label following oral dosing. The distribution of radioactivity in tissues did not differ greatly between oral and intravenous dosing, with the exception that the concentration in the residual carcass is somewhat higher in the latter case. Following both oral and intravenous administration, most of the dose was excreted unchanged as AE 0317309. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S61
• 危险类别码：
  R52/53
• WGK Germany：
  1

制备方法与用途

理化性质

Pyrasulfotole，试验代号AE0317309。商品名称包括Huskie、Infinity、Precept和Tundra，是由拜耳公司开发的除草剂。该产品于2007年与2008年在北美洲及澳大利亚使用，并于2012年2月获得美国许可应用于小麦。其形态为米黄色粉末，工业品纯度≥96.0%。熔点为201℃，蒸气压为2.7×10^-4mPa（在20℃下）。pH值分别为4、7和9时的KowlgP值分别为0.276、-1.362和-1.580。Henry常数为1.42×10^-9Pa·m³/mol（在pH 7，20℃条件下），相对密度为1.53。水中溶解度分别为4.2、69.1和49g/L（在pH 4、7和9时）。其他溶剂中的溶解度（20℃）分别为乙醇21.6、正己烷0.038、甲苯6.86、丙酮89.2、二氯甲烷120～150、乙酸乙酯37.2和二甲基亚砜≥600g/L。稳定性方面，Pyrasulfotole在pH 5、7和9的水溶液中无生物水解；在pH 7时，它可通过光降解。

毒性

大鼠急性经口LD₅₀大于2000mg/kg。大鼠急性经皮LD₅₀也大于2000mg/kg。对兔皮肤无刺激作用，但对眼睛有轻微的刺激。对豚鼠的皮肤具有致敏性。基于大鼠慢性毒性及致癌性的研究，NOAEL为25mg/L（雄大鼠1mg/(kg·d)）。ADIEPA)cRfD 0.01mg/kg[2007]。

作用机制

磺酰草吡唑主要通过叶片吸收。施用于叶片与叶鞘后2天，小麦分别吸收了约70%和66%，而卷茎蓼(Polygonum conooloulus)则分别吸收58%和18%。根处理后6天，两种植物仅吸收不到1%的Pyrasulfotole。在小麦植株中，处理后的48小时内，放射物中的33.7%通过韧皮部向未处理的幼芽与根传导；而在处理第一片叶鞘之后，除了韧皮部传导外，放射物质还在木质部进行移动。这表明Pyrasulfotole在植物体内既进行共质体传导也进行非共质体传导。在小麦中的代谢比杂草迅速，处理后48小时内，从提取的放射物中只有41%是母体化合物，其余均为代谢产物；而在卷茎蓼茎中，所有提取的放射物质都是母体化合物。这表明小麦通过快速代谢此除草剂来提高耐受性。

应用

Pyrasulfotole适用于各种类型的小麦、大麦及Triticale作物。推荐用量为25~50g/hm²，通过苗后喷雾可有效防治多种杂草。主要应用场景包括控制小麦田中的恶性杂草。

土壤/环境

Pyrasulfotole在谷物内的代谢包括N-脱甲基作用以及随后的植物体内葡糖基化，同时生成少量的谷胱苷肽。在大鼠的代谢产物中发现了吡唑环断开及形成2-甲磺酰基-4-三氟甲基苯甲酸的代谢途径。此外，在哺乳动物（如鼠和山羊）体内，吡唑甲基的羟基化也是一个次要的代谢途径。

Pyrasulfotole在植物体内的主要代谢途径是消除吡唑环形成2-甲磺酰基-4-三氟甲基苯甲酸。这种化合物也是大多数作物中的主要代谢产物。

土壤/环境中，该物质在有氧条件下迅速降解，第一阶段DT₅₀值为11～72天（实验室）和5~31天（田地）。在水中和土壤中无挥发性，在空气中的半衰期仅为0.4天。