氯虫苯甲酰胺 | 500008-45-7

• 物质功能分类: 化学农药原药 - 杀虫剂 - 有机氯杀虫剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 氯虫苯甲酰胺
• 中文别名: 3-溴-N-[4-氯-2-甲基-6-[(甲氨基甲酰基)苯]-1-(3-氯吡啶-2-基)-1-氢-吡啶--甲酰胺；氯虫酰胺；3-溴-N-[4-氯-2-甲基-6-[(甲氨基甲酰基)苯]-1-(3-氯吡啶-2-基)-1H-吡唑-5-甲酰胺；3-溴-N-[4-氯-2-甲基-6-[(甲氨基甲酰基)苯]-1-(3-氯吡啶-2-基)-1-氢-吡唑-5-甲酰胺；3-溴-N-[4-氯-2-甲基-6-[(甲氨基)羰基)苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺；暂无
• 英文名称: rynaxypyr
• 英文别名: chlorantraniliprole；3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide；3-bromo-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-1-(3-chloro-2-pyridine-2-yl)-1H-pyrazole-5-carboxamide；3-bromo-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide；Coragen；5-bromo-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloropyridin-2-yl)pyrazole-3-carboxamide
• CAS: 500008-45-7
• 化学式: C₁₈H₁₄BrCl₂N₅O₂
• 分子量: 483.151
• InChiKey: PSOVNZZNOMJUBI-UHFFFAOYSA-N

物化性质

• 熔点：
  approximate 225℃ (dec.)
• 沸点：
  526.6±50.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿：微溶； DMSO：微溶
• LogP：
  3.641 (est)
• 颜色/状态：
  Fine, crystalline, off-white powder
• 蒸汽压力：
  1.2X10-14 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Stable at normal temperatures and storage conditions. /DuPont Dermacor X-100 Seed Treatment/

• 解离常数：
  pKa = 10.88

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  88.9
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

在为期3个月的大鼠喂养研究中，测量了氯虫苯甲酰胺及其两种主要代谢物IN-GAZ70和IN-H2H20在大鼠血浆中的浓度（结构见附图1）。每组10只雄性和10只雌性Crl:CD(SD) IGS BR大鼠被给予含有氯虫苯甲酰胺（纯度95.9%）的饮食，浓度为0、600、2000、6000或20000 ppm，相当于雄性每天0、36.9、120、359或1188 mg/kg体重，雌性每天0、47.0、157、460或1526 mg/kg体重。在第59天取血，通过液相色谱/质谱（LC/MS）测定氯虫苯甲酰胺、IN-GAZ70和IN-H2H20的血浆浓度。提供了遵守质量保证（QA）和良好实验室规范（GLP）的声明。氯虫苯甲酰胺、IN-GAZ70和IN-H2H20在雌性大鼠血浆中的浓度（分别高达0.83、112和0.54微克/毫升）高于雄性大鼠（分别高达0.18、3.7和0.08微克/毫升），其中IN-GAZ70的浓度最高。在两种性别中，三个分析物在三个较高饮食浓度下的血浆浓度相似。

As part of a 3-month feeding study in rats, ... concentrations of chlorantraniliprole and the two major metabolites, IN-GAZ70 and IN-H2H20 (for structures, see Figure 1) were measured in the plasma. Groups of 10 male and 10 female Crl:CD(SD) IGS BR rats were given diets containing chlorantraniliprole (purity, 95.9%) at a concentration of 0, 600, 2000, 6000, or 20 000 ppm, equal to 0, 36.9, 120, 359, or 1188 mg/kg bw per day for males and 0, 47.0, 157, 460, or 1526 mg/kg bw per day for females. Concentrations of chlorantraniliprole, INGAZ70 and IN-H2H20 were determined by liquid chromatography (LC)/MS in plasma obtained on day 59. Statements of adherence to QA and GLP were provided. Chlorantraniliprole, IN-GAZ70 and IN-H2H20 were present in the plasma at greater concentrations in female rats (up to 0.83, 112 and 0.54 ug/mL, respectively) than in male rats (up to 0.18, 3.7 and 0.08 ug/mL, respectively) with concentrations of IN-GAZ70 being highest. The plasma concentrations of all three analytes were similar at the three higher dietary concentrations in both sexes

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯虫苯甲酰胺的代谢在两个Sprague-Dawley Crl:CD(SD)IGS BR大鼠的研究中进行了调查。...实验使用1:1（微居里:微居里）的混合物（(苯甲酰胺羰基(14)C)氯虫苯甲酰胺（放射性纯度，97%）和[吡唑羰基(14)C]氯虫苯甲酰胺（放射性纯度，99%），用氯虫苯甲酰胺技术（纯度，96.45%）稀释。大鼠以10或200毫克/千克体重的单次剂量或每日10毫克/千克体重的剂量通过灌胃给药14天。通过高效液相色谱（HPLC）和质谱（MS）或串联质谱（MS/MS）鉴定和定量代谢物。提供了遵守QA和GLP声明的证据。氯虫苯甲酰胺的代谢广泛，其特征是甲苯甲基和N-甲基碳羟基化，随后是N-去甲基化，氮到碳的环化失去一个水分子，形成嘧啶酮环，醇氧化成羧酸，酰胺桥断裂，胺水解和O-葡萄糖苷酸化。在两个剂量下，尿液和粪便中代谢物轮廓的性别差异显著，这表明雄性大鼠的甲苯甲基和N-甲基碳组的羟基化潜力大于雌性大鼠。例如，在10毫克/千克体重的大鼠中，二羟基化代谢物IN-K9T00占给药剂量的百分比在雄性（尿液，7.4%；粪便，10.4%）中高于雌性（尿液，2.2%；粪便，4.8%）。甲基苯基单羟基化代谢物IN-HXH44在雄性大鼠的尿液（4.6%）和粪便（7.4%）中的浓度高于雌性大鼠的尿液（2.4%）和粪便（3.5%）。IN-HXH44的羧酸代谢物IN-KAA24是在雄性大鼠尿液和粪便中观察到的一种显著代谢物（合计10.6%），但在雌性大鼠中未观察到。N-甲基碳羟基化代谢物IN-H2H20的百分比在雌性（尿液，3.4%；粪便，15.0%）中高于雄性（尿液，0.3%；粪便，1.4%）。在较高剂量下，尿液中母化合物的排泄量（78.9-85.5%）是较低剂量（4.9-7.3%）的12-16倍。200毫克/千克体重的大鼠的代谢物轮廓与10毫克/千克体重的大鼠相似。给予重复剂量的大鼠的尿液和粪便中的代谢物轮廓与给予单次剂量的大鼠相似。一些小的差异包括在重复剂量后羟基化和极性代谢物如IN-H2H20、IN-K7H29和INKAA24的百分比明显增加。IN-GAZ70在雌性大鼠给予7天和14天重复剂量后在粪便中观察到，但在单次剂量后未观察到。

The metabolism of chlorantraniliprole was investigated in two studies in Sprague-Dawley Crl:CD(SD)IGS BR rats. ... The experiments were performed with a 1 : 1 (uCi : uCi) mixture of (benzamide carbonyl (14)C)chlorantraniliprole (radiochemical purity, 97%) and [pyrazole-carbonyl 14C]chlorantraniliprole (radiochemical purity, 99%), diluted with chlorantraniliprole technical (purity, 96.45%). The rats were given a single dose at 10 or 200 mg/kg bw or daily doses of 10 mg/kg bw by gavage for 14 days. Metabolites were identified and quantified by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) or tandem mass spectrometry (MS/MS). Statements of adherence to QA and GLP were provided. The metabolism of chlorantraniliprole was extensive and characterized by tolyl methyl and N-methyl carbon hydroxylation, followed by N-demethylation, nitrogen-to-carbon cyclization with loss of a water molecule resulting in the formation of the pyrimidone ring, oxidation of alcohols to carboxylic acids, amide-bridge cleavage, amine hydrolysis, and O-glucuronidation. At both doses, a significant difference between the sexes was apparent in the profile of metabolites in the urine and faeces, which indicated greater potential for hydroxylation of the tolyl methyl and N-methyl carbon groups in male rats than in female rats. For example, in rats at 10 mg/kg bw, the percentage of the administered dose represented by the di-hydroxylated metabolite IN-K9T00 was greater in males (urine, 7.4%; feces, 10.4%) than in females (urine, 2.2%; feces, 4.8%). Concentrations of the methylphenyl mono-hydroxylated metabolite IN-HXH44 were higher in the urine (4.6%) and feces (7.4%) of males than urine (2.4%) and feces (3.5%) of females. IN-KAA24, a carboxylic-acid metabolite of IN-HXH44, was a significant metabolite observed in the urine and faeces of males (10.6% combined), but not in females. Percentages of the N-methyl carbon hydroxylated metabolite IN-H2H20 were higher in females (urine, 3.4%; feces, 15.0%) than in males (urine, 0.3%; feces, 1.4%). At the higher dose, excretion of the parent compound in the urine and feces (78.9-85.5%) was 12-16-fold that at the lower dose (4.9-7.3%). The profile of metabolites in rats at 200 mg/kg bw was similar to that in rats at 10 mg/kg bw. The profile of metabolites in the urine and faeces of rats given repeated doses was similar to that observed for rats given single doses. Some minor differences included an apparent increase in the percentages of hydroxylated and polar metabolites such as IN-H2H20, IN-K7H29, and INKAA24 after repeated doses. IN-GAZ70 was observed in the faeces of female rats after 7 and 14 days of repeated doses, but not after a single dose.

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"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（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

• 人类毒性摘录

/遗传毒性/ 在一项细胞遗传学分析中，将原代人类淋巴细胞培养暴露于DPX-E2Y45技术级（氯虫苯甲酰胺）直至沉淀水平（≥750微克/毫升），未观察到细胞结构畸变或多倍体的百分比有统计学上的显著增加。

/GENOTOXICITY/ In a cytogenetic assay, primary human lymphocyte cultures were exposed to DPX-E2Y45 Technical (chlorantraniliprole) at concentrations up to precipitating levels (> or = 750 ug/mL) and there were no statistically significant increases in the percentages of cells with structural aberrations or in polyploidy.

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/在一项使用Magnusson和Kligman最大化测试的皮肤致敏研究中，20只Dunkin Hartley豚鼠暴露于氯虫苯甲酰胺技术（纯度，96.45%；固体粉末）。在初步测试阶段，用于皮内诱导、局部诱导和局部挑战的测试物质浓度分别为5%（w/w）、80%（w/w）和20%（w/w），这是最高的非刺激浓度。溶剂是矿物油。对照组由10只豚鼠组成。第一次诱导阶段涉及三对皮内注射0.1 mL测试物质，0.1 mL 50%（v/v）混合完整 Freund佐剂的水和0.1 mL含有测试物质的完整 Freund佐剂。对照组的豚鼠也用溶剂进行了类似处理。局部诱导阶段在1周后进行：在局部应用0.5 g氯虫苯甲酰胺之前24小时，豚鼠用十二烷基硫酸钠预处理，然后在一块纱布上封闭48小时。在挑战阶段，研究开始后21天，豚鼠接受局部应用0.5 mL挑战剂量和0.5 mL挑战剂量的33%稀释液24小时。在去除贴片后24小时和48小时，根据Magnusson和Kligman评分量表对皮肤刺激程度进行评分。使用了适当的历史对照组暴露于alpha-己基肉桂醛技术（HCA）作为阳性对照。包括遵守QA和GLP的声明。在皮内和局部诱导阶段之后，在大多数接受氯虫苯甲酰胺处理的豚鼠和处理组豚鼠的处理部位，观察到非常轻微到中度的红斑（评分，0.5-2）。在挑战时，在最高非刺激浓度的氯虫苯甲酰胺处理的一些豚鼠和处理组的一些豚鼠中，观察到非常轻微的红斑（评分，0.5）。在应用33%稀释液的处理部位，没有观察到皮肤反应。

/LABORATORY ANIMALS: Acute Exposure/ In a study of dermal sensitization using the Magnusson and Kligman maximization test, 20 Dunkin Hartley guinea-pigs were exposed to chlorantraniliprole technical (purity, 96.45%; solid powder). During the preliminary testing phase, the concentrations of the test substance used for the intradermal induction, topical induction and topical challenge, respectively, were 5% (w/w), 80% (w/w) and 20% (w/w), the highest non-irritating concentration. The vehicle was mineral oil. The control group consisted of 10 guinea-pigs. The first induction phase involved three paired intradermal injections of 0.1 mL of test substance, 0.1 mL of 50% (v/v) mixture of complete Freund adjuvant in distilled water and 0.1 mL of complete Freund adjuvant with test substance. The guinea-pigs in the control group were treated similarly with vehicle only. The topical induction phase was carried out 1 week later: the guinea-pigs were pre-treated with sodium lauryl sulfate 24 hr before topical applications of 0.5 g of chloroantraniliprole on a gauze pad for 48 hr under occlusion. In the challenge phase, 21 days after study initiation, the guinea-pigs received topical applications of 0.5 mL of the challenge dose and 0.5 ml of a 33% dilution of the challenge dose for 24 hr. At 24 hr and 48 hr after patch removal, the degree of dermal irritation was scored according to the Magnusson and Kligman grading scale. Data from appropriate historical controls exposed to alpha-hexylcinnamaldehyde technical (HCA) were used as the positive control. Statements of adherence to QA and GLP were included. After the intradermal and topical induction phases, very faint to moderate erythema (scores, 0.5-2) was noted at the treatment site in most guinea-pigs receiving chlorantraniliprole and in the control group. At challenge, very faint erythema (score, 0.5) was noted in some guinea-pigs receiving chlorantraniliprole at the highest non-irritating concentration and in some guinea-pigs in the control group. At treatment sites to which the 33% dilution was applied, no dermal reactions were noted.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一只哺乳的山羊每天口服一次1:1混合的BC标记和PC标记的氯虫苯甲酰胺，剂量为10 ppm，连续7天。每天收集一次粪便和尿液，每天收集两次乳汁。最后一次给药后23小时处死山羊。主要代谢物是通过N-脱甲基、在苄基位置羟基化并进一步氧化成羧酸以及环化失去水生成各种环状代谢物形成的。大部分给药剂量通过粪便和尿液排出。未降解的母体是肾脏、肌肉和脂肪中主要的最终残留物，也是肝脏和乳汁中的残留物。

/A lactating goat/ was given a single daily oral dose of 1:1 mixture of BC-labeled and PC-labeled chlorantraniliprole at 10 ppm for 7 consecutive days. Feces and urine were collected once daily and milk collected twice daily. The goat was sacrificed 23 hours after the last dose. The major metabolites were formed by N-demethylation, hydroxylation at the benzylic position and further oxidation to carboxylic acid and cyclization with loss of water to yield various cyclic metabolites. The majority of the administered dose was eliminated through the feces and urine. Undegraded parent was the major terminal residue identified in kidney, muscle, and fat, and it was also a residue in liver and milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

至少五只雄性和五只雌性Crl:CD (SD)IGS BR大鼠被给予氯虫苯甲酰胺（纯度大约100%）以0、25、100和1000 mg/kg bw/天的剂量通过灌胃连续14天。在第14和15天的测试日，从每个组的3只雄性大鼠中收集血液，分别在25、100和1000 mg/kg bw的剂量下，给药前立即，以及给药后30和60分钟，2、4、8、12和24小时，以测定氯虫苯甲酰胺的血浆浓度。在第14天，每组五只雄性和五只雌性大鼠的肝脏组织被处理用于肝脏生化评估（β-氧化活性，总细胞色素P450含量和特定细胞色素P450含量）。血液被分离成血浆和红细胞。在额外分配到每天25、100和1000 mg/kg bw剂量的雄性大鼠中，收集脂肪样本用于评估测试物质的潜在生物累积。氯虫苯甲酰胺的浓度-时间曲线下面积（AUC）与剂量不成正比，表明在高剂量下吸收减少。在25、100和1000 mg/kg bw/天的组中，大鼠体内氯虫苯甲酰胺的计算半衰期分别为3.4、3.4和4.0小时。在25、100和1000 mg/kg bw/天的组中，血浆峰值浓度分别发生在0.25、0.42和2.75小时。最大血浆浓度（在25 mg/kg bw时高达0.48 ug/ml）在所有剂量下相似。在给药后24小时，脂肪中测试物质的浓度低于定量限，表明母体化合物没有显著累积。

Groups of at least five male and five female Crl:CD (SD)IGS BR rats were given chlorantraniliprole (purity, approximately 100%) at a dose of 0, 25, 100 and 1000 mg/kg bw per day by gavage for 14 consecutive days. Blood was collected from three male rats in each of the groups at 25, 100, and 1000 mg/kg bw on test days 14 and 15 immediately before dosing, and then 30 and 60 min, 2, 4, 8, 12, and 24 hr after dosing for determination of plasma concentrations of chlorantraniliprole. On day 14, liver tissue of five male and five female rats per group was processed for hepatic biochemical evaluations (beta-oxidation activity, total and specific cytochrome P450 content). Blood was separated into plasma and erythrocytes. In additional male rats assigned to the groups at 25, 100, and 1000 mg/kg bw per day, fat samples were collected for the purpose of assessing potential bioaccumulation of the test substance. The area under the curve of concentration time (AUC) for chlorantraniliprole was not proportional to dose, indicating that absorption was decreased at higher doses. Calculated half-lives for chlorantraniliprole in rats in the groups at 25, 100, and 1000 mg/kg bw per day were 3.4, 3.4, and 4.0 hr, respectively). Peak plasma concentrations occurred at 0.25, 0.42 and 2.75 h in the groups at 25, 100, and 1000 mg/kg bw per day. The maximum plasma concentrations (up to 0.48 ug/ml at 25 mg/ kg bw) were similar at all doses. The concentrations of the test substance in fat were below the limit of quantitation at 24 hr after dosing, indicating no significant accumulation of the parent compound.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氯虫苯甲酰胺在Sprague Dawley Crl:CD(SD)IGS BR大鼠口服给药后能够被快速吸收，尽管吸收不完全且与剂量相关，低剂量给药后Tmax值为5-9小时，高剂量给药后为11-12小时。在10 mg/kg体重的剂量下，雄性和雌性大鼠的血浆浓度分别达到3.0和5.4微克当量/克。24小时后，雄性和雌性大鼠的血浆浓度分别约为1.4和3.6微克当量/克。在200 mg/kg体重的剂量下，雄性和雌性大鼠的血浆浓度分别达到5.1和7.1微克当量/克。在胆管插管大鼠的实验中，10 mg/kg体重剂量给药后总吸收率为73-85%，200 mg/kg体重剂量给药后为12-13%。在低剂量下，给药后48小时内有18-30%和49-53%的吸收放射性标记分别通过尿液和胆汁排出，而2-6%和10-20%分别在组织和粪便中找到。在高剂量下，给药后48小时内有4%和5-7%的吸收放射性标记分别通过尿液和胆汁排出，而3%和55-71%分别在组织和粪便中找到。(14)C残留物在组织中广泛分布。在低剂量的雄性和雌性大鼠中，给药后168小时从组织中回收了0.8%和3.3%的给药剂量。在这个时间点，高剂量的雄性和雌性大鼠组织中分别含有0.2%和0.5%的给药剂量。没有显著放射性以(14)C标记挥发性物质或(14)CO2的形式呼出。红细胞和组织中的(14)C残留物浓度低于血浆。雄性大鼠的平均血浆消除半衰期(38-43小时)短于雌性大鼠(78-82小时)。

Chlorantraniliprole was readily absorbed after oral administration /in Sprague Dawley Crl:CD(SD)IGS BR rats/, although absorption was incomplete and dose-related, with Tmax values of 5-9 hr after the lower dose and 11-12 hr after the higher dose. At a dose of 10 mg/kg bw, plasma concentrations peaked at 3.0 and 5.4 ug equivalents/g in males and females, respectively. After 24 hr, plasma concentrations in males and females were about 1.4 and 3.6 ug equivalents/g. At 200 mg/kg bw, plasma concentrations peaked at 5.1 and 7.1 ug equivalents/g in males and females, respectively. In the experiment with bile-duct cannulated rats, total absorption was 73-85% after a dose of 10 mg/kg bw and 12-13% after a dose of 200 mg/kg bw. At the lower dose, 48 hr after dosing 18-30% and 49-53% of the absorbed radiolabel was excreted in urine and bile respectively, while 2-6% and 10-20% was found in tissue and feces respectively. At the higher dose, 48 hr after dosing 4% and 5-7% of the absorbed radiolabel was excreted in the urine and bile, respectively, while 3% and 55-71% was found in tissue and feces, respectively. (14)C residues showed extensive distribution in the tissues. In the rats at the lower dose, 0.8% and 3.3% of the administered dose was recovered from the tissues of males and females, respectively, at 168 hr after dosing. At this time-point, tissues of males and females at the higher dose contained 0.2% and 0.5%, respectively, of the administered dose. No significant radioactivity was exhaled as (14)C-labelled volatiles or (14)CO2. Concentrations of (140C residues were lower in erythrocytes and tissues than in plasma. The mean plasma elimination half-lives were shorter in males (38-43 hr) than in females (78-82 hr) rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在遵循OECD指南417的动力学研究中，给予Sprague-Dawley Crl:CD(SD)IGS BR大鼠雄性和雌性最高14天的每日剂量为10 mg/kg bw的[14C]氯虫苯甲酰胺。实验使用的是(苯甲酰胺羰基(14)C)-氯虫苯甲酰胺(放射性纯度为97%)和(吡唑羰基(14)C)氯虫苯甲酰胺(放射性纯度为99%)的1:1微居里/微居里混合物，用氯虫苯甲酰胺技术(纯度为96.45%)稀释。大鼠每天接受毒性临床体征检查。每组三只雌性大鼠，在第5、9、12、17和27天对全血、血浆、红细胞、脂肪、肾脏、肝脏和肌肉中的(14)C残留物进行定量。在第15天和第21天，对每组三只雄性和三只雌性大鼠的21种组织中的(14)C残留物分布进行了评估。对雄性和雌性大鼠的物质平衡以及尿液和粪便排泄的速率和程度进行了量化，直到第21天(最后一次给药后七天)。在第一次、第七次和最后一次(第十四次)给药后24小时的时间间隔内收集尿液和粪便中的代谢物(累积剂量的百分比)，并进行分析。...超过98.4%的给药剂量被回收。血浆和组织浓度表明，在雄性大鼠连续给药14天后达到了稳态动力学行为。在雌性大鼠中，在第14天给药期结束时，血浆和组织中的放射性标记浓度接近稳态。在第15天，雄性和雌性大鼠的血浆浓度分别达到4.6和32微克当量/克，这些浓度比单次给药10 mg/kg bw后24小时高约两倍和七倍。在最后一次给药后168小时，(14)C残留物在组织中的浓度在雌性大鼠中高于雄性大鼠(分别为给药剂量的2.35%和0.35%)。给药后，雌性大鼠选定组织中14C残留物的浓度下降，半衰期范围为3.9至7.7天。血浆中的半衰期(T1/2 = 7.2天)是单次给药后最多5天内收集的血浆的约两倍(T1/2 = 3.4天)。对21种不同组织中残留物进行了更广泛的评估，得到了与单次给药研究中观察到的浓度和剂量百分比的相似谱。组织和血浆中浓度的比值小于1。大部分给药剂量通过粪便排出(雄性72.9%，雌性81.6%)。在尿液中，分别有16.7%和12.1%的给药剂量由雄性和雌性排出。多次给药(10 mg/kg bw/天X 14天)的分布和排泄总体模式通常介于单次低剂量(10 mg/kg bw)和单次高剂量(200 mg/kg bw)给药观察到的模式之间。

In a kinetic study that complied with OECD guideline 417, male and female Sprague-Dawley Crl:CD(SD)IGS BR rats were given up to 14 daily doses of [14C]chlorantraniliprole at 10 mg/kg bw per day by gavage. The experiments were performed with a 1 : 1 uCi/uCi mixture of (benzamide carbonyl (14)C)-chlorantraniliprole (radiochemical purity, 97%) and (pyrazole-carbonyl (14)C)chlorantraniliprole (radiochemical purity, 99%), diluted with chlorantraniliprole technical (purity, 96.45%). Rats were checked daily for clinical signs of toxicity. In three females per group, (14)C residues were quantified in whole blood, plasma, erythrocytes, fat, kidney, liver and muscle on days 5, 9, 12, 17, and 27. An evaluation of the distribution of (14)C residues in 21 tissues of three males and three females per group was performed on days 15 and 21. Material balance and rate and extent of urine and faecal excretion by male and female rats was quantified until day 21 (seven days after the last dose). Metabolites in urine and feces (% of accumulating dose), collected for intervals of 24 hr after the first, seventh, and last (fourteenth) day of dosing were profiled. ... More than 98.4% of the administered dose was recovered. Plasma and tissue concentrations indicated that steady-state kinetic behaviour was reached in male rats after 14 days of dosing. In female rats, concentrations of radiolabel in the plasma and tissue were near steady-state at the end of the 14-day dosing period. At day 15, plasma concentrations peaked at 4.6 and 32 ug equivalents/g in males and females, respectively, these concentrations being about two- and seven-fold higher than 24 hr after a single dose at 10 mg/kg bw. The concentrations of (14)C residues in tissues were higher in females than in males (2.35% vs 0.35% of the administered dose) at 168 hr after the last dose. After dosing, the concentration of 14C residues in the selected tissues of female rats declined, with half-lives ranging from 3.9 to 7.7 days. The half-life in plasma (T1/2 = 7.2 days) was approximately twofold that determined from plasma collected for up to 5 days after administration of a single dose (T1/2 = 3.4 days). A more extensive evaluation of tissue residues in 21 different tissues produced profiles of concentration and percent of dose that were similar to those observed in the single-dose study. Ratios of concentrations in tissue and plasma were less than 1. Most of the administered dose was excreted in the faeces (males, 72.9%; females, 81.6%). In the urine, 16.7% and 12.1% of the administered dose was excreted by males and females, respectively. The overall pattern of distribution and excretion for multiple dosing (10 mg/kg bw per day X 14 days) generally resided between the pattern observed for administration of a single low dose (10 mg/ kg bw) and a single high dose (200 mg/kg bw).

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2933399021
• WGK Germany：
  3

SDS

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模块 1. 化学品
1.1 产品标识符
: 氯虫酰胺
产品名称
1.2 鉴别的其他方法
DPX E2Y45
3-Bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-
carboxamide
3-Bromo-4′-chloro-1-(3-chloro-2-pyridyl)-2′-methyl-6′-(methylcarbamoyl)pyrazole-5-carboxanilide
1.3 有关的确定了的物质或混合物的用途和建议不适合的用途
仅用于研发。不作为药品、家庭或其它用途。

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模块 2. 危险性概述
2.1 GHS-分类
急性毒性, 吸入 (类别 5)
眼睛刺激 (类别 2A)
特异性靶器官系统毒性（一次接触） (类别 3)
2.2 GHS 标记要素，包括预防性的陈述
象形图
警示词 警告
危险申明
H319 造成严重眼刺激。
H333 吸入可能有害。
H335 可能引起呼吸道刺激。
警告申明
预防措施
P261 避免吸入粉尘/烟/气体/烟雾/蒸气/喷雾.
P264 操作后彻底清洁皮肤。
P271 只能在室外或通风良好之处使用。
P280 穿戴防护手套/ 眼保护罩/ 面部保护罩。
事故响应
P304 + P340 如吸入: 将患者移到新鲜空气处休息，并保持呼吸舒畅的姿势。
P305 + P351 + P338 如与眼睛接触，用水缓慢温和地冲洗几分钟。如戴隐形眼镜并可方便地取
出，取出隐形眼镜，然后继续冲洗.
P312 如感觉不适，呼救中毒控制中心或医生.
P337 + P313 如仍觉眼睛刺激：求医/就诊。
安全储存
P403 + P233 存放于通风良的地方。 保持容器密闭。
P405 存放处须加锁。
废弃处置
P501 将内容物/ 容器处理到得到批准的废物处理厂。
2.3 其它危害物 - 无

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模块 3. 成分/组成信息
3.1 物 质
: DPX E2Y45
别名
3-Bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-
chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide
3-Bromo-4′-chloro-1-(3-chloro-2-pyridyl)-2′-methyl-6′-
(methylcarbamoyl)pyrazole-5-carboxanilide
: C18H14BrCl2N5O2
分子式
: 483.15 g/mol
分子量
组分 浓度或浓度范围
3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-
carboxamide
-
化学文摘登记号(CAS 500008-45-7
No.)

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模块 4. 急救措施
4.1 必要的急救措施描述
一般的建议
请教医生。 向到现场的医生出示此安全技术说明书。
吸入
如果吸入,请将患者移到新鲜空气处。 如呼吸停止,进行人工呼吸。 请教医生。
皮肤接触
用肥皂和大量的水冲洗。 请教医生。
眼睛接触
用大量水彻底冲洗至少15分钟并请教医生。
食入
切勿给失去知觉者通过口喂任何东西。 用水漱口。 请教医生。
4.2 主要症状和影响，急性和迟发效应
据我们所知，此化学，物理和毒性性质尚未经完整的研究。
4.3 及时的医疗处理和所需的特殊处理的说明和指示
无数据资料

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模块 5. 消防措施
5.1 灭火介质
灭火方法及灭火剂
用水雾,抗乙醇泡沫,干粉或二氧化碳灭火。
5.2 源于此物质或混合物的特别的危害
碳氧化物, 氮氧化物, 氯化氢气体, 溴化氢气
5.3 给消防员的建议
如必要的话,戴自给式呼吸器去救火。
5.4 进一步信息
无数据资料

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模块 6. 泄露应急处理
6.1 作业人员防护措施、防护装备和应急处置程序
使用个人防护用品。 避免粉尘生成。 避免吸入蒸气、烟雾或气体。 保证充分的通风。
人员疏散到安全区域。 避免吸入粉尘。
6.2 环境保护措施
不要让产品进入下水道。
6.3 泄漏化学品的收容、清除方法及所使用的处置材料
收集和处置时不要产生粉尘。 扫掉和铲掉。 放入合适的封闭的容器中待处理。
6.4 参考其他部分
丢弃处理请参阅第13节。

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模块 7. 操作处置与储存
7.1 安全操作的注意事项
避免接触皮肤和眼睛。 避免形成粉尘和气溶胶。
在有粉尘生成的地方,提供合适的排风设备。一般性的防火保护措施。
7.2 安全储存的条件,包括任何不兼容性
贮存在阴凉处。 使容器保持密闭，储存在干燥通风处。
7.3 特定用途
无数据资料

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模块 8. 接触控制和个体防护
8.1 容许浓度
最高容许浓度
没有已知的国家规定的暴露极限。
8.2 暴露控制
适当的技术控制
根据良好的工业卫生和安全规范进行操作。 休息前和工作结束时洗手。
个体防护设备
眼/面保护
带有防护边罩的安全眼镜符合 EN166要求请使用经官方标准如NIOSH (美国) 或 EN 166(欧盟)
检测与批准的设备防护眼部。
皮肤保护
戴手套取 手套在使用前必须受检查。
请使用合适的方法脱除手套(不要接触手套外部表面),避免任何皮肤部位接触此产品.
使用后请将被污染过的手套根据相关法律法规和有效的实验室规章程序谨慎处理. 请清洗并吹干双手
所选择的保护手套必须符合EU的89/686/EEC规定和从它衍生出来的EN 376标准。
身体保护
防渗透的衣服, 防护设备的类型必须根据特定工作场所中的危险物的浓度和数量来选择。
呼吸系统防护
如须暴露于有害环境中,请使用P95型(美国)或P1型(欧盟 英国
143)防微粒呼吸器。如需更高级别防护,请使用OV/AG/P99型(美国)或ABEK-P2型 (欧盟 英国 143)
防毒罐。
呼吸器使用经过测试并通过政府标准如NIOSH（US）或CEN（EU）的呼吸器和零件。

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模块 9. 理化特性
9.1 基本的理化特性的信息
a) 外观与性状
形状: 粉末
颜色: 淡黄
b) 气味
特征的
c) 气味阈值
无数据资料
d) pH值
无数据资料
e) 熔点/凝固点
192 - 215 °C
f) 沸点、初沸点和沸程
无数据资料
g) 闪点
无数据资料
h) 蒸发速率
无数据资料
i) 易燃性(固体,气体)
无数据资料
j) 高的/低的燃烧性或爆炸性限度 无数据资料
k) 蒸气压
无数据资料
l) 蒸汽密度
无数据资料
m) 密度/相对密度
1.519 g/cm3 在 20 °C
n) 水溶性
0.001 g/l
o) n-辛醇/