Avermectin B1, 4''-deoxy-4''-(methylamino)-, (4''R)- | 119791-41-2

• 物质功能分类: 化学农药原药 - 杀虫剂 - 其他杀虫剂
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Avermectin B1, 4''-deoxy-4''-(methylamino)-, (4''R)-
• 英文别名: 2-butan-2-yl-21',24'-dihydroxy-12'-[4-methoxy-5-[4-methoxy-6-methyl-5-(methylamino)oxan-2-yl]oxy-6-methyloxan-2-yl]oxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
• CAS: 119791-41-2
• 化学式: C₄₉H₇₅NO₁₃
• 分子量: 886.1
• InChiKey: CXEGAUYXQAKHKJ-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷（少许）、氯仿（少许）、甲醇（少许）
• 颜色/状态：
  White to off-white powder
• 熔点：
  141-146 °C /Emamectin benzoate/
• 密度：
  1.20 at 23 °C /Emamectin benzoate/
• 蒸汽压力：
  3.8X10-8 mm Hg at 21 °C /Emamectin benzoate/
• 旋光度：
  Specific optical rotation: -6.9 deg (c = 0.5% in methanol)
• 分解：
  When heated to decomposition it emits toxic vapors of /Nitrogen oxide/.
• 解离常数：
  pKa: 4.18 (acidic, attributed to benzoate counter ion), 8.71 (basic, attributed to emamectin moiety)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  63
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

大西洋鲑鱼（约1.3公斤）在5±1摄氏度的海水罐中饲养，通过饲料以50微克/公斤/天的名义速率给予[(3)H]依玛菌素B1苯甲酸盐，连续7天。在最终剂量后的3小时和12小时以及1、3、7、15、30、45、60和90天，从每组10条鱼中收集组织、血液和胆汁。从最终剂量前开始，每天从罐中收集粪便，直到最终剂量后的90天。在给药期间，每日粪便样本的总放射性残留物（TRR）达到0.25 ppm的最大值，且在覆盖给药期的合并粪便中>97%的TRR是依玛菌素B1a。粪便TRR随后迅速下降，到最终剂量后1天大约降至0.05 ppm。90天给药期间组织的平均TRR范围如下：肾脏，1.4-3 ppm；肝脏，1.0-2.3 ppm；皮肤，0.04-0.09 ppm；肌肉，0.02-0.06 ppm；骨骼，<0.01 ppm。按给药间隔合并的肝脏、肾脏、肌肉和皮肤样本的残留物组成为依玛菌素B1a（81-100% TRR）和去甲基依玛菌素B1a（0-17% TRR），在一些肌肉样本中可见到N-甲酰依玛菌素B1a的微量（<2%）。选作依玛菌素残留监管监测的标志残留物是依玛菌素B1a。使用高效液相色谱-荧光法在个体皮肤和肌肉样本中定量依玛菌素B1a水平，在所有分析的样本中（给药后3小时至30天）均低于85 ppb。

Atlantic salmon (approximately 1.3 kg) maintained in tanks of seawater at 5 +/- 1 degrees C were dosed with [(3)H]emamectin B1 benzoate in feed at a nominal rate of 50 ug of emamectin benzoate/kg/day for 7 consecutive days. Tissues, blood, and bile were collected from 10 fish each at 3 and 12 hr and at 1, 3, 7, 15, 30, 45, 60, and 90 days post final dose. Feces were collected daily from the tanks beginning just prior to dosing to 90 days post final dose. The total radioactive residues (TRR) of the daily feces samples during dosing were 0.25 ppm maximal, and >97% of the TRR in pooled feces covering the dosing period was emamectin B1a. Feces TRR then rapidly declined to approximately 0.05 ppm by 1 day post final dose. The ranges of mean TRR for tissues over the 90 days post dose period were as follows: kidney, 1.4-3 ppm; liver, 1.0-2.3 ppm; skin, 0.04-0.09 ppm; muscle, 0.02-0.06 ppm; and bone, <0.01 ppm. The residue components of liver, kidney, muscle, and skin samples pooled by post dose interval were emamectin B1a (81-100% TRR) and desmethylemamectin B1a (0-17% TRR) with N-formylemamectin B1a seen in trace amounts (<2%) in some muscle samples. The marker residue selected for regulatory surveillance of emamectin residues was emamectin B1a. The emamectin B1a level was quantified in individual samples of skin and muscle using HPLC-fluorometry and was below 85 ppb in all samples analyzed (3 hr to 30 days post dose).

来源:Hazardous Substances Data Bank (HSDB)

代谢

...已鉴定出一个哺乳动物代谢物。这种代谢物被特征化为乙螨唑的N-去甲基化副产物。

...a single mammalian metabolite has been identified. This metabolite is characterized as an N-demethylation byproduct of emamectin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(3)H/(14)C-标记的4"-脱氧-4"-表甲基氨基阿维菌素B1a（MAB1a）苄酸盐的代谢，这是阿维菌素类杀虫剂埃玛菌素苄酸盐的主要同系物（>/=90%），在产蛋鸡中进行了研究。十只白来航鸡（Gallus domesticus）每天口服一次，连续7天（1毫克/千克体重/天）。每天收集鸡蛋和排泄物，然后将鸡蛋分离成蛋白和蛋黄。最后一次给药后20小时内对鸡进行安乐死，并收集肝脏、肾脏、心脏、肌肉、脂肪、卵巢、肌胃、胃肠道及其内容物和尸体。大约70%和6%的总给药剂量分别回收在排泄物加胃肠道及其内容物和组织和鸡蛋中。确定了两种新的代谢物，即原化合物的24-羟甲基衍生物（24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a）和24-羟甲基-4"-脱氧-4"-表甲基氨基阿维菌素B1a的N-去甲基衍生物（24-羟甲基-4"-脱氧-4"-表氨基阿维菌素B1a）。此外，还分离和鉴定了这两种代谢物的八个脂肪酸共轭物，占组织和鸡蛋中总放射性残留物的8-75%。尽管这在迄今为止报道的外源化学物质中代表了一些最广泛的体内脂肪酸结合，但由于本研究的剂量水平大约是作物中MAB1a残留水平的1000倍，且大部分应用的剂量在排泄物中被回收，因此人类通过食用鸡肉对MAB1a残留的潜在暴露会非常低。根据这些发现，MAB1a的鸟类生物转化与哺乳动物生物转化有显著差异。

The metabolism of (3)H/(14)C-labeled 4"-deoxy-4"-epimethylaminoavermectin B1a (MAB1a) benzoate, the major homologue (>/=90%) of the avermectin insecticide emamectin benzoate, was studied in laying chickens. Ten Leghorn hens (Gallus domesticus) were orally dosed once daily for 7 days (1 mg/kg of body weight/day). Eggs and excreta were collected daily, and eggs were subsequently separated into whites and yolks. Chickens were euthanized within 20 hr after the last dose, and liver, kidney, heart, muscle, fat, ovaries, gizzard, gastrointestinal tract and contents, and carcass were collected. Approximately 70 and 6% of the total administered dose were recovered in the excreta plus gastrointestinal tract and contents and in the tissues plus eggs, respectively. Two novel metabolites, i.e. the 24-hydroxymethyl derivative of the parent compound (24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a) and the N-demethylated derivative of 24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a (24-hydroxymethyl-4"-deoxy-4"-epiaminoavermectin B1a), were identified. In addition, eight fatty acid conjugates of each of these two metabolites, comprising 8-75% of total radioactive residues in tissues and eggs, were isolated and identified. Although this represents some of the most extensive in vivo fatty acid conjugation to a xenobiotic reported to date, potential human exposure to MAB1a residues from consumption of chicken would be extremely low, because the dosage level in this study was approximately 1000-fold greater than the MAB1a residue levels seen in crops and because the majority of the applied dose was recovered in the excreta. Based on these findings, the avian biotransformation of MAB1a differs substantially from the mammalian biotransformation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苄氨基阿维菌素苯甲酸盐在哺乳动物体内并未广泛代谢，有限的代谢物信息表明代谢过程并未使苄氨基阿维菌素苯甲酸盐解毒。苄氨基阿维菌素苯甲酸盐的一个植物代谢物比其本身更具毒性。

While emamectin benzoate is not extensively metabolized in mammals, the limited information on the metabolites of emamectin benzoate suggests that metabolism does not result in the detoxification of emamectin benzoate. One plant metabolite of emamectin benzoate is somewhat more toxic than emamectin benzoate itself.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

家蝇（Musca domestica L.）是全球乳品作业的重要害虫，能够适应广泛的环境条件。目前有多种杀虫剂用于它们的防治，但抗药性的发展是一个严重的问题。杀虫剂混合使用可以提高杀虫剂对具有抗性的害虫的毒性，因此可能成为一种潜在的害虫抗药性管理工具。本研究评估了单独使用以及混合使用时， bifenthrin（联苯菊酯）、cypermethrin（氯氰菊酯）、deltamethrin（溴氰菊酯）、chlorpyrifos（毒死蜱）、profenofos（丙氟磷）、emamectin benzoate（甲氨基阿维菌素苯甲酸盐）和fipronil（氟虫腈）对家蝇的毒性。与实验室敏感品系相比，现场收集的家蝇群体对所有调查的杀虫剂均表现出显著抗性。大多数杀虫剂混合物，如将一种拟除虫菊酯与其他化合物混合，在两种条件下（1:1-"A"和LC50:LC50-"B"）显著提高了拟除虫菊酯对现场群体的毒性。在两种条件下，拟除虫菊酯与其他化合物的组合指数在大多数情况下显著低于1，表明有协同作用。当酶抑制剂PBO和DEF与杀虫剂联合用于抗性群体时，bifenthrin、cypermethrin、deltamethrin和emamectin的毒性显著提高，这表明存在酯酶和单加氧酶基础的抗性机制。通过将bifenthrin、cypermethrin和deltamethrin与chlorpyrifos、profenofos、emamectin和fipronil联合使用，可以增强这些杀虫剂对家蝇抗性群体的毒性。目前的研究结果可能对家蝇抗性管理具有实际意义。

House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1?1-"A" and LC50: LC50-"B") significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

早期中毒迹象包括瞳孔扩张、肌肉失调和肌肉震颤。在接触后半小时内呕吐可以减少误食该产品后的毒性；接触后迅速（<15分钟）反复给予大量水中的医疗活性炭……。如果接触中毒已经进展到引起严重呕吐，应评估由此引起的液体和电解质失衡的程度。应根据临床迹象、症状和测量给予适当的支持性静脉补液替代疗法，以及其他必要的支持性措施（例如维持血压水平和适当的呼吸功能）。在严重病例中，应继续观察至少数天，直到临床状况稳定和正常。由于认为乙螨唑苯甲酸盐在动物中增强GABA活性，因此避免给可能接触有毒乙螨唑苯甲酸盐的患者使用增强GABA活性的药物（巴比妥类药物、苯二氮卓类药物、丙戊酸）可能是明智的。

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