噻虫胺 | 210880-92-5

• 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 - 唑类
• 中文名称: 噻虫胺
• 中文别名: 可尼丁；(E)-1-(2-氯-1,3-噻唑-5-基甲基)-3-甲基-2-硝基胍；(E)-1-(2-氯-5-噻唑基甲基)-3-甲基-2-硝基胍；1-(2-氯-5-噻唑基甲基)-3-甲基-2-硝基胍
• 英文名称: clothianidine
• 英文别名: clothianidin；(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine；(E)-N-[(2-chloro-5-thiazolyl)methyl]-N′-methyl-N″-nitroguanidine；chlothianidin；dantotsu；(E)-1-(2-chlorothiazol-5-ylmethyl)-3-methyl-2-nitroguanidine；1-[(2-Chloro-1,3-thiazol-5-yl)methyl]-3-methyl-2-nitroguanidine；1-[(2-chloro-1,3-thiazol-5-yl)methyl]-3-methyl-2-nitroguanidine
• CAS: 210880-92-5
• 化学式: C₆H₈ClN₅O₂S
• 分子量: 249.681
• InChiKey: PGOOBECODWQEAB-UHFFFAOYSA-N

物化性质

• 熔点：
  178.8 °C
• 沸点：
  412.5±55.0 °C(Predicted)
• 密度：
  1.61
• 溶解度：
  DMF：30 mg/ml； DMSO：30 mg/ml； DMSO:PBS (pH 7.2) (1:1)：0.50 mg/ml
• LogP：
  0.7 at 25℃
• 碰撞截面：
  152.55 Ų [M-H]-; 151.65 Ų [M+H]+; 160.71 Ų [M+Na]+
• 颜色/状态：
  Colorless powder
• 气味：
  Odorless
• 蒸汽压力：
  1.3X10-7 mPa (9.8X10-10 mm Hg) at 25 °C
• 亨利常数：
  Henry's Law constant = 2.9X10-16 atm-cu m/mol at 20 °C
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 分解：
  Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx), sulfur oxides, hydrogen chloride gas.
• 解离常数：
  pKa = 11.09 at 20 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

已建立的新烟碱类杀虫剂包括氯吡啶甲基（吡虫啉、噻虫啉、啶虫脒和硝虫腈）、氯噻唑甲基（噻虫嗪或TMX和噻虫胺或CLO）或四氢呋喃甲基（ dinotefuran或DIN）取代基。我们最近报告了氯吡啶甲基新烟碱类化合物在小鼠体内的代谢命运，作为比较研究的第一部分，现在考虑氯噻唑甲基和四氢呋喃甲基类似物。将TMX、CLO、两个去甲基衍生物（TMX-dm和CLO-dm）和DIN以20 mg/kg的剂量ip给予小鼠，通过HPLC/DAD和LC/MSD对大脑、肝脏、血浆和尿液的代谢物和药代动力学进行分析。每种化合物在24小时内以19-55%的未代谢形式排出尿液，并且组织残留物在4小时内大部分消失。通过与合成标准比较，确定了TMX、TMX-dm、CLO和CLO-dm的37个代谢物，或者通过分子量和35Cl:37Cl比率提出它们的结构，通常由以前的报告或序列研究中重新给药的中间体补充。一个简单的反应序列涉及TMX --> TMX-dm或CLO --> CLO-dm。据报道，CLO-dm在小鼠中是TMX致肝癌的一个因素，出人意料的是，部分在脑中重新甲基化为CLO。在组织中检测到硝基胍、氨基胍和脲衍生物，在尿液中检测到甲基硝基胍、甲基胍和硝基胍。与来自其他新烟碱类化合物的氯吡啶甲酸和四氢呋喃甲酸相比，TMX和CLO的氧化裂解产生的氯噻唑甲酸醛在大脑、肝脏尤其是血浆中相当持久。氯噻唑甲酸与甘氨酸或葡萄糖醛酸结合，或转化为S-甲基和巯基尿酸衍生物。DIN的代谢涉及硝基还原、N-去甲基化、N-亚甲基羟基化和胺裂解，以及四氢呋喃甲基在2-、4-和5-位的羟基化，产生了29个暂时确定的代谢物。生物降解位点的多样性和多种途径确保了母体化合物的积累，但提供了据报道作为烟碱激动剂和可诱导一氧化氮合酶抑制剂活性的中间体。

The established neonicotinoid insecticides have chloropyridylmethyl (imidacloprid, thiacloprid, acetamiprid, and nitenpyram), chlorothiazolylmethyl (thiamethoxam or TMX and clothianidin or CLO) or tetrahydrofuranylmethyl (dinotefuran or DIN) substituents. We recently reported the metabolic fate of the chloropyridylmethyl neonicotinoids in mice as the first half of a comparative study that now considers the chlorothiazolylmethyl and tetrahydrofuranylmethyl analogues. TMX, CLO, two desmethyl derivatives (TMX-dm and CLO-dm), and DIN were administered ip to mice at 20 mg/kg for characterization of metabolites and pharmacokinetic analysis of brain, liver, plasma, and urine by HPLC/DAD and LC/MSD. Each compound is excreted 19-55% unmetabolized in urine within 24 hr, and tissue residues are largely dissipated by 4 hr. Thirty-seven metabolites of TMX, TMX-dm, CLO, and CLO-dm are identified by comparison with synthetic standards or their structures are proposed by molecular weights and 35Cl:37Cl ratios often supplemented by previous reports or sequence studies in which intermediates are readministered. A facile reaction sequence involves TMX --> TMX-dm or CLO --> CLO-dm. CLO-dm, reported to be a contributor to TMX hepatocarcinogenesis in mice, is unexpectedly remethylated in part to CLO in brain. The nitrosoguanidine, aminoguanidine, and urea derivatives of the parent compounds are detected in the tissues and methylnitroguanidine, methylguanidine, and nitroguanidine in the urine. Chlorothiazolecarboxaldehyde from oxidative cleavage of TMX and CLO is quite persistent in brain, liver, and particularly plasma compared with chloropyridinecarboxaldehyde and tetrahydrofurancarboxaldehyde from the other neonicotinoids. Chlorothiazolecarboxylic acid is conjugated with glycine or glucuronic acid or converted to S-methyl and mercapturate derivatives. DIN metabolism involves nitro reduction, N-demethylation, N-methylene hydroxylation, and amine cleavage, and tetrahydrofuranylmethyl hydroxylation at the 2-, 4-, and 5-positions giving 29 tentatively identified metabolites. The diversity of biodegradable sites and multiple pathways insures against parent compound accumulation but provides intermediates reported to be active as nicotinic agonists and inducible nitric oxide synthase inhibitors.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在标准代谢研究中，使用0.5%阿拉伯胶悬浮液通过灌胃方式给予SD大鼠，大多数测试采用了硝基亚胺-14C标记或噻唑基-2-(14)C标记的噻虫胺（有效成分纯度为99.8%：两种标记材料的放射性纯度均大于99%）。未改变的噻虫胺在尿液中占给药剂量的55-73%。主要的尿代谢物及其占给药剂量的百分比分别是：(1) N-去甲基化产物（命名为“TZNG”，占7-12%），(2) 在噻唑基团上的亚甲基碳与相邻硝基胍基团上的氮之间断裂的产物（命名为“MNG”，占8-13%），(3) 两个事件产生的产物，即MNG的去甲基化产物（命名为“NTG”，占1-4%）。噻唑环上的亚甲基碳，作为MNG（上述代谢物#2）的互补断裂产物的一部分，迅速被氧化成羧酸（命名为CTCA，占1%）。随后通过共轭作用取代氯基团，然后裂解该共轭物，产生了比初始CTCA更丰富的代谢物，生成了甲基硫醚类似物（命名为MTCA，占10%）。除了大约10到11%的母体在噻唑基团的亚甲基碳之间被代谢，主要产生MNG、CTCA和MTCA之外，还有一种值得注意的代谢物是在硝基亚胺标记碳和连接在亚甲基碳上的二级氨基团之间裂解的产物。这种产物，命名为ACT，占给药剂量的1%。没有其他单独的尿液排泄产物在标记中占1%以上。在这些研究中，只有大约2-7%的尿液代谢残留物未被表征。粪便残留物包括大约相等的部分(1)母体噻虫胺和(2)无硝基团的母体（命名为TMG）：约占给药剂量的1%到2%。从粪便中提取的没有其他化合物占给药剂量的1%以上。

/In/ a standard metabolism study with gavage dosing of CD rats using suspensions in aq. 0.5% tragacanth, ... the majority of tests employed nitroimino-14C label or thiazolyl-2-(14)C in clothianidin (purity of the a.i. 99.8%: radiopurity of both labeled materials > 99%). ...Unaltered clothianidin in urine comprised 55-73% of administered label. Primary urinary metabolites and associated percentages of administered dose were (1) the N-demethylated product (designated "TZNG," 7-12%), (2) the cleavage product separating the methylene carbon on the thiazolyl group from the adjacent nitrogen of the nitroguanidine group (designated "MNG", 8-13%), and (3) the product of both events, producing a demethylated product of MNG, (designated "NTG," 1-4%). The methylene carbon on the thiazolyl ring, part of the complementary cleavage product to MNG (metabolite #2 above) was quickly oxidized to the carboxylic acid (designated CTCA, 1%). Subsequent conjugation to displace the chlorine moiety, followed by cleavage of that conjugate provided a more abundant metabolite than the initial CTCA, produced the methylthioether analog (designated MTCA, 10%). In addition to about 10 to 11% of parent being metabolized between the methylene carbon on the thiazolyl group to produce primarily MNG, CTCA, and MTCA, one additional noteworthy metabolite was the product of cleavage between the nitroimino-labeled carbon and the secondary amino group attached to the methylene carbon. This product, designated ACT, constituted 1% of administered label. No other individual urinary excretion product characterized constituted as much as 1% of label. Only about 2-7% of urinary metabolic residues were not characterized in these studies. Fecal residues included about equal parts of (1) parent clothianidin and (2) parent without the nitro group (designated TMG): about 1% to 2% of either substance. No other compound extracted from feces comprised as much as 1% of dose administered.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... clothianidin在大鼠体内的主要代谢反应是氧化脱甲基，形成N-(2-氯噻唑-5-基甲基)-N'-硝基胍，以及噻唑基甲基部分和硝基胍部分之间的碳氮键断裂。含有硝基胍部分的分子主要转化为N-甲基-N'-硝基胍，而噻唑部分则进一步代谢为2-(甲硫基)噻唑-5-羧酸。... clothianidin的药代动力学、排泄、分布和代谢速率并未因剂量水平和性别而有明显影响。

... The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. ... The rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.

来源:Hazardous Substances Data Bank (HSDB)

代谢

已建立的新烟碱类杀虫剂包括氯吡啶甲基（吡虫啉、噻虫啉、啶虫脒和硝苯吡豆），氯噻唑甲基（噻虫嗪或TMX和噻虫胺或CLO）或四氢呋喃甲基（丁氟螨或DIN）取代物。我们最近报道了氯吡啶甲基新烟碱类杀虫剂在小鼠体内的代谢命运，作为比较研究的第一部分，现在考虑氯噻唑甲基和四氢呋喃甲基类似物。TMX、CLO、两个去甲基衍生物（TMX-dm和CLO-dm）和DIN以20 mg/kg的剂量通过腹膜内给药给小鼠，通过HPLC/DAD和LC/MSD对大脑、肝脏、血浆和尿液的代谢物和药代动力学进行分析。每种化合物在24小时内以19-55%的未代谢形式排出尿液，组织残留物在4小时内大部分消散。通过与合成标准比较，确定了TMX、TMX-dm、CLO和CLO-dm的37种代谢物，或者根据分子量和35Cl:37Cl比率提出其结构，通常由先前的报告或序列研究补充，其中中间体被重新给药。一个简单的反应序列涉及TMX --> TMX-dm或CLO --> CLO-dm。据报道，CLO-dm在小鼠中是TMX导致肝细胞癌的一个因素，出人意料的是，部分在脑中重新甲基化为CLO。在组织中检测到硝基胍、氨基胍和脲衍生物，在尿液中检测到甲基硝基胍、甲基胍和硝基胍。与来自其他新烟碱类杀虫剂的氯吡啶甲酸和四氢呋喃甲酸相比，由TMX和CLO的氧化裂解产生的氯噻唑甲酸醛在大脑、肝脏，尤其是血浆中非常持久。氯噻唑甲酸与甘氨酸或葡萄糖醛酸结合，或转化为S-甲基和巯基尿酸衍生物。DIN的代谢涉及硝基还原、N-去甲基化、N-甲基烯醇化、胺裂解，以及四氢呋喃甲基在2-、4-和5-位的羟基化，产生29种暂时确定的代谢物。生物降解位点的多样性和多条途径确保了母体化合物的积累，但提供了据报道作为烟碱激动剂和可诱导一氧化氮合酶抑制剂活性的中间体。

The established neonicotinoid insecticides have chloropyridylmethyl (imidacloprid, thiacloprid, acetamiprid, and nitenpyram), chlorothiazolylmethyl (thiamethoxam or TMX and clothianidin or CLO) or tetrahydrofuranylmethyl (dinotefuran or DIN) substituents. We recently reported the metabolic fate of the chloropyridylmethyl neonicotinoids in mice as the first half of a comparative study that now considers the chlorothiazolylmethyl and tetrahydrofuranylmethyl analogues. TMX, CLO, two desmethyl derivatives (TMX-dm and CLO-dm), and DIN were administered ip to mice at 20 mg/kg for characterization of metabolites and pharmacokinetic analysis of brain, liver, plasma, and urine by HPLC/DAD and LC/MSD. Each compound is excreted 19-55% unmetabolized in urine within 24 hr, and tissue residues are largely dissipated by 4 hr. Thirty-seven metabolites of TMX, TMX-dm, CLO, and CLO-dm are identified by comparison with synthetic standards or their structures are proposed by molecular weights and 35Cl:37Cl ratios often supplemented by previous reports or sequence studies in which intermediates are readministered. A facile reaction sequence involves TMX --> TMX-dm or CLO --> CLO-dm. CLO-dm, reported to be a contributor to TMX hepatocarcinogenesis in mice, is unexpectedly remethylated in part to CLO in brain. The nitrosoguanidine, aminoguanidine, and urea derivatives of the parent compounds are detected in the tissues and methylnitroguanidine, methylguanidine, and nitroguanidine in the urine. Chlorothiazolecarboxaldehyde from oxidative cleavage of TMX and CLO is quite persistent in brain, liver, and particularly plasma compared with chloropyridinecarboxaldehyde and tetrahydrofurancarboxaldehyde from the other neonicotinoids. Chlorothiazolecarboxylic acid is conjugated with glycine or glucuronic acid or converted to S-methyl and mercapturate derivatives. DIN metabolism involves nitro reduction, N-demethylation, N-methylene hydroxylation, and amine cleavage, and tetrahydrofuranylmethyl hydroxylation at the 2-, 4-, and 5-positions giving 29 tentatively identified metabolites. The diversity of biodegradable sites and multiple pathways insures against parent compound accumulation but provides intermediates reported to be active as nicotinic agonists and inducible nitric oxide synthase inhibitors.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在标准代谢研究中，使用0.5%阿拉伯胶悬浮液通过灌胃方式给予SD大鼠，大多数测试采用了硝基亚胺-14C标记或噻唑基-2-(14)C在 clothianidin（有效成分纯度为99.8%：两种标记材料的放射性纯度均大于99%）中进行。未改变的clothianidin在尿液中占给药剂量的55-73%。主要的尿代谢物及其占给药剂量的百分比分别是：（1）N-去甲基化产物（命名为“TZNG”，占7-12%），（2）将噻唑基上的亚甲基碳与相邻的硝基胍基团之间的氮原子分离的裂解产物（命名为“MNG”，占8-13%），以及（3）两个事件的产物，产生了MNG的去甲基化产物（命名为“NTG”，占1-4%）。噻唑环上的亚甲基碳，是MNG（上述代谢物#2）的互补裂解产物的一部分，迅速被氧化成羧酸（命名为CTCA，占1%）。随后，为了取代氯基团，该羧酸与葡萄糖醛酸结合，裂解该结合物产生了比最初的CTCA更丰富的代谢物，生成了甲硫醚类似物（命名为MTCA，占10%）。除了大约10到11%的母体在噻唑基的亚甲基碳之间被代谢，主要产生MNG、CTCA和MTCA之外，还有一种值得注意的代谢物是在硝基亚胺标记碳和与亚甲基碳相连的二级氨基团之间裂解的产物。这种产物，命名为ACT，占给药剂量的1%。没有其他单个尿液排泄产物在标记中占1%以上。在这些研究中，只有大约2-7%的尿液代谢残留物未被表征。粪便残留物包括大约相等的部分（1）母体clothianidin和（2）无硝基团的母体（命名为TMG）：占给药剂量的约1%至2%。从粪便中提取的没有其他化合物占给药剂量的1%以上。

/In/ a standard metabolism study with gavage dosing of CD rats using suspensions in aq. 0.5% tragacanth, ... the majority of tests employed nitroimino-14C label or thiazolyl-2-(14)C in clothianidin (purity of the a.i. 99.8%: radiopurity of both labeled materials > 99%). ...Unaltered clothianidin in urine comprised 55-73% of administered label. Primary urinary metabolites and associated percentages of administered dose were (1) the N-demethylated product (designated "TZNG," 7-12%), (2) the cleavage product separating the methylene carbon on the thiazolyl group from the adjacent nitrogen of the nitroguanidine group (designated "MNG", 8-13%), and (3) the product of both events, producing a demethylated product of MNG, (designated "NTG," 1-4%). The methylene carbon on the thiazolyl ring, part of the complementary cleavage product to MNG (metabolite #2 above) was quickly oxidized to the carboxylic acid (designated CTCA, 1%). Subsequent conjugation to displace the chlorine moiety, followed by cleavage of that conjugate provided a more abundant metabolite than the initial CTCA, produced the methylthioether analog (designated MTCA, 10%). In addition to about 10 to 11% of parent being metabolized between the methylene carbon on the thiazolyl group to produce primarily MNG, CTCA, and MTCA, one additional noteworthy metabolite was the product of cleavage between the nitroimino-labeled carbon and the secondary amino group attached to the methylene carbon. This product, designated ACT, constituted 1% of administered label. No other individual urinary excretion product characterized constituted as much as 1% of label. Only about 2-7% of urinary metabolic residues were not characterized in these studies. Fecal residues included about equal parts of (1) parent clothianidin and (2) parent without the nitro group (designated TMG): about 1% to 2% of either substance. No other compound extracted from feces comprised as much as 1% of dose administered.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

识别和使用： Clothianidin是一种无色粉末。Clothianidin是一种新烟碱类杀虫剂，种子处理/保护剂。人体研究：Clothianidin处理影响了体外人单核细胞系的激活。动物研究：家兔原眼刺激试验显示轻度结膜炎，24小时内清除。在28天内以0（仅饮食）、500、1000、2000或4000 ppm的剂量水平处理的小鼠中，在4000 ppm时雄性和雌性均观察到身体震颤。在2000和4000 ppm时，观察到两性的与治疗有关的蜷缩姿势和乏力。在1000、2000和4000 ppm时，观察到两性的平均体重增加减少。在2000和4000 ppm的雄性和2000 ppm的雌性中观察到平均相对脑重增加。在大鼠饮食中剂量为0、150、500、1500或3000 ppm的Clothianidin处理2年后，未诱发肿瘤。在3000 pm的肾脏和腺胃中观察到主要变化。Clothianidin对雄性大鼠生殖系统的有害影响很小。Clothianidin在小鼠的神经行为参数中产生了不利影响。以0、10、25、75和100 mg/kg/天的剂量处理家兔，在75和100 mg/kg/天时注意到发育毒性。在100 mg/kg/天时，吸收量增加，平均仔重显著降低。在Salmonella typhimurium菌株TA1535、TA1537、TA98和TA100以及Escherichia coli菌株WP2uvrA中测试了Clothianidin。根据TA1535菌株的反应，该测试呈阳性。与代谢激活的反应通常比没有代谢激活的反应略强。生态毒理学研究：研究发现Clothianidin通过生殖细胞断裂和胚胎发育抑制或延迟影响雄性鹌鹑的繁殖。非靶标水生昆虫对重复径流事件和这些化学物质长期残留的早期发育阶段的慢性新烟碱类杀虫剂暴露很敏感。Clothianidin对春季产卵前的工作蜜蜂极为有毒，使其成为迄今为止识别的最敏感的蜜蜂阶段。以Clothianidin为食的Bombus impatiens Cresson蜂群可以改变行为（减少工蜂活动、消耗、蜂蜡生产和大黄储存），从而对蜂群（女王存活和蜂群重量）产生有害影响。依赖觅食工蜂的野生大黄蜂可能受到20 ppb的慢性新烟碱类暴露的负面影响。Clothianidin损害了独居蜜蜂Osmia cornuta的视觉指导和导航记忆的使用。用1 ng的Clothianidin处理的蜜蜂在实验期间的总移动距离显著增加。此外，在治疗后的60分钟与未处理的蜜蜂相比，休息时间减少，倒立放置的时间长度和频率增加。此外，在剂量（0.5 ng/蜜蜂）首先在60分钟后的实验期间观察到对测试参数的显著影响。冬季蜜蜂长期暴露于15 ug/kg的特异性影响早期长期记忆（24小时）的特异性。与未处理的蜜蜂相比，在实验期间，最低剂量（0.1 ng/蜜蜂）对蜜蜂的运动活动的影响不显著。在1 ppb时，观察到帝王蝶（幼虫大小）的亚致死效应。

IDENTIFICATION AND USE: Clothianidin is a colorless powder. Clothianidin is a neonicotinoid insecticide, seed treatment/protectant. HUMAN STUDIES: Clothianidin treatment affected activation of human monocytic cell line in vitro. ANIMAL STUDIES: Primary eye irritation study in rabbits showed mild conjunctivitis which cleared within 24 hours. In mice treated for 28 days at dose levels of 0 (diet only), 500, 1000, 2000, or 4000 ppm body tremors were observed in males and females at 4000 ppm. Treatment-related hunched posture and lethargy were observed in both sexes at 2000 and 4000 ppm. A treatment-related decrease in mean body weight gain was observed in both sexes at 1000, 2000, and 4000 ppm. A treatment-related increase in mean relative brain weight in males at 2000 and 4000 ppm and in females at 2000 ppm was observed. In rats dosed in the diet for 2 years at 0, 150, 500, 1500, or 3000 ppm clothianidin, treatment did not elicit tumors. Major changes were noted at 3000 pm in kidneys and glandular stomach. Clothianidin had little detectable detrimental effects on the reproductive system of male rats. Clothianidin produced adverse effects in the neurobehavioral parameters in mice. In rabbits treated at 0, 10, 25, 75, and 100 mg/kg/day clothianidin, developmental toxicity was noted at 75 and 100 mg/kg/day. At 100 mg/kg/day there were increased resorptions, and a significant decrease in mean pup weights. Clothianidin was tested in Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100 and Escherichia coli strain WP2uvrA. The test was positive for mutagenicity, based on responses of strain TA1535. Response with metabolic activation was typically slightly stronger than without. ECOTOXICITY STUDIES: It was found that clothianidin affected the reproduction of the male quail through the fragmentation of germ cells and the inhibition or delay of embryonic development. Nontarget aquatic insects were susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Clothianidin was extremely toxic to winter worker honey bees prior to brood production in spring, making this the most sensitive bee stage identified to date. Feeding colonies of Bombus impatiens Cresson on clothianidin can cause changes in behavior (reduced worker movement, consumption, wax pot production, and nectar storage) that result in detrimental effects on colonies (queen survival and colony weight). Wild bumblebees depending on foraging workers can be negatively impacted by chronic neonicotinyl exposure at 20 ppb. Clothianidin compromised visual guidance and the use of navigational memory in the solitary bee Osmia cornuta. Bees treated with 1 ng clothianidin show a significant increase in total distance moved over the experimental period. Moreover, a reduction in the resting time and increase of the duration and frequency of bouts of laying upside down at these doses are found. Furthermore, significant effects on the tested parameters are observed at the dose (0.5 ng/bee) first at 60 min post-treatment compared to untreated bees. Chronic exposure of winter bees to 15 ug/kg affected the specificity of the early long-term memory (24 hr)The lowest dose (0.1 ng/bee) has non-significant effects on the motor activity of honeybees compared to untreated bees over the experimental period. Sublethal effects in Monarch butterflies (larval size) were observed at 1 ppb.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

氯吡硫磷（CPF）、仲丁威（FEN）、噻虫胺（CLO）和乙草胺（ACE）是常用的农药，它们在全球范围内广泛用于作物。在本研究中，使用蚯蚓Eisenia fetida作为测试生物，评估了它们的二元、三元和四元混合物的联合毒性。混合毒性研究使用了组合指数（CI）方法，并通过等毒图进行了可视化，然后与传统浓度加和（CA）和独立作用（IA）模型进行了比较。CPF+FEN和FEN+ACE的两种二元混合物，CPF+CLO+FEN和CPF+FEN+ACE的两种三元混合物，以及CPF+FEN+ACE+CLO的四元混合物表现出明显的协同效应。CI方法与CA和IA的经典模型进行了比较，表明CI方法可以准确预测化学物质的联合毒性。结果表明，由于存在复杂的协同和拮抗反应，仅从作用方式来预测这些农药的联合效果是困难的。应该更多地关注化学物质相互作用的潜在协同效应，这可能会导致严重的生态问题。

As commonly used pesticides, chlorpyrifos (CPF), fenobucarb (FEN), clothianidin (CLO) and acetochlor (ACE) are widely applied on crops worldwide. In this study, the combined toxicities of their binary, ternary and quaternary mixtures were evaluated using the earthworm Eisenia fetida as test organism. Mixture toxicities were studied using the combination index (CI) method and visualized by isobolograms, and then data were compared with traditional concentration addition (CA) and independent action (IA) models. Two binary mixtures of CPF+FEN and FEN+ACE, two ternary mixtures of CPF+CLO+FEN and CPF+FEN+ACE, and quaternary mixture of CPF+FEN+ACE+CLO exhibited a clear synergistic effect. The CI method was compared with the classical models of CA and IA, indicating that the CI method could accurately predict the combined toxicities of the chemicals. The results indicated that it was difficult to predict combined effects of these pesticides from mode of action alone because of existence of complicated synergistic and antagonistic responses. More attention should be paid to the potential synergistic effects of chemicals interactions, which might cause serious ecological problems.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

背景：新烟碱类杀虫剂被认为是导致蜜蜂多样性下降的一个重要因素。然而，关于它们在野外条件下影响的不确定性仍然存在。大多数研究都是在Apis mellifera（西方蜜蜂）上进行的，并且测试的是单一化合物。然而，在农业环境中，蜜蜂常常暴露于多种农药之下。我们探讨了在实验室口服暴露下，新烟碱类杀虫剂（克百威）和抑制麦角甾醇生物合成的杀菌剂（丙硫菌唑）对三种蜜蜂物种（A. mellifera, Bombus terrestris, Osmia bicornis）的协同致死作用。结果：我们开发了一种基于二项比例检验的新方法来分析协同相互作用。我们估计了在种子包衣油菜田觅食的蜜蜂每次觅食过程中摄入的克百威量。我们发现，在暴露于丙硫菌唑的非致死剂量和各自克百威的LD10剂量下，所有三种蜜蜂物种都出现了显著的协同致死作用。A. mellifera（4和24小时）和B. terrestris（4小时）仅在第一次评估时发现显著协同作用，但在O. bicornis中这种协同作用在整个实验期间（96小时）持续存在。O. bicornis也是对克百威最敏感的物种。结论：我们的结果强调了在农业环境中可能发生的农药组合进行测试的重要性，并应在环境风险评估方案中包括多种蜜蜂物种。

BACKGROUND: Neonicotinoid insecticides have been identified as an important factor contributing to bee diversity declines. Nonetheless, uncertainties remain about their impact under field conditions. Most studies have been conducted on Apis mellifera and tested single compounds. However, in agricultural environments, bees are often exposed to multiple pesticides. We explore the synergistic mortality between a neonicotinoid (clothianidin) and an ergosterol-biosynthesis-inhibiting fungicide (propiconazole) in three bee species (A. mellifera, Bombus terrestris, Osmia bicornis) following oral exposure in the laboratory. RESULTS: We developed a new approach based on the binomial proportion test to analyse synergistic interactions. We estimated uptake of clothianidin per foraging bout in honey bees foraging on seed-coated rapeseed fields. We found significant synergistic mortality in all three bee species exposed to non-lethal doses of propiconazole and their respective LD10 of clothianidin. Significant synergism was only found at the first assessment times in A. mellifera (4 and 24 hr) and B. terrestris (4 hr), but persisted throughout the experiment (96 hr) in O. bicornis. O. bicornis was also the most sensitive species to clothianidin. CONCLUSION: Our results underscore the importance to test pesticide combinations likely to occur in agricultural environments, and to include several bee species in environmental risk assessment schemes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

披露杀虫剂和蜜蜂感染之间的相互作用是最有趣的，以了解传粉者面临的挑战以及蜜蜂健康的受损程度。在这里，我们探讨三种不同杀虫剂（地亚硫磷、克洛西尼定和阿佛菌素）和美洲腐臭病（AFB）感染对蜜蜂幼虫的死亡和细胞免疫反应的个别和联合效应。我们证明...当幼虫接触到地亚硫磷或克洛西尼定的亚致死剂量与AFB的致病菌芽孢杆菌共同暴露时，存在协同作用。与每个单独应激源效应的预期总和相比，共同暴露的幼虫的死亡率显著提高，这与总血细胞计数和差异化血细胞计数的急剧减少平行。我们的结果强调了表征幼虫对单个和共同应激源的细胞反应，可以揭示以前未被发现的杀虫剂对蜂群健康的亚致死效应。

Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate ... a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

背景：新烟碱类杀虫剂是一种新型杀虫剂，已经在全球范围内使用，因为它们对节肢动物具有选择性毒性，对脊椎动物相对无毒。有研究表明，几种新烟碱类杀虫剂对哺乳动物的神经发育具有毒性。本研究的目的是建立人类摄入新烟碱类杀虫剂与通过尿液排出之间的关系，以便于生物监测，并估计日本成年人的膳食新烟碱类杀虫剂摄入量。方法/主要结果：九名健康成年人摄入了氘标记的新烟碱类杀虫剂（乙螨唑、克百威、丁氟螨酯和吡虫啉）微剂量，并在给药后连续四天收集24小时汇集的尿液样本。使用一室和二室模型对排泄动力学进行建模，然后在涉及12名健康成年人的非氘标记新烟碱类杀虫剂微剂量研究中进行了验证。给药后观察到标记新烟碱类杀虫剂尿液中浓度增加。克百威在3天内未改变被回收，大部分丁氟螨酯在1天内未改变被回收。大约10%的吡虫啉剂量未改变被排出。大部分乙螨唑被代谢为去甲基乙螨唑。分析了373名日本成年人的点尿液样本中新烟碱类杀虫剂，并估计了每日摄入量。估计这些新烟碱类杀虫剂的日均摄入量为0.53-3.66微克/天。在研究人群中，任何一种新烟碱类杀虫剂的最高摄入量为64.5微克/天，这低于可接受日摄入量的1%。

BACKGROUND: Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults. METHODOLOGY/PRINCIPAL FINDINGS: Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 hr pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53-3.66 ug/day. The highest intake of any of the neonicotinoids in the study population was 64.5 ug/day for dinotefuran, and this was <1% of the acceptable daily intake.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

经口给予小鼠单次剂量为5毫克/千克体重的药物后，在168小时内被迅速吸收并排泄，其中98.7-99.2%的放射性剂量被回收。

Of the administered radioactivity /in mice/, 98.7-99.2% was recovered. Readily absorbed and excreted within 168 hours following a single oral dose of 5 mg/kg bw.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中的整体恢复率为95-100%。在单次口服剂量为2.5 mg/kg体重或重复口服剂量为25 mg/kg体重后，药物在96小时内被迅速吸收和排泄，但是在250 mg/kg的剂量下，吸收变得双相并且达到饱和。

Overall recovery /in rats/: 95-100%. Readily absorbed and excreted within 96 hours following a single 2.5 mg/kg bw or repeated oral dose of 25 mg/kg bw, but at a dose of 250 mg/kg, absorption became biphasic and was saturated.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一个标准的代谢研究中，使用0.5%阿拉伯树胶水悬浮液对CD大鼠进行灌胃给药...大多数测试使用硝基亚胺-(14)C标记物或噻唑基-2-(14)C标记的涕灭威（活性成分的纯度为99.8%：两种标记材料的放射性纯度均大于99%）...硝基亚胺-(14)C标记的涕灭威（2.5 mg/kg）吸收良好，根据尿液中89%至95%的放射性活度发现，与之相比，雄性大鼠粪便中为6-9%，雌性大鼠粪便中为3%，口服给药后72小时。这与放射自显影研究一致，后者显示快速灌注到体内，随后迅速清除。到72小时，剩余器官中浓度最高的是肝脏，仅为最初几小时内肝脏水平的不到1%。关于观察到的快速排泄，没有令人信服的证据表明性别效应、高剂量效应或重复给药的效应。

/In/ a standard metabolism study, with gavage dosing of CD rats using suspensions in aq. 0.5% tragacanth, ... the majority of tests employed nitroimino-(14)C label or thiazolyl-2-14C in clothianidin (purity of the a.i. 99.8%: radiopurity of both labeled materials > 99%). ... /Nitroimino-(14)C labeled/ clothianidin (2.5 mg/kg) was well absorbed, based on findings of 89% to 95% radioactivity in urine, compared to 6-9% in feces of males and 3% in feces of females, at 72 hr after oral dosing. This was consistent with autoradiography studies, which showed rapid perfusion into the body, followed by rapid clearance. By 72 hr, highest remaining organ concentrations were in the liver, at less than 1% of levels in liver during the first few hours. Relating to the rapid excretion observed, there was no compelling evidence of a sex effect, a high dose effect, nor of an effect of repeated dosing.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

clothianidin的吸收、分布、排泄和代谢研究clothianidin[(E)-1-(2-氯-1,3-噻唑-5-基甲基)-3-甲基-2-硝基胍]在给雄性和雌性大鼠单次口服给药[nitroimino-(14)C]-或[噻唑基-2-(14)C]clothianidin5mg/kg bw(低剂量)或250mg/kg bw(高剂量)后的吸收、分布、排泄和代谢进行了研究。低剂量口服给药后2小时，两种标记的clothianidin在血液中的放射性C-14达到最高浓度，然后放射性C-14在血液中的浓度降低，半衰期为2.9-4.0小时。口服给药的放射性C-14在给药后2小时内迅速、广泛地分布到所有组织和器官中，尤其是肾脏和肝脏，但随后又迅速、几乎完全地从所有组织和器官中消除，无积累现象。口服给药的放射性C-14在给药后2天内几乎完全通过尿液和粪便排出体外，约90%的给药剂量通过尿液排出。排泄物中的主要化合物是clothianidin，占总给药剂量的60%以上。clothianidin在大鼠中的主要代谢反应是氧化脱甲基生成N-(2-氯噻唑-5-基甲基)-N'-硝基胍和噻唑基甲基部分与硝基胍部分之间的碳氮键断裂。含有硝基胍部分的分子部分主要转化为N-甲基-N'-硝基胍，而噻唑部分进一步代谢为2-(甲硫基)噻唑-5-羧酸。clothianidin的生物动力学、排泄、分布和代谢速率不受剂量水平和性别的影响。

Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg bw (low dose) or 250 mg/kg bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 hr after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 hr. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 hr after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. ... The rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn,Xi
• 安全说明：
  S22,S26,S36,S36/37/39,S46,S60,S61
• 危险类别码：
  R22,R20/21/22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2934100016
• RTECS号：
  ME9565000
• 危险类别：
  6.1
• 包装等级：
  III
• 危险品运输编号：
  UN2811

制备方法与用途

噻虫胺概述

噻虫胺是日本住化武田与拜耳联合开发的新型烟碱类杀虫剂的重要品种，具有广谱低毒、高效等特点，在农业生产中应用广泛。近年来，其销售额稳居全球前10位，引起了农药研究者的广泛关注。

噻虫胺是一种新烟碱类杀虫剂，作用机理类似于烟碱乙酰胆碱受体，具备触杀、胃毒和内吸活性。主要应用于水稻、蔬菜、果树及其他作物上防治蚜虫、叶蝉、蓟马、飞虱等半翅目、鞘翅目、双翅目和某些鳞翅目类害虫。噻虫胺具有高效、广谱、用量少、毒性低、药效持效期长、对作物无药害、使用安全以及与常规农药无交互抗性等优点，且具备卓越的内吸和渗透作用，是替代高毒有机磷农药的理想选择。

应用

噻虫胺因其应用灵活，广泛用于防治水稻、果树、蔬菜、茶叶、棉花及其他作物上的同翅目害虫，尤其擅长防治蓟马、鞘翅目和某些鳞翅目等害虫。此外，噻虫胺与同类其他杀虫剂相比具有较好的内吸性和渗透性。

研究显示，噻虫胺对韭菜迟眼蕈蚊成虫的击倒毒力较高，分别是阿维菌素的5.75、3.86和3.51倍；对2龄和4龄幼虫的毒力均以噻虫胺最高，分别为阿维菌索的27.00倍和25.23倍。目前市场主要使用方向为韭蛆蒜蛆特效药。

登记证情况

噻虫胺在国内共有109个登记证，其中原药登记11个，制剂单剂登记56个，复配制剂登记42个。其剂型包括悬浮剂、颗粒剂、水分散粒剂、悬浮种衣剂、可湿性粉剂、微囊悬浮-悬浮剂、种子处理微囊悬浮剂、种子处理悬浮剂和拌种剂。

市场情况

噻虫胺由拜耳公司和日本Takeda武田公司共同进行全球市场开发。该品种已在日本用于水稻、果树、茶叶、草皮和观赏作物。与第一代的烯啶虫胺相比，噻虫胺的分子结构进行了改进，提高了对刺吸害虫的活性，并增强了对咀嚼口器害虫的效果。

2009年12月26日，噻虫胺国内化合物专利CN1026981C届满。尽管近年来植保界对其寄予厚望，但因烟碱类杀虫剂对蜜蜂环境高风险、登记数量少和成本高等原因，噻虫胺在国内的登记并未迅速火爆起来。2008年日本住友化学株式会社才首次携噻虫胺（95%噻虫胺原药、50%噻虫胺水分散粒剂）登陆中国市场。

自2002年上市以来，噻虫胺表现出强劲的增长势头。从2004年至2009年的五年间，其全球销售额平均增长率达到了27.9%，并在2011年增长至4.05亿美元。无论是在国际市场上还是国内市场前景方面，噻虫胺都是一个值得期待的杀虫剂品种。

注意事项

对蜜蜂接触高毒，经口剧毒，极高风险性；对家蚕剧毒，极高风险性。使用时应注意，蜜源作物花期禁用，施药期间密切关注对附近蜂群的影响；禁止在河塘等水域中清洗施药器具；蚕室及桑园附近禁用。每季最多使用3次，安全间隔期为7天。

反应信息

• 作为反应物：
  描述：

  噻虫胺 在 P₄₅₀ cytochrome b5 、 recombinant CYP₃A_4.1 from human 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 生成 N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine
  参考文献：
  名称：

  10.1016/j.cbi.2024.111154

  摘要：

  DOI：

  10.1016/j.cbi.2024.111154
• 作为产物：
  描述：

  N-[1-[(2-chloro-1,3-thiazol-5-yl)methyl]-5-propyl-1,3,5-triazinan-2-ylidene]nitramide 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 噻虫胺
  参考文献：
  名称：

  A novel method for the preparation of N,N′-disubstituted-N′′-nitroguanidines, including a practical synthesis of the neonicotinoid insecticide clothianidin

  摘要：

  A novel method is described for the synthesis of N,N'-disubstituted-N"-nitroguanidines 3 via 2-nitroiminohexahydro-1,3,5-triazine intermediates 12, allowing the introduction of the heteroarylmethyl group either from a heteroarylmethyl amine 9 or a heteroarylmethyl chloride 14, respectively. This method enables an efficient synthesis of the neonicotinoid insecticide clothianidin (3b) in four steps from S-methyl-N-nitroisothiourea (10). (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)01225-9

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
  申请人：BASF SE

  公开号：WO2014206910A1

  公开（公告）日：2014-12-31

  The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式（I）中变量如索权和说明中所定义的自行车基取代异噻唑啉化合物。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种通过使用这些化合物来控制无脊椎动物害虫的方法，以及包含所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] AZOLINE COMPOUNDS<br/>[FR] COMPOSÉS AZOLINE
  申请人：BASF SE

  公开号：WO2015128358A1

  公开（公告）日：2015-09-03

  The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及式（I）的噁唑啉化合物，其中A、B1、B2、B3、G1、G2、X1、R1、R3a、R3b、Rg1和Rg2如权利要求和描述中所定义。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种利用这些化合物控制无脊椎动物害虫的方法，以及包括所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

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

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。