Imidacloprid吡蟲啉

1、Imidacloprid Neonicotinoids (2) 2013.102Referencev1. Friederike Kramer, Norbert Mencke. Flea biology and control The Biology of the Cat Flea Control and Prevention with Imidacloprid in Small AnimalsM. Berlin:Springer-Verlag Berlin Heidelberg New York, 2001: 63-98.v2. Imidacloprid general fact sheet.

2、 National Pesticide Information Center. /factsheets/imidagen.html.v3. Imidacloprid general fact sheet. National Pesticide Information Center. /factsheets/imidacloprid.html.v4. /profiles/extoxnet/haloxyfop-methylparathion/imidacloprid-ex

3、t.html. v5. Toxicological evaluations imidacloprid. Pesticide residues in food 2001. /documents/jmpr/jmpmono/2001pr07.htm.3OutlinevHistory of ImidaclopridvPhysical / Chemical PropertiesvHow does imidacloprid work?vToxicological effectsvFate in the BodyvSummary 4History of Imidacl

4、opridIn the 1960s the naturally occurring insecticide nicotine was simplified by Yamamoto to 3-pyridylmethylamines, but none of these were of practical value. In recent times a knock-down fly product against M. domestica L.家蠅家蠅 containing nithiazine has been available. In 1985 finally the chemists o

5、f Nihon Tokushu Noyaku Seizo K.K. in Japan synthesized among other compounds the nitroguanidine NTN 33893, known today as imidacloprid. The addition of a heterocyclic substituent雜環(huán)取代基雜環(huán)取代基, the 6-chloro-3-pyridyl-methyl moiety, to the nitromethylene substituted heterocycles (NMHs) increased the inse

6、cticidal activity remarkably and further optimization 優(yōu)化優(yōu)化finally resulted in the invention of imidacloprid from Nihon Bayer Agrochem. K.K. Thus imidacloprid was the first commercialized member of a new class of insecticides, called chloronicotinyl 氯化煙酰氯化煙酰. NSNOONithiazineNNHNCH2ClNNOOImidaeloprid5

7、Physical / Chemical PropertiesvImidacloprid is made up of colorless crystals with a slight but characteristic odor 氣味氣味.vMelting point: 144vSolubility (water): 0.61 g/L at 20 vHydrolysis half-life: 30 days (25 at pH 7) vAnaerobic 厭氧的厭氧的 half-life: 27.1 days vAerobic 好氧的好氧的 half-life: 997 days vSoil

8、photolysis half-life: 38.9 days vField dissipation half-life: 26.5 229 days vSoil adsorption coefficient 吸附系數(shù)吸附系數(shù): Kd=0.956 4.18 / Koc=132310 6How does imidacloprid work?Imidacloprid disrupts 破壞破壞 the nerves ability to send a normal signal, and the nervous system stops working the way it should. Imi

9、dacloprid is much more toxic to insects and other invertebrates 無脊椎動(dòng)物無脊椎動(dòng)物 than it is to mammals 哺乳動(dòng)物哺乳動(dòng)物 and birds because it binds better to the receptors of insect nerve cells. Imidacloprid is a systemic insecticide 內(nèi)吸性殺蟲劑內(nèi)吸性殺蟲劑, which means that plants take it up from the soil or through the lea

10、ves and it spreads throughout the plants stems 莖莖, leaves, fruit, and flowers. Insects that chew 咀嚼咀嚼 or suck 吸允吸允 on the treated plants end up eating the imidacloprid as well. Once the insects eat the imidacloprid, it damages their nervous system and they eventually die. 7Toxicological effects vAcu

11、te ToxicityOralImidacloprid is moderately toxic 中等毒性中等毒性 if ingested 攝取攝取. Oral LD50 values in rats were estimated to be 450 mg/kg for both sexes in one study and 500 and 380 mg/kg in males and females, respectively in another study. In mice, LD50 values were estimated at 130 mg/kg for males and 170

12、 mg/kg for females. Inhalation 吸入吸入Imidacloprid is variable 變量變量 in toxicity if inhaled. The inhalation LC50 was estimated to be greater than 5323 mg/m3 for dust 粉劑粉劑 and 69 mg/m3 for aerosol 氣霧氣霧 exposure in rats. Imidacloprid dust is considered slightly toxic but the aerosol form is highly toxic.

13、8Toxicological effectsvAcute ToxicityDermal 皮膚皮膚Imidacloprid is very low in toxicity via dermal exposure. The dermal LD50 in rats was estimated at greater than 5000 mg/kg. Researchers did not observe eye or skin irritation 刺激刺激 in rabbits 兔子兔子. Imidacloprid is not considered a skin sensitizer 皮膚敏化劑皮

14、膚敏化劑 although reports of hypersensitivity 過敏癥過敏癥 in skin following exposure to imidacloprid have been reported in companion animals. 9Toxicological effectsvAcute ToxicitySigns of Toxicity AnimalspSalivation and vomiting 流涎和嘔吐流涎和嘔吐 have been reported following oral exposure. Very high oral exposures

15、may lead to lethargy 嗜睡嗜睡, vomiting, diarrhea 腹瀉腹瀉, salivation, muscle weakness and ataxia運(yùn)動(dòng)失調(diào)運(yùn)動(dòng)失調(diào), which are all indicative of imidacloprids action on nicotinic receptors. Other signs of exposure at high doses are uncoordinated gait 步態(tài)不穩(wěn)步態(tài)不穩(wěn), tremors 顫抖顫抖, and reduced activity. pHypersensitivity re

16、actions 過敏反應(yīng)過敏反應(yīng) in skin have been reported following dermal applications of products containing imidacloprid. pNeither persistent neurotoxic 神經(jīng)毒性神經(jīng)毒性 effects nor effects with a delayed onset have been reported for imidacloprid. 10Toxicological effectsvAcute ToxicitySigns of Toxicity HumanspA 69-yea

17、r-old woman ingested a formulated product產(chǎn)品配方產(chǎn)品配方 containing 9.6% imidacloprid in N-methyl pyrrolide solution. The woman suffered severe cardiac toxicity心臟毒性心臟毒性 and death 12 hours after the exposure. Signs of toxicity soon after the ingestion included disorientation迷失方向迷失方向, sweating出汗出汗, vomiting嘔

18、吐嘔吐, and increased heart and respiratory rates 呼吸速率呼吸速率. pA 24-year-old man who accidentally inhaled a pesticide containing 17.8% imidacloprid while working on his farm was disoriented 迷失方向迷失方向, agitated 焦慮焦慮, incoherent 語(yǔ)無倫次語(yǔ)無倫次, sweating and breathless following the exposure. pPet owners have repo

19、rted contact dermatitis following the use of veterinary products 獸藥產(chǎn)品獸藥產(chǎn)品 containing imidacloprid on their pets. 11Toxicological effectsvChronic Toxicity 慢性慢性A 2-year feeding study in rats fed up to 1,800 ppm resulted in a No Observable Effect Level (NOEL) of 100 ppm (5.7 mg/kg body weight in males

20、and 7.6 mg/kg in females). Adverse effects副作用副作用included decreased body weight gain in females at 300 ppm, and increased thyroid lesions 甲狀腺病變甲狀腺病變 in males at 300 ppm and females at 900 ppm. A 1-year feeding study in dogs fed up to 2,500 ppm resulted in a NOEL of 1,250 ppm (41 mg/kg). Adverse effec

21、ts included increased cholesterol 膽固醇膽固醇 levels in the blood, and some stress to the liver (measured by elevated liver cytochrome 細(xì)胞色素細(xì)胞色素 p-450 levels). 12Toxicological effectsvMutagenic Effects 誘變誘變Imidacloprid may be weakly mutagenic. In a battery of 23 laboratory mutagenicity assays致突變?cè)囼?yàn)致突變?cè)囼?yàn), i

22、midacloprid tested negative for mutagenic effects in all but two of the assays. It did test positive for causing changes in chromosomes 染色體染色體 in human lymphocytes 淋巴細(xì)胞淋巴細(xì)胞, as well as testing positive for genotoxicity 基因毒性基因毒性 in Chinese hamster ovary cells 倉(cāng)鼠卵巢細(xì)胞倉(cāng)鼠卵巢細(xì)胞. vEndocrine Disruption 內(nèi)分泌紊亂

23、內(nèi)分泌紊亂No data were found evaluating the potential of imidacloprid to disrupt endocrine function. 13Toxicological effectsvCarcinogenicity 致癌致癌Imidacloprid is considered to be of minimal carcinogenic risk, and is thus categorized by EPA as a Group E carcinogen (evidence of noncarcinogenicity for humans

24、). There were no carcinogenic effects in a 2-year carcinogenicity study in rats fed up to 1,800 ppm imidacloprid. vReproductive Effects 生殖生殖A three generation reproduction study in rats fed up to 700 ppm imidacloprid resulted in a NOEL of 100 ppm (equivalent to 8 mg/kg/day) based on decreased pup bo

25、dy weight observed at the 250 ppm dose level. 14Toxicological effectsvTeratogenic Effects 致畸致畸A developmental toxicity study in rats given doses up to 100 mg/kg/day by gavage 灌胃灌胃 on days 6 to 16 of gestation 妊娠妊娠 resulted in a NOEL of 30 mg/kg/day (based on skeletal abnormalities骨骼異常骨骼異常 observed a

26、t the next highest dose tested of 100 mg/kg/day). In a developmental toxicity study with rabbits given doses of imidacloprid by gavage during days 6 through 19 of gestation, resulted in a NOEL of 24 mg/kg/day based on decreased body weight and skeletal abnormalities observed at 72 mg/kg/day (highest

27、 dose tested). 15Toxicological effects16Fate in the BodyvAbsorptionThe gastrointestinal tract胃腸道胃腸道 of rats absorbed 92% of an unspecified dose. Plasma concentrations peaked 血漿濃度達(dá)到高峰血漿濃度達(dá)到高峰 2.5 hours after administration.Researchers tested imidacloprid absorption using human intestinal cells 腸腸細(xì)胞細(xì)胞

28、. Cells rapidly absorbed imidacloprid at a very high rate of efficiency. Researchers concluded that an active transport system was involved. vDistributionResearchers administered a single oral dose of radio-labeled imidacloprid at 20 mg/kg to male rats. One hour after dosing, imidacloprid was detect

29、ed throughout the bodies with the exception of fatty tissues 脂肪組織脂肪組織 and the central nervous system. 17Fate in the BodyvMetabolismTwo main routes of metabolism responsible for t h e d e g ra d a t i o n o f i m i d a c l o p r i d w e r e identified. The main metabolites were 6-chloronicotinic acid

30、 and its glycine conjugate, which were found only in urine. NNHNNNClOONNHNNNClONHNHNNOONNHNNNClOOOHNNHNNNClOOOHNNHNNNH2ClNNClNNNOCH3NClOHONNHNNHClNNHNNNClOONHNHNNOONClNHOOHONOHOHONSOHONHCH3OOHONSOHOCH3NSNHOOHOCH3ImidaclopridNitroso metabolite4-Hydroxyimidacloprid5-HydroxyimidaclopridTriazinone6-Chlo

31、ronicotinic acidGuanidine-type metaboliteOlefinic metaboliteGlycine conjugate of6-chloronicotinic acid6-Hydroxynicotine acidMercapturic acid derivativeof 6-chloronicotinic acid6-Methylmercaptonicotinic acid Glycine conjugate of 6-methylmercaptonicotinic acid2-NitroaminoimidazolineFigure . Proposed m

32、etabolic pathway of imidacloprid in rats.18Fate in the BodyvExcretion 排泄排泄The metabolic products 5-hydroxy and olefin derivatives resulting from hydroxylation of the imidazolidine ring are excreted in both the feces 糞便糞便 and urine. Metabolites found in urine include 6-chloronicotinic acid and its gl

33、ycine conjugate, and accounted for roughly 20% of the original radio-labeled dose. Rats excreted 96% of radio-labeled imidacloprid within 48 hours following an unspecified oral dosing, with 90% excreted in the first 24 hours. Radio-labeled imidacloprid was present in low amounts in organs and tissue

34、s 24 hours after male rats were orally dosed with 20 mg/kg. 19SummaryvChemical Class: Chloro-nicotinyl.vUse: Systemic insecticide used for seed 種子種子 treatment, soil insects, termites 白蟻白蟻 and a host of other agricultural and residential insect pests.vToxicity rating: Moderately toxic 中等毒性中等毒性. vHeal

35、th Effects: It is linked to reproductive and mutagenic effects and is neurotoxic 毒害神經(jīng)的毒害神經(jīng)的.vEnvironmental Effects: Highly toxic to bees and other beneficial insects, and is toxic to upland game birds高地獵鳥高地獵鳥. It is generally persistent in soils and can leach to groundwater.Ring necked pheasantBobwhite quailBlue GrouseSage GrouseChukarMountain QuailWild TurkeyDovesRuffed Grouse20RemarksvLD50/LC50: A common measure of acute toxicity is the lethal dose (LD50) or lethal concentr