Imidacloprid吡蟲啉

1、Imidacloprid Neonicotinoids (2) 2013.102Reference1. 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: 63-98.2. Imidacloprid general fact sheet. N

2、ational Pesticide Information Center. /factsheets/imidagen.html.3. Imidacloprid general fact sheet. National Pesticide Information Center. /factsheets/imidacloprid.html.4. /profiles/extoxnet/haloxyfop-methylparathion/imidacloprid-ext.ht

3、ml. 5. Toxicological evaluations imidacloprid. Pesticide residues in food 2001. /documents/jmpr/jmpmono/2001pr07.htm.3Outline History of Imidacloprid Physical / Chemical Properties How does imidacloprid work? Toxicological effects Fate in the Body Summary 4History of Imidacloprid

4、In 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 containing nithiazine has been available. In 1985 finally the chemists of Nihon

5、 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, the 6-chloro-3-pyridyl-methyl moiety, to the nitromethylene substituted heterocycles (NMHs) increased the insecticidal act

6、ivity remarkably and further optimization 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. NSNOONithiazineNNHNCH2ClNNOOImidaeloprid5Physical / Chemica

7、l PropertiesvImidacloprid is made up of colorless crystals with a slight but characteristic odor 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 half-life: 27.1 days vAerobic 好氧的 half-life: 997 days vSoil photolysis half-life: 38.9

8、 days vField dissipation half-life: 26.5 229 days vSoil adsorption coefficient 吸附系數(shù): Kd=0.956 4.18 / Koc=132310 6How does imidacloprid work?Imidacloprid disrupts 破壞 the nerves ability to send a normal signal, and the nervous system stops working the way it should. I m i d a c l o p r i d i s m u c h

9、 m o re tox i c to i n s e c t s a n d o t h e r invertebrates 無脊椎動物 than it is to mammals 哺乳動物 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, which means that plants take it up from the soil or through the leaves and it sprea

10、ds throughout the plants stems 莖, leaves, fruit, and flowers. Insects that chew 咀嚼 or suck 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 Acute Toxicity OralImidac

11、loprid is moderately toxic 中等毒性 if ingested 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 mg/kg for females. Inhalat

12、ion 吸入Imidacloprid is variable 變 量 in toxicity if inhaled. The inhalation LC50 was estimated to be greater than 5323 mg/m3 for d u s t 粉 劑 a n d 6 9 m g / m3 f o r a e r o s o l 氣 霧 e x p o s u r e i n rats. Imidacloprid dust is considered slightly toxic but the aerosol form is highly toxic. 8Toxico

13、logical effectsAcute Toxicity Dermal 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 in rabbits 兔子. Imidacloprid is not considered a skin sensitizer 皮膚敏化劑 although repo

14、rts of hypersensitivity 過敏癥 in skin following exposure to imidacloprid have been reported in companion animals. 9Toxicological effectsAcute Toxicity Signs of Toxicity Animalsp Salivation and vomiting 流涎和嘔吐 have been reported following oral exposure. Very high oral exposures may lead to lethargy 嗜睡,

15、vomiting, diarrhea 腹瀉, salivation, muscle weakness and ataxia運動失調(diào), which are all indicative of imidacloprids action on nicotinic re c e p to rs . O t h e r s i g n s o f ex p o s u re at h i g h d o s e s a re uncoordinated gait 步態(tài)不穩(wěn), tremors 顫抖, and reduced activity. p Hypersensitivity reactions 過敏

16、反應(yīng) in skin have been reported following dermal applications of products containing imidacloprid. p Neither persistent neurotoxic 神經(jīng)毒性 effects nor effects with a delayed onset have been reported for imidacloprid. 10Toxicological effectsAcute Toxicity Signs of Toxicity Humansp A 69-year-old woman inge

17、sted a formulated product產(chǎn)品配方 containing 9.6% imidacloprid in N-methyl pyrrolide solution. The woman suffered severe cardiac toxicity心臟毒性 and death 12 hours after the exposure. Signs of toxicity soon after the ingestion included disorientation迷失方向, sweating出汗, vomiting嘔吐, and increased heart and res

18、piratory rates 呼吸速率. p A 24-year-old man who accidentally inhaled a pesticide containing 17.8% imidacloprid while working on his farm was disoriented 迷失方向, agitated 焦慮, incoherent 語無倫次, sweating and breathless following the exposure. p Pet owners have reported contact dermatitis following the use of

19、 veterinary products 獸藥產(chǎn)品 containing imidacloprid on their pets. 11Toxicological effectsChronic Toxicity 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 and 7.6 mg/kg in females). Adverse effects副作用includ

20、ed decreased body weight gain in females at 300 ppm, and increased thyroid lesions 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 effects included increased cholesterol 膽固醇 levels in the blood,

21、and some stress to the liver (measured by elevated liver cytochrome 細(xì)胞色素 p-450 levels). 12Toxicological effectsMutagenic Effects 誘變Imidacloprid may be weakly mutagenic. In a battery of 23 laboratory mutagenicity assays致突變試驗, imidacloprid tested negative for mutagenic effects in all but two of the as

22、says. It did test positive for causing changes in chromosomes 染色體 in human lymphocytes 淋巴細(xì)胞, as well as testing positive for genotoxicity 基因毒性 in Chinese hamster ovary cells 倉鼠卵巢細(xì)胞. Endocrine Disruption 內(nèi)分泌紊亂No data were found evaluating the potential of imidacloprid to disrupt endocrine function. 1

23、3Toxicological effectsCarcinogenicity 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). There were no carcinogenic effects in a 2-year carcinogenicity study in rats fed up to 1,800 ppm

24、imidacloprid. Reproductive Effects 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 body weight observed at the 250 ppm dose level. 14Toxicological effectsTeratogenic Effects 致畸A developmen

25、tal toxicity study in rats given doses up to 100 mg/kg/day by gavage 灌胃 on days 6 to 16 of gestation 妊娠 resulted in a NOEL of 30 mg/kg/day (based on skeletal abnormalities骨骼異常 observed at the next highest dose tested of 100 mg/kg/day). In a developmental toxicity study with rabbits given doses of im

26、idacloprid 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 dose tested). 15Toxicological effects16Fate in the BodyAbsorption The gastrointestinal tract胃腸道 of rats absorbed

27、92% of an unspecified dose. Plasma concentrations peaked 血漿濃度達(dá)到高峰 2.5 hours after administration. Researchers tested imidacloprid absorption using human intestinal cells 腸細(xì)胞. Cells rapidly absorbed imidacloprid at a very high rate of efficiency. Researchers concluded that an active transport system

28、was involved. DistributionResearchers administered a single oral dose of radio-labeled imidacloprid at 20 mg/kg to male rats. One hour after dosing, imidacloprid was detected throughout the bodies with the exception of fatty tissues 脂肪組織 and the central nervous system. 17Fate in the BodyMetabolismTw

29、o main routes of m e t a b o l i s m responsible for the d e g r a 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 a n d i t s g l y c i n e conjugate, which were found only in urine. NNHNNNClOONNHNNNClONHNHNNOONNHNNNClOOOHNNHNNNClOOOHNNHN

30、NNH2ClNNClNNNOCH3NClOHONNHNNHClNNHNNNClOONHNHNNOONClNHOOHONOHOHONSOHONHCH3OOHONSOHOCH3NSNHOOHOCH3ImidaclopridNitroso metabolite4-Hydroxyimidacloprid5-HydroxyimidaclopridTriazinone6-Chloronicotinic acidGuanidine-type metaboliteOlefinic metaboliteGlycine conjugate of6-chloronicotinic acid6-Hydroxynico

31、tine acidMercapturic acid derivativeof 6-chloronicotinic acid6-Methylmercaptonicotinic acid Glycine conjugate of 6-methylmercaptonicotinic acid2-NitroaminoimidazolineFigure . Proposed metabolic pathway of imidacloprid in rats.18Fate in the BodyExcretion 排泄 The metabolic products 5-hydroxy and olefin

32、 derivatives resulting from hydroxylation of the imidazolidine ring are excreted in both the feces 糞便 and urine. Metabolites found in urine include 6-chloronicotinic acid and its glycine conjugate, and accounted for roughly 20% of the original radio-labeled dose. Rats excreted 96% of radio-labeled i

33、midacloprid 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 tissues 24 hours after male rats were orally dosed with 20 mg/kg. 19SummaryChemical Class: Chloro-nicotinyl.Use: Systemic ins

34、ecticide used for seed 種子 treatment, soil insects, termites 白 蟻 and a host of other agricultural and residential insect pests.Toxicity rating: Moderately toxic 中等毒性. Health Effects: It is linked to reproductive and mutagenic effects and is neurotoxic 毒害神經(jīng)的.Environmental Effects: Highly toxic to bees

35、 and other beneficial insects, and is toxic to upland game birds高地獵鳥. It is generally persistent in soils and can leach to groundwater.Ring necked pheasantBobwhite quailBlue GrouseSage GrouseChukarMountain QuailWild TurkeyDovesRuffed Grouse20RemarksLD50/LC50: A common measure of acute toxicity is th

36、e lethal dose (LD50) or lethal concentration (LC50) that causes death (resulting from a single or limited exposure) in 50 percent of the treated animals.u LD50 is generally expressed as the dose in milligrams (mg) of chemical per kilogram (kg) of body weight.u LC50 is often expressed as mg of chemic

37、al per volume (e.g., liter (L) of medium (i.e., air or water) the organism is exposed to. Chemicals are considered highly toxic when the LD50/LC50 is small and practically non-toxic when the value is large. However, the LD50/LC50 does not reflect any effects from long-term exposure (i.e., cancer, bi

38、rth defects or reproductive toxicity) that may occur at levels below those that cause death. 21RemarksThe half-life is the time required for half of the compound to break down in the environment. u 1 half-life = 50% remainingu 2 half-lives = 25% remainingu 3 half-lives = 12% remainingu 4 half-lives

39、= 6% remainingu 5 half-lives = 3% remaining Half-lives can vary widely based on environmental factors. The amount of chemical remaining after a half-life will always depend on the amount of the chemical originally applied. It should be noted that some chemicals may degrade into compounds of toxicolo

40、gical significance. Thank you !23Reference1. 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: 63-98.2. Imidacloprid general fact sheet. National

41、 Pesticide Information Center. /factsheets/imidagen.html.3. Imidacloprid general fact sheet. National Pesticide Information Center. /factsheets/imidacloprid.html.4. /profiles/extoxnet/haloxyfop-methylparathion/imidacloprid-ext.html. 5.

42、Toxicological evaluations imidacloprid. Pesticide residues in food 2001. /documents/jmpr/jmpmono/2001pr07.htm.24Toxicological effectsAcute Toxicity Signs of Toxicity Humansp A 69-year-old woman ingested a formulated product產(chǎn)品配方 containing 9.6% imidacloprid in N-methyl pyrrolide s

43、olution. The woman suffered severe cardiac toxicity心臟毒性 and death 12 hours after the exposure. Signs of toxicity soon after the ingestion included disorientation迷失方向, sweating出汗, vomiting嘔吐, and increased heart and respiratory rates 呼吸速率. p A 24-year-old man who accidentally inhaled a pesticide cont

44、aining 17.8% imidacloprid while working on his farm was disoriented 迷失方向, agitated 焦慮, incoherent 語無倫次, sweating and breathless following the exposure. p Pet owners have reported contact dermatitis following the use of veterinary products 獸藥產(chǎn)品 containing imidacloprid on their pets. 25Toxicological effectsMutagenic Effects 誘變Imidacloprid may be weakly mutagenic. In a battery of 23 laboratory mutagenicity assays致突變試驗, imidacloprid tested negative for mutagenic effects in all but two of th