Imidacloprid

Imidacloprid[1]
IUPAC name N-[1-[(6-Chloro-3-pyridyl)methyl]-4,5-dihydroimidazol-2-yl]nitramide
Identifiers
CAS number	138261-41-3 Y
PubChem	86418
ChemSpider	77934 Y
UNII	3BN7M937V8 Y
DrugBank	DB07980
KEGG	C11110 Y
ChEBI	CHEBI:39169 Y
ChEMBL	CHEMBL406819 Y
ATCvet code	QP53AX17
Jmol-3D images	Image 1
SMILES [O-][N+](=O)NC/1=N/CCN\1Cc2cnc(Cl)cc2
InChI InChI=1S/C9H10ClN5O2/c10-8-2-1-7(5-12-8)6-14-4-3-11-9(14)13-15(16)17/h1-2,5H,3-4,6H2,(H,11,13) Y Key: YWTYJOPNNQFBPC-UHFFFAOYSA-N Y InChI=1/C9H10ClN5O2/c10-8-2-1-7(5-12-8)6-14-4-3-11-9(14)13-15(16)17/h1-2,5H,3-4,6H2,(H,11,13) Key: YWTYJOPNNQFBPC-UHFFFAOYAZ
Properties
Molecular formula	C9H10ClN5O2
Molar mass	255.661
Appearance	Colorless crystals
Melting point	136.4-143.8 °C
Solubility in water	0.51 g/L (20 °C)
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Imidacloprid is a nicotine-based, systemic insecticide, which acts as a neurotoxin and belongs to a class of chemicals called the neonicotinoids. Although it is now off patent, the primary manufacturer of this chemical is Bayer CropScience, (part of Bayer AG). It is sold under the trade names Kohinor, Admire, Advantage (Advocate) (flea killer for pets), Gaucho, Mallet, Merit, Nuprid, Prothor, Turfthor, Confidor, Conguard, Dominion 2L, Hachikusan, Premise, Prothor, Provado, Intercept, and Winner. Imidacloprid is one of the most widely used insecticides and can be applied by soil injection, tree injection, application to the skin, or broadcast foliar or ground application as a granular or liquid formulation or as a pesticide-coated seed treatment.^[2][3]

In France, beekeepers reported a significant loss of honeybees in the 1990s, which they attributed to the use of imidacloprid (Gaucho). See Imidacloprid effects on bee population. In response to this loss of bees called "mad bee disease," the French Minister of Agriculture convened a panel of expert scientists (Comite Scientifique et Technique) to examine the impact of imidacloprid on bees. After reviewing dozens of laboratory and field studies conducted by Bayer CropScience and by independent scientists, the panel concluded that there was a significant risk to bees from exposure to imidacloprid on sunflowers and maize (corn), the only crops for which they had exposure data. Following the release of this report, the French Agricultural Ministry suspended the use of imidacloprid on maize and sunflowers. Italy, Germany, and Slovenia have also suspended certain uses of the neonicotinoids based on concerns for bees.^{[4] [5]}

History

On January 21, 1986 a patent was filed, and granted on May 3, 1988, for imidacloprid in the United States (U.S. Pat. No. 4,742,060) by Nihon Tokushu Noyaku Seizo K.K. of Tokyo, Japan.^[6]

On March 25, 1992, Miles, Inc. (later Bayer CropScience) applied for registration of imidacloprid for turfgrass and ornamentals in the United States. On March 10, 1994, the U.S. Environmental Protection Agency approved the registration of imidacloprid.^[7]

On January 26, 2005, the Federal Register notes the establishment of the '(Pesticide Tolerances for) Emergency Exemptions' for imidacloprid. It use was granted to Hawaii (for the) use (of) this pesticide on bananas(,) and the States of Minnesota, Nebraska, and North Dakota to use (of) this pesticide on sunflower(s).^[8]

Biochemistry

Imidacloprid is a systemic chloronicotinyl pesticide, belonging to the class of neonicotinoid insecticides. It is very widely used on a wide array of plants including many major crops. In the landscape the largest use by far is on lawns or sports turfgrass as a treatment for Japanese beetle larvae. A much smaller use is on trees, but this is growing, because imidacloprid is one of the most effective products used to save Hemlocks from the Hemlock woolly adelgid - a killer of the giant Hemlocks throughout Appalachia. Recently it was found to be highly effective against the Emerald ash borer and other boring insects of Oaks and Birch. It is also used as a de-wormer and a flea treatment for dogs and cats because of its very low toxicity to mammals.

A two-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). A one-year feeding study in dogs fed up to 2,500 ppm resulted in a NOEL of 1,250 ppm (41 mg/kg). If a dog were to ingest more than this concentration (which is very unlikely), adverse effects would include increased cholesterol levels in the blood and some stress to the liver (measured by elevated liver cytochrome p-450 levels) (6).

Imidacloprid acts as a neurotoxin and interferes with the transmission of nerve impulses in insects by binding to specific nicotinic acetylcholine receptors. Not all insects are affected, however. For example, Lepidoptera (butterflies and moths) are typically unaffected by imidacloprid. Spiders and spider mites are also unaffected. As a systemic pesticide, imidacloprid translocates or moves from the soil into the leaves, pollen, and nectar of a plant. Since imidacloprid is efficacious at very low levels (nanogram and picogram), it can be applied at low concentrations (e.g., 0.05–0.125 lb/acre or 55–140 g/ha) to be effective.

The main routes of dissipation of imidacloprid in the environment are aqueousphotolysis (half-life = 1–4 hours) and plant uptake. The major photo-metabolites include imidacloprid desnitro, imidacloprid olefine, imidacloprid urea, and five minor metabolites. The end product of photodegradation is chloronicotinic acid (CNA). Since imidacloprid has a low vapor pressure, it normally does not volatilize readily.^[9]

Imidacloprid is moderately soluble in water. When it is exposed to sunlight, it breaks down very rapidly (with a half-life of about 3 hours). Imidacloprid is very unstable in high pH water and breaks down rapidly. In acidic water, and in the absence of sunlight, it has a half-life of about 70–110 days, depending on other conditions. In soil under aerobic conditions, imidacloprid is relatively persistent – with a half-life that can be as long as 6 months. It has a low mobility in most soils and generally has an attraction to clay and loam soil particles. It binds very aggressively to organic matter, which can tie it up and make it unavailable to the plants that are being treated. Pure sand soils do not hold imidacloprid well.

Imidacloprid has a very low risk of water contamination. Despite widespread testing, imidacloprid is rarely found in surface water or well water. In all instances, the amounts found were from 0.5 ppb to 7 ppb. Such extremely low concentrations are evidence of the chemical's low mobility and rapid decomposition. In comparison, the EPA tolerance for imidacloprid in eggs is 0.3 ppm. On hops (used for making beer), the EPA allows 3 ppm.

Major soil metabolites include imidacloprid nitrosimine, imidacloprid desnitro, hydroxynicotinic acid, and imidacloprid urea, which ultimately degrade to chloronicotinic acid, CO₂, and bound residues. Long-term soil dissipation studies in apple orchards and with seed-treated barley crops showed little accumulation of imidacloprid residues in soil with repeated applications. Imidacloprid does not bio-accumulate.^[9]

Toxicology

Imidacloprid, like many insecticides is highly toxic to honeybees with a contact acute LD₅₀ = 0.078 ug a.i./bee and an acute oral LD₅₀ = 0.0039 ug a.i./bee.^[10] Several 10-day chronic oral studies published in peer-reviewed literature have demonstrated NOAEC values ranging from < 4 ppb to 10 ppb in honey bees and bumble bees.^{[11][12][13][14]} The olefine and hydroxy metabolites of imidacloprid, which are found in plants, are very toxic to honeybees.^[14] A large number of published studies have also shown that low levels of imidacloprid and its metabolites produce sublethal and behavioral effects in bees, including disorientation and effects on foraging, learning performance, motor coordination, and food consumption.^{[15][16][17][18][19][20][21][22]} Chronic or long-term toxicity to bees is still not well understood despite the large number of field studies that have been conducted. Effects of imidacloprid on brood and queen are also not known.^[5][23]

Imidacloprid is considered to be moderatly toxic to certain birds. In bobwhite quail (Colinus virginianus), imidacloprid was determined to be moderately toxic with an acute oral LD₅₀ of 152 mg a.i./kg. This is a very large amount that would not likely be found with normal use. Birds seem to avoid treated plants and seeds. It was slightly toxic in a 5-day dietary study with an acute oral LC₅₀ of 1,420 mg a.i./kg diet, a NOAEC of < 69 mg a.i./kg diet, and a LOAEC = 69 mg a.i./kg diet. Birds exposed in studies to these large quantities exhibited ataxia, wing drop, opisthotonos, immobility, hyperactivity, fluid-filled crops and intestines, and discolored livers. In a reproductive toxicity study with bobwhite quail, the NOAEC = 120 mg a.i./kg diet and the LOAEC = 240 mg a.i./kg diet. Eggshell thinning and decreased adult weight were observed at 240 mg a.i./kg diet.^[24][7]

Overall, imidacloprid poses little or no danger to fish and mammals. It requires large doses for adverse effects.

Overdosage

Persons who might orally ingest acute amounts would experience emesis, diaphoresis, drowsiness and disorientation. This would need to be intentional since a large amount would need to be ingested to experience a toxic reaction. In dogs the LD 50 is 450 mg/Kg of body weight. Blood imidacloprid concentrations may be measured to confirm diagnosis in hospitalized patients or to establish the cause of death in postmortem investigations.^[25]

Uses

The most widely used applications for imidacloprid in California are pest control in structures, turf pest control, grape growing, and head and leaf lettuce growing. Other widespread crop uses are rice, grains/cereals including corn (maize), potatoes, vegetables, sugar beets, fruit, cotton, and hops. Target insects include sucking insects (e.g., aphids, whiteflies, leafhoppers and planthoppers, thrips, scales, mealybugs, bugs, psyllids, and phylloxera), beetles (e.g., longhorn beetles, leaf beetles, Colorado potato beetles, rice water-weevils, wireworms, grubs, and flea beetles), and others (e.g., leafminers, some diptera, termites, locusts, and fleas).

As an insecticide spray, it is used on a wide variety of agricultural crops, ornamentals, and turf. It is also marketed for termite control, for flea control on pets, and for household cockroach control.

A systemic insecticide

Imidacloprid, which is a systemic pesticide, is readily taken up by plant roots and translocates up into the plant leaves, pollen, and nectar via the xylem. Insects that eat the leaves or plant fluids may be killed, and pollinators that feed on the pollen and nectar may be exposed to imidacloprid. The products Confidor and Admire are intended for application via irrigation, application to the soil, or on foliage, while Gaucho is intended for use as a seed dressing, applied to the seed before sowing.

Imidacloprid is the active ingredient in Bayer's Advantage brand flea drops.^[26]

See also

• Fipronil
• Insecticide
• Neonicotinoid
• Pesticide toxicity to bees

References

1. ^ Imidacloprid at Extoxnet
2. ^ [1] USDA Forest Service. Imidacloprid: Human Health and Ecological Risk Assessment. Final Report. Dec 28, 2005.
3. ^ [2] National Pesticide Information Center. Imidacloprid: General Fact Sheet. May 2010.
4. ^ Pesticides: Germany bans chemicals linked to honeybee devastation - UK Guardian
5. ^ ^{a b} [3] French Scientific and Technical Report on the Impact of Imidacloprid to Bees.
6. ^ U.S. Pat. No. 4,742,060 - uspto.gov
7. ^ ^{a b} [4] Imidacloprid Cleared Science Reviews. U.S. EPA.
8. ^ Imidacloprid; Pesticide Tolerances for Emergency Exemptions Federal Register: January 26, 2005 (Volume 70, Number 16), Page 3634-3642- epa.gov
9. ^ ^{a b} European Draft Assessment Report: Imidacloprid. Annex B, B.7. February 2006.
10. ^ [5] There are reports of bee die offs around the world and Imidacloprid has been closely scrutinized as a major culprit. However, reports have been released in recent months that have pinned the bee colony collapse disorder on a group of virus and parasites. Bee colony collapse disorder is still happening in France, despite the fact that Imidacloprid and all neonicatoid insecticides have not been used there in more than 10 years. In Australia, where Imidacloprid is widely used, bee colony collapse disorder is not a problem. Environmental Fate and Effects Problem Formulation for the Registration Review of Imidacloprid. Nov 13, 2008. USEPA
11. ^ Moncharmont, F.D., A. Decourtye, C.H. Hantier, O. Pons, M. Pham-Delegue. 2003. Statistical analysis of honeybee survival after chronic exposure to insecticides. Environ Toxicol Chem 22(12): 3088-94
12. ^ Decourtye, A, Lacassie, E, Pham-Delegue, MH (2003) Learning performances of honeybees (Apis mellifera L) are differentially affected by imidacloprid according to the season. Pest Manage Sci 59:269–278
13. ^ Mommaerts, V., Reynders, S., Boulet, J., Besard, L., Sterk, G., Smagghe, G. Risk assessment for side-effects of neonicotinoids against bumblebees with and without impairing foraging behavior. Ecotoxicology 19:207-215
14. ^ ^{a b} Suchail, S., Guez,D., and Belzunces, L.P. 2001. Discrepancy between acute and chronic toxicity induced by imidacloprid and its metabolites in Apis mellifera. Environ. Toxicol. Chem. 20: 2482–2486
15. ^ Yang, E.C., Chuang, Y.C., Chen, Y.L., and Chang, L.H. 2008. Abnormal foraging behavior induced by sublethal dosage of imidacloprid in the honeybee (Hymenoptera: Apidae). J. Econ Entomology 101(6):1743-1748
16. ^ Medrzycki P., Montanari, R., Bortolotti, L., Sabatini, A. G., Maini, S., and Porrini, C. 2003. Effects of imidacloprid administered in sub-lethal doses on honey bee behaviour. Laboratory tests. Bulletin of Insectology 56 (1): 59-62
17. ^ Desneux, N., Decourtye, A., and Delpuech, J-M. 2007. The sublethal effects of pesticides on beneficial arthropods. Annual Review of Entomology 52: 81–106
18. ^ Armengaud, C., Lambin, M., and Gauthier, M. 2002. Effects of imidacloprid on the neural processes of memory. In J. Devillers and M.H. Pham-Delegue(eds). Honey bees: estimating the environmental impact of chemicals (pp. 85-100). New York: Taylor & Francis
19. ^ Bonmatin, J.M., Moineau, I., Charvet, R., Collin, M.E., Fleche, C., and Bengsch, E.R. 2005. Behavior of Imidacloprid in Fields. In E.Lcihtfourse, J. Schwarzbauer, and D. Robert (eds). Toxicity for Honey Bees in Environmental Chemistry: Green Chemistry and Pollutants in Ecosytems. New York: Springer
20. ^ Aliouane, Y., Kacimi El Hassani, A., Gary, V., Armengaud, C., Lambin, M., Gauthier, M. (2009) Subchronic exposure of honeybees to sublethal doses of pesticides: effect on behavior. Environ Toxicol Chem 28:113–122
21. ^ Bortolotti, L., Montanari, R., Marcelino, J., Medrzycki, P., Maini, S., and Porrini, C. 2003. Effects of sub-lethal imidacloprid doses on the homing rate and foraging activity of honey bees. Bulletin of Insectology 56(1): 63-67
22. ^ Decourtye, A., Lacassie, E., Pham-Delegue, MH. (2003) Learning performances of honeybees (Apis mellifera L) are differentially affected by imidacloprid according to the season. Pest Manage Sci 59:269–278
23. ^ [6] Environmental Fate and Effects Problem Formulation for the Registration Review of Imidacloprid. Nov 13, 2008. USEPA
24. ^ [7] Canadian Water Quality Guidelines: Imidacloprid, Scientific Support Document. 2007. Canadian Council of Ministers of the Environment.
25. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 764-765.
26. ^ Advantage for Dogs, Bayer Animal Health Australia

Sources

• PAN Pesticides Database

External links

• Pesticide Information Profile from Extension Toxicology Network
• Breakdown Chart of Imidacloprid forming toxic 2-chloro pyridine
• Imidacloprid Fact Sheet, with 18 References, from the Sierra Club of Canada
• Bayer's "Expert Overview"