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Pest Management Science Pest Manag Sci 64:1099–1105 (2008)

Mini-reviewApplied aspects of neonicotinoid uses incrop protection†

Alfred Elbert,1∗ Matthias Haas,1 Bernd Springer,1 Wolfgang Thielert2 and Ralf Nauen2

1Bayer CropScience, Development, Agronomic Development, Alfred-Nobel-Straße 50, D-40789 Monheim, Germany2Bayer CropScience, Research Insecticides, Biology Insecticides, Alfred-Nobel-Straße 50, D-40789 Monheim, Germany

Abstract: Neonicotinoid insecticides comprise seven commercially marketed active ingredients: imidacloprid,acetamiprid, nitenpyram, thiamethoxam, thiacloprid, clothianidin and dinotefuran. The technical profiles andmain differences between neonicotinoid insecticides, including their spectrum of efficacy, are described: use forvector control, systemic properties and versatile application forms, especially seed treatment. New formulationshave been developed to optimize the bioavailability of neonicotinoids through improved rain fastness, betterretention and spreading of the spray deposit on the leaf surface, combined with higher leaf penetration. Combinedformulations with pyrethroids and other insecticides are also being developed with the aim of broadening theinsecticidal spectrum of neonicotinoids and to replace WHO Class I products from older chemical classes. Theseinnovative developments for life-cycle management, jointly with the introduction of generic products, will, withinthe next few years, turn neonicotinoids into the most important chemical class in crop protection. 2008 Society of Chemical Industry

Keywords: neonicotinoid insecticides; imidacloprid; thiacloprid; clothianidin; thiamethoxam; acetamiprid;nitenpyram; dinotefuran

1 INTRODUCTIONNeonicotinoids are among the most effective insec-ticides for the control of sucking insect pests suchas aphids, whiteflies, leaf- and planthoppers, thrips,some micro lepidoptera and a number of coleopteranpests. Their broad spectrum of efficacy, togetherwith systemic and translaminar action, pronouncedresidual activity and a unique mode of action,make the neonicotinoids the most rapidly expand-ing insecticidal class since the launch of the firstcompound, imidacloprid, by Bayer CropScience in1991.1–3 In the 10 years that followed, six additionalneonicotinoid insecticides were launched: acetamiprid(Nippon Soda, 1995),4–6 nitenpyram (SumitomoChemical Takeda Agro Company, 1995),7,8 thi-amethoxam (Syngenta, 1998),9–11 thiacloprid (BayerCropScience, 2000),12–14 clothianidin (SumitomoChemical Takeda Agro Company, Bayer Crop-Science, 2001)15,16 and dinotefuran (Mitsui Chem-icals, 2002).17 The outstanding development ofneonicotinoid insecticides for crop protection, con-sumer/professional products and animal health mar-kets between 1990 and today reflects the uniquesuccess of this chemical class. The technical pro-files and multiple uses of neonicotinoid insecticidesare described using imidacloprid, the forerunner andmost successful molecule from this chemical class, asan example.

2 STATUS OF NEONICOTINOID INSECTICIDES2.1 Market environmentThe unique success of neonicotinoids is reflected intheir turnover figures in 1990 as compared with 2005.In 1990, before launch of the first neonicotinoidinsecticide imidacloprid, the agrochemical market,with a total volume of ¤7.942 billion, was dominatedby organophosphates (OPs) (43%), pyrethroids (18%)and carbamates (16%). In 2005, neonicotinoids hadgained a market share of 16% from a total market of¤7.162 billion, mainly at the expense of OPs (25%)and carbamates (10%) (Fig. 1) (reference 18 andinternal data from Bayer CropScience).

The turnover figures for seed treatment are veryimpressive: a niche market of ¤155 million forinsecticidal seed treatment in 1990 was dominated bycarbamates. It has been developed to a ¤535 millionmarket, with a share for neonicotinoid insecticides of77% in 2005 (Fig. 2).

2.2 Structural diversity, spectrum of efficacyand systemicityAll neonicotinoids act as agonists on the insect nico-tinic acetylcholine receptor (nAChR). The sevenproducts that were launched between 1991 and2002 illustrate the high attractiveness and inten-sive research and development efforts of thecrop protection industry for this chemical class.

∗ Correspondence to: Alfred Elbert, Bayer CropScience, Development, Agronomic Development, Alfred-Nobel-Straße 50, D-40789 Monheim, GermanyE-mail: [email protected]†Extended version of a presentation given at the XVI International Plant Protection Congress, Glasgow, UK, 17 October 2007(Received 26 February 2008; accepted 7 April 2008)Published online 16 June 2008; DOI: 10.1002/ps.1616

2008 Society of Chemical Industry. Pest Manag Sci 1526–498X/2008/$30.00

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Neonicotinoids can be classified according tothe pharmacophore as N-nitroguanidines (imidaclo-prid, thiamethoxam, clothianidin and dinotefuran),nitromethylenes (nitenpyram) and N-cyano-amidines(acetamiprid and thiacloprid) (Fig. 3). An excellent

overview on neonicotinoid chemistry, mode of actionand biological activity is given by Jeschke andNauen,19,20 Jeschke and Moriya21 and Maienfisch.22

Today, neonicotinoid insecticides represent themost effective chemical class for the control of suckinginsect pests such as aphids, whiteflies, leaf- andplanthoppers, thrips, some micro lepidoptera and anumber of coleopteran pest species. Furthermore, theyconstitute effective tools for controlling parasites ofcompanion animals/cattle and hygiene pests such ascockroaches, houseflies and termites.20

This extraordinary spectrum of efficacy, togetherwith full exploitation of the nAChR, plant systemicity,long-lasting effect and versatile uses and applications,have contributed to the unique success of this chemicalclass. Older products like the botanical insecticide(S)-nicotine or cartap act at the same target butwithout the neonicotinoid level of effectiveness orsafety.23 Fundamental differences between the nAChRof insects on the one hand and mammals on the otherconfer remarkable selectivity to the neonicotinoids.

One of the main success factors for neonicotinoidsis their plant systemicity. Applied into the soil or tothe seed, the products are taken up via the roots,are distributed in the plant and give consistent andlong-lasting control of sucking insects. Followingfoliar application, neonicotinoids penetrate into theleaf lamina and control pests on the lower side ofthe leaf owing to their good translaminar activity.Furthermore, they are distributed acropetally (xylemmovement) and can protect new growing shoots.

2.3 Control of pests resistant to conventionalinsecticidesAnother success factor is the ability of neonicotinoidsto control pests that had developed resistance againsta wide range of insecticides dominating the marketsat that time. A prominent example is the widespread

Figure 3. Structural diversity of neonicotinoid insecticides and year of market introduction.

1100 Pest Manag Sci 64:1099–1105 (2008)DOI: 10.1002/ps

Global uses of neonicotinoid insecticides

metabolic resistance in aphids to OPs, and to someextent to carbamates and pyrethroids, owing to highlevels of carboxylesterases E4/FE4 which inactivateOPs in particular.24 Fig. 4 highlights the results of amonitoring study conducted in Myzus persicae (Sulzer)field populations from Great Britain, France, Poland,Greece and Germany in 1995. High variations inthe response of populations to the tested pyrethroidsand carbamates were found, indicating insufficientfield performance. In contrast, a uniform control ofthese resistant field populations with imidacloprid wasachieved.25 The results demonstrate full efficacy underfield conditions, which has been confirmed for aphidsdown to the present day.

On the other hand, after 16 years of use, some insectpests such as the whiteflies Bemisia tabaci (Genna-dius) and Trialeurodes vaporariorum (Westwood),26–28

the brown planthopper Nilaparvata lugens (Stal),29

the Colorado potato beetle Leptinotarsa decemlineata(Say)29 and a few others like the mango leafhop-per Idioscopus clypealis (Lethierry) have developedresistance to neonicotinoids in some parts of theworld. How individual companies and the Insecti-cide Resistance Action Committee (IRAC) respondhas been described by McCaffery and Nauen30

and Elbert et al.31 Bayer CropScience has success-fully developed resistance management guidelines forimidacloprid,24 and consequently for its three neoni-cotinoid insecticides.32

2.4 Neonicotinoids for vector controlThe exceptional fit of neonicotinoids for plant virusvector and hence for disease control was discoveredduring the early development of imidacloprid sup-ported by antifeedant effects at sublethal imidaclopridconcentrations.33 Applied as a pellet of 90 g AI unit−1,beet mild yellow virus (BMYV) was effectively con-trolled in sugar beet, as demonstrated in field trialsconducted in the UK between 1989 and 1991.34,35

Outstanding crop protection was achieved with seed-treatment or foliar applications in cereals againstaphids and barley yellow dwarf virus (BYDV),36–39

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Figure 4. Control of pests resistant to conventional insecticides.European field monitoring of imidacloprid in five Myzus persicaepopulations 1995, FAO dip test, diagnostic concentration (LC99) ofimidacloprid 15 mg L−1, E = England, F = France, P = Poland,G = Greece, GER = Germany.

in tobacco against thrips and tomato spotted wilt virus(TSWV),40,41 in tomato against whiteflies and tomatoyellow leaf curl virus (TYLCV), and in citrus againstglassy-winged sharpshooters as vector for the bac-terium Xylella fastidiosa (Wells et al.), to mention justa few.

2.5 Versatile application methods forneonicotinoidsThe success of this chemical class also relies onversatile application methods such as applicationwith irrigation water in drip or drench systemsfor vegetables42 or in floating systems for tobacco,through which long-lasting control of aphids andwhiteflies is achieved.43 Seedling box application inrice gives excellent control of hopper species and ricewater weevil.42,44 Soil drenching in permanent cropsprotects young citrus trees against Phyllocnistis citrella(Stainton).41,45,46

Applications to the base of the trunk result inefficient control of Eriosoma lanigerum (Hausmann)in apple trees. Drench and drip applications arewell suited for the control of Perileucoptera coffeella(Guerin-Meneville) in coffee41 and Planococcus sp. andother mealy bug species in grapevines.41 Soil injectionto protect emerging vegetable seedlings against soil-inhabiting and sucking pests is common practice in theUSA. Banana weevil and banana thrips are controlledvia trunk and bud injection respectively. Again, this isonly a brief compilation of different application formsthat have been developed or optimized for the use ofneonicotinoids.

Another aspect is the fit of neonicotinoids for IPMsystems, as non-target organisms are not affectedto the extent that has been seen in older chemicalclasses. Selectivity for beneficials and pollinators hasespecially been optimized by selectivity in space.41,47

Application into the soil by different techniques allowstransport of the insecticide to the pest within theplant without harming beneficial organisms.48 Anotheroption is selectivity in time, allowing, for example,foliar applications against starting pest populationswhen beneficial arthropods are still absent.

2.6 Seed treatment with neonicotinoidsNew horizons of crop protection have beenopened by the development of seed treatment withneonicotinoids.41,49 Seed dressing, film coating, pel-leting or multilayer coating allow for environmentallysafe and perfect protection of young plants againstinsect attack. Today, neonicotinoids are widely usedfor seed treatment in cotton, corn, cereals, sugar beet,oilseed rape and other crops. Table 1 reflects the excel-lent fit of clothianidin in corn against a broad range ofpest species from different orders such as Coleoptera,Lepidoptera, Diptera, Homoptera, Hemiptera andHymenoptera.15,16

Compared with former soil insecticides, neoni-cotinoids have a broad spectrum of activity andlong-lasting effects against early-season pests. Each

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Table 1. Clothianidin seed treatment for the control of insect pests in

corn

Insect order Pest species

Coleoptera Diabrotica spp.Melanotus spp.Agriotes spp.Chaetocnema pulicania (Mersheimer)Colaspis brunnea (F.)Popillia japonica (Newman)Heteronychus arator (F.)Tanymecus spp.

Lepidoptera Agrotis sp.Diptera Delia platura (Meigen)

Oscinella frit (L.)Homoptera Rhopalosiphum maidis (Fitch)

Empoasca spp.Macrosteles spp.Zyginida spp.

Hemiptera Blissus leucopterus (Say)Nezara viridula (L.)

Hymenoptera Solenopsis sp.

individual plant is protected from the very beginningby the use of accurate application rates per seed.This results in low rates per field unit. Older prod-ucts with high dose rates for whole-area or in-furrowapplications have been replaced. Impacts on the envi-ronment have been reduced; seed treatments withneonicotinoids fit into IPM programmes and reducethe operator exposure to a minimum.49

2.7 Profiles of neonicotinoid insecticidesKey crops for neonicotinoids are vegetables, pomeand stone fruit, citrus, rice, cotton, corn, potato, sugarbeet, oilseed rape and soybean, among many others.Table 2 characterizes all seven neonicotinoids in acomprehensive way. The numbers of crop uses areindicated (e.g. foliar and soil applications in potatoare defined as two crop uses). Besides the typicalneonicotinoid pest spectrum described above, eachproduct has its specific target spectrum, mentionedhere under additional spectrum. The products alsodiffer considerably with respect to soil and seed-treatment uses, as soil stability is limited for someof them. Uses are classified as follows: +++ broad,++ good, + limited, − not relevant.

Following its market launch in 1991, imidaclopridgained registration for over 140 crop uses inmore than 120 countries under the main brands

Confidor, Admire and Gaucho. Its versatilityallows worldwide application against sucking andmany chewing insect pests on all major cropsincluding cotton, sugar crops, oilseed rape, cereals,rice, fruit, vegetables and ornamentals. In additionto crop protection, imidacloprid and others alsofind application in the animal health, lawn, homeand garden domains.20 Since patent expiry inmost countries in 2006, generic products based onimidacloprid have entered the market and led to abroader scale of use of this compound. However, thiswill definitely facilitate the development and spread ofresistance to neonicotinoid insecticides, because it hasbeen demonstrated that in many cases the whole classis affected once resistance to imidacloprid develops.50

It is anticipated that imidacloprid, as the largest-sellinginsecticide in the world, will also continue to grow inthe future.

The major success of nitenpyram, developed byTakeda jointly with Syngenta and launched in 1995,is cat flea control in the animal health domain.51

However, additional uses for the control of suckinginsects in rice, fruit, tea, vegetables and field cropsin Japan have been developed under the commercialname Bestguard.

Launched in Japan in 1995, Nippon Soda’sacetamiprid achieved registration in many countriesin Europe and the Americas. Today, brands suchas Mospilan and others are registered in cotton,vegetables, potato, orchards for codling moth control,vines, citrus, tea and ornamentals. The product is alsoused for the control of termites and household pests.

Launched in 1998 by Syngenta, thiamethoxam ismarketed as Actara for foliar and as Cruiser forseed-treatment uses; to date, thiamethoxam holdsregistration for 115 crop uses in at least 64 countrieson a wide range of crops such as vegetables, potatoes,rice, cotton, fruit, tobacco and cereals. It is the secondbiggest neonicotinoid in terms of sales. The pestspectrum includes all major sucking pests, as wellas some chewing and soil-living pests.

Thiacloprid, Bayer CropScience’s second neonicoti-noid launched under the brand name Calypso in2000, acts against sucking and chewing pests on cropssuch as pome fruit, cotton, vegetables, oilseed rape,cereals, potato, rice and ornamentals. Besides aphids,various species of beetles, lepidopteran leafminers andCydia pomonella (L.) are controlled. The compound

Table 2. Biological profiles of neonicotinoid insecticides

Neonicotinoid Number of crop uses Additional spectrum Foliar uses Soil uses Seed treatment

Imidacloprid 140 Thrips, mealybugs, leafminers, termites ++ (+) +++ ++ (+)Nitenpyram 12 – ++ + −Acetamiprid 60 Codling moth, diamondback moth +++ + −Thiamethoxam 115 Mealybugs, plant bugs, leafminers, termites +++ +++ ++Thiacloprid 50 Codling moth, pollen beetle +++ − −Clothianidin 40 Woolly aphid, oriental fruit moth, corn rootworm ++ (+) ++ +++Dinotefuran 35 Soft scales, thrips, mealybugs +++ ++ −



has a favourable beneficial profile and is bee safe, andhence it can also be spayed on flowering crops.52,53

Clothianidin, a joint development of SumitomoChemical Takeda Agro Company and Bayer Crop-Science, was launched in 2002. The product coversa broad pest spectrum, which results in uses as aseed-treatment (Poncho), soil-applied (Dantotsu)or foliar-applied (Dantop) insecticide. Main targetswere identified in the classes of Coleoptera, Diptera,Hemiptera and to some extent Lepidoptera. The pro-duct’s target crops are rice, cereals, corn, oilseed rape,fruit, potatoes, sugar beets and vegetables.

Developed and launched in 2002 by MitsuiChemicals for use against sucking pests in vegetables,apples, sugar beets and rice in Japan under the tradename Starkle, dinotefuran is also marketed in theUSA under the brand names Safari in ornamentalsand Venom in fruit, cotton, potato and vegetables.Further sales growth is expected after its launch inEuropean countries.

3 OUTLOOK3.1 New formulation concept forneonicotinoids: oil dispersionThe distribution of systemic insecticides largelydepends on conditions during and after application.Often, even when good delivery to the plantsurface is ensured after spray application, there arelimitations for maximum systemic performance iffoliar penetration is low. Bayer CropScience hasdeveloped the new formulation technology O-TEQ

(oil dispersion, OD) for foliar application of itsneonicotinoids Confidor and Calypso.54–56 TheO-TEQ formulations facilitate leaf penetration,particularly under suboptimal conditions for foliaruptake. Systemicity and rain fastness of neonicotinoidsreach a level not demonstrated previously, and thus asuperior bioavailability for systemic active ingredientsis obtained. In comparison with conventional SCformulation retention, leaf coverage and spreading ofthe spray deposit on the leaf surface are improved.Runoff is minimized, rain fastness is higher, andpenetration through the cuticle and translocationwithin the plant are optimized.57

3.2 Broad-spectrum neonicotinoidcombinations as replacements for WHO Class IinsecticidesNew formulations are also being developed withthe aim of broadening the insecticidal spectrumof neonicotinoids and to substitute WHO Class Iproducts from older chemical classes. A few examplesare given below.

Confidor S, a combination of imidaclopridand cyfluthrin, is a formulation for the controlof tobacco pests in South America; Leverage,another combination of the aforementioned activeingredients, is a well-established brand in the USAfor broad-spectrum pest control in cotton; Muralla,

a combination of imidacloprid and deltamethrin, isa regional solution for Central America and Chilefor vegetable and rice; Confidor Energy, anothercombination of imidacloprid and deltamethrin, isused in Europe for broad-spectrum insect control invegetables, potatoes, tobacco, sugar beets and cereals;Connect consists of a combination of imidaclopridand β-cyfluthrin and is targeted against stinkbugsand other pests in soybean; and finally Solomon

and Thunder, combinations of imidacloprid and β-cyfluthrin, are cost-competitive solutions for Africanand Asian markets.

3.3 Foliar sprays for higher yields during stressPlant growth and yield are greatly influenced byenvironmental stress to which crops are continuouslyexposed. Stress can be biotic, imposed by insectpests, weeds and pathogens, or abiotic, arising froman excess or deficit in the physical or chemicalenvironment such as cold, heat, oxygen deficiencyor drought. Field-trial analyses indicated that multiplefoliar applications of imidacloprid improved healthand increased growth even in situations without insectinfestations. Water-deficit field studies confirmed thepotential of Trimax, an optimized imidaclopridformulation to moderate water stress in plants withan average lint yield increase in cotton of 10%.58

The response of Trimax-treated plants to pureabiotic stress stimuli was investigated in detail inorder to elucidate the underlying physiological andbiochemical mechanisms: for barley, a significantleaf-area growth improvement following imidaclopridsoil application could be demonstrated after short-term drought stress. Plants from these tests wereanalysed at different elapsed time intervals using DNAmicroarrays, a tool for profiling gene activity in plants.

Firstly, the expression level of drought-stress markergenes in barley is significantly delayed in imidacloprid-treated plants, suggesting a mitigation of droughtstress.

Secondly, in imidacloprid-treated plants, photo-synthesis-related genes are simultaneously expressedat a higher level, so keeping the energy productionongoing, whereas in untreated plants photosynthesisdeclines more rapidly.

Finally, a most surprising effect of imidacloprid-treated barley plants was observed: in contrast tonon-treated plants, numerous pathogenesis-relatedproteins were found to be overexpressed, explain-ing field observations of synergistic fungicidal andbactericidal effects.58

Consequently, in addition to its insecticidal proper-ties, a stress shield mode of action of imidacloprid wasidentified. It supports plants in moderating the effectsof abiotic and biotic stress.

4 CONCLUSIONSNeonicotinoids are a unique chemical class forsucking-insect pest control owing to their broad


A Elbert et al.

spectrum of activity. Acting as agonists on nAChR,they control pest populations resistant to conventionalinsecticides and exhibit long-lasting residual effects,especially in seed-treatment and soil application.Excellent plant virus vector control, high systemicityand versatile application methods, combined with highoperator and consumer safety, make these productsideal tools for modern agriculture.

Over the last 3 year period, sales of the total grouphave nearly doubled, and future expansion will bedriven by growth of the established neonicotinoids.The class will further benefit from OP restrictions.18

Generic competition will lead to price erosions, whichalso will open new opportunities in low-price markets.Combined with active life-cycle management suchas optimized formulations and new combinations,neonicotinoids will be the most important chemicalclass within the next few years in crop protection forinsect control.

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