Pest Management Science

Pest Manag Sci 64:10991105 (2008)

Mini-review
Applied aspects of neonicotinoid uses in
crop protection
Alfred Elbert,1 Matthias Haas,1 Bernd Springer,1 Wolfgang Thielert2 and Ralf Nauen2
1 Bayer
2 Bayer

CropScience, Development, Agronomic Development, Alfred-Nobel-Strae 50, D-40789 Monheim, Germany

CropScience, Research Insecticides, Biology Insecticides, Alfred-Nobel-Strae 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 and
main differences between neonicotinoid insecticides, including their spectrum of efficacy, are described: use for
vector control, systemic properties and versatile application forms, especially seed treatment. New formulations
have been developed to optimize the bioavailability of neonicotinoids through improved rain fastness, better
retention and spreading of the spray deposit on the leaf surface, combined with higher leaf penetration. Combined
formulations with pyrethroids and other insecticides are also being developed with the aim of broadening the
insecticidal spectrum of neonicotinoids and to replace WHO Class I products from older chemical classes. These
innovative developments for life-cycle management, jointly with the introduction of generic products, will, within
the 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 INTRODUCTION
Neonicotinoids are among the most effective insecticides for the control of sucking insect pests such
as aphids, whiteflies, leaf- and planthoppers, thrips,
some micro lepidoptera and a number of coleopteran
pests. Their broad spectrum of efficacy, together
with systemic and translaminar action, pronounced
residual activity and a unique mode of action,
make the neonicotinoids the most rapidly expanding insecticidal class since the launch of the first
compound, imidacloprid, by Bayer CropScience in
1991.1 3 In the 10 years that followed, six additional
neonicotinoid insecticides were launched: acetamiprid
(Nippon Soda, 1995),4 6 nitenpyram (Sumitomo
Chemical Takeda Agro Company, 1995),7,8 thiamethoxam (Syngenta, 1998),9 11 thiacloprid (Bayer
CropScience, 2000),12 14 clothianidin (Sumitomo
Chemical Takeda Agro Company, Bayer CropScience, 2001)15,16 and dinotefuran (Mitsui Chemicals, 2002).17 The outstanding development of
neonicotinoid insecticides for crop protection, consumer/professional products and animal health markets between 1990 and today reflects the unique
success of this chemical class. The technical profiles and multiple uses of neonicotinoid insecticides
are described using imidacloprid, the forerunner and
most successful molecule from this chemical class, as
an example.

2 STATUS OF NEONICOTINOID INSECTICIDES

2.1 Market environment
The unique success of neonicotinoids is reflected in
their turnover figures in 1990 as compared with 2005.
In 1990, before launch of the first neonicotinoid
insecticide imidacloprid, the agrochemical market,
with a total volume of 7.942 billion, was dominated
by organophosphates (OPs) (43%), pyrethroids (18%)
and carbamates (16%). In 2005, neonicotinoids had
gained 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 and
internal data from Bayer CropScience).
The turnover figures for seed treatment are very
impressive: a niche market of 155 million for
insecticidal seed treatment in 1990 was dominated by
carbamates. It has been developed to a 535 million
market, with a share for neonicotinoid insecticides of
77% in 2005 (Fig. 2).
2.2 Structural diversity, spectrum of efficacy
and systemicity
All neonicotinoids act as agonists on the insect nicotinic acetylcholine receptor (nAChR). The seven
products that were launched between 1991 and
2002 illustrate the high attractiveness and intensive research and development efforts of the
crop protection industry for this chemical class.

Correspondence to: Alfred Elbert, Bayer CropScience, Development, Agronomic Development, Alfred-Nobel-Strae 50, D-40789 Monheim, Germany
E-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 1526498X/2008/$30.00

A Elbert et al.
10
8
16.0

16.3
10.6

bn

6
43.0

25.3

14.2
5.6
28.0

18.0
1.8
21.2

2
0

2005
7.162

1990
Total market ( bn) 7.942
neonicotinoids

carbamates

OPs

pyrethroids

fiproles

others

Figure 1. Development of insecticidal classes in crop protection,

19902005, expressed as percentage of total.

500
400
77.2

mio

300
200
100

77.4

19.3
3.3

1990
Total market( m) 155

neonicotinoids
pyrethroids

9.0
2.8
1.1
9.5

2005
535
carbamates
fiproles

OPs

Figure 2. Development of insecticidal classes in seed treatment,

19902005, expressed as percentage of total.

Neonicotinoids can be classified according to

the pharmacophore as N-nitroguanidines (imidacloprid, thiamethoxam, clothianidin and dinotefuran),
nitromethylenes (nitenpyram) and N-cyano-amidines
(acetamiprid and thiacloprid) (Fig. 3). An excellent

overview on neonicotinoid chemistry, mode of action

and biological activity is given by Jeschke and
Nauen,19,20 Jeschke and Moriya21 and Maienfisch.22
Today, neonicotinoid insecticides represent the
most effective chemical class for the control of sucking
insect pests such as aphids, whiteflies, leaf- and
planthoppers, thrips, some micro lepidoptera and a
number of coleopteran pest species. Furthermore, they
constitute effective tools for controlling parasites of
companion animals/cattle and hygiene pests such as
cockroaches, houseflies and termites.20
This extraordinary spectrum of efficacy, together
with full exploitation of the nAChR, plant systemicity,
long-lasting effect and versatile uses and applications,
have contributed to the unique success of this chemical
class. Older products like the botanical insecticide
(S)-nicotine or cartap act at the same target but
without the neonicotinoid level of effectiveness or
safety.23 Fundamental differences between the nAChR
of insects on the one hand and mammals on the other
confer remarkable selectivity to the neonicotinoids.
One of the main success factors for neonicotinoids
is their plant systemicity. Applied into the soil or to
the seed, the products are taken up via the roots,
are distributed in the plant and give consistent and
long-lasting control of sucking insects. Following
foliar application, neonicotinoids penetrate into the
leaf lamina and control pests on the lower side of
the leaf owing to their good translaminar activity.
Furthermore, they are distributed acropetally (xylem
movement) and can protect new growing shoots.
2.3 Control of pests resistant to conventional
insecticides
Another success factor is the ability of neonicotinoids
to control pests that had developed resistance against
a wide range of insecticides dominating the markets
at that time. A prominent example is the widespread

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

1100

Pest Manag Sci 64:10991105 (2008)

DOI: 10.1002/ps

Global uses of neonicotinoid insecticides

metabolic resistance in aphids to OPs, and to some

extent to carbamates and pyrethroids, owing to high
levels of carboxylesterases E4/FE4 which inactivate
OPs in particular.24 Fig. 4 highlights the results of a
monitoring study conducted in Myzus persicae (Sulzer)
field populations from Great Britain, France, Poland,
Greece and Germany in 1995. High variations in
the response of populations to the tested pyrethroids
and carbamates were found, indicating insufficient
field performance. In contrast, a uniform control of
these resistant field populations with imidacloprid was
achieved.25 The results demonstrate full efficacy under
field conditions, which has been confirmed for aphids
down to the present day.
On the other hand, after 16 years of use, some insect
pests such as the whiteflies Bemisia tabaci (Gennadius) 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 leafhopper Idioscopus clypealis (Lethierry) have developed
resistance to neonicotinoids in some parts of the
world. How individual companies and the Insecticide Resistance Action Committee (IRAC) respond
has been described by McCaffery and Nauen30
and Elbert et al.31 Bayer CropScience has successfully developed resistance management guidelines for
imidacloprid,24 and consequently for its three neonicotinoid insecticides.32
2.4 Neonicotinoids for vector control
The exceptional fit of neonicotinoids for plant virus
vector and hence for disease control was discovered
during the early development of imidacloprid supported by antifeedant effects at sublethal imidacloprid
concentrations.33 Applied as a pellet of 90 g AI unit1 ,
beet mild yellow virus (BMYV) was effectively controlled in sugar beet, as demonstrated in field trials
conducted in the UK between 1989 and 1991.34,35
Outstanding crop protection was achieved with seedtreatment or foliar applications in cereals against
aphids and barley yellow dwarf virus (BYDV),36 39
100

% mortality

80
60
40
20
0
E

F
pyrethroid

P
carbamate

GER

imidacloprid

Figure 4. Control of pests resistant to conventional insecticides.

European field monitoring of imidacloprid in five Myzus persicae
populations 1995, FAO dip test, diagnostic concentration (LC99 ) of
imidacloprid 15 mg L1 , E = England, F = France, P = Poland,
G = Greece, GER = Germany.

Pest Manag Sci 64:10991105 (2008)

DOI: 10.1002/ps

in tobacco against thrips and tomato spotted wilt virus

(TSWV),40,41 in tomato against whiteflies and tomato
yellow leaf curl virus (TYLCV), and in citrus against
glassy-winged sharpshooters as vector for the bacterium Xylella fastidiosa (Wells et al.), to mention just
a few.
2.5 Versatile application methods for
neonicotinoids
The success of this chemical class also relies on
versatile application methods such as application
with irrigation water in drip or drench systems
for vegetables42 or in floating systems for tobacco,
through which long-lasting control of aphids and
whiteflies is achieved.43 Seedling box application in
rice gives excellent control of hopper species and rice
water weevil.42,44 Soil drenching in permanent crops
protects young citrus trees against Phyllocnistis citrella
(Stainton).41,45,46
Applications to the base of the trunk result in
efficient control of Eriosoma lanigerum (Hausmann)
in apple trees. Drench and drip applications are
well suited for the control of Perileucoptera coffeella
(Guerin-Meneville) in coffee41 and Planococcus sp. and
other mealy bug species in grapevines.41 Soil injection
to protect emerging vegetable seedlings against soilinhabiting and sucking pests is common practice in the
USA. Banana weevil and banana thrips are controlled
via trunk and bud injection respectively. Again, this is
only a brief compilation of different application forms
that have been developed or optimized for the use of
neonicotinoids.
Another aspect is the fit of neonicotinoids for IPM
systems, as non-target organisms are not affected
to the extent that has been seen in older chemical
classes. Selectivity for beneficials and pollinators has
especially been optimized by selectivity in space.41,47
Application into the soil by different techniques allows
transport of the insecticide to the pest within the
plant without harming beneficial organisms.48 Another
option is selectivity in time, allowing, for example,
foliar applications against starting pest populations
when beneficial arthropods are still absent.
2.6 Seed treatment with neonicotinoids
New horizons of crop protection have been
opened by the development of seed treatment with
neonicotinoids.41,49 Seed dressing, film coating, pelleting or multilayer coating allow for environmentally
safe and perfect protection of young plants against
insect attack. Today, neonicotinoids are widely used
for seed treatment in cotton, corn, cereals, sugar beet,
oilseed rape and other crops. Table 1 reflects the excellent fit of clothianidin in corn against a broad range of
pest species from different orders such as Coleoptera,
Lepidoptera, Diptera, Homoptera, Hemiptera and
Hymenoptera.15,16
Compared with former soil insecticides, neonicotinoids have a broad spectrum of activity and
long-lasting effects against early-season pests. Each
1101

A Elbert et al.
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.
Agrotis sp.
Delia platura (Meigen)
Oscinella frit (L.)
Rhopalosiphum maidis (Fitch)
Empoasca spp.
Macrosteles spp.
Zyginida spp.
Blissus leucopterus (Say)
Nezara viridula (L.)
Solenopsis sp.

Lepidoptera
Diptera
Homoptera

Hemiptera
Hymenoptera

individual plant is protected from the very beginning

by the use of accurate application rates per seed.
This results in low rates per field unit. Older products with high dose rates for whole-area or in-furrow
applications have been replaced. Impacts on the environment have been reduced; seed treatments with
neonicotinoids fit into IPM programmes and reduce
the operator exposure to a minimum.49
2.7 Profiles of neonicotinoid insecticides
Key crops for neonicotinoids are vegetables, pome
and stone fruit, citrus, rice, cotton, corn, potato, sugar
beet, oilseed rape and soybean, among many others.
Table 2 characterizes all seven neonicotinoids in a
comprehensive way. The numbers of crop uses are
indicated (e.g. foliar and soil applications in potato
are defined as two crop uses). Besides the typical
neonicotinoid pest spectrum described above, each
product has its specific target spectrum, mentioned
here under additional spectrum. The products also
differ considerably with respect to soil and seedtreatment uses, as soil stability is limited for some
of them. Uses are classified as follows: +++ broad,
++ good, + limited, not relevant.
Following its market launch in 1991, imidacloprid
gained registration for over 140 crop uses in
more than 120 countries under the main brands

Confidor , Admire and Gaucho . Its versatility

allows worldwide application against sucking and
many chewing insect pests on all major crops
including cotton, sugar crops, oilseed rape, cereals,
rice, fruit, vegetables and ornamentals. In addition
to crop protection, imidacloprid and others also
find application in the animal health, lawn, home
and garden domains.20 Since patent expiry in
most countries in 2006, generic products based on
imidacloprid have entered the market and led to a
broader scale of use of this compound. However, this
will definitely facilitate the development and spread of
resistance to neonicotinoid insecticides, because it has
been demonstrated that in many cases the whole class
is affected once resistance to imidacloprid develops.50
It is anticipated that imidacloprid, as the largest-selling
insecticide in the world, will also continue to grow in
the future.
The major success of nitenpyram, developed by
Takeda jointly with Syngenta and launched in 1995,
is cat flea control in the animal health domain.51
However, additional uses for the control of sucking
insects in rice, fruit, tea, vegetables and field crops
in Japan have been developed under the commercial
name Bestguard .
Launched in Japan in 1995, Nippon Sodas
acetamiprid achieved registration in many countries
in Europe and the Americas. Today, brands such
as Mospilan and others are registered in cotton,
vegetables, potato, orchards for codling moth control,
vines, citrus, tea and ornamentals. The product is also
used for the control of termites and household pests.
Launched in 1998 by Syngenta, thiamethoxam is
marketed as Actara for foliar and as Cruiser for
seed-treatment uses; to date, thiamethoxam holds
registration for 115 crop uses in at least 64 countries
on a wide range of crops such as vegetables, potatoes,
rice, cotton, fruit, tobacco and cereals. It is the second
biggest neonicotinoid in terms of sales. The pest
spectrum includes all major sucking pests, as well
as some chewing and soil-living pests.
Thiacloprid, Bayer CropSciences second neonicotinoid launched under the brand name Calypso in
2000, acts against sucking and chewing pests on crops
such as pome fruit, cotton, vegetables, oilseed rape,
cereals, potato, rice and ornamentals. Besides aphids,
various species of beetles, lepidopteran leafminers and
Cydia 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
Nitenpyram
Acetamiprid
Thiamethoxam
Thiacloprid
Clothianidin
Dinotefuran

140
12
60
115
50
40
35

Thrips, mealybugs, leafminers, termites

Codling moth, diamondback moth

Mealybugs, plant bugs, leafminers, termites
Codling moth, pollen beetle
Woolly aphid, oriental fruit moth, corn rootworm
Soft scales, thrips, mealybugs

++ (+)
++
+++
+++
+++
++ (+)
+++

+++
+
+
+++

++
++

++ (+)

++

+++

1102

Pest Manag Sci 64:10991105 (2008)

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Global uses of neonicotinoid insecticides

has a favourable beneficial profile and is bee safe, and

hence it can also be spayed on flowering crops.52,53
Clothianidin, a joint development of Sumitomo
Chemical Takeda Agro Company and Bayer CropScience, was launched in 2002. The product covers
a broad pest spectrum, which results in uses as a
seed-treatment (Poncho ), soil-applied (Dantotsu )
or foliar-applied (Dantop ) insecticide. Main targets
were identified in the classes of Coleoptera, Diptera,
Hemiptera and to some extent Lepidoptera. The products target crops are rice, cereals, corn, oilseed rape,
fruit, potatoes, sugar beets and vegetables.
Developed and launched in 2002 by Mitsui
Chemicals for use against sucking pests in vegetables,
apples, sugar beets and rice in Japan under the trade
name Starkle , dinotefuran is also marketed in the
USA under the brand names Safari in ornamentals
and Venom in fruit, cotton, potato and vegetables.
Further sales growth is expected after its launch in
European countries.

3 OUTLOOK
3.1 New formulation concept for
neonicotinoids: oil dispersion
The distribution of systemic insecticides largely
depends on conditions during and after application.
Often, even when good delivery to the plant
surface is ensured after spray application, there are
limitations for maximum systemic performance if
foliar penetration is low. Bayer CropScience has
developed the new formulation technology O-TEQ
(oil dispersion, OD) for foliar application of its
neonicotinoids Confidor and Calypso .54 56 The
O-TEQ formulations facilitate leaf penetration,
particularly under suboptimal conditions for foliar
uptake. Systemicity and rain fastness of neonicotinoids
reach a level not demonstrated previously, and thus a
superior bioavailability for systemic active ingredients
is obtained. In comparison with conventional SC
formulation retention, leaf coverage and spreading of
the spray deposit on the leaf surface are improved.
Runoff is minimized, rain fastness is higher, and
penetration through the cuticle and translocation
within the plant are optimized.57
3.2 Broad-spectrum neonicotinoid
combinations as replacements for WHO Class I
insecticides
New formulations are also being developed with
the aim of broadening the insecticidal spectrum
of neonicotinoids and to substitute WHO Class I
products from older chemical classes. A few examples
are given below.
Confidor S , a combination of imidacloprid
and cyfluthrin, is a formulation for the control
of tobacco pests in South America; Leverage ,
another combination of the aforementioned active
ingredients, is a well-established brand in the USA
for broad-spectrum pest control in cotton; Muralla ,
Pest Manag Sci 64:10991105 (2008)
DOI: 10.1002/ps

a combination of imidacloprid and deltamethrin, is

a regional solution for Central America and Chile
for vegetable and rice; Confidor Energy , another
combination of imidacloprid and deltamethrin, is
used in Europe for broad-spectrum insect control in
vegetables, potatoes, tobacco, sugar beets and cereals;
Connect consists of a combination of imidacloprid
and -cyfluthrin and is targeted against stinkbugs
and other pests in soybean; and finally Solomon
and Thunder , combinations of imidacloprid and cyfluthrin, are cost-competitive solutions for African
and Asian markets.
3.3 Foliar sprays for higher yields during stress
Plant growth and yield are greatly influenced by
environmental stress to which crops are continuously
exposed. Stress can be biotic, imposed by insect
pests, weeds and pathogens, or abiotic, arising from
an excess or deficit in the physical or chemical
environment such as cold, heat, oxygen deficiency
or drought. Field-trial analyses indicated that multiple
foliar applications of imidacloprid improved health
and increased growth even in situations without insect
infestations. Water-deficit field studies confirmed the
potential of Trimax , an optimized imidacloprid
formulation to moderate water stress in plants with
an average lint yield increase in cotton of 10%.58
The response of Trimax -treated plants to pure
abiotic stress stimuli was investigated in detail in
order to elucidate the underlying physiological and
biochemical mechanisms: for barley, a significant
leaf-area growth improvement following imidacloprid
soil application could be demonstrated after shortterm drought stress. Plants from these tests were
analysed at different elapsed time intervals using DNA
microarrays, a tool for profiling gene activity in plants.
Firstly, the expression level of drought-stress marker
genes in barley is significantly delayed in imidaclopridtreated plants, suggesting a mitigation of drought
stress.
Secondly, in imidacloprid-treated plants, photosynthesis-related genes are simultaneously expressed
at a higher level, so keeping the energy production
ongoing, whereas in untreated plants photosynthesis
declines more rapidly.
Finally, a most surprising effect of imidaclopridtreated barley plants was observed: in contrast to
non-treated plants, numerous pathogenesis-related
proteins were found to be overexpressed, explaining field observations of synergistic fungicidal and
bactericidal effects.58
Consequently, in addition to its insecticidal properties, a stress shield mode of action of imidacloprid was
identified. It supports plants in moderating the effects
of abiotic and biotic stress.

4 CONCLUSIONS
Neonicotinoids are a unique chemical class for
sucking-insect pest control owing to their broad
1103

A Elbert et al.

spectrum of activity. Acting as agonists on nAChR,

they control pest populations resistant to conventional
insecticides and exhibit long-lasting residual effects,
especially in seed-treatment and soil application.
Excellent plant virus vector control, high systemicity
and versatile application methods, combined with high
operator and consumer safety, make these products
ideal tools for modern agriculture.
Over the last 3 year period, sales of the total group
have nearly doubled, and future expansion will be
driven by growth of the established neonicotinoids.
The class will further benefit from OP restrictions.18
Generic competition will lead to price erosions, which
also will open new opportunities in low-price markets.
Combined with active life-cycle management such
as optimized formulations and new combinations,
neonicotinoids will be the most important chemical
class within the next few years in crop protection for
insect control.
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