Rotation of insecticide products with different modes of action as a

Rotation of insecticide products with different
modes of action as a strategy for minimizing
insecticide resistance
Development of pest insect populations resistant to active ingredients in
insecticides is well documented. For example, researchers tracked the
occurrence of a specific genetic mutation implicated in resistance to pyrethroid
insecticides in horn flies.1
The genetic mutation was found in horn fly populations in cattle operations
that were geographically isolated from each other, indicating the mutation
The insecticide strategy
an operation uses can
affect insecticide
resistance.
manifests independently. Researchers further determined the mutation was
likely associated with the insecticide strategy used at the operations in which it
was found.1 Clearly, the ways insecticides are used can contribute to selection
pressures that yield resistant populations.
In the example above, the operations relied too heavily on pyrethroid
insecticides, using them year after year, and pyrethroid-resistant horn flies
emerged. This paper explains in detail what insecticide resistance is, how
it can happen, and how to help keep it from happening by using good
insecticide resistance management practices.
Resistance and susceptibility
Resistance is defined by the Insecticide Resistance Action Committee (IRAC)
as “a heritable change in the sensitivity of a pest population that is reflected in
the repeated failure of a product to achieve the expected level of control when
used according to the label recommendation for that pest species.”2
Resistance is heritable; it is the result of selection pressure. Just as cattle
Insecticide resistance
is the repeated, absolute
failure of an insecticide to
produce the intended
effect on an insect
population as a result
of selection pressure.
Reduced susceptibility
is not absolute failure
of a product, but reduced
sensitivity to it relative to
previous sensitivity.
producers use selection to improve herds, they may also inadvertently use the
same mechanism to breed resistant populations of pests.3
Resistance is the “repeated failure” of a product — that is, the product’s absolute
failure, not merely an increase in the amount of time or product that is required to
achieve the expected level of control.
Susceptibility, on the other hand, is the degree of sensitivity of a pest to a
product, reflected in the efficiency of the product’s ability to achieve the expected
level of control. Susceptibility is not an absolute value; rather, it is a relative value
along a continuum.
A product will fail when applied to a resistant pest because the product’s mode
If an insecticide’s MOA
no longer affects
the target pest in the
expected way at all —
regardless of dosage
or duration of exposure —
then the pest is
resistant to it.
of action (MOA) does not affect the pest in the expected way. In the face of true
resistance, product dosage and duration of exposure are irrelevant.
When applied to a pest with reduced susceptibility, on the other hand, the MOA
still affects the pest in the expected way and produces the expected level of
control, although it may require more time or a higher dose in order to do so.
In other words, as long as a product’s MOA produces the intended effect on a
pest, the pest has some susceptibility to it and is not resistant.
Mechanisms of resistance
There are several ways resistance can emerge. The active ingredient of a
particular product is intended to act on a specific site within a pest. If that target
site is genetically modified in a way that interferes with the ingredient’s activity on
the site, then the product may no longer produce the intended effect on that pest.
Target site resistance is the type found in the research cited at the beginning of
this paper. The genetic mutation interfered with the pyrethroid insecticides’ ability
to act on the target site, thus impeding the insecticides’ MOA and rendering them
ineffective on pests expressing the mutation.1
Another type of resistance is metabolic, caused by a genetic change that
enhances the pest’s ability to metabolize the active ingredient. An insecticide to
which a pest has developed metabolic resistance may fail without the addition
of a synergist such as piperonyl butoxide (PBO), which inhibits the activity of
enzymes involved in metabolic resistance.
Insecticide resistance
can emerge in several
ways, including genetic
alteration of either the
site targeted by the
active ingredient or
the pest’s ability to
metabolize it.
Active ingredients
in insecticides are
grouped by MOA.
Resistance to an
insecticide increases
the likelihood of
cross-resistance to
other insecticides in
the same MOA group.
Resistance may also be caused by a change that makes it difficult for the active
ingredient to sufficiently penetrate the pest. Even a change in a pest’s behavior
may lead to resistance.2
MOA groups and cross-resistance
IRAC has classified insecticide active ingredients by MOA. Active ingredients in
the same IRAC group all have the same MOA and act on the same target site.
The difference between MOAs of different groups can be significant. For
example, compounds in MOA group 3* are sodium channel modulators. They
disrupt a specific function of the pest’s nerves, so the pest becomes paralyzed
and dies. Compounds in MOA group 7*, juvenile hormone mimics, do something
completely different. The compounds in this group prevent immature insects
from maturing to adult insects, so they die without reproducing.
Group 21*, mitochondrial complex I electron transport inhibitors, includes
compounds with yet another distinct MOA: killing pests by preventing their cells
from being able to use energy.
If a pest is resistant to one active ingredient in a particular MOA group, there is an
increased likelihood of resistance to others in the same group, since they all have
the same MOA. This is called cross-resistance.
Subgroups
Compounds in two
different subgroups of
the same group have:
Many MOA groups are further divided into subgroups, distinct chemical classes
- Less risk of metabolic cross-resistance
compared with
compounds within
the same subgroup
Compounds in two subgroups of the same group are structurally different
- Less risk of target-site
cross-resistance to
the MOA compared
with compounds within
the same subgroup
same subgroup. However, there is higher risk of these types of cross-resistance
that share the same MOA and target site.
enough from each other that there is less risk of metabolic cross-resistance,
compared with compounds within the same subgroup. There’s also lower risk of
target-site cross-resistance to the MOA, compared with compounds within the
compared with compounds from completely different groups.
- Higher risk of these
types of cross-resistance
compared with
compounds from
completely different
groups
Zetacypermethrin
Bifenthrin
Betacyfluthrin
Alphacypermethrin
Cyfluthrin
Pyrethrins
(Pyrethrum)
Esfenvalerate
Cypermethrin
Lambdacyhalothrin
Etofenprox
Deltamethrin
DDT
Methoxychlor
Tefluthrin
3A Pyrethroids
Pyrethrins
3B DDT
Methoxychlor
Group 3*, sodium channel modulators, is divided into two subgroups
Insecticide resistance management (IRM)
Insecticide resistance management (IRM) is the practice of using insecticides in
a way that minimizes development of resistant pests. IRM has two objectives:
• Prevent or delay the evolution of insect resistance to insecticides2
• Regain lost susceptibility of insects to insecticides2
A key part of IRM is rotation, the strategic periodic alternation of insecticide
products used at a particular operation. An effective rotation strategy alternates
between products from completely different MOA groups — not just
between different brands, active ingredients or even products in different
subgroups of the same group.
For example, a product whose active ingredient is imidacloprid, from the
nAChR agonists group (IRAC Group 4A), may be rotated with a product
whose active ingredient is beta-cyfluthrin, a sodium channel modulator
group (IRAC Group 3).
Zetacypermethrin
Bifenthrin
Betacyfluthrin
Alphacypermethrin
Cyfluthrin
Pyrethrins
(Pyrethrum)
Esfenvalerate
Cypermethrin
DDT
Lambdacyhalothrin
Etofenprox
Deltamethrin
Methoxychlor
Tefluthrin
3A Pyrethroids
Pyrethrins
3B DDT
Methoxychlor
Group 3*, sodium channel modulators
Acetamiprid
Dinotefuran
Clothianidin
Thiamethoxam
Imidacloprid
Thiacloprid
Nicotine
Sulfoxaflor
4B Nicotine
4C Sulfoxaflor
Nitenpyram
4A Neonicotinoids
Group 4*, nAChR agonists
Rotate between different groups whenever possible*
When possible, rotate
between insecticides
from different groups
to minimize the risk
of resistance.
Rotation pitfalls
The biggest mistake in a rotation strategy may be failure to rotate between MOA
subgroups. For example, it would be ineffective to rotate a product containing
imidacloprid with a product containing dinotefuran. Although the two products
have different active ingredients, those two compounds belong to not only the
Two mistakes to avoid
in an insecticide rotation
program:
same group, but also the same subgroup: neonicotinoids. Therefore, they both
have the same MOA and act on the same target site, so it is not true rotation.
- Failure to rotate between
insecticides from
different subgroups
Acetamiprid
- Failure to rotate between
insecticides from
different groups, when
appropriate insecticides
from different groups
are available
Dinotefuran
Clothianidin
Thiamethoxam
Imidacloprid
Thiacloprid
Nicotine
Sulfoxaflor
4B Nicotine
4C Sulfoxaflor
Nitenpyram
4A Neonicotinoids
Group 4*, nAChR agonists
Imidacloprid and dinotefuran are both members of the same subgroup, neonicotinoids, so they share
the same MOA, and alternating between them would not be an effective rotation strategy*
Another common rotation mistake is the failure to rotate between groups,
when an effective alternative from another group is available. For example,
it would be ineffective to rotate between a carbamate and an
organophosphate — both having the same MOA, being in subgroups of the
same group — rather than choosing a product from a different group entirely,
such as an appropriate pyrethroid (IRAC Group 3).
Carbosulfan
Benfuracarb
Carbofuran
Aldicarb
Carbaryl
Methomyl
Methiocarb
Fenobucarb
Triazamate
Thiodicarb
Oxamyl
1A Carbamates
Group 1*, AChE inhibitors
Malithion
Chlorpyrifos
Diazinon
Acephate
Dimethoate
Parathion-methyl
Monocrotophos
Methamidophos
Terbufos
Profenofos
1B Organophosphates
Group 1*, AChE inhibitors
Carbamates and organophosphates are subgroups of the same MOA group, so alternating between
them is a less effective rotation strategy than alternating between two different groups*
Summary
There are several different mechanisms for the emergence of insecticide resistance, including target site
resistance, metabolic resistance, cross-resistance, and others. The use of insecticides from different
MOA groups in rotation is an important part of an IRM strategy. Limiting pests’ exposure to any one
insecticide MOA helps sidestep the potential impact of cross-resistance and helps reduce selection pressure
for resistance by any mechanism, minimizing the emergence of new resistant pest populations.
Successful IRM and rotation practices
■ Rotate insecticides with different MOAs,2,3 not just different brands
or active ingredients
■ Rotate late in the season to cut down on resistant overwintering flies3
■ Discontinue using insecticide ear tags as soon as horn fly numbers decline in the fall,
to minimize the flies’ exposure time to the insecticide and help ensure fly populations
that proliferate later in the season remain susceptible3
■ Rotate MOA classes between applications when applying insecticides more than once
per season or year2
■ Use insecticides at their full doses according to product label recommendations2
■ If mixing insecticides as a short-term measure for a resistance problem, be sure each
component of the mixture is from a different MOA group2 and use both at the
full label dose.
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*Illustrations adapted with permission from the IRAC Mode of Action Classification Poster Edition 3, February 2012.
Available at:
pyrethrin
http://www.irac-online.org/wp-content/uploads/pp_moa_structure_poster_ed3.7_23May12.pdf. Accessed May
24, 2012.
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Bayer is committed
to raising awareness
of the role of MOA
rotation in managing
insecticide resistance.
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Sabatini GA, Ribolla PEM, Barros ATM, et al. (2009). Knockdown resistance in pyrethroid-resistant horn fly (Diptera: Muscidae) populations in Brazil. Rev Bras Parasitol Vet. 18(3):8-14.
IRAC MoA classification scheme. (2012). Insecticide Resistance Action Committee website. Available at: http://www.irac-online.org/teams/mode-of-action/. Accessed May 3, 2012.
Managing pyrethroid-resistant horn flies. University of Kentucky College of Agriculture website. Available at: http://www.ca.uky.edu/entomology/entfacts/ef501.asp. Accessed May 1, 2012.
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©2012 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201
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