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. OU Cl a e Chemical C las s at an rg anophosph ate To O T Org ot Pyrethroid/ pyrethrin Pyrethroid/ *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. o GR d em i c a l A N AT E M O n oi e Ch TER op o ti ta t AL ss Ro A N R TO P FOR BE S LTS IN CONTRO LL ESU IN TR S EST GP Bayer is committed to raising awareness of the role of MOA rotation in managing insecticide resistance. hos p h ate o r N e on ic 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. 1 2 3 ©2012 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201 Bayer and the Bayer Cross are registered trademarks of Bayer. I12894
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