October 6, 1999
ISBN: N/A
Cat. No.: N/A
(DIR99-06)
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The Pest Management Regulatory Agency (PMRA) has introduced a voluntary pesticide resistance-management labelling initiative based on target site/mode of action for agricultural uses of herbicides, fungicides/bactericides and insecticides/acaricides. This document provides schemes of classification of pesticides according to their sites/modes of action (Appendices I-III), a standard format for showing group identification symbols on the end-use product labels, and guidelines for labelling resistance-management strategies in the use directions. It covers both new products governed by the registration process and old (existing) products governed by the re-evaluation process.
This document replaces Regulatory Proposal Pro96-03, Pesticide Resistance Management Labelling, published for public comments in December 1996. Comments received were taken into consideration in the final version of the guidelines.
Canada, the United States (U.S.) and Mexico, working cooperatively under the auspices of the North American Free Trade Agreement (NAFTA), are developing and publishing these guidelines for voluntary pesticide resistance-management labelling to a uniform standard for implementation in North America. This activity forms part of the work done by the Risk Reduction Subcommittee of the NAFTA Technical Working Group (TWG) on Pesticides. A uniform approach across North America will help reduce the development of pesticide resistance and support joint registration decisions by providing consistency in the resistance-management labelling being considered for approval in any or all of the NAFTA countries.
This Directive applies to resistance-management labelling for herbicide, fungicide/ bactericide and insecticide/acaricide products that are intended for general agricultural use. This document covers both new products governed by the registration process and old (existing) products governed by the re-evaluation process.
The implementation of this program is to be on a voluntary basis by the pesticide industry. Close cooperation of all registrants is required to achieve this important task. Registrants are encouraged to add the resistance-management grouping symbols and statements to both new and existing product labels. Revisions to labels for existing products can be made at the next printing of the labels. All new and existing products are encouraged to have the resistancemanagement grouping symbols and statements on the label by January 1, 2004. Information on amending labels can be obtained from the PMRA Information Service at 1-800-267-6315 (toll-free within Canada) or (613) 736-3799. In view of the importance of resistance management to a sustainable pest-management system, the PMRA will closely monitor the progress of the industry's implementation of resistance-management labelling.
The PMRA, the U.S. Environmental Protection Agency (EPA) and the Cicoplafest of Mexico are committed to encouraging the development of sustainable pest-management systems. Under the auspices of NAFTA, Canada, the U.S. and Mexico have joined together to develop and publish guidelines for voluntary pesticide resistance-management labelling for implementation in North America. The development of these guidelines is part of the activities of the Risk Reduction Subcommittee of the NAFTA TWG on Pesticides. A uniform approach across North America will help reduce the development of pesticide resistance and support joint registration decisions by providing consistency in resistance-management labelling being considered for approval in any or all of the NAFTA countries.
Pesticide resistance, defined for the purpose of this document as a heritable and significant decrease in the sensitivity of a pest population to a pesticide, reduces the field performance of pesticides. Pests include insects, mites, weeds, fungi and bacteria. The management of pesticide resistance development is an important part of sustainable pest-management and this, in conjunction with alternative pest-management strategies and integrated pest-management (IPM) programs, can make significant contributions to reducing risks to humans and the environment. In support of this goal, the purpose of this document is to provide guidance on resistance-management labelling to registrants.
Pesticides are important pest-management tools. Many pesticides have gradually lost their effectiveness due to the development of resistance by pests. An important proactive pesticide resistance-management strategy is to avoid the repeated use of a particular pesticide, or pesticides, that have a similar site of action, in the same field, by rotating pesticides with different sites of action. This approach will slow the development of one important type of resistance, target-site resistance, without resorting to increased rates and frequency of application and will prolong the useful life of pesticides.
A resistance-management strategy should also consider more detailed information regarding cross-resistance between pesticides with different modes of action resulting from the development of other types of resistance (e.g., enhanced metabolism, reduced penetration, or behavior changes). All members of a class may not be cross-resistant based merely on mode of action. However, this labelling initiative will provide pesticide users with easy access to important information regarding target-site resistance, the cornerstone of most resistancemanagement programs.
To ensure consistency in pesticide grouping and labelling, and to contribute to the management of the pesticide-resistance problem, the following guidelines have been developed for agricultural uses of herbicides, fungicides/bactericides and insecticides/acaricides. The following classification schemes are based on target site of action.
Herbicides, fungicides/bactericides and insecticides/acaricides are separately grouped according to their primary sites of action (or target site modes of action) by various technical/research committees consisting of representatives of the pesticide industry, researchers, extension specialists and regulatory officials. The industry committees providing guidance on the pesticide groupings were the Herbicide Resistance Action Committee (HRAC), the Fungicide Resistance Action Committee (FRAC) and the Insecticide Resistance Action Committee (IRAC). Primary guidance for herbicides was provided by the Weed Science Society of America (WSSA). The site of action groups plus the identifier numbers for herbicides, fungicides/bactericides and insecticides/acaricides are located in Appendix I, II and III, respectively.
The site of action identification symbol should be shown on all end-use product labels (except products for homeowner/residential uses) in a standard format as outlined below, and should:




Resistance-management statements are recommended to be included in the use directions for all end-use products for the control of weeds, plant pathogens (diseases), insects and arthropods (except products for homeowner/residential uses) under the heading "Resistance-Management Recommendations". The section "Resistance-Management Recommendations" should be segregated under the "General" portion of "Use Directions" in the U.S., and under "Use Directions" in Canada. Product-specific labelling is recommended. The recommended standard resistance-management labelling statements listed below focus on the prevention and mitigation of pest resistance and should be used where applicable. Efforts should be made to include all appropriate active ingredients and products. These recommendations should also be included in any product-specific literature.
For resistance management, (name of product) is a Group (site of action group number) herbicide. Any weed population may contain or develop plants naturally resistant to (name of product) and other Group (site of action group number) herbicides. The resistant biotypes may dominate the weed population if these herbicides are used repeatedly in the same field. Other resistance mechanisms that are not linked to site of action, but specific for individual chemicals, such as enhanced metabolism, may also exist. Appropriate resistance-management strategies should be followed.
To delay herbicide resistance:
Note The above is a standard statement for products containing one or more active ingredients from the same group. For products containing two or more active ingredients from different groups, the statement should be modified to reflect the situation.
For example:
For resistance management, please note that (name of product) is both a Group (site of action group number) and a Group (site of action group number) herbicide. Any weed population may contain plants naturally resistant to Group (site of action group number) and/or Group (site of action group number) herbicides. The resistant biotypes may dominate the weed population if these herbicides are used repeatedly in the same fields.
For resistance management, please note that (name of product) contains a Group (group number) (fungicide/bactericide). Any (fungal/bacterial) population may contain individuals naturally resistant to (name of product) and other Group (group number) (fungicides/bactericides). A gradual or total loss of pest control may occur over time if these (fungicides/bactericides) are used repeatedly in the same fields. Other resistance mechanisms that are not linked to site of action but specific for individual chemicals, such as enhanced metabolism, may also exist. Appropriate resistance-management strategies should be followed.
To delay fungicide/bactericide resistance:
Note This statement may be modified if repeated application is necessary, e.g., Avoid application of more than (maximum number) and consecutive sprays of (name of product) or other (fungicides/bactericides) in the same group in a season.
Note The above is a standard statement for products containing one or more active ingredients from the same group. For products containing two or more active ingredients from different groups, the statement should be modified to reflect the situation.
For example:
For resistance management, please note that (name of product) contains both a Group (group number) and Group (group number) fungicide/bactericide. Any fungal/bacterial population may contain individuals naturally resistant to (name of product) and other Group (group number) or Group (group number) fungicides/bactericides. A gradual or total loss of pest control may occur over time if these (fungicides/bactericides) are used repeatedly in the same fields.
For resistance management, please note that (name of product) contains a Group (group number) insecticide (or acaricide). Any (insect/mite) population may contain individuals naturally resistant to (name of product) and other Group (group number) (insecticides/acaricides). The resistant individuals may dominate the insect/mite population if this group of insecticides/acaricides are used repeatedly in the same fields. Other resistance mechanisms that are not linked to site of action but are specific for individual chemicals, such as enhanced metabolism, may also exist. Appropriate resistance-management strategies should be followed.
To delay insecticide resistance:
Note The above statement may be modified on a pest by pest basis if a number of applications each year are necessary, e.g., Avoid application of more than (maximum number) and consecutive sprays of (name of product) or other insecticides in the same group in a season.
Note The above is a standard statement for products containing one or more active ingredients from the same group. For products containing two or more active ingredients from different groups, the statement should be modified to reflect the situation.
For example:
For resistance management, please note that (name of product) contains both a Group (group number) and Group (group number) insecticides/acaricides. Any insect/mite population may contain individuals naturally resistant to (name of product) and other Group (group number) or Group (group number) insecticides/ acaricides. The resistant individuals may dominate the insect/mite population if these insecticides/acaricides are used repeatedly in the same fields.
Some herbicides, fungicides, bactericides, insecticides and acaricides have not been assigned to any particular target site/mode of action group or have not been shown on the lists in this document because of the lack of clear understanding of their target site/mode of action or the absence of a history of resistance development for the product. The registrants should establish the appropriate group identifications for their products in consultation with representatives of the pesticide industry, researchers, extension specialists and regulatory officials. The use directions should include the appropriate resistance-management statements for this product, i.e., herbicides, fungicides/ bactericides and insecticides/acaricides.
The above procedure also applies to new pesticides when they are registered for use. The pesticide lists (Appendices I-III) will be updated from time to time (approximately annually) to include product names and/or new/revised site/mode of action classification. The revised appendicies will be posted on the Agency's web site under the title of this Regulatory Directive. Hard copies will be made available from the Agency upon request.
This list is based on the Herbicide Classification of the Weed Science Society of America (Weed Technology, 1997, 11:384-393). Microbial herbicides are not included.
Site of Action: Inhibitors of acetyl CoA carboxylase ACCase
Chemical Family: Aryloxyphenoxy propionates
Active Ingredient:
Chemical Family: Cyclohexanediones
Active Ingredient:
Site of Action: Inhibition of acetolactate synthase (ALS) and also called aceto-hydroxyacid synthase (AHAS)
Chemical Family: Sulfonylureas
Active Ingredient:
Chemical Family: Imidazolinones
Active Ingredient:
Chemical Family: Pyrimidinylthio-benzoateFootnote *
Chemical Family: Triazolopyrimidime
Active Ingredient:
Site of Action: Microtubule assembly inhibitors
Chemical Family: Dinitroanilines
Active Ingredient:
Chemical Family: Pyridazine
Active Ingredient:
Site of Action: Unknown
Chemical Family: None
Active Ingredient:
Site of Action: Synthetic auxins (action like indoleacetic acid)
Chemical Family: Phenoxys
Active Ingredient:
Chemical Family: Benzoic acids
Active Ingredient:
Chemical Family: Carboxylic acids
Active Ingredient:
Chemical Family: Quinoline carboxylic acid
Active Ingredient:
Chemical Family: Semicarbazone
Active Ingredient:
Site of Action: Inhibitors of photosynthesis at photosystem II Site A
Chemical Family: Triazines
Active Ingredient:
Chemical Family: Triazinones
Active Ingredient:
Chemical Family: Uracils
Active Ingredient:
Chemical Family: Pyridazinone
Active Ingredient:
Chemical Family: Phenyl-carbamates
Active Ingredient:
Site of Action: Similar to group 5, but different binding behavior
Chemical Family: Nitriles
Active Ingredient:
Chemical Family: Benzothiadiazoles
Active Ingredient:
Chemical Family: Phenyl-pyridazine
Active Ingredient:
Site of Action: Inhibitors of photosynthesis at photosystem II Site B
Chemical Family: Ureas
Active Ingredient:
Chemical Family: Amide
Active Ingredient:
Site of Action: Inhibition of lipid synthesis, not ACCase inhibition
Chemical Family: Thiocarbamates
Active Ingredient:
Chemical Family: None
Active Ingredient:
Site of Action: Unknown
Chemical Family: None
Active Ingredient:
Site of Action: Inhibitors of 5- enolpyruvylshikimate-3- phosphate (EPSP) synthase
Chemical Family: None
Active Ingredient:
Site of Action: Inhibitors of glutamine synthetase
Chemical Family: None
Active Ingredient:
Site of Action: Bleaching: Inhibitors of carotenoid biosynthesis (unknown target)
Chemical Family: Triazole
Active Ingredient:
Site of Action: Bleaching: Inhibitors of carotenoid biosynthesis at the phytoene desaturase step (PDS)
Chemical Family: PyridazinoneFootnote *
Chemical Family: NicotinanilideFootnote *
Chemical Family: Others
Active Ingredient:
Site of Action: Bleaching: Inhibition of all diterpenes
Chemical Family: Isoxazolidinone
Active Ingredient:
Site of Action: Inhibitors of protoporphyrinogen oxidase (PPO)
Chemical Family: Diphenylethers
Active Ingredient:
Chemical Family: N-phenylphthalimidesFootnote *
Chemical Family: Oxadiazole
Active Ingredient:
Chemical Family: TriazolinoneFootnote *
Site of Action: Unknown
Chemical Family: Chloroacetamides
Active Ingredient:
Chemical Family: Acetamides
Active Ingredient:
Chemical Family: OxyacetamidesFootnote *
Site of Action: Unknown
Chemical Family: Benzofuran
Active Ingredient:
Site of Action: Unknown
Chemical Family: Organoarsenicals
Active Ingredient:
Site of Action: Inhibits dihydropteroate (DHP) synthase step
Chemical Family: Carbamate
Active Ingredient:
Site of Action: Inhibits indoleacetic acid action
Chemical Family: Phthalamate
Active Ingredient:
Site of Action: Inhibits cell wall synthesis Site A
Chemical Family: Nitrile
Active Ingredient:
Site of Action: Inhibits cell wall synthesis Site B
Chemical Family: Benzamide
Active Ingredient:
Site of Action: Photo system I-electron diverters
Chemical Family: Bipyridyliums
Active Ingredient:
Site of Action: Inhibitors of mitosis
Chemical Family: Carbamates
Active Ingredient:
Site of Action: Uncoupling membrane disruptors
Chemical Family: Dinitrophenol
Active Ingredient:
Site of Action: Unknown
Chemical Family: Arylaminopropionic acid
Active Ingredient:
Site of Action: Unknown
Chemical Family: None
Active Ingredient:
Site of Action: Unknown
Chemical Family: Various
Active Ingredient:
Site of Action: Inhibition of 4-hydroxyphenyl- pyruvatedioxygenase (4-HPPD)
Chemical Family: benzoylisoxazoleFootnote *
Chemical Family: IsoxazoleFootnote *
Chemical Family: PyrazoleFootnote *
Chemical Family: TriketoneFootnote *
This list is based on the fungicide listing compiled by the Fungicide Resistance Action Committee (FRAC). FRAC is a Specialist Technical Group of the Global Crop Protection Federation (GCPF). Microbial fungicides are not included.
Activity Group/ Site of Action: Inhibition of tubulin formation
Chemical Group: Benzimidazole
Active Ingredient:
Activity Group/ Site of Action: Affect cell division, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, and metabolism
Chemical Group: Dicarboximide
Active Ingredient:
Activity Group/ Site of Action: Demethylation Inhibitor (DMI): Inhibition of demethylation in sterol biosynthesis
Chemical Group: ImidazolesFootnote *
Chemical Group: Piperazine
Active Ingredient:
Chemical Group: PyridineFootnote *
Chemical Group: PyrimidinesFootnote *
Chemical Group: Triazoles (includes conazoles)
Active Ingredient:
Activity Group/ Site of Action: Phenylamides Affect RNA synthesis
Chemical Group: Acylamines
Active Ingredient:
Chemical Group: OxazolidinonesFootnote *
Chemical Group: ButyrolactonesFootnote *
Activity Group/ Site of Action: Morpholines Inhibition of an isomerase in sterol biosynthesis
Chemical Group: Morpholines
Active Ingredient:
Chemical Group: PiperidineFootnote *
Chemical Group: SpiroketalamineFootnote *
Activity Group/ Site of Action: Phosphorothiolate Inhibition of chitin and phospholipid synthesis
Chemical Group: OrganophosphorousFootnote *
Activity Group/ Site of Action: Oxathiin Affect mitochondrial transport chain
Chemical Group: Anilide (Oxathiin)
Active Ingredient:
Activity Group/ Site of Action: Hydroxyprimidine
Chemical Group: PyrimidinolFootnote *
Activity Group/ Site of Action: Anilinopyrimidine Inhibition of amino acid synthesis
Chemical Group: Anilinopyrimidine
Active Ingredient:
Activity Group/ Site of Action: N-Phenyl carbamates Interfere with cell division
Chemical Group: DiethofencarbFootnote *
Activity Group/ Site of Action: Strobilurin Type Action and Resistance (STAR) Inhibit mitochondrial respiration
Chemical Group: StrobilurinFootnote *
Chemical Group: OxazolidinedioneFootnote *
Activity Group/ Site of Action: Phenylpyrroles
Chemical Group: Phenylpyrroles
Active Ingredient:
Activity Group/ Site of Action: Quinolines
Chemical Group: Quinoline
Active Ingredient:
Activity Group/ Site of Action: Aromatic hydrocarbons
Chemical Group: Chlorophenyl
Active Ingredient:
Chemical Family: Thiadiazole
Active Ingredient:
Activity Group/ Site of Action: Cinnamic acids
Chemical Group: Cinnamic acidFootnote *
Activity Group/ Site of Action: Melanin Biosynthesis Inhibitors (MBI)
Chemical Group: Reductase inhibitorsFootnote *
Chemical Group: Dehydratase inhibitorsFootnote *
Activity Group/ Site of Action: Hydroxyanilide
Chemical Group: HydroxyanilideFootnote *
Activity Group/ Site of Action: Antibiotics
Chemical Group: Antibiotics
Active Ingredient:
Activity Group/ Site of Action: Polyoxins
Chemical Group: PolyoxinFootnote *
Activity Group/ Site of Action: Phenylurea
Chemical Group: PhenylureaFootnote *
Activity Group/ Site of Action: Plant host defence inducers
Chemical Group: Benzothiadiazole (BTH)Footnote *
Activity Group/ Site of Action: Unknown Miscellaneous
Chemical Group: Amino acid amideFootnote *
Chemical Group: Carbamate
Active Ingredient:
Chemical Group: Cyano-acetamide oximeFootnote *
Chemical Group: Organo-tins
Active Ingredient:
Activity Group/ Site of Action: Multi-site activity
Chemical Group: Inorganics
Active Ingredient:
Chemical Group: Dithiocarbamates and relatives
Active Ingredient:
Chemical Group: Phthalimide
Active Ingredient:
Chemical Group: Chloronitrile
Active Ingredient:
Chemical Group: SulphamideFootnote *
Chemical Group: Guanidine
Active Ingredient:
Chemical Group: Anilazine
Active Ingredient:
Chemical Group: Phenyl-pyridinamineFootnote *
Chemical Group: Quinoxaline
Active Ingredient:
The classification scheme was developed in consultation with the Insecticide Resistance Action Committee (IRAC). IRAC is a Specialist Technical Group of the Global Crop Protection Federation (GCPF). It is recognized that resistance of insects and mites to insecticides and acaricides can also result from enhanced metabolism, reduced penetration or behavioral changes that are not linked to any site of action classification, but are specific for individual chemicals or chemical groups. All members of a class may not be cross-resistant based merely on site of action. Most biological insecticides are not included in this Appendix because they are thought not to pose a great concern for resistance development. Microbial products involving Bacillus sp. are included as well as products derived from the Neem tree such as azadirachtin.
Site of Action: Acetylcholinesterase inhibitors
Inhibition of the enzyme acetylcholinesterase, interrupting the transmission of nerve impulses
Chemical Group: Carbamates
Active Ingredient:
Site of Action: Acetylcholinesterase inhibitors
Inhibition of the enzyme acetylcholinesterase, interrupting the transmission of nerve impulses
Chemical Group: Organophosphates
Active Ingredient:
Site of Action: Gamma-aminobutyric acid (GABA)-gated chloride channel antagonists
Interferes with GABA receptors of insect neurons, leading to repetitive nervous discharges
Chemical Group: Chlorinated cyclodienes
Active Ingredient:
Chemical Group: Polychlorocycloalkanes
Active Ingredient:
Site of Action: GABA-gated chloride channel antagonists
Interferes with GABA receptors of insect neurons, leading to repetitive nervous discharges - fiprole site
Chemical Group: PhenylpyrazolesFootnote *
Site of Action: Sodium channel modulators
Acts as an axonic poison by interfering with the sodium channels of both the peripheral and central nervous system stimulating repetitive nervous discharges, leading to paralysis
Chemical Group: diphenylethanes
Active Ingredient:
Chemical Group: Synethetic pyrethroids
Active Ingredient:
Chemical Group: Pyrethrins
Active Ingredient:
Site of Action: Acetylcholine receptor agonists/antagonists
Binds to nicotinic acetylcholine receptor, disrupting nerve transmission
Chemical Group: Chloronicotines (nitroguanidines)
Active Ingredient:
Chemical Group: Nicotine CartapFootnote * BensultapFootnote *
Active Ingredient:
Site of Action: Acetylcholine receptor modulators
Alters acetylcholine receptor site and disrupts binding
Chemical Group: SpinosynsFootnote *
Site of Action: Chloride channel activators
Interferes with the GABA nerve receptor of insects.
Chemical Group: Avermectin
Active Ingredient:
Chemical Group: MilbemycinFootnote *
Site of Action: Juvenile hormone mimics (insect growth regulator)
Mimic juvenile hormones, which prevent moulting from the larval to the adult stage
Chemical Group: Juvenile hormone analogues
Active Ingredient:
Site of Action: Unknown or non-specific site of action (fumigants)
Chemical Group: Fumigant
Active Ingredient:
Site of Action: Unknown or non-specific site of action (fumigants)
Chemical Group: Fumigant
Active Ingredient:
Site of Action: Compounds of unknown or non-specific site of action (feeding disruptors)
Chemical Group: Feeding disruptorsFootnote * (pymetrozine, cryolite)
Site of Action: Compounds of unknown or non-specific site of action (mite growth inhibitors)
Chemical Group: Mite growth inhibitors (ovicide)
Active Ingredient:
Site of Action: Microbial disruptors of insect mid-gut membranes (includes Cry proteins expressed in transgenic plants)
Organism has protein inclusions that are released in the gut of the target pest resulting in gut paralysis and a cessation of feeding
Chemical Group: Bt Microbials (biological insecticide/larvicide)
Active Ingredient:
Site of Action: Inhibition of oxidative phosphorylation at the site of dinitrophenol uncoupling [disrupt adenosine triphosphate (ATP) formation]
Chemical Group: Organotin matricides
Active Ingredient:
Site of Action: Uncoupler of oxidative phosphorylation (disrupt H proton gradient formation)
Chemical Group: Pyrrole compoundFootnote * (broad spectrum contact and stomach poison)
Site of Action: Inhibit magnesium - stimulated ATPase
Chemical Group: Sulfite ester matricides
Active Ingredient:
Site of Action: Inhibit chitin biosynthesis
Chemical Group: Substituted benzoylurea
Active Ingredient:
Site of Action: Inhibit chitin biosynthesis type 1 - Homopteran
Chemical Group: ThiadiazineFootnote *
Site of Action: Inhibit chitin biosynthesis type 2- Dipteran
Chemical Group: Triazine
Active Ingredient:
Site of Action: Ecdysone agonist/disruptor
Disrupts insect molting by antagonizing the insect hormone ecdysone
Chemical Group: Benzoic acid hydrazide
Active Ingredient:
Chemical Group: BotanicalFootnote * (Neem oil or azadirachtin)
Site of Action: Octopaminergic agonist
Chemical Group: Triazapentadiene
Active Ingredient:
Site of Action: Site II electron transport inhibitors
Chemical Group: None
Active Ingredient:
Site of Action: Site I electron transport inhibitors
Chemical Group: Botanical
Active Ingredient:
Chemical Group: Pyridazinone
Active Ingredient:
The unknown group, designated by symbol "U," comprises a set of miscellaneous compounds for which that biochemical mode of action may or may not be known, but are not able to be placed with certainty in any other groupings.
The multi-site activity grouping, designated by symbol "M", comprises a collection of various chemicals that act as general toxophores with several sites of action. These sites may differ between group members
Other resistance mechanisms that are not linked to site of action, such as enhanced metabolism, are common for this group of chemicals. All members of this class may not have developed significant cross-resistance. When only this group of products are available, alternation of compounds from subgroup A and subgroup B are recommended.
Not registered for use in Canada at the time of publication of this document.