Version 5 – February 2018 Universal classification of plant protection products according to their modes of action and their chemical structures Opening remark: Tables presented in this document are in French. Nevertheless, this explicative introduction is written in English. A full English version of this classification is under progress. We apologize for this temporary inconvenience to English-speaking readers. Pest, disease or weed control involves plant protection products (PPPs), of natural or synthetic origin. Independent classifications of PPPs have been proposed according to their category (fungicides: FRAC; acaricides-insecticides: IRAC; herbicides: HRAC or WSSA). They do not take into account the fact that highly different organisms may share common biochemical targets that can be inhibited by substances with the same modes of action. Furthermore, biocontrol solutions are often partially represented in these classifications, whereas many are registered in France and their use will gradually increase in the coming years. Some of them may face the adaptation of targeted pests, which justifies their inclusion in this nomenclature of PPPs. The unified classification of PPPs presented in this document takes these characteristics into account and assigns one single code to the modes of action registered against plant pathogens, pests (insects and mites) and / or weeds. It includes: ● A unified classification valid for all PPPs, showing the correlation between the R4P, RACs and WSSA group codes. ● A comprehensive list of fungicides, insecticides-acaricides and herbicides classified according to their modes of action, including their general uses, their dates of registration in France, and the resistance cases reported in France and globally ● A classification of active substances affecting the toxicity of PPPs. In these documents, active ingredients are classified according to their general mode of action, i.e. their ability to affect the following vital processes or structures: ● A – Mitochondrial respiration and energy supply ● B – Photosynthesis (chloroplasts) ● C – Carbohydrate metabolism (oses, osides or polyols) ● D – Lipid metabolism (acetogenins and derivatives) ● E – Sterol metabolism ● F – Biosynthesis of amino-acids or proteins ● G – Biosynthesis of nucleic acids or of their precursors ● H - Biosynthesis of pigments ● I – Biosynthesis of coenzymes ● K – Cell division (mitotic spindle) and cytoskeleton ● L – Hormonal regulation ● M – Cellular signalling ● N – Nervous system or muscles of arthropods ● O – Cell membrane integrity. Version 5 – February 2018 In most cases, the toxicity of a PPP results from its interaction with an enzyme or a non-enzymatic protein, which is its primary target site. In some cases, for the same target site, it is possible to distinguish several classes of inhibitors, according to the interaction modalities. Resistance to PPPs often results from qualitative (and, more rarely, quantitative) changes in their target sites (i.e., target-site-based resistance). These alterations often, but not always, cause positive cross-resistance to all substances with the same primary target descriptor (R4P code, second digit), regardless of the substance chemical class. The classification of PPPs can help establishing anti-target-site-based-resistance strategies based on a rational use of the various modes of action. However, in the case of non-target site resistance, the cross-resistance spectrum can include several different modes of action or only concern some, but not all, substances within the same mode of action group. This requires specific studies to issue recommendations adapted to each specific situation. The PPPs distributed within the S, W and Y classes are little or not concerned by resistance phenomena. They are : ● S – Inducers of host plant response or SDP (mostly against micro-organisms) ● W – Multi-site inhibitors (interacting in a non-specific manner, in particular with - SH or -NH2 groups of respiratory enzymes, in various pests) ● Y - Microbial biopesticides. Class X (unknown biochemical mode of action; XF: Fungicides, XA: Acaricides, XI: Insecticides, XH: Herbicides) includes old or new active substances whose mode of biochemical action remains unknown. The NC class includes unclassified novel active substances. Finally, class Z includes compounds affecting the toxicity of PPPs (ZP: safeners and ZS: synergists). They are not concerned by resistance but can indirectly contribute to its selection by promoting the effectiveness of PPP active substances. They are therefore presented separately from the previous active substances. Besides their classification in groups by biochemical modes of action, PPPs have been classified into subgroups according to their chemical structure. A deliberately simplified name for chemical structures was chosen. A breakdown by chemical class is proposed. When deemed necessary, a secondary subdivision per chemical subclass is also provided. Depending on the available information on evolved resistance (in particular cross-resistance spectra), a descriptor of chemical structure is sometimes proposed within certain classes of action modes. Note that for multi-site inhibitors (Class W) and active ingredients with unknown modes of action (Class X), classification is based solely on the chemical structure of the active ingredients, pending elucidation of its mode of action. All PPPs, whatever their target (weed, pest or fungi) are thus grouped in one single, homogeneous classification, primarily according to their biochemical action mode of action, and secondarily according to their chemical class. This last indication can be useful for reasoning cross resistances within the same mode of action. To avoid confusion of this new nomenclature with existing ones, the letter "U" (for “Universal” nomenclature) is added in front of all codes. This is exemplified below. Version 5 – February 2018 In this example, the code A1b corresponds to inhibitors of mitochondrial respiration and energy supply (A) which bind to the mitochondrial complex I (ubiquinone binding zone essentially involving the PSST subunit) (1), represented chemically by rings containing two nitrogens (b). These active ingredients can be fungicides (code FRAC C1 / 39) or insecticides (code IRAC 21A). Acknowledgments: R4P warmly thanks Pierre Leroux, Christian Gauvrit, Jean-Philippe Guillemin, Bruno Chauvel, Laurent Thibault, Hélène Tombette and Véronique Mironet for their invaluable help in the design and development of this classification and the research of the characteristics associated with active substances. As errors or gaps in these summaries may persist, readers are strongly encouraged to report them at [email protected]. Sources : - FRAC classification : http://www.frac.info/ - IRAC classification : http://www.irac-online.org/ - HRAC classification : http://www.hracglobal.com/ - WSSA classification : http://wssa.net/ - E-Phy database : https://ephy.anses.fr/ - Index phytosanitaire ACTA 2017, Ed. ACTA : http://acta-publications.com/index-phytosanitaire- acta-2017.html - The Compendium of Pesticide Common Names: http://www.alanwood.net/pesticides/index.html - MatPhyto Database : http://matphyto.acta-informatique.fr/Accueil - Compendium of Pesticides Common Names: http://www.alanwood.net/pesticides/index.html - The Pesticide Manual 17th Edition, Ed. British Crop Production Council : https://www.bcpc.org/product/bcpc-online-pesticide-manual-latest-version Version 5 – February 2018 Table legends Unified classification of PPPs: - Columns “Abbreviations”, “Chemical classes”. - : no particular abbreviation is used for this group of inhibitors. Classifications according to PPP category (fungicides, herbicides, insecticides-acaricides): - Columns “Abbreviations”, “Chemical classes”. - : no known element. - Columns « Codes ». - : no known code because no active ingredients with this mode of action are known for this class of PPPs; NC : unclassified ; U or UN : unknown mode of action. - Column « Use ». + : yes ; (+) : limited use ; - : no ; Columns « Use/Others ». A : acaricide ; B : bactericides ; F : fungicide ; G : turf ; I : insecticide ; H : herbicide ; M : medical fungicide ; N : nematicide ; R : plant growth regulator ; X : algae or moss killers ; - : none. - For fungicides only: Column « Use ». E : take-all ; F : head-blight ; H : helminthosporiums ; O : powdery mildews ; P : rice blast ; R : rhizoctonia. - Column « Registration in France ». - : no ; + : yes. - Column « Registration year in France ». First date of registration of the molecule in France, whatever the use, the crop and the target pest. - Column « Date of first use ». First year of use of the active ingredient in France, whatever the use, the crop and the targeted pest. This date may regularly differ from the previous one for regulatory reasons or crop timing. - Column « Removal date ». Last year of withdrawal of the active ingredient, whatever the use, the crop and the target pest (final withdrawal from the market). - Column “Resistance in France”. - : No resistance reported in France; + : at least one resistance case reported in France. - Column “Resistance outside of France”. - : no resistance reported in a country other than France,; + : at least one resistance case reported in a country other than France. - “Resistance Mechanism” columns: For each mode of action, the numbers indicate the associated resistance mechanism, as described in the diagram and table below. Category of mechanism not detected for this mode of