FRAC Code List ©*2018: Fungicides Sorted by Mode of Action (Including FRAC Code Numbering)

FRAC Code List ©*2018: Fungicides sorted by mode of action (including FRAC Code numbering)

INTRODUCTION

The following table lists commercial fungicides, mainly for use in plant protection, according to their mode of action and resistance risk. The most important bactericides are also included. Grouping is considering the biochemical mode of action, but a main driver is to identify cross- resistance patterns between chemistries.

The Table headings are defined as:

MOA Code Different letters (A to I, with added numbers) are used to distinguish fungicide groups according to their biochemical mode of action (MOA) in the biosynthetic pathways of plant pathogens. The grouping was made according to processes in the metabolism starting from nucleic acids synthesis (A) to secondary metabolism, e.g. melanin synthesis (I) at the end of the list, followed by host plant defence inducers (P), recent molecules with an unknown mode of action and unknown resistance risk (U, transient status, until information about mode of action and mechanism of resistance becomes available), and chemical multi-site inhibitors (M). Fungicidal compositions of biological origin are grouped according to the main mode of action within the respective pathway categories. A newly introduced category “Biologicals with multiple modes of action” (BM) is used for agents from biological origin showing multiple mechanisms of action without evidence of a dominating mode of action.

Target Site and Code If available, the biochemical mode of action is given. In several cases the precise target site may not be known, however, a grouping within a given pathway / functional cluster is still possible. Grouping can also be made due to cross resistance profiles within a group or in relation to other groups.

Group Name The Group Names listed are based on chemical relatedness of structures which are accepted in literature (e.g. The Pesticide Manual). They are based on different sources (chemical structure, site of action, first important representative in group).

Common name BSI/ISO accepted (or proposed) common name for an individual active ingredient expected to appear on the product label as definition of the product.

Comments on Resistance Details are given for the (molecular) mechanism of resistance and the resistance risk. If field- resistance is known to one member of the Group, it is most likely but not exclusively valid that cross resistance to other group members will be present. There is increasing evidence that the degree of cross resistance can differ between group members and pathogen species or even within species. For the latest information on resistance and cross resistance status of a particular pathogen / fungicide combination, it is advised to contact local FRAC representatives, product manufacturer’s representatives or crop protection advisors. The intrinsic risk for resistance evolution to a given fungicide group is estimated to be low, medium or high according to the principles described in FRAC Monographs 1, 2 and 3. Resistance management is driven by intrinsic risk of fungicide, pathogen risk and agronomic risk (see FRAC pathogen risk list).

Similar classification lists of fungicides have been published by T. Locke on behalf of FRAG – UK (Fungicide Resistance, August 2001), and by P. Leroux (Classification des fongicides agricoles et résistance, Phytoma, La Défense des Végétaux, No. 554, 43-51, November 2002).

FRAC Code Numbers and letters are used to distinguish the fungicide groups according to their cross resistance behaviour. This code should be used to define the GROUP Number on product labels. The numbers were assigned primarily according to the time of product introduction to the market. The letters refer to P = host plant defence inducers, M = chemical multi-site inhibitors, U = unknown mode of action and unknown resistance risk, and BM = biologicals with multiple modes of action. Reclassification of compounds based on new research may result in codes to expire. This is most likely in the U – section when the mode of actions gets clarified. These codes are not re-used for new groups; a note is added to indicate reclassification into a new code.

Last update: February 2018 Next update decisions: January 2019

* Disclaimer The FRAC Code List is the property of FRAC and protected by copyright laws. The FRAC Code List may be used for educational purposes without permission from FRAC. Commercial use of this material may only be made with the express, prior and written permission of FRAC. Inclusion to the FRAC Code List is based on scientific evaluation of the mode of action of the active ingredients; it does not provide any kind of testimonial for the use of a product or a judgment on efficacy.

MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE benalaxyl benalaxyl-M Resistance and cross resistance (=kiralaxyl) well known in various acylalanines furalaxyl Oomycetes but mechanism

A1 unknown. PA – fungicides metalaxyl

(PhenylAmides) metalaxyl-M 4 RNA polymerase I (=mefenoxam) High risk. See FRAC Phenylamide oxazolidinones oxadixyl Guidelines for resistance management

butyrolactones ofurace metabolism A2 Medium risk. Resistance and hydroxy- bupirimate cross resistance known in hydroxy- (2-amino-) dimethirimol powdery mildews. (2-amino-) pyrimidines 8 adenosin- pyrimidines ethirimol Resistance management deaminase required. A3 isoxazoles hymexazole DNA/RNA synthesis heteroaromatics Resistance not known. 32

A: nucleic acids A: (proposed) isothiazolones octhilinone A4 Bactericide. Resistance known. Risk in fungi unknown. carboxylic acids carboxylic acids oxolinic acid 31 DNA topoisomerase Resistance management type II (gyrase) required.

FRAC Code List© 2018 Page 3 of 14 MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE Resistance common in many benomyl fungal species. Several target carbendazim benzimidazoles site mutations, mostly fuberidazole E198A/G/K, F200Y in β-tubulin thiabendazole MBC - gene. B1 fungicides Positive cross resistance (Methyl ß-tubulin assembly between the group members. 1 Benzimidazole in mitosis Negative cross resistance to N- Carbamates) thiophanate thiophanates Phenylcarbamates. thiophanate-methyl High risk. See FRAC Benzimidazole Guidelines for resistance management. Resistance known. Target site B2 N-phenyl mutation E198K. Negative cross N-phenyl carbamates diethofencarb resistance to benzimidazoles. ß-tubulin assembly carbamates 10 in mitosis High risk. Resistance

protein management required. benzamides toluamides zoxamide B3 Low to medium risk. Resistance management 22 ß-tubulin assembly thiazole ethylamino-thiazole- ethaboxam required. in mitosis carboxamide carboxamide B4 cell division phenylureas phenylureas pencycuron Resistance not known. 20 (unknown site) B5 pyridinylmethyl- delocalisation of benzamides fluopicolide Resistance not known. 43 spectrin-like benzamides proteins B: Cytoskeleton and motor Cytoskeleton motor B: and Resistance known in Fusarium graminearum. Target site mutations in the gene coding for cyanoacrylates aminocyanoacrylates phenamacril myosin-5 found in lab studies. 47 Medium to high risk. B6 Resistance management required. actin/myosin/fimbrin Less sensitive isolates detected function benzophenone metrafenone in wheat powdery mildew. Medium risk. aryl-phenyl- Resistance management ketones 50 required. benzoylpyridine pyriofenone Reclassified from U8 in 2018

FRAC Code List© 2018 Page 4 of 14 MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE pyrimidinamines pyrimidinamines diflumetorim C1 pyrazole-5- pyrazole-MET1 tolfenpyrad Resistance not known. complex I NADH carboxamides 39 Oxido-reductase quinazoline quinazoline fenazaquin benodanil phenyl-benzamides flutolanil mepronil phenyl-oxo-ethyl isofetamid thiophene amide pyridinyl-ethyl- fluopyram benzamides furan- carboxamides fenfuram oxathiin- carboxin Resistance known for several carboxamides oxycarboxin fungal species in field thiazole- thifluzamide populations and lab mutants. carboxamides Target site mutations in sdh benzovindiflupyr gene, e.g. H/Y (or H/L) at 257, bixafen 267, 272 or P225L, dependent C2 SDHI fluindapyr on fungal species. (Succinate- complex II: fluxapyroxad Resistance management dehydrogenase 7 succinate-dehydro- pyrazole-4- furametpyr required. inhibitors) genase carboxamides inpyrfluxam isopyrazam Medium to high risk. penflufen

penthiopyrad See FRAC SDHI Guidelines sedaxane for resistance management. N-cyclopropyl-N- benzyl-pyrazole- isoflucypram carboxamides N-methoxy-(phenyl-

C. respiration C. ethyl)-pyrazole- pydiflumetofen carboxamides pyridine- boscalid carboxamides pyrazine- pyraziflumid carboxamides azoxystrobin coumoxystrobin enoxastrobin methoxy-acrylates flufenoxystrobin picoxystrobin Resistance known in various pyraoxystrobin fungal species. Target site mutations in cyt b gene (G143A, methoxy-acetamide mandestrobin F129L) and additional C3 pyraclostrobin mechanisms. methoxy-carbamates pyrametostrobin complex III: triclopyricarb cytochrome bc1 QoI-fungicides Cross resistance shown kresoxim-methyl 11 (ubiquinol oxidase) (Quinone outside oximino-acetates between all members of the QoI at Qo site (cyt b Inhibitors) trifloxystrobin group. gene) dimoxystrobin fenaminstrobin oximino-acetamides High risk. metominostrobin orysastrobin See FRAC QoI Guidelines oxazolidine-diones famoxadone for resistance management. dihydro-dioxazines fluoxastrobin Imidazolinones fenamidone benzyl-carbamates pyribencarb

FRAC Code List© 2018 Page 5 of 14 MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE Resistance risk unknown but cyano-imidazole cyazofamid assumed to be medium to high C4 (mutations at target site known QiI - fungicides in model organisms). complex III: (Quinone inside sulfamoyl-triazole amisulbrom Resistance management cytochrome bc1 Inhibitors) required. 21 (ubiquinone reductase) at Qi site No spectrum overlap with picolinamides fenpicoxamid Oomycete fungicides cyazofamid and amisulbrom binapacryl

dinitrophenyl- Resistance not known. meptyldinocap C5 crotonates Also acaricidal activity. dinocap uncouplers of Low risk. However, resistance 29 2,6-dinitro-anilines fluazinam oxidative phos- claimed in Botrytis in Japan. phorylation (continued) (pyr.-hydrazones) (ferimzone) Reclassified to U 14 in 2012. C6 fentin acetate inhibitors of organo tin tri-phenyl tin Some resistance cases fentin chloride oxidative phos- compounds compounds known. Low to medium risk. 30 phorylation, ATP fentin hydroxide synthase

C: respiration C: C7 thiophene- thiophene- silthiofam Resistance reported. Risk low. ATP transport carboxamides carboxamides 38 (proposed) C8 Not cross resistant to QoI

complex III: QoSI fungicides fungicides. cytochrome bc1 (Quinone outside Resistance risk assumed to (ubiquinone Inhibitor, triazolo-pyrimidylamine ametoctradin be medium to high 45 reductase) at stigmatellin (single site inhibitor). Qo site, stigmatellin binding type) Resistance management binding sub-site required. Resistance known in Botrytis D1 and Venturia, sporadically in Oculimacula. methionine AP - fungicides cyprodinil anilino-pyrimidines biosynthesis (Anilino- mepanipyrim Medium risk. 9 (proposed) Pyrimidines) pyrimethanil (cgs gene) See FRAC Anilinopyrimidine Guidelines for resistance management. D2 Low to medium risk. enopyranuronic enopyranuronic acid protein synthesis blasticidin-S Resistance management acid antibiotic antibiotic 23 (ribosome, required. termination step) Resistance known in fungal D3 and bacterial (P. glumae) hexopyranosyl hexopyranosyl protein synthesis kasugamycin pathogens. Medium risk. antibiotic antibiotic 24 (ribosome, initiation Resistance management step) required. D4 Bactericide. Resistance glucopyranosyl glucopyranosyl known. High risk. protein synthesis streptomycin 25 (ribosome, initiation antibiotic antibiotic Resistance management step) required.

D: amino synthesis D: and acids protein D5 Bactericide. Resistance tetracycline known. High risk. protein synthesis tetracycline antibiotic oxytetracycline 41 (ribosome, antibiotic Resistance management elongation step) required.

E1 Resistance management aza- signal transduction required. Cross resistance naphthalenes 13 (mechanism found in Erysiphe (Uncinula) quinazolinone proquinazid unknown) necator but not in Blumeria

graminis. E2 Resistance found sporadically, mechanism speculative. MAP/Histidine- PP-fungicides fenpiclonil phenylpyrroles Low to medium risk. Kinase in osmotic (PhenylPyrroles) fludioxonil 12 signal transduction Resistance management (os-2, HOG1) required. Resistance common in Botrytis and some other pathogens. Several mutations in OS-1, E3 chlozolinate mostly I365S.

E:signal transduction dimethachlone Cross resistance common MAP/Histidine- dicarboximides dicarboximides iprodione 2 Kinase in osmotic between the group members. procymidone signal transduction vinclozolin (os-1, Daf1) Medium to high risk. See FRAC Dicarboximide Guidelines for resistance management.

FRAC Code List© 2018 Page 7 of 14 MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE F1 formerly dicarboximides edifenphos phosphoro- Resistance known in specific F2 phosphoro-thiolates iprobenfos (IBP) thiolates fungi. Low to medium risk. pyrazophos phospholipid Resistance management 6 biosynthesis, required if used for risky dithiolanes dithiolanes isoprothiolane methyltransferase pathogens. biphenyl AH-fungicides chloroneb (Aromatic Resistance known in some

aromatic hydrocarbons dicloran Hydrocarbons) fungi. F3 quintozene (PCNB) (chlorophenyls, Low to medium risk. tecnazene (TCNB) nitroanilines) Cross resistance patterns 14 cell peroxidation tolclofos-methyl (proposed) complex due to different activity spectra. heteroaromatics 1,2,4-thiadiazoles etridiazole

F4 iodocarb Low to medium risk. cell membrane carbamates carbamates propamocarb Resistance management 28 permeability, fatty prothiocarb required. acids (proposed) F5 formerly CAA-fungicides Bacillus amyloliquefaciens synonyms for Bacillus strain QST 713 amyloliquefaciens are Bacillus subtilis and B. subtilis var. Bacillus amyloliquefaciens (previous F6 amyloliquefaciens Bacillus sp. and the taxonomic classification). microbial strain FZB24 fungicidal lipopeptides microbial disrupters (Bacillus sp.) Bacillus Resistance not known. 44

transport / membrane integrity/ transport or function membrane of pathogen cell produced amyloliquefaciens membranes strain MBI600 Induction of host plant defence Bacillus described as additional mode amyloliquefaciens of action for strain QST 713 strain D747 and FZB24 extract from Melaleuca alternifolia F7 terpene hydrocarbons, (tea tree) cell membrane plant extract terpene alcohols and Resistance not known. 46 plant oils (mixtures): disruption terpene phenols (proposed) eugenol, geraniol, F: lipid F: synthesisor thymol amphoteric macrolide antifungal antibiotic Resistance not known natamycin F8 polyene from Streptomyces agricultural, food and topical (pimaricin) 48 ergosterol binding natalensis or medical uses. S. chattanoogensis OSBPI Resistance risk assumed to be oxysterol binding medium to high (single site F9 piperidinyl-thiazole- protein oxathiapiprolin inhibitor). Resistance lipid homeostasis isoxazolines 49 and transfer/storage homologue management required. inhibition (Previously U15).

MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE piperazines triforine pyrifenox pyridines pyrisoxazole fenarimol pyrimidines nuarimol imazalil There are big differences in the oxpoconazole activity spectra of DMI imidazoles pefurazoate fungicides. prochloraz triflumizole Resistance is known in various fungal species. Several azaconazole resistance mechanisms are bitertanol known incl. target site mutations bromuconazole in cyp51 (erg 11) gene, e.g. cyproconazole V136A, Y137F, A379G, I381V; difenoconazole cyp51 promotor; ABC diniconazole G1 DMI-fungicides transporters and others. epoxiconazole (DeMethylation etaconazole C14- demethylase Inhibitors) Generally wise to accept that fenbuconazole 3 in sterol cross resistance is present biosynthesis fluquinconazole (SBI: Class I) between DMI fungicides active flusilazole (erg11/cyp51) against the same fungus. flutriafol

triazoles hexaconazole DMI fungicides are Sterol imibenconazole Biosynthesis Inhibitors (SBIs), ipconazole but show no cross resistance to metconazole other SBI classes. myclobutanil

penconazole Medium risk. propiconazole

simeconazole See FRAC SBI Guidelines tebuconazole for resistance management. tetraconazole triadimefon triadimenol triticonazole triazolinthiones prothioconazole aldimorph G2 Decreased sensitivity for G: sterol G: in membranes biosynthesis dodemorph powdery mildews. morpholines fenpropimorph Cross resistance within the 14  -reductase amines tridemorph group generally found but not to and (“morpholines”) other 8 7- fenpropidin   piperidines SBI classes. 5 piperalin isomerase (SBI: Class II) in sterol Low to medium risk. biosynthesis spiroketal-amines spiroxamine See FRAC SBI Guidelines (erg24, erg2) for resistance management. G3 KRI fungicides (KetoReductase hydroxyanilides fenhexamid Low to medium risk. 3-keto reductase, Inhibitors) Resistance management 17 C4- de-methylation amino-pyrazolinone fenpyrazamine required. (erg27) (SBI: Class III)

G4 Resistance not known, thiocarbamates pyributicarb fungicidal and herbicidal activity. squalene-epoxidase (SBI class IV) 18 in sterol naftifine biosynthesis allylamines Medical fungicides only. (erg1) terbinafine

FRAC Code List© 2018 Page 9 of 14 MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE H3 formerly glucopyranosyl reclassified to U18 26 antibiotic (validamycin) Resistance known. H4 peptidyl pyrimidine Medium risk. polyoxins polyoxin nucleoside Resistance management 19 chitin synthase required.

dimethomorph Resistance known in cinnamic acid amides flumorph Plasmopara viticola but not in pyrimorph Phytophthora infestans. H5 CAA-fungicides benthiavalicarb Cross resistance between all (Carboxylic Acid valinamide 40 iprovalicarb members of the CAA group. cellulose synthase Amides) carbamates valifenalate Low to medium risk. H: cell H: biosynthesis wall See FRAC CAA Guidelines for mandelic acid amides mandipropamid resistance management.

I1 MBI-R isobenzo-furanone fthalide (Melanin Resistance not known. Biosynthesis pyrrolo-quinolinone pyroquilon reductase in 16.1 melanin Inhibitors – triazolobenzo- biosynthesis Reductase) tricyclazole thiazole cyclopropane- MBI-D carpropamid I2 carboxamide Resistance known. (Melanin Medium risk. Biosynthesis carboxamide diclocymet dehydratase in Resistance management 16.2 Inhibitors – melanin required. biosynthesis Dehydratase) propionamide fenoxanil

I3 MBI-P (Melanin trifluoroethyl- polyketide synthase Biosynthesis carbamate tolprocarb Resistance not known. in melanin Inhibitors – 16.3

I: melanin synthesis in cell melanin I: wall synthesisin biosynthesis Polyketide synthase)

benzo- benzo-thiadiazole acibenzolar-S- P 1 thiadiazole Resistance not known. (BTH) methyl P01 salicylate-related (BTH)

probenazole

P 2 (also antibacterial benzisothiazole benzisothiazole Resistance not known. P02 salicylate-related and antifungal activity) P 3 thiadiazole- thiadiazole- tiadinil Resistance not known. P03 salicylate-related carboxamide carboxamide isotianil

P 4 natural polysaccharides laminarin Resistance not known. polysaccharide compound P04 elici0tors complex mixture, extract from P 5 ethanol extract Reynoutria plant extract Resistance not known. anthraquinone (anthraquinones, sachalinensis P05 elicitors resveratrol) (giant knotweed)

Bacillus mycoides P 6 microbial Bacillus cereus group Resistance not known.

P: host plant defence induction P:defence plant host P06 microbial elicitors isolate J

ethyl phosphonates fosetyl-Al Few resistance cases reported in few pathogens. P07 P 7 phosphonates phosphonates phosphorous acid Low risk. (33)

and salts Reclassified from U33 in 2018

MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC AND CODE CODE Resistance claims described. cyanoacetamide- cyanoacetamide- Low to medium risk. unknown cymoxanil oxime oxime Resistance management 27 required. formerly phosphonates (FRAC code 33), reclassified to P 07 in 2018 teclofthalam unknown phthalamic acids phthalamic acids Resistance not known.

(Bactericide) 34

unknown benzotriazines benzotriazines triazoxide Resistance not known. 35 benzene- benzene- unknown flusulfamide Resistance not known. 36 fungicides) sulfonamides sulphonamides

unknown pyridazinones pyridazinones diclomezine Resistance not known. 37

formerly methasulfocarb (FRAC code 42), reclassified to M 12 in 2018 Resistance in Sphaerotheca. phenyl- unknown phenyl-acetamide cyflufenamid Resistance management acetamide U06 required Resistance known in cell membrane Venturia inaequalis. disruption guanidines guanidines dodine Low to medium risk. U12 (proposed) Resistance management recommended. cyano-methylene- unknown thiazolidine flutianil Resistance not known.

thiazolidines U13 U: Unknown mode action of U: pyrimidinone- pyrimidinone- Resistance not known unknown ferimzone hydrazones hydrazones (previously C5). U14 Not cross resistant to QoI. complex III: Resistance risk unknown but cytochrome bc1, 4-quinolyl- 4-quinolyl-acetates tebufloquin assumed to be medium. unknown binding acetate U16 Resistance management

(Unumbers not appearing inthe list derive reclassified from site (proposed) required. Resistance not known. Unknown tetrazolyloxime tetrazolyloximes picarbutrazox Not cross resistant to U17 PA, QoI, CAA. Resistance not known. Unknown glucopyranosyl glucopyranosyl Induction of host plant defense (Inhibition of validamycin antibiotic antibiotics by trehalose proposed U18 trehalase) (previously H3).

NC: mineral oils, not organic oils, clas- unknown diverse diverse inorganic salts, Resistance not known. NC si- material of fied biological origin inorganic copper inorganic (electrophiles) (different salts) M01 inorganic inorganic sulphur (electrophiles) M02 ferbam mancozeb maneb dithiocarbamates metiram dithio-carbamates and relatives propineb and relatives M03 (electrophiles) thiram zinc thiazole zineb

ziram

captan phthalimides phthalimides captafol (electrophiles) M04 folpet chloronitriles Generally considered as a low risk group without any signs of

site activity (phthalonitriles) chloronitriles

- chlorothalonil (unspecified (phthalonitriles) resistance developing to the M05 mechanism) fungicides. multi-site sulfamides dichlofluanid contact sulfamides (electrophiles) tolylfluanid M06 activity bis-guanidines (membrane guazatine bis-guanidines disruptors, iminoctadine M07 detergents) triazines (unspecified triazines anilazine M08

mechanism) M: Chemicals with M: multi quinones quinones (anthraquinones) dithianon (anthra-quinones) M09 (electrophiles)

quinoxalines chinomethionat / quinoxalines (electrophiles) quinomethionate M10

maleimide maleimide fluoroimide (electrophiles) M11

thiocarbamate thiocarbamate methasulfocarb Reclassified from U42 in 2018 (electrophiles) M12

MOA TARGET SITE GROUP NAME CHEMICAL GROUP COMMON NAME COMMENTS FRAC

CODE

multiple effects on extract from the cell wall, ion polypeptide cotyledons of Resistance not known membrane (from polypeptide (lectin) lupine plantlets (previously M12). BM01 transporters; plant extract) (“BLAD”) chelating effects

competition, modes of action of modes mycoparasitism, microbial Trichoderma spp. and Trichoderma Biologicals with antibiosis, lytic (Trichoderma the fungicidal atroviride strain Resistance not known BM02 enzymes and spp.) metabolites produced SC1

BM: BM: induced resistance multiple