Resistance management: a global industry response from the IRAC. The IRAC Codling Moth working group: aims & scope IFP Avignon, Oct.30-08
IRAC Structure
IRAC s Growing Membership Currently 14 IRAC Executive member companies IRAC Spring Meeting, Washington DC, April 2008 Plus an international coordinator Group still actively expanding Additional members warmly welcomed
IRAC mode of action classification
Members of the IRAC Codling Moth Working Group (Sep. 2008) Working Group Members Geography Company Enrique Ariso South America Makhteshim Andrea Bassi EU, Middle East, Africa Du Pont Daniel Camus France / EU Makhteshim Jim Dripps USA / Global Dow Agrosciences Matthias Haas EU / Global Bayer Cropscience Eric Harrestrup Andersen EU / Global Cheminova Werner Heck EU / Global Basf Robert Senn EU / Global Syngenta
IRAC Codling Moth WG Poster
Working group aims Gather and share updated feedback on codling moth resistance (industry, expert panel, fruit growers) Facilitate networking between the industry and the scientific/advisory community Support research projects aimed to standardize bioassay methods and to improve their reliability Foster adoption of confirmatory assays on target insect-stage Ensure a longer effective life for the available toolbox Provide Resistance Management guidance and contribute to local IRM strategies, including the new chemical classes recently introduced (resistance avoidance).
Evolution in action First documented case of Codling Moth resistance was in 1928 in the US, to arsenite. Since then the situation has evolved in relation to the control tools available. Effective use of semio-chemicals for Mating Disruption can be a major factor in reducing insecticide driven selection pressure
Scenario changes 2000 2000 2010 2010 2015 2015 No. No. of of MoA MoA available available for for codling codling moth moth control*/** control*/** 8 8 10 10 n.a. n.a. No. No. of of individual individual insecticides insecticides available*** available*** High High Decreasing Decreasing Fewer Fewer Use Use of of semiochemicals semiochemicals (Mating (Mating Disruption) Disruption) Minor Minor Major Major Microbial Microbial insecticides insecticides Minor Minor Biological Biological control control Minor Minor Minor Minor Minor Minor Regulatory Regulatory pressure pressure Low Low High High Food-chain Food-chain pressure pressure Low Low High High Field Field Resistance Resistance issues***/**** issues***/**** Decreasing Decreasing Low Low Resistance Resistance knowledge knowledge and and investigation investigation tools tools Increasing Increasing High High * 4 introduced in 1997-2000, 2 in 2007-10 ** MoA according to IRAC Moa classification (version 6.1) *** in terms of chemical control measures, the cut-off and substitution criteria included in the current revision of EU Directive 91/414 may concern 60-80% of currently available insecticides, with a great impact on sustainable control **** this element will be determined by the implementation of the other factors. Assumption is that sustainable insecticide use will continue to be possible and implemented. In this respect, increased adoption of non-chemical tools will play a key role
Major factors affecting the current scenario vs year 2000 Increasing adoption of semio-chemicals for Mating Disruption Reduction of chemical toolbox, due to regulatory and foodchain pressure Improved investigation tools for resistance detection and confirmatory assays
Chemical products & MoA available for Codling Moth control MOA GROUP MOA GROUP PRIMARY TARGET PRIMARY SITETARGET SITE CHEMICAL CHEMICAL CLASS CLASS COMMON NAMES COMMON NAMES 1A Acetylcholinesterase inhibitors Carbamates Carbaryl, Methomyl 1A Acetylcholinesterase inhibitors Carbamates Carbaryl, Methomyl 1B Acetylcholinesterase inhibitors Organophosphates 1B Acetylcholinesterase inhibitors Organophosphates 3A Sodium channel modulators Pyrethroids 3A Sodium channel modulators Pyrethroids 15 Chitin biosynthesis inhibitors, type 0 Benzoylureas 15 Chitin biosynthesis inhibitors, type 0 Benzoylureas Azinphos-methyl, Chlorpyrifos, Malathion, Azinphos-methyl, Chlorpyrifos, Malathion, Diazinon, Parathion, Phosmet, Phosalone etc Diazinon, Parathion, Phosmet, Phosalone etc lambda-cyhalothrin, beta-cyfluthrin, lambda-cyhalothrin, beta-cyfluthrin, Cypermethrin, Deltamethrin, Etofenprox, etc. Cypermethrin, Deltamethrin, Etofenprox, etc. Diflufenuron, Flufenoxuron, Lufenuron, Diflufenuron, Flufenoxuron, Lufenuron, Novaluron, Teflubenzuron, Triflumuron, etc Novaluron, Teflubenzuron, Triflumuron, etc 4A Nicotinic acetylcholine receptor agonists Neonicotinoids Acetamiprid, Thiacloprid 4A Nicotinic acetylcholine receptor agonists Neonicotinoids Acetamiprid, Thiacloprid 22A Voltage dependant Na + channel 22A Voltage dependant Na + blockers Oxadiazines Indoxacarb channel blockers Oxadiazines Indoxacarb 5 Nicotinic acetylcholine receptor allosteric activators Spinosyns Spinosad, Spinetoram 5 Nicotinic acetylcholine receptor allosteric activators Spinosyns Spinosad, Spinetoram 18 Ecdysone receptor agonists Diacylhydrazines Tebufenozide, Methoxyfenozide 18 Ecdysone receptor agonists Diacylhydrazines Tebufenozide, Methoxyfenozide 7B Juvenile hormone mimic 7B Juvenile hormone mimic Phenoxyphenoxyethylcarbamate Phenoxyphenoxyethylcarbamate Fenoxycarb Fenoxycarb 6 Chloride channel activators Avermectins Emamectin-benzoate 6 Chloride channel activators Avermectins Emamectin-benzoate 28 Ryanodine receptor modulators Diamides Flubendiamide, Chlorantraniliprole 28 Ryanodine receptor modulators Diamides Flubendiamide, Chlorantraniliprole The toolbox is not empty. 10 different MoA are currently available for codling moth control whose 2 are novel. Although efficacy level may vary, all of them are relevant to ensure the MoA diversity needed for sustainable control The available toolbox should be locally qualified with the no. of authorized MoA/products, the year of consistent introduction for c. moth control and the relative efficacy level provided.
The mechanisms of Codling Moth resistance Target-site resistance (KDR*, MACE**) Metabolic resistance (modified enzymatic activity: MFO, GST, EST) Reduced penetration Behavioral changes * point mutation in the gene sequence coding for the sodium channel protein (kdr=knockdown resistance) confering resistance to pyrethroids and DDT ** a modified acetylcholinesterase (MACE) which results selectively insensitive to some AcChase inhibitors
Importance of diagnosing the mechanism of resistance A given insecticide may lose its efficacy on codling moth due to various resistance mechanisms
Molecular tools for detection of target-site detection Where target site-resistance has been identified in codling moth (i.e. AcChE2 mutation confering Azynphos-methyl resistance) suitable molecular tests for screening of target-site mutation have been developed Rapid RFLP strategy can be set up to put in evidence both KDR* and MACE** phenotypes * point mutation in the gene sequence coding for the sodium channel protein (kdr=knockdown resistance) confereing reistance to pyrethroids and DDT ** a modified acetylcholinesterase (MACE) which results selectively insensitive to some AcChase inhibitors
Metabolic (cross)-resistance and its diversity: a major threat The most relevant type of resistance in Codling Moth Can concern various insecticide MoA/products* The diversity of the metabolic resistance found in codling moth is significant across the different geographical areas Different metabolic profiles (enzymatic activity) can selectively affect different sets of insecticide MoA/products Although differential response between products within the same MoA can be observed
Enzymatic activity: a helping tool in diagnosing metabolic resistance (1) The analysis of the enzymatic activity (MFO, GST, EST) in a codling moth population is a key element for resistance evaluation. There is a differential enzymatic activity between Codling Moth life-stages within the same population nm/min/ m g 20 18 16 14 12 10 8 6 4 2 0 Diapausing ESTs activiy * 5th instars Sensible OPs resistant Larval stage (courtesy of Cassanelli et al., 2008)
Effective IRM When the mechanism(s) of resistance is not characterized and in order to prevent the onset of resistance phenomena (resistance avoidance) : intelligent use of MoA alternation (i.e. between consecutive c.m. generations) use of semio-chemical, bio-technical and cultural tools is best IRM practice, since such practice will always minimize selection pressure
Need to rely on diversified weapons To avoid putting excessive pressure on the new MoA To set up sustainable IRM programs These days there is a concrete risk that too many effective insecticides will be banned, as a result of the proposed changes to the Directive 91/414 (the cutoff and substitution criteria).
Monitoring for field resistance In the past decade, large scale monitoring for field resistance mostly relied on topical application to diapausing larvae. Recent studies (Reyes et al., 2008) have confirmed their validity for IGRs, but questioned their reliability for prediction of field resistance with some neurotoxic insecticides
Bioassaying the target-stage Validatory bioassays should be performed on the targeted insect-stage. This is best practice to avoid false-positives vs field performance For neurotoxic products, ingestion bioassays on neonate larvae (F1or F2 of the feral population), normally provide a more reliable indication of the field situation than topical application to diapausing larvae
Some short-term objectives Insecticide Resistance Action Committee Provide the indication of a recommended bioassay by active substance Foster early publication of bioassay method for the new compounds Collect updated feedback on C. moth resistance from extended geographies (C.M. Questionnaire ) Encourage the creation of expert panels on specific technical subjects 2008-09 Survey of Codling Moth Resistance Issued, September 2008 Version 1.0
Conclusive remarks Insecticide Resistance Action Committee IRAC C.M. Working Group: Scenario changes Effective and sustainable IRM will depend on: - Insecticide diversity available and MoA rotation - Extended adoption of non-chemical tools (MD) - Higher tier investigation of C.M. resistance