Insecticide Resistance Action Committee. IRAC views and news. IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 1

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IRAC views and news IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 1

Introductory statement 25 Insecticide Resistance Action Committee (IRAC) Formed in 1984 now in its 25 th year and still growing Specialist technical expert group of the agrochemical industry Association with CropLife International Provides a coordinated industry response to the development of resistance in insect and mite pests More than 60 representatives and specialist members in different working groups IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 2

IRAC Mission IRAC Mission: Facilitate communication and education on insecticide and acaricide resistance Promote development of resistance management strategies to maintain efficacy and support sustainable agriculture and improved public health Pool expertise Cross-industry advocacy and lobbying group Industry commitment to product stewardship and sustainability Foster communication and education on IRM Mode of action classification etools on website (eg emethods) Wide range of educational material (posters, bochures, IRM guidelines) IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 3

IRAC Company Membership 2005-2009 Executive member comp April 2005 6 April 2008 13 April 2009 15 16 14 12 10 8 6 4 2 0 Q1 2005 Q2 2005 Q3 2005 Q4 2005 Sumitomo May 2006 Q1 2006 Makhteshim Agan Industries February 2007 Q2 2006 Q3 2006 Q4 2006 Chemtura October 2007 ufarm October 2007 Monsanto May 2007 Q1 2007 Q2 2007 Q4 2007 Cheminova January 2008 Q1 2008 Q4 2008 Q1 2009 ihon ohyaku February 2008 Vestergaard Frandsen October 2008 Belchim February 2009 Aims of increased membership: IRAC to be more representative of the whole industry To speak with authority on behalf of the industry To spread the workload within IRAC IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 4

IRAC and its members Currently 15 IRAC Executive member companies 44 th IRAC Annual Meeting, Barcelona, April 2009 Plus an international coordinator Group still actively expanding & additional members warmly welcomed IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 5

IRAC Annual Meeting attendance Insecticide Resistance Action Committee IRAC Annual Spring meeting attendance 50 40 30 20 10 0 Brussels 2004 Florence 2005 Edinburgh 2006 Rothamsted 2007 Washington 2008 Barcelona 2009 IRAC is still growing Largest IRAC meeting ever in its 25 year history and hence the largest industry commitment to collective IRM to date There is considerable expectation and much onus on us! IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 6

Companies Insecticide Resistance Action Committee ITERATIOAL Working Groups Steering Group Public Health EXECUTIVE Committee Executive Biotechnology Methods Mode of Action Comm/Education Crop Protection Public Health EU Liaison Plant Biotechnology 15 Companies 13 International Working Groups R Database (MSU) Pollen Beetle Sucking Pest Codling Moth Country/Regional Groups IRAC Spain IRAC US IRAC SE Asia IRAC Argentina* IRAC Australia IRAC Brazil IRAC India IRAC S Africa Lepidotpera* Diamide *under developement IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 7

IRAC information materials Information packs (incl MoA posters) IRAC/CropLife Bulletin IRAC Vector Manual IRAC ewsletter econnection IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 8

IRAC econnection Issue 20 covering: Tuta absoluta IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 9

IRAC new website underway! IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 10

eonicotinoids - IRM Guidelines for Sustainable Whitefly Control Introduction and background The use of neonicotinoid insecticides has grown considerably since the forerunner of this group - imidacloprid was first introduced in 1991 Today seven insecticides belonging to this chemical class are available to farmers all over the world and classified as Group 4A within the IRAC Mode of Action Classification Scheme All neonicotinoids are agonists of insect nicotinic acetylcholine receptors 1 Both Bemisia tabaci (sweet potato whitefly) and Trialeurodes vaporariorum (greenhouse whitefly) have been shown to possess a high potential for resistance development and represent some of the principal targets for which IRAC specific guidelines have been developed 2-4 Global Resistance Management Guidelines were designed by the eonicotinoid Working Group of the Insecticide Resistance Action Committee and are based on guidelines published and updated earlier 5 In modern protected vegetable production sites often an integrated whitefly control approach is chosen and includes chemical and biological control measures CH 3 C C CH 2 CH 3 Cl Acetamipr id Mode of Action Classification Group 4 Insecticide Class taken from Version 61 of the IRAC Mode of Action Classification Scheme Group 4: icotinic acetylcholine receptor agonists H O CH 3H O 2 2 C C CH Cl 3 CH S 2 H H CH 2CH 3 CH 2 Cl O 2 Clothianid itenpyra in Cl CH 2 H m S C H H O Imidaclopr CH3 CH id 2 O2 Cl Dinotefur Thiaclopr an id CH 3 O O 2 CH 2 S Cl Thiamethoxa m 4A eonicotinoids Amblyseius swirski, an important predatory mite 4B icotine More information on IRAC and the Mode of Action Classification is available from: wwwirac-onlineorg or enquiries@irac-onlineorg H CH 3 icotine Bemisia tabaci resistance around the globe I like farmers who don t rotate their products! References 1 Jeschke P & auen R (2008) eonicotinoids: From zero to hero in insecticide chemistry Pest Manag Sci 64, 1084 2 Rauch & auen R (2003) Biochemical markers linked to neonicotinoid cross-resistance in Bemisia tabaci Arch Insect Biochem Physiol 54, 165 3 auen R & Denholm I (2005) Resistance of insect pests to neonicotinoid insecticides: Current status and future prospects Arch Insect Biochem Physiol 58, 200 4 Gorman K et al (2007) Report of resistance to the neonictonoid insecticide imidacloprid in Trialeurodes vaporariorum Pest Manag Sci 63, 555 5 Elbert A et al (2005) Bayer CropScience guidelines on resistance management for neonicotinoids Pflanzenschutz achr Bayer 58, 3 IRAC Guidelines for eonicotinoid Resistance Management 1 Always use products at the recommended label rates and spray intervals with the appropriate application equipment 2 Rotation of insecticide chemistries acts against rapid selection of resistant populations 3 Use suitable rotation partners for neonicotinoids An extensive range of insecticides with different modes of action which can be used as rotation partners for neonicotinoid insecticides, are available to the farmer Advice on suitable rotation partners can be obtained from IRAC's mode of action classification available from the website(http://wwwirac-onlineorg) The table on the bottom lists common whitefly MoA s In whiteflies, there is also cross-resistance to Group 9B (pymetrozine) This cross resistance is not found in other pests 4 The use of neonicotinoids against different pests in the same crop Multiple uses of different neonicotinoids against more than one pest species in the same crop is feasible but needs at the local level, to take into account the pest populations dynamics, overlapping of the various species, their relative importance and each species' potential risk for developing resistance 5 Do not control a multi-generation pest exclusively with neonicotinoids 6 ever use neonicotinoids for follow up treatments where resistance has already reduced their effectiveness 7 The use of non specific products helps to prevent the development of resistance 8 Plan the use of neonicotinoid insecticides in such a way that they complement the efficacy of the prevalent beneficial organisms 9 Good agricultural practices should be applied alongside physical and biological pest control methods 10 Crop pest host management 11 Monitor problematic pest populations in order to detect first shifts in sensitivity The full IRAC eonicotinoid RM Guidelines are included in a five page document and can be downloaded from the website Insecticide classes for whitefly IRM IRAC lists 26 mode of action groups (42 including sub-groups); 10 of these are commonly used for whitefly control MoA Primary target site of action Chemical sub-group or Group exemplifying active ingredient 1A Acetylcholinesterase inhibitors Carbamates 1B Organophosphates 2A GABA-gated chloride channel Cyclodienes antagonists 3A Sodium channel modulators Pyrethroids 4A icotinic acetylcholine receptor eonicotinoids agonists/antagonists 7C Juvenile hormone mimics Pyriproxyfen 9B Selective homopteran feeding blockers Pymetrozine 12A Inhibitors of mitochondrial ATP synthase Diafenthiuron 16 Inhibitors of chitin biosynthesis, type 1, Buprofezin Homopteran 23 Inhibitors of acetyl CoA carboxylase Spiromesifen ote: Group 9B shows cross resistance to group 4A in whiteflies This poster is for educational purposes only Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how this Designed & produced by IRAC eonicotinoid WG, October 2008, Poster Ver 21 IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 11 information is used or interpreted Advice should always be sought from local experts or advisors and health and safety recommendations followed For further information visit the IRAC website: wwwirac-onlineorg

Summary/ Review Slides 2008/09 IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 12

Insecticide Resistance Action Committee The IRAC Codling Moth Working Group: Aims & Scope wwwirac-onlineorg Introduction to IRAC IRAC formed in 1984 to provide a coordinated industry response to the development of resistance in insect and mitepests The IRAC Mission is to: Facilitate communication and education on insecticide and acaricide resistance Promote the development of Insect Resistance Management (IRM) strategies in crop protection and vector control to maintain efficacy and support sustainable agriculture and improved public health IRAC International today operates in three major sectors (Crop Protection, Public Health, Plant Biotechnology) It comprises 13 International Working Groups and 7 Country/Regional Groups (India, SE Asia, Brazil, S Africa, US, Spain, Australia) IRAC sees IRM as an integral part of IPM IRAC Codling Moth Working Group The Codling Moth Working Group was established in 2000 to deal with increased occurrence of C Moth resistance in the 90 s Since then the scenario has significantly changed IRAC has reactivated the Codling Moth Working Group to tackle the issues and opportunities for improved IRM (Insect Resistance Management) as a result of the new scenario Insect resistance is 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 recommendationfor that pest species Insect Resistance is an example of evolution in action, showing how selective forces can produce changes in the gene frequency of a population First documented case of C Moth resistance was in 1928 in the US, to arsenite Since then the situation has evolvedin relation to the control tools available Scope of the Codling Moth Working Group 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 work aimed to standardize bioassay methods & improve their reliability Foster adoption of confirmatory assays on target insect stage Ensure a longer effective life for the available toolbox Provide IRM guidance and contribute to local IRM strategies, including the new chemical classes recently introduced (resistance avoidance) Effective use of semiochemicals for Mating Disruption can be a major factor in reducing insecticide driven selection pressure Codling Moth Resistance Mechanisms & IRM Mechanisms Resistance to a specific insecticide can be due to different resistance mechanisms Metabolic resistance (modified enzymatic activity: MFO, GST, EST) Target-site resistance (KDR, MACE) Reduced penetration and behavioural changes 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 (ie between consecutive Codling Moth generations) and other semio-chemical, bio-technical and cultural tools remains best IRM practice, since such practicewill always minimizeselection pressure Metabolic cross-resistance and its diversity: a major threat The most relevant type of resistance in Codling Moth Can concern insecticides across different MoA, but differential response between products within the same MoA can be observed There can be diverse patterns of metabolic resistance (differential enzymatic activity) The diversity of the metabolic resistance found in Codling Moth can be significant across the different geographical areas Different metabolic profiles (enzymatic activity) can impact different MoA/products Bioassay and Monitoring for Resistance Diagnosing metabolic resistance 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 life-stages within the same population In resistant strains, the enzymatic activity may not only differ in quantitative terms, but also qualitatively (eg esterase isoforms) By itself, knowing the enzymatic profile of a given population does not allow to predict the field resistance nor the effectiveness of insecticide X Cross-resistance does not always concern all the insecticides with the same MoA Azinphos-resistant C Moth may be susceptible to Chlorpyrifos and viceversa 5 th instar Sensitive OP Resistant Electrophoretic banding pattern showing diversified esterase isoforms in OP resistant 5th instar Codling Moth larvae (Courtesy of Dr Manicardi) Routine vs validatory assays In the last decade, large scale monitoring for field resistance mostly relied on topical application to diapausing Codling Moth larvae Recent authoritative studies have confirmed their validity for IGRs, but questioned their reliability for the prediction of field resistance with some neurotoxic insecticides By itself, significantly higher response in a routine monitoring conducted on non-target insect stage, does not allow to predict field resistance, unless validated with additional target-specific assays Validatory tests should include multiple insecticide concentrations Bioassaying the target-stage Resistance monitoring should be preferentially done on the target instar For larvicidal 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 Scenario Changes & Trends 2000 2010 2015 o of MoA available for codling moth control*/** 8 10 na o of individual insecticides available*** High Decreasing Fewer Use of semiochemicals (Mating Disruption) Minor Moderate Major Microbial insecticides Minor Moderate Moderate Biological control Minor Minor Minor Regulatory pressure Low High Decreasing Food-chain pressure Low High Decreasing Field Resistance issues***/**** Moderate Decresing Low Resistance knowledge and investigation tools Moderate Increasing High * four introduced in 1997-2000, two in 2007-10 ** according to IRAC MoA classification (version 61) *** in terms of chemical control measures, the cut-off criteria in the current revision of EU Directive 91/414 may concern 60-80% of the available insecticides, with a great impact on sustainable control **** it ll depend on the implementation of the other factors Assumption is that sustainable insecticide use will continue to be possible and implemented In this respect, increased use of non-chemical tools will play a key role Major factors affecting the current scenario vs year 2000 Increased adoption of semio-chemicals for Mating Disruption Reduction of chemical toolbox due to regulatory & food-chain pressure Improved investigation tools for resistance detection and confirmatory assays Insecticides & MoA for Codling Moth MOA GROUP PRIMARY TARGET SITE CHEMICAL CLASS 1A Acetylcholinesterase inhibitors Carbamates Carbaryl, Methomyl 1B Acetylcholinesterase inhibitors Organophosphates 3A Sodium channel modulators Pyrethroids 15 Chitin biosynthesis inhibitors, type 0 Benzoylureas COMMO AMES Azinphos-methyl, Chlorpyrifos, Malathion, Diazinon, Parathion, Phosmet, Phosalone etc lambda-cyhalothrin, beta-cyfluthrin, Cypermethrin, Deltamethrin, Etofenprox, etc Diflufenuron, Flufenoxuron, Lufenuron, ovaluron, Teflubenzuron, Triflumuron, etc 4A icotinic acetylcholine receptor agonists eonicotinoids Acetamiprid, Thiacloprid 22A Voltage dependant a + channel blockers Oxadiazines Indoxacarb 5 icotinic acetylcholine receptor allosteric activators Spinosyns Spinosad, Spinetoram 18 Ecdysone receptor agonists Diacylhydrazines Tebufenozide, Methoxyfenozide 7B Juvenile hormone mimic Phenoxyphenoxyethylcarbamate Fenoxycarb 6 Chloride channel activators Avermectins Emamectin-benzoate 28 Ryanodine receptor modulators Diamides Flubendiamide, Chlorantraniliprole The toolbox is not empty Ten differentmodes of action are currently availablefor control of Codling Moth, whose two are novel Although efficacylevel 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 introductionfor C Moth control and the relativeefficacylevel provided This poster is for educational purposes only Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how this information is used or interpreted Advice should always be sought from local experts or advisors and health and safety recommendations followed IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) Designed & produced by IRAC Codling Moth WG, Setember 2008, Poster Ver 10 13

Insecticide Resistance Action Committee Introduction and biological background Green peach aphid Myzus persicae (Sulzer) is a cosmopolitan and polyphagous pest Primary hosts are predominantly Prunus persica (including var nectarina), while secondary hosts include plants in 40 different plant families as well as economically important crops In addition to direct plant damage, M persicae is a highly efficient vector of over 100 different plant viruses First reports of insecticide resistance in M persicae date to 1955 Three major resistance mechanisms presented here in short have been detected to date Altogether, they particularly confer resistance of M persicae to carbamates, organophosphates (OP s) and pyrethroids Whereas no validated field resistance reports are known for MoA groups 4A, 9 and 23 Combined use of resistance detection techniques against field populations provides farmers with information on possible problems with certain insecticides and helps in better management strategies for M persicae control 1 Enhanced expression of esterases esterases are soluble enzymes hydrolysing ester bonds carboxylesterases (E4 and EF4) sequester or degrade esters of organophosphate and carbamate insecticides before they reach their target site overproduction of named carboxylesterases causes resistance of M persicae to organophosphates, carbamates and some pyrethroids detection is done by artificial model substrates or by ELISA simple handling and quick determination are further advantages Mechanisms of insecticide resistance in green peach aphid First Myzus actions persicae Sulzer Myzus persicae resistance around the globe wwwirac-onlineorg pyrethroid insecticides cause knock-down resistance ( kdr or super kdr ), conferred by changes in a voltage-gated sodium channel protein OUTSIDE II III IV voltage-gated sodium channel in the central nervous system has 4 transmembrane domains with 6 subunits each substitution of leucine to phenylalanine results in kdr genotypes, a mutation found in many pyrethroid resistant pest species found (but long manifested in laboratory individuals =20 years!) kdr resistant individuals usually also show high levels of E4 esterase (which contributes to pyrethroid resistance) overall effects in M persicae is a loss in fitness 2 MACE (modified acetylcholinesterase) Resistance Management Guidelines carbamates and OP s act by inhibiting acetylcholinesterase (AChE) substitution of a serine at position 431 by a phenylalanine in AChE-2 leads to target site resistance to dimethylcarbamates, such as pirimicarb the resistance mechanism is genetically dominant resistant aphids are identified with microplate AChE inhibition assays 3 kdr (knock-down resistance) ISIDE I 1 2 3 4 5 6 H2 1 2 3 4 5 6 Leu 1014 to Phe (kdr mutation) Met 918 to Thr (super-kdr mutation) 1 2 3 4 5 6 1 2 3 4 5 6 COOH compounds should be used according to the label recommendations rotating compounds from different mode of action groups is strongly recommended non-chemical control measures should be incorporated (integrated pest management) Homogenizer ELISA detection of E4 Electrophoresis 80 Inhibition of References 1 Jeschke P & auen R (2008) eonicotinoids: From zero to hero in insecticide chemistry Pest Manag Sci 64, 1084 2 Devonshire AL (1998) The evolution of insecticide resistance in the peach-potato aphid, Myzus persicae Phil Trans R Soc Lond B 353, 1677 3 Foster SP et al, (2008) Correlated responses to neonicotinoid insecticides in clones of the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae) Pest Manag Sci 64, 1111 4 abeshima T et al (2003) An amino acid substitution on the second acetylcholinesterase in pirimicarb-resistant strains of the peach-potato aphid, Myzus persicae Biochem Biophys Res Comm 307, 15 5 auen R & Denholm I (2005) Resistance of insect pests to neonicotinoid insecticides: Current status and future prospects Arch Insect Biochem Physiol 58, 200 6 auen R & Elbert A (2003) European monitoring of resistance to insecticides in Myzus persicae and Aphis gossypii (Hemiptera: Aphididae) with special reference to imidaclopird Bull Ent Res 93, 47 7 Van Emden HF & Harrington R (2007) Aphids as crop pests CAB International Remaining activity, % 100 60 40 20 0 Roznava H7-03 T02 10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 Pirimicarb, [M] acetylcholinesterase by pirimicarb in different strains of aphids (strain Roznava is homozygously susceptible; strains H7-03 and T02 are heterozygously and homozygously resistant, resp) MOA Group 1 Primary Site of Action Acetylcholinesterase inhibitors erve action Chemical Sub-group or exemplifying Active Ingredient 1A Carbamates 1B Organophosphates 3 Sodium channel modulators 3A erve action Pyrethroids Pyrethrins 4 icotinic acetylcholine receptor agonists 4A 9 erve action Selective homopteran feeding blockers eonicotinoids 9B Pymetrozine 9C Flonicamid 23 Inhibitors of acetyl CoA carboxylase Spirotetramat Lipid synthesis, growth regulation This poster is for educational purposes only Details are accurate to the best of our knowledge but IRAC and its member companies cannot accept responsibility for how this information is used or interpreted Advice should always be sought from local experts or advisors and health and safety recommendations followed Designed & produced by IRAC Sucking Pest WG, March 2009, Poster Ver 5 For further information visit the IRAC website: wwwirac-onlineorg IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 14

IRAC MoA classification (v63) IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 15

To learn more about IRAC go to wwwirac-onlineorg Open (public) area Members area IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 16

IRAC Conference Contributions Insecticide Resistance Action Committee IRAC representation at: ational Congress of Entomology, Brazil, August 2008 AgChem Forum, Berlin, Sept 2008 European Whitefly Conference, Almeria, October 2008 Expert CM Workshop, ov 2008 ESA Meeting, December 2008 Annual SW Ag Summit, March 2009 6th Intl IPM Symposium, March 2009 CropLife Malaysia, December 2009 ESA Meeting, December 2009 IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 17

IRAC IRM Workshop Organized by IRAC SEA & CropLife Malaysia December 7th, 2009 IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 18

Thank you very much for your attention IRAC overview EPPO Resistance Panel Meeting 2009 (Vienna, Austria; Oct 27 th, 2009) 19