DOI: 10.1039/b305508f Pest ic ide Outlook – June 2003 111

This journal is © The Royal Society of Chemistry 2003

IntroductionPesticide resistance is defined as a heritable and significantdecrease in the sensitivity of a pest population to a pesticide.World wide there are 525+ insects and mite species, 100+plant pathogens species, and 270+ weed biotypes that havebeen reported to have developed resistance to pesticides(Hart and Pimentel, 2002). Virtually every chemical pestsuppression tactic known has elicited some form of anadaptive response in the target pest. Pesticide resistanceoften leads to unsatisfactory pest control, increased crop lossand increased use of pesticides, especially in the absence ofalternatives. The United Nations Environmental Programlisted pest resistance to pesticides as the third most seriousthreat to global agriculture behind soil erosion and waterpollution. Crop losses due pesticide resistance are estimatedto be approximately $1.4 billion dollars annually in theUnited States assuming a 10% crop loss due to resistance(Hart and Pimentel, 2002). Thirty to fifty percent ofemergency exemption applications to the United States Envi-ronmental Protection Agency (EPA) under Section 18 of theFederal Insecticide, Fungicide, and Rodenticide Act (FIFRA)for the use of unregistered pesticides are based partially orcompletely on loss of control of registered alternatives dueto pest resistance (Matten et al., 1996).

Implementation of the Food Quality Protection Act(FQPA) in 1996 has led to the cancellation of certain uses ofbroad-spectrum pesticides, such as the organophosphateclass of insecticides, that have been used as key componentsof resistance management programs. Without broad-spectrum pesticides, minor pests are becoming majorproblems and resistance is expected to increase. Loss ofthese broad-spectrum pesticides will put more selectionpressure on pests to develop resistance to the remainingpesticide product classes, especially the narrower spectrum,reduced risk classes, and transgenic crops. Several of therecently registered products in the U.S. have a narrowerspectrum and single sites of action that have been shown tobe prone to resistance. Thus, pest resistance is expected toincrease in importance as the diversity of active ingredients

registered with a broad-spectrum of action decreases and asmore reduced risk and narrower spectrum pesticides areapproved and adopted. Two of EPA’s strategic goals are toensure food safety when pesticides are used and pollutionprevention including the adoption of reduced risk pesticidesand biopesticides. To protect human health and theenvironment, resistance management will become morecritical to achieving EPA’s performance goals.

The Office of Pesticide Programs (OPP) of the EPA hasdeveloped voluntary pesticide resistance managementlabeling guidelines based on target site/mode of action(MOA) for agricultural uses of herbicides, fungicides, bacte-ricides, insecticides, and acaricides. MOA refers to thebiochemical mechanism by which the pesticide acts tocontrol the pest and should not be interpreted to imply thatthese chemicals share a common toxicological mechanismfor purposes of cumulative human health risk assessmentunder FIFRA and the Federal Food, Drug, and CosmeticsAct (FFDCA). Rotation of MOA action was selected as aprimary pest/pesticide resistance management strategy forthis voluntary regulatory initiative rather than metabolicresistance because it is the easiest for reducing the likelihoodof resistance, especially monogenic resistance, and it willhelp reduce the likelihood of resistance caused by othermechanisms. The rotation of MOA is a scientifically-sound,flexible, and practical resistance management strategy.Other management practices that will reduce resistanceinclude application timing, crop rotation and other culturalpractices, and application equipment cleaning.

The resistance management guidelines based on rotationof MOA were published as Pesticide Registration Notice2001–5 in June 2001 (http://www.epa.gov/opppmsd1/PR_Notices/) and were developed under the auspices of theNorth American Free Trade Agreement (NAFTA) by boththe U.S. and Canada. Canada published similar guidelines tothose of the U.S. in October 1999 as Regulatory Directive99-06 (http://www.hc-sc.gc.ca/pmra-arla). Both countriesagreed that uniform labeling guidance across North Americawould encourage adoption of resistance managementstrategies and help reduce the development of pestresistance. The objective of these guidelines is to includeresistance management grouping symbols and statements onthe labels of all new and existing pesticide products for agri-cultural uses. The management of pesticide resistance is animportant part of sustainable pest management and this, inconjunction with alternative pest management strategies and

U.S. EPA’S VOLUNTARY LABELING GUIDELINES FOR PESTICIDERESISTANCE MANAGEMENT BASED ON ROTATION OF MODE OFACTION†

Sharlene Matten from the U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs, Biopesti-cides and Pollution Prevention Division (7511C) in Washington D.C. discusses the US system of voluntaryresistance management labeling guidance

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†Disclaimer: a U.S. Government employee authored this article as part oftheir official duties. In consideration of Section 105 of the Copyright Act(17 U.S.C. Section 105), the work is not subject to U.S. copyrightprotection. The viewpoints expressed in this article are those of the authorand do not necessarily represent those of the U.S. Environmental ProtectionAgency or the U.S. Government. The use of trade names does not implyendorsement by the U.S. EPA or the U.S. Government.

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Integrated Pest Management (IPM) programs, can make asignificant contribution to reducing pesticide risk to humansand the environment and is key to EPA’s regulatory mission.In support of these goals, the resistance managementguidelines based on rotation of MOA provide guidance tousers about pesticide classes and pesticide managementstrategies. Adoption of these guidelines will provide userswith easy access to information regarding target site/modeof action resistance.

Target site/mode of action grouping and identification symbolVarious technical/research committees consisting of repre-sentatives of the pesticide industry, academia, extensionspecialists and regulatory officials separately groupherbicides, fungicides, bactericides, insecticides, andacaricides according to their MOA. EPA and Canada’s PestManagement Regulatory Agency (PMRA) based theirnumerical MOA groupings on those previously defined bythe following industry resistance technical committees:Herbicide Resistance Action Committee (HRAC), FungicideResistance Action Committee (FRAC), and InsecticideResistance Action Committee (IRAC) and the Weed ScienceSociety of America (WSSA). EPA’s and PMRA’s MOAnumerical classification systems are found in the Appendicesof PR Notice 2001–5 and DIR 99-06, respectively. Whenused, the MOA numerical classification symbol(s) should beshown on the front-panel of end-use product labels.

Resistance management labeling statements In the U.S., just as the use of the MOA classification systemis voluntary, so is the use of the resistance managementstatements. If used, these statements should be included inthe general “Use Directions” for end-use products for thecontrol of weeds, plant pathogens (diseases), insects andmites under the general heading “Resistance ManagementRecommendations.” These statements should be clearlydistinguished from mandatory statements (see PR Notice2000–5, “Guidance for Mandatory and Advisory LabelingStatements”) on the pesticide label to avoid confusion to theusers, e.g. Resistance Management Recommendations. PRNotice 2001–5 provides examples of standard resistancemanagement labeling statements that focus on the followingareas:

● avoid repeated or sequential use of products in the sameMOA class through rotation of MOA

● if tank mixes or premixes are legally allowed, makes sureeach compound is from a different MOA class

● use an effective IPM program● monitor for loss of product performance● contact your extension specialist, certified crop

consultant, or manufacturer for the latest resistancemanagement information

● contact the pesticide producer to report loss of efficacy.Alternatively, registrants may supply their own resistancemanagement labeling statements that address these sameareas.

ImplementationEPA encourages registrants to include both the MOA classi-fication and resistance management labeling statements onthe product label whenever submitting new or revisedlabeling. Registrants who wish to add the appropriate MOAclassification and the resistance management statementsmay do so by notification to the EPA. Notification meansthat there will be an expedited review of the label by theAgency (e.g., PR Notice 98-10, “Notice for Notifications,Non-Notifications, and Minor Formulation Amendments”).PR Notice 2001-5 provides the pesticide registrants,formulators, and manufacturers two options with which toimplement the resistance management labeling statements.The first option is a set of recommended standardized labelstatements that appear in the PR Notice. The second optionis completely flexible and allows for each registrant todevelop their own resistance management labelingstatements based on the six areas above. However, if thereare other labeling changes made, in addition to resistancemanagement labeling, a label amendment may be required.

StatusCanada has set a target date of January 1, 2004 for imple-mentation of its DIR 99-06, for voluntary resistancemanagement guidelines based on MOA. To date, PMRA hasapproved approximately 300 labels with either theresistance management labeling and/or classification. Thisrepresents approximately 18% of the total (approximately1600) eligible pesticide products.

EPA has set no target date for implementation of PRNotice 2001–5, but has stated that it wishes to harmonizeefforts on pesticide resistance management labeling withCanada. To date, EPA has approved just six labels with theresistance management labeling and classification: fourinsecticide labels (all from Dow AgroSciences) and twofungicide labels (active ingredient, pyraclostrobin (BASF)),out of approximately 20,000 total pesticide products. Thepyraclostrobin labels were completed in conjunction withthe joint review process of this new active ingredientbetween the U.S. and Canada. These labels represent thefirst time that the resistance management guidelines basedon MOA were implemented on the same products as part ofthe joint review process. It is hoped that the joint reviewprocess will encourage more registrants to implement thevoluntary resistance management labeling guidance onfuture pesticide products.

Why the difference?Canada/PMRA published its voluntary resistancemanagement guidelines, DIR 99-06, to PR Notice 2001–5,in October 1999. From October 1999 to February 2002,there were just 30 labels adopting the guidelines. However,PMRA decided that this level of implementation neededimproving. PMRA now states that registrants should addthe classification and resistance management statements totheir final product labels. This has increased the successfulimplementation of DIR 99-06 from just 30 labels to approx-imately 300 labels adopting the guidelines through January

112 Pest ic ide Outlook – June 2003

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2003. In contrast, only six labels in the U.S. have adoptedthe voluntary resistance management guidelines.

One reason that adoption has been so low in the U.S. isthat the pesticide industry has not come to a consensusabout the value of implementation of these voluntaryguidelines. In addition, there is a concern that the voluntarypesticide resistance management guidelines will turn intomandatory (more rigid) resistance management require-ments, as well as the potential for additional productliability. However, the primary reason for lack of adoption isbased on a perception that if one registrant implements thesevoluntary resistance management guidelines based onrotation of MOA that they will be at a competitive disad-vantage if another registrant with compounds in the sameproduct class does not. EPA is working with the membercompanies of Crop Life America (CLA) and the ChemicalProducers and Distributors Association (CPDA) to addressthese concerns and encourage active implementation of thesevoluntary resistance management guidelines. It is hoped thatonce the concerns over competitive disadvantage are put torest, as well as the assurance from EPA that these guidelinesare flexible, that industry will more readily adopt theguidance set forth in PR Notice 2001–5.

AcknowledgementsThe author wishes to acknowledge the valuable input byDennis Szuhay, U.S. EPA, Office of Pesticide Programs,Pierre Beauchamp, Pest Management Regulatory Agency inCanada, and Janis McFarland, Syngenta Crop Protection.

ReferencesHart, K. and D. Pimentel. 2002. Environmental and Economic

Costs of Pesticide Use. In: Encyclopedia of Pest Management(D. Pimentel, Ed.). New York: Marcel Dekker, Inc. Pp.237–239.

Matten, S.R., Lewis, P.I., Tomimatsu, G., Sutherland, D.W.S.,Anderson, N., and Colvin-Snyder, T.L. 1996. The US Environ-mental Protection Agency’s Role in Pesticide ResistanceManagement. In Molecular Genetics and Evolution of PesticideResistance. T.M. Brown (ed.) pp. 243–253. American ChemicalSociety Symposium Series No. 645, American Chemical Society,Washington D.C.

Pest ic ide Outlook – June 2003 113

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Sharlene Matten has worked for the US-EPA from 1991 until thepresent on biotechnology product registrations, pesticide resistancemanagement policy, and Bt crops (resistance management, humanhealth risk assessment and benefit assessments). From February toJune 2003 she was on detail to the Council for Agricultural Scienceand Technology (CAST) as a Science Policy Fellow.

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