Insect Resistance Management for Bt Plant-Incorporated Protectants

• Overview of insect resistance management (IRM)
• How does EPA manage resistance to Bt crops?
• How does EPA monitor Bt crops for pest resistance?
• What happens if resistance in Bt crops is detected?
• How does EPA manage refuge compliance?
• How do I get additional information on IRM?

Overview of Insect Resistance Management (IRM)

Description of Bt PIPs

Bt plant-incorporated protectants (PIPs) are plants that have been genetically altered to produce proteins that are harmful to certain insect pests. This has been accomplished by transferring specific genetic material from a bacterium, Bacillus thuringiensis (Bt), to the plant’s genome.  The genetic material encodes these proteins that have specific toxicity to certain insect pests, but do not affect mammals or non-target organisms. 

Beginning in 1995, EPA has registered numerous cotton and corn PIPs that have since been widely adopted by growers in the United States and other countries. For example:

• Bt cotton PIPs are designed to control lepidopteran (moth) larvae (budworms and bollworms).
• Bt corn PIPs have been developed for the control of lepidopteran larvae (corn borers) and/or coleopterans (corn rootworm beetles). 

Benefits of Bt PIPs

Bt crops have provided substantial human health, environmental and economic benefits. Growers planting Bt crops may need to use less conventional (chemical) insecticides for pest control, which has both human health and environmental benefits. At the same time, growers may realize increased crop yields through better pest control and lower overall input costs. 

Furthermore, Bt is well known as a low risk pesticide with little or no toxicity to mammals or non-target organisms. Pesticide products containing microbial Bt have been used in organic agriculture for many years. These benefits may be eroded, however, if insects develop resistance to the Bt PIPs. 

Risk of Resistance for Bt PIPs

Like most pesticides, insects are capable of developing resistance to Bt proteins. In Bt PIPs, this risk may be heightened by the fact that: 

• Bt proteins are expressed at high levels in most or all plant tissues;
• the proteins are produced by the plant continually during the growing season (i.e., throughout the lifespan of the plant); and
• some of the major target pests, such as European corn borer, corn rootworm, and pink bollworm, feed almost exclusively on corn or cotton.  

These factors can increase insect exposure to the controlling toxins (Bt protein) and hence, increase selection pressure for resistance. That means that if the toxin kills susceptible insects, those that survive and reproduce are more likely to be resistant to the toxin.

Why IRM for Bt PIPs?

EPA places a high value on the efficacy of Bt PIPs and on preserving their significant agricultural and environmental benefits. Therefore, the Agency is committed to maintaining effective oversight of these products to mitigate the development of resistance in the target pests.  To counter the threat of resistance, EPA has mandated the implementation of an Insect Resistance Management (IRM) plan for each commercially registered Bt PIP. The goal of IRM is to delay the onset of resistance for as long as possible, though it is important to note that it may not be possible to entirely prevent resistance from evolving.  

How were the current IRM strategies developed?

EPA has used the best available science to develop the current IRM strategies for Bt PIPs:

• IRM plans are developed using a risk assessment process in which the Agency evaluates information on the biology of the target pests and the nature of the PIP (i.e., how much of the Bt toxin is expressed by the plant and how susceptible the target pests are to it).
• EPA also considers the potential for cross resistance, in which resistance to one Bt PIP confers resistance to other Bt PIPs.
• Finally, EPA evaluates simulation models that evaluate how resistance can evolve to PIPs among target pests and which IRM strategies work best.

Detailed IRM assessments for specific PIPs, including summaries of the data and information reviewed to develop the strategy, can be found in EPA’s “Biopesticide Registration Action Documents” (BRADs) for each registered PIP.  View information about available BRADs.

To aid in developing IRM plans for Bt PIPs, EPA has frequently sought advice from the FIFRA Scientific Advisory Panels (SAP). These panels consist of scientists who are experts in resistance management and have provided feedback and recommendations to EPA on how to best manage resistance concerns. View a list of the relevant SAP meetings for IRM.

How Does EPA Manage Resistance to Bt Crops?

The Risk of Resistance:  Pyramids vs Single Toxin Products 

Many of the registered Bt PIPs are deployed as “pyramids” that include two or more Bt proteins targeted at the same target pest(s). Pyramids are inherently more durable and less at risk of resistance than varieties that contain only one Bt toxin. For this reason, pyramided Bt products generally have lower resistance management requirements than single trait products (see the “Refuge” section below).

Other Bt PIP products include “stacked” toxins that target multiple target pests (e.g., lepidopteran stalk borers and corn rootworm). These stacked PIPs allow grower to manage different pest complexes with the same product.

The Role of Refuges in Resistance Management

The primary resistance mitigation measure for Bt crops has been the use of refuges. Simply put, a refuge is intended to provide a source of large numbers of Bt-susceptible insects to counter any resistant insects. Overall, the IRM refuge strategy has largely been successful in delaying insect resistance.

It is called refuge because the insects living on these non-Bt plants are sheltered from the pesticidal effects of Bt and are consequently not pressured into developing resistance to Bt proteins. If one assumes that any insects emerging from the Bt field will be resistant to Bt (and few in number), susceptible insects from the refuge should be able to overwhelm the resistant insects and dilute the frequency of resistance genes in the pest population. Typically, a refuge is a portion of a farmer’s operation that is planted to a non-Bt variety of the crop.

Refuges have a size component – usually a percentage of the total Bt crop planted – and must be planted close enough to the Bt field(s) to ensure that the susceptible insects are able to mate with any resistant ones. The size of the refuge is determined by resistance risk. For example, refuge requirements for Bt corn are larger in southeastern cotton-growing regions due to a target pest (corn earworm) in this area that feeds on both corn and cotton. Successive generations of this insect can be exposed to PIP proteins in both Bt corn and Bt cotton during the same growing season, which increases the resistance risk.

Refuge Approaches

For Bt PIPs, there have been three different refuge approaches:

• Structured refuges are a dedicated portion of the farming operation devoted to a non-Bt variety. These refuges are planted as discrete fields (blocks), border rows surrounding a Bt field(s), or rows within the Bt field(s). The key components for structured refuge are its size (as a percentage of the corresponding Bt crop) and proximity to the Bt field(s). Refuges must be able to generate a sufficient number of susceptible insects and be close enough to the Bt field so that susceptible insects (from the refuge) and resistant insects (from the Bt fields) can interact and mate. 
• Seed blends (“refuge-in-the-bag”) incorporate non-Bt seed (refuge) with Bt seed in the same seed bag. The advantage of seed blends is that growers don’t need to coordinate the planting of a separate refuge – refuge compliance is therefore assured.
  
  To date, seed blends have been approved for some Bt corn PIP products. EPA has held several FIFRA Scientific Advisory Panel (SAP) meetings on seed blends – for more information on these meetings refer to the links listed below under “Information Sources.” 

• “Natural refuge” refers to wild hosts, weeds, or other cultivated crops that can serve as a source of susceptible insects. Such a refuge can be effective if the target pest(s) feeds on multiple plant hosts and doesn’t specialize solely on the Bt crop. Natural refuge has been approved only as an IRM strategy for Bt cotton in the southeastern United States. EPA held an SAP meeting on natural refuge in 2006 – for more information refer to SAP links listed below under “Information Sources.”

Registered Bt corn and cotton products for commercial use are required to use one of the above refuge strategies. Structured refuges and seed blends have been employed for Bt corn products, while natural refuge has been used for Bt cotton in the southeastern United States. 

The following tables list the current refuge requirements for Bt crops.

² “Combined refuge” refers to a single refuge meant to address both lepidopteran and coleopteran target pests.
³ “Separate refuges” refers to two different refuges that are planted for lepidopteran and coleopteran target pests

¹ A “sprayed” refuge allows grower to treat the refuge with insecticides to manage pest insects. An “unsprayed” refuge cannot be treated with insecticides.

Integrated Pest Management (IPM) with IRM

Integrated Pest Management (IPM) incorporates the use of multiple tools to manage a pest population, including scouting, economic thresholds, cultural practices, and the judicious use of control measures (e.g., traps, pheromones, pesticides, etc.). The principles of IPM can also be used with Bt crops to reduce selection for resistance. IPM techniques include:

• rotating crops to break pest cycles;
• using of different Bt PIP traits (where available) year-to-year; and
• planting non-PIP varieties if pest pressure is low.  

View more information on IPM.

How Does EPA Monitor Bt Crops for Pest Resistance?

Registrants of Bt PIPs are required to annually monitor pest populations for indications that resistance may be developing among the key target pests. For Bt corn, these target pests include:

• European corn borer;
• southwestern corn borer;
• corn earworm; and
• corn rootworm.  

The target pests of Bt cotton for resistance monitoring include:

• tobacco budworm;
• cotton bollworm;
• and pink bollworm.  

Corn earworm and cotton bollworm are actually the same insect and feed on both corn and cotton – when feeding on corn, it is known as corn earworm, while on cotton it is referred to as the cotton bollworm.

Monitoring for resistance consists of two main components:  

• investigating reports of unexpected pest damage to Bt crops from growers, extension agents, or consultants; and
• monitoring for changes in susceptibility to Bt PIPs through targeted pest sampling and testing.  

Unexpected damage reports may reveal the occurrence of localized resistance (or hot spots) before the effects can spread to neighboring areas. Resistance monitoring through targeted field sampling can indicate changes in susceptibility of geographically representative populations, ideally before damaging effects are seen at the field level.

The specific monitoring strategies employed for Bt PIPs are described in EPA’s Biopesticide Registration Action Documents” (BRADs). View information about available BRADs.

Bt registrants are required to submit an annual report describing their resistance monitoring activities, including reports of unexpected damage, pest sampling, and bioassay results. These reports can be obtained through the Freedom of Information Act (FOIA) – see the “Information Sources” section below for more details. 

What Happens if Resistance in Bt Crops Is Detected?

If a resistant pest population is detected through the resistance monitoring efforts described above, Bt registrants are required to implement a mitigation (“remedial action”) plan. The goals of the mitigation are to limit or contain the spread of the resistant population and maintain the durability of Bt traits in areas where they are still effective.  

• The primary methods used as part of the mitigation strategy include:
  • using alternate control measures to limit the spread of the resistant population; and
  • curtailing the use of the affected Bt trait in the affected area.
• Alternate control measures can include the use of:
  • Insecticides;
  • other Bt PIPs; or
  • cultural controls such as crop rotation.
• Registrants may also:
  • increase resistance monitoring in surrounding areas; and
  • notify other stakeholders (e.g., farmers, extension agents, crop consultants).

Mitigation strategies for resistant populations are fully described in EPA’s “BRAD” documents.

How Does EPA Manage Refuge Compliance?

Some Bt PIP products require the Bt corn registrant to ensure that their growers plant a structured refuge. As described in “The Role of Refuges in Resistance Management” section above, these refuges must be of a certain size and proximity to the Bt field(s). 

To ensure that growers plant these refuges, registrants must implement a “Compliance Assurance Plan” (CAP). The compliance strategy includes an educational component, an anonymous on-line survey of growers to measure rates of refuge compliance, and on-farm visits (conducted by the registrant) to verify that the correct refuge was planted. All of these activities are directly coordinated and implemented by the registrant, though EPA maintains oversight of the process.

Many growers find that planting a refuge is logistically challenging or they may not fully understand the refuge requirements. To address these concerns, each registrant develops a grower guide (commonly referred to as a technology use guide) that explains the IRM requirements and outlines options for planting an appropriate refuge. Registrants also use other means, such as media advertisements, grower meetings and seminars, to provide IRM educational materials to growers.

If a grower is found to be out of compliance with the refuge requirements during a registrant’s on-farm visit, the registrant will implement a “phased compliance approach.” The goal is to bring the grower back into compliance in subsequent growing seasons. The first incidence of non-compliance results in a warning letter from the registrant, additional IRM education and compliance assistance, and a follow-up visit by the registrant the next growing season. If a grower is found out of compliance for two consecutive years, they can lose access to the registrant’s Bt PIP product line the following growing season.

For more information about the CAP and phased compliance approach, refer to EPA’s “BRAD” documents.

Information Sources (How Do I Get Additional Information on IRM?)

Biopesticide Registration Action Documents (BRADs) 

For most registered Bt PIPs, EPA has developed “BRAD” documents that describe EPA’s risk assessments and regulatory conclusions. These documents also contain an extensive discussion of IRM, including the data and information used to develop the IRM strategy and detailed information about resistance monitoring and refuge compliance.

View a list of available BRADs. 

General IRM Docket  

EPA has established a specific docket for IRM-related materials.  This docket includes EPA’s reviews of resistance monitoring and compliance reports, as well as other sources of information on IRM.  This docket will also contain publically-available summaries of resistance monitoring and compliance reports submitted by Bt PIP registrants.

EPA’s IRM docket can be accessed through www.regulations.gov under docket number EPA-HQ-OPP-2011-0922.

Industry Resistance Monitoring and Compliance Reports

As described above, EPA receives annual resistance monitoring and refuge compliance reports from Bt PIP registrants. Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), data submitted to EPA are protected from unlawful disclosure. In particular, FIFRA section 10(g) protects companies’ data from foreign and multinational competitors. Therefore, requests for the compliance and monitoring reports must be vetted through the Freedom of Information Act (FOIA) process, which assures that the data requestor does not represent a multinational pesticide producer. 

The links below include lists of all of the monitoring and compliance reports submitted to EPA.  Individual studies are identified by year and MRID numbers. When making a FOIA request, indicate the year(s), insect(s), toxin(s) and corresponding MRID number(s) of the reports desired. Make a FOIA request. 

Public summaries of some monitoring and compliance reports may be available in EPA’s general IRM docket, which can be obtained without a FOIA request. The information on the pages below includes which studies have public summaries:

• Corn Resistance Monitoring Reports (Lepidopteran Pests)
• Corn Resistance Monitoring Reports (Corn Rootworm)
• Cotton Resistance Monitoring Reports
• Refuge Compliance Reports

Corn Rootworm IRM Framework

EPA has recently implemented a new IRM framework for corn rootworm. This new framework incorporates an IPM-based approach for management of rootworm resistance and establishes new methods for conducting resistance monitoring and mitigation. In addition, the framework establishes a phase-out process for single trait products, which are more at risk of resistance.

View more information on this strategy.

FIFRA Scientific Advisory Panel Meetings 

A key component of EPA’s assessments of IRM for Bt PIPs has been the FIFRA Scientific Advisory Panel (SAP). The SAP serves as an independent peer review body and consists of scientific experts in a range of disciplines relevant to health and environmental issues for pesticides. Meetings are open to the public, with opportunities to provide written and/or oral comments, and are conducted in accordance with the Federal Advisory Committee Act. 

SAPs conducted in 1998 and 2000 (several years after the first Bt PIP registrations were approved) helped establish core mitigation strategies including the use of refuge to delay the development of resistance. Subsequent SAPs have provided guidance on corn rootworm IRM (2002, 2013), the use of natural refuge for Bt cotton (2006), and seed blends as an alternate refuge strategy for Bt corn (2009, 2010).

 A list of SAP meeting relevant to IRM is contained in the table below. View reports from these SAP meetings (except the March 1995 meeting).

EPA Contact

For additional information on EPA's IRM program for Bt PIPs, please contact:

• Alan Reynolds ([email protected]), 703-605-0515; or 
• Jeannette Martinez ([email protected]), 703-305-1016