New Pest Management Tools: Integrating Biotech, New Chemistry, and Regulations

A Report on the ESA Section F Symposium held during

the ESA National Meeting in Ft. Lauderdale, FL on November 18, 2002

 

Mike Tolley of Dow AgroSciences introduced the symposium giving an overview of the state of Pest Management Technologies. In the new chemistry arena, high activity is being coupled with targeted use of environmentally soft novel approaches typified by the increased use of baiting for insect control. In the Biotech arena, we have narrow spectrum traits with selectivity of expression, an emphasis of minimizing gene flow, and the employment of environmentally soft materials. Given the choice of materials, multiple approaches will be necessary for broad-spectrum control of pests. Twenty-first Century intelligent pest management requires the integration of multiple approaches for sustainability.

Walt Mullins of Monsanto Company gave a talk on "Bollgard II: The next generation of transgenic insect control in cotton." The Bollgard II cotton seed has 2 genes from Bacillus thuriengiensis (Bt), the Cry 1 Ac and the Cry 2 Ab inserted into the genome. This results in an expanded spectrum of activity and increased efficacy against Lepidoptera pests of cotton leading to a better pest management tool. The expanded spectrum includes armyworms and loopers. Using ELISA methods to evaluate protein levels Bollgard II (Event 15985) was found to have Cry 1 Ac levels equivalent to the current Bollgard I cotton, however the expression of the Cry 2 Ab gene was ten times greater. Looking at bioassay at 20,000-fold dilution overlaid on diet against 1st instar tobacco budworm, which dilutes out any secondary chemical effects, Bollgard II was 4-5 times more active than Bollgard I. There is a decline over the season, but overall a 3-4 fold increase in activity holds throughout the season. The ELISA shows no decline, so the bioassay results are more appropriate to the field. The two toxins show an additive effect in Bollgard II. Some larvae may be found, but bollworm is greatly suppressed by Bollgard II. The weak point for Bollgard I was the low expression of Bt toxin in flowers. At 72 hours there was only 50-63% survival in Bollgard II compared to 92-93% survival in Bollgard I. Fall armyworm is a tough pest to control, but in cage tests infested weekly over a 6-week period in Loxly, Alabama, Bollgard II showed no economic damage under heavy pressure. Soybean loopers are not affected by Bollgard I, but are very well controlled by Bollgard II. Bollgard I shows some suppression of beet armyworm, but is very well controlled by Bollgard II. Bollgard II will control the entire worm complex on cotton. From a resistance management standpoint, Cry 2 Ab is less than 20% homologous to Cry 1 Ac and does not cross-react. They have seen no cross-resistance in lab Cry 1 Ac selected colonies of tobacco budworm, bollworm, and pink bollworm, so it is highly unlikely that cross-resistance would occur in the field. Thus, Bollgard II shows increased activity, increased spectrum, and will be a better resistance management tool in cotton.

Nick Storer of Dow AgroSciences gave a talk on "Corn rootworm: New options for management with transgenic corn." Nick gave an introduction to the four species complex of corn rootworms responsible for $1 billion dollars of damage annually to the corn crop. Rootworms have developed resistance to crop rotation, the best cultural alternative by either selection for a 2-year diapause (Northern) or increasing egg lay in soybeans (Western). Currently, soil insecticides are the best alternative, but they are difficult to apply and can be weather dependent for activation. Adult control with aerial application has historically been strong in a few locations, but resistance is appearing in many of these areas. The transgenic approach with control built into the plant could give more reliable insurance against economic damage. The through the seed approach is no extra work, preserves beneficial organisms, and fits into Integrated Pest Management (IPM). It also builds on the grower’s positive experience with Bt corn. Farmers are familiar with this technology. Currently there are two technologies under development that hold promise to fulfill this need, Yieldgard Rootworm (Mon 863) with Cry 3B protein from Monsanto, and Cry 34/Cry 35 (formerly 149B1) from Dow AgroSciences. These two genes differ in mode of action and their effects on the pest complex. The Cry 34/Cry 35 is a binary protein composed of Cry 34Ab1 a 14 Kdalton protein and Cry 35Ab1 a 44 Kdalton protein. These proteins, as with other Bt’s, act on the insect mid-gut swelling cells and causing them to slough off. Nick reported on the field data. Overall, the results in the field has shown minimal feeding (<0.20) compared to Lorsban 15G (1.0-0.8) and the untreated check (2.0). The regulatory issues for transgenics include product efficacy, human health, ecotoxicity, and environmental fate. Agencies generally require Non-Target Field Effects Data including field surveys of beneficial organisms and non-targets, including visual monitoring, sticky trap and pit fall trap data, and effects on the insect community when non-significant foliar insects can be significant. The agencies are also concerned about product durability insisting on resistance management plans while companies are interested in recovering investments. Nick has worked with the regulatory agencies to model resistance development in rootworm. Factors important to the model are pest biology, dose level, adult effects, refugia, and mode of action. The higher dose is more durable, and more than one product with different modes of action brings down the resistance potential to both materials. The Cry 34/Cry 35 material is safe, has no adverse environmental effects, and fits IPM. It will be simpler to use than current methods and expand grower options for resistance management.

Mike Schwarz of Bayer Corporation presented the talk "The use of the seed treatment insecticide, Clothiandin, in conjunction with transgenic traits to control all economically important insect pests of corn." Clothiandin has had extensive trials in corn and canola since 1996. The regulatory package was submitted in May 2001 and registration is expected in March 2003. It has the nitroguanadine backbone and has had extensive testing over 10 years. The material travels in the transpiration stream even to far out lateral roots. The insect receives the toxicant by feeding on the plant. The material acts as a post synaptic acetylcholine receptor agonist in the insect central nervous system. Even sub lethal doses may stop normal behavior. The material translocates from the roots to the upper portions of the plant systemically making seed treatment for foliar pests a possibility. Seed treatment can be advantageous due to minimal exposure, no chronic effects, and no calibration or application problem. Planting is more efficient with less environmental loading due to lower use rates. The rate of 1.25 milligrams per kernel in corn is equivalent to 37.5 grams per acre, which gives results equivalent to standards in the field. This rate will control rootworm, cutworm, wireworm, imported fire ant, seed corn maggot, flea beetle, corn seed beetle, corn leaf aphid, white grub, Southern green stink bug, grape colaspis, and Southern corn billbug--in short, all the early season pests of corn. Root ratings in corn rootworm tests have varied from 2.8-2.9 depending on rate with the 1.25 mg/kernel rate giving an average of 2.84. This compares to Thiacloprid at 3.19, Aztec at 2.55, Lorsban at 2.78, Regent at 2.86, Force at 2.60, Counter at 2.53, Prescribe at 3.23 and Untreated at 4.35. At 1.25 milligrams per kernel, Clothiandin was equivalent to Lorsban over all pressures in the untreated against rootworm. In the field it is common to see moribund larvae at the base of the plants. Unique among the chloronicotinoids, Clothiandin has very good cutworm control in the field. They consistently see higher plant populations, which translates into higher yields (192 vs. 160 bushels). For resistance management, the refugia is in the bag because they see no big difference in adult rootworm emergence from treated to untreated plots with equivalent sex ratios. There should be no change in population dynamics with the use of Clothiandin. The material is equal to or better than the standards as a seed treatment. At the high rate it will control corn rootworm and all other early season pests of corn, it shows positive agronomic potential, and can play a strong role in IRM.

Lamar Buckelew from Bayer Corporation presented the paper entitled "BSN 2060 a novel acaricide-insecticide." Spiromesifen (BSN 2060) is a new tetronic acid derivative from Bayer showing promise in the control of spider mites and whiteflies. It has a novel mode of action, acting by inhibiting lipid biosynthesis. Its trade name will be Oberon. It has a very short soil half-life of 5 days and with a water solubility of 130 milligrams per liter no potential for leaching. It is safe on honeybee, birds, mammals, and beneficials. It has slight to moderate activity on non-harmful mites. It is effective on all stages of Bemisia, Trialeuroides, and Tetranychus. There is a slight delay in activity but it is quicker than the benzoyl phenyl ureas. The mode of action involves inhibition of lipid synthesis, which leads to dehydration. There are no new lipids synthesized after treatment. It is active against nymphs and at higher rates, adults. Females show decreased fecundity and it is effective on resistant strains of mites and whiteflies. It is better than pyriproxyfen on whitefly and very good compared to Applaud and Knack. Against Tetranychus, the material is less effective on adult females. In early season cotton, the material is comparable to Zephyr and superior to Savey and Comite. They have seen no cross-resistances and good plant compatibility. It is safe on predators except predatory mites. Spiromesifen represents a new mode of action with no cross resistance, the registration package was submitted the end of November 2002 with registration expected by the end of 2004.

John Andaloro of DuPont Crop Protection gave the presentation "Indoxacarb: Review of efficacy, behavior, and species spectrum." Indoxacarb is a member of the oxadiazine chemistry, which acts on insects by blocking sodium channels in the nervous system. The material had a Section 18 in cotton in 2000 and was registered in 2001 and 2002. The use rates are generally in the range of 25-125 grams per hectare around the world. It has high lipophilicity and is not systemic. Avaunt is the trade name for vegetables and tree fruit and Steward is the trade name for row crops. Currently the material is registered in 65 countries. It differs from the pyrethroids in that while the pyrethroids keep the channel open, indoxicarb blocks the channel. Symptoms seen in insects include mild tremors, cessation of feeding, and death usually in a couple of hours. In the field it takes 1-3 days for death with a rapid cessation of feeding. The material contains 75% of the active isomer, which is a pro insecticide metabolized in the insect into DCMP, the active principle. In the laboratory, ingestion LC50’s vary from 0.10-3.0 PPM with contact activity 2-10 fold less. The delayed activity of the material impacts marketing of the product. More education is necessary so needless retreatments do not occur. Also the material requires good coverage so is not ideal for rescue treatments. It is however ideal for urban pests such as roaches and termites. DuPont has employed robust resistance monitoring systems using treated leaves. Contact with the material can take place through ingestion, contact, translaminar action, during preening, and at rewetting of surfaces. Indoxacarb can be ovicidal, larvicidal, or adulticidal in action. With registration and with spread use, various behavior anomalies have been noted including quick paralysis, delayed larval growth, growth regulator effects (related to insect growth stage), failure to enter the soil for pupation, prolonged or incomplete pupation, and uncoordinated adults. Generally indoxacarb is safe on beneficial insects and mites, however, ladybird beetles can pick up enough of the material through preening in the first 24 hours after spraying to produce mortality. Indoxacarb was discovered in 1991 and MP062, the resolved isomer material was field tested in 1996 all against worm pests. Now the material is labeled for leafhoppers, plant hoppers, and plant bugs. An understanding of surfactants has led to exploring activity on roaches, ants, and termites and even some activity on grubs. Within the Lepidoptera indoxicarb is not quite as active on looper or salt marsh caterpillar as other Lepidoptera. Also susceptibility of Heliothis armigera is different around the world. Indoxicarb is effective on Lygus lineolaris in the East but less active on Lygus hesperus in the Western U.S. Granulated cutworm, tomato pinworm, hornworm, and cabbage worm are all well controlled by indoxicarb. They are looking toward registration of indoxicarb for chemigation on corn and cranberries in 2003 and have an emergency exemption for cotton boll weevil. Agridex and other crop oils increase the activity of indoxicarb on Liriomyza trifolii especially on small larvae. They are seeing a reduction in stink bug damage in cotton that may be due to repellency. The advantages for indoxacarb in the urban market include a lack of odor, a new mode of action active on resistant insects, good residual activity, and excellent roach and fire ant activity. Trials are ongoing in 2003 on ants, cockroaches, termites, flies, and mosquitoes. Indoxacarb exhibits a new mode of action. It is ideal for IPM and IRM. It is a safe broad-spectrum plant protection agent with attributes that also fit into urban settings.

Michelle Smith and Mike Tolley presented the paper "Noviflumuron: Development and registration of an IGR for urban pest management markets." Companies are always looking for new active ingredients, which are generally exploited in the large agricultural markets first and then if a fit is discovered the material will be expanded into the urban markets. However, the pest complex is different in urban markets, and the attributes necessary may vary greatly between agricultural and urban customers. A good example is the development of the Sentricon Termite Colony Elimination System. Here intrinsic activity may be overshadowed by a need for bait acceptability and slow kill to allow trophalaxis to spread the material through the entire colony. Key to the selection of Noviflumuron as a new active for this business was its 4-fold slower clearance rate than the current hexiflumuron in termite colonies. It was also faster acting and more effective in field trials. These trials employed mark and recapture technology to characterize the colonies. The trials were conducted in urban and suburban environments. In this kind of study a good working relationship with the homeowner is essential. A greater than 40% improvement in days to elimination was seen against the most important termite species. In German cockroaches, horizontal transfer and bait acceptability were also studied and found to be excellent. Exposure to contaminated frass was found to transfer Noviflumuron horizontally. At 12 weeks after treatment, 80% control was seen, as good as the best. Many additional urban targets are being considered by the business either alone or in partnership. There are unique challenges with pest control product development in urban areas. Urban pest control formulations are unique with many bait matrices that must be picked up and fed upon by the target insect. The novel urban insect management tool, Noviflumuron is very stable but insoluble in water. Using an aqueous Suspension Concentrate (SC) a cellulose bait matrix is coated with the active ingredient which is rolled and placed into the Recruit III bait station for termite control. In addition we have seen very favorable activity as a gel bait for roach control and in other baits for ant control. The regulatory environment is different for urban materials. Tolerances are not required, but there are efficacy requirements. Those materials used on urban animals and those used for human health each have efficacy requirements. Very few actives are developed specifically for urban uses. In the case of hexaiflumuron, there were already agricultural uses for the product so all that was required was efficacy data and an expanded toxicology package. On the other hand, Noviflumuron is being developed exclusively for the urban market. Dow AgroSciences was in a unique position with the first termite bait system. We had to benchmark the product with few regulatory guidelines. This has changed as we now expect to have guidelines from the EPA following Scientific Advisory Panel review in July 2002. The industry argued that high benchmark standards were appropriate due to high liability concerns. State regulators also have required input on future bait registrations. So once again Dow AgroSciences will take the lead again being the first through these new guidelines with Noviflumuron. Dow AgroSciences has received reduced risk status for Noviflumuron and we are involved in EUP programs that will be used as the framework for others to follow. In the urban area we need new markets and control systems for the future.

Barb Nead-Nylander from Dow AgroSciences presented the talk "Global registration challenges to organophosphate insecticides." Barb started with the current trends in agriculture. Currently we are being challenged to grow more on the same amount of land. We have fewer people than ever before involved in agriculture and there is widespread mistrust of science and government. The general public feels a need to reduce the perceived risk in farming through the use of regulation. Agricultural pest control is a declining business. The organophosphate insecticides are the largest class on the market today. Their broad spectrum and reasonable cost due to generic pressures have kept them in the marketplace. In general these materials are not persistent but some are highly toxic and need to be handled with care. Resistance can be an issue with individual products but generally does not extend to the class as a whole. Since some materials in this class (Sarin and Tabun) have been used as nerve gases, the entire class has been tainted. This is an older area of chemistry with a poor public image and lower prices. Given greater regulatory scrutiny many of these materials no longer make economic sense to companies. The resultant exit of these materials reinforces the need to get rid of further products. This produces an ugly spiral of further cancellations. The U.S. Food Quality Protection Act (FQPA) has made major impacts around the world. With cumulative Risk Assessment as part of the reregistration process, risk cups shrank putting pressure on the business to give up perfectly safe uses. In European Agricultural Chemistry Regulations, the complexities caused a virtual standstill and a duplication of the process. Most insecticides do not pass the initial screen and are not supported due to the expense of further data generation. The organophosphate insecticides globally account for 41% of the insecticide business or about $560 MM in size. Eliminating the 1A and 1B materials will most effect developing nations. OSPAR is a combination of the Oslo and Paris Commissions concerned about the marine environment. They have placed 115 pesticides on their concern list. Many of these are organophosphate insecticides. Prior Informed Consent (PIC) is a program to identify potential hazards issues and inclusion on the list requires only 2 regions in support. There are currently 22 pesticides on this list and it will be expanding in the future. Persistent Organic Pollutants (POPS) is a list of the most dangerous highly toxic materials. There are currently no organophosphate insecticides on this list, but many are pushing to add these to the list. Additional pressures on the organophosphate insecticides come from a misinterpretation of FQPA around the world. As a result many countries have cancelled urban uses of organophosphate insecticides and some Asian countries wanted to ban the agricultural uses. All this results in greater paperwork, which adds to costs on already thin margins. No government reviews have the same priorities but companies have the obligation to provide tools and information. The increased cost can discontinue uses or whole products. Loss of these uses will effect IRM programs and the economics of alternatives will drive more people out of farming. The organophosphate insecticides are only the first group to undergo this process with the carbamates and pyrethroids coming next. We need to standardize commonly conducted tests and formats around the world. This will at least help with costs.

John Jachetta of Dow AgroSciences presented the paper "Spray drift regulatory issues in agriculture." Nobody wants spray drift. It is a waste of chemical, a waste of effort, and can bring lawsuits. The regulators also see no use for spray drift and are focusing on regulating droplet size, release height, and wind speed. Enormous data sets exist on the phenomenon from the work of the Spray Drift Task Force, a group of 40 companies that spent $26MM and supplied all the data to the EPA. Canadian studies show drift mitigation for ground applications and European data orchard air blast studies show a great deal of drift mitigation with hedgerows. All these data come to the same conclusions, that nozzle height, droplet size, wind speed and direction, aircraft position, boom length, physical properties, and canopy tree spacing all effect spray drift. An AAPCO survey show a total of 2,000 drift incidents recorded with insecticides, herbicides, and fungicides out of millions of applications. There are about 2500 6a(2) reports per year on pesticides. The Worker Protection Standards (WPS) requires the statement "Do not apply when contact through drift is possible". In August 2001 the U.S. EPA proposed new labeling standards for spray and drift mitigation. The comment period closed March 31, 2002. The agency proposed a zero drift policy around sensitive sites. All newly amended and reregistered products would be required to carry the statement, while other materials would change at the next label amendment. This will lead to a non-uniform implementation and ambiguous enforcement standards. The proposed standards mandated wind speeds, aerial boom width restrictions, droplet size, and carried over into home and garden products as well. The EPA would set buffers around sensitive areas and it would take registration priorities to challenge them. The buffers are to be set without allowance for the wind or topography. To date, 31 insecticidal materials have been assessed with 45% requiring 1,000 feet or more. Needless to say the response to the PR notice was high with 5,269 total comments recorded from 1,771 individual letters. Most expressed concern over the approach, concern for zero tolerance, and the need for performance based label statements. The EPA is evaluating the responses and will issue another draft. Over half the respondents were independent growers, while only 17% were agricultural retailers, and 44 were members of Congress. In addition, states have rights of their own. Many have adopted statements such as "Do not allow spray to drift from the target site and contact sensitive areas." States have concerns over application height, wind speed, and upwind and downwind areas. They are also concerned about the enforceability and complexity of labels. States have limited wind speeds for aerial application, and prescribed drift limits. Mitigation of drift is promoted. Many states are promoting nation wide advance notice requirements. People are looking for causes and it only takes one careless application to spark further regulation. Currently registrants can voluntarily use the draft statements or use the old do not drift statements. Label based mitigation is unavoidable and true drift mitigation tactics need to be encouraged.

Sharlene Matten from the U.S. Environmental Protection Agency (EPA) gave a talk entitled "Mode of action labeling for insecticides: A joint industry regulatory initiative." Significantly, this paper was co-authored by Dave Marsden of DuPont and Gary Thompson of Dow AgroSciences. The International Resistance Management Committee (IRAC) has been cooperating with the U.S. EPA to develop mode of action labeling as a resistance management tool. This initiative resulted from discussions at a 1997 NAFTA Reduced Risk Subcommittee Meeting between Canada and the U.S. Although other mechanisms were considered, the focus came down to needing a common scheme based on mode of action identification. Voluntary, performance management labeling guidelines based on rotational mode of action are the focus of PR2001-5. The guidelines propose to have a number on the front panel of the label as a numerical classification, for example, spinosad would be Group 5 (spinosyns). In addition, under "Directions for Use" there should be statements to alert users to avoid repeated consecutive use of the same mode of action. Use in an effective IPM Program would also be stressed as well as the importance of monitoring product performance. The first insecticide to use the voluntary guidelines was spinosad from Dow AgroSciences. In the future, the Reduced Risk screening and the joint regional process with Canada should include the use of the guidelines in a PR notice. The EPA has a good relationship with PMRA in Canada. IRAC has been the most forward thinking on global harmonization of resistance management and is moving toward this end. IRAC is working on educational materials and urging their members to put the numerical mode of action numbers in presentations. Sharlene worked with the pesticide manufacturers before the notice went out and as a result there were only 5-7 comments on the PR notice. This is a great example of the EPA embracing stakeholders. Key discussions were about label design. Her focus on numbers rather than colors has helped. Generic or multiple registrants can be a challenge, but Sharlene has found that working through the technical people to convince them they will not lose market share has been helpful. It helped to start with industry and have them talk to the market. We will need this system to be adopted in Extension Program use guides, Technical Bulletins, and IRAC posters and brochures. IRAC is currently working on a tri-fold brochure that lists all 22 modes of action. The Australians have an almost identical system, so this system is catching on around the world and fits Resistance Management Strategies in different crops and different geographies.

L. L. Larson
Dow AgroSciences, Discovery Research
9330 Zionsville Road
Indianapolis, IN 46268-1053