1. The Benefits of Agrochemical Research: Case Study of Imidacloprid
Sujatha Sankula & Leonard Gianessi
National Center for Food and Ag. Policy
Washington, DC

2. Agrochemical categories
Herbicides (47%)
Insecticides (29%)
Fungicides (18%)
Fumigants & growth regulators (6%)
Agrochemicals are chemicals used in crop and food production. Agrochemicals include pesticides, feed additives, veterinary drugs, and related compounds. The focus of my today's talk is on agrochemicals that have pesticide properties. These chemicals are categorized into herbicides, insecticides, fungicides, and fumigants depending on the type of agrochemical action. Herbicides rank number one among pesticides with a market share of almost 50%.

3. Agrochemicals are necessary to…
 Prevent yield losses
 Ensure quality
 Make crop production
easier & cheaper
Agrochemical use is pivotal to crop production to prevent yield losses from pest populations, ensure produce quality, and to make crop production simpler and cheaper.

4. Crop yield response to agrochemicals
Without agrochemical use; With agrochemical use
Theoretical attainable yield
Abstinence of agrochemicals will have a serious economic impact on crop production. Estimates suggest that theoretical yields of major crops would decline from 16 to 40% depending on the crop if agrochemicals are not used for pest protection. For example, potato yield loss would be 32% while cotton suffers 40% losses if agrochemicals are not used in the production of respective crops.

5. Area farmed globally for food production in 2000
Billion ha
Thanx to agrochemicals, global farm area needed to feed world population in 2000 was 1.5 billion ha in contrast to 4 billion ha without agrochemicals.

6. Global value of agrochemicals in 1998
$31.25 billion (crop uses)
$10.5 billion (non-crop uses)
The market value of agrochemicals used for crop pest protection is valued at billion dollars at the user level in Pesticide demand for non-crop use applications such as home, garden, and golf courses has been increasing each year and was valued at 10.5 billion dollars in the same year.

7. Worldwide crop protection markets in 2001
Sales in mil. $
13 countries account for almost 80% of the global agrochemical market. The developed countries such as the United States, Europe, and Japan account for the lion’s share of demand, with approximately 70% of the value.

8. Goal of agrochemical research
To discover, develop, and understand new products for the safe and effective pest control and to maximize food production
The primary goal of agrochemical research is to discover and develop new products to address the unmet crop protection needs thereby enhancing the food production. Therefore, agrochemical research is a dynamic and continual process to provide solutions for new pest management challenges.

9. Agrochemical discovery & development programs are driven by:
Population growth
Food and health needs
Pest resistance issues
Safety considerations
Economic incentives
Replacements and phase-outs
The agrochemical discovery programs involve sifting of millions of compounds through random screening. These research and discovery programs are driven by several factors of which the important ones are population growth demands, food and health needs, pest resistance and safety considerations, economic incentives, and chemical replacements.

10. Recent setbacks to agrochemical discovery programs:
Fewer players
Large investments
Great risks
High stakes
Economics
Higher standards of potency and safety
However, the last few years have been difficult for agrochemical research. The discovery process has slowed to one with fewer players, larger investments, great risks, and high stakes. Only a few agrochemicals have been developed in the past few years for reasons such as economics and higher standards of safety.

11. Insecticide categories
Organic (eg. DDT, chlorpyriphos)
Botanicals (eg. pyrethrum, nicotine)
Inorganic (eg. boric acid, sulfur)
Today, I want to focus on the benefits of agrochemical research taking the insecticide imidacloprid as an example. Just to give some background information on insecticide categories, based on chemical makeup, insecticides are classified as organic and inorganic. Organic insecticides contain carbon in their backbone, while inorganic insecticides lack carbon. Plant-derived insecticides contain carbon and therefore are considered organic.

12. Market dominance of commercial insecticide categories
Category #
Inorganics
Botanical
Synthetic organics
Synthetic organic insecticides comprise about 96% of the current commercial insecticide market. Inorganic insecticides are used to a little extent due to high use rates and marginal control while natural botanicals are limited in availability and expensive.

13. Major insecticide classes by importance as of 1995
Class ~ Entry year Market value (%)
Chlorinated hydrocarbons
Organophosphates
Methylcarbamates
Pyrethroids
Benzoylureas
Others
This is The evolution of various insecticide classes over time is an example of why agrochemical research is needed. Chlorinated hydrocarbons, the first and oldest class of synthetic insecticides used in crop production entered the market in 1940s. Toxicological and environmental contamination issues led to severe restrictions on this group and subsequent entry of OPs and carbamate insecticides in the mid to late 1960s.

14. Human toxicity and insect resistance to the first generation neuro-active insecticides such as carbamates and OPs led to the search for new agrochemicals Significant discovery - Imidacloprid
Organophosphate and carbamate insecticides interfere with normal synaptic transmission of the nervous system and therefore are toxic to human beings. In addition, several insect species have developed resistance to chemicals in both these classes rendering their use ineffective. This led to search for alternative chemicals that circumvent resistance and are safe to humans. A significant product of this search is the discovery and development of imidacloprid.

15. Imidacloprid Classification: Chloronicotinyl
First registered insecticide in its class
Year of registration in US: 1995
Imidacloprid was first synthesized by Bayer in It belongs to the class chloronicotinyls. It was first registered for crop use in 1992 in Europe and Asia and subsequently in the United States in 1995.

16. World sales of top selling pesticides in 2001
Glyphosate $2.4 billion
Imidacloprid $540 million
Due to its unique combination of characteristics, imidacloprid is the most widely used insecticide worldwide. Based on a 2001 estimate, it is the top selling pesticide after the herbicide glyphosate or Roundup.
Source: PANUPS 2002

17. Structural comparison of nicotine and imidacloprid
Chloronicotinyl insecticides are synthetic nicotinoids modeled after the insecticide nicotine. Thus, imidacloprid possess structural resemblance to nicotine and acts similar to nicotine.

18. Characteristics of imidacloprid
Novel mode of action
Broad spectrum of activity
Favorable environment fate
The characteristic features that set imidacloprid apart from the other insecticides to which insects developed resistance are its novel mode of action, broad spectrum of activity, and favorable environmental fate.

19. Mode of action of imidacloprid
Binds to nerve receptors called nicotinic
acetylcholine receptors (nAChRs), interferes
with the transmission of stimuli in the insect
nervous system leading to the accumulation
of acetylcholine resulting in paralysis.
Similar to nicotine, imidacloprid mimics the mimics the action of a neurotransmitter called acetylcholine. Acetylcholine normally turns on a nerve impulse but its effects are terminated very quickly. Imidacloprid turns on the nerve impulse but cannot terminate it because of its chemical structure. Therefore, the nervous system is overexcited resulting in tremors and finally paralysis.

20. Site of action is different than other insecticides
to which insects developed resistance.
Low toxicity to vertebrates due to low binding
to nACh receptors.
Unlike OPs and carbamates which bind to the enzyme acetylcholinesterase, the site of action of imidacloprid is different. Moreover, imidacloprid toxicity to veterbrates is extremely low due to poor binding to acetylcholine receptors. .

21. Imidacloprid provides a broad spectrum of activity against:
Sucking insects (leaf and plant hoppers, aphids,
thrips, whiteflies, scales, and plant bugs)
Some coleopteran insects (CPB, leaf beetles)
Select lepidopteran and dipteran insects
No activity on mites and nematodes
Imidacloprid has a broad spectrum of activity against a wide range sucking insect pests such as aphids, white flies, scale insects and mealy bugs, as well as select coloepteran, lepidopteran, and dipteran insects. However, it has no activity against mites and nematodes.

22. Imidacloprid has both contact and systemic action.
Imidacloprid can be applied as a soil, seed, or foliar treatment.
Readily absorbed by plant roots and transmitted through xylem.
Effective at low rates than conventional insecticides (0.33 lb versus 1-2 lb of OPs)
Imidacloprid possess both contact and systemic activity. Following the application, it is taken up into the plant by the roots and is then transported to the shoot to protect young plants for a length of time. It can be applied in a wide variety of methods, as seed, soil or foliar treatments. Other favorable characteristics include low use rates, strong binding to organic matter, and long residual control.

23. Trade names of imidacloprid
Gaucho (seed treatment)
Admire (soil applied)
Provado (foliar)
Based on the method of application, imidacloprid is marketed under Gaucho, Admire, or Provado. While Admire is the soil applied formulation, Provado is a foliar formulation.

24. Use range of imidacloprid
Potato Apple
Tomato Grape
Broccoli Citrus
Lettuce Corn
Sugarbeet Hops
Cotton Rice
Tobacco
Imidacloprid is used on a wide range of crops including cereals, field crops, vegetables, fruits, turf, and ornamentals.

25. Impacts of imidacloprid on US crop production
I am going to switch gears now and talk about the benefits of agrochemical research on US agriculture using imidacloprid as a case study. A major impact of imidacloprid is the reduction in aphid and whitefly problems in American crop production which I am going to discuss in detail next.

26. First discovered in 1986 in FL Widespread damage in 1991 in CA and AZ
Silverleaf whitefly
First discovered in 1986 in FL
Widespread damage in 1991 in CA and AZ
Reduction in planted crop acreage
Yield and quality losses; transmits viruses
(ToMoV and YLCLV)
Silverleaf whitefly was first identified in Florida greenhouses in 1986 as a new strain of sweet potato whitefly. Silverleaf whitefly is a notorious pest due to its explosive reproductive potential. It was introduced in CA and AZ in the early 1990s and caused extensive damage on cole crops and melons. Production of some crops was ceased altogether due to the economic losses caused by this insect. In addition, silverleaf whitefly acts as vector in transmitting the mosaic virus and yellow leaf curl virus to tomato.

27. Silverleaf whitefly is a billion dollar pest
Estimates of monetary costs to US agriculture due to crop loss and control costs are now approaching one billion dollars making it an expensive pest similar to European corn borer.

28. Primary hosts of silverleaf whitefly
Broccoli
Cauliflower
Cabbage
Lettuce
Melons
Cucumbers
Tomatoes
Cotton
The host range of silverleaf whitefly is wide and encompasses agronomic crops and weeds. These plants include cole crops such as broccoli and cauliflower, melons such as cantaloupes, and other crops such as tomato and cotton.

29. Silverleaf whitefly management
Three classes of effective insecticides (pyrethroids,
OPs, & chlorinated hydrocarbons)
Most common combination: bifenthrin + endosulfan
(2-3) fb. esfenvalerate + endosulfan (1-3)
No residual control and periodic treatments
(4-6 sprays)
Insect resistance to three chemical classes
The insecticides most commonly used for silverleaf whitefly control belonged to the classes pyrethroids, OPs, and chlorinated hydrocarbons. Most of these insectides are applied as foliar treatments and have no residual activity necessitating repeated applications through out the growing season. It is not uncommon for growers to apply 4 to 6 sprays to manage whitefly infestations. In addition, silverleaf whitefly developed resistance to all the three chemical classes used for its control.

30. Section 18 permits for imidacloprid (Admire) in California
First issue
Reissue
Broccoli/Cauliflower
Lettuce
Cucurbits
Tomatoes
Silverleaf whitefly first invaded CA in 1991 and growers endured serious yield losses. In 1991, Imidacloprid was still under testing and was not registered for use in CA. In view of the extent of losses caused due to this pest, emergency use permits were first issued in 1993 for cole crops, 1994 for tomatoes, and in 1995 for cucurbits in CA. The permits were renewed for a second time for cole crops and cucurbits.

31. Vegetable production statistics for CA
2001 Acreage (% of US total)
Broccoli 92
Lettuce (head)
88 (leaf)
Cauliflower 89
Tomato 32 (fresh)
92 (processed)
Cantaloupe 58
The development and registration of imidacloprid has special significance to CA agriculture because CA is a leading vegetable producing state and silverleaf whitefly has been a serious problem in CA vegetable production. CA produces 92% of national broccoli, 88% of leaf lettuce, 89% of cauliflower, 92% of processed tomato, and 58% of cantaloupe.

32. Use of imidacloprid (Admire) in California in 1995
% treated acreage
In 1995, the first year of commercial introduction of imidacloprid, it was used on 40% of cantaloupe acreage and on more than 50% of the lettuce, cole crop and tomato acreage.

33. Impacts of imidacloprid (Admire) on CA crop production
.. And this is how imidacloprid used in the form of soil treatment Admire impacted CA crop production.

34. Number of insecticide applications with Admire and next best alternative
# treatments
A major impact of imidacloprid on CA crop production is the reduction in the number of insecticide applications. Whitefly control using imidacloprid consisted of a soil application of Admire followed by 1 or 2 applications of esfenvalerate + endosulfan. This is in contrast to the prior alternatives which were applied 4 to 6 times. As a result, number of insecticide treatments were reduced by 50% in broccoli, cauliflower, tomato, and cantaloupe and 80% in head and leaf lettuce due to imidacloprid compared to the traditional alternatives.

35. Cost of insecticide programs with Admire and next best alternative
Cost of programs ($)
Insecticide programs involving imidacloprid costed 30% less than the next best alternative for cole crops, 60% less for lettuce, 40% less for tomato, and 43% less for cantaloupe. This is mainly due to a reduction in number of applications with imdacloprid. Higher cost of imidacloprid was offset by low use rate and cheaper application costs associated with soil application.

36. Yield increase due to Admire compared to traditional alternatives in CA
Though not huge, imidacloprid use resulted in yield increase in CA crops. Yield increase ranged between 2 to 4%, with greatest increases recorded in lettuce and melons.

37. Value of delayed planting
Warm weather: heavy whitefly pressure
Growers shift the planting date to cooler periods to
avoid peak infestations
Imidacloprid facilitated marketing at the height of
infestation
Other area where imidacloprid use benefited CA growers significantly is the flexibility in timing the planting. In response to severe whitefly pressure in warm temperatures, growers were planting their crops in cooler parts of the year. However, with the introduction of imidacloprid, growers were able to plant any time during the season and were able to market the crop during the months of higher prices.

38. Increase in grower benefits due to delayed planting facilitated by Admire
As a result, grower benefits with imidacloprid use increased by 3 to 7% in CA, depending on the crop.

39. 1992 2000 Impact of imidacloprid on insecticide use in FL
fresh tomato for whitefly and other sucking pest control
1992
2000 lb
Buprofezin
Chlorpyrifos 22,
Endosulfan 89, ,900
Esfenvalerate 5, ,200
Imidacloprid ,400
Methamidophos 74, ,100
Methomyl 47,
Permethrin 10, ,000
Total , ,600
In Florida where imidacloprid was used on 65% of the fresh tomato acreage in 2000 for whitefly and other sucking pest control, growers were able to reduce their insecticide use by 74% following the use of imidacloprid. Florida is the number one fresh tomato producer in the United States.

40. Colorado Potato Beetle
Colorado potato beetle is the number one defoliating insect pest problem in potato production. Both the larval and adult stages of the beetle feed on leaves, reduce the photosynthetic area thereby causing severe yield and quality losses.

41. Green peach aphids
Green peach aphid is another most damaging pest on potato. It transmits the potato leaf roll virus which causes tuber net necrosis leading to serious losses

42. Insecticide use: CPB/aphids
1920’s ’s Lead arsenate
1950’s ’s DDT, Parathion,
Endrin
1970’s - Present Aldicarb, Phorate,
Methamidophos,
Carbofuran,
Endosulfan
Permethrin
Growers have been using a wide variety of insecticides belonging to arsenials, carbamates, OCs,OPs, and pyrethroids to combat both the beetle and aphid populations.

43. CPB management problems
CPB resistance to all synthetic insecticides
registered for use
Cross-resistance of CPB between insecticide
classes
Imidacloprid – unrelated chemistry and thus a
new tool in resistance management programs
A major problem in Colorado potato beetle management is its legendary ability to develop resistance to a wide range of insecticides used against it. The first instance of CPB resistance to synthetic insecticides was noted for DDT in In subsequent years, it has developed resistance to almost all the insecticides used for its control. Imidacloprid use for CPB control began in 1995 as a tool in resistance management programs.

44. Imidacloprid treated potato acreage (%) in 1999
Idaho 8
Maine 90
Michigan 93
Minnesota 70
North Dakota 68
Oregon 35
Pennsylvania 81
Washington 4
Wisconsin 74
Consequently, acres treated with imidacloprid increased tremendously in states where resistance was a serious problem. Adoption of imidacloprid was low in WA and ID where the beetle is still susceptible to most insecticides and has not developed the level of resistance noted elsewhere.

45. Leading insecticides used for CPB control in 2001 (in order of importance)
Imidacloprid
Carbofuran
Permethrin
Phorate
Esfenvalerate
Endosulfan
Methamidophos
Azinophos-methyl
Aldicarb
Methyl parathion
Dimethoate
As of 2001, imidacloprid is the number one insecticide used for CPB control in the United States. The top potato insecticides account for 60% of the total.

46. Reduction in insecticide use following imidacloprid use in potato (1994 –1999)
In Maine and Michigan where imidacloprid adoption was very high due to insect resistance problems, insecticide use was reduced significantly. While insecticide use reduction in Maine was 75%, it was 61% in MI.
Source: NASS

47. Pierce’s disease on grapes
The long history of Pierce’s disease in grapes in California coupled with the recent introduction of the glassy-winged sharpshooter in 1996 has created a high level of concern in grape and wine industry. Within 2 years of the introduction of glassywinged sharpshooter, an estimated 12 million dollars were lost in CA due to vine removal.

48. Sharpshooters Bluegreen Glassy-winged
The traditional vector of Pierce’s disease, the bluegreen sharpshooter, has only one generation and a limited host range. Infections by bluegreen sharpshooter do not spread very far down the vine and can be pruned out. However, the glassy winged sharpshooter is a strong flier, has a wide host range, feeds on larger and older canes thus spreading the disease from vine to vine.
Glassy-winged

49. Pesticides registered for sharpshooter control
Average use rate
(lb/A)
Dimethoate
Kaolin
Imidacloprid
(Admire)
There is no cure for Pierce’s disease. The best way to prevent the disease is to control the sharpshooters that transmit the disease. Only 2 insecticides have been labeled for the control of sharpshooters in grape. They are dimethoate and Kaolin. Dimethoate is not very effective on adult sharpshooters. Kaolin applications are limited due to its high use rates. In 2000, an emergency exemption was granted to use Admire in CA. Since then, CA grape growers replaced traditional insecticide use imidacloprid and were able to reduce the spread of Pierce’s disease significantly due to reduced feeding by sharpshooters.

50. Other grape insects controlled by Admire
Grape mealybug
Vine mealybug
Leafhopper
Phylloxera
In addition to sharpshooters, imidacloprid can also control other economically important grape pests such as mealy bugs, leafhoppers, and phylloxera.

51. Insect management problems in citrus in CA and FL
Glassy-winged sharpshooter (overwintering host)
California red scale ( resistant to OP &carbamates)
Citricola scale (increasing in problem)
Brown citrus aphid (vectors citrus tristeza virus)
Citrus is one of the primary overwintering hosts of glassywinged sharpshooter in CA and high population of sharpshooters are usually noticed when citrus and grape border each other. Even if they are not, glassywinged sharpshooter is a strong flier and infests citrus orchards. Other citrus pest problems in CA include red scale and citricola scale. Citrus growers discontinued using OP and carbamate insecticides as California red scale has developed resistance. As a result, citricola scale which is usually sensitive to these insecticides has become an increasing problem.
Brown citrus aphid was introduced from central America into FL in Brown citrus aphid is a cause for concern because it transmits tristeza virus, the most devastating citrus disease. It is spreading fast in FL but control has become difficult due its fast multiplication.

52. Use of imidacloprid on citrus (Section 18 in CA and FL)
Glassy-winged sharpshooter
CA red scale
Citrus brown aphid
Citrus leaf miner
To address these problems, Section 18 permits were issued in 2001 for imidacloprid use to control sharpshooters and red scale in CA and brown aphid and leaf miner in FL.

53. Cotton pest problems Escalation of secondary pest problems
Insecticide resistance
The combination of boll weevil eradication programs and Bt cotton in mid south and southeast has led to a reduction of OP and pyrethroid sprays but also allowed the escalation of secondary pests such as aphids from occasional to severe pest. Moreover cotton aphids have developed resistance to pyrethroid and OP insecticides used for their control. In California in particular, use of growth regulators to promote plant growth in 1990s and use of the pyrethroid Capture resulted in aphid resistance and led to a severe outbreak in 1995.

54. Losses due to aphids in CA cotton in 1997
Crop loss Control costs
Aphids
All insects and mites
Million $
A 1997 estimate suggests that yield losses due to aphids account for 50% of the total crop loss and 25% of the total control costs, suggesting that aphids management is crucial in cotton production.

55. Imidacloprid treated cotton acreage in California
% treated acres
In response to the 1995 aphid outbreak that caused severe losses to CA growers, imidacloprid adoption has increased rapidly. By 1998, the number of acres treated with imidacloprid increased by 157% compared to 1995.
Source: NASS

56. Summary Sucking pests have not been a significant problem
to growers in the recent years, largely because of the
advances in agrochemical research that resulted in
the development of imidacloprid.
American growers were able to increase crop yields,
reduce crop production costs, and insecticide use
following the introduction of imidacloprid.
No agrochemical is immune to problems.
In summary, sucking pests which have been a major problem due to insecticide resistance issues prior to the introduction of imidacloprid have turned out to be less of a problem lately. American growers were able to benefit significantly from this agrochemical in terms of yield gains and reduction in production costs. However, similar to other insecticides, imidacloprid is not a magic bullet and is immune to problems. Reports that cite insect resistance to imidacloprid have been surfacing recently emphasizing the need for continued agrochemical research. To combat resistance, imidacloprid is now used as a tool in integrated programs to preserve its efficacy.

57. Conclusions
With the increasing safety and environmental concerns, there will be loss of some agrochemicals. Search for replacement products that can live up to both regulatory and grower standards necessitates continued agrochemical research.
Agrochemical research should continue to meet the increasing demands of growing population.
Continued agrochemical research will provide solutions to evolving pest and their management problems.
In view of the toxicity and environmental issues, some of the agrochemicals may be removed from the market in the next few years, and the organophosphate and carbamate insecticides are being targeted as prime candidates for reduced use. Therefore, continued agrochemical research will facilitate the development of products that can live up to both regulatory and grower standards. Furthermore, agrochemical research should go on to meet the increasing demands of ever the growing population to provide solutions to the evolving pest and management problems.

58.
This concludes my presentation and I will take any questions u may have.