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Development of Spinosad and Attributes of A New Class of Insect Control Products


Gary D. Thompson, Scott H. Hutchins and Thomas C. Sparks
Dow AgroSciences LLC
9330 Zionsville Rd., Indianapolis, IN, 46268, USA


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INTRODUCTION

The discovery and characterization of the soil actinomycete Saccharopolyspora spinosa represented a novel opportunity to develop a portfolio of progressive insect management tools (Thompson et al.1997, Sparks et al. 1998). Indeed, the discovery and subsequent development of this unique organism (Figure 1) has provided the world with an entirely new class of products - with Tracer* Naturalyte* Insect Control being the first to be commercialized.

The name is based on the utility of naturally produced metabolites that by definition possess rapid efficacy competitive with the best synthetic standards and safety profiles similar to benign biologicals. Spinosad is a mixture of the two most active naturally occurring metabolites (spinosyns A and D) produced by S. spinosa (Figure 2, Kirst et al., 1992).

Structurally, these compounds are macrolides and contain a unique tetracyclic ring system to which two different sugars are attached. A unique mode of action coupled with a high degree of activity on targeted pests and low toxicity to non-target organisms (including many beneficial arthropods) make spinosad an excellent new tool for management of insect pests. Dow AgroSciences is aggressively pursuing additional spinosyns and other metabolites from natural organisms as future entries to the Naturalyte class. This paper provides an overview of the physical and biological properties of spinosad. When these properties are considered, in total, it is clear that Naturalyte does not conform to the previous characteristics of either chemical or biological insecticides.

Physical Properties and Environmental Fate

Spinosad is a secondary metabolite from the aerobic fermentation of S. spinosa on nutrient media. Following fermentation, spinosad is extracted and processed to form a highly concentrated conventional aqueous suspension for ease of use and distribution. Spinosad is a light gray to white crystalline solid with an earthy odor similar to slightly stale water. It has a pH of 7.74, is stable to metal and metal ions for 28 days, and has a shelf life of three years as formulated material. It is considered nonvolatile with vapor pressures around 10-10 mm Hg. Table 1 summarizes other physical and chemical properties of spinosyns A and D (Anonymous, 1996).

Table 1. Physical and chemical properties of spinosyns A and D.

  Spinosyn A Spinosyn D
Molecular Weight 731.98 746.00
Empirical Formula C42H67NO16 C41H65NO16
Melting Point 84 - 99.5°C 161.5 - 170°C
Vapor Pressure 2.4 x 10-10 1.6 x 10-10
Solubility in Water at pH 5.0 290 ppm 29 ppm
Solubility in Water at pH 7.0 235 ppm 0.332 ppm
Solubility in Water at pH 9.0 16 ppm 0.053 ppm
Octanol/Water

Partition Coefficient at pH 5.0

 

log P = 2.8

 

log P = 3.2

Octanol/Water

Partition Coefficient at pH 7.0

 

log P = 4.0

 

log P = 4.5

Octanol/Water

Partition Coefficient at pH 9.0

 

log P = 5.2

 

log P = 5.2

 

The degradation of spinosad in the environment occurs through a combination of routes, primarily photodegradation and microbial degradation to its natural components of carbon, hydrogen, oxygen and nitrogen. The half-life of spinosad degraded by soil photolysis is 9-10 days. It is less than 1 day for aqueous photolysis and leaf surface photolysis results in a half-life of 1.6 to 16 days. The half-life of spinosad degraded by aerobic soil metabolism in the absence of light is 9-17 days. Hydrolysis does not contribute significantly to degradation as spinosad is relatively stable in water at a pH of 5-7 and has a half-life of at least 200 days at a pH of 9. The leaching potential of spinosad is very low due to a moderate Kd (5-323), low to moderate water solubility and short residual in the environment. Thus, it does not pose a threat to groundwater when used properly and no buffer zones are required by the United States Environmental Protection Agency (Saunders and Bret, 1997).

Nontarget Toxicology

Table 2 summarizes acute mammalian, aquatic and avian toxicology (Anonymous, 1996). Spinosad is relatively low in toxicity to mammals and birds and is only slightly toxic to fish.

Table 2. Acute mammalian, aquatic and avian toxicity of spinosad.

Species Test Result EPA Category
Mammalian      
Rat (male/female) Acute oral LD50 3738/>5000 mg/kg Caution (IV)
Mouse Acute oral LD50 >5000 mg/kg Caution (IV)
Rabbit Acute dermal LD50 >5000 mg/kg Caution (IV)
Rat Acute inhalation LC50 >5 mg/kg Caution (IV)
Rabbit Eye irritation slight, clearing in 2 days Caution (IV)
Rabbit Skin irritation no irritation Caution (IV)
Guinea pig Dermal sensitization no sensitization N. A.
Aquatic      
Daphnia 48 hr acute LC50 92.7 mg/L Slightly toxic
Grass shrimp 96 hr acute LC50 >9.8 mg/L Slightly toxic
Carp 96 hr acute LC50 5.0 mg/L Moderately toxic
Bluegill 96 hr acute LC50 5.9 mg/L Moderately toxic
Sheepshead minnow 96 hr acute LC50 7.9 mg/L Moderately toxic
Rainbow trout 96 hr acute LC50 30.0 mg/L Slightly toxic
Avian      
Bobwhite quail Acute oral LD50 >2,000 mg/kg Practically non-toxic
Mallard duck Acute oral LD50 >2,000 mg/kg Practically non-toxic
Bobwhite quail 5 day dietary LC50 >5,000 mg/kg Practically non-toxic
Mallard duck 5 day dietary LC50 >5,000 mg/kg Practically non-toxic

 

In addition, chronic toxicology tests in mammals have shown that spinosad is not carcinogenic, teratogenic, mutagenic or neurotoxic. Spinosad exhibits wide margins of safety to many beneficial insects and related organisms (Schoonover and Larson, 1995). Spinosad has relatively low activity against predaceous beetles, sucking insects, lacewings and mites. Table 3 demonstrates the reduced activity of spinosad on some.

Table 3. Toxicity of spinosad and cypermethrin to selected beneficial organisms.

Beneficial species Spinosad LC50 Cypermethrin LC50
Honeybee, Apis mellifera 11.5 ppm 1.2 ppm
Whitefly parasitoid, Encarsia formosa 29.1 ppm 1.9 ppm
Minute pirate bug, Orius insidiosus 200 ppm 0.2 ppm
Lady beetle, Hippodamia convergens >200 ppm 0.2 ppm
Lacewing, Chrysopa rufilabris >200 ppm <0.2 ppm
Predaceous mite, Phytoseiulus persimilis >200 ppm <0.2 ppm

 

Against lepidoptera targets the activity values for spinosad and cypermethrin generally overlap. It is extremely exciting to have this level of activity coupled with large margins of selectivity, for predacious insects, which are an important component of IPM programs. The topical acute activity of spinosad against honeybees is less than 1 µg per bee which places spinosad in the highly toxic to bees category of the EPA. However, once residues have dried completely, toxicity of foraging bees is considered negligible (Mayer and Lunden, 1998). There are minimal safety precautions and preharvest and reentry intervals for this reduced risk product.

Physiological Properties and Resistance Management

Spinosad demonstrates rapid contact and ingestion activity in insects which is unusual for a biological product. The mode of action of spinosad is characterized by excitation of the insect nervous system, leading to involuntary muscle contractions, prostration with tremors, and paralysis. These effects are consistent with the activation of nicotinic acetylcholine receptors by a mechanism that is clearly novel and unique among known insect control products. Spinosad also has effects on GABA receptor function that may contribute further to its insect activity. This mode of action is unique. Imidacloprid and other nicotinic receptor-based insecticides act at a different site than spinosad. Avermectin, although a natural product and a macrocyclic lactone, also acts at a different site than spinosad. No other class of products affects the insect nervous system with the same mode of action and no cross resistance to spinosad has been demonstrated (Salgado et al., 1997; Salgado, 1998; Salgado et al. 1998).

The unique mode of action, lack of cross resistance, selectivity that leaves predacious insects, and moderate residual profile result in a low probability of resistance development. This is particularly true if Naturalyte insect control products are brought into rotations with current and other new insect control products. However, the adaptability of insects has been proven over and over. Therefore, Dow AgroSciences is promoting resistance management of spinosad through labeling, education and marketing efforts in support of good stewardship and IPM practices but not because of any underlying concerns that would affect spinosad more than any other active ingredient.

In the field, spinosad activity is characterized by cessation of feeding and paralysis of exposed insects within minutes. However, these insects may remain on the plant for up to two days. For this reason, growers and scouts should wait a minimum of two to three days to evaluate control.

Foliar applications of spinosad are not highly systemic in plants although some translaminar movement in leaf tissue has been demonstrated. The addition of a penetrating surfactant increases translaminar movement and activity on pests that mine leaves (Larson, 1997). No phytotoxicity has been demonstrated with this product.

Spectrum of Activity and Labeling Efforts

Spinosad has been tested extensively on a global basis since 1990 (Carson and Trumble, 1997; Fouche et al., 1998; Kerns, 1996; Linduska et al., 1998; McLeod, 1998; Palumbo, 1997; Riley, 1998; Schuster, 1997, Stansly and Connor, 1998; Walgenbach and Palmer, 1997; Webb, 1998). Table 4 lists several of the insect pests against which spinosad is being labeled.

Table 4. Examples of Insect pests controlled by spinosad on current or future labels.

Common name Scientific name gm/ha
European corn borer Ostrinia nubilalis 25 -50
Tomato fruitworm Helicoverpa zea 40 - 100
Cabbage Looper Trichoplusia ni 50 - 100
Diamondback moth Plutella xylostella 15 -50
Southern armyworm Spodoptera eridania 50 - 100
Leafminers Liriomyza spp. 70 - 150
Melon thrips Thrips palmi 70 - 100
Fall armyworm Spodoptera frugiperda 25 - 100
Beet armyworm Spodoptera exigua 50 - 100
Colorado potato beetle Leptinotarsa decemlineata 25 - 80
Imported cabbageworm Pieris rapae 50 - 100
Tomato pinworm Keiferia lycopersicella 50 - 100
Grape Berry Moth Lobesia lobina 25 - 50
Cotton Leafworm Alabama argillacea 25-50
American bollworm Heliothis armigera 50 -100
Tomato hornworm Manduca quinquemaculata 40 - 100
Western flower thrips Frankliniella occidentalis 70 - 100

In general, spinosad provides effective control of pests in the insect orders Lepidoptera, Diptera, and Thysanoptera. It is also effective for some species Coleoptera and Orthoptera that consume large amounts of foliage. Spinosad is generally not effective for control of most sucking insects, and mites but some use patterns are being investigated.

Product Labeling

Spinosad is currently labeled in the U.S. on the brassica vegetable group (broccoli, Chinese broccoli, Brussels sprouts, cabbage, Chinese cabbage - bok choy and napa, cauliflower, cavalo, collards, kale, kohlrabi, mizuna, mustard greens, mustard spinach, Chinese mustard cabbage - gai choy, and rape greens), fruiting vegetable group (eggplant, ground cherry, pepino, pepper, tomatillo, and tomato), leafy vegetable group (including head and leaf lettuce, celery, arugula, chervil, edible chrysanthemum, corn salad, cress, dandelion, dock, endive, fennel, parsley, garden purslane, radicchio, rhubarb, spinach, and Swiss chard), apples, almonds and citrus. Crops for which additional U. S. labeling is being pursued include cucurbits, legumes, sweet corn, potatoes, and strawberries. Table 5 lists the global registration status at the time this paper was

Table 5. Current and Pending Naturalyte* Insect Control Registrations

County  Trademarks  Crops  First Registration** 
Argentina  Tracer*, Success*  Cotton, Tomato  1998 
Australia  Tracer  Cotton  1998 
Laser  Brassica  1999 
Success  Vegetables   2000 
Benelux  -  Pome fruit, Vegs.  2002 
Bolivia  Tracer  Cotton/Soybeans  1998 
Brazil  Tracer, Credence*  Tomato, Corn  1998 
Soybean, Cotton,   1999 
Canada  Success  Apples, Potatoes  1999 
Stone Fruit  2000 
Chile  Success  Nectarines, Tomato  1998 
China  Success

Tracer 

Vegetable

Cotton 

1998

1998 

Columbia  Tracer 120SC  Flowers, Cotton, Begs.  1998 
Cyprus  Tracer 48 SC  Vegetables, Potatoes  1998 
Ecuador  Tracer  Corn, Vegetables  1998 
France  -  Vines  2001 
Ornamentals  2001 
Germany  -  Flybait, Ornamentals  2000 
Greece  -  Vines, Pome fruit, Vegs.  2001 
Guatemala  Tracer  Cotton

Cucurbits, Brassica  

1998

2000 

Honduras  Tracer  Cotton  1998 
Indonesia  Success  Vegetable  1998 
Israel  _  Vines, Vegetables  1998 
Italy  _  Ornamentals, Vegs.  2001 
Grapes, Pome fruit  2001 
       
Japan  Spinoace*, Naturalyte

Caribstar* 

Turf

Brassica

Peach, Pear 

1999

1999

2001 

       
Korea  Boomerang  Cucumber  1997 
    Cabbage, Rose  1998 
       
Lebanon  -  Vegetable, Potatoes  1998 
       
Malaysia  Success 25SC  Vegetables  1998 
       
Mexico  Tracer, Success  Cotton  1997 
    Fruiting Vegetables  1998 
    Brassica & Leafy Veg.  1998 
       
New Zealand  Success  Vegetables  1998 
       
Philippines   Success 25 SC  Vegetable  1998 
       
Spain  -  Vines  2001 
    Pepper, Tomatoes  2001 
       
Taiwan  Success  Vegetable  1999 
       
Thailand  Success  Vegetable  1998 
       
Tunisia    Vegetables, Citrus  1998 
       
Turkey  -  Grapes  1998 
       
U.S.  Tracer, Conserve*

SpinTor*, Success 

Cotton

Turf & Ornamentals 

1997

1997 

    Brassica Crops  1998 
    Apple, Tomato  1998 
    Tobacco  1998 
    Leafy Vegetables  1998 
    Citrus, Almonds  1998 
    Cucurbits, Legumes  1998 
    Stone Fruit, Potatoes  1999 
    Cereal Grains  1999 
    Minor Crops  1999+ 
       
UAE  _ Vegetable  1998 
       
Uruguay  Success  Citrus  1998 
       
Venezuela  Tracer  Corn  1998 

*Trademark of Dow AgroSciences LLC

** Registration Dates are estimates

The favorable mammalian and environmental profile, insect selectivity and IPM fit, unique mode of action and resistance management properties, and outstanding efficacy are resulting in rapid registrations and adoption by growers around the world documenting the value to agriculture.

LITERATURE CITED

Anonymous. 1996. Spinosad technical guide. DowElanco (now Dow AgroSciences LLC), 25 pp.

Carson, W. G. and J. T. Trumble. 1997. Effect of insecticides on celery insects, 1995. Arthropod Management Tests: 1997, vol. 22:117.

Fouche, C., M. Canevari and D. Cutter. 1998. Evaluation of insecticides for control of leafminers on lima beans, 1997. Arthropod Management Tests. 23:74-75.

Kerns, D. L. 1996. Control of lepidopterous larvae and leafminers in lettuce, 1995. Arthropod Management Tests. 21:117-118.

Kirst, H. A., K. H. Michel, J. S. Mynderse, E. H. Chao, R. C. Yao, W. M. Nakatsukasa, L. D. Boeck, J.

Occlowitz, J. W. Paschel, J. B. Deeter and G. D. Thompson. 1992. Discovery, isolation and structure elucidation of a family of structurally unique fermentation-derived tetracyclic

macrolides. In: D. R. Baker, J. G. Fenyes and J. J. Steffens, Eds., Synthesis and chemistry of agrochemicals III. Am. Chem. Soc., Washington, D. C., pp. 214-225.

Larson, L. L. 1997. Effects of adjuvants on the activity of Tracer™ 480SC on cotton in the laboratory, 1996. Arthropod Management Tests. 22:415-416.

Linduska, J. J., M. Ross, D. Baumann and A. Parr. 1998. Foliar sprays to control ear-invading insects on sweet corn, 1997. Arthropod Management Tests: 23:95-96.

Mayer, D. F. and J.D. Lunden. 1998. Research Reports: 72nd Annual Western Orchard Pest & Disease

Management Conference. Oregon Extension Service. pp73-74.

McLeod, P. 1998. Evaluation of insecticides for control of corn earworm on snap bean, 1997. Arthropod Management Tests. 23:75.

Palumbo, J. C. 1997. Evaluation of selective insecticides for control of lepidopterous larvae in lettuce.  Arthropod Management Tests. 22:136.

Riley, D. G. 1998. Evaluation of insecticide treatments on cabbage, 1997. Arthropod Management Tests. 23:82.

Salgado, V. L. 1997. The mode of action of spinosad and other insect control products. Down to Earth. 52(1), 35-44.

Salgado, V.L. 1998. Studies on the mode of action of spinosad: Insect symptoms and physiology correlates. Pesticide Biochemistry and Physiology. 60(2):91-102.

Salgado, V. L. , J.J. Sheets, G. B. Watson, A. L. Schmidt. 1998. Studies on the mode of action of spinosad:  The internal effective concentration and the concentration dependence of neural excitation. Pesticide Biochemistry and Physiology. 60(2):103-110.

Schoonover, J. R. and L. L. Larson. 1995. Laboratory activity of spinosad on non-target beneficial arthropods, 1994. Arthropod Management Tests. 20:357.

Schuster, D. J. 1997. Management of insects on fresh market tomatoes, spring, 1996A. Arthropod Management Tests. 22:182.

Sparks, T. C.; G. D Thompson,. H. A. Kirst,. M. B. Hertlein, J. S. Mynderse, J. R Turner,.T. V. Worden, (1998). Fermentation-Derived Insect Control Agents The Spinosyns. In: Methods in

Biotechnology, Biopesticides: Use and Delivery. (eds. F. R. Hall and J. J. Menn). 5: 171-188. Humana Press. Totowa, NJ.

Stansly, P. A. and J. M. Connor. 1998. Impact of insecticides alone and in rotation on tomato pinworm, leafminer and beneficial arthropods in staked tomato, 1997. Arthropod Management Tests: 23:162-165.

Walgenbach, J. F. and C. R. Palmer. 1997. Control of lepidopterous insects on cabbage, 1996.  Arthropod Management Tests. 22:113.

Webb, S. E. 1998. Control of pickleworm on squash with selective insecticides, 1997. Arthropod Management Tests. 23:142-143.