EA040491B1 - MICROCAPSULES ENCAPSULATED WITH LAMBDA-CYGALOTHRIN - Google Patents

Description

The present invention relates to certain compositions containing microcapsules encapsulating a pyrethroid insecticide and to methods for controlling plant damage using such compositions.

Microencapsulation of pesticides and other agricultural chemicals has been carried out over a number of years using various microencapsulation methods or techniques and with a number of different active ingredients.

WO 97/44125, WO 96/33611, WO 95/13698 and US 4285720 each disclose microencapsulation of pesticides.

WO 97/44125 describes that pyrethroids, in particular lambda-cyhalothrin, when applied foliarly must be encapsulated because of the risk they pose to workers, but the capsules must also be such that lambda-cyhalothrin is released relatively quickly to control target leaf pests.

Microencapsulation of different active ingredients requires different principles, and WO 97/44125 states that a polyurea shell made from a certain mixture of isocyanates in a certain ratio will be preferred.

The present inventors have found that microcapsules encapsulating pyrethroids do need to have a specific defined polyurea shell, but the properties of the shell now considered desirable are in conflict with the properties of the shell described in WO 97/44125, in particular in terms of providing improved levels of performance. harmful effects on workers, such as an improved toxicological profile, while maintaining effective activity in pest control.

Accordingly, in a first aspect, the present invention provides a composition comprising a polyurea-shell microcapsule encapsulating a pyrethroid insecticide, preferably lambda-cyhalothrin, wherein the polyurea shell of the microcapsule is made of polyurea polymers derived from a blend of an aromatic polyisocyanate (A) and an aromatic diisocyanate (B), wherein the ratio by weight of (A) and (B) is about 1:1, the content of polymer (or shell) in each microcapsule is from about 6 to about 9, preferably from about 7 to about 8 wt.%, and the amount of pyrethroid insecticide, preferably lambda-cyhalothrin is from about 15 to about 60, preferably from about 20 to about 55% by weight, each based on the weight of the microcapsule.

In a second aspect, the present invention provides an aqueous composition comprising the composition of the first aspect, provided that the composition does not contain one or more of the following: an active ingredient with a melting point that is 25° C. or less than or equal to 50° C.; the active ingredient in the form of a salt; and a free or dispersed hydrophobic oil phase.

In a further aspect, the present invention provides a composition comprising the aqueous composition of the first or second aspects and one or more additional active ingredients.

In a further aspect, the present invention provides a method of controlling pest damage to a plant, comprising applying an effective amount of a composition of each of the aspects of the present invention to the pest, plant, or location thereof.

In one embodiment of each aspect, the pyrethroid insecticide is lambda-cyhalothrin. The pyrethroid insecticide is present in the central part of the capsules, and in the case of lambda-cyhalothrin, it is dissolved in an organic solvent.

In one embodiment of the first aspect, the median diameter d50 of the microcapsule in the composition is from about 0.5 to about 5, preferably from about 1 to about 4 microns.

In one embodiment of the first aspect, the number of microcapsules in the composition is from about 45 to about 55, preferably from about 47 to about 53 wt.%, based on the weight of the composition.

In one embodiment of the first aspect, the pyrethroid is present in an amount of from about 20 to about 55, preferably from about 40 to about 50, more preferably from about 43 to about 47 wt.%, based on the weight of the microcapsule.

In a further embodiment of the first aspect, the organic phase also includes dispersed titanium dioxide particles with a median particle diameter d50 of about 0.1 to about 0.6, preferably about 0.15 to about 0.5 µm, which are present in an amount from about 3 to about 7, preferably from about 3.5 to about 6 wt.%, based on the weight of the microcapsule.

In one embodiment, the aromatic polyisocyanate is polymethylene polyphenylisocyanate and the aromatic diisocyanate is toluene diisocyanate, preferably a mixture of toluene diisocyanate isomers, such as about 80% of the 2,4 isomer and about 20% of the 2,6 toluene diisocyanate isomer.

In one embodiment of the first aspect, the composition comprises a polyurea shell microcapsule encapsulating lambda-cyhalothrin and dispersed titanium dioxide particles, where the polyurea shell of the microcapsule is made of polyurea polymers obtained from a mixture of polymethylene polyphenylisocyanate (A) and a mixture of isomers of toluene diisocyanate (B), provided that the median particle diameter d50 for titanium dioxide particles is from about 0.15 to about 0.5 μm, the median diameter d50 of the microcapsule in the composition is from 1 to 4 μm, the ratio by weight of (A) and (B) is approximately 1: 1, the content of polymer (or shell) in each microcapsule is from about 7 to about 8 wt.%, titanium dioxide is present in an amount of from about 3.5 to about 6 wt.%, and the amount of lambda-cyhalothrin is from about 40 up to about 50% by weight, based on the weight of the microcapsule; and further provided that the amount of microcapsules in the composition is from about 47% to about 53% by weight, each based on the weight of the composition.

General methods for preparing microencapsulated formulations of the present invention are described in WO 97/44125. However, as noted, one of the significant differences is the ratio of isocyanate monomers used to manufacture the polyurea shell of the microcapsule.

Accordingly, the method, in brief, comprises encapsulating a water-immiscible material (in this case preferably an organic phase containing a pyrethroid insecticide) in separate polyurea capsules. In this process, an isocyanate monomer is hydrolyzed to form an amine via a carbamic acid intermediate, which in turn reacts with another isocyanate monomer to form a polyurea. In general, the method involves two stages.

In the first step, a physical dispersion of the water-immiscible phase in the aqueous phase is obtained. The water-immiscible phase contains the pesticide, which is to be encapsulated along with other material as described below. As is known in the art, the dispersion is produced using a high shear device and this step is carried out until the desired droplet size is obtained (as discussed below). The rest of the process requires only light agitation.

In the second step, the dispersion is agitated at high shear and maintained in a temperature range of about 20°C to about 90°C, during which the reaction between the organic diisocyanate and the organic polyisocyanate occurs to form a polyurea at the interface between the droplets of the organic phase and the aqueous phase. By adjusting the pH of the resulting mixture and the temperature range in the second stage, this condensation reaction is allowed to proceed.

The aqueous phase is prepared from water, a protective colloid and preferably a surfactant.

In general, the surfactant or surfactants in this phase may be anionic or nonionic surfactants with an HLB range of about 12 to about 16. If more than one surfactant is used, then individual surfactants may have HLB values below 12 or above 16 if the total HLB value for the combined surfactants is in the range of 12 to 16. Suitable surfactants include polyethylene glycol ethers of linear alcohols, ethoxylated nonylphenols, naphthalenesulfonates, salts of long chain alkylbenzenesulfonates, block copolymers of propylene oxide and ethylene oxide, anionic/nonionic blends, and the like. Preferably, the hydrophobic part of the surfactant has chemical characteristics similar to those of the water-immiscible phase. Thus, if the latter contains an aromatic solvent, then one suitable surfactant would be ethoxylated nonylphenol. Particularly preferred surfactants include block copolymers of propylene oxide and ethylene oxide and anionic/nonionic mixtures.

The protective colloid present in the aqueous (or continuous) phase must be extensively absorbed onto the surface of the oil droplets and may be selected from a wide range of materials such as polyacrylates, methylcellulose, polyvinyl alcohol, polyacrylamide, poly(methyl vinyl ether/maleic anhydride), grafted copolymers of polyvinyl alcohol and a simple methyl vinyl ether/maleic acid [simple hydrolyzed methyl vinyl ether/maleic anhydride (see US patent No. 4448929, which is incorporated herein by reference)]; and lignosulfonates of alkali or alkaline earth metals. However, preferably the protective colloid is selected from alkali and alkaline earth metal lignosulfonates, most preferably sodium lignosulfonates such as TERGITOL™ NP7, Tergitol XD, Tergitol NP40, Tergitol 15-S-20, WITCONATE™ 90.

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The range of concentration of surfactant in the process is from about 0.01 to about 10.0 wt.% in terms of the aqueous phase, but higher concentrations of surfactant can be used. The protective colloid is typically present in the aqueous phase in an amount of from about 0.1 to about 5.0% by weight. The amount of protective colloid used will depend on various factors such as molecular weight, compatibility, etc., as long as it is sufficient to completely cover the surfaces of all oil droplets. The protective colloid can be added to the aqueous phase before adding the organic phase, or added to the overall system after adding the organic phase or its dispersion. Surfactants should be chosen so as not to displace the protective colloid from droplet surfaces.

The organic phase contains the pyrethroid to be encapsulated, one or more solvents, an aromatic diisocyanate and an aromatic polyisocyanate. Suitable solvents include aromatic hydrocarbons such as xylenes, naphthalenes or mixtures of aromatics; aliphatic or cycloaliphatic hydrocarbons such as hexane, heptane and cyclohexane; alkyl esters, including alkyl acetates and alkyl phthalates, ketones such as cyclohexanone or acetophenone, chlorinated hydrocarbons, vegetable oils, or mixtures of two or more of these solvents. Preferably, the pyrethroid is lambda-cyhalothrin and is dissolved in an organic solvent.

If a UV protectant such as titanium dioxide is used, it will also be encapsulated and therefore the titanium dioxide particles are also contained in the organic phase as well as the dispersants used to disperse the particles. Suitable dispersing agents for dispersing titanium dioxide particles are certain non-ionic surfactants which act by steric hindrance and are only active at the protective solid/organic liquid interface, but do not act as emulsifying agents. Such dispersants preferably consist of (a) a polymer chain having a strong affinity for liquid and (b) a group which will be strongly absorbed by a solid. Examples of such dispersants are those of the HYPERMER™ and ATLOX™ lines, including Hypermer PS1, Hypermer PS2, Hypermer PS3, Atlox LP1, Atlox LP2, Atlox LP4, Atlox LP5, Atlox LP6 and Atlox 4912; and AGRIMER™ polymers such as Agrimer AL-216 and AL-220.

The present inventors have found that by carefully modifying the properties of the microcapsules, such as the ratio of aromatic polyisocyanate to aromatic diisocyanate, as well as the composition and amount of the polymer wall, microcapsules are obtained that provide improved characteristics in terms of the level of harmful exposures to workers (such as an improved toxicological profile, for example , at least one of better oral, dermal and inhalation toxicity, improved skin and eye irritation score, and better skin sensitizer score), but which are released relatively quickly when applied to an agricultural environment. Shells are formed only from a mixture of aromatic diisocyanates with aromatic polyisocyanate, in which the ratio of polyisocyanate and diisocyanate is approximately 1:1.

Diisocyanate and polyisocyanates that can be used in this invention are those described in US patent No. 4285720. Diisocyanates used in the method of the present invention include m-phenylene diisocyanate, p-phenylene diisocyanate; 1-chloro-2,4-phenylene diisocyanate; 4,4'-methylenebis(phenylisocyanate); 3,3'-dimethyl-4,4'-biphenylenediisocyanate; 4,4'-methylenebis(2-methylphenylisocyanate); 3,3'-dimethoxy-4,4'-biphenylenediisocyanate; 2,4-toluene diisocyanate; 2,6-toluene diisocyanate, mixtures of isomers of 2,4- and 2,6-toluene diisocyanate and 2,2',5,5'-tetramethyl-4,4'-biphenylenediisocyanate.

Mixtures of isomers of 2,4- and 2,6-toluene diisocyanate are preferred.

The aromatic polyisocyanates used in this invention have 3 or more isocyanate groups and include polymethylene polyphenylisocyanate, triphenylmethane triisocyanate (DESMODUR™ R) and an adduct formed from 1 mole of trimethylol propane and 3 moles of toluene diisocyanate (Desmodur TH).

Although the prior art discloses the use of mixtures of these two types of isocyanates, in particular toluene diisocyanate and polymethylene polyphenylisocyanate, with many active ingredients, more toluene diisocyanate than polymethylene polyphenylisocyanate is suggested for pyrethroids.

The total amount of organic isocyanates used in this process will determine the shell composition of the resulting microcapsules. Typically, isocyanates (and, accordingly, the microcapsule shells formed therefrom) will contain from about 6 to about 9 wt.% of the microcapsule, preferably from about 7 to about 8 wt.%.

The size of the resulting microcapsules, which corresponds to the droplet size of the organic phase in an oil-in-water emulsion, is approximately a median diameter d50 of 0.5 to 5, preferably 1 to 4 µm. Droplet size can be controlled by the speed and time of agitation, and the type and amount of surfactant used, as is generally known in the art.

To obtain an appropriate emulsion, the organic phase is added to the aqueous phase with stirring. A suitable dispersing aid is used to disperse the organic phase in the aqueous phase. This device can be any high shear device operating to produce the desired droplet size (and corresponding microcapsule particles) in the range of about 0.5 to about 5, preferably about 1 to about 4 microns. Once the correct droplet size has been obtained, the disperser is stopped and only light agitation is required for the rest of the process.

The temperature of the biphasic mixture is then raised from ambient temperature to about 20°C to about 90°C, preferably from about 40°C to about 90°C, to form microcapsules.

Depending on the system, as described in US Pat. No. 4,285,720, the pH can be adjusted to a suitable level.

The microencapsulated composition of the present invention may also contain standard formulation auxiliaries such as bactericides, defoamers, anti-freeze agents, pH adjusters, buffers and viscosity adjusters.

In a further aspect, the present invention provides a process for preparing a composition as defined in the first aspect, the process comprising the steps of (a) providing an organic phase containing a pyrethroid insecticide, preferably lambda-cyhalothrin to be encapsulated, an aromatic polyisocyanate (A), an aromatic diisocyanate (B ), where the weight ratio of (A) and (B) is 1:1, and optionally titanium dioxide particles having a median particle size d50 of 0.1 to about 0.6, preferably 0.15 to about 0.5 µm dispersed in the organic phase with a dispersing agent; (b) introducing an organic phase into an aqueous phase containing water, a protective colloid and optionally a surfactant to form a dispersion of the organic phase in the aqueous phase; (c) mixing the dispersion under high shear to form an oil-in-water emulsion in which the oil droplets of the emulsion have a median diameter d50 of 0.5 to 5, preferably 1 to 4 micrometers; (d) adjusting, if necessary, the temperature and/or pH of the oil-in-water emulsion so that a polymerization reaction occurs to form polyurea microcapsules containing an organic phase.

The microencapsulated formulation of the present invention is an aqueous formulation containing capsules and will therefore have the formulation designation code CS. The microencapsulated formulations of the present invention are storage stable and have acceptable handling characteristics so that they can be routinely used, for example, in the field of horticulture. To ensure capsule integrity for such CS formulations, an aqueous composition containing capsules does not contain one or more of the following: an active ingredient with a melting point that is 25° C. or less than or equal to 50° C.; the active ingredient in the form of a salt; and a free or dispersed hydrophobic oil phase.

The microencapsulated compositions of the present invention may be combined with additional active ingredients.

In one embodiment, the aqueous composition of the present invention comprises the encapsulated lambda-cyhalothrin of the first aspect and one or more additional insecticides and/or acaricides, preferably one or more additional insecticides and acaricides not encapsulated with pyrethroids.

Examples of one or more additional active ingredients are from the class of neonicotinoids (such as imidacloprid, acetamiprid, thiamethoxam, thiacloprid), carbamates, plant compounds, diamides (such as chlorantraniliprole), macrocyclic lactones (such as abamectin, spinosad and emamectin), organophosphorus compounds (such as acephate), tetramic acids (such as spirotetramat), tetronic acids (such as spiromesifen, spirodiclofen) and insect growth regulators (such as lufenuron).

The additional active ingredient is usually suspended in an aqueous composition containing capsules of the present invention using conventional formulation techniques; if necessary, to obtain a stable composition of the mixture, additional standard means for compositions are used, where the resulting composition will have the designation code ZC.

In one embodiment, the aqueous composition of the present invention comprises the encapsulated lambda-cyhalothrin of the first aspect and, as an additional active ingredient, suspended thiamethoxam or suspended acetamiprid.

In a further embodiment, the aqueous composition of the present invention comprises the encapsulated lambda-cyhalothrin of the first aspect and, as an additional active ingredient, suspended thiamethoxam or suspended acetamiprid and suspended lufenuron.

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As used herein, the term d50 refers to the 50th percentile or median value measured based on volume by the CIPAC MT 187 method for laser diffraction particle size analysis. Malvern S, 2000 or 3000 instruments are the industry standard for light diffraction particle size measurement, but similar instruments made by Cilas, Coulter-Beckman, Horiba, Sympatec, and others are also acceptable.

General procedure for the encapsulated composition of the present invention

A solution of lambda-cyhalothrin was prepared in SOLVESSO 200 solvent. Dispersants were added, followed by titanium dioxide, and the resulting suspension was stirred using a high shear mixer. After the titanium dioxide was well dispersed, polymethylene polyphenylisocyanate and an isomeric mixture of toluene diisocyanate were added to supplement the organic phase. This phase was introduced into the aqueous phase while stirring with a high shear mixer to form an oil in water emulsion. The median droplet size was approximately 3.0±1 µm. The temperature was then raised to 50°C over a 30 minute period while maintaining gentle agitation, and then kept at 50°C for 3 hours. ) to adjust the viscosity and bactericidal agent, and the pH was adjusted to 5.0.

The compositions of the present invention are suitable for pest control by foliar application, but also for other applications such as on soil or in or around buildings. Examples of pests are sucking insects (e.g. psyllids, thrips (e.g. Thrips tabaci), stink bugs (e.g. Euschistus heros), planthoppers and aphids (e.g. Aphis gossypii, Myzus persicae)) and chewing insects (e.g. cutworms and cabbage moths (DBM). ), caterpillars, beetles, slugs and snails).

Suitable target plants are, in particular, potatoes, cereals (wheat, barley, rye, oats), rice, maize, nuts, alfalfa, cabbage and stem cabbage (including, without limitation, broccoli, cabbage, cauliflower), sugar beet, cotton. , varieties of millet, sorghum, tobacco, sunflower, beans, peas, oil plants (rapeseed, canola), soybeans, cabbage, tomatoes, eggplant, peppers and other vegetables and spices, as well as ornamental shrubs and flowers. Target crops also include transgenic crop plants of the above varieties.

Depending on the objectives to be achieved and the given circumstances, the compositions of the present invention are applied at a rate per hectare, based on the active ingredient, from 1 to 500 g/ha, for example from 5 to 300 g/ha, for example from 10 to 100 g/ha.

The following examples serve to illustrate the present invention. The present invention can be distinguished from other prior art based on greater efficiency at low application rates and an improved toxicological profile, which can be verified by one of skill in the art using the experimental procedures described in the examples below, using lower rates if necessary.

Examples

The main components and characteristics of compositions with polyurea microcapsules are shown in table. 1 and 2, with each composition being a type of CS composition.

The general procedure for preparing microencapsulated lambda-cyhalothrin products is described in Example 3 of WO 97/44125.

Tables 1 and 2 provide details of the various lambda-cyhalothrin encapsulated formulations. Each formulation in Tables 1 and 2 contained microcapsule titanium dioxide in an amount of approximately 4.6% (based on microcapsule weight) and had a median particle size d50 of approximately 0.2-0.4 microns.

Some of the encapsulated lambda-cyhalothrin formulations were then combined with thiamethoxam or simultaneously with thiamethoxam and lufenuron. Two-component (lambda-cyhalothrin and thiamethoxam) and three-component (lambda-cyhalothrin, thiamethoxam and lufenuron) mixture formulations were of the ZC formulation type, which is a formulation containing capsules as well as suspended solids. Thiamethoxam and lufenuron were suspended in the aqueous phase, and lambdacyhalothrin was encapsulated in microcapsules. Products formulated with the two-component mixture and the three-component mixture were prepared using conventional formulation methods, for example, including suitable bactericidal agents, surfactants, dispersing agents, an anti-freeze agent, and viscosity control agents to suspend the active ingredients and/or microcapsules and improved storage stability.

Details of the products obtained, formulated with a two-component mixture and a three-component mixture, are given in table.3.

Biology

Q1: Release characteristics of various lambda cyhalothrin capsules

A sample of the CS formulation (0.30-0.35 g) was weighed into a 2 oz cylindrical glass bottle. Then 6 ml of water are added and the sample is dispersed, with gentle shaking, until homogeneous.

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The same sampling procedure is repeated at 0.5, 2, 4, 8, 24 and 96 hour intervals and the resulting lambda-cyhalothrin concentration is plotted against time to determine the capsule release rate profile.

The results for certain formulations are shown in Table A.

Q2: efficacy trials on Euschistus heros (nymphs and adults)

The effectiveness of example 3, L and M were evaluated with each other in the field. Each formulation was applied to soybean plants approximately ten weeks after planting date at 200 ml/ha in separate, randomized, grouped plots of 96 m ² in Brazil. Nymphs (third instar and older) and adult stink bugs were counted using a standardized control device three, seven and ten days after application of the composition. The untreated area was also evaluated against nymphs and adult stink bugs as controls. Each test was performed in four repetitions.

The averages of the three scores (three, seven and ten days post-application) versus control for each of the formulations are presented in Table B.

Safety and toxicology

Certain formulations were evaluated for one or more of oral toxicity, dermal toxicity, risk of inhalation, skin irritation, eye irritation and skin sensitization (LLNA) using the OECD test methods listed in Table 1 below. WITH.

Table D shows the test results.

Table 1 Encapsulated formulations of lambda-cyhalothrin I

Example 1 Example A Example B Example C Weight. % lambda cyhalothrin 22.8 22.8 22.8 9.7 Weight. % isocyanate monomers 3.8 3.8 3.8 2.8 The ratio of polymethylene polyphenylisocyanate and a mixture of toluene diisocyanate isomers (80% 2,4-isomer; 20% 2,6-isomer) 1:1 1:30 1:30 1:1 Weight. % organic phase 49.7 50.6 49.7 21.4 Weight. % aqueous phase 50.3 49.3 50.3 78.6 Median diameter d50 microcapsules, micrometers 1.5-3.5 1.5-3.5 1.5-3.5 10-12 Weight. % polyurea polymer (or shell content) per capsule 7.7 7.5 7.7 13.1

Table 2 Encapsulated formulations of lambda-cyhalothrin II

Example E Example F Example G Example H Weight. % lambda cyhalothrin 22.8 22.8 22.8 22.8 Weight. % isocyanate monomers 5.9 5.9 3.8 3.8 The ratio of polymethylene polyphenylisocyanate and a mixture of isomers toluene diisocyanate (80% 2,4- isomer; 20% 2,6-isomer) 1:30 1:15 n/a 1:15 Weight. % organic phase 52.4 52.4 49.7 49.7 Weight. % aqueous phase 47.7 47.7 50.3 50.3 Median diameter d50 microcapsules, micrometers 10-12 10-12 1.5-3.5 1.5-3.5 Weight. % content polyurea polymer (or shell content) per capsule AND 2 AND 2 7.7 7.7

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Table 3 Composition of the 2- and 3-component mixture for encapsulated formulations of lambda-cyhalothrin

Example 2 Example I Example J Example K Example 3 Example L Source encapsulated lambda composition cyhalothrin Example 1 Example A Example B Example B Example 1 Example B Weight. % lambdacyhalothrin 9.48 9.48 9.48 9.48 8.80 8.80 Weight. % thiamethoxam 12.60 12.60 12.60 12.60 13.20 13.20 Weight. % Lufenuron 6.60 6.60

Comparative composition L contained the same components in the same amounts as comparative composition K, except that a smaller amount was used, i. 0.19 wt.%, not 0.28 wt.%, antimicrobial component (PROXEL™ GXL) - 20% solution of 1,2-benzisothiazolin-3-one in dipropylene glycol and water.

Table A1: Release profile (by weight) of lambda-cyhalothrin in 96 hours*

Time, h Example 1 Example B Example WITH Example E Example F Example G Example H 0.1 0 0.11 0.07 0.97 1.36 0 0.35 0.5 0.04 0.6 0.27 2.9 3.64 0.03 0.58 2 0.19 1.71 1.13 6.17 8.61 0.19 1.39 4 0.62 4.99 2.48 8.58 11.61 0.56 3.24 8 1.93 19.84 7.52 15.01 18.16 2.3 15.27 24 7.26 25.72 23.38 27.4 25.6 17.39 26.6 96 22.74 25.67 27.13 27.27 25.59 30.14 26.59

* All formulations exhibited comparable storage stability.

Table A2: Release profile (in terms of %) of lambda-cyhalothrin in 96 hours (based on table A1)

Time, h Example 1 Example B Example C Example E Example F Example G Example H 0.1 0.0% 0.5% 0.3% 4.3% 6.0% 0.0% 1.5% 0.5 0.2% 2.6% 1.2% 12.7% 16.0% 0.1% 2.5% 2 0.8% 7.5% 5.0% 27.1% 37.8% 0.8% 6.1% 4 2.7% 21.9% 10.9% 37.6% 50.9% 2.5% 14.2% 8 8.5% 87.0% 33.0% 65.8% 79.6% 10.1% 67.0% 24 31.8% 112.8% 102.5% 120.2% 112.3% 76.3% 116.7% 96 99.7% 112.6% 119.0% 119.6% 112.2% 132.2% 116.6%

Table B Efficacy against Euschistus heros (nymphs and adults)

% control nymphs adults Example 3 80 74 Example L 80 78

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Table C. OECD Methods Used in Table D Tests and Brief Description

Test Evaluation Procedure Test method according to OECD Short description Acute oral toxicity OECD 425 This method allows estimation of the LD50 with a confidence interval, and the results allow the substance to be classified for acute toxicity in accordance with the Globally Harmonized System of Classification and Labeling of Chemicals. The easiest way is to use materials that cause death within a few days. This Test Guide is intended for use in rodents (preferably female rats). There is a maximum allowable concentration test and a main test. The exposure limit test can be used effectively to identify chemicals that may have low toxicity. The test substance is usually administered as a single dose by gavage to animals that have been fasted prior to dosing. Individual animals are dosed in turn, typically at 48 hour intervals. The first animal is dosed one step below the best preliminary LD50 estimates. The second animal receives a lower dose (if the first animal dies) or a higher dose (if the first animal survives). Animals are observed with particular attention during the first 4 hours and daily thereafter for a total of 14 days. Animal weights should be determined at least weekly. All animals should be autopsied for macroscopic changes. In general, LD50 is calculated using the maximum likelihood method. After that, it may be possible to calculate interval estimates for LD50; the narrower the interval, the better the LD50 score. OECD 223 This Test Guide describes procedures for assessing the acute oral toxicity of substances to birds and provides three test options: (1) Dose Limit Test, (2) LD50 Slope Test, and (3) LD50 Only Test . The LD50 and LD50 only options are sequential test procedures.

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The choice of test method will depend on whether a fixed median dose (LD50) and a steep dose-response curve are needed. The exposure limit test is the preferred test if toxicity is expected to be low and lethality at the exposure limit is unlikely. The maximum allowable dose should be adequate for evaluation purposes and is usually 2000 mg/kg body weight. Five or ten birds are tested at the maximum allowable dose in addition to the control group. The LD50 slope test is the preferred test if regulatory or other requirements dictate that dose-response slope and/or confidence intervals are needed in addition to the LD50 estimate. It is a 3- or 4-stage test using 24 or 34 birds in addition to the control group. An LD50-only test is the preferred test if regulatory or other requirements specify that only the median lethal dose is needed, but neither the steepness of the dose-response curve nor the confidence interval for the LD50 is required. This test may be suitable for assessing the percentile of the LD50 distribution for species susceptibility and providing information for product labeling purposes. This trial consists of two stages using 14 birds in addition to the control group. Acute dermal toxicity OECD 402 This method provides information on the health hazard that may result from short-term dermal exposure to a solid or liquid test substance. This test guide is intended primarily for use in rodents (rat, rabbit or guinea pig may be used). At least 5 animals (of the same sex) are used for each dose. The test substance is applied to the skin (at least 10% of the body surface area) in graduated doses to several groups of experimental animals, one dose per group. At least three dose levels should be used at appropriate intervals to obtain a dose-response curve. It is possible to test with a maximum allowable dose for at least 2000 mg/kg. The observation period should

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be at least 14 days. Animals should be observed frequently during the first day, and observations should be made daily thereafter. It is necessary to conduct an autopsy of all animals and record all macroscopic pathological changes. The study of acute toxicity by the dermal route and the determination of the dermal LD provide an estimate of the relative toxicity of a substance by the dermal route of exposure, and this can form the basis for classification and labelling. This is the first step in the design of dosing regimens for subacute and other studies and may provide information on dermal absorption and the mode of action of a substance in this route. Acute inhalation toxicity OECD 403 This method provides information about health hazards that may result from short-term exposure test item (test item in the form of gas, vapor or aerosol/particulates) by inhalation. The revised Test Guidelines describe two studies: the standard LC50 protocol and the Concentration x Time (C x t) protocol. It can be used to estimate the median lethal concentration (LC50), non-lethal threshold concentration (LC01) and slope, as well as to determine possible sex-related susceptibility. This Test Guide allows you to quantify the risk and classify the product under test in accordance with the Globally Harmonized System of Classification and Labeling of Chemicals. According to the standard LC50 protocol, animals are exposed to one exposure limit or three concentrations for at least a predetermined period of time, typically 4 hours. Typically, 10 animals should be used for each concentration. In the C x T protocol, animals are exposed to a single exposure limit or series of concentrations over several periods of time. Typically, 2 animals are used per C x t interval. Animals (rat being the preferred species) should be observed for at least 14 days. The study includes measurements (including weighing), daily and detailed

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observations, as well as an autopsy with a macroscopic examination. Skin irritation OECD 404 This method provides information on the health hazards that may result from exposure to a liquid or solid test substance when applied to the skin. This Test Guidelines recommend sequential testing strategies that include performing approved and accepted in vitro or ex vivo corrosion/irritation tests. The albino rabbit is the laboratory animal of choice. The test substance is applied in a single dose to a small area of skin (approximately 6 cm ² ) of the experimental animal; and untreated skin areas of the experimental animal serve as a control. The exposure period is 4 hours. The remaining test substance must then be removed. A dose of 0.5 ml (liquid) or 0.5 g (solid) is applied to the test site. The method consists of two tests: an initial test and a confirmation test (used only if no corrosive effect was observed in the initial test). All animals should be examined for signs of redness and swelling within 14 days. Skin irritation scores should be assessed in relation to the nature and severity of the lesions and their reversibility or non-reversibility. If responses persist until the end of the 14 day observation period, then the test substance should be considered an irritant. Eye irritation OECD 405 This method provides information on the health hazards that may result from exposure to the test substance (liquids, solids and aerosols) when applied to the eye. This Test Guide is intended preferably for use on the albino rabbit. The test substance is instilled in a single dose into the conjunctival sac of one eye of each animal. The other eye, which remains untreated, serves as a control. One animal is used in the initial test; where the dose level depends on the nature of the test substance. Confirmation test required

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If no corrosive effect is observed in the original test, an irritant or negative response must be confirmed using up to two additional animals. It is recommended to do this sequentially one animal at a time, but not to expose these two additional animals at the same time. Period length observations should be sufficient to fully assess the magnitude and reversibility of the observed effects. Eyes should be checked at 1, 24, 48 and 72 hours after application of the test substance. Eye irritation scores should be assessed in relation to the nature and severity of the lesions and their reversibility or non-reversibility. Describes the use of local anesthetics and systemic analgesics to prevent or minimize pain and distress in ophthalmic safety testing procedures. OECD 438 The Isolated Chicken Eye (ICE) test method is an in vitro test method that can be used to classify substances as "corrosives and severe eye irritants". The ICE method uses eyes collected from chickens obtained from slaughterhouses where they are slaughtered for human consumption, eliminating the need for laboratory animals. The eye is cleaned and fixed in the eye holder, with the cornea placed horizontally. The test substance and negative/positive controls are applied to the cornea. Corneal toxicity is measured by qualitative assessment of opacity, qualitative assessment of epithelial damage in terms of fluorescein retention, quantitative measurement of increased thickness (swelling), and qualitative assessment of macroscopic morphological surface damage. Endpoints are evaluated separately to obtain an ICE class for each endpoint, which are then combined to obtain an irritation classification for each test substance. Skin Sensitization (LLNA) OECD 429 The basic principle underlying the mouse regional lymph node assay (LLNA) is that sensitizers induce primary lymphocyte proliferation in the ear lymph nodes draining the site.

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applying a chemical. This proliferation is proportional to the dose used and provides a measure of sensitization. The described method is based on the use of a radioactive label to measure cell proliferation. A minimum of four animals per single dose group, with a minimum of three concentrations of test substance, plus a vehicle-only negative control group and a positive control, as appropriate. The experimental analysis schedule is 6 days. The animals are then sacrificed and a suspension of lymph node cells is prepared. Incorporation of 3H-methylthymidine is measured by Ascintillation counting as disintegrations per minute (DPM). This Test Guide includes performance standards that can be used to evaluate validation results for new and/or modified test methods that are functionally and mechanistically similar to LLNA. The reduced LLNA approach, which can use up to 40% fewer animals, inclusive, is also described as an option. This study includes: measurements (weighing, DPM) and daily clinical observations. The results are expressed as stimulation index (SI). SI is obtained by calculation and must be made up of jY3 before validation classification of the test material as a skin sensitizer. OECD 406 This method provides information on the health hazards that may result from exposure to the test substance through intradermal injection and/or epidermal application. In this Test Guide The preferred methods are the guinea pig maximization test (GPMT) by Magnusson and Kligman, which uses an adjuvant, and the non-adjuvanted Buhler test. This Test Guide is primarily intended for use in the guinea pig, but mouse models have recently been developed to evaluate sensitization potential. For GPMT use at least 10 animals per treatment group and 5 per control group. For the Buhler test, at least 20 animals in the treatment group and at least 10 animals in the control group are used. Experimental animals are initially exposed to the test substance. After a rest period, an induction period (10-14 days) during which an immune response may develop, the animals are exposed to provocative dose. GPMT is carried out for approximately 23-25 days, Buhler's test for approximately 30-32 days. Concentration the test substance used for each inducing effect should be well tolerated systemically and should be the highest to cause mild to moderate skin irritation; for provocative influence it is necessary to use the highest non-irritating dose. All skin reactions and any unusual findings should be noted and recorded (additional procedures may be performed to clarify questionable responses).

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Table D. Toxicological and safety studies

Acute oral toxicity, (mg/kg) Acute dermal toxicity, (mg/kg) Acute inhalation toxicity, (mg/l) Skin irritation Eye irritation Skin Sensitization (LLNA) Example 1 >2000 >5000 >2.4 Absent Weak Positive Test Method OECD 425 OECD 402 OECD 403 OECD 404 OECD 405 OECD 429 Example A 180 >4000 nt Weak Moderate Positive Test method OECD 223 OECD 402 But OECD 404 OECD 405 OECD 429 Example B 310 >2000 3.12 Weak Weak Positive Test method OECD 425 OECD 402 OECD 403 OECD 404 OECD 405 OECD 406 Example 2 1596 nt >2.0 nt Minimum negative Test method OECD 425 h/o OECD 403 h/o OECD 405 OECD 429 Comparative composition J 310 >2000 >2.15 Moderate Weak negative Test method OECD 425 OECD 402 OECD 403 OECD 404 OECD 405 OECD 406 Comparative composition K 310 nt nt nt Absent nt Test method OECD 425 h/o h/o h/o OECD 438 But Example 3 341 >5000 2.57 mildly irritating Category III Positive Test method OECD 425 OECD 402 OECD 403 OECD 404 OECD 405 (EPA) OECD 406 Comparative composition L 103 5000 0.54-2.08 mildly irritating Category IV negative Test method OECD 425 OECD 402 OECD 403 OECD 404 OECD 405 (EPA) OECD 406

nt = not tested: n/a = not applicable

Claims (7)

CLAIM 1. An insecticidal composition containing a microcapsule with a polyurea shell encapsulating lambda-cyhalothrin and dispersed particles of titanium dioxide, where the polyurea shell of the microcapsule is made of polyurea polymers obtained from a mixture of aromatic polyisocyanate (A) and aromatic diisocyanate (B), provided that the median the particle diameter d50 for titanium dioxide particles is from 0.15 to 0.5 µm, the median diameter d50 of the microcapsule in the composition is from 1 to 4 µm, the ratio by weight (A) and (B) is 1:1, the polymer content in the shell in each microcapsule is from 7 to 8 wt.%, titanium dioxide is present in an amount of from 3.5 to 6 wt.%, and the amount of lambda-cyhalothrin is from 40 to 50 wt.%, each in terms of the weight of the microcapsule ; and the number of microcapsules in the composition is from 47 to 53 wt.% in terms of the weight of the composition. 2. The composition of claim 1 wherein the aromatic polyisocyanate is polymethylene polyphenylisocyanate. 3. Composition according to claim 1 or 2, wherein the aromatic diisocyanate is toluene diisocyanate, preferably a mixture of toluene diisocyanate isomers. 4. An aqueous insecticidal composition comprising a composition according to any one of claims 1 to 3 and one or more additional active ingredients selected from imidacloprid, acetamiprid, thiamethoxam, thiacloprid, chlorantraniliprole, abamectin, spinosad and emamectin, acephate, spirotetramate, spiromesifen, spirodiclofen and lufenuron. 5. The composition of claim 4, wherein the composition further comprises suspended thiamethoxam or suspended acetamiprid. 6. The composition of claim 4, wherein the composition further comprises lufenuron and suspended thiamethoxam or suspended acetamiprid. 7. A method for controlling plant damage by pests, comprising the use of an effective amount of an insecticidal composition according to any one of paragraphs. 1-6 in relation to the pest, plant or their location, in which the amount of the composition is from 5 to 300 g/ha.