WO2003077651A1

WO2003077651A1 - Microparticle formulation with reduced aquatic toxicity

Info

Publication number: WO2003077651A1
Application number: PCT/DK2003/000159
Authority: WO
Inventors: Morten Pedersen; Henning Gjelstrup Kristensen; Henrik K. Frederiksen
Original assignee: Cheminova A/S
Priority date: 2002-03-15
Filing date: 2003-03-13
Publication date: 2003-09-25
Also published as: AU2003226888A1

Abstract

Compositions having a reduced aquatic toxicity are provided, the compositions comprising microparticles consisting of a matrix and one or more pesticidal active ingredients distributed in the matrix. The compositions are applied to soil, to seeds, to animals or to plants without causing any risk to the surrounding aquatic life forms.

Description

MICROP ARTICLE FORMULATION WITH REDUCED AQUATIC TOXICITY

The present invention relates to microparticle compositions having a reduced aquatic toxicity, containing one or more pesticidal active ingredients entrapped in a matrix within the microparticles. The compositions are applied without causing any risk to the surrounding aquatic life forms.

Background

When pesticidal active ingredients enter the aquatic systems, the environmental costs can be high and concerns have been raised regarding potential risks to aquatic organisms (particularly fish and aquatic arthropods). Entry may happen during direct application to the target areas, but also during transportation and handling during production and by the end-user or even by misapplication. Entry may also happen due to wind drift at the time of application by aerial or ground methods and low humidity and high temperatures increase the evaporation of spray droplets and therefore the likelihood of increased spray drift and as such sets a limitation on when or how the pesticide is applied to the target areas. A re- suit of this is that many pesticidal active ingredients have a restricted use especially when applied in or near aquatic sites. Many insecticides, especially pyre- throids and organophosphates, posses this unfortunate characteristic, and it has been suggested in US patent no. 4,670,246, that microencapsulation of the active insecticidal ingredient may lower the toxicity towards fish. However, this tech- nique is technically relatively complicated, only a few pesticidal active ingredients can be encapsulated for chemical and physical reasons and complete encapsulation of the active ingredient may not be achieved leading to an inadequate reduction in aquatic toxicity of the final composition. The object of the present invention is to provide pesticidal compositions having a reduced aquatic toxicity but which may be applied without causing any signifi- cant reduction in the effectiveness of the active ingredient(s) in the composition. Patents and published patent applications disclosing various techniques for producing microparticle compositions containing pesticidal active ingredients entrapped in a matrix in the microparticles include PCT applications WO 99/00013, US patents no. 4,303,642; 4,512,969; 4,517,006; 5,741,521 and 5,785,976, European patent publications 201 214 A2, East German patent publication 273 542 A3 and Australian patent publication A-28951/89. However, there is no teaching in these prior documents about the decrease in aquatic toxicity when applying the technique which is the object of the present invention.

Summary of the invention

It has been found that compositions comprising microparticles consisting of a matrix and one or more pesticidal active chemicals distributed in the matrix have a reductive effect on the aquatic toxicity of the active ingredient(s) taken alone or compared to conventional formulation techniques, e.g. emulsifiable concentrates (EC) and emulsions in water (EW). Compositions according to the present invention expands the range of compounds that may be used for agricultural and veterinary application without causing any risk to the surrounding aquatic life forms in the areas where they are directly applied, manufactured, transported or after disposal or cleaning of used containers having carried said compositions.

The aquatic toxicity of pesticidal chemicals and compositions containing them are often measured on a comparative scale by their EC₅₀ values, which is the effective concentration to immobilise 50% of a defined specie after exposure for a defined period of time or by the LC₅₀ value which is the lethal dose required to kill 50%) of a defined specie after exposure for a defined period of time. The EC50 value is usually based on tests with an aquatic invertebrate, e.g. Daphnia {Daphnia magnά) exposed over a 48-hour period, and the LC₅₀ value based on tests with fish exposed over a 96-hour period. According to EEC regulations 67/548/EEC as amended (Directive 2001/59/EC - published August 21, 2001), pesticidal chemicals are classified based on their EC₅₀ or LC₅o values:

A list of the most common agricultural chemicals and their aquatic EC₅Q/LC₅₀ values can be found in 'The Pesticide Manual' - 11. Edition published by the British Crop Protection Council.

According to one aspect of the present invention, such compositions reduce the aquatic toxicity of the pesticidal chemical also when compared to conventional formulations of the chemical, e.g. emulsifiable concentrates and emulsions in water, and does not give rise to a significant reduction of the chemical's effectiveness when applied to soil, to seeds, to animals or to plants. This reduction, i.e. safening of the chemical towards aquatic organisms, is at least two fold, preferably at least ten fold. The pesticide is preferably selected among those where the EC₅₀ or LC₅₀ values are less than 100 mg/1, in particular those where the EC₅₀ or LC₅₀ is lower than 10 mg/1 and more particular those where the ECs₀ or LC₅₀ values are less than 1 mg/1. Especially the pesticidal chemicals possessing insecticidal behaviour are known to be highly toxic to aqueous living organisms. By the term 'pesticide' is meant a substance or mixture of substances intended for preventing, destroying or controlling any pest, including vectors of human or animal disease, unwanted species of plants or animals causing harm or otherwise interfering with the production, processing, storage, transport, or marketing of food, agricultural commodities, wood, wood products or animal feed- stuffs, or which may be administered to animals for the control of insects, mites/spider mites or other pests in or on their bodies. The term includes sub- stances intended for use as a plant growth regulator, defoliant, desiccant, or agent for thinning fruit or preventing the premature fall of fruit, and substances applied to crops either before or after harvest to protect the commodity from deterioration during storage or transport. However, the invention may also be utilised to other chemicals, which are known to be a hazard to aquatic life forms. Preferably the pesticidal chemical is selected among herbicides, insecticides, fungicides and plant growth regulators, more preferably herbicides and insecticides, and even more preferably aryloxyphenoxypropionates, pyrethroids, or- ganophosphates and avermectins. According to another aspect of the invention, such compositions can advanta- geously be applied in or near aquatic sites, e.g. areas where surface water is present such as in the vicinity of aquatic areas such as lakes, reservoirs, rivers, permanent streams, marshes or natural ponds, estuaries, and commercial fish farm ponds. According to yet another aspect of the invention, such compositions are applied for preventing, destroying or controlling pests. Advantageously such compositions are applied in or near aquatic sites, especially to crops grown in or near water, e.g. rice crops, or for the control of insects, e.g. mosquitoes, in water in which the insects or their larvaes breed, hatch, develop and live.

Brief description of the drawings

Figure 1 shows the daphnia toxicity (EC₅₀) as a function of particle size of the Gamma-cyhalothrin polystyrene microparticle formulations of example 5.

Figure 2 shows the effect (LD₅₀) on the Cotton Stainer as a function of particle size of the Gamma-cyhalothrin polystyrene microparticle formulations of example 5.

Detailed description of the invention

The matrix microparticles of the present invention are characterised by consist- ing of a matrix that includes at least one or more pesticidal active compounds that is distributed throughout the matrix. By matrix is meant a surrounding material in which another material is entrapped, sorbed, dissolved or dispersed. The isolated microparticles appear throughout as solid particles wherein the pesticidal ingredient is distributed or dispersed homogeneously or inhomogeneously in the matrix material.

Matrix microparticles can be used according to any known formulation including a suspension of matrix microparticles in an aqueous medium, wettable powders and wettable or dry granules.

The matrix microparticles can be produced by any process that results in a matrix having active ingredients distributed therein, and include polymeric matrixes, solid lipid matrixes and inorganic matrixes, e.g. clays, and silicas; or combinations thereof. Such methods include, but not limited to, solvent evapora- tion, hot melt microencapsulation, solvent partition and sorption to blank matrix microparticles.

Several methods are known in the art for preparing compositions containing pesticidal chemicals comprising microparticles in which the active ingredient is en- trapped in a polymeric matrix and distributed therein and may be used as appropriate.

A preferred process includes the following steps:

1) A lipophilic solution is prepared (the oil phase), including an active pesticidal ingredient and a polymer in an organic solvent. 2) A hydrophilic solution is prepared (the aqueous phase) including water (or other hydrophilic solvents) and optionally one or more dispersing agents. 3) The two phases formed under (1) and (2) are combined and homogenised whereby an emulsion is formed consisting of suspended micro- droplets. 4) Removing the organic solvent by evaporation under normal or reduced pressure and by mechanical stirring, whereby the matrix microparticles are formed suspended in the aqueous phase. The organic solvent used in the preparation of the hydrophobic phase should be suitable for dissolving the desired amount of active ingredient, the polymer as well as any other components of the organic phase and having such properties that it does not interact with these ingredients. In order to ease the final evaporation step, the solvent advantageously should have a low boiling point at ambient pressure. The amount used is not critical but should as a minimum dissolve both active ingredient and polymer. Preferred amounts range from about 1 to about 10 times the combined weight of the active ingredient and the polymer. Hydrocarbons, xylene, methylene chloride, dichloromethane, carbon tetrachloride, chloroform, methanol and N-alkylpyrrolidones are examples of suitable solvents. Polymers used in the present invention are water-insoluble, have no or low per- meability to water and are able to be dissolved in an organic solvent as mentioned above. Prepolymers may also be used and are converted into polymers upon heating or by chemical means, e.g. by adding an initiator or a crosslinking agent. If pre-polymers are used, the active substance maybe added prior to or after the polymerisation takes place. Not all polymers are useful, and should be se- lected to allow passage of the active ingredient from the polymeric matrix to its target without inhibiting the desired effect. Examples of polymers, pre-polymers and mixtures thereof which may be utilised are optionally substituted poly(styrene), polyorthoesters, poly(methylmethacrylate), vinyl polymers and copolymers, polyanhydrides, polyglutamates, polyurea and polyurethane, with poly(styrene) and polyurea being preferred. Preferably the amount of polymer is between 1 and 90 % by weight of the composition and more preferably between 5 and 50%. In addition, a plasticiser maybe included along with the polymer.

A prefeπed process for the solid lipid particles, among several known with in the art, includes the following steps: 1) A lipophilic solution is prepared (the lipid phase), including at least one lipid in melted or softened state and the active pesticidal ingredient dissolved therein.

2) A hydrophilic solution is prepared (the aqueous phase) including wa- ter (or other hydrophilic solvents) and optionally one or more dispersing agents.

3) The two phases formed under (1) and (2) are combined and homogenised whereby an emulsion is formed consisting of suspended micro- droplets. Optionally the emulsion is further high pressure homoge- nised.

4) The emulsion is left upon standing or cooling by physical means, whereby the matrix microparticles are formed suspended in the aqueous phase.

The lipids may be selected among those that are solid at room temperature and can be used as single component as well as mixed systems. The lipids can be polar or nonpolar. Examples of lipids include natural and syntetic mono-, di- and triglycerides, saturated or unsaturated fatty acids and their esters, natural and synthetic waxes, wax alcohols and their esters, fatty alcohols and their esters, and sterols. Preferably the amount of lipid is between 1 and 90 % by weight of the composition and more preferably between 5 and 50%.

Examples of suitable dispersing agents include water-soluble polymers such as polyvinyl alcohol, alkyl sulfonates, alkyl aryl sulfonates, hydroxyethyl cellulose, polyacrylic acid, methyl cellulose, polyvinyl pyrrolidone, block copolymers of polyethylene and polypropylene, polyoxyethylene-polyoxypropylene- ethylenediamine copolymers and low molecular polyalkylene glycols (e.g. polyethylene glycols and polypropylene glycols) and the like.

The amount of the dispersing agent necessary will vary depending on a number of factors but will generally be from about 0.01 to 10% by weight of the final composition. One of ordinary skill in the art will also understand that biologically inert ingredients may in addition be included in all embodiments of the pesticidal compositions of the present invention. Inert ingredients may be used to provide a more satisfactory formulation, provided the ingredients do not detract from the effect of the pesticidal active compound(s). Such inert ingredients include surfactants, thickeners, emulsion stabilisers, preservatives, dyes, UN-protectants and antifreeze compounds.

Following the above general procedures, the aqueous suspension may additionally be filtrated whereby isolating the microparticles or may be spray dried forming a solid powder, which in turn can be granulated to form granules. Granules may also be produced according to known methods, by absorbing the suspended matrix microparticles on to solid carrier materials.

It should be noted that the above mentioned ingredients should be chosen as not to posses any hazard to the surrounding environment, especially aquatic organisms, and should not interfere with the effectiveness of the active ingredient. This goes for the ingredients in them selves but also to possible breakdown products.

The size of the final microparticles is greatly depended on stirring speed and time in the emulsion forming steep of the above mentioned procedures, i.e. the entrapment of active ingredient in the matrix material. The higher the energy in- put in the homogenisation step, the smaller the droplet size of the active ingredient plus matrix forming substance in the aqueous phase. Large particles tend to cause plugging of spray nozzles and other equipment, and may not disperse rapidly in water. Microparticles suitable according to the invention are of an average diameter of about 0.5 to about 200 microns, preferably from about 1 to about 100 microns. Examples of pesticides which may be carried by the microparticles of this invention are:

Insecticides: Pyrethroids - Lambda-cyhalothrin - Cyhalothrin

- Deltamethrin - Peπnethrin

- Bifenthrin - Cyfluthrin

- Cypermethrin - Esfenvalerate

- Tefiuthrin - Tau-fluvalinate

- Gamma-cyhalothrin - Acrinathrin

- Etofenprox - Halfenprox

- Silafluofen - Flufenprox

- Fenpropathrin - Flucythrinate

- Resmethrin - Transfluthrin

Organophosphates

- Chlorpyrifos ■ Chlorpyrifos-methyl

- Malathion ■ Acephate - Dimethoate Methyl parathion

- Thiometon - Monocrotophos

- Terbufos

Benzoylureas - Lufenuron Novaluron - Hexaflumuron ^■ Triflumuron

- Diflubenzuron ^■ Chlorfluazuron

Carbamates - Carbofuran - Aldicarb - Methomyl - Carbaryl - Carbosulfan - Benfuracarb Avermectins

Fipronil

Imidacloprid

Clofentezine Buprofezin

Herbicides: Diphenyl ethers

- Acifluorfen - Aclonifen

- Oxyfluorfen - Bifenox

- Fluroglycofen-ethyl

Chloroacetanilides

- Acetochlor - Alachlor

- Butachlor - Metolachlor

Aryloxyphenoxypropionates

- Fenoxaprop-ethyl ■ Quizalofop-ethyl - Diclofop-methyl ■ Haloxyfop-methyl

- Clodinafop-propargyl - Fluazifop-butyl

Fungicides: Benzimidazoles - Carbendazim Benomyl

- Thiophanate Thiabendazole

Triazoles Epoxiconazole Hexaconazole • Propiconazole • Flutriafol ■ Difenoconazole - Cyproconazole Flusilazole Myclobutanil Tebuconazole

Strobilurins - Kresoxim-methyl • Azoxystrobin

- Picoxystrobin Trifloxystrobin

- Pyraclostrobin

Morpholines Dimethomorph Tridemorph

- Spiroxamine ■ Fenpropidin

- Fenpropimorph

Plant growth regulators: Paclobutrazol Daminozide Flurprimidol

The concentration of the active ingredient is preferably about 0.01% to about 60%o by weight(w/w), more preferably from about 0.1 % to about 50%o. While concentrated compositions are more prefeπed as commercially available goods, the end consumer uses, as a rule, dilute compositions. Such pesticidal compositions are part of the present invention.

The invention is illustrated by the following examples:

Example 1 - Preparation of a GCH-polystyrene formulation stock solutions

A stock solution of 20% polystyrene (Aldrich bimodal, Mw 200.000 and 4000) in dichloromethane (Merch, analytical grade) was prepared by dissolving the polystyrene in the dichloromethane by magnet stirring overnight. A stock solution of 15% w/w polyvinyl alcohol (Airvol 205, Air Products) was prepared by dissolving the polyvinyl alcohol (PNA) in water and heating to 90 °C for at least ^XA hour.

16.05 g of the viscosity enhancer Kelzan (Xanthan gum - available from Kelco International Ltd.) and 8.61 g the preservative Proxel GXL (1,2- benzisothiazolin-3-one - available from Avecia Biocides) was dissolved with stirring in 775.12 g of water to produce a stock solution.

Formulation 3.04 g of Gamma-cyhalothrin (GCH) was dissolved in 103.81 g of the polystyrene solution under magnet stirring.

By dilution in water, a 1.5% w/w PVA solution was obtained from the above PNA stock solution. 180.98 g of the PNA solution was added to the GCH- polystyrene solution and the mixture was homogenised with a high shear mixer fitted up with a propel stiπer at 6000 rpm. The stirring was continued for 30 minutes.

The emulsion was then transfeπed to a 1 liter (L) round bottom flank and attached to a rotary evaporator to remove the dichloromethane at a reduced pressure. The temperature of the solution was kept at 15 °C for the first hours of the evaporation and then raised to 40 °C and kept there for the last hours of the evaporation. The final residue of dichloromethane was analysed to be less than 5 mg/L.

28.27 g of the above Kelzan/Proxel stock solution was added to the Gamma- cyhalothrin suspension and the mixture was stirred with an anchor stiπer at 300 rpm for two hours.

The mean diameter by volume of the polystyrene particles was determined by laser diffraction (Malvern Mastersizer) to 10.1 μm.

Bioassays of the formulations The fish toxicity experiments were conducted on zebra fish (Brachydanio rerio). The experiments were carried out as a static dose-response trial with 11 concentrations.

In every experiment each of 12 aquarias were filled with 25 L water. 8 fish (average weight of 0.33 g) from a housebondary culture were added to each aquar- ium. After an equilibration period of 24 hours, the formulation (amount on regard of the experimental protocol) was added to the aquarium. One of the aquarias was left untreated and served as control. The fish were maintained at a light cycle of 16 hours of light followed by 8 hours of darkness in housebondary and experiment situation. The water was not aerated and the fish not fed during the experiment.

After 96 hours, the experiment was settled, the number of dead fish was determined and in turn the LD₅₀ value calculated.

The daphnia (Daphnia magna) toxicity experiments were carried out as a static dose-response trial with six concentrations and four replicates (OECD Guidelines for testing of chemicals no. 202 (1984)).

In brief, 50 ml (diameter 2.5, height 9.5 cm) test tubes were used. To each tube was added 40.00 ml daphnia growth medium (M7, Elendt & Bias (1990)), 1.00 ml formulation in water (diluted on regard of the experimental protocol) and 5-8 juvenile (12-24 hours old) daphnia in 4.00 ml of water.

The tubes were placed at 20 ± 2 °C, at a light cycle of 16 hours of light followed by 8 hours of darkness. The experiment was settled after 48 hours where the number of immobilised daphnia was counted. Non-treated daphnia were used as controls.

Efficacy experiments were carried out on the cotton stainer (Dystercus cingula- tus). Cotton leaves were sprayed with formulation, and the insects allowed access to the leaves in petri dishes throughout the experiment. The insects were exposed to the sprayed leaves for 72 hours, where after the number of dead specimens was determined. The test on the cotton stainer was a contact test i.e. the insects did not feed on the leaves. The LD₅₀ value was established by applying 4 doses with 10 insects per dose. There were two replicates.

The properties of the formulation are given below

Formulation Physico-chemical properties

GCH (% w/w) 1.2

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.3

Daphnia (EC₅₀ μg a.i. per 1.) 23.5

Fish (LC₅₀ μg a.i. per 1.) 92.4

Example 2 - GCH-compritol formulations

40.11 g of the lipid docosanoic acid, 1,2,3-propantriyl ester (Compritol 888 ATO - available from GatteFosse) and 3.61 g of Gamma-cyhalothrin was melted in a glass vial placed in a 90 °C oil bath. The stock solution of PNA (example 1) was diluted to a 0,11% w/w PNA solution and placed in a 90 °C oil bath for approximately 30 minutes.

360.47 g of the PNA solution was added to the lipid phase and the mixture remained in the oil bath. The mixture was homogenised for approximately 30 sec- onds with a Ultra Tuπax homogeniser at 8000 rpm. The resulting crude emulsion was transfeπed to a high pressure homogeniser, which was preheated to 90 °C by passing boiling water through it. The emulsion was passed 2 times through the homogeniser at a pressure of 400 bar. After the second cycle, the emulsion was cooled quickly to about 35 °C by passing it through a long reflux condenser cooled with flowing tap water. The collecting vial was placed in ice water to further cool the suspension. 20.0 g of poly(vinylpyrrolidone) (Agrimer 90, ISP) and 14.02 g of Proxel GXL was dissolved in 166.14 g water to a prepare a stock solution. 4.02 g of this solution was added to the lipid suspension under gently agitation.

Efficacy experiments were carried out on larvae of the cotton leafworm (Spo- doptera littoralis) .

Cotton leaves were sprayed with formulation, and the larvae allowed access to the leaves in petri dishes throughout the experiment. The insects were exposed to the sprayed leaves for 72 hours, where after the number of dead species was determined.

The test on the cotton leafworm was a feeding test i.e. the larvae feeds on the cotton leaves. The LD50 was found by applying 5 doses, with 5 animals per dose. There were four replicates.

Other bioassays were performed as described in example 1.

The properties of the formulation are given below.

Formulation

Physico-chemical properties

GCH (% w/w) 0.68

Mean particle size (μm) 6.4

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.1

Cotton leafworm (LD₅₀ g a.i. per ha.) 0.4

Daphnia (EC₅₀ μg a.i. per 1.) 17

Fish (LC₅₀ μg a.i. per 1.) 2.5

Example 3 - Comparative (Illustrating the effect and aquatic toxicity of a conventional EC formulation).

A Gamma-cyhalothrin emulsifiable concentrate (EC) formulation was prepared. 1.25%) of GCH, 7.0% of emulsifiers (non- and anionic types), 1%> of an antioxi- dant and xylene ad. 100%o was mixed in a beaker and stiπed in a magnet stiπer until a clear solution was obtained. The formulation spontaneously formed an emulsion when added to water. The mean droplet size was around 5 μm.

The biological properties of the formulation are given below.

Formulation

Physico-chemical properties

GCH (% w/w) 1.25 Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.2

Cotton leafworm (LD₅₀ g a.i. per ha.) 0.2

Daphnia (EC₅₀ μg a.i. per 1.) 0.11

Fish (LC₅Q μg a.i. per 1.) 0.3

Example 4 - GCH-polystyrene formulation

A stock solution of 40% polystyrene in dichloromethane was prepared following the procedure of example 1. 2.04 g of GCH was dissolved in 27.18 g of the polystyrene solution under magnet stirring.

The stock solution of PVA (example 1) was diluted to a 1.0 %> w/w PNA solution. 180.22 g of this was added to the GCH polystyrene solution and homoge- nised 2 minutes with a Ultra Tuπax at 20500 rpm. The formulation was evaporated at room temperature in a rotary evaporator and left overnight at reduced pressure to eliminate the last residue of dichloromethane. 28.42 g of the Kel- zan/proxel stock solution (example 1) was then added to the formulation. The properties of the formulation are given below:

Formulation Physico-chemical properties

GCH (% w/w) 0.87

Mean particle size (μm) 15.0

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.3

Cotton leafworm (LD₅₀ g a.i. per ha.) 0.3

Daphnia (EC₅₀ μg a.i. per 1.) 921 Example 5 - GCH-polystyrene particle with different particle sizes.

Following the general procedure of example 1, a series of GCH-polystyrene particles were prepared with different particle sizes. The particle sizes were controlled by varying the homogenisation intensity.

The physico-chemical properties of the formulations are given below:

Formulations

42 50 49 37 38 39

GCH-concentration 0.90 0.90 0.80 0.86 0.88 0.86

(% w/w)

Particle size 2.12 11.9 12.4 15.0 26.0 40.9

The biological properties of the formulations are given in figure 1 and 2.

Example 6 - GCH-polystyrene particles with different concentration of dispersing agent

Following the general procedure of example 1, GCH-polystyrene particles were prepared with different concentrations of the dispersing agent PNA. In order to obtain the same particle size in the different formulations, the stirring speed in the homogenisation step was varied. The organic phase consisted of GCH dissolved in a 20%) polystyrene in dichloromethane solution. The properties of the formulations are given below. Formulations

PNA (% w/w) 0.5 1.0 5.0

Physico-chemical properties

GCH (% w/w) 0.85 0,89 0.82

Mean particle size (μm) 15.0 14,3 14.3

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 2.4 1.8 1.5

Cotton leafworm (LD₅₀ g a.i. per ha.) 1.1 1.8 1.2

Daphnia (EC₅₀ μg a.i. per 1.) 371 781 757

Example 7 - GCH-polystyrene particles, effect of varying the molecular weight of the dispersing agent

Following the general procedure of example 1, GCH-polystyrene particles were prepared with different molecular weight grades of the dispersing agent PVA. The properties of the formulations are given below.

Formulations

PNA Mw (Da) 40,500 115,500 155,000

Physico-chemical properties

GCH (% w/w) 1.3 1.3 0.77

Mean particle size (μm) 14.3 20.6 39.5

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.7 2,9 3.2

Daphnia (EC₅₀ μg a.i. per 1.) 466 839 >1000 Example 8 - GCH-polystyrene formulations, effect of higher loading

Following the general procedure of example 1, GCH-polystyrene particles were prepared with increased concentrations of GCH and polystyrene. A 40 % polystyrene in dichloromethane and a 5% aqueous PNA solution were used in the preparation.

The properties of the formulations are given below.

Formulations

Physico-chemical properties

GCH (% w/w) 3.1 3.7

Mean particle size (μm) 9.1 14.2

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.5 0.3 Cotton leafworm (LD₅₀ g a.i. per ha.) 0.8 0.1 Daphnia (EC₅₀ μg a.i. per 1.) 120 36

Example 9 - Spraydried GCH-polystyrene formulations.

Following the general procedure of example 1, GCH-polystyrene particles were prepared. However, the final step, i.e. the addition of the Kelzan/Proxel solution, was not accomplished. Instead, the formulations were spray dried. The spraydrier was a LabPlant SD-05 fit up with a 1.0 mm two fluid jet nozzle. Applied spraying parameters were: pump setting 6 ml/min, nozzle pressure 1 bar, airflow 55 m/Vhour, inlet temperature 100 °C, outlet temperature 62 °C. Two formulations with different particle size were prepared (2 x 200 ml of each were prepared and pooled). Half of the formulations were spray dried, half used as crude. The composition of the formulations are given below:

Formulations

A B A B

Crude Spray dried Crude Spray dried

Physico-chemical properties

GCH-concentration (% w/w) 0.98 8.3 1.0 8.3 Mean particle size (μm) *) 11.3 9.4 32.9 20.1

Biological properties

Cotton stainer (LD₅₀ g a.i. per ha.) 0.6 0.2 1.2 0.2

Daphnia (EC₅₀ μg a.i. per 1.) 45 15 54 29

*) In case of spray dried formulations, the particle size was measured after resus- pension in water.

Example 10 - Formulations consisting of GCH and in situ polymerised polystyrene

Sodium dodecylsulfate, 120.3mg, was dissolved in 50ml distilled water at 80°C in a round bottomed three necked flask. A solution of 107.4mg GCH in 20.07g styrene was emulsified in the water (80°C) by Ultra-tuπax stirring for 15 min. A solution of ammonium persulfate (126.6mg) in 20ml distilled water was added drop wise to the emulsion. Additional 10ml of distilled water was used for rinsing and added to the emulsion. Nitrogen gas was bubbled through the reaction flask to remove oxygen from the system. The gas flow was continued throughout the styrene polymerisation reaction. The polymerisation was carried out under constant and gentle stirring for six hours.

The mean diameter of the formed GCH polystyrene matrix particles was 8μm. The daphnia EC₅₀ value was 203 μg per 1.

Example 11 — Formulations consisting of in situ polymerised polyurea and GCH, deltamethrin, abamectin or chloφyrifos

Suspensions of matrix particles of polyurea and GCH, deltamethrin, abamectin or chloφyrifos in water were produced by in situ polymerisation of isocyanates. A mixture of toluene-diisocyanate and polymethylene-polyphenylisocyanate (weight ratio 1:2) was applied. Typically the suspensions contained 1%> w/w of the active ingredient and 10% w/w of the mixture of isocyanates mentioned above. The solutions of active ingredient and isocyanates were emulsified in wa- ter using emulsifiers, hydrocoUoids and solvents. The polymerisation of the isocyanates were done at 68°C and lasted 6 hours.

Daphnia EC50 data for the above-mentioned polyurea matrix formulations are shown in the table below. In addition, daphnia EC₅₀ values for emulsifiable concentrates of the four active ingredients are tabulated. Formulation Daphnia EC₅₀ value μg a.i. per 1.

GCH polyurea matrix 374

GCH emulsifiable concentrate 0.13

D eltamethrin polyurea matrix 117

Deltamethrin emulsifiable concentrate 0.019

Abamectin polyurea matrix 9.4

Abamectin emulsifiable concentrate 0.18

Chloφyrifos polyurea matrix 7.8

Chloφyrifos emulsifiable concentrate 0.55

Example 12 - Fenoxaprop-P-ethyl-porystyrene formulation

A fenoxaprop-P-ethyl-polystyrene suspension concentrate formulation was prepared applying the procedure described in example 1. The mean diameter of the matrix particles was 18μm. The content of fenoxprop-P-ethyl in the formulation was 0.69% w/w.

The daphnia EC₅₀ value for this formulation was 71μg a.i. per ml. The daphnia EC₅₀ value for an emulsion in water (EW) of fenoxaprop-P-ethyl was 2.4μg a.i. per ml.

Claims

PATENT CLA S

1. Use of a composition comprising microparticles consisting of a matrix and at least one pesticidal chemical distributed in the matrix as well as usual additives, fillers or excipients, for preventing, destroying or controlling pests in or near aquatic sites.

2. Use of a composition according to claim 1, where in the composition further comprises one or more dispersing agents.

3. Use of a composition according to claim 1 or 2, wherein the pesticidal chemical is selected among herbicides, insecticides, fungicides and plant growth regulators .

4. Use of a composition according to claim 3, wherein the pesticidal chemical is selected among insecticides.

5. Use of a composition according to claim 4, wherein the pesticidal chemical is selected among pyrethroids, organophosphates and avermectins.

6. Use of a composition according to any of the previous claims, wherein the pesticidal chemical has a 48 hour EC ₀ value for an aquatic invertebrate or a 96 hour LC₅o value for fish of less than 100 mg/liter.

7. Use of a composition according to claim 6, wherein the pesticidal chemical has a 48 hour EC₅₀ value for an aquatic invertebrate or a 96 hour LC₅₀ value for fish of less than 10 mg/liter.

8. Use of a composition according to claim 7, wherein the pesticidal chemical has a 48 hour EC₅₀ value for an aquatic invertebrate or a 96 hour LC₅₀ value for fish of less than 1 mg/liter.

9. Use of a composition according to claim 1 , wherein the matrix material is se- lected from lipids or polymers.

10. Use of a composition according to claim 9, wherein the matrix material is optionally substituted poly(styrene) or polyurea.

11. Use of a composition according to claim 1, wherein the pesticidal chemical is present in an amount of about 0.01% to about 60%> based on weight of the composition.

12. Use of a composition according to claim 11, wherein the pesticidal chemical is present in an amount of about 0.1%> to about 50%> based on weight of the composition.

13. Use of a composition according to claim 5, wherein the pesticidal chemical is selected among the compounds cyhalothrin, lambda-cyhalothrin, gamma- cyhalothrin, deltamethrin, bifenthrin, cypermethrin, tefluthrin, permethrin, cyfluthrin, esfenvalerate, tau-fluvalinate, acrinathrin, etofenprox, halfenprox, flufenprox, silafluofen, fenpropathrin, flucythrinate, resmethrin and transflu- thrin

14. Use of a composition according to claim 13, wherein the pesticidal chemical is selected among the compounds deltamethrin, cyhalothrin, lambda- cyhalothrin and gamma-cyhalothrin.

15. Use of a composition according to claim 1, wherein the composition is in the form of a suspension of the microparticles in an aqueous medium, a powder or granules.

16. Use of a composition according to any one of the previous claims, wherein such composition is applied where surface water is present, preferably in the vicinity of aquatic areas such as lakes, reservoirs, rivers, permanent streams, marshes or natural ponds, estuaries, and commercial fish farm ponds.