United States Patent (19) 11) Patent Number: 4,897,386 Matthewson (45) Date of Patent: Jan. 30, 1990

54 SYNERGISTIC COMPOSITIONS 3,993,774 11/1976 Searl et al...... 424/304 75 Inventor: Michael D. Matthewson, FOREIGN PATENT DOCUMENTS Berkhamsted, England 50-58237 5/1975 Japan. 73 Assignee: Burroughs Wellcome Co., Research 1448228 9/1976 United Kingdom. Triangle Park, N.C. Primary Examiner-Allen J. Robinson (21) Appl. No.: 575,486 Attorney, Agent, or Firm-Donald Brown 22 Filed: Jan. 31, 1984 (57) ABSTRACT A method of controlling veterinary ectoparasites of Related U.S. Application Data mammals and birds of the sub-Orders Ixodoidea and 60 Division of Ser. No. 391,455, Jun. 23, 1982, abandoned, Sarcoptiformes comprising the application of a parasiti which is a continuation of Ser. No. 863,738, Dec. 23, cidally effective, non-toxic amount of a pyrethroid of 1977, abandoned. formula 30 Foreign Application Priority Data Cl Dec. 24, 1976 GB United Kingdom...... 54049 / CH2OC CHC 51) Int. Cl...... A01N 53/00; A01N 57/00 N 52 U.S. C...... 514/108; 514/531 O O Cl 58 Field of Search ...... 424/205; 514/108,531 CH3 CH3 56 References Cited U.S. PATENT DOCUMENTS together with at least one parasiticidal organophos

2,873,228 2/1959 Willard et al...... 424/205 phoruscompound active against said ectoparasites. 2,982,686 5/1961. Whetstone et al...... 424/212 3,944,666 3/1976 Montgomery et al...... 514/531 4 Claims, No Drawings 4,897,386 1. 2 makes it difficult to predict potentiation in one group of. SYNERGISTC COMPOSITIONS arthropod pests from a knowledge of potentiation in another group. This unpredictability is demonstrated by PRIORAPPLICATIONS the absence of potentiation of insecticidal activity be This application is a division of Ser. No. 06/391,455, tween a compound of formula () and an organophos filed June 23, 1982, now abandoned, which is a continu phorus compound in respect of Insects of veterinary ation of Ser. No. 863,738, filed Dec. 23, 1977, now aban importance. (See Tables 6 to 9 below). doned. The pyrethroid for use in the present invention is This invention relates to novel potentiating composi selected from the esters embraced by formula (I) de tions, their preparation, formulations containing them, O fined above. Structural formula (I) is intended to en the preparation of such formulations and to their use for compass all the possible geometric and optical isomers. the control of pests of the sub-Orders Ixodoidea and More particularly the acid moiety of the ester may be Sarcoptiformes. selected from the (--)-cis-isomer, the (--)-trans-isomer, Pyrethroids embraced by formula (I): the (-)-cis-isomer, the (E)-trans-isomer and the 15 (-)-cis-trans-isomer; the stereochemistry referring to Cl that of the cyclopropane ring. / The preferred pyrethroid of this invention is 3 CH2OC CHEC N phenoxybenzyl-(+)-cis,trans-2,2-dimethyl-3-(2,2di O C1 chlorovinyl)cyclopropane-1-carboxylate (permethrin). The activity of these esters against pests of the sub CH3 CH3 Orders Ixodoidea and Sarcoptiformes is potentiated when used in combination with at least one organophos are known from UK Pat. No. 1,413,491 to possess insec phorus compound. ticidal activity, and are known from South African Pat. No. 3211/1975 to possess acaricidal activity. 25 More particularly, the esters may be used in combina Pests of the Class Insecta and of the Order Acarina tion with phosphate and phosphorothioate compounds are troublesome to man, animal and plants. They are possessing intrinsic acaricidal activity. The organophos vectors of disease, and economic losses result from their phorus compounds found to be effective are: depredations on plants and animals. Control of such O,O,-diethyl-O-(3-chloro-4-methyl-7-coumarinyl) pests over the years has come to depend strongly upon 30 phosphorothioate (coumaphos); the use of chemical pesticides which can be naturally O,O-diethyl-O-(2,5-dichloro-4-bromophenyl) phos occuring compounds or synthetic organic chemicals. phorothioate (bromophos-Ethyl); Organophosphorus pesticides are used in both the 2,3-p-dioxanedithiol-S,S-bis, O,O-diethyl phosphorodi agricultural and veterinary fields with varying degrees thioate (dioxathion), of success. Some of these substances are common to 35 O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl) phosphoro both fields such as diazinon and malathion whilst others thioate (chlorpyrifos); have been solely employed in the agricultural field, for O,O,O,O'-tetraethyl, S,S'-methylenediphosphorodithi example fenitrothion. In recent years resistance to or oate (ethion); ganoposphorus compounds has evolved in certain 3-(Dimethoxyphosphinyloxy)-N-dimethyl-cis-crotona strains of Insects and Acarids both of agricultural and mide (dicrotophos); veterinary importance and accordingly the need for O-ethyl-O-(quinol-3-yl)phenylphosphorothioate new, effective insecticides and acaricides has arisen. inothiophos); It is known from Japanese Patent Publication No. (S-5,7-dichlorobenzoxazol-2-yl-methyl-O,O-diethyl 058-237/1975, that potentiatior of activity occurs be phosphorodithioate) (benoxaphos); tween a pyrethroid of formula (I) and certain organo 45 S-(4-chlorophenyl)-thiomethyl-O,O-diethyl phos phosphorus compounds against Insects and certain phorodithioate (carbophenothion); Mites of agricultural importance. Employing such po S-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-methyl)- tentiating compositions, renders the use of pyrethroids O,O-dimethylphosphorodithioate (phosmet); of formula (I) more economic. The Japanese publication 2-Chloro-1-(2,4-dichlorophenyl) vinyldiethyl phosphate also suggests that the potentiation is due to the interac 50 (chlorfenvinphos) tion between the inhibition of the enzyme acetyl and a 1:1 weight by weight mixture of chlorofenvinphos cholinesterase by the organophosphorus compound at and dioxathion. the ganglionic junctions of the pest, which results in Particularly high potentiation is achieved with com ganglionic nerve paralysis, and the disturbance of axo binations containing coumaphos, chlorfenvinphos, nal nerve transmittance through the cell membranes of 55 diazinon, ethion and the mixture of dioxathion and the nerve axons of the pest by the pyrethroid, which chlorfenvinphos. results in impaired axonal nerve transmission. The potentiating compositions of this invention are It has now been surprinsingly found that there is highly effective against strains of acarines which are potentiation between a pyrethroid of formula (I) and susceptible to conventional organophosphorus acari certain organophosphorus compounds against pests of 60 cides as well as to those strains which are resistant to veterinary importance which are resistant to conven conventional organophosphorus acaricides such as Bo tional organophosphorus compounds and which belong ophilus microplus (Can) and B. decoloratus (Koch) and in to the sub-Orders Ixodoidea and Sarcoptiformes. It is addition those strains resistant to pyrethroids. The com believed that the potentiation is due to the inhibition by positions of this invention may therefore be used to the organophosphorus compound of certain esterases 65 control acarine ectoparasites of animals, particularly which degrade pyrethroids. The various rates at which those ticks of the genera Boophilus, Rhipicephalus, different groups of arthropod pests, even within the Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Der same Order of classification metabolise a pyrethroid macentor, and Anocentor, and mites of veterinary im 4,897,386 3 4. portance for example the sheep scab mite Psoroptes ovis, Greases may be prepared from vegetable oils, syn and other ectoparasites of the sub-Orders Ixodoidea and thetic esters of fatty acids or wool fat together with an Sarcoptiformes. Such ectoparasites infest stock and inert base such as soft paraffin. A composition of this domestic animals and fowls, depending upon the loca invention is preferably distributed uniformly through tion of the host and the particular ectoparasite. Com the mixture in solution or suspension. Greases may also mon hosts are cattle, pigs, sheep,goats, horses, camels, be made from emulsifiable concentrates by diluting chickens, dogs and cats. them with an ointment base. The compositions of this invention may be used for Pastes are also semi-solid preparations in which a protecting the host against infestations of Ixodid and composition of this invention may be present as an uni Sarcoptic pests by application of the compositions 10 form dispersion in a suitable base such as soft or liquid themselves or in a diluted form in known fashion, as a paraffin or made on a non-greasy basis with glycerin, dip, a spray, a dust, a paste, cream, gel, foam, shampoo mucilage or a suitable soap. As greases and pastes are or grease, a pressure-pack, an impregnated article, or a usually applied without further dilution they should pour-on formulation. Dips are not applied per se, but contain the appropriate percentage of the composition the animals are immersed in a dipping bath containing 15 required for treatment. the dip wash. Sprays may be applied by hand or by Aerosol sprays may be prepared as a simple solution means of a spray race or arch or automatic treadle. of the active ingredients in the aerosol propellant and a Dusts may be distributed over the animals by means of co-solvent such as halogenated alkanes and the solvents a powder gun by hand application from suitable con referred to above, respectively. Pour-on formulations tainers or incorporated in perforated bags attached to 20 may be made as a solution emulsion or suspension of a trees or rubbing bars. Pastes, foams, creams, gels, sham composition of this invention in a liquid medium which poos and greases may be applied manually or distrib is of a viscosity such as to minimize loss of the formula uted over the surface of an inert material against which tion by run off from the surface of the animals. The animals rub and transfer the material to their skins. pour-on formulation may be applied by a drenching Pour-on formulations are dispensed as a unit of liquid of 25 gun, syringe or ladle or any other method known in the small volume on to the backs of animals such that all or art. most of the liquid is retained on the animals. A composition of the present invention preferably The compositions may be presented either as formu contains (5-95%) of a defined pyrethroid for example lations ready for use on the animals or as formulations one selected from structural formula (I) and between requiring further dilution prior to application, but both 30 (5-95%) of an organophosphorus compound defined types of formulations comprise a pyrethroid as defined hereinabove. The concentration of a composition ap above in combination with at least one organophospho plied to the pests or to their environment may be in the rus compound as defined above in intimate admixture range of (0.0001-20%). with one or more carriers or diluents. The carriers may It will be appreciated from the foregoing that what be gaseous or solid or liquid or comprise mixtures of 35 such substances and may be selected from one or more we will claim may comprise any novel feature described of the following: a solvent, an inert carrier, wetting, herein, principally and not exclusively, for example: stabilising, emulsifying, thickening, dispersing and sur (a) A novel composition comprising an ester of formula face active agents. (I) in combination with at least one organophospho Dusts may be prepared by intimate-admixture of the rus compound; chosen compound with a powered solid inert carrier for (b) A pesticidal formulation comprising a composition example suitable clays, kaolin, talcs, powdered chalk, as defined in paragraph (a) together with a carrier calcium carbonate, Fuller's Earth, gypsum, diatoma therefor; ceous earths and vegetable carriers. (c) A method of producing such a formulation; and Sprays of a composition of this invention may com 45 (d) A method of controlling veterinary ectoparasites of prise a solution in an organic solvent (e.g. those listed the sub-Orders Ixodoidea and Sarcoptiformes com below) or an emulsion in water (dip wash or spray prising the application to the ectoparasite or its envi wash) prepared in the field from an emulsifiable concen ronment, a composition or formulation as defined in trate (otherwise known as a water miscible oil) or a paragraph (a) or (b). water dispersible powder which may also be used for 50 The following Examples are privided by way of an dipping purposes. The concentrate preferably com illustration of the present invention and should not be prises a mixture of the active ingredients, with or with construed as in any way constituting a limitation out an organic solvent and one or more emulsifiers. thereof. Solvents may be selected from kerosene, ketones, alka EXAMPLE 1. nols, xylene, aromatic naphtha, and other solvents 55 Engorged female ticks of the Biarra strain of Boophi known in the formulating art. The concentration of lus microplus are immersed, in groups of 20 ticks per emulsifiers may be varied within wide limits and are concentration, in a range of dilutions of the organo conveniently non-ionic or a mixture of non-ionic and phosphorus compound in combination with 3-phenoxy anionic surfactants. The non-ionic surfactants will in benzyl (-t-) cis, trans-2,2-dimethyl-3-(2,2-di clude polyoxyalkylene ethers or alkyl phenols, or of 60 chlorovinyl)cyclopropane-1-carboxylate (hereinafter alcohols. The anionic compounds include salts of alkyl referred to as Permethrin) at different ratios of organo aryl sulphonic acids. phosphorus compound to Permethrin. Dip washes may be prepared not only from emulsifi The composite wash is prepared immediately prior to able concentrates but also from wettable powders com the test by dilution (with water) of the two constituents. prising a composition of this invention in intimate ad 65 The constituents may be in the form of miscible oil or mixture with an inert carrier and one or more surface wettable powder formulations. The desired range of active agents, and possibly a stabiliser and/or an antioxi concentrations for the test is obtained by further dilu dant. tion of this master solution or wash. 4,897,386 5 6 The ticks are removed from the wash after 10 min utes, dried, and stuck dorsal side down on double-sided EXAMPLE 3 adhesive tape. They remain in this position for 14 days Miscible-Oil Formulations when the numbers laying viable eggs are determined. From this data a regression line is plotted (concentra tion against % inhibition of egg-production) and the 20:1 1:1 :20 Dioxathion 20,0 10.5 10 pts. by wt. IR90 and IR99 values determined (Table 1). Permethrin 1.0 10.5 20.0 y IR90=concentration at which 90% inhibition of egg Esso Solvent 200 59.0 54.0 49.0 production occurs. Ethylan KEO 20,0 20,0 20.0 IR99= concentration at which 99% inhibition of egg- 10 Cyclohexanone 5.0 10.0 production occurs. 100.0 100.0 100.0 The values so obtained for the composite wash are compared with similar values obtained for the constitu Ethylan KEO is an emulsifying agent which is a ents of the composite wash when used alone. By refer nonyl phenyl ethoxylate condensate with an ethylene ence to the equation for the harmonic mean, the factor 15 oxide average chain length of 9.5 mols, supplied by of potentiation is determined (Table 2). Lankro Chemicals Ltd. The equation for the harmonic mean is: Esso Solvent 200 is a mobile oil which consists of 95% of aromatic hydrocarbons. -- Proportion of A-E Proportion of B T Proportion of 4 Proportion of B 20 EXAMPLE 4 R90A R90 B Dusting Powder Formulations Y -- IR90 mixture of A and B 20: 1:1 :20 Factor of Potentiation (FOP) = - YX EProportion of A - 25 Coumaphos O.O. 0.10 0.20 pts. by wt. Proportion of A - B Pernethrin 0.20 0.10 0.01 Taic 99.79 99.8 99.79 sy The FOP figures for the IR99 values were calculated 100.0 100.0 100.0 -1 in the same way. TABLE IHCO/99 Values for the Ixodicidey alone and Compositions of these with Permethrin at various Ratios PERMETHRIN XODICDE COMPOSTE ALONE RATIO 11 RATIO 1:5 RATIO 5:1 RATIO 10:l RATIO 20:1 WITH R90 R99 IR90 IR99 R90 IR99 IR90 IR99 IR90 IR99 IR90 IR99 Coumaphos 1.0 - 0.016 0,024 0016 003O 0.030 0.092 Composition A 0.75 2.6 0.01 0.07 0031 00:53 0.060 0.15 Bromophos Ethyl 0.18 0.38 0.00 0.06.0.058 0.098 0.064 0.2 Diazinon .0 -- 0.095 0.21 0030 .0056 0.017 0.038 Dioxathion 10 0.016 0.038 0028 0.023 0.044 0,060 Chlorpyrifos 0.085 0.24 0.008 0.014 0046 .0062 0.020 0.024 Ethiola 0.14 0.23 0015 0.024 0.032 00:55 0.033 0.054 Dicrotophos 1.0 0.063 0.15 0080 0.016 0.044 0.094 Chlorfenvinphos 0.15 0.42 0.013 0.024 OO15 0030 0.08 0.085 0.043 0.070 0.067 0.096 Composition A:A 1:1, weight by weight mixture of Chlorfenwin.phos and Dioxathion Key:- Ratio Ixodicide/Permethrin

TABLE 2 Factors of Potentiation of composites of certain Ixodicides and Pernethrin PERMETHRIN COMPOSITE RATIO 1:1 RATIO 1:5 RATIO 5:1 RATIO 10: RATIO. 20:1 WITH R90 IR99 R90 R99 R90 IR99 R90 IR99 IR90 IR99 COUMAPHOS >3.9 - > 8.1 - > 1.8 COMPOSITONA 5.5 7.3 4.2 4.8 3.8 3.5 BROMOPHOSETHYL 4.9 6. 2.1 2.6 .8 2.0 DIAZINON >0.7 - > 4.5 - > 4.6 - DIOXATHION >3.9 - > 4.7 - >5.6 CHLORPYRFOS 4.6 6.0 2S 3.8 3.4 7.3 ETHION 3.0 3.5 3.8 4.2 3.0 3.1 DCROTOPHOS > 1.0 - > 1.6 - > 5.6 CHLOR- 3.1 4. 8. 8. 5.7 3.0 2.8 4.6 2.0 3.8 FENVINPHOS Composition A:A 1:1, weight by weight mixture of Chlorfenvinphos and Dioxanthion Key:- Ratio Ixodicide/Permethrin 4,897,386 7 8 EXAMPLE 5 -continued Wettable Powder Formulations 50/50 mixture of trichlorofluoromethane 60,000.0% w/w and dichlorodifluoromethane 100,000.0% w/w 5 ww w/w ww Counaphos 1.0% 15.0% 40.0% Example B Permethin 20.0 15.0 2.0 Diatomaceous Earth 76.5 500 - Kaolin 7.5 54.0 Pesticide mixture Dispersing Agent 2.0 2.0 3.0 10 (either No. 1, 2 or 3 above) 20% w/w Wetting Agent 0.5 0.5 1.0 Methyl chloroform 50% w/w 100.0 100.0 000 Dichlorodifluoromethane 30% w/w waw wAw 100% w/w Ethion 2.0 25.0 Permethin 20.0 1.5 15 Diatonaceous Earth 60.5 36.0 EXAMPLE 7 Fullers Earth S.0 35.0 Highly tick susceptible cattle were placed in tick WettingDispersing Agent Agent 2.O0.5 2.00.5 stalls and artificiallya infested witho 0.25 g if B. microplus 100.0 100.0 (Biarra strain) larvae before and after treatment. 20 Twenty-four days after introduction the animals were divided into four groups and power-hand sprayed with EXAMPLE 6 36 liters of wash per animal. The washes contained the following concentrations of active ingredients: Pressure-Pack Formulations Group 1: 500 ppm Ethion In the following examples one of three pesticide mix- 25 Group 2: 100 ppm permethrin tures may be used: Group 3: 100 ppm permethrin and 500 ppm Ethion Group 4: 50 ppm permethrin and 500 ppm Ethion Mixture Dioxathion 10 parts by weight Engorged female ticks were collected daily from the Chlorfenvinphos 10 parts by weight washing baskets and counted. The results are illustrated Permethin l part by weight 30 in Table 5. Mixture 2 Dioxathion 0.5 parts by weight Chlorfenvinphos 0.5 parts by weight EXAMPLE 8 Permethrin 1 part by weight Mixture 3 Dioxathion 0.5 parts by weight Engorged female ticks of the Biarra strain of B. mi Chlorfenvinphos 0.5 parts by weight croplus were immersed in serial ranges of concentrations Permethrin 20 parts by weight 35 of certain ixodicides alone. The ticks were then dried and stuck, dorsal side down, on double-sided sellotape. The above pesticide mixtures may be employed to for After 14 days the numbers of ticks laying viable egg mulate pressure packs containing between 0.0001% batches were determined and the percentage plotted w/w and 20% w/w of each pesticide mixture as illus against concentration and a regression line drawn. The trated by the following examples: 0 IR90/99 values were then determined as in Example 1. Having thus established the IR90/99 values for each of Example A the chemicals under test equitoxic mixtures each com prising permethrin with one of the other ixodicides

Pesticideestice milixture were prepared at o the ratio of the IR99 values obtained. (either No. 1, 2 or 3 above) 0.000% w/w 45 The master solutions were then diluted with water to Odourless kerosene 10.0000% w/w the required range for the immersion test. Methyl chloroform 29.9999% w/w The results are illustrated in Table 10. TABLE 5 DAILY TICK COUNTS Group 3 100 ppm Time Group 1 Group 2 permethrin Group 4 in Control 100 ppm 500 ppm 50 ppm permethrin Days 500 ppm Ethion permethrin Ethion 500 ppm Ethion -2 147 107 220 37 - 1 148 26 520 122 Spray O 220 79 270 8O 1. 148 31 3 3 2 176 17 3 432 41 O 3 4. 490 13 O 9 5 235 27 O 7 6 258 51 O O 7 233 38 O O 8 187 71 O O 9 265 17 O O 10 289 86 O 73 11 245 32 O O 12 500 2 O 7 4,897,386 9 10 TABLE 5-continued DALY TCK COUNTS Group 3 100 ppm Time Group 1 Group 2 permethrin Group 4 in Control 100 ppm 500 ppm 50 ppm permethrin Days 500 ppm Ethion permethrin Ethion 500 ppm Ethion 13 300 O O 7 14 285 27 O 19 5 300 7 O O 6 250 4. O O 7 230 O O 9 18 200 4. O 6 19 10 2 O 2 20 360 O O O 2 700 O O O 22 420 O O 1. 23 220 O O O 24 220 4. O O 25 490 2 O O 26 200 30 O O 27 700 14 O O 28 530 126 O O 29 40 13 O O 30 30 79 O O 31 77 81 O O 32 490 12 O O 33 450 130 4 l 34 780 178 27 38 35 1250 2S4 27 97 Percentage control compared with Ethion treated group days i-21 inclusive: No 2 100 ppm pormethrin - 91.3% No 3500 ppm ethion 100 ppm permethrin - 99.9% No. 4500 ppm ethion 50 ppm permethrin -96.8% Protective period against larval reinfestation: No 1 Nil No 22 days s No 3 11 days No 4 11 days

TABLE 6 LC50 values of individual organophosphorus insecticides and compositions of these with permethrin obtained both theoretically and by experiment against Musca domestica (CTB strain) (ratio 1:1) Experimental Calculated LC50 Mixture LC50 Mixture - LC50 Alone as permethrin LC50 Total as perimethrin Factor of Compound (ig/9) (ig/9) (ig/9) (ig/9) Potentiation

Permethin 0.027 o o Bromophos ethyl 0.02 0.029 0.043 0.021 0.74 Chlorpyrifos 0.094 0.025 0.042 0.02 0.84 Bromophos 0.14 0,021 0.043 0.022 1.02 Malathion 349 0.036 0.053 0.026 0.73 Diazinon 0.041 0.025 0.032 0.016 0.66 LC50 is the minimum lethal dose expressed in tug required to kill 50% of the flies

TABLE 7 LC95 values of individual organophosphorus insecticides and compositions of these with permethrin obtained both theoretically and by experiment against Musca domestica (CTB strain) (ratio 1:1) - Experimental - - Calculated - LC95 Mixture LC95 Mixture LC95 Alone as permethrin LC95 Total as permethrin Factor of Compound (ig/9) (g/9) (ug/9) (ig/9) Potentiation Perimethrin 0.054 Bromophos ethyl 0.70 0.097 0.082 0.04 0.43 Chlorpyrifos 0,161 0.083 0.081 0.041 0.49 Bromophos 0.241 0.063 0.088 0.044 0.70 Malathion 3.671 0.05 0.107 0.053 0.51 Diazinon 0.160 0.066 0.081 0.040 0.61 LC95 is the minimum lethal dose expressed in ug required to kill 95% of the flies 4,897,386 11 12 TABLE 8 LD50 values for individual organophosphorus insecticides and compositions of these with permethrin at various ratios against Musca domestica (Piggery II strain) Ratio 1:1 Ratio 1:10 (permethrin/OP) Ratio 1:25 (permethrin/OP) LD50 Cal- Calculated Calculated Calculated Compound (ug/9) culated observed observed Calculated observed observed Calculated observed observed

Permethrin 0.235 o - m ------Dimethoate 0.179 0.20 0.20 1.0 0.18 0.13 1.4 - - - Diazinon 2.075 0.41 0.35 1.2 1.2 0.89 1.4 - - - Malathion 4.70 0.46 0.42 1.1 2.45 2.49 1.0 5.36 3.0 1.8 Chlorpyri- 2.171 0.41 0.38 .1 1.25 0.76 1.7 - - - fos Bromophos 2.663 0.42 0.39 . 1.38 0.50 2.8 - -- ethyl Pirimiphos 5,130 0.44 0.38 1.2 1.78 1.22 5 2.85 1.77 1.6 methyl LD50 is the minimum lethal dose expressed in pig required to kill 50% of the flies OP = organophosphorus compound calculated value Factor of potentiation = observed value

TABLE 9 LD95 values for individual organophosphorus insecticides and compositions of these with permethrin at various ratios against Musca domestica (Piggery II strain) Ratio 1:1 Ratio 1:10 (permethrin/OP) Ratio 1:25 (permethrin/OP) LD95 Cal- Calculated Calculated Calculated Compound (ug/9) culated observed observed Calculated observed observed Calculated observed observed

Pernethin 0.63 - m ------Dimethoate 0.66 0.65 0.53 1.2 0.66 0.62 1.1 - --- - Diazinon 5.12 1.16 1.06 1.1 3.11 2.84 1.1 - - - Malathion 177.5 30 1.03 1.3 6.70 9.00 0.7 15.05 3.00 1.9 Chlorpyri- 10.66 1.23 0.85 1.5 4.36 1.79 2.4 - --- - fos Bromophos 11.62 1.24 0.91 .4 4.50 1.82 2.5 -- - ethyl Pirimiphos 15.6 1.26 0.91 1.4 4.92 3.28 15 8.15 5.02 1.6 methyl LD95 is the minimum lethal dose expressed in ug required to kill 95% of the flies OP = organophosphorus compound Factor of potentiation = calculated value p a. observed value

TABLE 10 The activity of equitoxic mixtures of certain organo phosphorus ixodicides with permethrin against viable oviposition of engorged female ticks of the Biarra of B. microplus EOUITOXIC MIXTURE Permethrin ALONE Expected Value Actual Value Factor of Potentiation Composite with R90 R99 IR90 IR99 R90 R99 R90 IR99 Ethion 0.14 0.23 0.0 0.8 0.012 0.024 8.3 7.5 Chlorfenvinphos 0.15 0.42 0. 0.28 0.025 0.059 4.4 4.7 Permethrin 0.066 0.13

Factor of Potentiationarian =- ExpectedActual Value Value IR90 = concentration at which 90% inhibition of egg laying occurs IR99 = concentration at which 99% inhibition of egg laying occurs

EXAMPLE 9 EXAMPLE O % w/w 60 Aqueous Suspension Formulations (a) (b) (c) % w/w Permethrin 1.0 8.0 20.0 Diluent Free Formulations (a) (b) (c) Coumaphos 20.0 8.0 1.0 Pernethrin 3.5 38.0 72.0 Sodium Dioctyl Sulphosuccinate 0.2 0.2 0.2 Diazinon 700 38.0 3.6 Xanthan Gum 0.3 0.4 0.3 65 Epichlorhydrin 7.0 4.0 0.4 Water 78.5 83.4 78.5 Ethylan KEO 19.5 20.0 24.0 100.0 100.0 100.0 100.0 100.0 100.0 4,897,386 13 14 Ethylan KEO is an emulsifying agent which is a and LC95 value was calculated for each mixture by nonyl phenol ethoxylate condensate with an ethylene means of the equation of the harmonic mean. The theoretical and experimental values were then oxide average chain length of 9.5 mols, supplied by compared in order to give factors of potentiation val Lankro Chemicals Ltd. S. Reference Example A The results are given in Tables 6 to 9, which indicate that little or no potentiation was observed. Mixtures of permethrin in combination with various What we claim is: organophosphorus compounds were prepared at 1:1, 1. A method of controlling veterinary ectoparasites 1:10 and 1:25 ratios (ratios permethrin to organophos O of mammals and birds of the sub-orders IXODOIDEA and Sarecoptiformes comprising the application of a phorus compound). Solutions of the pesticides alone synergistic composition comprising a parasiticidially were similarly prepared. effective, non-toxic amount of permethrin together with The individual pesticides and the mixtures were di Ethion, said composition containing 5 to 95% of per luted appropriately and applied by means of a microsyr 15 methrin and 5 to 95% of Ethion. inge to the dorsal thorax of female CTB or Piggery II 2. A method of claim 1 in liquid form which the strain musca domestica flies. This topical application concentration of permethrin to Ethion 50 to 500 to 100 technique was performed on twenty females flies for to 500 ppm. each concentration of each mixture. The flies were then 3. The method of claim 1 in which the weight ratio of 20 Permethrin to Ethion is 1 to 1 to 5 to 1. placed in a cardboard carton with access to sugar water 4. A method of controlling veterinary ectoparasites for one day in order to assess mortality. Each concen of mammals and birds of the sub-orders IXODOIDEA tration of each mixture was tested five times in a linked and Sarecoptiformes comprising the application of a sequence over a period of several weeks. synergistic composition comprising permethrin in com The LC50 and LC95 value of each mixture was deter 25 binations with Ethion in a ratio of 1 to 5 to 5 to 1. mined by means of probit analysis. A theoretical LC50 : s : k

30

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55

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