FR2746596A1 - EXTERNAL PEST CONTROL DEVICE FOR N-PHENYLPYRAZOLE-BASED CATTLE, ESPECIALLY EAR LOOPS - Google Patents

Abstract

An external device such as a ring, particularly an earring, for controlling cattle parasites and horn fly (Haematobia irritans) in particular, consisting of a matrix that includes 0.1-40 wt.%, preferably 2.5-10 wt.%, based on the weight of the earring, of an active substance that is at least one compound of formula (I), is disclosed. Said external device is designed to be effective for over 30 weeks.

Description

 The present invention relates to external antiparasitic devices for cattle, in particular in the form of a loop and more particularly of an ear loop (ear loop).

 It also relates to the use of active compounds for the manufacture of such external devices, as well as to a treatment method relating thereto.

One of the main parasites of cattle is a fly called Haematobia irritans (horn fly in English) whose adult is a permanent blood-sucking parasite of cattle. This parasite, which is found mainly in North America but also in
Europe, Australia, South Africa, can cause considerable economic losses, both in terms of weight gain and milk production, especially when the parasite pressure exceeds 50 flies per animal, whereas, in certain regions, it does not is not uncommon to exceed 200 flies per animal.

 We do not know today how to fight effectively against this parasite. The difficulty of control largely results from the fact that the parasite pressure is constant, because it is a winged parasite in its adult form, which can therefore pass from one flock to another and therefore permanently reinfest herds for which a pest control procedure has been implemented. In addition, in some areas, parasite pressure lasts throughout the year.

Breeders currently have few effective means of control, especially in the case of extensive grazing, even by ensuring a constant fight against these parasites, that is to say by regular and close contributions of insecticides , especially since flies have developed resistance to pyrethroids and organophosphorus compounds.

 Ear loops have also been proposed, intended, as their name suggests, to be fixed on the animal's ear and to release an active substance over a more or less long period. These loops consist of a matrix, usually a plastic matrix, incorporating the active substance and capable of releasing it over time. The loops are therefore theoretically intended to provide lasting protection.

 However, despite the activity claims, the loops do not exhibit the effectiveness required in the field to ensure the actual elimination of these parasites. The cause may be the low activity of the active substance included in the matrix. Another cause may be the accelerated degradation of these active substances under the influence of climatic factors, such as light, heat, rain. Finally, the control of the release of the active substance from the matrix is greatly overestimated. The release is generally difficult and variable, it can depend strongly on the manufacturing conditions which may vary from one batch to another, and the conditions of use, in particular climatic variations and in particular the humidity and temperature, etc. In addition, only a relatively small amount of the active ingredient incorporated is actually released and it proves difficult to want to control and optimize the release.

 Only the organophosphates made it possible to obtain a release of approximately 4 months but with considerable concentrations of active substance, of the order of 40% by weight.

Patent applications WO-A-87/03781, EP-A-0 295 117, EP
AO 296 381 and EP-A-0 500 209 relate to a family of insecticides which are N-phenylpyrazoles. These substances are described as being active against a very large number of parasites encountered in various fields, namely agriculture, public health, human and veterinary medicine.

 EP-A-0 500 209 indicates that, in the field of public health, these compounds can be used to combat a large number of insects, in particular flies among which are cited "hornflyW or Haematobia irritans.

Haematobia irritans is not mentioned in the context of the treatment of animals.

 These substances can be applied in different ways, namely by the oral, parenteral, percutaneous or topical route. The topical administration itself covers various possibilities, namely sprays, powders, baths, showers, jets, greases, shampoos, creams, waxes, preparations of the skin solution type (pour-on) and external devices such as loops ear and necklaces to ensure local or systemic treatment.

 EP-A-0 295 117 and EP-A-0 500 209 additionally propose a composition for slow release which can be put in the form of a necklace or ear loops to fight against harmful insects. Such a formulation can comprise from 0.5 to 25% of active material, from 75 to 99.5% of polyvinyl chloride and a catalytic amount of a plasticizer, dioctyl phthalate.

 US-A-5,472,955 illustrates the difficult nature of the fight against Haematobia irritans and indicates that it is necessary to use a combination of two active compounds, diazinon and chlorpyrifos, in high concentration within a slow release device. This document indicates that the compounds taken alone are not as effective as the synergistic combination of the two compounds. Diazinon simply provides acceptable control of Haematobia irritans over 3 to 5 months while chlorpyrifos seems incapable. This document specifies at the end that an ear mouth containing a 40% mixture was much more active than 2 ear loops applied to the same animal and containing 21.4% of diazinon as the only active ingredient. If the proportion of active principle can range in theory from 8 to 40%, it is preferably between 20 and 40%. In the case of ear loops the proportion is from 10 to 50% by weight, preferably from 30 to 45% and optimally from 40% by weight.

None of the cited documents describes or suggests that it is possible to effectively protect cattle from
Haematobia irritans, over a long period of time, using ear loops comprising a single active compound, for which, in addition, the specialist could expect to encounter the classic problems of release from the loops and therefore of activity.

 Like the other insecticides of the prior art, these Nphenylpyrazoles are indeed subject to the same difficulties in the context of external release devices such as ear loops.

 It therefore did not seem conceivable to want to fight effectively against parasites suspected of being found anywhere in the animal, which is moreover winged parasites inducing a parasitic pressure as strong and constant as Haematobia irritans.

 However, the Applicant has surprisingly found that it was actually possible to effectively eliminate Haematobia irritans in cattle by using an ear loop using an N-phenylpyrazole under specific concentration conditions. The Applicant has surprisingly found that, despite the problems associated with release by the ear loops, the effectiveness extends to the entire body of the animal and is very long-lasting and that, for example with loops loaded at 10%, we could exceed 32 weeks of efficiency greater than 90%.

 The active substance acts by simple contact, the parasite impregnating it on contact with hair and skin.

dans laquelle
R1 est CN ou méthyle ou un atome d'halogène
R, est S(O)nR3 ou 4,5-dicyanoimidazol 2-yl ou haloalkyle
R3 est alkyle ou haloalkyle
R4 représente un atome d'hydrogène ou d'halogène ; ou un radical NRsR6, S(O)P,, C(O)R7, C(O)O-R7, alkyle, haloalkyle ou Oh ou un radical -N=C(R,) (R10) ;
R5 et h représentent indépendamment l'atome d'hydrogène ou un radical alkyle, haloalkyle, C(O)alkyle, alcoxycarbonyl,
S(O)rCF3 ; ou R5 et R6 peuvent former ensemble un radical alkylène divalent qui peut être interrompu par un ou deux hétéroatomes divalents, tels que l'oxygène ou le soufre
R7 représente un radical alkyle ou haloalkyle
Re représente un radical alkyle, haloalkyle ou un atome d'hydrogène
R9 représente un radical alkyle ou un atome d'hydrogène
Rlo représente un groupe phényl ou hétéroaryle éventuellement substitué par un ou plusieurs atomes d'halogène ou groupes tels que OH, -O-alkyle, -S-alkyle, cyano, ou alkyle;
R11 et R12 représentent, indépendamment l'un de l'autre, un atome d'hydrogène ou d'halogène, ou éventuellement CN ou NO2 ;
R13 représente un atome d'halogène ou un groupe haloalkyle, haloalkoxy, S(O)qCF3 ou SFs
m, n, q, r représentent, indépendamment l'un de l'autre, un nombre entier égal à 0, 1 ou 2
X représente un atome d'azote trivalent ou un radical C
R12, les trois autres valences de l'atome de carbone faisant partie du cycle aromatique
sous réserve que, lorsque R1 est méthyle, soit R3 est haloalkyle, R4 est NH2, R11 est Cl, R13 est CF3, et X est N ; soit
R2 est 4,5-dicyanoimidazol 2-yl, R4 est C1, R1l est Cl, R13 est
CF3 et X est =C-C1. The present invention therefore relates to an external device such as a loop, in particular an ear loop, intended for the elimination of parasites from cattle, in particular from
Haematobia irritans, formed of a matrix including from 0.1 to 40% by weight relative to the ear loop, of an active substance which is at least one compound of the following formula (I)

in which
R1 is CN or methyl or a halogen atom
R, is S (O) nR3 or 4,5-dicyanoimidazol 2-yl or haloalkyl
R3 is alkyl or haloalkyl
R4 represents a hydrogen or halogen atom; or a radical NRsR6, S (O) P ,, C (O) R7, C (O) O-R7, alkyl, haloalkyl or Oh or a radical -N = C (R,) (R10);
R5 and h independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxycarbonyl,
S (O) rCF3; or R5 and R6 may together form a divalent alkylene radical which may be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur
R7 represents an alkyl or haloalkyl radical
Re represents an alkyl or haloalkyl radical or a hydrogen atom
R9 represents an alkyl radical or a hydrogen atom
Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;
R11 and R12 represent, independently of one another, a hydrogen or halogen atom, or optionally CN or NO2;
R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SFs group
m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2
X represents a trivalent nitrogen atom or a radical C
R12, the other three valences of the carbon atom being part of the aromatic cycle
with the proviso that, when R1 is methyl, either R3 is haloalkyl, R4 is NH2, R11 is Cl, R13 is CF3, and X is N; is
R2 is 4,5-dicyanoimidazol 2-yl, R4 is C1, R1l is Cl, R13 is
CF3 and X is = C-C1.

 this external device being designed to ensure an effectiveness of more than 30 weeks.

Preferably, the compound of formula (I) is such that
R1 is CN or methyl
R2 is S (O) nR3
R3 is alkyl or haloalkyl
R4 represents a hydrogen or halogen atom; or a radical NRsR6, S (O) = R "C (O) R7, alkyl, haloalkyl or OR8 or a radical -N = C (R ');
R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or R5 and R6 may together form a divalent alkylene radical which may be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur
R7 represents an alkyl or haloalkyl radical
R8 represents an alkyl or haloalkyl radical or a hydrogen atom;
R9 represents an alkyl radical or a hydrogen atom
Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;
R11 and R12 represent, independently of each other, a hydrogen or halogen atom
R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group;
m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2
X represents a trivalent nitrogen atom or a radical CR, 2, the three other valences of the carbon atom being part of the aromatic ring provided that, when R1 is methyl, that is to say R3 is haloalkyl, R4 is NH2, R11 is Cl, R13 is CF3, and X is N.

Particularly noteworthy are the compounds of formula (I) in which R1 is CN. We will also retain the compounds in which R2 is S (O) nR3, preferably with n = 1, R3 preferably being CF3 or alkyl, for example methyl or ethyl or alternatively n = 0, R3 preferably being CF3, as well as those in which X = C-R12, R12 being a halogen atom. Preference is also given to the compounds in which R11 is a halogen atom as well as those in which R13 is haloalkyl, preferably
CF3. In the context of the present invention, the compounds combining two or more of these characteristics will advantageously be retained.

A preferred class of compounds of formula (I) consists of the compounds such that R1 is CN, R3 is haloalkyl, preferably CF3, or ethyl, R, is NH2, R11 and R12 are independently of one another one halogen atom, and / or
R13 is haloalkyl.

The alkyl radicals of the definition of the compounds of formulas (I) generally contain from 1 to 6 carbon atoms. The ring formed by the divalent alkylene radical representing Rs and R6 as well as the nitrogen atom at which Rs and
R6 are attached, is generally a 5, 6 or 7-membered ring.

 A compound of formula (I) very particularly preferred in the invention is l- [2,6-Cl2 4-CF3 phenyl] 3-CN 4- [SO-CF3] 5 pyrazole, hereinafter called compound A.

Mention may also be made of the two compounds which differ from the preceding A by the following characteristics
1- n = 0, R3 = CF3
2- n = 1, R3 = ethyl.

 The preparation of compounds of formula (I) can be carried out according to one or other of the methods described in patent applications WO-A-87/3781, 93/6089, 94/21606 or European EP-AO 295 117 , or any other process falling within the competence of a person skilled in the art of chemical synthesis. For the chemical production of the products of the invention, those skilled in the art are considered to have at their disposal, among other things, all the content of the Chemical Abstracts "and of the documents cited therein.

However, low concentrations of 1 to 15% by weight are preferred and more particularly, in particular for the compound
A, from 2.5 to 10%. Optimally, the loops according to the invention comprise from 5 to 10% by weight of active substance, in particular of compound A.

 In the context of the present invention, the external devices naturally include any device intended to be fixed to the body of the animal and making it possible to release the active substance under the conditions of effectiveness of the invention.

 By acting on the concentration of active substance and / or on the composition, it is possible to manufacture ear loops having an efficiency with respect to Haematobia irritans which can exceed 90% and even 95% for more than 30 weeks, especially for 32 weeks .

 It is remarkable that this total effectiveness and of very long duration is obtained by the only compound according to the invention without the addition of another insecticide.

 The active substance may, however, comprise, in addition to the compound of formula (I), another insecticide, for example pyrethroids (in particular permethin, cypermethrine, etc.), organophosphorus compounds (for example diazinon), imidacloprid and IGR (regulators of insect growth).

 This combination of active substances can be done in different ways. Either the active substances are combined within the same ear loop, including a composite ear loop, i.e. made in two parts, each part including one of the active substances, or two separate ear loops are used, each comprising one of the active substances, and intended to be placed, preferably, each on a different ear of the animal. In the latter case, the subject of the invention is a kit comprising these two ear loops.

 The matrix of the external devices according to the invention can be based on polyvinyl chloride (PVC) (see US-A-3,318,769, 3,852,416, 4,150,109, 5,437,869) and other vinyl polymers, optionally supplemented with additives such as plasticizers, pigments, etc. In general, it is possible to use the matrices usually used in usual external devices such as ear loops and necklaces.

 The plasticizers can in particular be chosen from adipates, phthalates, phosphates and citrates.

One or more plasticizers will preferably be added to the PVC, in particular chosen from the following compounds
- diethyl phthalate
- Dioctyle sebaçate
- Dioctyle adipate
- Diisodecyl phthalate
- Acetyl tributyl citrate
- Diethyl hexyl phthalate
- Di-n-butyl phthalate
- Benzyl butyl phthalate
- acetyl tributyl citrate
- tricresyl phosphate
- 2-ethylhexyl diphenyl phosphate.

Even more preferably, a matrix will be used
PVC in the presence of a residual primary plasticizer as described above and of a secondary plasticizer, in particular according to EP-A-0 539 295 and EP-A-0 537 998.

 Among the secondary plasticizers, mention may be made of the following products - Acetyl triethyl citrate - Triethyl citrate - Triacetin - Diethylene glycol monoethyl ether - Triphenyl phosphate.

 You can also add a standard stabilizer to it.

 The present invention also relates to a process for eliminating external parasites, in particular Haematobia irritans, from cattle, especially bred in the open air and more particularly in extensive grazing, consisting in fixing the earring (s) on the animal according to the present invention and ensuring the effective and lasting protection described above.

 This process generally consists in attaching to the animal 1 or 2 ear loops or the like loaded with compound according to the invention, preferably with compound A. These loops have the specifications mentioned above.

 The method may also include the combined use of other insecticides, by the use of loops, composite loops or different loops as described above.

 In general, the method according to the invention provides for the animal to wear the loop (s) throughout the year.

 The aim of the method is non-therapeutic and in particular to clean the skin and the hair of the animals by eliminating the parasites which are present there as well as their residues and excrements. As a result, the animals are no longer stressed by the parasites and their bites, which has positive consequences for example on their growth and on the use of their food ration.

 Another object of the invention is a therapeutic method using the external device according to the invention, intended for the treatment and prevention of parasitoses having pathogenic consequences.

 The present invention also relates to the use of a compound corresponding to formula (I) above, for the production of external devices such as loops, in particular ear loops, intended to be attached to cattle to ensure the elimination of Haematobia irritans at a high degree of effectiveness and over a period exceeding 30 weeks. The devices as described before are targeted. Preferably, the use according to the invention provides for the incorporation of 0.1 to 40% by weight, preferably from 1 to 15% by weight, of the compound of formula (I) in a matrix intended to form the external device. . Even more preferably, the incorporation is carried out at a rate of 2.5 to 10% by weight, and even from 5 to 10%.

 Preferably, the use according to the invention aims at the manufacture of ear loops.

 Preferably, the use according to the invention aims at ia production of external devices or ear loops having an efficiency greater than 90% or 95%.

The present invention will now be described in more detail using an embodiment taken without limitation and referring to the drawing in which
- Figure 1 is a graph showing the population of
Haematobia irritans in a control group, with time (weeks) on the abscissa and the arithmetic mean on the ordinate and
- Figure 2 is a graph with time (week) on the abscissa and the arithmetic mean of the count of Haematobia irritans on the ordinate.

We performed the following groups
Group A: controls: 10 heifers
Group B: 10 heifers having received ear loops loaded with 2.5% of compound A. Each animal receives a loop.

 Group C: 10 heifers having received ear loops loaded with 10% of compound A. Each animal receives a loop.

 Group D: 10 heifers having received ear loops loaded with 10% of compound A. Each animal receives two loops, one per ear.

 The ear loops are made from polyvinyl chloride (PVC), added with a stabilizer (Mark 152S), a plasticizer (acetyl tributyl citrate) and a pigment (titanium dioxide). They are produced by injection molding.

 Each group of animals is placed in a pasture of approximately 100 to 150 acres (40 to 60 hectares).

 The infestation with Haematobia irritans is of natural origin.

The schedule is as follows
on day 0, we place the earrings. The Haematobia irritans parasites are then counted every 6, 7 or 8 days.

 With all the formulations according to the invention, an efficiency greater than 90% and even greater than 95%, which can reach 100%, was obtained over long periods. The 2.5% composition has been shown to be more than 90% effective for 18 weeks. The 10% composition, placed on one or both ears, also provides more than 90% protection, and over a much longer period of time, which reaches 32 weeks. The use of two earrings per animal provides superior protection which is close to 100% over the entire 32-week period.

 The results are reported in Figures 1 and 2.

Claims (26)

 1. External device such as a loop, in particular an ear loop, intended for the elimination of Haematobia irritans in cattle, formed of a matrix including from 0.1 to 40% by weight relative to the ear loop, of a active substance which is at least one compound of formula (I) below

 this external device being designed to ensure an effectiveness of more than 30 weeks. CF3 and X is = C-Cl R2 is 4,5-dicyanoimidazol 2-yl, R4 is Cl, R11 is Cl, R13 is  with the proviso that, when R1 is methyl, either R3 is haloalkyl, R4 is NH2, R1l is C1, R13 is CF3, and X is N; is R12, the other three valences of the carbon atom being part of the aromatic cycle  X represents a trivalent nitrogen atom or a radical C  m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2  R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group;  R1l and R12 represent, independently of one another, a hydrogen or halogen atom, or optionally CN or NO2  Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;  R9 represents an alkyl radical or a hydrogen atom  R8 represents an alkyl or haloalkyl radical or a hydrogen atom  R7 represents an alkyl or haloalkyl radical S (O) rCF3; or R5 and R6 may together form a divalent alkylene radical which may be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur  R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxycarbonyl,  R4 represents a hydrogen or halogen atom; or a radical NRR ', S (O) = R7, C (O) R7, C (O) O-R7, aikyle, haloalkyle or OR8 or a radical -N = C (R9) (R10)  R3 is alkyl or haloalkyl  R2 is S (O) nR3 or 4,5-dicyanoimidazol 2-yl or haloalkyl  R1 is CN or methyl or a halogen atom  in which  2. Device according to claim 1, characterized in that the compound of formula (I) is such that  R1 is CN or methyl  R2 is S (O) nR3  R3 is alkyl or haloalkyl  Rs represents a hydrogen or halogen atom; or a radical NRR ', S (O) R ,, C (O) R7, alkyl, haloalkyl or OR8 or a radical -N = C (R9) (Rlo);  Rs and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or Rs and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur  R7 represents an alkyl or haloalkyl radical;  R8 represents an alkyl or haloalkyl radical or a hydrogen atom  R9 represents an alkyl radical or a hydrogen atom;  Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;  R11 and R12 represent, independently of each other, a hydrogen or halogen atom  R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) QCF3 or SF5 group;  m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2  X represents a trivalent nitrogen atom or a radical C R12, the other three valences of the carbon atom being part of the aromatic cycle  provided that when R1 is methyl then R3 is haloalkyl, R4 is NH2, R11 is Cl, R13 is CF3, and X is N.  3. Device according to claim 1 or 2, characterized in that the compound of formula (I) is such that R1 is CN.  4. Device according to one of claims 1 to 3, characterized in that the compound of formula (I) is such that R13 is haloalkyl, preferably CF3.  5. Device according to one of claims 1 to 4, characterized in that the compound of formula (I) is such that R2 is S (O) nR3, preferably with n = 1, R3 preferably being CF3 or alkyl, in particular methyl or ethyl, or n = 0, R3 preferably being CF3.  6. Device according to one of claims 1 to 5, characterized in that the compound of formula (I) is such that X is C-R12, R12 being a halogen atom.  7. Device according to one of claims 1 to 6, characterized in that the compound (I) is chosen from those for which R1 is CN, R3 is haloalkyl, Ri is NH2, R11 and R12 are independently one of l the other a halogen atom, and / or R13 is haloalkyl.  8. Device according to claim 2, characterized in that the compound of formula (I) is 1- [2,6-Cl2 4-CF3 phenyl] 3-CN 4- [SO-CF3] 5-NH2pyrazole.  9. Device according to any one of claims 1 to 8, characterized in that the compound of formula (I) is present in an amount of 1 to 15% by weight.  10. Device according to any one of claims 1 to 9, characterized in that the compound of formula (I) is present in an amount of 2.5 to 10%, preferably 5 to 10% by weight.  11. Device according to any one of claims 1 to 10, characterized in that it is in the form of an ear loop.  12. Device according to any one of claims 1 to 11, characterized in that it comprises a concentration of active substance conferring an effectiveness of more than 90% and even more than 95% over a long period of time exceeding 30 weeks .  13. Use of a compound corresponding to the following formula (I)  in which

 for the production of an external device such as a loop, in particular an ear loop, intended to be attached to a bovine to ensure the elimination of Haematobia irritans at a high degree of efficiency and over a period exceeding 30 weeks. CF3 and X is = C-Cl R2 is 4,5-dicyanoimidazol 2-yl, R4 is Cl, R11 is Cl, R13 is  with the proviso that, when R1 is methyl, either R3 is haloalkyl, R4 is NH2, R11 is Cl, R13 is CF3, and X is N; is  X represents a trivalent nitrogen atom or a C Rl2 radical, the other three valences of the carbon atom being part of the aromatic cycle  m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2  R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group;  R11 and R12 represent, independently of one another, a hydrogen or halogen atom, or optionally CN or NO2;  Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;  Rg represents an alkyl radical or a hydrogen atom  Rs represents an alkyl or haloalkyl radical or a hydrogen atom  R represents an alkyl or haloalkyl radical S (O) rCF3; or R5 and R6 may together form a divalent alkylene radical which may be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur  Rs and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxycarbonyl,  Rs represents a hydrogen or halogen atom; or a radical NR5R6, S (O); R7, C (O) R7, C (O) O-R7, aikyl, haloalkyl or OR, or a radical -N = C (R ') (R10);  R3 is alkyl or haloalkyl;  R2 is S (O) nR3 or 4,5-dicyanoimidazol 2-yl or haloalkyl;  R1 is CN or methyl or a halogen atom;  14. Use according to claim 13, characterized in that the compound of formula (I) is such that  R1 is CN or methyl  R2 is S (O) nR3;  R3 is alkyl or haloalkyl  R4 represents a hydrogen or halogen atom; or a radical NR5R6, S (O), R7, C (O) R7, alkyl, haloalkyl or OR6 or a radical -N = C (R9) (Rlo);  Rs and R6 independently represent the hydrogen atom or an aikyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or Rs and R6 may together form a divalent alkylene radical which may be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur;  R7 represents an alkyl or haloalkyl radical;  R6 represents an alkyl or haloalkyl radical or a hydrogen atom  Rg represents an alkyl radical or a hydrogen atom  Rlo represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano, or alkyl;  R11 and R12 represent, independently of each other, a hydrogen or halogen atom  R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group  m, n, q, r represent, independently of one another, an integer equal to 0, 1 or 2  X represents a trivalent nitrogen atom or a radical C R12, the other three valences of the carbon atom being part of the aromatic cycle  provided that when R1 is methyl then R3 is haloalkyl, R4 is NH2, R11 is Cl, R13 is CF3, and X is N.  15. Use according to claim 13 or 14, characterized in that the compound of formula (I) is such that R is CN.  16. Use according to one of claims 13 to 15, characterized in that the compound of formula (I) is such that R13 is haloalkyl, preferably CF3.  17. Use according to one of claims 13 to 16, characterized in that the compound of formula (I) is such that R2 is S (O) nR3, preferably with n = 1, R3 preferably being CF3 or alkyl, in particular methyl or ethyl, or n = 0, R3 preferably being CF3.  18. Use according to one of claims 13 to 17, characterized in that the compound of formula (I) is such that X is C-Rl2 with R12 being a halogen atom.  19. Use according to one of claims 13 to 18, characterized in that the compound of formula (I) is such that R1 is CN, R3 is haloalkyl, R, is NH2, R11 and R12 are independently one of l the other a halogen atom, and / or R13 is haloalkyl.  20. Use according to claim 14, characterized in that the formula (I) is  1- [2,6-C12 4-CF3 phenyll3-CN 4- [SO-CF3] 5-NH2 pyrazole.  21. Use according to one of claims 13 to 20, characterized in that the compound of formula (I) is incorporated in an amount of 0.1 to 40% by weight, preferably from 1 to 15% by weight, in a matrix intended to form the collar or other external device.  22. Use according to one of claims 13 to 21, characterized in that the compound of formula (I) is incorporated in an amount of 2.5 to 10% by weight, preferably 5 to 10%, in a matrix intended to form the external device.  23. Use according to one of claims 13 to 22, characterized in that it is oriented towards the manufacture of ear loops.  24. Use according to one of claims 13 to 23, characterized in that the efficiency is greater than 90% or 95%.  25. Use according to one of claims 13 to 24, characterized in that the effectiveness is maintained over a long period of time exceeding 30 weeks.  26. A method of treating cattle against Haematobia irritans, consisting in attaching to the animal at least one external device as described, and under the conditions indicated, in any one of the preceding claims.