NZ205946A - Controlling sheep ectoparasites using pyrethroids - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £05946 i § 205946 Under the provisions of RegfifSj iaticsfi 23 (!) the ; .

Coi*i?l-ef~c Specification has been ante-datedl tO P. A/0 1/^ 19 J / J Priority Dst.s(s; „. .w cwfete Specification Filed: 0O.M.& .......... vftQi\N9.uP®-'- 3 0 SEP. 1987 Publication Date. •«••••• P.O. Journal, No. t " ^ «f Att AMENDED under Section P«en« A* ■«» 'J ^b' r*r [* V OCT 1983 initials W SU8STITUT!3N OF APPLICANT UNOjEA SECTION 24 COoPE^S (VroiMfl-i- +^AKTPH. kiMiTTEp j ■ Li im NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION "SHEEP ECTOPARASITE CONTROL" I WE/ T-HE—WE'LLGQME—FQU-NDAT-I-QN--IrrMITEE); a Company incorporated in England of 183-193 Euston Road, London W.W.I., England, do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is performed to be particularly described in and by the following statement: - I- « 205946 The present invention relates to a method of controlling sheep ectoparasites selected from keds, mites and blowflies, particularly on merino sheep.

Traditionally, sheep have been treated for the control 5 of ectoparasites by dipping or spraying the whole external surface of the sheep. However, this is ah inconvenient and time-consuming and labour-intensive operation. Attempts have been made to treat infested sheep, particularly lice-infested sheep, with a large variety of known insecticides 10 by various other routes,; including pour-on treatments, subcutaneous injection and by oral dosage. Hitherto, none of the treatments had any significant effect on the control of the lice populations. In particular, merino sheep have not responded to such treatments.

I The pour-on method of application is known. In this method, a low volume of a concentrated parasiticidal formulation is applied as a line or spot to the head or back of the animal. This gives protection over the whole animal. The pour-on method is very advantageous to the farmer or 20 grazier since it allows the animal to be treated in a matter of seconds and requires a minimum of labour, thereby keeping costs down. The pour-on method is well established for cattle and a pour-on formulation containing the organophos-phorus compound famphur is commercially available under the 25 trade mark "Warbex".

However, attempts by the applicant over a long period to develop a corresponding pour-on for sheep have hitherto 205946 met with disappointing results. As shown in the comparative tests hereafter, a large number of established parasiticides proved,ineffective when applied as pour-ons to sheep. This difference in activity is surprising since the previously 5 widely-held view was that the parasiticide worked systemic-ally, i.e. passed through the skin into the bloodstream. If such a mechanism were correct the difference in activity between cattle and sheep is difficult to explain. Thus, up to the present no pour-ons had been available for the treatment 10 of sheep (particularly merino sheep), which could be used as a substitute for conventional dipping or spraying.

The present invention is based on the discovery that a class of known insecticides, the pyrethroids, are surprisingly effective in controlling sheep ectoparasites when 15 applied by the pour-on method. £rho pyrothroido aro oyntho-tic analoguoG of the naturally occurring pyrothrins and are— typically doooribod in Britioh Patent Cpecification number 1, 413,49lj Thus, the present invention provides a method of con-20 trolling sheep ectoparasites selected from keds, mites and blowfiles which comprises the application onto a localised region of the skin or fleece of a sheep of a pyrethroid of the formula wherein £nr - CH CH - CH = C flow AMENDED 205946 CH - CH - C X2 ,Xi VX2 or and wherein Xi to Xi, are independently selected from halo, Cj-Cu alkyl, halogen-s,ubstituted Cj-Ci, alkyl, \ \ and halogen-substituted^phenyl; Xs is -H or tv^lo; Ri is -H or cyano; and R2 is halogen-substituted phenyl.

By "localised application" is meant that the pyrethroid is only applied to a minor portion of the skin or fleece of the sheep, generally as a linear spot on the^sheep's back. It has been surprisingly discovered that, notwithstanding the presence of a sometimes dense )poating of woolL* the pyrethroid appears to act over the entire surface of the sheep.

\ \ It is believed as a hypothesis that 1^he pyrethroid\is transmitted over the surface of the sheep b^y diffusion through the wool grease.

\ AS AMENDED _ _ _ _ 2 05 94 5 or wherein M is - CO - CH CH - CH = C^ \ / vx2 c / \ CH 3 CH 3 ^Xi - CO - CH CH - CH - C \ / I 1^*2 C X3 x„ / \ CH 3 CH 3 - CO - CH - R2 I CH / X ch3 ch3 and wherein Xi to Xi, are independently selected from halo, .Ci-C%"alkyl, halogen-substituted Ci~Ch alkyl, and halogen-substituted phenyl; X5 is -H or halo; Ri is -H or cyano; and **2 is halogen-substituted phenyl, with the proviso that when M is - CO - CH CH - CH = C / V Xi CH.

CH. and Xiand X2 :ire CI, and X5 is H, then Ri shall not be H. - 4 - (followed by page 4A) AS AMENDED By "localised application" is meant that the pyrethroid is only applied to a minor portion of the ^kin or fleece of the sheep, generally as a line or spot on the sheep's back,^ to give effect over substantially the entire surface of the sheep.

It has been surprisingly discovered that, notwithstanding the presence of a sometimes dense coating of wool, the pyrethroid appears to act over the entire surface of the sheep. It is believed as a hypothesis that the pyrethroid is transmitted over the surface of the sheep by diffusion through the wool grease. # — 4-A - 205946 * s % 10 • 20 The pyrethroid is generally applied as a liquid formulation, a paste or as a solid powder. Surprisingly, it has been found that it is not necessary that the pyrethroid be dissolved to be effective.

The localised application is preferably carried out as a pour-on treatment by pouring a liquid formulation comprising the pyrethroid along the back of thesheep (i.e.a so-called "backline" application).Surprisingly, it is not necessary to totally immerse the sheep in the formulation so that the treatment of large numbers of sheep is facilitated.

Alternatively, the application may be carried out by means of a localised spray or aerosol, usually along thesheep's back as it passes througha sheep race. The aerosol might comprise the pyrethroid dissolved in a liquid propellant, such as liquid carbon dioxide, or any other propellant known in the art.

Without wishing to be limited by any theoretical mode of action, it is believed that the pyrethroid acts superficially and is not dermally and systemicelly absorbed. It is therefore surprising that protection over the entire sheep is attainable from a localised application. jfgfH AM£Nd® 205946 m The pyrethroid is preferably selected from the group of light suable pyrethroids. Deltamethrin (also known as decanethrin)\is preferred and is a solid under normal conditions. Xiitable pyremroids are disclosed in Tables V , I to III. The formulae encompass all isomers and mixtures thereof.

TABLEXI No. Xi Xi X|\^X«, X» Rj\y trivial name 1 CI CI 2 CH i CH i 3 Br Br 4 CI Cl CI CF, 6 CI 7 CI Cl 6 CM t CH) ^parmthrin phenothrin deltamethrin eypernsthrin cyhalothrin flumethrin cyflutlirin cyphenothr^n 0SEPV>8§ AS AMENDED 205946 The pyrethroid is preferably selected from the group of light stable pyrethroids. Deltamethrin (also known as decanethrin) is preferred and is a solid under normal conditions. Suitable pyrethroids are disclosed in Tables I to III. The formulae encompass all isomers and mixtures thereof. Permethrin, whilst disclosed in examples, is not one of the pyrethroids included in the claims of this invention.

TABLE I » K ■ I o O - CH CH — \/ /\ CH, CH, CH - ■"•x, MO.

Xi X? X, X* Xi Ri trivial name 1 Cl Cl i - .

H B perms thrin 2 CH j CH i — — H H phenothrin 3 Br Br — ■ — H CN deltamethrin 4 Cl Cl — — H CN eypermethrin Cl CF, .

— — H CN cyhalothrin 6 Cl — — F CN flumethrin 7 Cl Cl — F CN cyfluthrin 6 CH, CH, — — H CN cyphenotKrin 2 05 94 6 TABLE II /XX m = - co - ch ch - ch - c \ / || x3 x* CH 3 CH 3 No.

Xi x2 x3 x- X5 Ri trivial name 9 Br Br Br Br H CN tralomethrin Cl Cl Br Br H CN tralocythrin TABLE III M « - CO - CH - R 2 I CH / \ CH3 CH 3 No. R2 X5 Ri trivial name 11 nOVci H CN f envalerate <3- -7 _ js _ 205946 It is a particular advantage of the present method that only small volumes of pyrethroid or pyrethroid-containing formula need to be applied.

Depending on the site of the sheep, thevolume applied will generally lie in the range 2 to IS ml per sheep. For convenience* the pyrethroid will generally be applied in a liquid formulation.

Depending on the efficacy of the particular pyrethroid employed, the formulation generally contains from 0.1 to 500, preferably 1 to 250 mg/ml of the pyrethroid.

Moreover, the pyrethroid is preferably applied to the sheep in an application of from 1 to 500, preferably 1.5 to 250 mg/kg body weight.

The formulation may be applied to full-woolled or sheared sheep. However, higher doses are required for full- woolled sheep.

The pyrethroid is preferably applied in theform of a pour-on formulation. The formulation may comprise one or more organic solvents, such as xylene, toluene, cyclohexanone, and a glycol.

One preferred solvent system comprises 30-70 wt t xylene, 20-40 wt I cyclohexanone and 5-25 wt I vegetable Suitable glycols include ethylene glycol and propylene glycol, polyethylene glycols and polypropylene glycols, oil.

V 205946 ethylene glycol-propylene glycol copolymers, and alkyl esters thereof, and glycol esters thereof of the general f oroiula and n - 1-40 10 Diethylene glycol mono-n-bytyl ether (i.e. fcx_j 2*(2-bytoxy-ethoxy)-ethanol) has been found to be particularly useful. It has been found to have minimal adverse effect on the skin in terms of a mild epidermal shedding seen with other solvents in some sheep. 15 Alternatively, the formulation may be an aqueous formulation containing the pyrethroid in the form of a suspension or emulsion and comprising suitable surfactants to stabilise the suspension or emulusion, and prevent undue run-off from the back of the sheep. Thus, it has 20 been surprisingly found that the pyrethroid is effective even when in the undissolved state.

Paraffin oils, vegetable oils, e.g. corn oil, peanut oil, castor oil, olive oil, can be added as viscosity modifiers and co-solvents.

Alkylamides and esters of fatty acids are useful RZ0 - (CH2-CHO)n-CO-R3 where R* ■ Cj alkyl or hydrogen, R2 ■ alkyl, hydrogen or -CO-R3 R"* i alkyl, 9 205946 formulation adjuncts e.g. n-butyl oleate, N,N-dimethyl ole-amide and isopropyl myristate (IPM).

It has been found that the inclusion of an antioxidant such as 2,6-ditert-butyl-4-cresol (BHT) or 2-tert-butyl-4-5 methoxyphenol (BHA) has a useful stabilising effect on the active ingredients in formulations based on glycols, glycol ethers, glycol ether esters and cyclohexanone.

The present invention will now be illustrated with reference to comparative tests showing the lack of activity of a large number of conventional insecticides, and with reference to specific examples illustrating the present invention.

(I) COMPARATIVE TESTS The effectiveness of a number of known insecticides in controlling sheep lice using pour-on formulations was assessed. A summary of the active agents and dose rates is given in Table 1.

IP - J» - 205946 TABLE 1 Chemical Pour-on (mg/kg) chlorfenvinphos 100 maldison 250 carbaryl 100 dimethoate 100 dioxathion 100 ethion 100 fenitrothion 100 trichlorphon 100 famphur 50,100 ronnel 100 crotoxyphos 100 bendiocarb 100 brombphos ethyl 100 dichlofenthion 100 crufomate 100 naled 100 w - w - 205946 All the pour-on treatments were formulated in a solvent system containing xylene, cyclohexanone and corn oil.

A total of 18 groups of lice-infested merino sheep divided into control (1) and treatment groups (17) were 5 selected and treated according to Table 1.

No pour-on treatment had any significant effect on existing lice burdens.

(II) TREATMENT ACCORDING TO THE PRESENT INVENTION A variety of pyrethroids were evaluated in the control of lice and keds on merino sheep, when applied by a liquid pour-on formulation.

Test 1 (xylene-cyclohexanone-corn oil solvent) Forty-eight merino sheep, half carrying full-wool and half carrying one month's wool, with significant louse infestations, were allocated equally into four groups of six animals.

Treatments, with formulations comprising a xylene (55 20 wt %) , cyclohexanone (30 wt %) , corn oil (15 wt %) solvent system were made as follows: Group 1 deltamethrin 10 mg/kg 10 mg/ml formulation Group 2 deltamethrin 50 mg/kg 50 mg/ml formulation Group 3 permethrin 100 mg/kg 100 mg/ml formulation Group 4 permethrin 250 mg/kg 250 mg/ml formulation.

IZ - - 205946 On full-woolled sheep, partings were made along the backline to place the formulation at skin level. After treatment the various groups, each with three full-woolled and three short-woolled sheep, were held in separate pens, remote from each other.

Post-treatment lice examinations were made at 1, 3 and 7 weeks, to assess the effects of the various treatments on the louse populations.

At seven weeks, groups 1 and 2 were run with a mob of fifteen infestor sheep, carrying considerable lice infestations, to gauge the persistence of deltamethrin. Further examinations were made at 9 weeks but subsequent examinations were prevented by wet weather.

Results The results of the pre-treatment and post-treatment lice examinations are shown in Table 2 and are outlined below. »> - vr- 20594 GROUP 1 deltamethrin (10 mg/kg) full wool short wool Infestations fell rapidly to extremely low levels and persisted at these low levels throughout the trial.

One light infestation was eradicated by Week 1. Moderate to heavy infestations were eradicated by Week 7.

GROUP 2 deltamethrin (50 mg/kg) full wool short wool At one week, two newly emerged lice were found in matted wool on one animal , only after an exhaustive search. No lice were seen on the other two ahimals. At Week 3 an exhaustive search of each animal revealed one or two newly emerged lice. No lice were found at Week 7 or at Week 9, after a fourteen-day challenge period.

No lice were seen at any examination after treatment.

GROUP 3 permethrin (100 mg/kg) full wool short wool Infestations were markedly reduced but were maintained at low levels throughout the trial.

Infestations were reduced to extremely low levels but lice were still present at Week 7.

GROUP 4 permethrin (250 mg/kg) full wool short wool Infestations were greatly reduced on two out of three sheep but persisted at low levels until Week 7. Lice were eradicated on the third animal by Week 7.

Light infestations were drastically reduced at Week 1 and eradicated at Week 3.

In the following tables, the numbers represent the total number of lice detected in twenty partings of the wool of the sheep, and L = light infestation 0 = no lice present M = moderate infestation H = high infestation + = lice present. - >3 - 2 ~ 3 9 4 6 TABLE 2 (First Three Sheep per Group Carrying Full-Wool, Second Three Carrying One Month's Wool) Group Sheep No. .

Pre-Treatment Week 1 Week 3 Week 7 Week 9 Comments B 34 H 13/20 24/20 16/20 2/20 GROUP 1 B 882 H L-M L-M 2/20* 8/20* *One heavy deltamethrin o 800 L 0 0 0 0 patch found (10 mg/kg) B 28 M-H 14/20 0 0 0 in neck fold y 749 M-H 3/20 1/20 0 0 B 883 M-H 0 /20 0 0 GROUP 2 deltamethrin (50 mg/kg) G 790 H 2/20** 1/20 0 0 . y B y 840 44 830 M-H M-H L-M 0 0 o 2/20 0 0 0 0 0 0 0 0 **Found in matted wool y 738 M 0 0 0 0 B 50 H L L L GROUP 3 permethrin (100 mg/kg) y Y B B 835 833 27 49 H a M-H M M L /20 17/20 M-H L 9/20 6/20 M-H 19/20 24/20 11/20 Y 744 L-M 7/20 3/20 4/20 B 887 H 12/20 7/20 3/20 GROUP 4 permethrin (250 mg/kg) B 38 L-M 7/20 0 0 B B B 42 29 H L L L-M 1/20 1/20 L-M 0 0 L 0 0 Y 991 L 1/20 0 0 47 L-M M-H M L L 877 H H H H H CONTROLS 742 H H H M-H M-H 754 L L-M L-M L L-M 37 M M L L L-M 736 L-M M L-M died /> - IA - 205946 Test 2 The results of the evaluation of deltamethrin on recently sheared merino sheep using xylene and DGBE-based solvent systems are given in Tables 3 and 4. The results of 5 the untreated control group are given in Table 5.

The xylene-based solvent system is the same as that given in Test 1.

The DGBE-based solvent system had a composition as follows: diethylene glycol mono-n-butyl ether (DGBE) 85 wt % isopropyl myristate (IPM) 15 wt % 2,6-ditert-butyl-4-cresol (BHT) 2.5 g/1. 205946 TABLE 3 Xylene-Based Solvent* * DalU-nethrin (9/1) Group Sheep No.

Body-■ weight Dose (ml) Poet-Treatment Inspections week week Challenge Inspections (Group 1 and Group 2) week week week 3 6 12 14 GROUP 1 (a) 51 50 6.3 0 0 0 0 1 8.0 1 mg/kg 90 46 .8 0 0 0 0 2 1 ml/8 kg 106 44 .5 0 0 0 0 0 GROUP 1 (b) 52 44 11.0 0 0 , 0 lartxd 4.0 1 mg/kg 55 48 12.0 0 0 0 0 1 ml/4 kg 139 43 .8 0 0 0 0 GROUP 2 (a) 54 50 6.3 0 0 0 0 2 16.0 2 mg/kg 112 44 .5 0 0 0 0 1 1 *1/8 kg 127 46 .8 0 0 0 0 1 GROUP 2 (b) 53 44 11.0 0 0 slaughtered (injury) 8.0 2 mg/kg 88 48 12.0 0 0 0 13 1 ml/4 kg 146 43 .8 0 0 0 0 2 GROUP 3 (a) 76 . 50 6.3 0 0 .0 2.5 mg/kg 126 44 .5 0 0 1 ml/8 kg 134 46 .8 0 0 GROUP 3 (b) 67 44 11.0 0 0 .0 2.5 mg/kg 75 42 .5 0 0 1 ml/4 kg 102 48 12 .0 0 0 GROW 4 (a) 113 50 6.3 0 0 24.0 3 mgAg 131 44 . 5.5 o 0 1 ml/8 kg 137 46 .8 0 0 CROUP 4 (b) 69 44 11.0 0 0 12.0 3 mg/kg 84 42 .5 o 0 1 ml/4 kg 143 48 12.0 0 0 GROUP S (a) 61 49 6.1 0 0 32.0 4 mg/kg 141 / 44 .5 0 0 1 ml/8 kg 147 46 .8 0 0 GROUP 5 (b) 71 44 U.O 0 0 16.0 4 mgAg 110 42 .5 0 0 1 ml/4 kg 118 47 11.8 0 0 GROUP 6 (a) 58 4S .6 0 0 40.0 mgAg 68 49 6.1 0 0 1 ml/8 kg 83 43 .4 0 0 GROUP 6 (b) 80 44 11.0 0 0 .00 mgAg 124 47 11.8 0 0 1 ml/4 kg 125 42 .5 0 0 •Figures shown in "week* columns are the number of lioe seen in twenty wool partings. '7 -J*- 205946 w DGBE- TABLE Based 4 Solvent * Deltamethrin Group Sheep No.

Body-weight Dose (ml) Post-Treat»ent Inspections Otallenge Inspections (Group 1 and Group 2) (g/1) (kg) week 3 week 6 week week 12 week 14 e.o GROUP 1 (c) 1 mgAg 1 ml/8 kg 60 73 85 45 49 43 .6 6.1 5.4 0 0 0 0 0 0 v 0 1 0 3 0 1 1 0 1 4.0 GROUP 1 (d) 1 mgAg 1 ml/4 kg 78 81 129 41 44 47 .3 11.0 11.8 <1/20 0 0 0 0 0 0 4 1 0 0 0 1 1 0 16.0 GROUP 2 (c) 2 mgAg 1 ml/8 kg 62 74 96 its 49 43 .6 6.1 5.4 0 0 0 0 0 0 0 3 0 1 slaughtered 2 1 (injury) e.o GROUP 2 (d) 2 sgAg 1 ml/4 kg 18 89 132 41 44 47 .3 11.0 11.8 0 0 0 0 0 0 0 1 0 1 0 1 0 1 2 .0 GROUP 3 (c) 2.5 mgAg 1 ml/8 kg 86 107 114 49 45 43 6.1 5.6 .4 <1/20 0 0 0 0 0 .0 GROUP 3 (d) 2.5 mgAg 1 ml/4 kg 91 94 144 41 44 47 .3 11.0 11.8 0 0 0 0 0 0 24.0 GROUP 4 (c) 3 mgAg 1 ml/8 kg 108 117 120 45 43 49 .6 5.4 6.1 0 0 0 0 0 0 12.0 GROUP 4 (d) 3 mgAg 1 ml/4 kg 56 57 97 40 46 44 .0 11.5 11.0 0 0 0 0 0 0 * 32.0 GROUP 5 (c) 4 mgAg 1 ml/8 kg 119 128 135 43 49 45 .4 6.1 5.6 0 0 0 0 0 0 16.0 GROUP 5 (d) 4 mgAg 1 ml/4 kg 66 70 98 40 46 44 .0 11.5 11.0 0 0 0 0 0 0 40.0 GROUP 6 (c) mgAg 1 ml/8 kg 133 136 145 43 49 45 .4 6.1 5.6 0 0 0 0 0 0 .0 GROUP 6 (d) 5 mgAg 1 ml/4 kg 72 87 101 40 46 44 .0 11.5 11.0 0 0 0 0 0 0 •Figures shown in "week" columns are the nunbar of lice seen in twenty wool partings. - vr - 2 0 5946 TABLE 5 Results of Examinations of Shorn Untreated Control Group* U n t Sheep No. r e a t e d Body-weight (kg) C o n t r o / Week . 3 1 s Week 6 65 51 77 56 9 8 79 52 17 82 38 24 31 95 54 18 29 104 28 37 105 52 8 111 29 24 23 116 44 16 122 39 22 18 123 36 19 18 130 18 17 ♦Figures show the number of lice seen in twenty wool partings.

Test 3 (varying solvent systems) Table 6 gives the results for formulations of deltamethrin in a variety of other solvent systems when applied to recently sheared werino sheep. - *8 - TABLE 6 Various Solvent Systems Sheep No.

Body wt (kg) Dose (ml) Pre-Treat-ment Week 4 Week 6 Week 8 Formulations 4 140 174 175 27 27 26 6 6 6 91 66 30 0 0 1 0 0 0 0 0 0 g/1 deltamethrin in xylene system of Test 1 172 178 180 17 33 34 9 8 8 47 90 47 1 0 0 0 0 0 0 0 0 g/1 deltamethrin 2.5 g/1 BHT to 1 litre with cyclohexanone containing 50 ppm SUDAN RED IV 131 132 138 29 28 6 6 6 51 34 87 0 0 0 0 0 0 0 0 0 g/1 deltamethrin 2.5 g/1 BHT 50 ppm SUDAN RED IV DGBE/cyclohexanone (65:35 w/w) to 1 litre 142 149 181 32 24 31 8 6 8 73 47 27 0 0 0 0 0 0 0 0 0 ' 10 g/1 deltamethrin 100 g/1 mineral oil 2.5 g/1 BHT 50 ppm SUDAN RED IV cyclohexanone to 1 litre 164 165 177 36 33 30 8 4 117 47 27 0 0 0 0 0 0 0 0 0 g/1 deltamethrin 100 g/1 mineral oil 2.5 g/1 BHT 50 ppm SUDAN RED IV diethylene glycol mono-n-butyl ether (DGBE) to 1 litre 143 155 162 31 21 25 8 6 6 90 44 75 1 1 1 0 0 0 0 0 0 g/1 deltamethrin 2.5 g/1 BHT 50 ppm SUDAN RED IV dipropylene glycol monomethyl ether (DPM) to 1 litre 137 163 169 29 28 21 6 6 6 60 72 39 0 . 0 0 0 0 0 0 0 0 g/1 deltamethrin 2.5 g/1 BHT 100 g/1 acetylated lanoline alcohols cyclohexanone to 1 litre 156 176 23 31 6 8 57 180 1 2 0 0 0 0 as for Example No. 10 129 130 154 160 171 29 23 25 36 14 IB 17 17 14 28 171 8 29 8 14 47 8 24 17 22 72 24 20 ■v V Controls N) O Cn sD O 2 05946 Test 4 (varying pyrethroids) The efficacy of a variety of different pyrethroids applied as liquid pour-on formulations to merino sheep was determined. The results are given in Table 7. A backline J application was made within 24 hours of shearing. All formulations used the xylene-based solvent system given in Test 1# except flumethrin which was formulated as a miscible oil formulation but which was diluted with the xylene-based solvent to achieve the lower concentrations. 10 The results show all the pyrethroids tested to be effec tive/although at the dosages used phenothrin and flumethrin did not give complete eradication.

Test 5 (effect of deltamethrin against keds) 15 The efficacy of deltamethrin against infestations of merino sheep with keds (Melophagus ovinus) was determined by applying 8 ml of deltamethrin in the xylene-based solvent system given in Test 1 a£ a backline treatment to twenty newly shorn sheep. Twenty further sheep were treated in the 20 same way with deltamethrin in the DGBE-based solvent system given in Test 2. The concentration of deltamethrin was 10 g/1.

All forty sheep were re-examined 10 weeks after treatment and no live keds were found. - >0 - 205946 TABLE 7 Control of the Sheep-Biting Louse by a Number of Pyrethroids Compound / Dose / Formulation Sheep No.

(No Result . of Lice) CYPERMETHRIN mg/kg (1 ml / 5 kg - 25 g/1 formulation) 782 . 767 732 0 7 26 50 mg/kg (1 ml/5 kg - 250 g/1 formulation) 756 746 733 0 0 0 (14/10 - D) PHENOTHRIN mg/kg (1 ml / 5 kg - 125 g/1 formulation) 721 765 727 8 23 3 400 mg/kg 724 779 753 8 (4 ml/5 kg - 500 g/1 formulstion) 18 FENVALERATE ) . . 10 mg/kg (1 ml / 5 kg-50 g/1 formulation) 744 740 769 9 3 2 (14/10 - D) 100 mg/kg 766 770 730 0 0 (2 ml/5 kg - 250 g/1 formulation) 0 FLUMETHRIN 0.5 mg/kg (1 ml/5 kg-2.5 g/1 formulation) 783 725 719 21 10 1 12-16 mgAg 722 755 748 0 s (25 ml / 30-40 kg - 20 g/1 formulation) 7 741 64 CONTROLS 737 764 52 83 no treatment 754 758 723 53 121 - 55 D = died between 14/10 and 21/10 " >4 - 2 05946 Test 6 (time to take effect) The time for the pyrethroid to fully clear the merino sheep following backline application of the liquid formulation was investigated and the results are shown in Table 8. These demonstrate that tJie pyrethroid takes a finite period to completely clear the sheep of lice. However, the sheep are substantially cleared within 15 days. The effect is also demonstrated in certain of the preceding Tables. - vr - * • 205946 TABLE 8 Process of Reduction in Lice Numbers Following Pyrethroid Backline Treatment Group Sheep No.

Lice Score Day 15 42 Cypermethrin 50 mg/kg 756 746 733 >20 >20 >20 7 7 9 3 2 3 0 5 0 21 21 0 0 0 0 Fenvalerate 100 mg/kg 766 770 730 >20 >20 >20 2 6 2 2 1 2 3 0 2 0 0 11 0 0 0 Flumethrin 12-16 mg/kg 722 755 748 >20 >20 >20 19 12 8 10 4 41 181 71 ,2A 0 31,2A 41, 3A Controls 741 737 764 754 758 723 >20 >20 >20 >20 >20 >20 14 16 10 22 20 64(18) 52(18) 83(19) 53(15) 121(19) 55(13) I = immature lice A «= adult lice - ?*. ' 2"5946 (iii) formulations for use according to the present invention Suitable formulations are presented in the following Examples. In general, a suitable solvent system contains 0 to 100% by weight xylene, 0 to 100% by weight cyclohexanone, and up to 20% by weight corn oil.

Example 1 .1 g _qf technical deltamethrin (989 g active per kg) , was dissolved in a solvent consisting of: cyclohexanone Sudan Red IV (oil soluble dye) 50 ppm and the volume adjusted to one litre to give a solution containing 10 g/1 deltamethrin.

Example 2 51 g of technical deltamethrin (989 g active constituent per kg) was dissolved in a solvent blend containing: xylene 55% by weight cyclohexanone 30% by weight corn oil 15% by weight Sudan Red IV 1000 ppm and the volume adjusted to one litre with the same solvent blend to give a solution containing 50 g/1 deltamethrin.

Example 3 - .1 g of technical deltamethrin (989 g active per kg) was Z? - - 205946 dissolved in a solvent blend, containing: Sudan Red IV xylene corn oil cyclohexanone 55% by weight 30% by weight 15% by weight 50 ppm and the volume adjusted to one litre with the same solvent blend, to give a solution containing 10 g/1 deltamethrin.

Example 4 51 g of technical deltamethrin (9 89 g active per kg) was dissolved in the same solvent blend given in Example 3 and the volume adjusted to give a solution containing 50 g/1 deltamethrin.

Example 5 .1 g of technical deltamethrin (989 g active per kg) was dissolved in a solvent consisting of: diethylene glycol monobutyl ether BHT antioxidant 2500 ppm Sudan Red IV 50 ppm and the volume adjusted to one litre with the same solvent to give a solution containing 10 g/1 deltamethrin.

Example 6 10.1 g of technical deltamethrin (989 g active per kg) was dissolved in a solvent blend containing: - y$ - 205946 cyclohexanone 50% by weight diethylene glycol monobutyl ether 50% by weight BHT antioxidant 2500 ppm Solvent Blue No. 36 , 50 ppm / • and the volume adjusted with the same solvent blend to give a solution containing 10 g/1 deltamethrin.

Example 7 .1 g, .of technical deltamethrin (989 g active per kg) was dissolved in a variety of solvent blends containing: diethylene glycol monobutyl ether or ethylene glycol monobutyl ether acetate 85-90% by weight isopropyl myristate 10-15% by weight BHT antioxidant 2500 ppm Sudan Red IV 50 ppm and the volume adjusted with the respective solvent blend to give a solution containing 10 g/1 deltamethrin.

Example 8 Amounts of 2.6, 10.5, 42.5 and 84.2 g of technical cyper-methrin (950 g active per kg) were dissolved in a solvent blend containing: xylene 55% by weight cyclohexanone 30% by weight corn oil 15% by weight and the volume adjusted to one litre with the same solvent blend to give solutions containing 2.5 g, 10 g, 40 g and 80 -2-7

Claims (42)

t + • ZQ594 3 g per litre respectively of cypermethrin. Example 9 103 g of technical permethrin (970 g active per kg) in which / 5 the cisitrans isomer (arising from the two asymmetric carbon atoms in the cyclopropane ring) ratio was 25:75 was dissolved in a solvent blend containing: xylene 55% by weight cyclohexanone 30% by weight 10 corn oil 15% by weight and the volume adjusted to one litre with the same solvent blend to give a solution containing 100 g/1 permethrin. Example 10 15 An aqueous suspension of deltamethrin was prepared by suspending 10.1 g of technical deltamethrin of average particle size 2 to 5 microns in an aqueous formulation containing: non-ionic wetting agent 1.5 g fl mole nonylphenol condensed \ 20 \with 15 moles of ethylene oxide/ fumed silicon dioxide 5.0 g xantham gum 4.0 g propylene glycol 60.0 g formaldehyde 1.0 g 25 silicone oil (antifoaming agent) 1.0 g water to one litre. Various other deltamethrin suspensions in the range 1 to 500 g/1 deltamethrin were also prepared. *2.9 -^7 - fifiw amended 205946 of c*\i . >s :~ the claimsxdefining swfr invention -are *9- follows : 1. A mtethod of controlling sheep ectoparasites selected from\keds, mites and blowflies which comprises the application onto a localised vregion of the skin or fleece of a sheep of a pyrethroid of they formula wherein or ch3'i ch3 and wherein Xx to are independently selected fr\om halo, Ci~Calkyl, halogen-substituted Ci~£i» alkyl, : i1 | ' \ and halogen-substituted\ phenyl; X5 is -H or halo; : 1 Ri is -H or cyano; and Ra is halogen-substituted phei^l. ^7 W- '5,f 205 946 ^ cAol*w ,"/; _ ¥Hfi CLAIMS DEFINING ¥»£- INVENTION -ARE AS~FOLLOWS:

1. A method of controlling sheep ectoparasites selected from keds, mites and blowflies which comprises the localised application (as hereinbefore defined) onto skin or fleece of a sheep of a pyrethroid of the formula wherein M is - CO - CH CH - CH = C \ / /c\ / V Xi CH. CH. / Xi - CO - CH CH - CH -• C ^ . \ / I I x2 c / \ CH3 CH- - CO - CH - Ra X3 X- CH. CH / \ CH. or and wherein X± to X^ are independently selected from halo, Ci-Ctj alkyl, halogen-substituted Ci-Ci* alkyl, and halogen-substituted phenyl; Xs is -H or halo; Ri is -H or cyano; and Ra is halogen-substituted phenyl ; with the proviso 2-7 - - (followed by page 29A) AS AMENDED that when M is m - co - ch ch - ch = c \ / ch, ch, / \ xi and Xiand X2;ire Cl, and Xsis H, then Ri shall not be H. - 3°!A ~ 4 fiOW amended" 205946

2. A method according to claim 1 wherein the pyrethroid :1s a light-stable pyrethroid.

3. A. method according to either preceding claim wherein M is - CO. - CH — CH - CH = Xi and X2 are independently selected from chloro and bromo; X5 is -H or halo; and Ri is -H or cykno.

4. A method according to claim 1^wherein the pyrethroid is selected from p&fmethrin, phenothrin, cyfluthrin, cyphenothrin, tralomethrin,\tralocythrin and fenvalerate (all as herein defined).

5. A method according to islaim 1 wherein\the pyrethroid is deltamethrin (as hereinVdefined). 6. A method according to claini 1 wherein the\pyre-throid is cypermethrin (as herein defined) 7. A method according to claim 1 wherein the pyrethroid is cyhalothrin (as herein defined)\ 8. A method according to claim 1 wherein the pyrethroid is flumethrin (as herein defined). 9. A method according to any preceding claim wherein the pyrethroid is applied to a sheared sheep. '• OO - - AS AMENDED 2 0 5 94 6 m 2. A method according to claim 1 wherein the pyrethroid is a light-stable pyrethroid. 3. A method according to either preceding claim wherein ' /Xl m is - co - ch — ch - ch = c T \ / X2 c / \ ch3 ch3 Xi and X2 are independently selected from chloro and bromo; X5 is -H or halo; and Ri is -H or cyano. 4. A method according to claim 1 wherein the pyrethroid is selected from phenothrin, cyfluthrin, cyphenothrin, tralomethrin, tralocythrin and fenvalerate (all as herein defined). 5- A method according to claim 1 wherein the pyre- . throid is deltamethrin (as herein defined).

6. A method according to claim 1 wherein the pyrethroid is cypermethrin (as herein defined).

* 7. A method according to claim 1 wherein the pyre throid .is cyhalothrin (as herein defined).

8. A method according to claim 1 wherein the pyrethroid is flumethrin (as herein defined).

- 9. A method according to any preceding claim wher the pyrethroid is applied to a sheared sheep. - ?9 - 205946

10. A method according to any one of the claims 1 to 9 wherein the pyrethroid is applied to a sheep within 24 hours of shearing.

11. A method according to any one of claims 1 to 9 wherein the pyrethroid is applied to a sheep having substantially one month's growth of wool.

12. A method according to any one of the preceding claims 1 to 8, wherein the pyrethroid is applied to a substantially full-wooled sheep.

13. A method according to any preceding claim wherein the sheep is a merino sheep.

14. A method according to any preceding claim wherein the pyrethroid is applied at a rate of from 1 to 500 mg per kilogram sheep body weight.

15. A method according to any preceding claim wherein a formulation comprising the pyrethroid in admixture with a carrier is applied.

16. A method according to claim 15 wherein the carrier is a liquid.

17. A method according to claim 16 wherein the formulation comprises a liquid carrier and 1 to 250 mg/ml of the pyrethroid.

18. A method according to claim 16 or 17 wherein 2 to - 31 - 20 5 946 15 ml of the liquid formulation is applied.

19. A method according to any one of claims 16 to 18 wherein the liquid carrier comprises one or more organic liquids. / . / • •

20. A method according to claim 19 wherein the liquid carrier comprises at least one organic liquid selected from xylene, cyclohexanone and vegetable oil.

21. A method according to claim 20 wherein the liquid carrier comprises 30-70 wt % xylene, 20-40 wt % cyclohexanone and 5-25 wt % vegetable oil.

22. A method according to any one of claims 16 to 19 wherein the liquid carrier comprises a glycol.

23. A method according to any one of claims 16 to 19 wherein the liquid carrier comprises an alkyl ether of a glycol.

24. A method according to claim 22 or 23 wherein the glycol is selected from ethylene glycol, propylene glycol, polyethylene glycols, polypropylene glycols, and ethylene glycol-propylene glycol copolymers.

25. A method according to claim 23 or 24 wherein the liquid carrier comprises diethylene glycol mono-n-butyl ether (also known as 2-(2-butoxyethoxy)-ethanol).

26. A method according to any one of claims 16 to 19 - 5T - 205946 wherein the liquid carrier comprises a glycol o-lkyA other ester.

27. A method according to claim 26 wherein the glycol / alkyj^-ethcg ester has the general formula 7 / R1 I R20 - (CHa-CH0)n - CO - R3 wherein R1 = Ci alkyl or hydrogen, R2 = Cx-Cs alkyl, hydrogen or -CO-R3, R3 = C!-Ci2 alkyl, and n = 1-40.

28. A method according to any one of claims 16 to 27 wherein the liquid carrier comprises an ester of a fatty acid.

29. A method according to any one of claims 16 to 28 wherein the liquid carrier comprises an alkylamide of a fatty acid.

30. A method according to any one of claims 16 to 29 wherein the liquid carrier comprises a paraffin oil.

31. A method according to any one of claims 16 to 27 wherein the liquid carrier comprises isopropyl myristate.

32. A method according to any one of claims 1 to 18 wherein a liquid formulation is applied which comprises a suspension or emulsion of the pyrethroid in an aqueous liquid. -57 - - 205946

33. A method according to any preceding claim wherein a liquid formulation which comprises the pyrethroid is locally applied as an aerosol.

34. A method according to claim 33 wherein the liquid aerosol formulation comprises the pyrethroid in a liquid carbon dioxide propellant.

35. A method according to any one of claims 1 to 32 wherein a liquid formulation which comprises the pyrethroid is locally applied as a spray.

36. A method according to any one of claims 33 to 35 wherein the liquid formulation is applied to the sheep's back as it passes through a sheep race.

37. A method according to any preceding claim wherein the pyrethroid is applied together with a dyestuff.

38. A method according to any preceding claim wherein after application the pyrethroid is transmitted over the surface of the sheep by diffusion through the wool grease.

39. A method according to any preceding claim wherein the sheep is infested with keds.

40. A method according to any one of claims 1 to 38 wherein the sheep is infested with mites.

41. A method according to any one of claims 1 to 38 wherein the sheep is infested with blowfly. !>t -^3 - .» - \

42. A method of controlling sheep ectoparasites selected from keds, mites and blowflies as claimed in claim 1, which comprises the application of a formulation substantially as disclosed in any Example herein. oft. raw 7 A. J. "Arac a SON per AGENTS FOR THE APPLICANTS