AU4736599A - Method of treatment of animals - Google Patents

Description

P/00/011 Regulation 3.2 -4

AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT 0* 00 *0 Invention Title

VOVO

09 METHOD OF TREATMENT OF ANIMALS NUFARM LIMITED Applicant: The following statement is a full description of this invention, including the best method of performing it known to me: 1 Document3 2 METHOD OF TREATMENT OF ANIMALS

FIELD

This invention relates to the application of pesticides to animals particularly sheep, cattle, goats, other cloven hoofed animals and domestic pets by dipping or theorise saturating the outer surface of the animal with a pesticidal composition.

BACKGROUND

Dipping of sheep and cattle is an inexpensive method of controlling a wide range of ectoparasites. The process of dipping animals consists of wetting of their external regions with pesticidal composition. Wetting is achieved either -by complete immersion of the animal in pesticidal liquor (a process referred to as •oo• plunge dipping), or by exposing the animal to a shower or spray of appropriately i diluted pesticide (a process referred to as shower dipping).

15 As animals pass through a dipping station, dipwash is retained in/on the surface regions of the animal and is removed from the sump. The removed dipwash must be replenished, and a particularly convenient method of replenishment of dipwash is the method of constant replenishment, which has been described in our previous application (Australian Patent Application No 19946/97 and US Patent Application Serial No. 09/052,394 filed 31 March 1998.

A dipping station operated under constant replenishment conditions is characterized by the use of an initial charge of pesticide in the sump (said charge having a concentration of pesticide denoted CIC), and is further characterized by the use of a constant replenishment charge of pesticide to the dipwash (said charge having a concentration of pesticide denoted CCR).

In traditional constant replenishment dipping practice, CIC is set at or close to the same value as CCR.

Pesticide in a dipwash commonly has a higher affinity for the surface of the animal than for dipwash. The resultant transfer of pesticide from dipwash to the animal surface is referred to as stripping, and is generally considered to be based on lipophilic interaction.

Although the volume of dipwash is maintained by the process of continuous replenishment charging, the effect of stripping in a dipping operation wherein CIC CCR is that the concentration of pesticide in the dipwash progressively decreases until a steady state concentration CSS is reached. At steady-state the relationship CIC SF x CSS (1) applies, where SF is the stripping factor. SF can be calculated in a variety of ways as described in our previous application. In general, SF depends on the nature of the active ingredient; the nature of the formulation comprising the active ingredient, and in particular the nature of the solvent in the said formulation, if the active ingredient is maintained in the dipwash as an emulsion; the dipping method (plunge or shower dip); and the sump volume of the dipping station, or some other factor(s) highly o 15 correlated with sump volume. These related factors presumably could include features of dip operation that influence degree of exposure of the dipping liquid (active ingredient) to the stripping effect of the animal surfaces (eg. length of the bath, swim distance and/or time in plunge dips and showering time pressure, nozzle type and sump turnover in shower 20 dips).

As an example of the dependence of stripping factor on dipping conditions, it may be noted that the diazinon formulation sold under the trade name Diprite (Nufarm Ltd) usually has a stripping factor in range of 3-6 for small 4000 Litre) sump plunge dips and for small 500 Litre) sump shower dips. The same formulation usually has a stripping factor of 6-12 in large 4000 Litre) sump plunge dips and large (>500 Litre) sump shower dips.

From equation 1, the implication of a large stripping factor (eg. SF 12) is that the concentration of active ingredient in the dip at early times (CIC) can be 12 times greater than the concentration of active ingredient in this dip at later times.

This condition will lead to either of the following undesirable consequences: the sheep dipped first will be overdosed or S(b) the sheep dipped last (during the steady state regime) may be underdosed.

Some active ingredients, (eg. Ivermectin and other macrocylic lactones) have much higher stripping factors and these actives cannot be usefully applied at all using conventional dipping methodology.

Constant replenishment dips are normally run using a concentration of initial charge (Cic) which equals the concentration of the replenishment charge (CcR) and heterogeneity of the dose applied due to stripping will generally be a problem.

Our previous application provides a method for operating constant replenishment dips under near steady state conditions for the entirety of the dipping operation.

15 This is achieved by establishing a concentration of pesticide which provides a safe and effective pesticide treatment. This concentration (Cic) is initially o charged to the sump, and maintaining the volume of dipwash by addition thereafter of a composition containing a second concentration of pesticide, CCR where CCR is greater then Cic and is obtained from the relationship SF x CIC 1 (3)

CCR

19946/97 provides detailed instructions for evaluating the stripping factor SF required in For a high-stripping diazinon situation with SF 12, the replenishment concentration CCR established from equation is twelve times greater than the initial concentration CIC.

Since the process of our previous application provides for a more constant concentration of pesticide in the dipwash throughout the entire dipping operation, the consistency of dosing is vastly improved compared with conventional dipping processes.

However despite the achievement of a more constant concentration of pesticide in the dipwash, we have found that the delivery of an optimal dose of pesticide to each animal in a heterogeneous group remains problematic. For instance, for large dips (diazinon, merino sheep) the stripping factor SF can lie anywhere in the range 6-12, and we have found by experiment that small, short-wool merino sheep need, at the very least, 210mg diazinon per head for effective lice control. For these small, short-wool sheep the volume of dipwash removed VR can lie anywhere in the range 0.8 -1.2 litres per sheep. Using the procedure of our previous application it may be established that given the above range of SF and V R the minimum initial concentration (CIC) of diazinon required to provide an acceptable i 15 dose in all circumstances (take for the extreme case SF 6, VR 0.8) is 44 mg per litre in dipwash. However under these conditions (CIC 44 mg per litre), large long-wool sheep (VR in range 4.6 6.5) could received a dose of up to 2432 mg diazinon per head (take for the extreme case SF 12, VR This represents substantial overdosing.

By decreasing the pesticide concentration in the dipwash, acceptable doses can be delivered to the large long-wool sheep. If this is done however, the dose of pesticide applied to small short wool sheep is too low to provide effective louse control.

No prior art dipping procedures apparently address the different dose requirements of animals having different physical characteristics.

SUMMARY OF THE INVENTION We have found that by segregating the animals of a diverse herd into dose specific categories based on the volume of dipwash removed by an animal VR and by using different values for the concentration of the initial charge CIC and the replenishment charge CCR for each dose-specific category it is possible to reliably achieve target pesticide dose ranges for all animals.

Accordingly we provide a method of dipping a herd of animals of the same species in a dip containing pesticide dipwash to reduce the incidence of overdosing and underdosing, the method including: providing a plurality of treatment categories for animals, the categories each defining a range in the volume of dipwash removed by an animal; assigning animals to the treatment categories based on the anticipated volume of dipwash removed by each animal within the herd; providing an initial pesticide concentration of dipwash for each category for providing effective pesticidal control in the dip for animals of said catgegory; providing a second pesticide concentration for each category for replenishing dipwash removed from the dip to maintain an effective concentration of pesticide in the dip.

This method may involve dipping sheep of at least one said category and preferably at least two categories in the respective first concentration for said 15 category or categories; and replenishing the dipping liquid removed with the respective second concentration for said category.

There should be provided at least 2 dose-specific categories based on VR preferably at least 3 categories. The ranges will generally be mutually distinct ranges.

In relation to the dosing of pesticide on merino sheep, an appropriate set of dose-specific categories denoted A-E can be established according to the following *oe*.

table.

Table 1: Categorisation of merino sheep on the basis of volume of dipwash removed per head (VR) Dose- Volume of dipwash specific removed VR (Litre/head) Category A 0.8-1.3 B 1.3-2.1 C 2.1-3.1 D 3.1 4.6 E 4.6 The volume of dipwash removed by a merino sheep is generally taken to be the volume of dipwash remaining on the animal after 5 minutes draining. This quantity may be established by weighing the animals after the set drainage time or by collection and measurement of the volume of drainage water from sheep after dipping as outlined in Example 6 of this application.

For other animals non-merino sheep), categories can be chosen in an analogous way by measuring volume removed VR and dividing the range of VR values into intervals, each such interval corresponding to a given category.

We have found that in sheep, there is a good correlation between the volume removed VR and the product of bodyweight (kg) and time off-shears (weeks) for sheep dipped within the normal interval of 2 to 6 weeks after shearing.

Accordingly in a particularly preferred embodiment the invention provides a method of dipping a herd of animals of the same species in a dip containing a 15 pesticide dipwash to reduce the incidence of overdosing and underdosing the method including: providing a plurality of treatment categories for the animals, each category defining a distinct range in the product of bodyweight and time since shearing; grouping animals which fall into the same category of the product of 20 bodyweight and time since shearing; providing an initial pesticide concentration for each category for providing effective pesticidal control of sheep in said category; and providing a second pesticide concentration for each category for replenishing dipwash, the second concentration being sufficient to compensate for the effect of stripping of pesticide from the initial concentration during dipping of animals of said category.

In a preferred embodiment the invention will include separately dipping each category of animals using a dip containing pesticide of the corresponding initial concentration for the category and during the dipping process replenishing dipwash removed by animals with the second pesticide concentration for the category.

In the drawings Figure 1 shows the relationship between the product of the body weight and time-off shears and the volume of body weight and time-off shears and the volume of dipwash removed per animal as determined in field trials.

8 Figure 2 shows the relationship between diazinon concentration and the volume of dipwash removed during a conventional dipping procedure of Example 1.

The correlation between VR and the product of bodyweight (Kg) and time offshears (weeks) for merino sheep is summarized in Table 2 and in quantitative terms in Figure 1 of the drawings.

Table 2: Relationship of VR to the product of bodyweight and time since shearing (generally referred to in the art as time off-shears*).

a a a.

a o Dose- Range in volume Bodyweight (kg) x specification of dipwash time off-shears category removed (weeks) range (VR, Uhead) (kg week) A 0.8 1.3 40 B 1.3 2.1 >80 120 C 2.1 3.1 >120 170 D 3.1 4.6 >170 260 E 4.6 6.5 260 Mean of values derived from field trials with plunge and shower dips.

The near linear relationship shown in Table 2 and Figure 1 permit the allocation of groups of sheep into dose specific categories based on their body weight and time off-shears. In order to facilitate the allocation, use can be made of a formate shown in Table 3, which presents essentially the same information in a more user-friendly form.

Table 3: Allocation of Categories 9 For non-sheep animals, an analogous procedure can be devised whereby the various VR categories can be correlated (using standard methodology) against some set of available physical parameters, for example parameters chosen from the set consisting of breed, coat density, fibre diameter, fibre length, bodyweight, age, time off-shears etc.

Once an animal has been allocated into a dose specific category into an interval of the parameter VR), it is possible by experiment to establish an acceptable dose range. This acceptable dose range is expressed in mg/head for each category.

For the case of merino sheep treated with a diazinon formulation ("DIPRITE" Nufarm Ltd Diazinon 500g/L), the experimentally determined acceptable dose range is provided in Table 4.

15 Table 4: Target dose range acceptable dose range)* a Category Dose Range mglhead A 210 780 B 260 975 C 302 1134 D 347 1302 E 442 1652 Merino sheep, Diprite formulation For cases other than the merino sheep and DIPRITE (diazinon formulation) scenario, an analogous table can be established by experiment.

Given the target dose range (eg. Table 4) and the volume removed range (eg. Table 1) for each category, it is possible, for a given range of stripping factors (corresponding to a range of sump volumes of dips and dipping methods), to find values of the initial charge concentration CIC and the constant replenishment charge concentration CCR in each category which ensures that animals in each category are all adequately dosed as defined in Table 4 (or its equivalent) under near steady state conditions for the entire dipping operation. The relevant equations (which are justified in 19946/97) are d CIC x SF x VR (4) CCR CIC x SF a a a O• f where d represents dose.

Table 5a shows values of CIC and CCR for the categories A to E for merino sheep treated with Diprite formulation in large dips (SF in range 6-12). Table shows corresponding information for small dips (SF in range It is apparent from Tables 5a and 5b that the method of the current invention enables acceptable dose targets to be closely achieved for each category. Most importantly, the invention enables avoidance of under-dosing or undue overdosing.

Table 5a Large Dips (SF 6-12) Use of Current Invention of Delivery of Appropriate Doses of Diazinon to Merino Sheep Category VR CIC CCR Achieved Achieved Target Acceptable range Dose Dose Dose Dose range L/head mg/L mg/L (min)* -mg/head mg/head mg/head mg/head A >0.8 50 325 240 720 260 210-780 1.2 B >1.2 37.5 250 270 900 325 260- 975 2 C >2 3 30 180 360 1080 378 302 1134 D >3 22.5 140 405 1215 434 347-1302 E >4.5 17.5 120 473 1365 552 442- 1656 mass balance based on lowest SF in the range, VR at minium of range mass balance based on highest SF in the range, VR at maximum of range 11 Table 5b Small Dips (SF 3 6) Use of Current Invention of Delivery of Appropriate Doses of Diazinon to Merino Sheep Category VR Cic CCR Achieved Achieved Target Acceptable range Dose Dose Dose Dose L/head mg/L mg/L (min)* mg/head range mg/head mg/head mg/head A 0.8-1.2 108 325 258 778 260 210-780 B 1.2-2 82.5 250 297 990 325 260- 975 C 2-3 60 180 360 1080 378 302-1134 D 3 4.5 47.5 140 428 1283 434 347 1302 E 4.5-6.5 40 120 540 1560 552 442-1656 For cases other than the merino/diazinon (DIPRITE) scenario, an process can be used based on equivalent experimentally derived target dose ranges provision of dose-specific categories based on volume of dipwash removed correlation of dose-specific categories with available physical parameters of animals to be dipped experimental determination of the relevant stripping factor range.

From a user point of view, much of the information provided in Tables and b is unnecessary the key user issues are: establishing the categories for the animals to be dipped (see Table 3) and describing the key operational parameters (CIC and CCR, see Table 6) 12 Table 6: Key operational parameters for dipping merino sheep Dose Specification Large dips Small dips Category mg/L* mg/L* CIC CCR CIC CCR A 50 325 108 325 B 37.5 250 82.5 250 C 30 180 60 180 D 22.5 140 47.5 140 E 17.5 120 40 120 0 0 00 9 Table 6 shows the key operational parameters from Tables 5a and b (Merino sheep/Diprite scenario). Generally, pesticide dose rates that are effective for merino sheep will be effective for British breed or cross-bred sheep, as the latter types of sheep tend to have greater fleece penetrability. Higher fleece penetration facilitates contact between wool-dwelling ectoparasites and pesticide in the dipping liquid.

Specific label instructions for non-merino breeds of sheep could however be developed using the methods of the invention. The units of the CIC and CCR values illustrated are milligrams of pesticide/Litre of dipwash. For field use however these values could be expressed in terms of volume or mass of supplied formulation per unit volume of dipwash or replenishment liquid. Table 7 provides field-use parameters for the DIPRITE diazinon formulation (500g/L diazinon).

13 Table 7 Initial charge (Cic) and constant replenishment (CcR) concentrations for large and small dips*.

Dose Specification Large Dips Small Dips Category (mL Diprite (mL Diprite formulation formulation O1000L of I1000L of dipwash) dipwash) CIC CCR CIC CCR A 100 650 215 650 B 75 500 165 500 C 60 360 120 360 D 45 280 95 280 E 35 240 80 240

S

as defined in the text As described in our previous application the tendency of pesticide in a dip to strip can be described by a measure called stripping factor (SF).

SF may be determined for any category by selecting an initial dip concentration (CIC) so that when a sheep is dipped, an effective dose of pesticide is achieved without underdosing or undesirable over-dosing. A second (replenishment) concentration (CCR) may then be selected experimentally, such the CIC is approximately maintained when using the selected CCR during an extended constant replenishment dipping operation using sheep of the same category. SF for the dip will then be equal to the ratio of the CIC to the CCR.

SF=CCR/CIC

SF may also be determined for each category using the procedures described in our previous patent application.

14 Thus SF may be determined for any category from an independent dipping operation in which animals are dipped in a dipping liquid of the first concentration (CIC) and the volume of dipping liquid is maintained by replenishment with dipping liquid of the first concentration.

Thus if sufficient animals of a category are dipped to allow a steady state concentration of pesticide (CSS) to develop in the dip, the tendency for the pesticide to strip can then be defined by the Stripping Factor wherein SF CIC/CSS Preferably the dipping liquid of the first concentration (CIC) has a Stripping Factor (SF) of at least two and said second concentration (CCR) and said first concentration comply with a relationship wherein that the product of the first concentration (CIC) and the Stripping Factor divided by the second 15 concentration (CCR) lies in the range 0.2 to 2.0 ie 0.2 CIC x SF/CCR the stripping Factor SF being determined as outlined above.

o 20 Surprisingly it has been found that to maintain an adequate level of pesticide in the dip, the replenishment concentration has to be at least twice the initial charge S"of the dip.

More preferably CIC x SF/CCR is in the range of 0.5 to Most preferably CIC x SF/CCR will be 0.8 to 1.2.

The invention also provides for use of an initial or first concentration of pesticide and an operational dip concentration that provides the animals with a pesticide dose equal to, or within a selected safety margin above, the minimum effective dose (MED).

The level of dipping liquid in the vessel may be maintained by continuous replenishment with a mixture of water and formulated pesticide to the sump over all or most of the dipping time. For a plunge dipping station, the process of continuous replenishment leads to the maintenance of the liquid level in sump at a fixed predetermined level when no sheep are in the dip (in practice, variations of less than and preferably less than 10% about the predetermined level can occur). For a shower dipping station, the process of continuous replenishment leads to the maintenance of liquid level in the sump at a predetermined level, with the proviso that said level is measured at a fixed stage of the batch spraying process, and allows for the volume of liquid taken up in the dispensing equipment.

In practice, the method of treatment in accordance with the invention may be represented using a chart, table, graph or equivalent representation for a particular suitable pesticide formulation, in which sump volume (or some factor highly correlated with sump volume) is related simply to an appropriate initial charge concentration of pesticide for the sump and a concentration of pesticide for constant replenishment. Recommended initial charge and replenishment concentrations would depend on whether dipping was being conducted by spray or plunge, but generally operator instructions relating to the invention may be much simpler than .the complex replenishment and reinforcement requirements of traditional dipping practices.

15 The extent of stripping is quantified by the Stripping Factor. This measure varies with factors including: the nature of the active ingredient; the nature of the formulation comprising the active ingredient, and in 20 particular the nature of the solvent in the said formulation, if the active ago* ingredient is maintained in the dipwash as an emulsion; the dipping method (plunge or shower dip); and the sump volume of the dipping station, or some other factor(s) highly correlated with sump volume. These related factors presumably could include features of dip operation that influence degree of exposure of the dipping liquid (active ingredient) to the stripping effect of the animal surfaces (eg. length of the bath, swim distance and/or time in plunge dips, showering time/sump turnover in shower dips).

The Stripping Factor applicable to this invention may be determined by quantifying the extent of stripping observed when for a given formulation of a given active ingredient using a given dipping method and a given sump volume, a dipping operation is carried out wherein the concentration of active ingredient in the initial charge of pesticide added to the sump may equal the concentration of active 16 ingredient in the replenishment charge added to the sump, as in traditional constant replenishment dipping practice.

Dipping is continued until an approximate steady state has developed between pesticide addition and removal. The concentration of pesticide in the dip at this state (Css) is used to evaluate the tendency for stripping to occur (SF) using the ratio CCR/CSS as previously described.

SF will always be greater than 1 where stripping occurs and the larger the value of SF the more prominent is the stripping effect.

In order to establish CSS and SF in a category, where insufficient animals have been dipped or are available to be dipped to allow confirmation that a steady state between pesticide addition and removal has been established, a curve-fitting procedure such as that hereinafter described may be used to approximate both CSS and SF. The stripping factor may also be determined by: dipping a number of animals in a dipping liquid of initial concentration CIC .'i 15 contained in the vessel and maintaining the level of liquid in the vessel during dipping by replenishment of the liquid removed with a dipping liquid of the first •concentration equal to CIC and preparing a graph of concentration of pesticide against numbers of animals.

(ii) generating an array of calculated stripping curves showing the change in o. 0 concentration of pesticide during dipping for a range of SF values using the formula VA ClC+ C n-1 Vs (Cn)= Vs+ VA

SF

wherein Vs is the volume of dipping liquid VA is the average volume of dipwash removed per animal Cn is the concentration after passage of the nth animal CIC is the first concentration; and comparing the graph determined in step with the array of calculated stripping curves to determine the stripping factor corresponding to the closest fitting calculated stripping curve.

4

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*050 The method of the invention may be used with a range of pesticides such as organophosphates carbamates, formamidines, pyrethroids, macrocyclic lactones and insect growth regulators such as the benzolyl phenyl ureas.

The invention may utilise known dipping equipment shown in our previous application.

The invention will now be illustrated with reference to the following nonlimiting Examples.

Example 1: Investigation of the decline in pesticide concentration in a plunge dip operated by conventional constant replenishment practice.

Methods Trial Location: Harrow, western district of Victoria, Australia.

Dip type: In ground plunge dip, 3360L capacity 15 Sheep type: Mean liveweight, 35Kg, 3 weeks off-shears Pesticide formulation: Topclip Blue Shield (Novartis Animal Health Australasia Pty Ltd containing diazinon as a 200g/L emulsifiable concentrate

(EC).

Number sheep dipped: 2865 Dip operation: The formulation was used according to the manufacturer's recommendations for constant replenishment operation (100mg/L diazinon in both the initial charge and the replenishment liquid)

RESULTS

The data illustrated in Figure 2 was derived by monitoring the concentration of diazinon in dipwash following use of the above formulation in a commercial situation.

CONCLUSION

The concentration of diazinon in the sump of the dip exhibited a rapid but decreasing rate of decline in concentration as an increasing number of sheep were dipped. After sufficient sheep were dipped, a steady state was achieved, whereby the rate of pesticide addition equalled the rate of removal on the dipped sheep. By this stage the dose /head of pesticide received by the dipped sheep equalled the 18 volume of dipwash they removed times the concentration of the replenishment liquid (100mg/L). In this instance, sheep dipped during the steady state part of the dipping operation would have received about 250mg/head (2.5L/head x 100mg/L).

The following examples are included to illustrate that doses of diazinon applied to merino sheep that are below the target doses outlined in Table 4 (including four field trials targeted at the above dose rate of 250mg/head), did not provide reliable control of sheep louse (Bovicola ovis).

Example 2: Lousicidal effect of a 150mg/head dose of diazinon on small sheep.

r Trial details Researcher: Location: Dip type: Sheep type: Group allocation: Pesticide Dose regime N. Sherwood, TLC Research Camden, NSW Portable plunge fitted with recirculation pump, 660L capacity Small frame, mixed sex merino sheep, naturally louse infected.

Mean liveweight, 23Kg (range 19-28Kg) Three groups of 5 sheep were dipped in pesticide at two, four and six weeks off-shears. Similar control group sheep were dipped in clean water Topclip Blue Shield (Novartis Animal Health, Australasia Pty Ltd). Diazinon 200g/L EC.

Two weeks off-shears group Initial charge of dip; 30.7mg/L Replenishment charge; 221mg/L Four weeks off-shears group Initial charge of dip; 22.6mg/L Replenishment charge; 163mg/ Six weeks off-shears group Initial charge of dip; 13.2mg/L Replenishment charge; TLC Research, according to National Registration Authorityrecommended protocol (20 x 100mm partings, each side of the sheep).

Lice counting

RESULTS

Results of the investigation are illustrated in Table 8.

o Table 8: Individual lice counts in sheep dipped 2, 4 and 6 weeks after shearing Treatment Group mean lice counts weeks after treatment (Standard deviation) Weeks [Diazinon] off- (mg/L) 0 2 4 6 10 12 shears 2 0 17.8 5.2 1.2 1.4 2.4 6.2 (11.84) (4.66) (0.84) (20.7) (3.78) (11.65) 2 150 17.4 0.0 0.4 0.4 0.2 (11.01) (0.89) (0.55) (0.45) (0.71) 4 0 27.4 9.2 1.2 1.4 2.4 8.6 (10.01) (2.95) (1.30) (1.67) (1.34) (5.77) 4 150 17.2 0.0 0.0 0.0 0.0 0.0 (5.68) (0.0) 6 0 41.2 13.6 3.2 4.4 10.6 43.8 (20.77) (8.79) (4.09) (5.68) (10.43) (81.64) 6 150 28.4 0.0 0.0 0.0 0.0 0.0 (11.78) (0.0)

CONCLUSION

Results indicate that the (small) short-wool not effectively treated at 150mg/head diazinon.

sheep (Category A, Table 3) were Example 3: Treatment of sheep lice with diazinon at approximately 250mg/head, in four field trials.

METHODS

Researcher: N. Sherwood, TLC Research, Camden NSW Dips were operated by constant replenishment in all cases, using diazinon 500g/L Diprite, Nufarm Ltd). Details of the experimental dips and trial sheep are shown in Tables 9a and b. The appropriate charge rates were evaluated by methods outlined in patent application 19946/97. The extent of stripping in each dip (SF) and the mean volume of dipwash removed by the sheep was evaluated in an independent preliminary trial.

Table 9a: Details of sheep dipped in field trials where sheep were treated with approximately 250mglhead diazinon Trial number 96/42196143 96/47 97/03 Sheep description Merino Merino Merino Merino Bodyweight 37 42 42 (mean, Kg) Category C C D C (Table3) Age 2 mixed mixed (ewes and wethers lambs) Condition score 2 2.4 2.7 3.3 Wool fibre 19 approx. 19 20 18 diameter Weeks off 3 3 5 3 shears Wool length 20 13 10 15.4 (mm) Number of 2522 3384 2299 909 sheep dipped a.

a a Table 9b: Details of the dips and operational parameters in the above field trials and parameters of the dipping Trial numbier 96/42. 96/43 96147 97/03 B Location T Iaraiga, Niangla, Marulan, Woolbro.ok, Dip type Shower, Shower, Plunge Shower, Sunbeam Sunbeam Commercial Sunbeam SSD60** SSD60** Portable Anti-strip Sump volume 2500 1165 3000 400

(L)

Dip operation Sump charge 8.1 9.2 13.9 12.5 rate (mg/L) Replenishment 73.7 62.5 55.6 59.6 rate (mg/L) Shower dips were replenished such that the operating volume of the sump was restored on completion of draining of a batch.

Pump output set to deliver 25-35L in five evenly spaced test buckets during a two minute test run. During operation, shower dips were operated through overhead sprays for three minutes, bottom sprays for one minute and finally for another two minutes through the overhead sprays.

Sheep (25) were nominated as 'tracer' sheep in each trial. Lice numbers on these sheep were assessed and they were individually ear-tagged prior to dipping. Lice counts were conducted according to methods recommended by the National Registration Authority (NRA), specifically being numbers observed in 40 x 100mm partings on either side of the sheep. Trials were discontinued and arrangements were made for re-treating the entire flock of sheep if (when) lice were evident in either the tracer or other sheep in the flock.

RESULTS

Lice counts of tracer sheep before and after dipping are shown in Table Table 10: Lice counts in tracer sheep before and after dipping a a a a Trial Site Mean lice cou.n pre-dipping (at weeks after treatment) Taralga 59.5 1.8(13) Niangla 53.8 0(8) Marulan 30.6 0.04(8) Woolbrook 12.6 0.36(5) *This trial was discontinued due to lice being found by the owner on four trial sheep

CONCLUSION

These trials demonstrated that a doses of diazinon outside the target range were not sufficient to remove lice from larger (average-sized) merino sheep.

The following example illustrates the results of three subsequent field trials in which the dose rate for dipping according to the invention was raised to the target dose range illustrated in Table 4.

Example 4 Seven field trials in which sheep were treated for lice infestation using diazinon at an intended dose regimen, applying 4-500mg/head for average size sheep.

Methods Dips were operated by constant replenishment in all cases, using Diprite formulation (diazinon 500g/L EW, Nufarm Ltd) Details of the experimental dips and trial sheep are shown in Tables 11a and b. The appropriate charge rates were derived using the example product label illustrated in Table 6. These instructions are derived using methods outlined in this application and patent application 19946/97.

a a.

a. a. 23 Table I Ia: Details of sheep dipped in field trials where sheep were treated according to Tables 3 and 6 Tria nuber9714 9/49 71110 8/N0 VRNDO3 VR NOO4 97/2 G ate I West Merino merino wethers ewes and wethers 'i An Bodyweight (mean, 21-32 Kg -I 3-/U

QQ-QO

Kg) I I I mixea wean~u I I IIA~U I I IIA~ Age mixed mixed, adult mixed, adult mixed weaner I I I AC I I I I~ -1'b Condition SCOT Wo-ol fibre dial (Pi) Weeks off she Wool length (r Category (Tab Number of st dipped mneter 2.5-3.0 t..U-f- I I I I I 16-18 10-L-1 ars 5t36 1.5 0A5-.6 A5-6 nm) -20 -15 2 A8-.10 A 5-1 20 15-20 ~le 3) ieep D DO DA A I.

1 4U I 3U0oo, 1437 603 2500 1402- I JUD OVU I L I a A. J a. 0 0 a a. a a a a. a a.

24 Table 11b Details of the dips and operational parameters in the above field trials and parameters of the dipping cW Category (Table 3) Sump Volume Sump charge rate (mg/L) Replenishment rate (mg/L) riunge, Concrete In-ground

D

6120 22.5 Shower, Sunbeam SSD60*

D

800 22.5 iPunge, Concrete In-ground

D

Portable plunge Portabli plunge roraDie plunge A A E D Shower (Sunbeam) 9000 4000L 3600L 3700 I 1 I ~m/ 22.5 108mg/L diazinon 325mg/L diazinon 108mg/L diazinon 325mg/L diazinon 40mg/L 120mg/L 678 22.5mg/L 140mg/L 140 140 140

II

The shower dip was replenished such that the operating volume of the sump was restored on completion of draining of a batch. Pump output set to deliver 25-35L in five evenly spaced test buckets during a two minute test run. During operation, shower dips were one minute and finally for another two minutes through the overhead operated through overhead sprays for three minutes, bottom sprays for sprays.

Sheep (25) were nominated as 'tracer' sheep in each trial. Lice numbers on these sheep were assessed and they were individually ear-tagged prior to dipping. Lice counts were conducted according to methods recommended by the National Registration Authority (NRA), specifically being numbers observed in 40 x 100mm partings on either side of the sheep. Trials were discontinued and arrangements were made for re-treating the entire flock of sheep if (when) lice were evident in either the tracer or other sheep in the flock.

10 RESULTS Lice counts of tracer sheep before and after dipping according to Tables 3 and 6 are shown in Table 12 Table 12: Lice counts in tracer sheep before and after dipping Bathurst 140 0.0(1.5) 0.0(3) 0.0(6) Nerrin Nerrin 19.4 NT 0.0(3) 0.0(6) Minninera 26.2 0.0(2) 0.0(5) 0.0(9.5) Barraba 45.8 0.0(2) 0.0(6) Walcha 124.8 (pre- 0.0(2) 0.0(6) shearing) Bogan 5.0 0.0(2) 0.0(3.5) 0.0(6)

CONCLUSION

These trials demonstrated that a dose rate of approximately 500mg/head diazinon within the target range was sufficient to remove sheep lice infestation from mediumsized merino sheep The following example is included to demonstrate how the VR categories outlined in Table 2 may be derived by determination of drainage profiles following dipping Example 5 Typical profile for dipwash drainage from a sheep following saturation in a plunge dip.

METHODS

Trial Location: TLC Research Facility, Camden NSW.

Dip type: Portable, Galvanised steel construction 660L capacity Drainage area Tilted toward collection vessel, Dipped sheep were confined 10 on a weighing platform Number sheep dipped: 6 Sheep type: Merino, mean liveweight, 45Kg (range 43.5-47.4Kg), 4 weeks off-shears (Category C, Table 3) Wool type 18-20p fibre diameter, approx. 13.3mm length Pesticide formulation: Diprite 500g/L Diazinon EW, Nufarm Ltd.

r r Dip operation: Each sheep was plunge dipped for about 20 seconds. On exit from the dip, sheep were weighed and the volume of dipwash drainage recorded, at 20 second intervals

RESULTS

The drainage profile of dipwash removal from the experimental plunge dipping process, measured by both the change in sheep weight and by the volumetric collection of dipwash, is illustrated in Table 13 The apparent time delay between mean weight change of the sheep and the volume (mass) of dipwash collected in this table was attributable to the time taken for the dipwash to run across the floor of the collection pen and be collected in the measuring cylinder.

55*5 5* 55 5 Table 13 Drainage of dipwash following dipping of six adult merino sheep, four weeks off-shears.

Time after dipping (minutes) Mean live- Proportion of Volumetric weight of. original live- proportion the sheep weight dipwash collected (K g) -1 44.9 0 50.7 100 1 47.7 51.7 23.4 2 47.7 51.4 52.0 3 46.8 67.2 59.1 4 47.2 59.2 66.3 46.5 72.4 66.7 6 47.1 62.1 70.5 7 46.3 74.6 71.3 8 47.4 56.0 75.8 9 NR** 76.0 NR 86.1 11 NR 86.1 12 NR 96.3 13 NR 96.3 14 46.9 64.6 100.0 Measured as percentage of mean total dipwash collected over sampling period. Values shown are group means.

NR Not recorded the 14 minute Clearly both methods of evaluating the drainage profile of dipped sheep demonstrate that about half the increase in weight (or volume of dipwash) drains from the sheep surface within minutes of the sheep emerging from the dip. The remainder of the volume of dipwash removed is slow to drain, with about 2L remaining on completion 28 of the 14 minutes draining period. By this time the rate of liquid run-off from the sheep surface was very slow and it appeared likely that much of the retained liquid would be lost from the surface by evaporation.

In the above trial, the dipped sheep would have been defined as being at the high end of category C. Field experimentation has indicated that such sheep are likely to remove about 3.1ULhead from the dip. The level of removal was slightly higher in this trial (at about 3.5L/head) presumably due to -lower drainage losses than would be expected in the field. Drainage loss was relatively slow seen after the first few 10 minutes draining. Typical draining intervals used under field conditions (5-10 minutes) are therefore likely to have only a minor influence on the estimations of VR *.ooo used for dose allocations.

a It will be appreciated that various alterations, modifications and/or additions may be 15 introduced into the constructions and arrangements of parts previously described without departing from the spirit or ambit of the present invention.

o° a a

Claims (10)

1. A method of dipping a herd of animals of the same species in a dip containing pesticide dipwash to reduce the incidence of overdosing and underdosing, the method including: providing a plurality of treatment categories for animals, the categories each defining a range in the volume of dipwash removed by an animal; assigning animals to the treatment categories based on the anticipated 10 volume of dipwash removed by each animal within the herd; providing an initial pesticide concentration of dipwash for each category for providing effective pesticidal control in the dip for animals of said catgegory; providing a second pesticide concentration for each category for replenishing dipwash removed from the dip to maintain an effective concentration of pesticide in 15 the dip.

2. A method according to claim 1 wherein the animals of the herd are separated into at least three categories according to the anticipated volume of dipwash removed by each animal. 20 3. A method of dipping a herd of animals of the same species in a dip containing a pesticide dipwash to reduce the incidence of overdosing and underdosing the method including: providing a plurality of treatment categories for the animals, each category defining a range in the product of bodyweight and time since shearing; grouping animals which fall into the same category of the product of bodyweight and time since shearing; providing an initial pesticide concentration for each category for providing effective pesticidal control of sheep in said category; and providing a second pesticide concentration for each category for replenishing dipwash, the second concentration being sufficient to compensate for the effect of stripping of pesticide from the initial concentration during dipping of animals of said category.

4. A method according to claim 3 wherein the animals are divided into at least three groups according to the product of body weight and time of shears for each animal.

5. A method according to any one of claims 1 to 4 further including separately dipping each category of animals using a dip containing pesticide of the corresponding initial concentration for the category and during the dipping process replenishing dipwash removed by animals with the second pesticide concentration for the category. S*

6. A method according to any one of the previous claims wherein the animals are treated by plunge dipping in a sump containing the initial pesticide concentration. S i

7. A method according to any one of claims 1 to 6 wherein the animals are 0 OV* 15 treated by shower dipping wherein the dipwash is delivered prior a sump containing S"the first pesticide concentration. A method according to claim 4 wherein the treatment categories include: a first group consisting of animals of body weight of from 15 to 30 kg and time off- 20 shears from 0 to 2 weeks; a second group consisting of each of the sub-groupings of: bodyweight 30 to 60 kg and time off-shears from 0 to 2 weeks and (ii) bodyweight 15 to 30 kg and time off-shears from 2 to 4 weeks; a third group consisting of each of the sub-groupings of: bodyweight 15 to 30 kg and time off-shears from 4 to 6 weeks, (ii) bodyweight 30 to 45 kg and time off-shears from 2 to 4 weeks and (iii) bodyweight 60 to 75 kg and time off-shears from 0 to 2 weeks; a fourth group consisting of each of the sub-groupings of: bodyweight 30 to 45 kg and time off-shears from 4 to 6 weeks, and (ii) bodyweight 45 to 60 kg and time off-shears from 2 to 4 weeks; and a fifth group consisting of each of the sub-groupings of: bodyweight 45 to 60 kg and time off-shears from 4 to 6 weeks, (ii) bodyweight 60 to 75 kg and time off-shears from 2 to 6 weeks.

9. A method according to claim 3 wherein for each said group said initial pesticide concentration (CIC) times the stripping factor (SF) divided by the second concentration of pesticide (CCR) lies within the range of from 0.2 to 2.0 and wherein the stripping factor SF is at least two and is defined according to the relationship SF ClC/CSS wherein CSS is a steady state concentration provided when the animals of said category are dipped in a dipping liquid of said first concentration contained in the -40--vessel and the level in the vessel is maintained during dipping by replenishment of the liquid removed with a dipping liquid of concentration equal to the first .concentration, the concentration of pesticide in the vessel being initially reduced as a 9*99 result of stripping of the pesticide by said group of animals until said steady state concentration is reached and from which no significant further reduction in S"15 concentration occurs. 9. A method of dipping according to claim 1, wherein said second and said first "concentration for each category are independently determined and comply with the relationship wherein the first concentration (CIC) times the Stripping Factor (SF), 20 divided by the second concentration (CCR) lies within the range of from 0.2 to and wherein the stripping factor (SF) is at least two and is determined by a curve fitting procedure comprising: dipping a number of animals of the category in a dipping liquid of the first concentration (CIC) contained in the vessel and maintaining the level of liquid in the vessel during dipping by replenishment of the liquid removed with a dipping liquid of the first concentration (CIC); (ii) preparing a graph of concentration of pesticide against numbers of animals; (iii) generating an array of calculated stripping curves showing the change in concentration of pesticide during dipping for a range of SF values using the formula VA C IC+ C n-1 Vs Vs+ VA SF 32 wherein Vs is the volume of dipping liquid VA is the average volume of dipwash removed per animal Cn is the concentration after passage of the animal CIC is the first concentration and equals the replenishment concentration in the procedure; and (iv) fitting the graph determined in step with the array of calculated stripping curves to determine the stripping factor corresponding to the closest fitting calculated stripping curve. :0 11. A method according to any one of the previous claims wherein the replenishment composition is contained in a replenishment vessel provided with Sl means for transferring liquid from the replenishment vessel to the dipping vessel in response to a drop in level of dipping liquid in the dipping vessel. l0e 1: 12. A method according to any one of the previous claims wherein in each *treatment category the second pesticide concentration is at least twice the initial concentration.

13. A method according to any one of the previous claims wherein the level of 20 dipping liquid is maintained with no greater than 10% variation from the initial level.

14. A method according to any one of the previous claims wherein the herd comprises at least 100 sheep.

15. A method according to any one of the previous claims wherein the pesticide is diazinon. DATED: 3 September, 1999 PHILLIPS ORMONDE FITZPATRICK Attorneys for: NUFARM LIMITED