NO137135B - RODENTICID AGENTS. - Google Patents

Description

The present invention relates to rodenticidal compositions. The invention provides a composition consisting of:

a) an anticoagulant rodenticide, and

b) a compound exhibiting vitamin D activity.

The weight ratio between component a) and component b) is from

99:1 to 1:99, preferably from 80:20 to 10:90.

'Warfariri' (3(α-phenyl-(3-acetyl)-ethyl-4-hydroxy coumarin) and

other anticoagulant compounds are almost always used to control rat and other rodent populations and have a cumulative toxicity in that rats and mice are killed with one dose

in the order of 1 mg/kg, and which is given in the form of bait for a period of 4 - 5 days. However, some rats and mice have developed a resistance to anticoagulants, and will now tolerate much higher levels than those normally required to euthanize the animals.

It is also known that compounds which exhibit vitamin D activity, such as e.g. "Calciferol", are toxic to rats and mice when administered over several days, as one of the causes of death is absorption of calcium from bones which is deposited in the kidneys. However, "Calciferol" itself is not suitable as a rodenticide due to that the quantity levels at which it must be used make the application too expensive, and because the slow killing when using economic concentrations.

The present invention has its origin in the discovery

that mixtures of anticoagulant rodenticides with compounds exhibiting vitamin D activity have a toxic effect on rodents greater than the sum of the toxicity of the two compounds. It is surprising that compounds with vitamin D activity are able to enhance the toxicity of anticoagulant compounds, not only in normal rats and mice, but also in rats and mice resistant to the anticoagulant compounds as such. The compositions according to the present invention are effective poisons for several pests, especially rodents such as rats and mice.

The anticoagulant rodenticides are generally substances that are known per se. The most important class is derivatives of 4-hydroxy-coumarin. These derivatives include 3,3'-methylene -

bis (4-hydroxy-coumarin), coumatetralyl £4-hydroxy-3-(1,2,3,4-tetrahydronaphthyl)coumarin ^ 3( α-phenyl-(3-acetyl)ethyl 1-4-hydroxy-coumarin and 3(α-heteromonocyclic β-acyl)-ethyl-4-hydroxy-coumarins. The acyl group in the latter two types of rodenticides is preferably an acetyl group. The phenyl group in the α-position can be substituted and then especially by a halogen atom or a nitro group. The heteromonocycle can contain one or more oxygen atoms as a heteroatom or heteroatoms. Examples of such compounds are 3-( a-parachloro of enyl-|3 -acetyl)-ethy 1-4-

hydroxycoumarin, 3-(α-phenyl-|3-acetyl)-ethyl-4-hydroxycoumarin and 3[α-(2'-furyl)-β-acetyl] ethyl-4-hydroxycoumarin. Aryl- and acyl-substituted indanediones can also be used, such as those containing a phenyl or substituted phenyl group and bis-methyl-propiolyl derivatives, e.g. 2,.2-bis(methylpropolyl)-indan-1,3-dione. Among the commercially available anticoagulant rodenticides are those known through I.S.O. Particularly interesting are agents according to the present invention which contain "Warfarin" (or coumafen or zoocoumarin), "Cou-metetralyl", "Diphacinone", "Chlorphacinone" and "Coumachlor", respectively the vitamin D-active components ergocalciferol and cholecalciferol. The latter are derivatives of 3[3-hydroxy-^ 5 7_ 17(3-substituted steroids, where the type of 17(3-substituent is not critical, and are generally obtained from steroids, such as ergosterol, by irradiation.

The agents according to the present invention can be present in

form of a rodenticide formulation, e.g. as bait or as a concentrate for dilution in application. Rodenticidal formulations may suitably contain from 0.005 to 0.5 weight percent anticoagulant rodenticide and from 0.005 to 0.5 weight percent of a compound exhibiting vitamin D activity. The nature of the residue in such rodenticidal formulations is not critical according to the invention.

Bait food is often based on solid grain food, e.g.

oats, oat flour, corn flour, wheat flour and corn starch and fish meal. Sugar is useful as an additive to other baits, and chocolate is an attractive bait. Chocolate can be used alone or together with other baits. Vegetable, animal or mineral oils, such as e.g. peanut oil, corn oil or mineral oil can be used alone or as additives to other baits.

Dye can also be added to the formulation to warn and avoid confusion. The type of dye is not critical,

but a blue or red color is preferred. An antioxidant can be used, and the type is not critical either.

The agent can be prepared as a concentrate in an inert

substance, e.g. powdered chalk or aluminum oxide, for dilution with a suitable edible substance that the rats like. Alternatively, the agent can be dissolved in an oil, e.g. corn oil,

for mixing with the bait diluent. The concentrate usually contains from 0.1 to 10% by weight of each of the components a) and b).

An example of a formulation is a mixture of 97.5% chalk powder, 0.5% "Warfarin" and 2.0% "Calciferol" which when diluted with 19 parts of oats gives a bait containing 0.025% "Warfarin" and 0.1% "Calciferol".

An example of the latter is a solution of 0.5% "Warfarin" and 2% "Calciferol" in corn oil or another suitable medium. A bait can be prepared by mixing one part of the solution with 19 parts of oats.

The following examples illustrate the invention, the parts are given in parts by weight. Examples 1 to 4 are ready-to-use rodenticide formulations.

EXAMPLE 1

EXAMPLE 2

EXAMPLE 3 EXAMPLE 4

Examples 5 to 7 are concentrates intended for dilution with 19 parts by weight of a base material acceptable to the user.

EXAMPLE 5

EXAMPLE 6

0.5% "Warfarin in 99.5% fine oatmeal

2.0% "Calciferol in 98.0% corn oil.

EXAMPLE 7

EXAMPLE 8

The reinforcing effect of a drug is shown in table.1,

wherein a bait containing 0.025% "Warfarin" and/or 0.01% "Calciferol" was given to "Warfarin" resistant rats for several days, whereby "Warfarin" and "Calciferol"

was administered in a bait consisting of plain oats.

It can be seen that "Warfarin" has very little effect on these resistant rats. "Calciferol" alone gives at most 33% mortality, while "Warfarin" and "Calciferol" together give 50% mortality of approx. 3.5 days and 100% mortality in anything over 8 days.

EXAMPLE 9

Baits were prepared with the formulations shown in Table 2 below by dispersing an acetone slurry with the active ingredients in ordinary oatmeal and drying the product for 24 hours. Confined animals were continuously

body exposed to bait, and in the course of the feeding period got

the animals no alternative fodder. Unlimited amounts of tap water were available. The bait was replaced each day and the remainder weighed to determine the amount consumed. The number of experimental animals that died each day was noted. Other details are given in table 2 below.

In no case were all resistant rodents killed

using anticoagulant alone.

"Calciferol" alone has always given lethality, but by

same concentrations, the killing rate and the percentage of dead animals were always greater when "Calciferol" was administered together with an anticoagulant.

E.g. in the case of resistant mice:

1. 0.025% "Warfarin" did not kill any mice over a 56 day administration period.

2. 0.005% "Calciferol" killed all mice, but only after

29 day administration. The mice died between the 16th and 29th day.

3. 0.005% "Calciferol" + 0.025% "Warfarin" administered in

12 days killed all resistant mice between days 4 and 12.

Example with resistant rats:

1. 0.025% "Warfarin" killed only one rat over a 10 day administration period. 0.025% "Coumatetralyl", "Diphacinone", "Chlorophacinone" and "Coumachlor" killed respectively. 3/5, 1/5, 2/5 and 0/5 over the course of a 10 day period. All anticoagulants tested in combination with "Calciferol" killed all tested rats within 10 days. 2. 0.025% "Warfarin" + 0.01% "Calciferol" killed 12/12 of the resistant rats within 10 days . The two substances tested separately at the same concentrations killed only 1/9 and 3/9 of the rats in .. 10 days. 3. 0.025% "Calciferol" administered alone for 10 days killed 10/12 of the resistant ones rats between 3. and 8.

the day. 0.025% "Calciferol" + 0.025% "Warfarin", which was administered only for 4 days, killed 14/14 of the rats between the 3rd and 6th day.

EXAMPLE 10

This example shows the effect of a field experiment whereby "Warfarin" was added to a "Calciferol"-containing bait.

Baits were prepared by preparing an oil solution of "Calciferol", mixing this with powdered "Warfarin" concentrate in the case that "Warfarin" was used, and then adding oatmeal.

Trial baits containing only oat groats were placed around each farm to determine the best-situated bait sites.

Trial baits were placed in common, commercially available bait tubs, each tub containing a surplus of bait as determined in the initial trials.

The bait was examined on the indicated days. When clear signs of rat activity could be observed, this was marked with "taken". The bait was collected and weighed to determine the amount of bait consumed. Fresh bait was placed at each trial.

The results are shown in Tables III and IV below.

Assessment of the trials:

(i) When 0.10% "Calciferol" was used alone, there was obviously a reduction in activity, and after 23 days of continuous bait feeding, some consumption could still be observed, indicating incomplete eradication. (ii) When using 0.10% "Calciferol" + 0.025% "Warfarin" the activity was reduced much faster, and no live rats could be detected after 9 days.

It should be noted that the latter results were obtained on farms infested with rats proven to be anticoagulant resistant.

Field trial data:

i) The effect of "Calciferol" without anticoagulant. Farm A, Lancashire.

Less rat infestation around outbuildings.

Formulation

0.10% "Calciferol"

5.00% corn oil

94.90% pinhead oatmeal..

ii) The effect of "Calciferol" with anticoagulant. Farm B, Merioneth.

Resistant rats. Standard laboratory tests confirmed resistance in 9/10 of the rats caught at the site.

Formulation

0.100% "Calciferol"

0.025% "Warfarin"

5,000% corn oil

94.875% medium fine oat flour.

Claims (5)

1. Rodenticide, characterized in that the active ingredient contains: a) an anticoagulant rodenticide, and b) a compound that has vitamin D activity, the weight ratio of component a) to component b) being from 99:1 to 1:99. 2. Agent according to claim 1, characterized in that the anticoagulant rodenticide is warfarin, coumatetralyl, diphacincne, chlorophacinone or coumachlor. 3. Agent according to claim 1 or 2, characterized in that the compound containing vitamin D activity is ergocalciferol or cholecalciferol• 4. Agent according to one of claims 1-3, characterized in that component a) is present in an amount of 0.005 to 0.5% by weight, and that component b) is present in an amount of 0.005 to 0.5% by weight . 5. Agent according to one of claims 1-3, characterized in that it exists in the form of a concentrate that can be prescribed for use as a rodenticide, where component a) occurs in an amount of 0.1 to 10% by weight and where component b ) occurs in an amount of 0.1 to 10% by weight.