Composition comprising bromadiolone, rodenticide bait, and method for controlling target rodent pests

Abstract

A rodenticidal bait composition includes bromadiolone mainly in the form of the homostereoisomer of formula 3-[3-(4-bromo-[1,1-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2-one, where carbons 1 and 3 of the 3-hydroxy-1-phenylpropyl group have the same absolute configuration. A method for controlling rodent pests using the rodenticidal bait is also described.

Claims

1. Rodenticidal bait, comprising a composition comprising bromadiolone in a majority in the form of the homostereoisomer of the formula 3-[3-(4-bromo-[1,1-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2-one, carbon atoms 1 and 3 of the 3-hydroxy-1-phenylpropyl grouping having the same absolute configuration, and an excipient which is edible for the target rodent pests and chosen in order to allow eating of the composition by the target rodent pests.

2. Bait according to claim 1, wherein the excipient which is edible comprises at least one food chosen from the group formed by cereal grains, ground cereal grains, cereal grain flours, cereal grain flakes, cereal bran and non-cereal grains.

3. Bait according to claim 1, wherein the bromadiolone is present in the bait with a proportion by weight of less than 200 ppm.

4. Bait according to claim 1, wherein the homostereoisomer of bromadiolone has, in proton NMR in CDCl.sub.3, two distinct multiplets, one centred at a chemical shift of the order of 2.35 ppm and the other at a chemical shift of the order of 3.05 ppm.

5. Method of combating target rodent pests, in which an amount of bait comprising: bromadiolone in a majority in the form of the homostereoisomer of the formula 3-[3-(4-bromo-[1,1-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2-one, carbon atoms 1 and 3 of the 3-hydroxy-1-phenylpropyl grouping having the same absolute configuration, and an excipient which is edible for the target rodent pests, is scattered.

6. Method according to claim 5, wherein the bait is chosen such that bromadiolone is present in the bait in a proportion by weight of less than 200 ppm.

7. Method according to claim 5, wherein the proportion by weight of bromadiolone in the bait is chosen in combination with the amount of bait scattered such that the target rodent pests eat an amount of bait in the course of a single period of 24 consecutive hours sufficient to be lethal to said target rodent pests which eat said bait.

8. Method according to claim 5, wherein the proportion by weight of bromadiolone in the bait is chosen in combination with the amount of bait scattered such that the target rodent pests eat an amount of bromadiolone which is: non-lethal to the target rodent pests which eat said bait during a period of 24 consecutive hours, and sufficient to be lethal to the target rodent pests which eat said bait during several periods of 24 consecutive hours.

9. Method according to claim 8, wherein the amount of bait scattered and the proportion by weight of bromadiolone in the bait are chosen to allow a daily ingestion of bromadiolone by a target rodent pest of between 0.20 and 10 mg per kilogram of target rodent pest.

10. Method according to claim 8, wherein the amount of bait scattered, the proportion by weight of bromadiolone in the bait and the proportion of the homostereoisomer of bromadiolone are adjusted such that eating of the bait is lethal to the target rodent pests eating the bait daily during at least 2 periods of 24 hours, said periods being successive.

11. Method according to claim 8, wherein the amount of bait scattered, the proportion by weight of bromadiolone in the bait and the proportion of the homostereoisomer of bromadiolone are adjusted in order to be able to achieve in the liver of the target rodent pests on the day following the third day of a period of three consecutive days, said period comprising at least one ingestion of bait per day, an amount of bromadiolone of less than or equal to 30 g of bromadiolone per gram of liver of the target rodent pest.

12. Bait according to claim 2, wherein the bromadiolone is present in the bait with a proportion by weight of less than 200 ppm.

13. Bait according to claim 2, wherein the homostereoisomer of bromadiolone has, in proton NMR in CDCl.sub.3, two distinct multiplets, one centred at a chemical shift of the order of 2.35 ppm and the other at a chemical shift of the order of 3.05 ppm.

14. Bait according to claim 3, wherein the homostereoisomer of bromadiolone has, in proton NMR in CDCl.sub.3, two distinct multiplets, one centred at a chemical shift of the order of 2.35 ppm and the other at a chemical shift of the order of 3.05 ppm.

15. Method according to claim 6, wherein said proportion by weight of bromadiolone in the bait is chosen in combination with the amount of bait scattered such that the target rodent pests eat an amount of bait in the course of a single period of 24 consecutive hours sufficient to be lethal to said target rodent pests which eat said bait.

16. Method according to claim 6, wherein said proportion by weight of bromadiolone in the bait is chosen in combination with the amount of bait scattered such that the target rodent pests eat an amount of bromadiolone which is: non-lethal to the target rodent pests which eat said bait during a period of 24 consecutive hours, and sufficient to be lethal to the target rodent pests which eat said bait during several periods of 24 consecutive hours.

17. Method according to claim 9, wherein the amount of bait scattered, the proportion by weight of bromadiolone in the bait and the proportion of the homostereoisomer of bromadiolone are adjusted such that eating of the bait is lethal to the target rodent pests eating the bait daily during at least 2 periods of 24 hours, said periods being successive.

18. Method according to claim 9, wherein the amount of bait scattered, the proportion by weight of bromadiolone in the bait and the proportion of the homostereoisomer of bromadiolone are adjusted in order to be able to achieve in the liver of the target rodent pests on the day following the third day of a period of three consecutive days, said period comprising at least one ingestion of bait per day, an amount of bromadiolone of less than or equal to 30 g of bromadiolone per gram of liver of the target rodent pest.

19. Method according to claim 10, wherein the amount of bait scattered, the proportion by weight of bromadiolone in the bait and the proportion of the homostereoisomer of bromadiolone are adjusted in order to be able to achieve in the liver of the target rodent pests on the day following the third day of a period of three consecutive days, said period comprising at least one ingestion of bait per day, an amount of bromadiolone of less than or equal to 30 g of bromadiolone per gram of liver of the target rodent pest.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Other objects, characteristics and advantages of the invention will emerge from reading the following description and the examples given purely as non-limiting and which refer to the attached figures, in which:

(2) FIG. 1 is a detail of a proton NMR spectrum of the heterostereoisomer of bromadiolone;

(3) FIG. 2 is a detail of a proton NMR spectrum of the homostereoisomer of the bromadiolone of a composition according to the invention;

(4) FIG. 3 is a detail of a proton NMR spectrum of a mixture of the homostereoisomer and heterostereoisomer of bromadiolone;

(5) FIG. 4 is a graphical representation of the course of the hepatic concentration of the configurational stereoisomers of bromadiolone, and

(6) FIG. 5 is a graphical representation as a histogram of the effect of a method according to the invention on the coagulation time of target rodents.

(7) A composition according to the invention comprises a proportion in a majority of the homostereoisomer of bromadiolone in the bromadiolone. The inventors have discovered that it is possible to obtain such a homostereoisomer of bromadiolone by separation of the configurational stereoisomers of bromadiolone.

(8) For example, chromatography of a mixture of the configurational stereoisomers of bromadiolone on thin layer silica gel or on a flash silica column of a Nova-pak Silica cartridge with a mobile phase formed by 70% petroleum ether and 30% chloroform (flow rate of 1 ml/min) allows separation of the two configurational stereoisomers of bromadiolone.

(9) It is also possible to separate the two configurational stereoisomers of bromadiolone by HPLC chromatography on a LiChrospher 100 RP-18 Endcapped, Merck reverse phase column having a length of 250 mm and of 4 mm internal diameter. The reverse stationary phase has a particle size of 5 m and a specific surface area of 220 m.sup.2/g. The mobile phase is made up of a mixture of methanol (72%) and water (28%) acidified with 0.0025 M H.sub.3PO.sub.4. The flow rate of the mobile phase is 1.0 ml/min and detection is carried out by spectrophotometry at 260 nm. The homostereoisomer of bromadiolone of which the retention time is of the order of 19.44 mm and the heterostereoisomer of bromadiolone of which the retention time is of the order of 21.71 min are detected and collected.

(10) The homostereoisomer of bromadiolone can also be prepared by purification by high performance liquid chromatography (HPLC) under the following conditions: the stationary phase is an XBRIDGE C.sub.18 grafted silica column, 150 mm4.6 mm; the mobile phase is formed by a gradient of compositions A and B, the characteristics of which are given in Table 1 below; the flow rate of the mobile phase in the stationary phase is 1 ml/min; the stationary phase is kept at the temperature of 40 C.; the detection is carried out by photometry at the wavelength of 265 nm; the injection volume is 10 l.

(11) TABLE-US-00001 TABLE 1 Composition A Composition B Elution time, min H.sub.2O + 0.2% (v/v) H.sub.3PO.sub.4 Methanol 0 40% 60% 20 20% 80% 20.1 40% 60% 25 40% 60%

(12) This chromatography allows separation of the homostereoisomer having a retention time of the order of 17.1 minutes and a second configurational stereoisomer of bromadiolone, named the heterostereoisomer, having a retention of the order of 17.9 minutes.

(13) However, it is to be noted that replacement of methanol by acetonitrile in composition B of the mobile phase has the effect of reversing the order of elution of the homostereoisomer and the heterostereoisomer of bromadiolone.

(14) Investigation of the configurational stereoisomers of bromadiolone by proton NMR (.sup.1H-NMR) in CDCl.sub.3 allows confirmation that: the configurational stereoisomer retained the least (retention time of the order of 17.1 min) has a proton NMR (.sup.1H-NMR) spectrum in CDCl.sub.3 of which a detail is reproduced in FIG. 2 and in which two distinct multiplets centred one at about 2.35 ppm and the other at 3.05 ppm each correspond to one of the two methylene protons carried by carbon atom 2 of the 3-hydroxy-1-phenylpropyl grouping of the homostereoisomer; the configurational stereoisomer retained the most (retention time of the order of 17.9 min) has a proton NMR (.sup.1H-NMR) spectrum in CDCl.sub.3 of which a detail is reproduced in FIG. 1 and in which a complex multiplet centred at about 2.75 ppm corresponds to the two methylene protons carried by carbon atom 2 of the 3-hydroxy-1-phenylpropyl grouping of the heterostereoisomer.

(15) Inhibition of Vitamin K Epoxide Reductase Complex 1 (VKORC1) In Vitro by the Homostereoisomer and by the Heterostereoisomer of Bromadiolone

(16) The inhibitory power of two preparations concentrated respectively in the homostereoisomer (Homo-SI) and heterostereoisomer (Hetero-SI) of bromadiolone was evaluated utilising measurement of the activity of vitamin K epoxide reductase (VKOR) catalysed by microsomes of the livers of rats sensitive to anti-vitamin K (AVK) compounds. The configurational stereoisomers of bromadiolone are partially purified by HPLC chromatography over a gradient of composition (A/B) as described in Table 1 above. The preparation concentrated in Homo-SI is made up of 96% Homo-SI and 4% Hetero-SI. The preparation concentrated in Hetero-SI is made up of 96% Hetero-SI and 4% Homo-SI. Analysis of the curves of inhibition of the VKOR activity as a function of the concentration of inhibitor shows values of the inhibition constants (K.sub.i) of the order of 30 nM for Homo-SI and of the order of 50 nM for Hetero-SI. The inhibitory power on the toxicological target of each of the two isomers is therefore similar.

(17) Hepatic Persistence of the Homostereoisomer (Homo-SI) and the Heterostereoisomer (Hetero-SI) of Bromadiolone in the Rat

(18) On D0 laboratory rats (Sprague Dawley rats, Charles River, Saint germain sur l'Arbresle, France) having a body weight of the order of 200 g are tube-fed with a solution of Homo-SI in a mixture of oil/DMSO or with a solution of Hetero-SI in an identical mixture of oil/DMSO in an amount of 3.0 mg of bromadiolone per kilogram of rat. The rats are kept alive by daily subcutaneous injection of a solution of vitamin K in an amount of 0.1 U per rat. On D+1, D+3, D+7, D+14 and D+21 4 rats are anaesthetised with isoflurane and then sacrificed, and the livers are removed and frozen until analysed. The course with respect to time of the mean hepatic contents of the configurational stereoisomers Homo-SI (.square-solid.) and Hetero-SI () are analysed by HPLC, given in Table 2 below and shown in FIG. 4 (the symbol (.square-solid.) represents Homo-SI and the symbol () represents Hetero-SI).

(19) TABLE-US-00002 TABLE 2 Hepatic content, g/g D + 1 D + 3 D + 7 D + 14 D + 21 Homo-SI 8.27 2.72 2.34 0.43 1.57 0.21 0.99 0.06 0.92 0.08 Hetero-SI 18.62 2.22 14.70 1.06 5.20 0.75 2.67 1.07 0.99 0.07

(20) From D+1 the mean content of Homo-SI in the liver of rats is lower than the mean content of Hetero-SI in the liver of tube-fed rats for an equal initial dose of bromadiolone ingested on D0. Homo-SI has a hepatic persistence significantly lower than that of Hetero-SI.

(21) Hepatic Persistence of the Homo-SI and Hetero-SI Configurational Stereoisomers of Bromadiolone in the Male Rat

(22) The following compositions concentrated in the Homo-SI or Hetero-SI configurational stereoisomers are prepared by one of the chromatography methods described above, in which the molar ratios are as follows: Homo-SI/Hetero-SI: 80/20; Homo-SI/Hetero-SI: 4/96.

(23) On D0 16 male laboratory rats (Sprague Dawley rats, Charles River, Saint germain sur l'Arbresle, France) having a body weight of the order of 200 g are tube-fed with a dose of the 80/20 mixture or the 4/96 mixture above in an amount of 3.8 mg of bromadiolone per kilogram of rat. The rats are kept alive by daily subcutaneous injection of a solution of vitamin K. On D+1, D+3, D+5 and D+10, 4 rats are anaesthetised with isoflurane and then sacrificed, and the livers are removed and frozen until analysed. The mean hepatic contents of the Homo-SI and Hetero-SI isomers of the male rats are analysed by HPLC and are given in Table 3 below.

(24) TABLE-US-00003 TABLE 3 Hepatic content, g/g Mixtures Bromadiolone D + 1 D + 3 D + 5 D + 10 Mixture Homo-SI 4.07 +/ 0.35 1.04 +/ 0.20 0.49 +/ 0.27 0.25 +/ 0.02 80/20 Hetero-SI 3.78 +/ 0.32 2.44 +/ 0.19 1.66 +/ 0.64 1.08 +/ 0.16 total 7.85 +/ 0.51 3.49 +/ 0.29 2.15 +/ 0.90 1.33 +/ 0.14 Mixture Homo-SI 0.27 +/ 0.21 0.10 +/ 0.09 0.05 0 4/96 Hetero-SI 14.69 +/1.82 9.98 +/ 3.20 9.93 +/ 1.01 2.40 +/ 1.17 total 14.96 +/ 2.0 10.08 +/ 3.3 9.99 +/ 1.0 2.39 +/ 1.16

(25) The hepatic content of total bromadiolone (7.85 g/g) of male rats treated with the 80/20 mixture (Homo-SI/Hetero-SI) of bromadiolone in an amount of 3.8 mg of bromadiolone per kilogram of rat is, in particular on D+1, lower than the hepatic content of total bromadiolone (14.96 g/g) of male rats treated with the 4/96 mixture (Homo-SI/Hetero-SI) on the same day. The 80/20 mixture is thus less persistent in the liver of the treated rats. These results demonstrate that the Homo-SI stereoisomer of bromadiolone has a hepatic persistence which is significantly lower than that of the Hetero-SI configurational stereoisomer of bromadiolone in the male rat.

(26) Hepatic Persistence of the Homo-SI and Hetero-SI Configurational Stereoisomers of Bromadiolone in the Female Rat

(27) The following compositions concentrated in the Homo-SI or Hetero-SI configurational stereoisomers are prepared by one of the chromatography methods described above, in which the molar ratios are as follows: Homo-SI/Hetero-SI: 80/20; Homo-SI/Hetero-SI: 20/80.

(28) The procedure with the female rats is the same as that with the male rats as described above. The mean hepatic contents of the Homo-SI and Hetero-SI isomers of the female rats are analysed by HPLC and are given in Table 4 below.

(29) TABLE-US-00004 TABLE 4 Hepatic content, g/g Mixtures Bromadiolone D + 1 D + 3 D + 5 D + 9 Mixture 80/20 Homo-SI 19.47 9.05 1.19 Hetero-SI 5.92 3.54 1.29 total 25.39 12.6 2.47 Mixture 20/80 Homo-SI 8.43 2.15 0.87 0.18 Hetero-SI 24.02 22.05 15.55 7 total 32.45 24.2 16.42 7.18

(30) The Homo-SI configurational stereoisomer of bromadiolone has a hepatic persistence which is significantly lower than that of the Hetero-SI configurational stereoisomer of bromadiolone in the female rat.

(31) Administration of a Composition Concentrated in Homo-SI by Multiple Ingestions (Multi-Feeding)

(32) A composition of bromadiolone comprising 96% Homo-SI and 4% Hetero-SI is administered daily by tube-feeding during three days (D0, D+1 and D+2) to groups of 3 male or female laboratory rats (Sprague Dawley rats of 200 g) in an amount of: 0.05 mg of bromadiolone per kilogram of rat, or 0.1 mg of bromadiolone per kilogram of rat, or 0.25 mg of bromadiolone per kilogram of rat, or 0.5 mg of bromadiolone per kilogram of rat, or 0.75 mg of bromadiolone per kilogram of rat.

(33) On these rats blood samples are taken and on D+3 the coagulation time (Quick time, expressed in seconds) of the plasma is measured by means of the Neoplastine CI Determination of Prothrombin Time kit (Diagnostica Stago, Asnire, France) by measurement on a Thrombotimer option 2 plus apparatus (Behnk Electronik, Norderstedt, Germany).

(34) The results obtained are given in FIG. 5, on which the hatched histograms represent the coagulation time of the female rats and the solid histograms represent the coagulation times of the male rats. By way of indication, the normal value for the coagulation time of untreated rats is of the order of 10 to 20 seconds.

(35) Repeated ingestion during 3 consecutive days of a daily dose of 0.25 mg of the mixture concentrated (96/4) in the Homo-SI configurational stereoisomer of bromadiolone is sufficient to obtain an anticoagulant effect, a haemorrhage in the rat (male or female) and its death.

(36) Bait Comprising 50 Ppm of Bromadiolone for Ingestion in Several Doses (Multi-Feeding) by Rodents

(37) A rodenticidal bait according to the invention is prepared by dispersing an amount of bromadiolone in a paste based on flour and vegetable fatty substance such that a bait comprising 50 mg of bromadiolone per kilogram of bait (50 ppm of bromadiolone) is obtained. Such a bait according to the invention is prepared with a composition (93/7) of bromadiolone comprising 93% Homo-SI and 7% Hetero-SI. By way of comparison baits comprising: 2% Homo-SI and 98% Hetero-SI (2/98), or 18% Homo-SI and 82% Hetero-SI (18/82) are also prepared.

(38) Rodents (15 Sprague Dawley (SD) rats, 9 males and 6 females, and 15 wild rats, 9 males and 6 females) are placed in individual cages. During 4 days (D1, D2, D3 and D4) each rat is supplied with an amount of bait sufficient to satisfy its appetite. At the end of these 4 days food free from bait is provided. The daily consumption of each bait is measured by weighing. On the death of the animal the liver of the dead animal is removed, frozen and stored until the hepatic content of the configurational stereoisomers of bromadiolone is analysed.

(39) The mean daily consumption of bait by the rats and the mean time to the death of the animals (mortality) are given in Table 5 below.

(40) TABLE-US-00005 TABLE 5 Homo-SI/ Mean weight of bait Hetero-SI consumed daily, g/day Time of death Mortality, % 93/7 11.45 D4 to D9 100 2/98 11.6 D4 to D8 100 18/82 12.25 D4 to D9 100

(41) A bait according to the invention (93/7) is eaten by the Sprague Dawley rats or by the wild rats with the same mean daily amount as the baits (2/98 or 18/82) not concentrated in the Homo-SI configurational stereoisomer of bromadiolone. A bait according to the invention (93/7) concentrated in the Homo-SI configurational stereoisomer of bromadiolone allows a mortality of 100% to be reached and therefore a maximum rodenticidal efficacy.

(42) The results of the hepatic assays are presented in Table 6 below, in which Homo-SI/Hetero-SI represents the amount (molar or by weight) of the homostereoisomer (Homo-SI) relative to the amount (molar or by weight) of the heterostereoisomer (Hetero-SI) in the bait made available to the rats and the term Residue represents the percentage of bromadiolone (Homo-SI and Hetero-SI) detected in the liver of the test rats relative to the total amount of bromadiolone ingested by each rat.

(43) TABLE-US-00006 TABLE 6 Homo-SI/ Hepatic content, g/g Hetero-SI Homo-SI Hetero-SI Residue, % 93/7 7.26 7.55 3.14 1.03 3.7 2.41 18/82 0.80 0.37 20.16 6.22 8.70 4.83 2/98 0 26.74 6.04 10.4 3.84

(44) The mean content of bromadiolone in the liver of the dead rats is 87 g per rat treated with the Homo-SI/Hetero-SI (93/7) bait according to the invention and 231 s per rat treated with the Homo-SI/Hetero-SI (2/98) bait.

(45) The percentage of residue of bromadiolone is minimised by using the bromadiolone 93/7 bait comprising a proportion in a majority of Homo-SI in comparison with using baits (2/98) and (18/82) comprising a proportion in a majority of Hetero-SI.

(46) A bait more concentrated in Homo-SI, that is to say a bait comprising the Homo-SI and Hetero-SI configurational stereoisomers of bromadiolone in a proportion of 95/5 or indeed 98/2, thus has the effect of limiting the residues of bromadiolone in the liver of rodents and their secondary toxicity to predators of the rodents or carrion eaters of corpses of rodents.

(47) Bait Comprising 15 Ppm of Bromadiolone for Ingestion in Several Doses (Multi-Feeding) by the Rodents

(48) Baits are prepared in the form of a paste based on flour and vegetable fatty substance comprising 15 mg of bromadiolone per kilogram of bait (15 ppm of bromadiolone). Such baits are prepared with compositions of bromadiolone comprising: 96% Homo-SI and 4% Hetero-SI(96/4), or 2% Homo-SI and 98% Hetero-SI(2/98).

(49) Rodents (10 Sprague Dawley (SD) rats, 5 males and 5 females) aged 8 weeks and of about 200 g are placed in individual cages. During 4 days (D1, D2, D3 and D4) each rat is supplied with an amount of bait sufficient to satisfy its appetite. At the end of these 4 days food free from bait is provided. The daily consumption of each bait is measured by weighing. On the death of the animal the liver of the dead animal is removed, frozen and stored until the hepatic content of isomers of bromadiolone is analysed.

(50) 1. Homo-SI/Hetero-SI (96/4) Bait Comprising 15 Ppm of Bromadiolone According to the Invention

(51) The mean amount of bait eaten daily by each of the 10 SD rats is 13.2 g (3.3 g). All the rats die between D4 and D7. The mean amount of bromadiolone ingested by the SD rats is 0.79 mg (0.19 mg), that is to say 0.76 mg (0.19 mg) of Homo-SI and 0.03 mg (0.008 mg) of Hetero-SI. The mean residual hepatic content of the total bromadiolone expressed in g of bromadiolone per gram of liver of rat on the death of the rat is 10.61 g/g. The mean residual hepatic contents of each of the Homo-SI and Hetero-SI isomers on the death of the rats are, respectively, 9.61 g/g and 0.99 g/g.

(52) 2. Homo-SI/Hetero-SI (2/98) Bait Comprising 15 Ppm of Bromadiolone

(53) By way of comparison, the mean amount of bait eaten daily by each of the 10 SD rats is 13.8 g (2.4 g). The rats die in general between D4 and D8, one rat dying on D10. The mean amount of bromadiolone ingested by the SD rats is 0.832 mg (0.145 mg), that is to say 0.016 mg (0.003 mg) of Homo-SI and 0.816 mg (0.143 mg) of Hetero-SI. The mean residual hepatic content of the total bromadiolone expressed in g of bromadiolone per gram of liver of rat on the death of the rat is 18.53 g/g. The mean residual hepatic contents of the Homo-SI and Hetero-SI configurational stereoisomers on the death of the rat are, respectively, 0.24 g/g and 18.29 g/g.

(54) A bait comprising a proportion in a majority of the homostereoisomer Homo-SI of bromadiolone thus allows limiting of the amount of residual bromadiolone in the corpses of the rodents which have eaten this bait while preserving a constant rodenticidal efficacy with respect to a bait comprising a proportion in a majority of the heterostereoisomer Hetero-SI of bromadiolone.

(55) It goes without saying that the invention may be subject to numerous embodiments and applications. In particular, a composition, a rodenticidal bait and a method of combating the target rodent pests are subject to an infinite number of variants both in the formulation of the bait and in the modes of implementation of the method.