WO1993007749A1 - Compositions de deratisation - Google Patents

Compositions de deratisation Download PDF

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Publication number
WO1993007749A1
WO1993007749A1 PCT/EP1992/002422 EP9202422W WO9307749A1 WO 1993007749 A1 WO1993007749 A1 WO 1993007749A1 EP 9202422 W EP9202422 W EP 9202422W WO 9307749 A1 WO9307749 A1 WO 9307749A1
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WIPO (PCT)
Prior art keywords
composition
days
treatment
rodents
day
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PCT/EP1992/002422
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English (en)
Inventor
Roger Valentine Short
Yuan Gao
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Akzo NV
Akzo Nobel NV
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Akzo NV
Akzo Nobel NV
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Publication of WO1993007749A1 publication Critical patent/WO1993007749A1/fr
Anticipated expiration legal-status Critical
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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N45/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds having three or more carbocyclic rings condensed among themselves, at least one ring not being a six-membered ring

Definitions

  • This invention relates to pest control generally and to chemical methods and composi- tions useful for reversibly or irreversibly sterilizing rodent populations specifically.
  • ⁇ -chlorohydrin has been found to-be of any use, and then only for rats. It has been shown to be highly toxic to male and female rats, killing 85% and leaving the adult male survivors ster ⁇ ile. ⁇ -Chlorohydrin is not palatable to rats, but microencapsulation increases its acceptability, although the consumption of a diet containing micro-encapsulated ⁇ -chlorohydrin was only half that of the basal diet, a- Chlorohydrin has no antifertility effect in female rats, or in mice of either sex.
  • Other compounds which have been considered for use include estrogens (e.g.
  • chemosterilants One problem with the use of chemosterilants is that, at a baiting station, one must ensure that the bait is highly palatable to the target species through- out the treatment period, especially when an abundance of alternative foods may exist. Rodents may develop a distaste for the prior art chemosterilants after prolonged administration.
  • the invention includes a method of controlling the number of animal pest species in a geographical area. Such a method includes distributing a composition con ⁇ taining an orally active progestogen associated with an ingestible carrier in the area.
  • the carrier is selected for its desirability or palatability to the pest species, its suitability for the local environment, and the ease with which it can be admixed or otherwise asso ⁇ ciated with the progestogen while still producing a bioavailable product.
  • the progestogen remains palatable to the members of the pest species when associated with the carrier.
  • the invention also includes new compositions which have been found to be eminently suited for use as chemosterilants in controlling rat and mouse plagues.
  • the compositions include orally active progestogenic compounds such as Org 5933, its derivatives, and mix ⁇ tures thereof incorporated into paraffin blocks.
  • the compositions may further contain cereal grains or other components which act as attractants for the particular rodent.
  • compositions are spread about infested areas and left for the infesting animals to ingest.
  • the compositions can be used in conjunction with an acute poisoning campaign, using conventional rodenti- cides or other poisons, with chronic provision of a chemosterilant to prevent the surviving animals from reproducing, thus decreasing the likelihood of spreading genetic resistance to the poison or chemosterilant.
  • the invention also includes methods of making and using such compositions.
  • Fig 1 Average daily consumption of steroid treated paraffin blocks vs. untreated control paraffin blocks by female rats in a free-choice feeding trial in the presence of their standard laboratory diet (unpaired t-test) .
  • Compounds useful for practicing the invention are orally active progestogenic compounds which are suffi ⁇ ciently potent to induce temporary or permanent steril ⁇ ity in rodents in the amounts used.
  • the compounds are highly palatable to rodents when incorporated into the paraffin.
  • Progestogens useful in the practice of the inven ⁇ tion include compounds disclosed in U.S. Patent No. 4,223,030 to de Winter, the contents of which are incor- porated by this reference. These compounds have the formula:
  • R is selected from the group consisting of F, OH and OR , and R is carbacyl of one to eighteen carbon atoms.
  • Org 5933 is 16 ⁇ -ethyl-21-hydroxy-rS ' 9 -19-norpregnadiene- 3,20-dione. Methods of preparing these compounds are described in U.S. Patent No. 4,223,030. Org 5933 is available from Organon International bv of Oss, NL.
  • Org 5933 at a concentration of 4 mg/kg paraffin block is highly palatable to female rats and mice, and at doses of about 420 ng/g body weight/day (daily inges- tion of about 20 grams of paraffin block containing 4 mg/kg of the compound) inhibits ovulation in rats within 3 to 4 days after the start of treatment. This infer ⁇ tility persists throughout the treatment period, but the animals conceived within 5 days after cessation of treatment.
  • a dose of about 930 ng/g body weight/day or Org 5933 was not completely effective in inhibiting ovula ⁇ tion in mice, but the females which were pregnant during treatment all gave birth to dead young.
  • this pro ⁇ gestogen was given to female rats and mice in the last days of pregnancy, the duration of gestation was signif ⁇ icantly prolonged, and most young were born dead; some of the females died in labour.
  • the great advantage of the progestogen Org 5933 is its high palatability and high potency.
  • the optimal concentration was found to be 4 milligrams per kilogram of paraffin block, although lower and higher amounts may be used.
  • the high palatability is shown by the fact that rats will consume up to 20 grams of block per day, and mice about 5 grams of block per day.
  • Another advantage of this particular progestogen is that there appears to be no aversion to it by pregnant or lactating animals. Thus all the individuals in a population could theoretically start to consume the com ⁇ pound at the commencement of baiting. This results in a suppression of estrus and ovulation within a few days in any animals that were cycling, and it would effectively prevent parturition or neonatal survival in any animals that were pregnant. The compound is also highly likely to inhibit spermatogenesis.
  • Paraffin blocks are ideally suited to chronic administration since the chemosterilant is not leached out by rain, or decomposed by exposure to sunlight, moisture, oxidation or bacterial contamination, and the block is unlikely to be consumed by humans, carnivores, herbivores or birds.
  • Paraffin blocks containing a mix ⁇ ture of cereal grains are highly palatable to rats and mice, and an ideal way of delivering a steroidal chemosterilant to rodent populations. No chance exists for the progestogen to leak out, and it will be pro ⁇ tected from decomposition in the block, thereby acting to stabilize the compound.
  • the blocks can, if desired, be secured inside baiting stations, e.g. drainpipes, to further reduce exposure to non-target species.
  • compositions are conveniently prepared by sim ⁇ ply melting the desired amount of a selected paraffin, ⁇ and then admixing therewith the desired progestogen.
  • Cereal grains and specific attractants e.g. other types of food or the urine of the particular rodent
  • Paraffins can be selected for their melting point to take into account local weather conditions.
  • the treatment period will preferably span at least one natural life span of the pest species. More prefer ⁇ ably the eradication period will extend over three or four generations of the pest species to insure complete erradication in the geographical area. In the case of rats and mice, this period will typically last one to two years.
  • inventive compositions are also eminently suited for use prophylactically to prevent a build up of significant numbers of the target species. It is pre- ferred to initiate long term preventative strategies to stop the population ever reaching plague proportions, and hence chronic baiting with a palatable composition has much to offer as a control strategy.
  • the composi ⁇ tions are then preferably used when the population is at a nadir, e.g. during winter,.
  • inventive compositions can be used in an alternate manner with a conventional acute poison ⁇ ing campaign.
  • the target population is first poisoned to reduce the numbers of infesting animals as rapidly and effectively as possible.
  • the survivors are then chronically exposed to the chemosterilant in a different bait, thereby not only preventing a population rebound, but also inhibiting the development of strains geneti ⁇ cally resistant to the initial poison.
  • the inventive compo ⁇ sitions also overcome the potential problem of secondary poisoning of non-target predators who might feed on the target species.
  • Another potential advantage of chemosterilants for rodent control relates to the humanitarian issue. Animal welfare groups are increasingly concerned about the way in which many conventional poisons kill rodents. A chemosterilant, which does not kill the animal, but rather stops it from breeding, therefore has some ethical advantages.
  • EXAMPLE I Ethinyl estradiol at a concentration of as low as 50 mg/kg paraffin blocks was so highly unpalatable to female rats that the amount of steroid ingested was not sufficient to interfere with their estrous cycles or inhibit ovulation.
  • Methyl testosterone at a concentration of 5000 mg/kg paraffin block although not as palatable as untreated blocks, was effective in inducing almost immediate infertility in female rats and mice at an ingested dose for rats of about 35 ⁇ g/g body weight/day. This infertility persisted throughout the duration of treatment, and lasted for several weeks after the cessa ⁇ tion of treatment. Male rats became infertile after 3 months of treatment due to suppression of spermatogene- sis.
  • Methyl testosterone was found to suffer from the disadvantage that the minimal effective concentration in the paraffin block needs to be about 5 grams per kilo ⁇ gram, giving a daily ingested dose of about 35 ⁇ g/g body weight for a rat. At this concentration, the bait begins to lose its palatability, although a rat will consume about 1.2 grams a day of the treated paraffin block. Any animals that are pregnant or lactating at the start of baiting show an aversion to the bait, and hence give birth to normal litters of young.
  • EXAMPLE III Org 5933 at a concentration of 4 mg/kg paraffin block was highly palatable to female rats and mice, and at doses of around 420 ng/g body weight/day was effective in inhibiting ovulation in rats within 3 to 4 days after the start of treatment. This infertility persisted throughout the duration of treat- ment, the animals conceived within 5 days after cessa ⁇ tion of treatment. A dose of about 930 ng/g body weight/day was not completely effective in inhibiting ovulation in mice, but those females which were pregnant during treatment all gave birth to dead young.
  • Paraffin wax (Paraplast, melting point 56°C, Monoject Scientific, St. Louis, MO, USA) was first melted in a oven at 65°C. The required amount of steroid was added to the melted paraffin which was stirred on a hot plate for 20 minutes. Then a mixture of blended cereals was added to give a ratio of 26% paraffin: 74% mixed cereals (wheat meal 29%, corn meal 28%, oat meal 28%, canary seed 7%, sugar 7% and defatted milk powder 1%) together with blue dye (3 ⁇ l dye: 1 gram cereal-paraffin mixture; Queen Fine Foods Pty. Ltd., Queensland, Australia) for the purpose of identifica ⁇ tion. The paraffin mixture was then poured into plastic dishes 7 cm 2 and 1 cm deep and allowed to set, to give individual paraffin blocks weighing approximately 35 grams when containing EE or MeT, or 25 grams when containing Org 5933.
  • Control paraffin blocks were prepared in the same way but without the addition of steroids.
  • Ethinyl estradiol Eighteen female rats were weighed and assigned at random to 6 groups of 3 animals per cage. In addition to the standard laboratory diet, they were given untreated paraffin blocks, or treated blocks containing either 50, 100, 200, 500 or 1000 mg of EE/kg for 3 periods of 6 days, separated by no-treatment periods of 2 days. This 2 day discontinuation is the conventional way of assessing re-acceptability of a bait.
  • the block was suspended inside the cage by a wire, and sawdust bedding was excluded from the area beneath the block by a wooden partition so that any chewed but non-ingested block could be weighed.
  • 18 female rats were weighed and assigned at random to 6 groups of 3 animals per cage.
  • they were given untreated paraffin blocks or paraffin blocks containing either 200, 500, 1250, 2500 or 5000 mg MeT/kg for 3 periods of 6 days, separated by no-treatment periods of 2 days.
  • Food intake and female fertility were monitored as in the EE experiment.
  • fertile males were caged with any females that had not produced young in the first 40 days after cessation of treatment, to determine when their fertility eventually returned.
  • any females that had become pregnant at lower dosages of MeT and were close to parturition were individually caged, and the dates of birth and number of young were recorded.
  • daily intake of the paraffin blocks was recorded. If any of the treated females pro ⁇ quiz young, on day 21 of lactation one female from each litter was randomly selected and kept for fertility tests in adulthood.
  • vaginal smears from the surviving young were examined daily for 6 days to see if estrou ⁇ cycles were occurring. The females were then paired with fertile males to test their fertility.
  • the left testis was decapsuled and homogenised in Triton buffer (0.9% sodium chloride, 0.05% Triton-X-100, 0.01% sodium azide) for 20 seconds using a tissue homogeniser (Ultra-Turrex, Janke and Kunkel GmbH & Co., KG, Ika-Werk Staufen, F.R.G). Nuclei of elongated sper- matids and spermatozoa in an aliquot of the suspension were counted using a haemocytometer. Spermatozoa from the caput, corpus and cauda of the left epididymis were also counted. Motility of the cauda sperm was assessed according to the World Health Organization Laboratory Manual (1987).
  • the progestogen Org 5933 In a study of non-preg ⁇ nant rats, 12 females were caged singly and vaginal smears were examined daily for 5 days to assess the nor- mality of their estrous cycles. Then they were weighed and randomly assigned to control or treatment groups of 6 animals which were given untreated paraffin blocks or paraffin blocks containing 4 mg Org 5933/kg for 38 days of the treatment, and during this period vaginal smears were also examined daily to see if ovulation had been inhibited. From day 9 of treatment, an untreated male was introduced into each cage overnight without being offered the paraffin blocks. Dates of birth and number of live young were recorded. On day 39, the treatment was stopped.
  • Ethinyl estradiol The average intake of treated blocks was very low in all treatment groups during the first two days of treatment; less than 1 g/rat/day vs. 17.4 g/rat/day of the untreated blocks, giving an aver ⁇ age consumption of EE of 0.08, 0.49, 0.92, 1.68 or 3.49 ⁇ g/g body weight/day respectively for the animals given paraffin blocks containing either 50, 100, 200, 500 or 1000 mg EE/kg.
  • day 3 and 4 consumption declined even further in the treatment groups, and after day 4, none of the treated animals consumed any of the blocks throughout the remainder of the treatment period.
  • the average daily consumption of the blocks for all treat ⁇ ment periods is shown in Fig. 1. Ingestion of EE during the first 2 days of treatment did not obviously affect the length of subsequent estrous cycles, as judged by vaginal smears.
  • Ethinyl estradiol is highly unpalatable to female rats in paraffin blocks, even at a concentration as low as 50 mg/kg.
  • the animals only consumed small amounts of the bait during the first 2 days of treatment, and the amount of steroid ingested was insufficient to interfere with subsequent estrous cycles or inhibit ovulation. Therefore EE is of no use as a chemosterilant for rat control.
  • Methyl testosterone The mean daily intake of the control and treated blocks containing different concen ⁇ trations of MeT by female rats is shown in Fig. 1. The animals given the higher concentration blocks showed decreased bait consumption.
  • the mean consumption of MeT ranged from 9.8 ⁇ 2.l (S.E.M.), 16.6 ⁇ 2.0, 17.5 ⁇ 2.5 or 15 ⁇ 2.7 ⁇ g/g body weight/day respectively for the animals given paraffin blocks containing either 200, 500, 1250 or 2500 mg MeT/kg. It was not possible to measure con ⁇ sumption of the paraffin blocks containing 5000 mg MeT/kg since after the first 2 days the animals gnawed the whole block into small pieces, scattering them around the cage. This phenomenon was also observed in other MeT experiments when a high concentration of steroid was used, but it was not observed at the lower MeT concentrations.
  • the average intake of the blocks during the first 2 days of treatment was 1.2 g/rat, giv ⁇ ing a consumption of 34.5 ⁇ g/kg body weight/day of MeT.
  • the mean intake of the standard laboratory diet for the controls or the treated animals given paraffin blocks containing either 200, 500, 1250, 2500, or 5000 mg MeT/kg was 1.6 ⁇ 0.3, 5.5 ⁇ 0.9, 7.2 ⁇ 0.5, 10.4 ⁇ 0.6, 10.8 ⁇ 0.7 or 12.7 ⁇ 1.1 g/rat/day respectively, indicating a high palatability of the untreated bait and showing that as the concentration of MeT in the blocks was increased, the animals increasingly preferred the standard laboratory diet to the blocks.
  • the progestogen Pro 5933 In a study of non-preg ⁇ nant rats, the mean daily consumption of paraffin blocks containing 4 mg/kg Org 5933 by females during the first 8 days of treatment was significantly higher (p ⁇ 0.01) than that of untreated blocks (Fig. l) giving an average consumption of 419 ng/g body weight/day of Org 5933.
  • mice showed normal estrous cycles, as judged by vaginal smears, before the treatment started, but 3 days after the start of treatment the smears from the treated females contained strings of mucus containing large numbers of metestrous-type cells. The first 3 days of treatment failed to prevent females progressing from poestrous to estrous smears.
  • Treatment was stopped after -65 days, and the fol ⁇ lowing day fresh males were introduced.
  • the 6 controls all gave birth to live young 29.712.0 days later; 4 out of 5 of the 0.4 mg/kg group gave birth to live young 26.511.9 days later, and all 5 of the 4 mg/kg group gave birth to live young 22.410.7 days later, a significant advance on the controls (p ⁇ 0.05, unpaired t-test).
  • progestogen was less effective in mice than in rats for inhibiting ovulation, but there was a pronounced adverse effect on parturition and neonatal survival. As in rats, the effects of the steroid were rapidly reversible following cessation of treatment.
  • mice All the 6 control mice gave birth to litters of live young, whereas 5 of the 6 treated females gave birth to dead litters. None of the females died in labour. One treated mouse gave birth to live young on day 20 of pregnancy. She then successfully suckled them until day 5 of lactation, when the experiment was terminated.

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Steroid Compounds (AREA)

Abstract

L'invention concerne des compositions stérilisantes stables utiles dans le contrôle des populations parasites, comprenant un composé progestatif actif oral selon la formule (I), dans laquelle R1 est sélectionné parmi le groupe comprenant OR2, OH et F, et R2 est un carbacyle avec 1 à 18 atomes de carbone et une paraffine solide. Les compositions sont d'un goût agréable pour les espèces de rongeurs et provoquent également la stérilité temporaire ou permanente chez ces rongeurs. De préférence les compositions comprennent du 16$(a)-éthyl-21-hydroxy-δ4,9-19-norprégnadiène-3,20-dione en quantité de 0,4 à 20 milligrammes par kilogramme de la composition. Un procédé de contrôle du nombre d'animaux parasites dans une zone comporte la distribution des compositions décrites dans la zone. Les animaux mangeant les parasites ne sont pas affectés par les progestatifs décrits, provoquant ainsi moins de problèmes dans la chaîne alimentaire.
PCT/EP1992/002422 1991-10-23 1992-10-16 Compositions de deratisation Ceased WO1993007749A1 (fr)

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EP91202739.8 1991-10-23
EP91202739 1991-10-23

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WO1993007749A1 true WO1993007749A1 (fr) 1993-04-29

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994026105A1 (fr) * 1993-05-14 1994-11-24 Orion-Yhtymä Oy Procede permettant de lutter contre des animaux nuisibles
WO2017201614A1 (fr) 2016-05-23 2017-11-30 Gerhard Gries Compositions et procédés comprenant des composés de phéromone d'androsténone, de testostérone, de progestérone et d'œstrogène
US12207642B2 (en) 2018-05-04 2025-01-28 Oms Investments, Inc. Attractants for mice

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655889A (en) * 1969-12-09 1972-04-11 Warner Lambert Co Quinestrol as a rodent control agent
EP0001308A1 (fr) * 1977-09-26 1979-04-04 Akzo N.V. Delta-4,9-pregnanes, leur utilisation comme agents progestatifs et/ou inhibiteurs d'ovulation et leur procédé de préparation
DE2940132A1 (de) * 1978-10-10 1980-04-24 Upjohn Co Steroide
US4252800A (en) * 1979-10-05 1981-02-24 United States Of America 7α-methylnorethindrone enanthate and its use in long term suppression of fertility in female mammals
CH654980A5 (en) * 1982-03-17 1986-03-27 Inst Igiena Sanatate Publica Poison rat bait and process for its preparation
GB2184020A (en) * 1985-12-12 1987-06-17 Rhodic Sa Rodenticidal bait
FR2641943A1 (fr) * 1989-01-25 1990-07-27 Rouquet Colette Produit pour la lutte contre les rats et autres vertebres nuisibles

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3655889A (en) * 1969-12-09 1972-04-11 Warner Lambert Co Quinestrol as a rodent control agent
EP0001308A1 (fr) * 1977-09-26 1979-04-04 Akzo N.V. Delta-4,9-pregnanes, leur utilisation comme agents progestatifs et/ou inhibiteurs d'ovulation et leur procédé de préparation
DE2940132A1 (de) * 1978-10-10 1980-04-24 Upjohn Co Steroide
US4252800A (en) * 1979-10-05 1981-02-24 United States Of America 7α-methylnorethindrone enanthate and its use in long term suppression of fertility in female mammals
CH654980A5 (en) * 1982-03-17 1986-03-27 Inst Igiena Sanatate Publica Poison rat bait and process for its preparation
GB2184020A (en) * 1985-12-12 1987-06-17 Rhodic Sa Rodenticidal bait
FR2641943A1 (fr) * 1989-01-25 1990-07-27 Rouquet Colette Produit pour la lutte contre les rats et autres vertebres nuisibles

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
E.HEFTMANN AND E.MOSETTIG 'Biochemistry of Steroids' 1960 , REINHOLD PUBLISHING CORPORATION , NEW YORK *
L.MARTINI AND A.PECILE ( ED. ) 'Hormonal Steroids: Biochemistry, Pharmacology, and Therapeutics, Volume 2' 1965 , ACADEMIC PRESS , LONDON *
V.H.T.JAMES AND L.MARTINI 'Hormonal Steroids' 1971 , EXCERPTA MEDICA , AMSTERDAM *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994026105A1 (fr) * 1993-05-14 1994-11-24 Orion-Yhtymä Oy Procede permettant de lutter contre des animaux nuisibles
US5672628A (en) * 1993-05-14 1997-09-30 Orion-Yhtyma Oy Method for controlling a pest population
WO2017201614A1 (fr) 2016-05-23 2017-11-30 Gerhard Gries Compositions et procédés comprenant des composés de phéromone d'androsténone, de testostérone, de progestérone et d'œstrogène
EP3462875A4 (fr) * 2016-05-23 2020-01-08 Gries, Gerhard J. Compositions et procédés comprenant des composés de phéromone d'androsténone, de testostérone, de progestérone et d' strogène
AU2017269610B2 (en) * 2016-05-23 2021-11-11 Gerhard Gries Attractants for rodents
US11185077B2 (en) 2016-05-23 2021-11-30 Gerhard Gries Attractants for rodents
US12207642B2 (en) 2018-05-04 2025-01-28 Oms Investments, Inc. Attractants for mice

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Publication number Publication date
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