GB1600968A - Safeguarded toxic chemical compositions containing an emetic - Google Patents

Description

(54) SAFEGUARDED TOXIC CHEMICAL COMPOSITIONS CONTAINING AN EMETIC (71) We, IMPERIAL CHEMICAL INDUSTRIES LIMITED, Imperial Chemical House, Millbank, London SWIP 3JF, a British Company, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to safeguarded chemical compositions, and in particular to safeguarded pesticidal chemical compositions.

There is, at the present time, in industrial, agricultural and domestic environments, a wide exposure of consumers throughout the world to chemical substances that are potentially toxic to human beings. Some of these substances are of necessity toxic to certain forms of life, for example pesticides and disinfectants.

Pesticides, when used with due care, and in accordance with governmentally approved codes of practice and the manufacturers' or suppliers' instructions, present no hazard to human life. However, in spite of efforts to encourage safe handling practices, instances of misuse do occur resulting in the deaths of human beings. These include cases where liquid pesticides are swallowed, often by being mistaken for beverages.

Equally tragic, and more numerous, are deaths resulting from suicides caused by the deliberate ingestion of pesticides, in particular insecticides, or of chemical household products and drugs.

The present invention provides a means whereby toxic chemicals are made safer by including in them small quantities of an emetic substance. Then, if the toxic product is swallowed in dangerous quantities, emesis is likely to occur; this can result, in some cases, in rapid removal of the chemical composition from the stomach before lethal amounts of the chemical have been assimilated by the body.

There are a number of reasons why presently known substances having emetic properties are not generally suitable for widespread use in admixture with toxic chemicals as a means for reducing the risk of poisoning. Known emetics may be unsuitable for administration to human beings for a number of reasons; they may not be suitable for oral administration and may have to be given by another route, e.g. intravenous injection; they may be physically or chemically unstable over reasonable periods of time, alone or when in admixture with the toxic chemical; they may be per se environmetally unacceptable; they may have unsuitable toxicological properties: they may have highly undesirable side-effects; or they may be completely insoluble. In this respect the unfavourable properties of several known emetics are referred to in "Treatment of Common Acute Poisonings", edited by H. Matthew and A. A. H. Lawson, published by Churchill Livingstone, Edinburgh and London, 1972, at pages 21-22. Emetic drugs such as apomorphine are dangerous as they may induce protracted vomiting and shock. Apomorphine is unstable in air, oxidising readily, so that it is supplied as ampules for injection.

Syrup of ipecacuanha has an emetic effect which is too slow and too uncertain, even at nearly lethal dosage rates. Furthermore the emetine content of the ipecacuanha may be absorbed and itself produce toxic effects.

Copper and antimony containing preparations, being metal salts and not biodegradable, could constitute an unacceptable environmental problem if the metal salts, in admixture with a pesticide, were to be regularly sprayed in the environment; in any event antimony is a highly poisonous substance in its own right. Matricaria comprises the ground-up heads of camomile plants and is unsuitable by being insufficiently soluble.

Rodenticide formulations have been proposed, for example as in Swiss Patent No. 348003 and French Patent Application No. 2,067,846, which include such known emetic substances.

The s-triazolopyrimidine compounds deployed in the safeguarded toxic compositions, and method, of the present invention, are themselves described and claimed in our U.K. Patent No. 1,234,635 and also in our U.S.A. Patent No.

3,689,488. Methods for preparing the compounds are recited therein. The description of the latter patents is incorporated herein by reference. The foregoing patent specifications describe the anti-bronchospasmodic, anti-allergic and other pharmacologically useful properties of the compounds, but do not disclose their emetic properties.

In our copending application U.K. Application No. 15584/76. Serial No.

1,507,407 there are described and claimed compositions comprising a herbicidal bipyridylium quaternary salt and a triazolo[l,5-alpyrimidine derivative, which compositions, if swallowed, tend to induce emesis, and thereby, expulsion of the composition. A corresponding patent application in the United States of America has given rise to U.S. Patent No. 4,046,552.

At the time when the above-mentioned U.K. Patent Application No. 15584/76 was filed it was believed that the novel and particular compositions disclosed and claimed therein were an unusual, instances of compatibility and effectiveness; and that it was in no way obvious to extend the invention of the combination of emetic substance and herbicidal bipyridylium quaternary ion (e.g. paraquat) or salt so as to safen other toxic chemicals from oral ingestion, because the foregoing herbicides, when ingested are only slowly absorbed into the bloodstream by humans. Thus it was believed that there would be, in addition to a lack of speed of action against fast-acting poisons, some chemical and/or biological interference, or other incompatibility, between at least some toxic chemicals and the emetics.

It has now been found, surprisingly, that even fast-acting highly toxic substances, such as the intensely poisonous organo-phosphorus pesticides parathion (having an LD50 of only 3 to 13 mg/kg in the rat) and malathion, can be substantially safened against poisoning by oral ingestion by admixing them with the emetic substances. This most remarkable discovery is supplemented by the further finding that the emetic substances can be readily formulated with a wide variety of toxic chemical substances without problems of incompatibility. Thus there appear to be few formulation or storage problems, and few instances of even a small degree of interference with the biological effects and mode of action of the emetic substances.

The wholly unique nature of the present invention is supported by the further unexpected finding that the emetic substances, in addition to being capable of inducing emesis, possess safening action by delaying uptake by the blood of a toxic chemical from the stomach and digestic tract (and do so even if emesis does not take place), by reducing the rate of gastric emptying. Gastric emptying generally means the passage from the stomach into the small intestine where digested food and most ingested foreign compounds, e.g. drugs and pesticides, are absorbed into the body system. Thus the results of experiments with rats and mice (non-vomiting species) and monkeys (vomiting species) has shown gastric emptying to be significantly delayed at sub-emetic dosages. The speed, and dual mode, of action of the emetic substances with respect to mammals in this regard is a novel and surprising discovery.

According to the present invention there is provided an emetic chemical composition comprising a toxic chemical substance as hereinafter defined (other than a herbicidal bipyridylium quaternary salt or a sympathominetic amine) and an emetic which is an s-triazololl,5-ralpyrimidine derivative of thc formula:--

Formula I wherein R1 is hydrogen or an alkyl radical containing from 1 to 4 carbon atoms, or an acyl radical of the formula R4. CO-- wherein R4 is an alkyl or alkoxy radical containing from 1 to 4 carbon atoms or a chlorophenyl radical, R2 is an alkyl or alkenyl radical containing from I to 4 carbon atoms, or a cyclopentyl radical, and R3 is an alkyl radical containing from 1 to 4 carbon atoms; or an addition salt thereof; the ratio of emetic to toxic chemical in the composition being such that a toxic dose of the composition tends to induce emesis. The s-triazolo [1,5alpyrimidine ring structure is numbered as shown below:

Particular derivatives of 5 - oxo - 4,5 - dihydro - s - triazolo[l,5 alpyrimidine of use in the practice of the invention are: 2-amino-6-methyl-4-n-propyl 2-acetamido-6-methyl-4-n-propyl 6-methyl-4-n-propyl-2-n-propylamino- 2-amino-6-methyl-4-n-butyl 2-amino-6-methyl-4-allyl- 2-isopropylamino-6-methyl-4-n-propyl 2-p-chlorobenzamido-6-methyl-4-n-propyl- 2-ethoxycarbonylamino-6-methyl-4-n-propyl- 2-amino-4,6-di-n-propyl 2-amino-6-methyl-4-s-butyl 2-amino-6-methyl-4-cyclopentyl 2-amino-6-n-butyl-4-n-propyl Whilst the first, second, third and ninth derivatives listed above are preferred, and especially useful triazolo-pyrimidine for use in the compositions of the invention is the first derivative, namely 2 - amino - 6 - methyl - 5 - oxo - 4 - n propyl - 4,5 - dihydro - s - triazolo[l,5 - a]pyrimidine having the formula:

Formula II This compound is typical of the foregoing s-triazolopyrimidines and has an LD > o value of 160 mg/kg (oral, male rats) which is indicative of the highly favourable toxicities which can be expected for the class, bearing in mind the extremely small amounts it is necessary to use in compositions according to the present invention because of their powerful emetic properties.

As used in this specification the term "toxic chemical substance" is intended to refer to chemicals having a utility in industry, agriculture or the home which are toxic to human beings when orally ingested. The term does not include toxic chemicals for which, upon ingestion, the induction of emesis is inadvisable on medical grounds, for example corrosive poisons such as concentrated acids or alkalis.

Preferred compositions according to the invention are compositions comprising a pesticide.

The term "pesticide" refers to biologically-active compositions containing chemicals which are effective in killing or repelling undesirable pests or preventing or controlling their growth. The pests may be plants, insects, mites, rodents, nematodes, microorganisms. algae, fungi, bacteria, viruses and the like. The term "pesticide" may also refer to compositions or chemicals which control or modify the rate of growth, or growth or mode of development, of desirable plant species.

All these chemicals and compositions are commonly known as herbicides, fungicides, insecticides, nematocides, miticides, molluscicides, anti-viral agents algicides. bactericides, plant growth regulants, defoliants, insect attractants and repellents, and the like.

Particularly preferred compositions according to the invention are compositions comprising an insecticide; and, more particularly, compositions comprising organo-phosphorus, carbamate, or oxime carbamate insecticides.

Examples of these classes of insecticides for use in the practice of the invention are set out in the Table below.

Common Name Chemical Name Carbaryl l-naphthyl methylcarbamate Parathion-Methyl dimethyl 4-nitrophenyl phosphorothionate Malathion S-[l ,2-di(ethoxycarbonyl)ethyll dimethyl phosphorothiolothionate Diazinon diethyl 2-isopropyl-6-methyl-4 pyrimidinyl phosphorothioate Fenitrothion dimethyl 3-methyl-4-nitrophenyl phosphorothioate Azinphos-Ethyl diethyl S[(4-oxo-1,2,3-benzotriazin 3(4H)-yl)methyl]phosphorothiolo thionate Parathion diethyl 4-nitrophenyl phosphorothionate Phorate diethyl S-(ethylthiomethyl) phosphoro thiolothionate Carbofuran 2,3-dihydro-2,2-dimethylbenzofuran 7-yl methylcarbamate Monocrotophos dimethyl cis-l-methyl-2-methyl carbamoylvinyl phosphate Dimethoate dimethyl S-methylcarbamoylmethyl phosphorothiolothionate Methomyl l-(methylthio)ethylideneamino methylcarbamate Aldicarb 2-methyl-2-(methylthio)propylidene- amino methylcarbamate.

Oxamyl N,N-dimethyl-a-methylcarbamoyloxy- imino-a-(methylthio)acetamide.

Dichlorvos dimethyl 2,2-dichlorovinyl phosphate.

Further compositions according to the invention comprise pesticides which behave as "uncouplers of oxidative phosphorylation" that is to say pesticides having a biological mode of action which interferes with the production of ATP from ADP in living cells. Nitro-substituted phenols such as 4,6-dinitro-o-cresol, common name DNOC, behave in this manner.

Yet further compositions according to the invention comprise an insecticidal pyrethroid. By the term 'pyrethroid' is meant an insecticidal ester of a suitably substituted cyclopropane carboxylic acid or suitably substituted arylacetic acid and a suitably substituted alcohol or cyanhydrin. Preferably the configuration of the cyclopropane carboxylic acid is IR, cis- and that of the arylacetic acid, alcohol, and cyanhydrin is S. Particular examples of pyrethroids for use in the practice of the invention are: S - 3 - phenoxy - a - cyanobenzyl (IR, cis) - 2 - (2,2 - dibromovinyl) - 3,3 dimethylcyclopropane - 1 - carboxylate, which has the common name 'Decamethrin'; 3 - Phenoxybenzyl 2 - (2,2 - dichlorovinyl) 3,3 - dimethylcyclopropan - I carboxylate, having the common name 'Permethrin'; 3 - Phenoxy - a - cyanobenzyl - 2- (2,2 - dichlorovinyl)- 3,3 dimethylcyclopropan - 1 - carboxylate, having the common name 'Cypermethrin'; 3 - Phenoxy - a - cyanobenzyl - 4 - chlorophenyl - a' - isopropyl phenylacetate, having the common name 'Phenovalerate'; and 3 - Phenoxy - a - cyanobenzyl - 2,2,3,3 - tetramethylcyclopropane - I - carboxylate.

A molluscicidal composition according to the invention comprises metaldehyde.

Chemical substances other than pesticides to which the invention may be applied may be found in industry and in the home. Examples of such substances are anti-freeze mixtures comprising ethylene glycol: brake fluids: petroleum tar distillates such as "Jeyes Fluid" (the words "eyes Fluid" are a Trade Mark) and creosote; carbolic acid preparations; bleaching fluids such as hypochlorites; and industrial solvents such as dry-cleaning solvents and industrial methylated spirit comprising methyl, ethyl, or isopropyl alcohols and preparations, e.g. hair sprays, containing them. The invention may also be applied to drugs, and in particular to drugs such as sleeping pills (e.g. barbiturates) which are popular as a means of attempting suicide. In compositions intended to be taken orally the concentration of emetic must not be so high that a normal dose has emetic effects.

The amount of the toxic chemical substance present in the compositions of the invention is generally from 0.1 to 99.9% by weight.

The compositions of the invention may be solids, e.g. granules or pellets, or liquids, e.g. aqueous solutions.

In a preferred aspect the invention provides a concentrated pesticidal composition comprising a liquid pesticidal composition and a triazolo-pyrimidine as hereinbefore defined. Preferably the pesticide is an insecticide.

The amount of pesticide present in the liquid composition is usually from 0.01 to 6.0 pounds per Imperial gallon (1 gram to 600 grams per litre) and preferably from 0.5 to 4.0 pounds per gallon (50 to 400 grams per litre).

Preferably the pesticidal composition also comprises a surface active agent.

Surface-active agents may be cationic, non-ionic or anionic. Examples of non-ionic surface-active agents for use in pesticidal compositions of the invention include the condensation products of ethylene oxide with alkyl phenols such as octylphenol, nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, for example sorbitan monolaurate; the condensation products of the said partial esters with ethylene oxide, and the lecithins. Examples of cationic surface-active agents include quaternary salts and condensates of ethylene oxide with amines, for example the substances sold under the Trade Marks "Ethomeen", "Ethoduomeen", Duoquad" and "Arquad".

The emetic properties of the invention compositions are primarily determined by the amount of triazolopyrimidine they contain. In deciding the most appropriate amount of triazolopyrimidine (I) to use in any composition, regard must be had to the efficacy of the chosen triazolopyrimidine relative to the toxicity of the chemical substance. The amount of triazolopyrimidine to be included is such that the composition contains sufficient of the triazolopyrimidine (I) to give it emetic properties.

Compositions according to the invention conveniently contain from 0.01 to 5 parts by weight of the triazolopyrimidine (I) per 100 parts of the composition. To obtain the necessary balance between toxic and emetic properties the proportion of toxic chemical may, if appropriate, be reduced, and the proportion of inert diluent or carrier increased.

In a further aspect the invention provides a method of avoiding or reducing the toxifying effect of chemicals ingested by a mammal other than a human, which comprises administering to the affected mammal an emetically effective amount of an s-triazolo-[ 1 5-alpyrimidine derivative as defined above.

Although the actual treatment of humans with the emetic separately or with the invention compositions falls outside the scope of the invention claimed, it is possible, nontheless, to use the emetic separately, i.e. on its own, to induce emecies in a human who has injected a toxic substance.

The invention is illustrated by the following Examples, Nos. 1 to 14 of which are pesticide formulations of varying kinds: Nos. 14 to 26 illustrate other toxic chemical compositions; and Examples 27 and 28 illustrate, respectively, the efficacy of safeguarded compositions according to the invention, and the delay in gastric emptying caused by the emetic. In the Examples proportions of constituents of compositions are in grams unless otherwise stated.

EXAMPLE 1 This Example illustrates a composition according to the invention which comprises 2 - amino - 6 - methyl - 5 - oxo - 4 - n - propyl - 4,5 - dihydro - 5 triazololl.5 - alpyrimidine, (hereinafter referred to as "Emetic of Formula II") and Malathion.

O(, w/v Malathion 90 Emetic of formula II above 0.05 Aromasol H (a solvent mixture to 100 ml of alkyl benzenes) EXAMPLE 2 This Example illustrates a composition according to the invention which is an emulsifiable concentrate comprising parathion.

"' w/v Parathion 50 Emetic of formula II 0.05 Arylan CA (calcium dodecyl benzene sulphonate) 5 Lubrol N13 (a condensate of 1 mole of nonyl phenol with 13 moles of ethylene oxide 5 Xylene to 100 ml EXAMPLE 3 This Example illustrates a wettable powder containing 25% on a weight/weight basis, of the insecticide malathion. The constituents, and proportions, are as follows: % w/w Malathion 25 Emetic of formula II 0.03 Kaolin clay 28.5 Polyfon H (a polymeric sodium lignin sulphonate) 3.0 Pluronic F68 (a polypropylene polyethylene block copolymer) 2.0 China clay to 100 grams The constituents are mixed together and then ground.

A similar formulation was prepared using instead of the emetic of formula III twice the amount of the emetic of formula:

EXAMPLE 4 This Example illustrates a composition according to the invention which comprises a herbicide.

% w/w Emetic of formula II 0.05 Potassium 2,4-dichlorophenoxy acetate 40 Water to 100 ml EXAMPLE 5 This Example illustrates a miscible liquid formulation containing the insecticide dimethoate.

," wlv Dimethoate 40 Lubrol N13 Emetic of formula II 0.05 Ethyl cellusolve to 100 ml EXAMPLE 6 This Example illustrates a wettable powder formulation containing an insecticide. The constituents were mixed and ground.

" , wlw Azinphos ethyl 25 Emetic of formula II 0.5 Dispersol T (a mixture of sodium sulphate and a condensate of formaldehyde with the sodium salt of naphthalene sulphonic acid) 5 % w/v Vancell E (lignin sulphonate-as sodium salt) 5 Silica K320 10 China clay to 100 grams In a further, similar, formulation the emetic of formula III was replaced by twice the amount of the emetics having the following formulae:

EXAMPLE 7 This Example illustrates an emulsifiable concentrate containing 20% (on a weight/volume basis) of diazinon.

% w/v Diazinon 20 Emetic of formula II 0.05 Arylan CA (calcium dodecyl benzene sulphonate) 5 Lubrol N13 (a condensate of 13 moles of nonyl phenol with 13 moles of ethylene oxide) 5 Epichlorhydrin 3 Aromasol H to 100 ml In exactly the same manner, using the same proportions of constituents, similar preparations were made replacing the diazinon with (a) 50 g of dichlorvos and (b) 175 g of phorate.

EXAMPLE 8 This Example illustrates a flowable liquid concentrate containing 50% of the insecticide carbaryl. The proportions (on a weight/volume basis) of the various constituents are as follows: % w/v Carbaryl 50 Emetic of formula II 0.03 Polyfon H (a polymeric sodium lignin sulphonate dispersing agent) 5 Bentonite (sodium montmorillonite) 1* Water to 100 ml The carbaryl was finely ground and dispersed in about 90% of the water containing the emetic and Polyfon H. The bentonite was separately dispersed in about 10 , of the water and then incorporated into the previously prepared mixture.

EXAMPLE 9 This Example illustrates a granular pesticide formulation.

% wiw Aldicarb 5 Emetic of formula II 0.05 Gypsum 10/40 B.S. mesh granules to 100 grams The aldicarb is dissolved in a solvent and then sprayed onto the gypsum in a fluid bed granulator.

EXAMPLE 10 This Example illustrates a water-soluble powder formulation of the pesticide methyl.

% w/w Methomyl 60 Emetic of formula II 0.05 Aerosol OT/B (dioctyl sodium sulphosuccinate adsorbed onto urea) 5 Sodium acetate to 100 grams The constituents were mixed and ground together.

EXAMPLE 11 This Example illustrates a soluble-liquid formulation of a pesticide.

%w/v Oxamyl 20 Emetic of formula II 0.03 Ethylene glycol 10 Water to 100 ml EXAMPLE 12 This Example illustrates an emulsifiable concentrate containing fenitrothion.

% w/v Fenitrothion 50 Emetic of formula II 0.05 Monolan M (an ethylene oxide/propylene oxide copolymer) 4.5 Ethylan A.C. 3.0 Arylan B.A. 7.5 (a blend of anionic and non-ionic surface active agents supplied by Lankro Chemicals Ltd) Epichlorhydrin 3.0 Aromasol H to 100 ml EXAMPLE 13 This Example illustrates an extruded rodenticide bait pellet.

% w/v Sodium chloride 0.5 Monosodium glutamate 0.5 China clay 5.0 Pigments 0.2 Whole ground wheat to 100 grams The above mix is extruded into granules.

The granules are then sprayed with a concentrate containing: % w/v Rodenticide (difenacoum or brodifacoum) 0.25 Emetic of formula II 0.05 Triethanolamine 3 4-Nitrophenol 2.5 Polyethylene glycol (Molecular weight 200) 3 Propylene glycol to 100 ml to a level of 2?,', w/w on the granules. Alternatively the formulations above are mixed as one and extruded to obtain pellets.

Difenacoum is: 3 - (3 - biphenyl- 4- yl- 1,2.3.4- tetrahydro - 1 - naphthyl) - 4 - hydroxycoumarin.

Brodifacoum is: 3 - 13 - (4' - bromobiphenyl - 4 - yl) - 1,2,3,4 - tetrahydro - - naphthyll - 4 - hydroxycoumarin.

EXAMPLE 14 This Example illustrates a rodenticide preparation in the form of a contact powder which rodents pick up upon their fur and ingest whilst preening themsclvcs.

?o wkv Emetic of formula II 0.05 Difenacoum rodenticide 0.2 Tale to 100 grams Instead of tale the following were used (singly or in admixture); basic slag, china clay and kieselguhr in further formulations, the difenacoum being replaced by the rodenticide brodifacoum. Both these latter rodenticide names are common names.

EXAMPLE 15 This Example illustrates a composition according to the invention which comprises a pharmaceutical chemical.

% w/v Phenobarbitone 50 mg Dextrose 50 mg Emetic of formula II 0.2 mg The composition was produced by admixture of the ingredients and then formulated in the form of a tablet.

EXAMPLE 16 This Example illustrates a composition according to the invention which comprises a pharmaceutical chemical.

% w/v Aspirin (acetylsalicylic acid) 100 mg Emetic of formula II 0.1 mg The composition was produced by admixture of the ingredients and then formulated in the form of a tablet.

EXAMPLE 17 This Example illustrates a composition according to the invention which comprises an anti-freeze mixture.

% w/v Emetic of formula II 0.05 Sodium Tetraborate 10 H2O 3 Phosphoric acid Triethanolamine 2 Benzotriazole 0.2 Ethylene glycol to 100 ml EXAMPLE 18 This Example illustrates a composition according to the invention comprising an anti-freeze mixture.

% w/v Emetic of formula II 0.05 Borax 3.0 Phosphoric acid 0.95 Triethanolamine 2.1 Benzotriazole 0.2 Water 4 Diethylene glycol to 100 ml EXAMPLE 19 This Example illustrates an industrial "methylated spirits" formulation (a) and "methylated spirit" for home use (B).

?4 w/v A. Methyl alcohol 4.9 Emetic of formula II 0.05 Pyridine base 0.5 Ethyl alcohol to 100 ml V w/v B. Methyl alcohol 45 Emetic of formula II 0.05 Mineral naphtha 0.4 Pyridine bases 0.5 Methyl violet 0.0002 Ethyl alcohol to 100 ml EXAMPLE 20 This Example illustrates a washing-up liquid.

? w/v Sodium linear alkyl benzene sulphonate 15 Sodium linear alcohol (C12-15) ether sulphate containing 3 moles of ethylene oxide 5 Coco fatty acid diethanolamide Perfume 0.1 Dye 0.01 Ethyl alcohol 5 Sodium chloride 6 Emetic of formula II 0.02 Water to 100 ml EXAMPLE 21 This Example illustrates a liquid metal polish preparation.

V w/w Emetic of formula II 0.05 Diglycol stearate 5 Water 20 Oleic acid 4 Mineral oil 5 Industrial methyl alcohol (IMS) ("methylated spirits") 10 Ammonia (0.910) 3 Ground chalk 25 Water to 100 grams The diglycol stearate and emetic are dissolved in the water and to this solution are added an emulsion of a mixture of the oleic acid, mineral oil and IMS to which the ammonia is added. The ground chalk is worked-in with vigorous stirring and then, in small amounts at a time, the remainder of the water, continuing vigorous stirring.

EXAMPLE 22 This Example illustrates a pine oil disinfectant.

% w/v Emetic of formula II 0.05 Pine oil 80 Sulphate castor oil 19.05 EXAMPLE 23 This Example illustrates a cresol disinfectant preparation for industrial or domestic use. w/w Rosin 24 Caustic soda 7 Creosote oil 24 Carbolic acid 0.4 Emetic of formula II 0.05 Water to 100 grams EXAMPLE 24 The following Example illustrates an after-shave formulation containing a safe-guarding proportion of the emetic of formula 11.

% w/w Glycerin 5 Alum Zinc sulphophenolate 0.5 Propyl alcohol 10 Rose water 10 Perfume 0.5 Emetic of formula II 0.05 Ethyl alcohol (96%) to 100 grams EXAMPLE 25 The following Example illustrates an Eau de Cologne formulation containing the emetic of formula III above.

V w/v Emetic of formula II 0.05 Lemon oil 0.9 Bergamot oil 0.8 Orange oil, sweet 0.25 Lavender oil 0.20 Mandarin oil 0.16 Petitgram oil, Grasse 0.16 Benzoic resinoid 0.14 Neroti oil, original 0.14 Orange oil, bitter 0.14 Lime oil 0.14 Rosemary oil 0.05 Eugenol 0.03 Cumene aldehyde 0.025 Muscated sage oil 0.015 Hyssop oil 0.005 Cardamon oil 0.005 Iris concentrate 0.005 Alcohol (96%) 86.9 Distilled water to 100 EXAMPLE 26 This Example illustrates a liqui

TABLE I

Rate of Dosage in Milligrams Per Animals in Time to Emesis Survival Kilogram of Live Which Emesis in Hours Number After Dosage Substance Body Weight Took Place and Minutes 14 Days Parathion only 200 1 1 hour 0 Malathion only 500 1 1 hour 0 35 minutes Parathion 200 2 6 minutes 2 Emetic of Formula II 2 and 10 minutes (admixture) respectively Malathion 2000 2 2 minutes 2 Emetic of Formula II 2 and 10 minutes (admixture) respectively The results demonostrate clearly the safeguarded properties of compositions according to the invention. The LD=O values for Parathion only, and Malathion only, are, respectively, approximately 100, and between 270 to 400, milligrams per kilogram of live body weight; the corresponding LD50 values for the compositions are approximately 400 and greater than 2000.

EXAMPLE 28 This Example illustrates the delay in gastric emptying in animals dosed with sub-emetic amounts of the emetic of formula II.

Rats, mice and Cynomolgus monkeys (Macaca fascicularis) were orally and subcutaneously (rats and mice only) dosed with compositions containing the compound 2 - amino - 6 - methyl - 5 - oxo - 4 - n - propyl - 4,5 - dihydro - s triazolo pyrimidine having the formula:

Formula II The dosage rate for the monkeys were approximately one-tenth of that required to produce emesis.

The results are given in Table 2 below and show the percentage inhibition of gastric emptying 1 hour after dosing against control experiments in which the foregoing substance was omitted from the composition administered. All compositions contained either radio-labelled chromium (sodium chromate) (rats and mice) or phenol-red dye (monkeys) and the stomach contents of the animals were analysed to determine the amount present one hour after dosing.

TABLE 2

Dosage Rate in Milligrams Percentage Per Kilogram of Inhibition of Species Live Body Weight I Administration Gastric Emptying Mice 1.0 Subcutaneous 86 2.5 oral 91 Rats 0.1 oral 37 1.0 ; oral 68 0.1 Subcutaneous 48 1.0 Subcutaneous 75 Monkeys 0.2 oral 61 These remarkable and surprising results clearly demonstrate that an emetic constituent of compositions according to the invention, even at sub-emetic dosage rates, achieves, after oral ingestion, a substantial reduction in the uptake by their bodies of their stomach contents by animals, thereby lessening the onset of toxic effects and enhancing their prospects of survival, more especially by providing more time for emesis to take place (in those instances where an emetic amount is administered) and/or other remedial measures to be taken, after oral ingestion.

In the foregoing text and Examples the following: "Aromasol" H "Dispersol" T "Lubrol" N13 "Aerosol" OT/B "Ethylan" AC "Arylan" CA "Arylan" 13A "Polyfon" H "Pluronic" F68 "Vancell" E "Crypoum" "Monolan" M are Trade Marks or Trade Names.

Claims (14)

WHAT WE CLAIM IS:-

1. An emetic composition comprising a toxic chemical substance as herein defined (other than a herbicidal bipyridylium quaternary salt or a sympathomimetric amine) and an emitic which is an s-tnazololl,5-alpyrimidine derivative of the formula:

Formula I wherein R' is hydrogen or an alkyl radical containing from 1 to 4 carbon atoms, or an acyl radical of the formula R4 . CO- wherein R4 is an alkyl or alkoxy radical containing from 1 to 4 carbon atoms or a chlorophenyl radical, R2 is an alkyl or alkenyl radical containing from I to 4 carbon atoms or a cyclopentyl radical, and R3 is an alkyl radical containing from 1 to 4 carbon atoms; or an acid addition salt thereof; the ratio of emetic to toxic chemical in the composition being such that a toxic dose of the composition tends to induce emesis.

2. An emetic composition according to claim 1 wherein the emetic is any of the following, substituted, 5 - oxo - 4,5 - dihydro - s - triazololl,5 - alpyrimidine derivatives: 2-amino-6-methyl-4-n-propyl 2-acetamido-6-methyl-4-n-propyl 6-methyl-4-n-propyl-2-n-propylamino 2-amino-6-methyl-4-n-butyl 2-amino-6-methyl-4-allyl 2-isopropylamino-6-methyl-4-n-propyl 2-p-chlorobenzamido-6-methyl-4-n-propyl 2-ethoxycarbonylamino-6-methyl-4-n-propyl 2-amino-4,6-di-n-propyl 2-amino-6-methyl-4-s-butyl 2-amino-6-methyl-4-cyclopentyl 2-amino-6-n-butyl-4-n-propyl with reference to the numbering of the ring atom positions hereinabove set forth.

3. An emetic composition according to Claim 1 wherein the emetic is 2 amino - 6 - methyl - 5 - oxo - 4 - n - propyl - 4,5 - dihydro - s - triazolo[l,5 a]pyrimidine having the formula:

Formula II

4. An emetic composition according to any one of the preceding claims wherein the toxic chemical substance is a pesticide.

5. An emetic composition according to any of the preceding claims wherein the toxic chemical is an insecticide.

6. An emetic composition according to Claim 5 wherein the insecticide comprises any of the following compounds: an organo-phosphorus, carbamate. or oxime carbamate; and uncoupler of oxidative phosphorylation; and pyrethroid.

7. An emetic composition according to any of Claims 4, 5 and 6 wherein the pesticide is any of the following specific substances: I-naphthyl methylcarbamate; dimethyl 4-nitrophenyl phosphorothionate; S-[1,2- di(ethoxycarbonyl)ethylldimethyl phosphorothiolothionate; diethyl 2 - isopropyl - 6 - methyl - 4 - pyrimidinyl phosphorothioate; dimethyl 3-methyl-4-nitrophenyl phosphorothioate: diethyl S[(4 - oxo - 1,2,3 - benzotriazin - 3(4H) - yl) methyl] phosphorothiolothionate; diethyl 4-nitrophenyl phosphorothionate; diethyl S-(ethylthiomethyl) phosphorothiolothionate; 2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate; dimethyl cis- 1 -methyl-2-methyl carbamoylvinyl phosphate; dimethyl S-methylcarbamoylmethyl phosphorothiolothionate; I-(methylthio)ethylideneamino methylcarbamate; 2-methyl-2-(methylthio)propylideneamino methylcarbamate; N,N - dimethyl - a - methylcarbamoyloxyimino - a - (methylthio) acetamide; dimethyl 2,2-dichlorovinyl phosphate.

8. An emetic composition according to any of the preceding claims wherein the toxic chemical substance is any of the following: an anti-freeze mixture comprising mono- or di-ethylene glycol; a petroleum tar distillate; a carbolic acid preparation; an industrial solvent such as industrial methylated spirit comprising methyl, ethyl, or isopropyl alcohol; a drug, especially a sleeping pill or acetylsalicylic acid.

9. An emetic composition according to any of the preceding claims and wherein the amount of the toxic chemical substance present in the compositions of the invention is from 0.1 to 99.9% by weight.

10. An emetic composition as claimed in any of the preceding claims and containing a surface active agent.

11. An emetic composition according to any of the preceding claims and containing from 0.01 to 5 parts by weight of the emetic per 100 parts of the composition.

12. A concentration pesticidal composition comprising a liquid pesticidal composition and a triazolo-pyrimidine as defined in any of Claims 1 to 3 in amount sufficient to cause emesis should the composition be orally ingested.

13. A composition according to Claim 12 wherein the amount of pesticide present in the liquid composition is 1 gram to 600 grams per litre and preferably from 50 to 400 grams per litre.

14. A method of avoiding or reducing the toxifying effect of chemicals ingested by a mammal other than a human which comprises administering to said mammal an emetically effective amount of an s-triazolo[l,5-a]pyrimidine derivative as defined in any of Claims 1 to 3.