Safeguarded toxic chemical compositions containing effective emesis-inducing S-triazolo-[1,5-.alpha.]pyrimidine derivatives

An emetic composition comprising a toxic chemical substance which is other than a herbicidal bipyridylium quaternary salt, which is not intended for oral ingestion but when so orally ingested passes into the blood through the stomach and digestive tract and for which treatment by induction of emesis is medically advisable and an emetically effective amount of an emetically active s-triazolo-[1,5-.alpha.]pyrimidine derivative, the ratio of emetic to toxic chemical being such as to induce emesis when the composition is orally ingested.

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 
environmentally unacceptable; they may have unsuitable toxicological 
properties; they may have highly undesirable side-effects; or they may be 
completely isoluble. 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 perparations, 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 Pat. 
No. 348003 and French Patent Application No. 2067846, 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. Pat. No. 1,234,635 and also in our U.S. 
Pat. 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 filed on April 
15, 1976 (which does not form part of the published prior art) there are 
described and claimed compositions comprising a herbicidal bipyridylium 
quaternary salt and a triazolo [1,5-a] pyrimidine 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. Pat. 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 a single, unusual, instance 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, suprisingly, that even fast-acting highly toxic 
substances, such as the intensely poisonous organo-phosphorus pesticides 
parathion (having an LD.sub.50 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 digestive 
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 (nonvomiting 
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 (other than a herbicidal 
bipyridylium quaternary salt) and an emetic which is an s-triazolo [1,5-a] 
pyrimidine derivative of the formula: 
##STR1## 
wherein R.sup.1 is an amino, alkylamino, phenylalkylamino, dialkylamino, 
ureido, carboxyl, hydroxyalkyl or carbazoyl group; R.sup.2 is an alkyl, 
cycloalkyl or alkenyl group; R.sup.3 is hydrogen, halogen or an alkyl or 
hydroxyalkyl group; one of X and Y stands for an oxo or thioxo radical, 
and the other of X and Y stands for hydrogen or an alkyl radical, and when 
X stands for an oxo or thioxo radical, the nucleus contains a double bond 
between the carbon atoms in positions 6 and 7, and when Y stands for an 
oxo or thioxo radical, the nucleus contains a double bond between the 
carbon atoms in positions 5 and 6; and the base addition salts of a 
triazolo-pyrimidine derivative defined above which contains an acidic 
group; or an acylated derivative, or base 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. Preferably alkyl and 
alkenyl groups in the above definition contain not more than 6 carbon 
atoms. The s-triazolo [1,5-a] pyrimidine ring structure is numbered as 
shown below: 
##STR2## 
A preferred group of triazolo-pyrimidine derivatives for use in the 
compositions of the invention are those of the following formula (II): 
##STR3## 
wherein R.sup.1 is hydrogen or an alkyl radical containing from 1 to 4 
carbon atoms, or an acyl radical of the formula R.sup.4 .CO--wherein 
R.sup.4 is an alkyl or alkoxy radical containing from 1 to 4 carbon atoms 
or a chlorophenyl radical, R.sup.2 is an alkyl or alkenyl radical 
containing from 1 to 4 carbon atoms, or a cyclopentyl radical, and R.sup.3 
is an alkyl radical containing from 1 to 4 carbon atoms. 
Particular derivatives of 5-oxo-4,5-dihydro-s-triazolo [1,5-a] pyrimidine 
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-amino-7-methyl-4-n-propyl- 
2-dimethylamino-6-methyl-4-n-propyl- 
2-di-n-propylamino-6-methyl-4-n-propyl- 
2-isopropylamino-6-methyl-4-n-propyl- 
2-p-chlorobenzamido-6-methyl-4-n-propyl- 
2-ethoxythiocarbonylamino-6-methyl-4-n-propyl- 
2-ethoxycarbonylamino-6-methyl-4-n-propyl- 
2-(3-phenylureido)-6-methyl-4-n-propyl- 
2-amino-4,6-di-n-propyl- 
2-N,N-diacetylamino-6-methyl-4-n-propyl- 
2-N-ethoxycarbonyl-N-.alpha.-phenylethylamino-6-methyl-4n-propyl- 
2-amino-6-methyl-4s-butyl- 
2-amino-6-methyl-4-cyclopentyl- 
2-amino-6-n-butyl-4-n-propyl- 
Whilst the first, second, third and fourteenth derivatives listed above are 
preferred, an especially useful triazolopyrimidine 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 [1,5-a] 
pyrimidine having the formula: 
##STR4## 
This compound is typical of the foregoing s-triazolopyrimidines and has an 
LD.sub.50 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 1-naphthyl methylcarbamate 
Parathion-Methyl 
dimethyl 4-nitrophenyl phosphoro- 
thionate 
Malathion S-[1,2-di(ethoxycarbonyl)ethyl] 
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]phosphorothioio- 
thionate 
Parathion diethyl 4-nitrophenyl phosphoro- 
thionate 
Phorate diethyl S-(ethylthiomethyl) phosphoro- 
thiolothionate 
Carbofuran 2,3-dihydro-2,2-dimethylbenzofuran- 
7-yl methylcarbamate 
Monocrotophos 
dimethyl cis-1-methyl-2-methyl 
carbamoylvinyl phosphate 
Dimethoate dimethyl S-methylcarbamoylmethyl 
phosphorothiolothionate 
Methomyl 1-(methylthio)ethylideneamino 
methylcarbamate 
Aldicarb 2-methyl-2-(methylthio)propylidene- 
amino methylcarbamate. 
Oxamyl N,N-dimethyl-.alpha.-methylcarbamoyloxy- 
imino-.alpha.-(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 1R, 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-.alpha.-cyanobenzyl (1R, 
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-1-carboxylate, having the 
common name `Permethrin`; 
3-Phenoxy-.alpha.-cyanobenzyl-2-(2,2-dichlorovinyl)-3,3-dimethylcyclopropan 
-1-carboxylate, having the common name `Cypermethrin`; 
3-Phenoxy-.alpha.-cyanobenzyl-4-chlorophenyl-.alpha.'-isopropyl 
phenylacetate, having the common name `Phenovalerate`; and 
3-Phenoxy-.alpha.-cyanobenzyl-2,2,3,3,-tetramethylcyclopropane-1-carboxylat 
e. 
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" 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 does 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 liter) and 
preferably from 0.5 to 4.0 pounds per gallon (50 to 400 grams per liter). 
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 triazolopyramidine (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 and especially a 
human, which comprises administering to the affected mammal or human an 
emetically effective amount of an s-triazolo-[1,5-a] pyrimidine derivative 
as defined above.

The invention is illustrated by the following Examples, No. 1 to 14 of 
which are pesticide formulations of varying kinds; No. 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-triazolo[1,5-a]pyrimidine, 
(hereinafter referred to as "Emetic of Formula III") and Malathion. 
______________________________________ 
% w/v 
______________________________________ 
Malathion 90 
Emetic of formula III 
above 0.05 
Aromasol H (a solvent 
mixture of alkyl 
benzenes) to 100 ml 
______________________________________ 
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 III 
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 III 
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: 
##STR5## 
EXAMPLE 4 
This Example illustrates a composition according to the invention which 
comprises a herbicide. 
______________________________________ 
% w/v 
______________________________________ 
Emetic of formula III 
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. 
______________________________________ 
% w/v 
______________________________________ 
Dimethoate 40 
Lubrol N13 1 
Emetic of formula III 
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. 
______________________________________ 
% w/w 
______________________________________ 
Azinphos ethyl 25 
Emetic of formula III 
0.5 
Dispersol % (a mixture of 
sodium sulphate and a 
condensate of formaldehyde 
with the sodium salt of 
naphthalene sulphonic 
acid) 5 
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: 
##STR6## 
EXAMPLE 7 
This Example illustrates an emulsifiable concentrate containing 20% (on a 
weight/volume basis) of diazinon. 
______________________________________ 
% w/v 
______________________________________ 
Diazinon 20 
Emetic of formula III 
0.05 
Arylan CA (calcium dodecyl 
benzene sulphonate) 5 
Lubrol N13 (a condensate 
or 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 III 
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. 
______________________________________ 
% w/w 
______________________________________ 
Aldicarb 5 
Emetic of formula III 
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 methomyl. 
______________________________________ 
% w/w 
______________________________________ 
Methomyl 60 
Emetic of formula III 
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 III 
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 III 0.05 
Monolan M (an ethylene oxide/ 
propylene oxide copolymer) 
4.5 
Ethylan A.C. (a blend of 3.0 
Arylan B.A. anionic and non- 
7.5 
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 III 
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-[3-(4'-bromobiphenyl-4-yl)-1,2,3,4-tetrahydro-1-naphthyl]-4-hydroxycouma 
rin. 
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 
themselves. 
______________________________________ 
% w/w 
______________________________________ 
Emetic of formula III 
0.05 
Difenacoum rodenticide 
0.2 
Talc to 100 grams 
______________________________________ 
Instead of talc 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 III 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 III 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 III 
0.05 
Sodium Tetraborate 10 H.sub.2 O 
3 
Phosphoric acid 1 
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 III 
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). 
______________________________________ 
% w/v 
______________________________________ 
A. Methyl alcohol 4.9 
Emetic of formula III 
0.05 
Pyridine base 0.5 
Ethyl alcohol to 100 ml 
B. Methyl alcohol 95 
Emetic of formula III 
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 
(C.sub.12-15) ether sulphate 
containing 3 moles of 
ethylene oxide 5 
Coco fatty acid diethanolamide 
1 
Perfume 0.1 
Dye 0.01 
Ethyl alcohol 5 
Sodium chloride 6 
Emetic of formula III 
0.02 
Water to 100 ml 
______________________________________ 
EXAMPLE 21 
This Example illustrates a liquid metal polish preparation. 
______________________________________ 
% w/w 
______________________________________ 
Emetic of formula III 
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 III 
0.05 
Pine oil 80 
Sulphated 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 III 
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 III. 
______________________________________ 
% w/w 
______________________________________ 
Glycerin 5 
Alum 1 
Zinc sulphophenolate 
0.5 
Propyl alcohol 10 
Rose water 10 
Perfume 0.5 
Emetic of formula III 
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. 
______________________________________ 
% w/v 
______________________________________ 
Emetic of formula III 
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 
Benzoin 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 liquid preparation useful for removing varnish 
from finger nails. 
______________________________________ 
% w/w 
______________________________________ 
Amyl acetate 20 
Ethyl acetate 20 
Emetic of formula III 
0.01 
Acetone to 100 grams 
______________________________________ 
The emetic was dissolved into the organic solvents. Perfume was added to 
complete the cosmetic preparation. 
EXAMPLE 27 
This Example demonstrates the efficacy of safeguarded compositions 
according to the invention. 
Parathion and malathion alone, and invention compositions comprising 
parathion or malathion and the compound 
2-amino-6-methyl-5-oxo-4-n-propyl-4,5-dihydro-s-triazolo [1,5-a] 
pyrimidine having the formula: 
##STR7## 
were orally admistered to 2 animals [Macaca fascicularis (Cynomolgus 
monkeys)] and the time lapse for emesis to take place recorded. The 
results of the experiment are shown in Table 1 below: 
TABLE 1 
__________________________________________________________________________ 
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 III 
2 and 10 minutes 
(admixture) respectively 
Malathion 2000 2 2 minutes 2 
Emetic of Formula III 
2 and 10 minutes 
(admixture) respectively 
__________________________________________________________________________ 
The results demonstrate clearly the safeguarded properties of compositions 
according to the invention. The LD.sub.50 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 
LD.sub.50 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 III. 
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: 
##STR8## 
The dosage rate for the monkeys was 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 
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.