Phosphorus organic compounds from the group of toxic substances. Phosphorus organic compounds from the group of toxic substances Phos application

Many FOS, due to their special chemical affinity for cholinesterase, inhibit, i.e., block, its molecules through interaction with the esterase center. As can be seen from the diagram below, the organophosphorus poison molecule reacts with the hydroxyl group of the enzyme, and its anionic center does not take part in the reaction:

However, at the beginning of the 1950s, in Tammelin's laboratory in Sweden, such OPs were synthesized that also react with the anionic center of the enzyme. At the same time, chemists proceeded from the assumption that if the poison is similar in structure to the natural substrate of cholinesterase (acetylcholine), then it will have a stronger inhibitory effect on this enzyme. Indeed, compounds that contain a choline residue in their composition, such as methylfluorophosphorylcholine, turned out to be such powerful anticholinesterase substances. It is quite natural that when it interacts with cholinesterase, the positively charged nitrogen atom will react with the anionic center of the enzyme. This provides additional contact of the poison with the active surface of cholinesterase and makes the connection between them stronger:

One can also imagine simultaneous inhibition by one molecule of methylfluorophosphorylcholine of two molecules of the enzyme: one at the anionic, the second at the esterase center. Be that as it may, Tammelin's poisons turned out to be ten times more toxic than even such a potent FOS as sarin. The resulting phosphorylated cholinesterase, in contrast to the acetylated one, is a sufficiently strong compound and does not undergo spontaneous hydrolysis. It turned out that the process of cholinesterase inhibition is a two-stage process. Initially, at the first stage, a reversible, i.e., unstable, blocking of the enzyme occurs, and only at the second stage does the enzyme block irreversibly. Both of these steps are the result of a complex, not yet fully understood molecular rearrangement in the FOS-cholinesterase complex. Running a little ahead, we note the significance of this phenomenon for the practice of using some antidotes, the effect of which is to break the chemical bond between the poison and the enzyme. Thus, under the influence of anticholineste - various substances, the destruction of acetylcholine molecules is inhibited and it continues to have a continuous effect on cholinergic receptors. It follows that FOS poisoning is nothing more than a generalized overexcitation of cholinergic receptors caused by intoxication with endogenous, i.e., having an internal origin, acetylcholine. That is why the main symptoms of FOS poisoning can be interpreted as a manifestation of excessive, inappropriate for the body activity of a number of structures and organs, which is provided by acetylcholine mediation (first of all, this is the function of nerve cells, striated and smooth muscles, and various glands).

Currently, there is evidence of a direct excitatory effect of some FOS on cholinergic receptors. Thus, it is not excluded that FOS have a toxic effect, bypassing the cholinesterase mechanism:

In the last 10–15 years, toxicologists have increasingly paid attention to this feature of the mechanism of the effect of OPs on biostructures. In particular, such a non-anticholinesterase action of them is manifested in the direct excitation of H-cholinergic receptors, on which, as experimental data show, the nicotine-like effects of FOS in turn depend. At the same time, their muscarino-like action is now considered with good reason to be the result of cholinesterase inhibition.

As for the comparative severity of muscarinic and nicotinic effects in various anticholinesterase substances, then, according to the study of V. B. Prozorovsky, * 3 groups can be considered:

* (Prozorovsky VB Questions of the mechanism of action and age-related toxicology of anticholineterase drugs. Abstract doc. dis. L.. 1969)

• 1) causing predominant excitation of M-cholinergic receptors (ezerin, nibufin, chlorophos);
• 2) causing excitation of both M- and H-cholinergic receptors (phosphacol, armin, diisopropylfluorophosphate);
• 3) causing a predominant effect on H-cholinergic receptors (prozerin, thiophos, mercaptophos).

From the foregoing, it follows, at least theoretically, that in case of poisoning with anticholinesterase poisons, including FOS, antidotes could be:

• 1) substances that enter into direct chemical interaction with poisons;
• 2) substances that inhibit the synthesis and release of acetylcholine into the synaptic cleft;
• 3) substances that replace the enzyme damaged by poisons (i.e., cholinesterase preparations);
• 4) substances that prevent the contact of the poison with the enzyme and thereby protect it from toxic effects;
• 5) substances that prevent the contact of acetylcholine with the cholinergic receptor;
• 6) substances that restore the activity of the enzyme by displacing the poison from its surface (i.e., reactivating the structure of cholinesterase).

Numerous toxicological experiments have shown that all these substances have some degree of specific effect on the toxic process, but the last 2 groups of antidotes are of the greatest practical importance. Let us consider in more detail the mechanisms of their action.

Organophosphorus compounds are most widely used in agriculture as active insectoacaricides and larvicides against endo- and ectoparasites of animals.
The hygienic advantage of this group of pesticides is their relatively low persistence in the environment, they pollute food products less, unlike HOS. Even in the presence of FOS in food products, they are quickly destroyed during heat treatment. However, it should be borne in mind that FOS is characterized by the ability to penetrate into the body through intact skin. This is dangerous for those who work with drugs, as acute poisoning can imperceptibly occur.
Among FOS there are preparations with different toxicity for humans and warm-blooded animals.
Highly toxic FOCs are banned in our country for the control of animal parasites. Basically, in practice, medium- and low-toxic drugs are used for humans and warm-blooded animals.
The mechanism of the toxic action of most organophosphorus compounds is based on the inhibition of a number of enzymes related to esterases, in particular, cholinesterases. It has been established that the inhibition of cholinesterase is associated with the phosphorylation of its active centers.
From a hygienic point of view, the most promising are those OPs in which detoxification processes prevail over activation processes in the body of warm-blooded animals and humans, and as a result, non-toxic metabolites are formed.
As a result of inhibition of cholinesterase, acetylcholine accumulates in the blood and tissues, causing cholinergic signs of poisoning (excitation, twitching and muscle paralysis, nausea, vomiting, tearing and salivation, increased intestinal motility, diarrhea, frequent urination, bronchospasm, miosis, pulmonary edema). Poisoning of animals with OPs occurs when plants are fed with it earlier than 6 days after treatment with contact preparations (neguvon, trichlormetafos-3, karbofos, baytex, neocidol, DDVP, etc.). FOS in the body completely or to a large extent undergo metabolic transformations. The most important for thionic and dithiophosphoric ethers is oxidative desulfurization, that is, the separation of sulfur associated with a phosphorus atom and its replacement with oxygen, as a result of this reaction, more active and, as a rule, more toxic compounds are formed. Thus, the activity of thiosphorus, metaphos, karbofos increases 10 thousand times.
As a result of reductase activity in the liver and kidneys, more toxic compounds can be formed during the metabolism of FOS.
Enzymatic hydrolysis of FOS is the main method of their neutralization, in which lipid-soluble substances become water-soluble and are removed by the kidneys. The main enzymes involved in the hydrolysis of FOS are phosphatases, carboxyesterases, carboxyamylases, united by the general term "hydrolases".
One of the transformations of FOS in the body after enzymatic hydrolysis is the formation of their compounds with glucuronic and sulfuric acids, glutamine. FOS are excreted unchanged through the respiratory tract (20-25%), with urine (30%). The rest (50%) is metabolized in the liver and excreted as metabolites.
Symptoms of poisoning with drugs of the FOS group are divided into muscarinic, nicotine-like and central. Muscarine-like (amenable to the influence of atropine) include nausea, vomiting, intestinal spasms, salivation, lacrimation, sweating, diarrhea, increased bronchial secretion, respiratory failure (bronchospasm), bradycardia, miosis.
Nicotine-like (atropine-resistant) symptoms are: twitching of the eye muscles, tongue, neck muscles, the appearance of nystagmus and fibrillar twitching of the muscles of the whole body.
Symptoms of CNS damage: mental disorder, ataxia, disorientation in space, tremor, clonic convulsions, depression and paralysis of the centers of the medulla oblongata. These phenomena are poorly influenced by atropine.
Significant changes under the action of FOS were found in the cardiovascular system: an increase or decrease in the maximum and minimum levels of blood pressure is observed. There is a number of data on the effect of FOS on the morphological and biochemical composition of blood. Those who were poisoned with FOS were found to have leukocytosis, a decrease in the number of eosinophils, and hyperglycemia. Eosinopenia and an increase in blood sugar are considered as the appearance of a stress response from the pituitary-adrenal cortex system.
Changes in the red blood are also described: with the introduction of small doses of organophosphorus compounds, an increase in the content of hemoglobin and the number of erythrocytes, which, apparently, is associated with the stimulation of erythropoiesis, and when exposed to large doses, anemia with a change in the size and shape of blood cells. In chronic OP poisoning, toxic granularity of leukocytes was noted. The earliest indicators of the impact of FOS on the body is a decrease in the activity of serum cholinesterase (up to 22.4% of the original value). In severe poisoning, the content of residual nitrogen increases, but the content of polysaccharides and peroxidase diastases decreases. An increase in the gamma globulin component of plasma and a decrease in the albumin fraction were noted. Perhaps the occurrence of metabolic and respiratory acidosis, an increase in the content of lactic acid, phosphates and potassium in the blood plasma. The noted changes may be the result of both hypoxia associated with impaired respiration, and the direct effect of OPs on the processes of cellular metabolism.
pathological changes. Those who died from OPC poisoning had convulsions in the legs, miosis, pulmonary and cerebral edema, inflammation of the meningeal membranes, pinpoint hemorrhages in the white and gray matter of the brain, vasodilation and, in particular, dilation of the parietal veins of the stomach, numerous petechial hemorrhages in the fundus of the stomach, acute duodenitis. The intestines are often in a contracted state. Often find catarrhal tracheobronchitis with petechial hemorrhages in the larynx, trachea and pleura. Regularly acute expansion of the ventricles of the heart.
Histological examination reveals the phenomena of cloudy swelling in the liver and heart muscle, fatty degeneration of the liver, changes in the parenchyma of the kidneys, and expansion of the perivascular spaces. Vessel ruptures in the region of the pons and the fourth ventricle of the brain, degenerative processes in the spinal cord are described.
First aid for FOS poisoning - as soon as possible, 1 ml of a 0.1% solution of atropine sulfate should be administered subcutaneously or intramuscularly. In case of moderate poisoning, the dose is increased by 2-3 times, and in case of severe poisoning - intravenously slowly 4-6 times the dose. If the signs of poisoning do not stop, then after 8-10 minutes intramuscular injections of atropine are resumed until the symptoms of poisoning completely disappear and dryness of the mucous membranes appears.
In recent years, cholinesterase reactivators have been used to treat OPC poisoning, which can displace OPC from its compounds with cholinesterase. They are effective in the first hours after the pesticide enters the body. After a day, their use is impractical.
As a cholinesterase reactivator, isonitrosin, alloxime and diectixime are successfully used.
Isonitrosin, 40% solution in 3 ml ampoules. It is a cholinesterase reactivator, which is phospholyzed by isonitrosin, gaining its active state. The drug is used for acute poisoning or suspected FOS poisoning intramuscularly or intravenously in dogs, a daily dose of 0.3-0.4 g / kg of animal body weight. Re-introduction is possible after 30-40 minutes.
Alloxim causes dephosphorylation, returning the active state to cholinesterase. This ensures the restoration of the biological activity of the central nervous system and the conduction of impulses in cholinergic synapses. Alloxim is a lyophinized powder in vials of 0.075 g, a sterile solution is administered to dogs at a dose of 4-16 mg/kg with an interval of 8 hours. The preparation for injection is prepared by dissolving 1 ml of sterile distilled water. More effective is the use of alloxim simultaneously with atropine.
Diectixim- 10% solution in 5 ml ampoules, administered intramuscularly to dogs 5-50 ml once. A course of treatment with atropine; vitamins B1, B6, C, glutamic acid, tranquilizers, sleeping pills and other compounds that accelerate the removal of cholinergic effects.
Dipyrexim(TMB-4) is used in the form of a 15% solution subcutaneously or intravenously in large animals, 3-5 ml, and in small animals, 1-3 ml once or with an interval of 6-8 hours. More effective in combination with atropine at the same time. Under the action of dipyrexime, the complex is dephosphorylated with the restoration of the activity of cholinesterase and the cholinomimetic complex.
Tropacin- M-anticholinergic substance (similar to atropine), blocks M-cholinergic receptors, which excludes the interaction of the neurotransmitter acetylcholine, which accumulates in the zone of M-cholinergic synapses, as a result of the anticholinesterase action of FOS, XOC and carbamates. This effect is enhanced as a result of its ganglioblocking action. The drug is produced in tablets of 0.001; 0.003; 0.005 and 0.1 g. Tropacin is used internally for horses, pigs, dogs, chickens and ducks at 0.005; cattle - 0.001; calves - 0.002; sheep, goats - 0.003; piglets - 0.004 and rabbits - 0.01 g / kg of live weight.
Phospholitin- thick oily liquid, produced sterile in vials. The drug has an M-anticholinergic effect, mainly in the central nervous system. It is used in pure form or in a mixture with dipyroxine (TMB-4), which increases the anti-phosphine activity of phospholitin. Like dipyroxine, phospholithine is an acetylcholinesterase reactivator, that is, it ensures the restoration of its activity by deformation.
Solutions for a mixture of phospholitin and dipyroxine are prepared separately. A 75% mixture of phospholitin with water and a 20% aqueous solution of dipyroxine prepared before use are mixed in a ratio of 1.5:1, respectively.
The drug is administered to animals intramuscularly. If only phospholitin is used, then it is used in doses: for cattle, buffaloes - 2.5-10; horses, camels - 2.5-12; deer, donkeys - 0.6-3; pigs - 0.3-1.5; sheep, goats - 0.1-0.5; dogs - 0.06-0.3 ml per animal. If mixtures of phospholitin with dipyroxine are used, then they are administered: horses, cattle, buffaloes, camels - 4-15; deer, donkeys - 1-1.5; pigs - 0.6-2.5; sheep, goats - 0.2-1; dogs - 0.1-0.5 ml per animal. In case of general oppression, in addition to the antidote, the animal is injected with a 25% glucose solution containing 0.2% ascorbic acid, 5 ml per 1 kg of live weight.
It should be remembered that even at optimal doses, chemotherapeutic substances, including insectoacaricides of any group, cause inhibition of intracellular metabolism, and therefore, in cases of poisoning, it is necessary to treat animals in a complex manner using vitamins, macro- and microelements, enzymes and other biologically active substances. This must also be done because chemotherapeutic substances increase the removal of vitamins, macro- and microelements from the body with simultaneous suppression of the biosynthesis of amino acids, vitamins and other biologically active substances by the gastrointestinal microflora.
Removal of the poison from the body is achieved by forced diuresis with the use of osmotic diuretics (hypertonic glucose solution or mannitol). If there are indications, drugs are used that restore the activity of the cardiovascular system.
In recent years, new antidotes for various toxic substances have been developed.
The mechanism of the antitoxic action of antidotes is different, therefore, several antidotes are often used against the toxic substance that caused the poisoning.
Organophosphorus compounds are often used in veterinary medicine. In cases where animals are treated with FOS preparations at recommended doses, when they are slaughtered, the biochemical parameters of meat do not change, but when using tenfold doses of FOS (from the recommended ones), a deviation from the norm of properties and commercial qualities of the product is observed. It is characterized by an increase in pH (6.4), doubtful or positive benzidine and sulphate reactions, deterioration in organoleptic properties, and a decrease in the content of most amino acids (especially essential ones). In meat containing 0.3 mg/kg and more FOS, when stored for 3 months at a temperature of -7°C, the preparations decompose by 10-15%. There is a decrease in bacterial contamination (in comparison with the initial one), the reaction to peroxidase is negative, there is no protein breakdown.
When exposed to high temperature, FOS is partially or completely destroyed. In meat, FOS residues are reduced by 25-50% in the process of minced meat preparation, boiling for 30-60 minutes. But the remains of some persistent FOS (neguvone, trichlormetaphos-3, etc.) are not completely destroyed during heat treatment. When meat is contaminated with large amounts of FOS (exceeding the MRL by 3-4 times), it can be used for the manufacture of boiled sausages, canned food, the technology of which requires high temperature.
To free milk from FOS, it is advisable to use ion-exchange resins. Milk containing less than 2 mg/l of phosphoric and thiophosphoric acids is completely neutralized from pesticide residues without changing the physical and chemical properties and presentation. When the content of non-guvone, sulfidophos, etc. in fresh milk is up to 1 mg / l, their amount decreases in pasteurized milk by 50%, when boiled, on average by 94.5%, in acidophilic yeast by 82%, curdled milk by 92%, kefir by 93% .
DDVF(dichlorvos, dichlorvos, chlorvinylphos "Estrozol", checker PPF-1, vapon). Transparent colorless or slightly yellow liquid with a boiling point of 74°C at 1 mm. rt. Art. Technical DDVF contains 85-96% of the active substance (a.i.), dissolves in water up to 1% and quickly hydrolyzes, in solar oil - up to 5.9%. Rapidly hydrolyzes in alkalis to form diethylphosphoric acid and dichloroacetalhyde. It is produced in the form of an emulsion 5%, granules 20%, checkers, sprays. DDVF is highly toxic, its LD50 is 23-87 mg/kg, and when applied to the skin: for rats - 113 mg/kg, for rabbits 205 mg/kg. The drug has a high volatility (145 mg/m3) at an air temperature of 20°C. It can easily enter the body of warm-blooded animals both through intact skin and through the respiratory tract. DDVF is used for spraying animals against insects and ticks. To combat estrosis in sheep, it is most promising to use it in the form of aerosols with a consumption rate of 40-60 mg/m3 and an exposure of 1-2 hours. For these purposes, the drug "Estrozol" is produced in the form of a spray in aluminum cans containing 12.5% ​​DDVF, PPF-1 checkers, 0.25 g / kg.
The drug degrades rapidly in the environment. It does not accumulate in the body of warm-blooded animals, it quickly undergoes biotransformation by hydrolysis with the formation of dichloroacetalhyde, which turns into dichloroethanol and is excreted in the urine in the form of glucuronide. Antidotes for poisoning: atropine, platifillin and other anticholinergics. Slaughter of sheep and goats for meat is allowed no earlier than 5 days, cattle and deer - 3 days after processing. Processing of cows is allowed only after milking.
Diazinon(neocidol, basudin, dimpigal, nucidol, manjin). Colorless oily liquid with a boiling point of 89°C. Poorly soluble in water, well - in most organic solvents. It has a contact and intestinal route of penetration into the parasite. Rapidly hydrolyzes in alkaline and acidic environments. Available in the following forms: 60% emulsion concentrate, 40% wettable powder, 5 and 10% granules and dust. Shelf life when stored in aluminum or iron containers with anti-corrosion coating - 2 years. Neocidol is manufactured by Siba-Geiga and is valid for 3 years. The drug is highly toxic, oral DD50 for mice is 80-135, for rabbits - 118, for sheep - 225 mg / kg. Cumulative properties are weakly expressed. With alimentary administration to cattle at a dose of 25 mg/kg, to sheep - 30 mg/kg of body weight, signs of toxicosis (salivation, increased diuresis, clonic convulsions) were observed. When feeding diazinone at doses of 4 and 8 mg/kg for 90-120 days to cattle BA. Paliev revealed the hepatotoxic effect of the drug, while the volume of bile secretion and hepato-intestinal transport of dry nitrogenous substances, lipids, bile acids and bile lipases are reduced.
Bazudin at doses of 5.7 and 17 mg/kg, administered daily to rabbits for 3 months, led to a decrease in their reproductive function. A low level of live weight of newborn rabbits, their high mortality in the early post-natal period was established. The most characteristic for animal poisoning with bazudine is the inhibition of cholinesterase and an increase in the activity of aldolase and aminotransferase. In case of chronic poisoning in the blood of animals, along with a decrease in the concentration of hemoglobin, a decrease in the number of erythrocytes, leukocytes, the content of sugar and total protein decreases. This is due to a decrease in albumin and globulins. A sharp decrease in beta and gamma globulins is a prognostically unfavorable factor. In veterinary medicine, diazinon, neocidol, bazudin are used to combat ectoparasites in animals.
In 1983, in some regions of Russia and Kazakhstan, neocidol poisoning of cattle was observed, due to the presence of toxic metabolites in it. Their formation occurred when the drug came into contact with alkalis, rainwater, detergents, air during long-term storage. In this regard, you should not leave neocidol in baths for several days. The death of animals occurred in 30-40 minutes. after treatment with symptoms of asphyxia, hypersalivation and convulsions. However, sheep tolerated purchases in emulsions with the presence of these metabolites satisfactorily. Diazinon can be inactivated in a bath with bleach (10 kg per 1 ton of solution), after which the drug decomposes within 2-3 days.
Slaughter of animals after treatment with neocidol (diazine) is allowed after 20 days.
Diacap - 300 CS is a concentrated suspension containing 30% diazinon in microcapsules, the drug is produced in Switzerland in plastic bottles of 1 liter. The drug is used for disinfestation in the fight against flies, bed bugs, cockroaches and other insects in the form of a 0.6% aqueous suspension (1 liter of concentrate per 50 liters of water) at the rate of 50 ml/m2. The treated room is closed and then thoroughly ventilated.
Diacap - 300. Microencapsulated diazinon. Contains stabilized diazinon (92% d.v.), soybean oil, gasoline and other solvents. The drug is a light yellow oily liquid with a slight specific odor. When mixed with water, it forms a white suspension, stable at neutral pH. Acute oral toxicity (DC50) for mice - 187, for rats - 300-1250 mg / kg. It does not irritate the skin, the mucous membrane of the eyes, is rapidly metabolized and completely excreted from the body with urine, does not accumulate in organs and tissues. The drug does not have oncogenic and mutagenic activity, embryotoxic, teratogenic and neurotoxic effects, does not affect reproductive properties.
Diacap- insectoacaricide of contact, intestinal and fumigating action, used for disinfestation of premises in the absence of animals and birds, a 0.6% aqueous suspension is used, the consumption rate is 50 ml / m2 of surface with an interval of 15-20 days. Poultry premises inhabited by bedbugs are treated with a 1.25% aqueous emulsion. The bird is introduced into the room after ventilation, cleaning and spraying the feeders with a 3% solution of soda ash. To destroy fleas in rooms where dogs and cats are kept, carpets, paths, rugs from the underside are treated with the drug, and after 3 days they are washed or cleaned with a vacuum cleaner.
Blotik(propetamphos, safrotin, seraphos). Yellowish liquid, slightly soluble in water and good in most organic solvents. Blotik is produced by Nippon Kayaku Co. Ltd., Japan, in the form of 20% emulsifying concentrate, in polyethylene containers of 0.2, 1 and 5 liters, by Sandoz, Switzerland, in the form of 50% wettable powder, 2% dust.
1 liter of emulsifying concentrate contains propetamphos - 200 g; emulsifiers 242 g, solvent 262 g and filler up to 1 liter. Propentafos is stable in neutral buffer solvents, thermally and photostable, toxic (acute oral toxicity LD50 for rats 287 mg/kg). The mechanism of insectoacaricidal action consists in inhibition of the acetylcholinesterase enzyme, with an inevitable increase in the neurotransmitter acetylcholine and the manifestation of a complex of cholinomimetic effects. Recommended against ectoparasites of cattle, sheep, goats, pigs, to combat sarcoptoid, ixodid, bird mites, lice, runes and myiasis. A single application in the form of spraying, bathing, dusting allows you to destroy ectoparasites and provide protection to animals for 30-120 days. For bathing cattle in baths, a concentration of a working emulsion of 1.75:1000 liters is used, which restores 1.75:500 liters of water. A restorative emulsion is added when the main (working) emulsion is lost by 10-20% (after bathing 250 heads of cattle, 300-400 unshorn or 400-500 sheared sheep). For bathing sheep, the initial (working) emulsion is prepared in the ratio of 0.5 l of blot per 1000 l of water, and the restoring emulsion is 0.5 l per 500 l of water. Animals are sprayed with working emulsion at a ratio of 1.75 blots per 1000 liters of water, up to 2 liters of working emulsion per animal, but for pigs a dilution of 1.0 per 1000 liters of water should be used. The working emulsion is prepared immediately before use under the supervision of a veterinarian. If for some reason bathing was not carried out, then the unused prepared emulsion retains its properties and can be used within 3 weeks; slightly contaminated (after buying) working emulsion - within 4 days. Before mass processing, it is necessary to conduct tests of the drug on 5-10 animals. In the absence of signs of toxicosis within 5-10 days, they begin to process the entire livestock. When processing animals, the temperature of the working solution should be in the range from +15°C to +25°C, and the ambient air - at least +12°C. It is forbidden to process sick, weakened, overheated, non-drinking animals; calves up to three months of age; females in the second half of pregnancy. In case of manifestation in animals after treatment of signs of intoxication, it is necessary to use a 1% solution of atropine - 5 ml per 100 kg of body weight subcutaneously. After buying the animals, a mixture of silt, sand, feces, residues of the working solution is poured with a neutralizing solution for 5-6 hours. As neutralizing solutions are used: hydrated or bleached lime (1 kg per 10 liters of water). Decontaminated residues and containers from under the drug are taken to burial sites specially designated for this purpose by local SES. Spraying of poultry houses is carried out with a solution of 1.75: 1000 l with the removal of birds. In the recommended doses and concentrations, the drug does not have a local irritating and sensitizing effect. Slaughter of animals for meat after 21 days, and the use of milk for food is allowed 48 hours after the use of the drug. Blotik retains its properties at temperatures from minus 20°C to plus 54°C, it is stored in unopened packaging for 3 years from the date of manufacture, in a dark, dry, well-ventilated area.
Neguwon(chlorophos, trichlorfon, dipterex, tugon, hinmiks, aerosols: psoroptol, cyperol, pezol, estrosol-2; oil solutions: chlorophos-hypodermine, dioxafos). White crystalline powder. Solubility in water 12.3%, soluble in chloroform, benzene and other organic solvents. It is stable in an acidic environment and quickly hydrolyzes in an alkaline environment, turning into a highly toxic compound DDVF, and then hydrolysis to non-toxic products occurs. Decomposes rapidly in the presence of light, especially in dilute solutions. During storage of aqueous solutions, partial hydrolysis of the drug occurs with the formation of phosphoric, dimethylphosphoric and hydrochloric acids. The drug belongs to moderately toxic, since LD50 for rats is 40 mg/kg, for mice 225 mg/kg. Penetrates through the skin. Has an irritating effect. Cumulative properties are weakly expressed.
With inhalation and intragastric exposure, it has an embryotoxic and teratogenic effect. With daily intake at a dose of 0.1 mg / kg, it affects the generative function, reduces the ability of animals to conceive and reduces their fertility. In experiments on laboratory animals, the carcinogenic properties of technical chlorophos have been established.
It was found that when chlorophos is administered to animals orally, intravenously and intramuscularly, it quickly breaks down and is excreted from the body during the first 4-7 days, mainly with urine, exhaled air and partly with feces.
With external processing, the drug and its transformation products are found in the body of animals for quite a long time, so when processing cattle by watering or spraying, the remains of the drug are installed in organs and tissues within 14-21 days. Preparations containing chlorophos have high insecticidal activity, but do not have a deterrent effect. The residual insecticidal effect on the skin and hair of the animal is very short, so when spraying calves with aqueous emulsions at a dose of 11.8 g, the residual effect of chlorophos against horseflies is 13 hours.
In veterinary practice, hypodermin-chlorophos is still widely used - an 11.6% oil-alcohol solution of chlorophos and dioxafos - a 16% solution of chlorophos in an organic solvent. Both drugs are used against the larvae of the subcutaneous gadfly. Apply it by pouring on the back from the withers to the sacrum in a thin stream in doses: hypodermin-chlorophos - 16 ml for animals up to 200 kg, 24 ml - more than 200 kg of live weight; dioxophos at a dose of 12 ml per animal weighing up to 200 kg and 16 ml - with a larger weight. The use of preparations containing chlorophos is contraindicated in sick, severely malnourished animals, as well as in cows 2 weeks before calving. It is forbidden to process dairy cattle with technical 80% chlorophos. Residues of chlorophos-containing preparations in animal products (meat, milk and dairy products) are not allowed.
Slaughter of cattle, horses, goats (when spraying and watering the back) - after 21 days, slaughter of goats, sheep with free watering and feeding - after 12 days, with aerosol treatments - after 7 days, when administered intranasally - after 3 days, slaughter of chickens - after 14 days.
Simultaneous processing of animals and direct delivery of milk from cattle to children's and medical institutions within 5 days is prohibited. It is forbidden to use goat milk for food for 10 days, when watering the backs of animals, when spraying - 6 days; goats and sheep with free watering, feeding, intranasal and aerosol treatments - within 8 days. It is forbidden to use horse milk for making koumiss for 5 days.
Non-guvone solution N- 100 ml of solution contains 10 g of metrifonate (active ingredient). The drug is produced in Germany in bottles of 1000 ml and is used to destroy the larvae of gadfly flies. The mechanism of larvicidal action is the inhibition of the cholinesterase enzyme, which subsequently causes the development of cholinomimetic effects and the death of parasites. The solution is applied by watering with a thin stream along the back from the shoulder blades to the tail at a dose: with a live weight of 150-200 kg - 12 ml; 200-400 kg - 18 ml and over 400 kg - 24 ml. It is impossible to process animals from the beginning of December to the end of March, because paralysis may occur from the larvae that died in the spinal canal. Simultaneously with the treatment with Neguvon solution N, other cholinesterase inhibitors, muscle relaxants, phenothiazine preparations should not be used. Slaughter of animals for meat not earlier than in 1 day.
Sulfidophos (leibacid, baicid, baytex, tiguvon, entex, fenthion, ethacid, baylyulin). Colorless oily liquid, practically insoluble in water (54-56 mg/l), highly soluble in many solvents, penetrates through the skin, has a pronounced cumulative property. Hydrolyzed, compatible with many insecticides and fungicides, except those with alkaline properties. The drug is resistant to weather and sunlight. Moderately dangerous when taken orally: LD50 for rats 250 mg/kg, for mice 295 mg/kg. In the body of warm-blooded animals, sulfidophos is oxidized to form sulfoxide and sulfone, which have a higher biological activity than the parent compound. Accumulates in fat, muscles, some internal organs, excreted in milk. When processed by watering at the rate of 10 mg/kg, it is excreted in milk within 7 days. It is excreted from the body of reindeer on the 29th day. Industry produces: 20, 50, and 70% a.e. (sulfidophos); 50% a.e. (leibacid); 50% oil solution (fenthion); 60% m.s. (etacid); 2, 10, 20% w.m. fenthion (tiguvon), 40% sp, 2% granules and 3% dust (leibacid, baytex). For ixodid ticks on KPC, sulfidophos is administered as a 0.1% aqueous emulsion. In the same concentration, it is effective against lice. In medical practice, dusts sulfolane (against flies, cockroaches, bedbugs and fleas), sulfopin containing 0.7% sulfidos and 0.3% neopicamine (against insects) have been developed and successfully used. To combat head lice, Biofos tablets have been developed containing 0.03% sulfidos and a filler. The formulation of the aerosol "Pedisulf" (containing 0.55% sulfidos) for the disinsection of lice has been developed. There is an aerosol formulation "Suzol" to combat bed bugs, cockroaches and fleas. It contains 0.9% sulfidos and 1.2% permethrin. To combat fleas in dogs and cats in Germany, they produce tiguvon-10, tiguvon-20 and tiguvon-20C - these drugs contain fenthion 10-20% as an active ingredient. The preparations are packaged in pipettes and applied dropwise to the skin of animals at a dose of 10 mg a.i. per 1 kg of body weight. Tiguvon-10 is used in cats starting from the first year of life and reaching a body weight of 2 kg, Tiguvon-20 is used to treat dogs weighing 3-10 kg at a dose of 15 mg/kg body weight, and Tiguvon-20G is used to treat dogs weighing more than 10 kg, at a dose of 10-20 kg 1 ml of the drug, weighing 25-50 kg - 2 ml and more than 50 kg - 3 ml. When treating animals with tiguvones, it must be remembered that it is impossible to use other cholinesterase inhibitors, phenothiazine derivatives, 10 days before and 10 days after treatment. It is not recommended to treat cats up to 1 year of age, weighing less than 2 kg and pregnant women a week before giving birth. When processing farm animals, it must be remembered that sulfidos and its preparations are stable in food during long-term storage (up to 3 months), in milk during boiling, pasteurization, and lactic fermentation. The qualitative composition of livestock products is changing (the content of amino acids, vitamins of group B). Slaughter of animals for meat is allowed no earlier than 35 days after treatment with sulfidos. The meat of animals slaughtered earlier than this period, if the residual amount of the drug in the meat is up to 5.4 mg/kg, can be fed to carnivores, and if it is higher, the meat is destroyed. The shelf life of sulfidos is 2 years from the date of manufacture.
Cyodrin(25 and 50% emulsion concentrate and aerosols: Dermatozol, Acrodex and Volfazol) - 0.0-dimethyl-0-1-methyl 2 (phenylcarbethoxy) vinyl phosphate, liquid with a low odor, soluble in organic solvents . It is used as an insectoacaricide against ectoparasites of farm animals and birds. It is recommended to use: for spraying the skin and hairline 1.0; 0.5 and 0.25% aqueous emulsions, for the treatment of auricles 0.5% oil solution, aerosols at a dose of 60-80 g per animal. Cyodrin belongs to potent toxic substances: LD50 for intragastric administration for mice 39.8. rats 35.3 -70 mg/kg. It is characterized by severe skin-resorptive toxicity. Cumulative properties are weakly expressed. After a double treatment of cows with 0.25% w.e. (dose 3.42 l per 1 animal) with an interval of 7 days, after 24 hours no drug residues were found in the muscles, liver, spleen, heart, brain and blood. The kidneys, perirenal fat, omentum and udder contained about 0.03 mg/kg; in milk - 0.01 mg / l. The organoleptic properties of milk do not change. The drug is destroyed by souring milk. The content of cyodrin in milk and products of its processing is not allowed, the MRL in meat is 0.005 mg/kg. It is forbidden to treat lactating animals with aqueous emulsions. Aerosols are recommended for the treatment of dairy herds immediately after milking. Slaughter of animals for meat is allowed 15 days after treatment with aqueous emulsions and 10 days after treatment with aerosols. When treating sheep with aerosol-cyodrine, slaughter for meat is allowed 5 days after treatment. The shelf life of the drug is 12 months from the date of manufacture, if stored at a temperature of +5°C-25°C.
"Dermatosol"- a preparation based on cyodrin and neopinamine. Available in aerosol and propellant-free containers. Toxicity is determined by the constituent components. Cyodrin refers to potent toxic substances. Neopamine has low toxicity. It is used as an insectoacaricide for ectoparasites of animals and birds. The presence of residual amounts of neopamine and cyodrine in milk and dairy products is not allowed. Slaughter of animals for meat - not earlier than 10 days after processing. The presence of neopamine in the meat is not allowed, the MRL for cyodrin is 0.005 mg/kg.
Cypen- insectoacaricidal drug, the active ingredient of which is cyodrin (20%) and organic emulsifiers. It is a transparent dark brown liquid produced in Russia. Cypen is packaged in plastic or metal containers of 500 ml, 1000 ml, in polyethylene cans of 3, 5, 10 liters, polyethylene barrels (cans) of 20 liters and in glass bottles of 1-20 ml. Store cypen in its original packaging at temperatures from 0°C to +25°C. Shelf life 24 months from the date of manufacture. Cypen is an effective insecticide-acaricide with contact action, it is active against flies, mosquitoes and other arthropods. It has a residual contact effect on surfaces up to 3 weeks. The preparation for warm-blooded animals is moderately toxic. In the recommended concentrations, it does not have a skin-resorptive, locally irritating and sensitizing effect. Cypen is used for disinfestation of livestock and utility rooms in order to combat zoophilic flies, mosquitoes, fleas, cockroaches. Premises are processed in the absence of animals. For surface treatment (walls, ceiling, floor, lamps, windows, etc.), a working emulsion containing 5% cypene is prepared immediately before use. The consumption rate of the working emulsion is 150-200 ml/m2. The drug should not fall into the feeders and drinkers. It is possible to treat the premises with cypene foam, for which a PG-1 foam generator or a similar device and UDP-M, UDS and other depressurization devices are used, capable of providing a pressure of the working emulsion at the outlet of 5-6 atm. It is forbidden to drain working solutions in places close to reservoirs, drinking water sources, drainage systems, etc.
Trichlormetaphos. White crystalline substance, poorly soluble in water, well - in most organic solvents. Low toxicity, LD50 for white mice 309-672 mg/kg, for rats 1600-1700 mg/kg. Toxic to beneficial insects. In Russia, it is produced in the form of 82% technical product, 50% emulsion concentrate, powder 25%, dust 5-10% ADV. The drug has a mild skin-resorptive effect, has cumulative properties. Within a few weeks, it is excreted in feces and urine. Unchanged drug is found in subcutaneous, perirenal, and mesenteric fat, in the spleen. Decay products are detected in the kidneys, brain, liver, adrenal glands and muscles. Excreted from the body with milk within 30 days. The mechanisms of insecticidal action and action on the body of warm-blooded animals and the pharmacodynamic spectrum of action are similar to those of DDVF. Trichlormetaphos residues in slaughter foods and milk and eggs are not allowed. Slaughter of animals for meat is allowed 60 days after the last treatment. It is forbidden to handle dairy cattle. The introduction of the bird into the room after thorough washing of the feeders and drinkers, 2 days after the treatment of the room with trichlormetaphos.
Hyphlophos- a drug whose active ingredient is dematef - dimethyl ester of b-acetoxy-B1B1B1-trichloroethylphosphoric acid. Hyphlophos is a light yellow transparent oily liquid, readily soluble in most organic solvents, rapidly hydrolyzed in an alkaline medium. Hyphlophos is produced in the form of a 15% solution of dematef in organic solvents, packaged in polyethylene, glass or metal containers of 1-50 liters. The drug is stored in its original container at a temperature from minus 25°C to plus 20°C. Guaranteed shelf life is 1 year from the date of manufacture. Hyphlophos is an insecticide of systemic and contact action, highly effective against larvae of subcutaneous gadflies of all stages of development. The drug is recommended for the treatment of young cattle by watering along the spine at a dose of 12 ml for animals weighing up to 200 kg and 16 ml - over 200 kg. During the period of appearance of nodules under the skin, treatment is proposed by wetting the skin and hair in the places where nodules are formed with a 2% aqueous emulsion of hypchlorvos, at a dose of 200-250 ml per animal. To prepare a 2% aqueous emulsion, take 200 ml of hypchlorvos and mix with 1300 ml of water at a temperature of plus 18-20°C. The emulsion is prepared immediately before use and should be used during the day. Slaughter for meat of young cattle after treatment with hypchlophos is allowed no earlier than 14 days after treatment. It is not allowed to treat dairy, pregnant animals with hypchlophos two weeks before calving, as well as sick and emaciated cattle.
Karbofos(malatol, marafel, maltox, malaspray, sumitox, emmaphos, phytanon, kipfos, zithiol, malathion, metaton, zition, malamar). Colorless oily liquid with a characteristic unpleasant odor. Soluble in water - 150 mg/g, freely soluble in organic solvents. Technical product 93-95% a.i. - dark brown liquid with an unpleasant odor. It may contain dimethyldithiophosphoric acid and xylene as impurities. Hydrolyzes slowly in water, decomposes rapidly in alkalis. It is produced in the form of 30 and 50% emulsion concentrate, in the form of 4% dust and 40% oil solution. In animal husbandry, it is used to combat synanthropic flies, cockroaches, fleas, ixodid ticks; it is used in the form of 0.25-1% water emulsion, 4% dust. Residual action 10-15 days. Karbofos is an ovocide and is detrimental to lice nits. For this purpose, Pedilin shampoo (0.5% malathion) has been developed. In aerosol form, karbofos is used under the name "Karbozol", which contains as a.i. 1.52% DDVF and 1.52% karbofos; "Exophos" contains 0.56 (0.67)% karbofos and 0.56 (0.67)% permethrin. To kill lice and lice eaters, cattle are sprayed with 0.5% aqueous emulsion of karbofos with a consumption rate of 2-4 liters, pigs - 0.5-2 liters per animal or dusted with 4% dust at a dose of 179 g per animal (for large cattle). Slaughter of animals for meat is allowed 14 days after the last treatment. After a single treatment of cows with a 0.5% aqueous emulsion, the drug was found in milk. Its isolation lasted 3 days. Karbofos is moderately toxic; DC50 for mice and rats 400-1400 mg/kg. It has a skin-irritating effect and cumulative properties. In the body of warm-blooded animals, it is activated by oxidation (desulfurization), turning into an active anticholinesterase agent - malooxon, which is detoxified mainly in the liver of animals. Synergism was noted under the action of karbofos and chlorophos. There are known cases of transformation of karbofos in the environment into much more active compounds - isomalation and malooxone. Impurities of maloxone, isomathion, tetramethyldithiophosphate, etc. were isolated from technical malathion. Potentiation of toxicity by impurities is possible. The preparation is destroyed during heat treatment of food products. The drug is to be stored in aluminum or iron containers with anti-corrosion coating.
Ectocide- insectoacaricide of contact and fumigate action, which contains a mixture of karbofos and DDVF as an active substance. It is an oily liquid, from light yellow to dark brown in color, emulsifies well with water, is frost-resistant, and hydrolyzes in an alkaline environment. The drug is produced in the form of a 3% emulsion concentrate in polyethylene or metal containers of 30, 40 and 50 liters, glass bottles of 10 or 20 liters and metal flasks of 25 liters. Ectocide is stored in hermetically sealed original packaging at temperatures from minus 30°C to plus 25°C, the warranty period is 1.5 years from the date of manufacture.
Ectocide has a wide spectrum of insecticidal action, is active against chicken mites, bed bugs and flies. The drug is used for disinfestation and desacarization of poultry premises by spraying with a working aqueous emulsion at the rate of 33 g of 3% ectocide concentrate per 1000 ml of water. The working emulsion is prepared immediately before use, given that the water temperature should not exceed plus 25°C. The treatment is carried out during the preventive break, i.e. in the absence of a bird, twice, taking into account the development of the parasite. To combat chicken bugs and flares, a 0.005-0.1% aqueous emulsion is used at the rate of 50-100 ml per 1 m2 of surface. To combat bed mites, 0.25% w.e. is used. 50-100 ml/m2. Exposure after treatment is 24 hours, after which the room is ventilated, feeders and drinkers are neutralized with a 3% solution of soda ash. The bird is injected after 2 days.
Sebacil (foxim, volaton, valexon, baytion). Low volatility brown liquid. Let's badly dissolve in water (7 mg/l), we will well dissolve in organic solvents. Hydrolyzes under the action of water and alkalis. In the light it is subject to rapid decay. Low toxicity for rats and mice: LD50, respectively, 1750 and 1455 mg / kg, moderately toxic for cats - LD50500 mg / kg, for dogs - 250-500 mg / kg. It has moderately pronounced cumulative properties (K.k.5). Pronounced skin-resorptive toxicity. No mutagenic effect was found. Sebacil is excreted in milk from cows within 3-5 days. It is removed from the body mainly with urine. After 14 days, its traces are established only in adipose tissue. In the organs and tissues of pigs treated with sebacil-puron (its composition is 7.58 g a.i. on isopropyl alcohol), the content of a.i. after 7 days in adipose tissue was 0.3-1.1 mg/kg, after 14 days - 0.03-0.1, after 18 days - 0.06-0.09 mg/kg. It is prescribed to young animals at a dose of 4 ml per 10 kg of body weight, for adults - 20 ml per 50 kg. In addition, in veterinary practice, water emulsions and aerosols of sebacil are used for spraying and bathing animals in the event of arachnoentomosis. Used in the form of baths and aerosols, sebacyl, according to T. Malanet, quickly decomposes in natural conditions and is non-toxic even with a 4-fold overdose.
Currently, Bayer in Germany produces sebacil 50% a.e., used in the form of aqueous emulsions with a concentration of 0.05%, prepared in a ratio of 1 liter of the drug per 1000 liters of water. When spraying, the consumption of the working emulsion is on average 3.5 liters. The solution is added to the bath at a volume of 1000 liters every 120-240 animals. The remaining working emulsion must not be dumped into natural and artificial reservoirs.
The drug is available in bottles of 250 ml; plastic bottles of 1000 ml and canisters of 5 liters. Shelf life in original packaging - 2 years.

Phosphorus organic means

Organophosphorus agents (chlorophos, metaphos) are fast - and potent substances. They are mainly used as insecticides. The hearth is unstable.

Aggregate states- aerosol, fine gray dust with an unpleasant odor. With a long stay in a polluted environment, there is a dulling of the sense of smell with the development of "addiction" to the reagent. The defeat occurs through the upper respiratory tract, digestive tract, intact skin and mucous membranes.

Signs of defeat- dizziness, convulsions, coma. With preserved consciousness, it is permissible to withdraw the victims from the contaminated area, accompanied by rescuers, using industrial gas masks or respirators. The latter can be replaced with a cotton-gauze bandage moistened with water. To prevent the development of painful phenomena, an injection of an antidote (serine type) with a syringe-tube from an individual first-aid kit is recommended. If the victims lose their ability to move independently, they are taken out on a stretcher using the methods and methods described above.

Hexochlorane- chloride insecticide, slow and strong acting. The hearth is stable. Aggregate states- gray dust or aerosol with an unpleasant odor. It enters the body through the upper respiratory tract or the digestive tract (with water or food). With a long stay in an infected focus, it is possible to get used to the smell of the poison and the occurrence of specific symptoms of the lesion - headache, convulsions, respiratory and cardiac disorders. Victims are usually taken out on foot in industrial gas masks, respirators or cotton-gauze bandages moistened with water.

Gronazan- slow-acting mercury-containing organic drug used in agriculture. The hearth is stable.

Aggregate states- an aerosol or dust of orange, violet, gray color. Inhalation causes a metallic taste in the mouth. The dangerous consequences of infection appear late, in connection with which all those in the outbreak must be delivered (on foot) to the collection points of the affected.

Organophosphorus compounds- substances in the molecules of which there is a phosphorus-carbon bond, i.e. a phosphorus atom directly bonded to a carbon atom (unlike other substances containing phosphorus and carbon, such as phosphates, where the bond between C and P is carried out through oxygen). Organophosphorus compounds include derivatives of hydrogen phosphide (РH3) - phosphines. Primary and secondary phosphines are chemically unstable, capable of self-ignition. Phosphines- strong poisons. The strong toxicity and exceptionally high biological activity of organophosphorus compounds served as the basis for their use as poisonous substances.

Organophosphorus compounds in low concentrations are able to suppress the activity of cholinesterase and other enzyme systems in the body of animals, which makes it possible to use organophosphorus compounds as drugs in the treatment of such serious diseases as glaucoma, malignant neoplasms, etc. A mutagenic effect of organophosphorus compounds has also been discovered, which opens up great prospects in the study of heredity.

Organophosphorus compounds- butifos, karbofos, metafos, methyl-nitrophos, octamethyl, preparation M-81 and M-82, thiophos, chlorophos, phosphamide are highly toxic to humans. Clinical signs of poisoning by various organophosphorus compounds (OPs) are similar, however, the speed of occurrence, the severity of pathological manifestations depend on the degree of toxicity of various pesticides in this group, as well as on the route of entry into the body.

The main role in the mechanism of action of organophosphorus compounds is played by the inhibition of the activity of the cholinesterase enzyme, which is involved in the destruction of the chemical mediator (conductor) of nervous excitation - acetylcholine. The accumulation of the latter leads to changes in the activity of the nervous system and internal organs.

Acute poisoning. The latent period of action is from several minutes to several hours. The first signs of poisoning are headaches, dizziness, general weakness, drowsiness, followed by insomnia, nausea, vomiting, cramping abdominal pain, increased salivation and sweating, pupillary constriction (miosis), blurred vision, nystagmus, decreased tendon reflexes. In the future, respiratory disorders (cough, shortness of breath, asthmatic attacks, when listening to abundant dry and wet rales), muscle twitching, unsteady gait, possible enlargement and soreness of the liver, leukocytosis, lymphopenia, eosinopenia, neutrophilic shift to the left. In severe acute poisoning, loss of consciousness occurs, muscle spasms of the whole body, respiratory disorders are significantly pronounced, resembling pulmonary edema (bubbling breath, abundant wet rales, cyanosis of the lips), and a coma.

Chronic poisoning. Toxic neurasthenia develops (headaches, dizziness, sleep disturbances, fatigue, irritability, memory loss) in combination with autonomic disorders (increased sweating, bright dermographism, arterial hypotension, bradycardia), dyspepsia (nausea, loss of appetite). In the future, changes in the psyche, depression, decreased intelligence, microsymptoms of organic damage to the central nervous system may join. An early sign of the toxic effect of organophosphorus compounds is a decrease in serum cholinesterase activity.

First aid and treatment. In case of acute poisoning, remove the victim from the poisoned area to fresh air to stop the entry of poison into the body through the respiratory tract. Remove contaminated clothing. Remove the poison from the skin with 10-15% ammonia solution or 2-5% sodium bicarbonate solution (soda), followed by treatment with warm water and soap. If FOS gets into the eyes, rinse with 2% sodium bicarbonate solution. If it enters the stomach, rinse with plenty of warm water or 2% sodium bicarbonate solution, then give a saline laxative. When the first signs of intoxication appear, antidote therapy with a 0.1% solution of atropine is carried out: with a mild degree of intoxication - 1 - 2 ml intramuscularly, moderate - 2-4 ml intramuscularly or intravenously, severe - 4 - 6 ml intramuscularly or intravenously, repeating through every 3-8 min. before the appearance of mild signs of atropinization (dilated pupils, dry mucous membranes). In severe acute poisoning, the administration of atropine can be increased to 30 ml or more. Pentafen, tropacin, amizil, cholinesterase reactivators (activity restorers): 2-PAM, TMB-4, dipyroxime can be used as antidote therapy.

In addition to antidote therapy, symptomatic treatment is carried out: for convulsions - hexenal, barbital sodium (medinal), for difficulty breathing - artificial respiration, oxygen, cardiac agents (corazol, cordiamin, mezaton), glucose, for the prevention of pneumonia - antibiotics, sulfonamides. In case of poisoning with avenin and methylacetophos, which do not inhibit the activity of cholinesterase, antidote therapy is not carried out, symptomatic agents are prescribed.

With chronic intoxication- Restorative and symptomatic treatment.

Poison can enter the body through the gastrointestinal tract, respiratory tract, mucous membranes and intact skin. There it undergoes transformations, as a result of which several toxic substances are formed. These poisons are excreted through the gastrointestinal tract, through the lungs (a characteristic "fume" is heard from patients) and with urine. They affect the nervous system (impaired transmission of impulses). The lethal dose is 0.5-2.0 g.

In case of FOS poisoning in addition to the nervous system, the respiratory, cardiovascular, digestive systems, as well as the liver and kidneys, suffer.

Mental disorders are manifested by the development of early asthenic syndrome: patients complain of general weakness, headache, dizziness, inability to concentrate, a feeling of fear, anxiety. In other cases, a mental disorder is characterized by the development of intoxication psychosis, when there is a sharp psychomotor agitation, motor anxiety, a feeling of panic fear, disorientation in time and space. And finally, an early development of a coma with a sharp inhibition or absence of pain sensitivity and pupillary response to light, a decrease in muscle tone and tendon reflexes is possible.

Almost all patients with a pronounced clinical picture of OPC poisoning have pupillary constriction, accompanied by visual impairment in the form of a "grid before the eyes" or double vision. The severity of poisoning corresponds to the degree of constriction of the pupils. In severe poisoning, "pinpoint" pupils are observed with the absence of their reaction to light. Signs of damage to the nervous system - severe muscle weakness, decreased muscle tone and soreness when palpated. A specific symptom of damage to the nervous system in case of OPC poisoning is small twitches of the tongue, observed in all cases. Minor twitches of mimic muscles are less often noted.

Respiratory disorders are due to the fact that FOS cause a sharp increase in the secretion of bronchial glands. A secret released in large quantities (sometimes up to 1.5 liters) clogs the airways, foam is released from the mouth and nose. The patient complains of chest tightness, shortness of breath.

Violation of the functions of the cardiovascular system is manifested by an increase in heart rate and a violation of the heart rhythm. The blood pressure rises. As the condition worsens, a sharp pallor of the skin and a drop in blood pressure, severe shortness of breath and impaired consciousness develop. There are nausea and vomiting, cramping pains in the abdomen, involuntary loose stools. Frequent urination indicates kidney damage. With any route of entry of FOS into the body, the clinical picture is the same, but the timing of the onset of symptoms, their severity and duration are different. When poison enters the gastrointestinal tract, three stages of poisoning are distinguished. The first stage is called the stage of excitation and occurs shortly after exposure to the poison (after 15-20 minutes). At the same time, psychomotor agitation is observed, which is accompanied by a feeling of fear. In this stage, victims are often aggressive and may refuse help. The stage is characterized by general toxic symptoms - dizziness, headache, nausea. Soon, increased sweating appears, salivation increases, pupils begin to narrow, chest tightness and shortness of breath appear (characteristic symptoms of FOS poisoning). Also, heart rate increases and blood pressure rises.

Second stage characterized by a complete picture of poisoning. Convulsions and violent involuntary movements (hyperkinesis) are observed. Coma may develop. Excitation either persists or passes into inhibition. This stage is characterized by twitching of facial muscles, increased muscle tone, pronounced constriction of the pupils and the absence of their reaction to light. Sweating becomes pronounced, the secretion of the salivary and bronchial glands increases, respiratory function disorders increase. Significantly increases blood pressure and slows down the pulse. Involuntary loose stools appear and urination becomes more frequent.

Third stage- stage of paralysis. In this stage, the victims are usually in a coma. All reflexes are either depressed or absent altogether, blood pressure is significantly reduced, the pulse is extremely rare (20-40 beats per minute). Sometimes it can increase. Respiration is sharply oppressed (superficial and rare).

Organophosphate compounds(or FOS) - insecticides and fungicides, derivatives of pentavalent phosphorus, which have similar mechanisms of action on insects.

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The disadvantage of organophosphorus compounds is the emergence of resistant populations and high acute for mammals, which requires appropriate precautions when using them.

Story

The history of detection of the toxic properties of organophosphorus compounds (OPs) goes back to the beginning of the 20th century.

Initially, they attracted attention as chemical warfare agents (sarin gas was synthesized in Germany in 1938). At the end of World War II, industrial plants were made to synthesize the former.

They have been introduced into agricultural production since 1965 to replace persistent and low ecological ones, and others. FOS proved to be easy to synthesize and highly effective against insects.

In the 1970s, half of the 20 most common in the world belonged to organophosphorus compounds, and 1/5 to methyl carbamates.

FOS have not lost their advantages to this day.

And

Action on harmful organisms

Organophosphorus compounds are nerve poisons that cause paralysis, including death.

Most organophosphorus is not ionized and exhibits significant lipophilic properties; therefore, a substance that has been inhaled or swallowed will be easily absorbed.

is as follows: the active substances, when ingested, phosphorylate the protein enzyme acetylcholinesterase (AChE). It is found in nerve tissues and plays an important role in the transmission of nerve impulses. This enzyme belongs to the group of carboxylic acid ester hydrolases. AChE is mainly localized at receptors on the postsynaptic membrane of the synapse and partially in the membrane of the neuron process (axon).

Organophosphorus compounds, interacting with esterases, suppress their activity by the type of competitive inhibition. The nerve cell, or neuron, is the main structural element of the animal nervous system. Neurons transmit information in the form of impulses (nerve signals).

A neuron is made up of:

• dendrites (numerous processes) associated with other nerve cells and collecting information;
• axon - the only long process ending in a thickening - a synoptic plaque, and transmitting information.

The membrane of one neuron, which is in contact with another cell (muscle cell or neuron), forms a synapse between excitable cells, a functional contact. It distinguishes the presynaptic part - the end of the axon of the first cell, the synaptic cleft - the intercellular space separating the membranes of the contacting cells, and the postsynaptic part - the section of the second cell.

In arthropods, information is transmitted in the form of an electrical signal (current) along the cell membrane. The synaptic cleft is filled with a gel-like substance with a large electrical capacity, and the signal cannot pass through it. The transmission of an electrical signal (excitation) through the gap is carried out by mediators - the chemicals norepinephrine and acetylcholine.

Humans and warm-blooded animals have five mediators (including adrenaline), insects have about 100. When mediators are inactive, they are in vesicles (synaptic vesicles) that isolate them from cellular contents. When the nerve impulse reaches the presynaptic part, the membrane of the cell ending is depolarized, which increases its permeability by calcium ions. The latter, entering the presynaptic part, cause the release of the mediator - the vesicle bursts, and acetylcholine, which has a high reactivity, enters the intercellular space and then into the postsynaptic space of another cell, thereby causing an electrical potential.

The role of the enzyme acetylcholinesterase is that, by hydrolyzing acetylcholine, it reduces arousal. The whole process takes place in a fraction of a second (milliseconds). If there is no acetylchoinesterase or it is blocked, then free acetylcholine accumulates in the synaptic cleft, as a result of which the normal passage of nerve impulses is disrupted. There is a tremor (convulsive activity of the muscles), turning into paralysis.

Organophosphorus preparations have a stronger effect on the postembryonic stages of development of insects and mites (, adults) and weaker on.

With the systematic use of preparations based on organophosphorus compounds for protection against ticks and insects, which give many generations per season, they quickly acquire group resistance. In the practice of plant protection, development must be prevented, for which they are used with various.

Application

preparations used in the form can be manifested in damage (burns) to leaves and especially flowers and buds.

In agriculture

preparations based on organophosphorus compounds are widely used in agriculture. The names of drugs, the method of processing, the listing of protected crops and can be found in the "Regulations for use" tab that exists for each.

The most limited use of highly toxic organophosphorus compounds with pronounced cumulative properties, such as and. They are recommended mainly for the protection of grain, industrial, fruit and citrus crops.

From vegetable crops, they can only process those cultivated for seeds.

Berries are allowed to be processed before flowering or after harvest.

A great advantage of organophosphorus compounds is the presence among them of substances that have the action (and).

These properties of substances are very important, since there are no others in the modern assortment that have such an effect.

In household plots

. In personal household plots, preparations based on, and are used.

Toxic action

Fosethyl aluminum

Fungicides

Action on harmful organisms

Application

Toxic action

Symptoms of intoxication may develop immediately or several hours after exposure. Symptoms may develop over a day or more and persist for several days.

If the intoxication is mild or the compound is easily excreted from the body, the severity of symptoms may decrease quite quickly, although it may take several weeks for the levels of depressed blood ChE to normalize. After acute intoxication, some chronic effects are likely to persist, and weakness and fatigue may persist over time.

When exposed to various organophosphorus compounds, the picture as a whole is similar. It is caused by the accumulation of acetylcholine (ACh) in the nerve endings. Much depends on the way the poison enters the body. If the substance comes into contact with the skin, the initial symptom may be the development of muscle fibrillations in this place. When inhaled, first there is difficulty in breathing, miosis, after which the central and autonomic nervous systems are affected. When taken through the stomach, vomiting, intestinal spasms, and later other symptoms of the resorptive action of substances usually occur.

herbicides

Of the organophosphorus compounds, it is a broad-spectrum herbicide and an arboricide. This compound has a selective and continuous action, it is used to combat annual and perennial weeds.

. has contact and partially systemic action. In the underground organs of the plant moves from the aboveground, being absorbed through the leaves. The compound is believed to inhibit the biosynthesis of phenylalanine.

Prevention of this synthesis leads to the death of plants. Precipitation residues of the drug can be washed away from plants into the soil. Plant roots do not absorb glyphosate from the soil.

Suppressed weed species.

Phosphorus organic compounds belong to the category of pesticides, which are designed to destroy weeds, insects and rodents.

These insecticides are widely used not only in the agricultural industry, but also in everyday life. Many varieties of FOS are highly toxic and can cause serious poisoning both when they enter the body, and when they come into contact with the mucous membranes of the nasopharynx and eyes, and even with intact skin.

FOS poisoning statistics

Acute intoxication with organophosphorus compounds actually ranks first among others, not only in severity, but also in frequency. The lethality of such poisonings is almost 20%, and the frequency is about 15% of all cases of intoxication. It is of interest that alcohol is a kind of antidote for poisoning with organophosphorus compounds. In victims who were in a state of severe alcohol intoxication at the time of poisoning with insecticides, the disease proceeds much easier (convulsions and paresis of the respiratory muscles are absent). However, hemodynamic disturbances may be more pronounced.

Possible Causes of Insecticide Poisoning

Poisoning with organophosphorus compounds can be associated with professional activities and occur as a result of non-compliance with the rules for handling toxic substances. The negligence of one or more people can result not only in serious poisoning for themselves, but also lead to mass intoxication.

In addition to organophosphorus compounds, they can be of a household nature. The causes of accidents can be different, for example:

• lack of designations on containers with poisonous liquid stored at home (a person can take poison inside by mistake, or intentionally for the purpose of intoxication);
• storage of insecticides in places accessible to children (children are very curious by nature, and even if the container with the pesticide is signed, a small child can still drink a dangerous liquid and get acute poisoning);
• non-compliance with safety regulations (neglect of protective equipment when using toxic substances in the household, such as a respirator, gloves, goggles, protective clothing).

When organophosphorus compounds enter the human body in significant doses, they can cause damage to various parts of the central nervous system, which leads to neuritis, paralysis and other serious consequences, up to death.

Classification of organophosphorus compounds according to the degree of toxicity

• the most toxic - insecticides based on thiophos, metaphos, mercaptophos, octamethyl;
• highly toxic - preparations based on methylmercaptophos, phosphamide, dichlorophosphate;
• moderately toxic - chlorophos, karbofos, methylnitrophos and insecticides based on them, as well as saiphos, cyanophos, tribufos;
• low-toxic - demufos, bromophos, temefos.

Symptoms of FOS poisoning

According to the severity of poisoning are divided into 3 stages. The clinic of organophosphorus poisoning is as follows:

With a mild degree of intoxication (stage I):

• psychomotor agitation and feeling of fear;
• labored breathing;
• dilated pupils (miosis);
• spastic pain in the abdomen;
• increased salivation and vomiting;
• severe headaches;
• high blood pressure;
• profuse sweating;
• hoarse breathing.

In moderate form (stage II):

• may persist or gradually give way to lethargy, and sometimes to a coma;
• pronounced miosis, pupils stop responding to light;
• symptoms of hyperhidrosis are maximally manifested (salivation (salivation), sweating, bronchorrhea (sputum secretion from the bronchi) is maximized);
• fibrillary twitching of the eyelids, chest muscles, legs, and sometimes all muscles;
• periodic appearance of general hypertonicity of the muscles of the body, tonic convulsions;
• sharply increases the tone of the chest;
• blood pressure reaches maximum levels (250/160);
• involuntary defecation and urination, accompanied by painful tenesmus (false urges).

Severe form of poisoning (stage III):

• the patient falls into a deep coma;
• all reflexes are weakened or completely absent;
• severe hypoxia;
• pronounced miosis;
• persistence of symptoms of hyperhidrosis;
• change of muscle hypertonicity, myofibrillation and tonic convulsions by paralytic muscle relaxation;
• breathing is strongly depressed, the depth and frequency of respiratory movements are irregular, paralysis of the respiratory center is possible;
• heart rate drops to critical levels (40-20 per minute);
• tachycardia increases (more than 120 beats per minute);
• blood pressure continues to fall;
• toxic encephalopathy develops with edema and numerous diapedetic hemorrhages, predominantly of a mixed type, caused by paralysis of the respiratory muscles and depression of the respiratory center;
• the skin becomes sharply pale, cyanosis appears (skin and mucous membranes become cyanotic).

Consequences of poisoning with phosphorus-containing insecticides

When organophosphorus compounds enter the body, first aid, provided in a timely and correct manner, is one of the fundamental factors determining the further course of the disease. The diagnosis of FOS intoxication is relatively easy to make according to the characteristic clinical picture, but whether the outcome is favorable or the victim dies depends largely on the subsequent actions of physicians.

Due to the high toxicity, organophosphorus compounds, when ingested, cause irreparable harm to almost all vital organs and systems. In this regard, even with a favorable outcome, it is not possible to completely restore the functions of some organs.

Among the complications that are usually accompanied by severe intoxication with organophosphorus substances are pneumonia, rhythm and conduction disturbances of the heart, acute intoxication psychoses, etc.

Course of the disease

During the first few days after poisoning, the patient is in a serious condition due to cardiovascular collapse. Then comes the gradual compensation and his health improves. However, after 2-3 weeks, the development of severe toxic polyneuropathy is not excluded. In some cases, a number of cranial nerves may be involved in the process.

The course of such late polyneuropathies is quite protracted, sometimes accompanied by persistent movement disorders. The restoration of the functions of the peripheral nervous system is going poorly. There may also be a recurrence of acute disorders such as cholinergic crises. This is explained by the fact that the deposited organophosphorus compound is “ejected” from various tissues into the circulatory system.

Treatment

When serious organophosphorus poisoning occurs, first aid should include aggressive cleansing of the digestive tract by gastric lavage with a tube, forced diuresis, etc., maintenance of breathing, and the use of specific antidotes. Further, a set of resuscitation measures is applied, including pharmacotherapy, aimed at maintaining and restoring damaged body functions, including measures to restore cardiac activity, treatment of homeostasis disorders and exotoxic shock.

Recovery of respiratory function

Organophosphorus compounds ingested in large quantities usually cause respiratory distress, the causes of which are excessive oropharyngeal secretion, bronchospasm and paralysis of the respiratory muscles. In this regard, the first thing that doctors try to do is to restore airway patency and provide adequate ventilation. In the presence of abundant vomit and oropharyngeal discharge, aspiration is used (liquid sampling using a vacuum). In case of acute poisoning with FOS, resuscitation measures include tracheal intubation, artificial ventilation of the lungs.

Antidote therapy

The use of antidotes (antidotes) is an essential part of emergency pharmacotherapy for acute poisoning. The drugs of this group affect the kinetics of a toxic substance in the body, ensure its absorption or elimination, reduce the effect of toxins on receptors, prevent dangerous metabolism and eliminate dangerous disorders of the vital functions of the body caused by poisoning.

An antidote for organophosphorus poisoning is taken along with other specialized drugs. Pharmacotherapy is carried out in parallel with general resuscitation and detoxification therapeutic measures.

It must be remembered that if there is no possibility of urgent resuscitation, then only an antidote of organophosphorus compounds can save the life of the victim, and the sooner it is administered, the more likely the victim will have a favorable outcome of the disease.

Classification of antidotes

Antidotes are divided into four groups:

• symptomatic (pharmacological);
• biochemical (toxicokinetic);
• chemical (toxicotropic);
• antitoxic immunopreparations.

When the first symptoms of organophosphorus poisoning appear, even at the stage of hospitalization of the victim, antidotes of the symptomatic and toxicotropic groups are used, since they have clear indications for use. Drugs with a toxicokinetic action require strict adherence to the instructions, since emergency doctors cannot always accurately determine the indications for their use. Antitoxic immunopreparations are used in a medical institution.

Specific therapy for acute organophosphorus poisoning

The complex of measures includes the use of anticholinergics (drugs such as atropine) in combination with cholinesterase reactivators. In the first hour after hospitalization of the patient, intensive atropinization is carried out. Atropine in large doses is administered intravenously until the symptoms of hyperhidrosis are relieved. There should also be signs of a mild overdose of the drug, expressed by dry skin and moderate tachycardia.

To maintain this state, atropine is administered repeatedly, but in smaller doses. Supportive atropinization creates a persistent blockade of the m-cholinoreactive systems of the damaged organism against the action of the acetylcholine preparation for the time necessary for the destruction and elimination of the toxin.

Modern ones are able to effectively activate the inhibited cholinesterase and neutralize various phosphorus-containing compounds. When carrying out specific therapy, cholinesterase activity is constantly monitored.