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Toxicity (from the Greek. toxikon - poison) - poisonousness, the property of certain chemical compounds and substances of a biological nature, when they enter a living organism (human, animal and plant) in certain quantities, cause violations of its physiological functions, resulting in symptoms of poisoning (intoxication, disease), and in severe cases, death.

A substance (compound) that has the property of toxicity is called a toxic substance or poison.

Toxicity is a generalized indicator of the body's response to the action of a substance, which is largely determined by the characteristics of the nature of its toxic effect.

The nature of the toxic effect of substances on the body usually means:

o the mechanism of the toxic action of the substance;

o the nature of pathophysiological processes and the main symptoms of damage that occur after the defeat of biotargets;

o dynamics of their development in time;

o other aspects of the toxic effect of the substance on the body.

Among the factors that determine the toxicity of substances, one of the most important is the mechanism of their toxic action.

The mechanism of toxic action is the interaction of a substance with molecular biochemical targets, which is a trigger in the development of subsequent intoxication processes.

The interaction between toxic substances and a living organism has two phases:

1) the effect of toxic substances on the body - the toxicodynamic phase;

2) the action of the organism on toxic substances - the toxicokinetic phase.

The toxicokinetic phase, in turn, consists of two types of processes:

a) distribution processes: absorption, transport, accumulation and release of toxic substances;

b) metabolic transformations of toxic substances - biotransformation.

The distribution of substances in the human body depends mainly on the physicochemical properties of substances and the structure of the cell as the basic unit of the body, in particular the structure and properties of cell membranes.

An important provision in the action of poisons and toxins is that they have a toxic effect when exposed to the body in small doses. Very low concentrations of toxic substances are created in target tissues, which are commensurate with the concentrations of biotargets. High rates of interaction of poisons and toxins with biotargets are achieved due to the high affinity for the active centers of certain biotargets.

However, before "hitting" the biotarget, the substance penetrates from the place of application into the system of capillaries of blood and lymphatic vessels, then it is carried by the blood throughout the body and enters the target tissues. On the other hand, as soon as the poison enters the blood and tissues of the internal organs, it undergoes certain transformations, which usually lead to detoxification and "expenditure" of the substance for the so-called non-specific ("side") processes.

One of the important factors is the rate of penetration of substances through cell-tissue barriers. On the one hand, this determines the rate of penetration of poisons through tissue barriers separating blood from the external environment, i.e. the rate of entry of substances through certain routes of penetration into the body. On the other hand, this determines the rate of penetration of substances from the blood into the target tissues through the so-called histohematic barriers in the area of ​​the walls of the blood capillaries of the tissues. This, in turn, determines the rate of accumulation of substances in the area of ​​molecular biotargets and the interaction of substances with biotargets.

In some cases, the rate of penetration through cell barriers determines the selectivity in the action of substances on certain tissues and organs. This affects the toxicity and nature of the toxic effect of substances. Thus, charged compounds penetrate poorly into the central nervous system and have a more pronounced peripheral effect.

In general, in the action of poisons on the body, it is customary to distinguish the following main stages.

1. The stage of contact with the poison and the penetration of the substance into the blood.

2. The stage of transport of a substance from the place of application by blood to target tissues, distribution of the substance throughout the body and metabolism of the substance in the tissues of internal organs - the toxic-kinetic stage.

3. The stage of substance penetration through histohematic barriers (capillary walls and other tissue barriers) and accumulation in the area of ​​molecular biotargets.

4. The stage of interaction of a substance with biotargets and the occurrence of disturbances in biochemical and biophysical processes at the molecular and subcellular levels - the toxic-dynamic stage.

5. The stage of functional disorders of the organism of the development of pathophysiological processes after the "defeat" of molecular biotargets and the onset of symptoms of damage.

6. The stage of relief of the main symptoms of intoxication that threaten the life of the affected person, including the use of medical protective equipment, or the stage of outcomes (with fatal toxodoses and untimely use of protective equipment, the death of the affected is possible).

Dose is a measure of the toxicity of a substance. The dose of a substance that causes a certain toxic effect is called the toxic dose (toxodose). For animals and humans, it is determined by the amount of a substance that causes a certain toxic effect. The lower the toxic dose, the higher the toxicity.

Due to the fact that the reaction of each organism to the same toxodose of a particular toxic substance is different (individual), then the severity of poisoning in relation to each of them will not be the same. Some may die, others will be injured in varying degrees of severity or not at all. Therefore, toxodose (D) is considered as a random variable. It follows from the theoretical and experimental data that the random variable D is distributed according to a logarithmically normal law with the following parameters: D - the median value of toxodose and the dispersion of the logarithm of toxodose - . In this regard, in practice, to characterize toxicity, median values ​​​​of relative, for example, to the mass of the animal, toxodose (hereinafter toxodose) are used.

Poisoning caused by the intake of poison from the human environment is called exogenous, in contrast to endogenous intoxications with toxic metabolites that can form or accumulate in the body in various diseases, often associated with impaired function of internal organs (kidneys, liver, etc.). In the toxigenic (when the toxic agent is in the body at a dose capable of exerting a specific effect) phase of poisoning, two main periods are distinguished: the resorption period, which lasts until the maximum concentration of the poison in the blood is reached, and the elimination period, from the specified moment until the blood is completely cleansed of the poison . The toxic effect may occur before or after the absorption (resorption) of the poison into the blood. In the first case, it is called local, and in the second - resorptive. There is also an indirect reflex effect.

With "exogenous" poisoning, the following main routes of entry of poison into the body are distinguished: oral - through the mouth, inhalation - when toxic substances are inhaled, percutaneous (cutaneous, in military affairs - skin-resorptive) - through unprotected skin, injection - with parenteral administration of poison , for example, with snake and insect bites, cavitary - when poison enters various cavities of the body (rectum, vagina, external auditory canal, etc.).

Table values ​​of toxodoses (except for inhalation and injection routes of penetration) are valid for an infinitely large exposure, i.e. for the case when extraneous methods do not stop the contact of a toxic substance with the body. In reality, for the manifestation of one or another toxic effect of the poison, there must be more than those given in the toxicity tables. This amount and the time during which the poison must be, for example, on the skin surface during resorption, in addition to toxicity, is largely due to the rate of absorption of the poison through the skin. So, according to US military experts, the chemical warfare agent Vigas (VX) is characterized by a skin-resorptive toxodose of 6-7 mg per person. For this dose to enter the body, 200 mg VX liquid drip must be in contact with the skin for about 1 hour, or approximately 10 mg for 8 hours.

It is more difficult to calculate toxodoses for toxic substances that contaminate the atmosphere with steam or fine aerosol, for example, in case of accidents at chemically hazardous facilities with the release of emergency chemically hazardous substances (AHOV - according to GOST R 22.0.05-95), which cause damage to humans and animals through the respiratory system .

First of all, they make the assumption that the inhalation toxodose is directly proportional to the concentration of hazardous chemicals in the inhaled air and the breathing time. In addition, it is necessary to take into account the intensity of breathing, which depends on the physical activity and the condition of the person or animal. In a calm state, a person takes about 16 breaths per minute and, therefore, on average absorbs 8-10 l / min of air. With moderate physical activity (accelerated walking, march) air consumption increases to 20-30 l/min, and with heavy physical activity (running, excavation) it is about 60 l/min.

Thus, if a person of mass G (kg) inhales air with a concentration of C (mg / l) in it of AHOV during time τ (min) at a breathing rate of V (l / min), then the specific absorbed dose of AHOV (the amount of AHOV that got into into the body) D(mg/kg) will be equal to

The German chemist F. Gaber proposed to simplify this expression. He made the assumption that for humans or a particular species of animals under the same conditions, the ratio V/G is constant, thus it can be excluded when characterizing the inhalation toxicity of a substance, and received the expression K=Cτ (mg min/l). Haber called the product Cτ the toxicity coefficient and took it as a constant value. This work, although not a toxodose in the strict sense of the word, makes it possible to compare various toxic substances by inhalation toxicity. The smaller it is, the more toxic the substance during inhalation action. However, this approach does not take into account a number of processes (exhalation of a part of the substance back, neutralization in the body, etc.), but nevertheless, the Cτ product is still used to assess inhalation toxicity (especially in military affairs and civil defense when calculating possible losses troops and the population under the influence of chemical warfare agents and hazardous chemicals). Often this work is even incorrectly called toxodose. The name of relative toxicity by inhalation seems to be more correct. In clinical toxicology, to characterize inhalation toxicity, preference is given to the parameter in the form of a concentration of a substance in the air, which causes a given toxic effect in experimental animals under conditions of inhalation exposure at a certain exposure.

The relative toxicity of OM during inhalation depends on the physical load on the person. For people engaged in heavy physical work, it will be much less than for people who are at rest. With an increase in the intensity of respiration, the speed of the OF will also increase. For example, for Sarin with pulmonary ventilation of 10 L/min and 40 L/min, the LCτ 50 values ​​are about 0.07 mg·min/L and 0.025 mg·min/L, respectively. If for the phosgene substance the product Cτ of 3.2 mg min/l at a respiratory rate of 10 l/min is moderately lethal, then with pulmonary ventilation of 40 l/min it is absolutely lethal.

It should be noted that the tabular values ​​of the constant Сτ are valid for short exposures, at which Сτ = const. When inhaling contaminated air with low concentrations of a toxic substance in it, but for a sufficiently long period of time, the value of Сτ increases due to the partial decomposition of the toxic substance in the body and incomplete absorption by the lungs. For example, for hydrocyanic acid, the relative toxicity during inhalation of LCτ 50 ranges from 1 mg · min / l for its high concentrations in the air to 4 mg · min / l when the concentrations of the substance are low. The relative toxicity of substances during inhalation also depends on the physical load on the person and his age. For adults, it will decrease with increasing physical activity, and for children - with decreasing age.

Thus, the toxic dose that causes damage equal in severity depends on the properties of the substance, the route of its penetration into the body, the type of organism and the conditions for using the substance.

For substances penetrating the body in a liquid or aerosol state through the skin, gastrointestinal tract, or through wounds, the damaging effect for each specific type of organism under stationary conditions depends only on the amount of poison that has penetrated, which can be expressed in any mass units. In toxicology, the amount of poison is usually expressed in milligrams.

The toxic properties of poisons are determined experimentally on various laboratory animals, therefore, the concept of specific toxodose is often used - a dose related to a unit of animal live weight and expressed in milligrams per kilogram.

The toxicity of the same substance, even when it enters the body in one way, is different for different animal species, and for a particular animal it differs markedly depending on the method of entry into the body. Therefore, after the numerical value of the toxodose, it is customary to indicate in brackets the type of animal for which this dose is determined, and the method of administration of the agent or poison. For example, the entry: "sarin D death 0.017 mg/kg (rabbits, intravenous)" means that a dose of the substance sarin 0.017 mg/kg injected into a rabbit's vein causes death in him.

It is customary to subdivide toxodoses and concentrations of toxic substances depending on the severity of the biological effect they cause.

The main indicators of toxicity in the toxicometry of industrial poisons and in emergency situations are:

Lim ir - the threshold of irritating action on the mucous membranes of the upper respiratory tract and eyes. It is expressed by the amount of a substance that is contained in one volume of air (for example, mg / m 3).

A lethal or lethal dose is the amount of a substance that causes death with a certain probability when it enters the body. Usually they use the concepts of absolutely lethal toxodosis, causing the death of the body with a probability of 100% (or the death of 100% of those affected), and medium-lethal (slow-fatal) or conditionally fatal toxodosis, the lethal outcome from the introduction of which occurs in 50% of the affected. For example:

LD 50 (LD 100) - (L from lat. letalis - lethal) medium lethal (lethal) dose that causes the death of 50% (100%) of experimental animals when the substance is injected into the stomach, into the abdominal cavity, onto the skin (except for inhalation) under certain conditions of administration and a specific follow-up period (usually 2 weeks). It is expressed as the amount of a substance per unit body mass of the animal (usually mg/kg);

LC 50 (LC 100) - average lethal (lethal) concentration in the air, causing the death of 50% (100%) of experimental animals upon inhalation exposure to a substance at a certain exposure (standard 2-4 hours) and a certain follow-up period. As a rule, the exposure time is specified additionally. Dimension as for Lim ir

The incapacitating dose is the amount of a substance that, when ingested, causes the failure of a certain percentage of those affected, both temporarily and fatally. It is designated ID 100 or ID 50 (from the English incapacitate - disable).

Threshold dose - the amount of a substance that causes the initial signs of damage to the body with a certain probability or, what is the same, the initial signs of damage in a certain percentage of people or animals. Threshold doses are designated PD 100 or PD 50 (from English primary - initial).

KVIO - coefficient of possibility of inhalation poisoning, which is the ratio of the maximum achievable concentration of a toxic substance (C max, mg / m 3) in the air at 20 ° C to the average lethal concentration of the substance for mice (KVIO = C max / LC 50). The value is dimensionless;

MPC - maximum allowable concentration of a substance - the maximum amount of a substance per unit volume of air, water, etc., which, with daily exposure to the body for a long time, does not cause pathological changes in it (deviations in the state of health, disease) detected by modern research methods in the process life or remote periods of life of the present and subsequent generations. There are MPC of the working area (MPC r.z, mg / m 3), maximum one-time MPC in the atmospheric air of populated areas (MPC m.r, mg / m 3), average daily MPC in the atmospheric air of populated areas (MPC s.s, mg / m 3), MPC in the water of reservoirs of various water uses (mg / l), MPC (or permissible residual amount) in food (mg / kg), etc .;

OBUV - an approximate safe level of exposure to the maximum allowable content of a toxic substance in the atmospheric air of populated areas, in the air of the working area and in the water of reservoirs for fishery water use. There are additionally TAC - the approximate allowable level of a substance in the water of reservoirs for household water use.

In military toxicometry, the most commonly used indicators are relative median values ​​of average lethal (LCτ 50), medium excretory (ICτ 50), average effective (ECτ 50), average threshold (PCτ 50) inhalation toxicity, usually expressed in mg min / l, as well as median values ​​of skin-resorptive toxodoses similar in toxic effect LD 50 , LD 50 , ED 50 , PD 50 (mg/kg). At the same time, toxicity indicators during inhalation are also used to predict (estimate) the losses of the population and production personnel in case of accidents at chemically hazardous facilities with the release of toxic chemicals widely used in industry.

In relation to plant organisms, instead of the term toxicity, the term activity of a substance is more often used, and as a measure of its toxicity, the value of CK 50 is mainly used - the concentration (for example, mg / l) of a substance in solution that causes the death of 50% of plant organisms. In practice, they use the rate of consumption of the active (active) substance per unit area (mass, volume), usually kg / ha, at which the desired effect is achieved.

Consciousness Disorder Syndrome. It is due to the direct effect of the poison on the cerebral cortex, as well as the disorders of cerebral circulation and oxygen deficiency caused by it. Such phenomena (coma, stupor) occur in severe poisoning with chlorinated hydrocarbons, organophosphorus compounds (FOS), alcohols, opium preparations, sleeping pills.

Syndrome of respiratory failure. It is often observed in coma, when the respiratory center is depressed. Disorders of the act of breathing also occur due to paralysis of the respiratory muscles, which greatly complicates the course of poisoning. Severe respiratory dysfunction occurs with toxic pulmonary edema and airway obstruction.

Blood lesion syndrome. Characteristic for carbon monoxide poisoning, hemoglobin oxidizers, hemolytic poisons. At the same time, hemoglobin is inactivated, the oxygen capacity of the blood decreases.

Syndrome of circulatory disorders. Almost always accompanies acute poisoning. The causes of dysfunction of the cardiovascular system can be: inhibition of the vasomotor center, dysfunction of the adrenal glands, increased permeability of the walls of blood vessels, etc.

Syndrome of violation of thermoregulation. It is observed in many poisonings and is manifested either by a decrease in body temperature (alcohol, sleeping pills, cyanides), or by its increase (carbon monoxide, snake venom, acids, alkalis, FOS). These changes in the body, on the one hand, are the result of a decrease in metabolic processes and increased heat transfer, and on the other hand, the absorption of toxic products of tissue decay into the blood, disorders in the supply of oxygen to the brain, and infectious complications.

convulsive syndrome. As a rule, it is an indicator of a severe or extremely severe course of poisoning. Seizures occur as a result of an acute oxygen starvation of the brain (cyanides, carbon monoxide) or as a result of the specific action of poisons on the central nervous structures (ethylene glycol, chlorinated hydrocarbons, FOS, strychnine).

Syndrome of mental disorders. It is typical for poisoning with poisons that selectively act on the central nervous system (alcohol, lysergic acid diethylamide, atropine, hashish, tetraethyl lead).

Syndromes of liver and kidney damage. They are accompanied by many types of intoxication, in which these organs become objects of direct exposure to poisons or suffer due to the influence of toxic metabolic products and the breakdown of tissue structures on them. This especially often accompanies poisoning with dichloroethane, alcohols, vinegar essence, hydrazine, arsenic, salts of heavy metals, yellow phosphorus.

Syndrome of disturbance of water and electrolyte balance and acid-base balance. In acute poisoning, it is mainly a consequence of a disorder in the function of the digestive and excretory systems, as well as secretory organs. In this case, dehydration of the body, a perversion of redox processes in tissues, and the accumulation of under-oxidized metabolic products are possible.

Dose. Concentration. Toxicity

As already noted, affecting the body in different quantities, the same substance causes an unequal effect. Minimum operating, or threshold, dose(concentration) of a toxic substance is its smallest amount, which causes obvious, but reversible changes in vital activity. Minimum toxic dose- this is already a much larger amount of poison, causing severe poisoning with a complex of characteristic pathological changes in the body, but without a fatal outcome. The stronger the poison, the closer the values ​​of the minimum effective and minimum toxic doses. In addition to those mentioned, in toxicology it is also customary to consider lethal (lethal) doses and concentrations of poisons, i.e. those quantities that lead a person (or animal) to death if left untreated. Lethal doses are determined as a result of animal experiments. In experimental toxicology, the most commonly used average lethal dose(DL 50) or concentration (CL 50) of the poison, at which 50% of the experimental animals die. If 100% of their death is observed, then such a dose or concentration is designated as absolute lethal(DL 100 and CL 100). The concept of toxicity (toxicity) means a measure of the incompatibility of a substance with life and is determined by the reciprocal of DL 50 (CL 50), i.e.).

Depending on the routes of entry of the poison into the body, the following toxicometric parameters are determined: mg/kg of body weight - when exposed to poison that has entered the body with poisoned food and water, as well as on the skin and mucous membranes; mg / l or g / m 3 of air - with inhalation (i.e., through the respiratory organs) penetration of the poison into the body in the form of gas, vapor or aerosol; mg / cm 2 of the surface - if the poison gets on the skin. There are methods for a more in-depth quantitative assessment of the toxicity of chemical compounds. So, when exposed through the respiratory tract, the degree of toxicity of the poison (T) is characterized by the modified Haber formula:

where c is the concentration of the poison in the air (mg/l); t - exposure time (min); ? - lung ventilation volume (l/min); g - body weight (kg).

With different methods of introducing poisons into the body, unequal amounts of them are required in order to cause the same toxic effect. For example, the DL 50s of diisopropyl fluorophosphate found in rabbits by various routes of administration are as follows (in mg/kg):

A significant excess of the oral dose over parenteral (i.e., introduced into the body, bypassing the gastrointestinal tract) indicates primarily the destruction of most of the poison in the digestive system.

Taking into account the value of average lethal doses (concentrations) for various routes of entry into the body, poisons are divided into groups. One of such classifications developed in our country is given in the table.

Classification of harmful substances according to the degree of toxicity (recommended by the All-Union Problem Commission on the Scientific Foundations of Occupational Health and Occupational Pathology in 1970)

With repeated exposure to the same poison on the body, the course of poisoning may change due to the development of cumulation, sensitization and addiction phenomena. Under cumulation refers to the accumulation of a toxic substance in the body material cumulation) or the effects it causes ( functional cumulation). It is clear that the substance that is slowly excreted or slowly neutralized is accumulated, while the total effective dose increases very quickly. As for functional cumulation, it can manifest itself in severe disorders when the poison itself does not linger in the body. This phenomenon can be observed, for example, with alcohol poisoning. The degree of severity of the cumulative properties of toxic substances is usually estimated cumulation factor(K), which is determined in an animal experiment:

where a is the amount of poison re-introduced to the animal, which is 0.1–0.05 DL 50; b is the number of doses administered (a); c - single dose.

Depending on the value of the cumulation coefficient, toxic substances are divided into 4 groups:

1) with a pronounced cumulation (K<1);

2) with pronounced cumulation (K from 1 to 3);

3) with moderate cumulation (K from 3 to 5);

4) with weakly expressed cumulation (K>5).

Sensitization- a state of the body in which repeated exposure to a substance causes a greater effect than the previous one. At present, there is no single view on the biological essence of this phenomenon. On the basis of experimental data, it can be assumed that the effect of sensitization is associated with the formation, under the influence of a toxic substance in the blood and other internal media, of protein molecules that have changed and become alien to the body. The latter induce the formation of antibodies - special structures of a protein nature that carry out the protective function of the body. Apparently, a repeated even much weaker toxic effect, followed by a reaction of the poison with antibodies (or altered receptor protein structures), causes a perverted response of the body in the form of sensitization phenomena.

With repeated exposure to poisons on the body, one can also observe the opposite phenomenon - a weakening of their effects due to addictive, or tolerance. Mechanisms for the development of tolerance are ambiguous. So, for example, it was shown that addiction to arsenic anhydride is due to the occurrence under its influence of inflammatory processes in the mucous membrane of the gastrointestinal tract and a decrease in the absorption of the poison as a result. At the same time, if arsenic preparations are administered parenterally, no tolerance is observed. However, the most common cause of tolerance is the stimulation, or induction, by poisons of the activity of enzymes that neutralize them in the body. This phenomenon will be discussed later. And now we note that addiction to some poisons, such as FOS, may also be due to a decrease in the sensitivity of the corresponding biostructures to them or an overload of the latter due to the massive impact on them of an excess amount of molecules of a toxic substance.

In connection with the foregoing, legislative regulation is of particular importance. maximum allowable concentrations(MAC) of harmful substances in the air of the working area of ​​industrial and agricultural enterprises, research and testing institutions, design bureaus. It is believed that the maximum allowable concentrations of these substances during daily eight-hour work throughout the entire working experience cannot cause diseases or deviations in the state of health in workers, detected by modern research methods directly in the process of work or in the long term. Compared with other industrialized countries, the USSR has a more rigorous approach to establishing MPCs for many chemical agents. First of all, this applies to substances that have an initially imperceptible, but gradually increasing effect. For example, the Soviet Union adopted lower MPC levels than the United States for carbon monoxide (20 mg/m 3 versus 100 mg/m 3), mercury and lead vapors (0.01 mg/m 3 versus 0.1 mg/m3). m 3), benzene (5 mg / m 3 versus 80 mg / m 3), dichloroethane (10 mg / m 3 versus 400 mg / m 3) and other toxic substances. In our country, enterprises and institutions operate special toxicological and sanitary laboratories that carry out strict control over the content of harmful substances in working premises, the introduction of new environmentally friendly technological processes, the operation of gas and dust collection plants, wastewater, etc. Any chemical product , produced by the industry of the USSR, is tested for toxicity and receives a toxicological characteristic.

Ways of entry of poisons into the body

The entry of poisons into the human body can occur through the respiratory system, the digestive tract and the skin. The huge surface of the lung alveoli (about 80–90 m 2) provides intensive absorption and a quick effect of the action of toxic vapors and gases present in the inhaled air. In this case, first of all, the lungs become the "entrance gate" for those of them that are well soluble in fats. Diffusing through the alveolar-capillary membrane with a thickness of about 0.8 microns, which separates the air from the bloodstream, the molecules of poisons penetrate the pulmonary circulation in the shortest way and then, bypassing the liver, reach the blood vessels of the large circle through the heart.

With poisoned food, water, as well as in a "pure" form, toxic substances are absorbed into the blood through the mucous membranes of the oral cavity, stomach and intestines. Most of them are absorbed into the epithelial cells of the digestive tract and further into the blood by a simple diffusion mechanism. At the same time, the leading factor in the penetration of poisons into the internal environment of the body is their solubility in lipids (fats), more precisely, the nature of the distribution between the lipid and aqueous phases at the site of absorption. The degree of dissociation of poisons also plays a significant role.

As for fat-insoluble foreign substances, many of them penetrate the cell membranes of the mucous membranes of the stomach and intestines through the pores or spaces between the membranes. Although the pore area is only about 0.2% of the entire membrane surface, it nevertheless allows the absorption of many water-soluble and hydrophilic substances. By the blood flow from the gastrointestinal tract, toxic substances are delivered to the liver, an organ that performs a barrier function in relation to the vast majority of foreign compounds.

As many studies show, the rate of penetration of poisons through intact skin is directly proportional to their solubility in lipids, and their further passage into the blood depends on the ability to dissolve in water. This applies not only to liquids and solids, but also to gases. The latter can diffuse through the skin as through an inert membrane. In this way, for example, HCN, CO 2 , CO, H 2 S and other gases overcome the skin barrier. It is interesting to note that the formation of salts with fatty acids of the fatty layer of the skin contributes to the passage of heavy metals through the skin.

Before being in a particular organ (tissue), the poisons in the blood overcome a number of internal cellular and membrane barriers. The most important of them are the hematoencephalic and placental - biological structures that are located on the border of the bloodstream, on the one hand, and the central nervous system and the maternal fetus, on the other. Therefore, the result of the action of poisons and drugs often depends on how pronounced their ability to penetrate barrier structures. So, substances that are soluble in lipids and quickly diffuse through lipoprotein membranes, such as alcohols, narcotic drugs, and many sulfanilamide drugs, penetrate well into the brain and spinal cord. They relatively easily enter the blood of the fetus through the placenta. In this regard, it is impossible not to mention the cases of the birth of children with signs of addiction to drugs, if their mothers were drug addicts. While the baby is in the womb, he adapts to a certain dose of the drug. At the same time, individual foreign substances do not penetrate well through the barrier structures. This is especially true for drugs that form quaternary ammonium bases in the body, strong electrolytes, some antibiotics, and colloidal solutions.

Transformation of toxic substances in the body

Poisons that penetrate the body, like other foreign compounds, can undergo a variety of biochemical transformations ( biotransformation), which most often result in the formation of less toxic substances ( neutralization, or detoxification). But there are many cases of increased toxicity of poisons when their structure in the body changes. There are also compounds whose characteristic properties begin to appear only as a result of biotransformation. At the same time, a certain part of the poison molecules is excreted from the body without any changes or even remains in it for a more or less long period, being fixed by the proteins of the blood plasma and tissues. Depending on the strength of the resulting "poison-protein" complex, the action of the poison slows down or is completely lost. In addition, the protein structure can only be a carrier of a toxic substance, delivering it to the appropriate receptors.

Fig.1. General scheme of intake, biotransformation and excretion of foreign substances from the body

The study of biotransformation processes allows solving a number of practical issues of toxicology. Firstly, knowledge of the molecular essence of detoxification of poisons makes it possible to encircle the body's defense mechanisms and, on this basis, outline ways of directed action on the toxic process. Secondly, the amount of the dose of poison (drug) that has entered the body can be judged by the amount of products of their transformation - metabolites - excreted through the kidneys, intestines and lungs, which makes it possible to control the health of people involved in the production and use of toxic substances; moreover, in various diseases, the formation and excretion of many biotransformation products of foreign substances from the body is significantly impaired. Thirdly, the appearance of poisons in the body is often accompanied by the induction of enzymes that catalyze (accelerate) their transformation. Therefore, by influencing the activity of induced enzymes with the help of certain substances, it is possible to accelerate or slow down the biochemical processes of transformations of foreign compounds.

It has now been established that the processes of biotransformation of foreign substances occur in the liver, gastrointestinal tract, lungs, and kidneys (Fig. 1). In addition, according to the results of research by Professor I. D. Gadaskina, a considerable number of toxic compounds undergo irreversible transformations in adipose tissue. However, the liver, or rather, the microsomal fraction of its cells, is of primary importance here. It is in the liver cells, in their endoplasmic reticulum, that most of the enzymes that catalyze the transformation of foreign substances are localized. The reticulum itself is a plexus of linoprotein tubules penetrating the cytoplasm (Fig. 2). The highest enzymatic activity is associated with the so-called smooth reticulum, which, unlike the rough one, does not have ribosomes on its surface. It is not surprising, therefore, that in diseases of the liver, the body's sensitivity to many foreign substances sharply increases. It should be noted that, although the number of microsomal enzymes is small, they have a very important property - high affinity for various foreign substances with relative chemical nonspecificity. This creates the opportunity for them to enter into neutralization reactions with almost any chemical compound that has entered the internal environment of the body. Recently, the presence of a number of such enzymes in other cell organelles (for example, in mitochondria), as well as in blood plasma and in intestinal microorganisms, has been proven.

Rice. 2. Schematic representation of a liver cell (Park, 1373). 1 - core; 2 - lysosomes; 3 - endoplasmic reticulum; 4 - pores in the nuclear envelope; 5 - mitochondria; 6 - rough endoplasmic reticulum; 7 - invagination of the plasma membrane; 8 - vacuoles; 9 - true glycogen; 10 - smooth endoplasmic reticulum

It is believed that the main principle of the transformation of foreign compounds in the body is to ensure the highest rate of their excretion by transferring from fat-soluble to more water-soluble chemical structures. In the last 10–15 years, when studying the essence of biochemical transformations of foreign compounds from fat-soluble to water-soluble, the so-called monooxygenase enzyme system with a mixed function, which contains a special protein, cytochrome P-450, has been increasingly important. It is similar in structure to hemoglobin (in particular, it contains iron atoms with variable valence) and is the final link in the group of oxidizing microsomal enzymes - biotransformers, concentrated mainly in liver cells. In the body, cytochrome P-450 can be found in 2 forms: oxidized and reduced. In the oxidized state, it first forms a complex compound with a foreign substance, which is then reduced by a special enzyme - cytochrome reductase. This now reduced compound then reacts with activated oxygen to form an oxidized and generally non-toxic substance.

The biotransformation of toxic substances is based on several types of chemical reactions, which result in the addition or elimination of methyl (-CH 3), acetyl (CH 3 COO-), carboxyl (-COOH), hydroxyl (-OH) radicals (groups), as well as sulfur atoms and sulfur-containing groups. Of considerable importance are the processes of decomposition of the molecules of poisons up to the irreversible transformation of their cyclic radicals. But a special role among the mechanisms for neutralizing poisons is played by synthesis reactions, or conjugations, resulting in the formation of non-toxic complexes - conjugates. At the same time, the biochemical components of the internal environment of the body that enter into irreversible interaction with poisons are: glucuronic acid (C 5 H 9 O 5 COOH), cysteine ​​( ), glycine (NH 2 -CH 2 -COOH), sulfuric acid, etc. Poison molecules containing several functional groups can be transformed through 2 or more metabolic reactions. In passing, we note one significant circumstance: since the transformation and detoxification of toxic substances due to conjugation reactions are associated with the consumption of substances important for life, these processes can cause a deficiency of the latter in the body. Thus, a different kind of danger appears - the possibility of developing secondary disease states due to a lack of necessary metabolites. Thus, the detoxification of many foreign substances is dependent on glycogen stores in the liver, since glucuronic acid is formed from it. Therefore, when large doses of substances enter the body, the neutralization of which is carried out through the formation of esters of glucuronic acid (for example, benzene derivatives), the content of glycogen, the main easily mobilized reserve of carbohydrates, decreases. On the other hand, there are substances that, under the influence of enzymes, are able to split off molecules of glucuronic acid and thereby contribute to the neutralization of poisons. One of these substances was glycyrrhizin, which is part of the licorice root. Glycyrrhizin contains 2 molecules of glucuronic acid in a bound state, which are released in the body, and this, apparently, determines the protective properties of licorice root in many poisonings, which have long been known to medicine in China, Tibet, and Japan.

As for the removal of toxic substances and their products from the body, the lungs, digestive organs, skin, and various glands play a certain role in this process. But the nights are the most important here. That is why, in many cases of poisoning, with the help of special agents that enhance the separation of urine, they achieve the fastest removal of toxic compounds from the body. At the same time, one has to reckon with the damaging effects on the kidneys of some poisons excreted in the urine (for example, mercury). In addition, the products of the transformation of toxic substances may be retained in the kidneys, as is the case with severe ethylene glycol poisoning. When it is oxidized, oxalic acid is formed in the body and calcium oxalate crystals precipitate in the renal tubules, preventing urination. In general, such phenomena are observed when the concentration of substances excreted through the kidneys is high.

To understand the biochemical essence of the processes of transformation of toxic substances in the body, let us consider several examples concerning the common components of the chemical environment of modern man.

Rice. 3. Oxidation (hydroxylation) of benzene to aromatic alcohols, formation of conjugates and complete destruction of its molecule (aromatic ring rupture)

So, benzene, which, like other aromatic hydrocarbons, is widely used as a solvent for various substances and as an intermediate in the synthesis of dyes, plastics, drugs, and other compounds, is transformed in the body in 3 ways with the formation of toxic metabolites (Fig. 3). The latter are excreted through the kidneys. Benzene can stay in the body for a very long time (according to some sources, up to 10 years), especially in adipose tissue.

Of particular interest is the study of the processes of transformation in the body toxic metals which have an ever wider impact on a person in connection with the development of science and technology and the development of natural resources. First of all, it should be noted that as a result of interaction with the redox buffer systems of the cell, in which electron transfer occurs, the valence of metals changes. In this case, the transition to a state of lower valency is usually associated with a decrease in the toxicity of metals. For example, hexavalent chromium ions pass in the body into a low-toxic trivalent form, and trivalent chromium can be quickly removed from the body with the help of certain substances (sodium pyrosulfate, tartaric acid, etc.). A number of metals (mercury, cadmium, copper, nickel) are actively associated with biocomplexes, primarily with the functional groups of enzymes (-SH, -NH 2 , -COOH, etc.), which sometimes determines the selectivity of their biological action.

In list pesticides- substances intended for the destruction of harmful living beings and plants, there are representatives of various classes of chemical compounds that are to some extent toxic to humans: organochlorine, organophosphorus, organometallic, nitrophenolic, cyanide, etc. According to available data, about 10% of all fatal poisonings currently caused by pesticides. The most significant of them, as is known, are FOS. When hydrolyzed, they usually lose their toxicity. In contrast to hydrolysis, the oxidation of FOS is almost always accompanied by an increase in their toxicity. This can be seen if we compare the biotransformation of 2 insecticides - diisopropyl fluorophosphate, which loses its toxic properties, splitting off a fluorine atom during hydrolysis, and thiophos (a derivative of thiophosphoric acid), which is oxidized to a much more toxic phosphacol (a derivative of phosphoric acid).

Among the widely used medicinal substances sleeping pills are the most common source of poisoning. The processes of their transformations in the body have been studied quite well. In particular, it has been shown that the biotransformation of one of the common derivatives of barbituric acid, luminal (Fig. 4), proceeds slowly, and this underlies its rather long hypnotic effect, since it depends on the number of unchanged luminal molecules in contact with nerve cells. The disintegration of the barbituric ring leads to the termination of the action of luminal (as well as other barbiturates), which, in therapeutic doses, causes sleep lasting up to 6 hours. In this regard, the fate of another representative of barbiturates, hexobarbital, is of interest in the body. Its hypnotic effect is much shorter even when using much larger doses than luminal. It is believed that this depends on the greater speed and on the greater number of ways in which hexobarbital is inactivated in the body (the formation of alcohols, ketones, demethylated and other derivatives). On the other hand, those barbiturates that are stored in the body almost unchanged, such as barbital, have a longer hypnotic effect than luminal. It follows that substances that are excreted unchanged in the urine can cause intoxication if the kidneys cannot cope with their removal from the body.

It is also important to note that in order to understand the unforeseen toxic effect of the simultaneous use of several drugs, due importance must be given to enzymes that affect the activity of the combined substances. For example, the drug physostigmine, when used together with novocaine, makes the latter a very toxic substance, as it blocks the enzyme (esterase) that hydrolyzes novocaine in the body. Ephedrine also manifests itself in a similar way, binding an oxidase that inactivates adrenaline and thereby prolonging and enhancing the action of the latter.

Rice. 4. Modification of the luminal in the body in two directions: through oxidation and due to the breakdown of the barbituric ring, followed by the conversion of the oxidation product into a conjugate

An important role in the biotransformation of drugs is played by the processes of induction (activation) and inhibition of the activity of microsomal enzymes by various foreign substances. So, ethyl alcohol, some insecticides, nicotine accelerate the inactivation of many drugs. Therefore, pharmacologists pay attention to the undesirable consequences of contact with these substances during drug therapy, in which the therapeutic effect of a number of drugs is reduced. At the same time, it should be borne in mind that if contact with the inducer of microsomal enzymes suddenly stops, then this can lead to the toxic effect of drugs and require a reduction in their doses.

It should also be borne in mind that, according to the World Health Organization (WHO), 2.5% of the population has a significantly increased risk of drug toxicity, since their genetically determined plasma half-life in this group of people is 3 times longer than the average. At the same time, about a third of all enzymes described in humans in many ethnic groups are represented by variants that differ in their activity. Hence - individual differences in reactions to one or another pharmacological agent, depending on the interaction of many genetic factors. Thus, it has been established that approximately one per 1–2 thousand people has a sharply reduced activity of serum cholinesterase, which hydrolyzes dithylin, a drug used to relax skeletal muscles for several minutes during certain surgical interventions. In such people, the action of dithylin is sharply prolonged (up to 2 hours or more) and can become a source of a serious condition.

Among people living in the Mediterranean countries, in Africa and Southeast Asia, there is a genetically determined deficiency in the activity of the enzyme glucose-6-phosphate dehydrogenase of erythrocytes (a decrease of up to 20% of the norm). This feature makes erythrocytes less resistant to a number of drugs: sulfonamides, some antibiotics, phenacetin. Due to the breakdown of red blood cells in such individuals, hemolytic anemia and jaundice occur during drug treatment. It is quite obvious that the prevention of these complications should consist in a preliminary determination of the activity of the corresponding enzymes in patients.

Although the above material gives only a general idea of ​​the problem of the biotransformation of toxic substances, it shows that the human body has many protective biochemical mechanisms that, to a certain extent, protect it from the undesirable effects of these substances, at least from their small doses. The functioning of such a complex barrier system is ensured by numerous enzymatic structures, the active influence on which makes it possible to change the course of the processes of transformation and neutralization of poisons. But this is already one of our next topics. In the further presentation, we will still return to the consideration of individual aspects of the transformation of certain toxic substances in the body to the extent that this is necessary for understanding the molecular mechanisms of their biological action.

Biological features of the body that affect the toxic process

What internal factors, i.e., those related to the human body and animals as an object of toxic effects, determine the occurrence, course and consequences of poisoning?

First of all, we must name species differences sensitivity to poisons, which ultimately affect the possibility of transferring experimental data obtained in experiments on animals to humans. For example, dogs and rabbits can tolerate up to 100 times the lethal dose of atropine in humans. On the other hand, there are poisons that have a stronger effect on certain types of animals than on humans. These include hydrocyanic acid, carbon monoxide, etc.

Animals occupying a higher position in the evolutionary series are, as a rule, more sensitive to most neurotropic, that is, chemical compounds acting primarily on the nervous system. Thus, the results of experiments cited by K. S. Shadursky indicate that large identical doses of certain FOS on guinea pigs act 4 times stronger than on mice, and hundreds of times stronger than on frogs. At the same time, rats are more sensitive to small doses of tetraethyl lead, a poison that also affects the central nervous system, than rabbits, and the latter are more sensitive to ether than dogs. It can be assumed that these differences are determined primarily by the biological characteristics inherent in animals of each species: the degree of development of individual systems, their compensatory mechanisms and capabilities, as well as the intensity and nature of metabolic processes, including the biotransformation of foreign substances. Such an approach, for example, makes it possible to evaluate biochemically the fact that rabbits and other animals are resistant to large doses of atropine. It turned out that their blood contains esterase, which hydrolyzes atropine and is absent in humans.

In relation to humans, in practical terms, it is generally accepted that, in general, it is more sensitive to chemicals than warm-blooded animals. In this regard, the results of experiments on volunteers (physicians from one of the Moscow medical institutes) are of undoubted interest. These experiments showed that humans are 5 times more sensitive than guinea pigs and rabbits and 25 times more sensitive than rats to the toxic effects of silver compounds. To substances such as muscarine, heroin, atropine, morphine, a person turned out to be ten times more sensitive than laboratory animals. The effect of some OPs on humans and animals differed little.

A detailed study of the picture of poisoning revealed that many signs of the effect of the same substance on individuals of different species sometimes differ significantly. On dogs, for example, morphine has a narcotic effect, as well as on humans, and in cats this substance causes severe excitement and convulsions. On the other hand, benzene, while causing suppression of the hematopoietic system in rabbits, as well as in humans, does not lead to such changes in dogs. It should be noted here that even the representatives of the animal world closest to man - monkeys - differ significantly from him in their reaction to poisons and drugs. That is why experiments on animals (including higher ones) to study the effects of drugs and other foreign substances do not always give grounds for certain judgments about their possible effect on the human body.

Another type of differences in the course of intoxication is determined gender features. A large number of experimental and clinical observations have been devoted to the study of this issue. And although at present there is no impression that sexual sensitivity to poisons has any general patterns, in general biological terms it is generally accepted that the female body is more resistant to the action of various harmful environmental factors. According to experimental data, female animals are more resistant to the effects of carbon monoxide, mercury, lead, narcotic and hypnotic substances, while males are more resistant to FOS, nicotine, strychnine, and some arsenic compounds. When explaining this kind of phenomena, at least 2 factors must be taken into account. The first is significant differences between individuals of different sexes in the rate of biotransformation of toxic substances in liver cells. It should not be forgotten that as a result of these processes, even more toxic compounds can be formed in the body, and it is they that can ultimately determine the speed of onset, strength and consequences of the toxic effect. The second factor determining the unequal response of animals of different sexes to the same poisons must be considered the biological specificity of male and female sex hormones. Their role in the formation of the body's resistance to harmful chemical agents of the environment is confirmed, for example, by the following fact: in immature individuals, differences in sensitivity to poisons between males and females are practically absent and begin to appear only when they reach puberty. The following example also testifies to this: if female rats are injected with the male sex hormone testosterone, and males with the female sex hormone estradiol, then the females begin to react to certain poisons (for example, drugs) like males, and vice versa.

Clinical and hygienic and experimental data indicate about the higher sensitivity to poisons of children than adults which is usually explained by the peculiarity of the nervous and endocrine systems of the child's body, the peculiarities of lung ventilation, absorption processes in the gastrointestinal tract, the permeability of barrier structures, etc. But still, as well as to understand the causes of sex differences in sensitivity to poisons, one must first in view of the low activity of the biotransformational liver enzymes of the child's body, which is why he tolerates poisons such as nicotine, alcohol, lead, carbon disulfide, as well as potent drugs (for example, strychnine, opium alkaloids) and many other substances that are neutralized mainly in the liver. But to some toxic chemical agents, children (as well as young animals) are even more resistant than adults. For example, due to less sensitivity to oxygen starvation, children under 1 year of age are more resistant to the action of carbon monoxide, a poison that blocks oxygen - which transfers the function of the blood. To this it must be added that in different age groups of animals, significant differences in sensitivity to many toxic substances are also determined. So, G. N. Krasovsky and G. G. Avilova in the above-mentioned work note that young and newborn individuals are more sensitive to carbon disulfide and sodium nitrite, while adults and old ones are more sensitive to dichloroethane, fluorine, and granosan.

The consequences of exposure to poisons on the body

A lot of data has already been accumulated, indicating the development of various disease states after a long period of time after exposure to the body of certain toxic substances. So, in recent years, increasing importance in the occurrence of diseases of the cardiovascular system, in particular atherosclerosis, is given to carbon disulfide, lead, carbon monoxide, and fluorides. Particularly dangerous should be considered blastomogenic, i.e., causing the development of tumors, the effect of certain substances. These substances, called carcinogens, are found both in the air of industrial enterprises, and in settlements and residential premises, in water bodies, soil, food, and plants. Common among them are polycyclic aromatic hydrocarbons, azo compounds, aromatic amines, nitrosoamines, some metals, arsenic compounds. Thus, in a book recently published in Russian translation by the American researcher Ekholm, cases of the carcinogenic effect of a number of substances in US industrial enterprises are cited. For example, people who work with arsenic in copper, lead, and zinc smelters without adequate safety precautions have a particularly high rate of lung cancer. Nearby residents are also experiencing more lung cancer than usual, presumably from inhaling airborne arsenic and other pollutants emitted by these factories. However, as the author notes, over the past 40 years, the owners of enterprises have not introduced any precautions when workers come into contact with carcinogenic poisons. All this applies even more so to uranium miners and dye workers.

Naturally, for the prevention of occupational malignant neoplasms, first of all, it is necessary to withdraw carcinogens from production and replace them with substances that do not have blastomogenic activity. Where this is not possible, the most correct solution that can guarantee the safety of their use is the establishment of their MPC. At the same time, in our country, the task is to drastically limit the content of such substances in the biosphere to quantities that are much lower than the MPC. Attempts are also being made to influence carcinogens and toxic products of their transformations in the body with the help of special pharmacological agents.

One of the dangerous long-term consequences of some intoxications are various malformations and deformities, hereditary diseases, etc., which depend both on the direct effect of the poison on the sex glands (mutagenic effect) and on the disturbance of intrauterine development of the fetus. Toxicologists include benzene and its derivatives, ethyleneimine, carbon disulfide, lead, manganese and other industrial poisons, as well as certain pesticides, to substances acting in this direction. In this connection, the infamous drug thalidomide, which was used as a sedative in a number of Western countries by pregnant women and which caused deformities for several thousand newborns, should also be mentioned. Another example of this kind is the scandal that broke out in 1964 in the United States around a drug called Mer-29, which was heavily advertised as a means of preventing atherosclerosis and cardiovascular diseases and which was used by more than 300 thousand patients. Subsequently, it was found that long-term use of Mer-29 led many people to severe skin diseases, baldness, decreased visual acuity, and even blindness. Concern "U. Merrel and Co., the manufacturer of this drug, was fined $80,000, while Mer-29 sold $12 million in 2 years. And now, 16 years later, at the beginning of 1980, this concern is again in the dock. He is being sued for $10 million in damages for numerous cases of deformities in newborns in the US and England whose mothers took a drug called bendectin for nausea in early pregnancy. The question of the dangers of this drug was first raised in medical circles in early 1978, but pharmaceutical companies continue to produce bendectin, which brings large profits to their owners.

Notes:

Sanotsky IV Prevention of harmful chemical effects on humans is a complex task of medicine, ecology, chemistry and technology. - ZhVHO, 1974, No. 2, p. 125–142.

Izmerov N. F. Scientific and technical progress, the development of the chemical industry and the problems of hygiene and toxicology. - ZhVHO, 1974, No. 2, p. 122–124.

Kirillov VF Sanitary protection of atmospheric air. M.: Medicine, 1976.

Rudaki A. Kasydy. - In the book: Iranian-Tajik poetry / Per. from farsi. M.: Artist. lit., 1974, p. 23. (Ser. B-ka world. Lit.).

(Luzhnnikov E. A., Dagaee V. N., Farsov N. N. Fundamentals of resuscitation in acute poisoning. M .: Medicine, 1977.

Tiunov L. A. Biochemical bases of toxic action. - To the book: Fundamentals of General Industrial Toxicology / Ed. N. A. Tolokoyatseva and V. A. Filov. L .: Medicine, 1976, p. 184–197.

Pokrovsky A. A. Enzymatic mechanism of some intoxications. - Success biol. Chemistry, 1962, v. 4, p. 61–81.

Tiunov L. A. Enzymes and poisons. - In the book: Issues of General Industrial Toxicology / Ed. I. V. Lazareva. L., 1983, p. 80–85.

Loktionov S. I. Some general questions of toxicology. - In the book: Emergency care for acute poisoning / Ed. S. N. Golikova. M.: Medicine, 1978, p. 9–10.

Green D., Goldberger R. Molecular aspects of life. M.: Mir, 1988.

Gadaskina ID Theoretical and practical significance of the study. transformation of poisons in the body. - In the book: Mater. scientific session, dosvyashch. 40th anniversary of the Research Institute of Occupational Health and prof. diseases. L., 1964, p. 43–45.

Koposov E. S. Acute poisoning. - In the book: Resuscitation. M.: Medicine, 1976, p. 222–229.

With regard to drug therapy, the proximity of these two indicators often indicates the unsuitability of the corresponding pharmacological preparations for therapeutic purposes.

Franke Z. Chemistry of poisonous substances / Per. with him. ed. I. L. Knunyants and R. N. Sterlin. Moscow: Chemistry, 1973.

Demidov A. V. Aviation toxicology. M.: Medicine, 1967.

Zakusav V. V., Komissarov I. V., Sinyukhin V. N. Repeated action of medicinal substances. - In the book: Clinical pharmacology / Ed. V. V. Zakusova. M.: Medicine, 1978, p. 52–56.

Cit. Quoted from: Khotsyanov L.K., Khukhrina E.V. Labor and health in the light of scientific and technological progress. Tashkent: Medicine, 1977.

Amirov V. N. Mechanism of absorption of medicinal substances when taken orally. - Health. Kazakhstan, 1972, No. 10, p. 32–33.

By the term "receptor" (or "receptor structure" we will denote the "point of application" of poisons: the enzyme, the object of its catalytic action (substrate), as well as protein, lipid, mucopolysaccharide and other bodies that make up the structure of cells or participate in metabolism. Molecularly -pharmacological ideas about the essence of these concepts will be considered in Chapter 2.

Under metabolites it is also customary to understand various biochemical products of normal metabolism (metabolism).

Gadaskina I.D. Adipose tissue and poisons. - In the book: Topical issues of industrial toxicology / Ed. N. V. Lazareva, A. A. Golubeva, E. T. Lykhipoy. L., 1970, p. 21–43.

Krasovsky GN Comparative sensitivity of humans and laboratory animals to the action of toxic substances. - In the book: General issues of industrial toxicology / Ed. A, V. Roshchin and I. V. Sanotsky. M., 1967, p. 59–62.

Krasovsky G. N., Avilova G. G. Species, sex and age sensitivity to poisons. - ZhVHO, 1974, No. 2, p. 159–164.

From cancer (Latin - cancer), genos (Greek - birth).

Ekholm E. Environment and human health. Moscow: Progress, 1980.

Ogryzkov N. I. Benefits and harms of drugs. Moscow: Medicine, 1968.

In repair production, and sometimes in everyday life, machine operators have to come into contact with many technical fluids, which, to varying degrees, have a harmful effect on the body. The toxic effect of toxic substances depends on many factors and, above all, on the nature of the toxic substance, its concentration, duration of exposure, solubility in body fluids, as well as external conditions.

Poisonous substances in gas, vapor and smoke state enter the body through the respiratory system with the air that workers breathe while in the polluted atmosphere of the working area. In this case, toxic substances act much faster and stronger than the same substances that have entered the body in other ways. As the air temperature rises, the risk of poisoning increases. Therefore, cases of poisoning are more common in summer than in winter. Often, several toxic substances act on the body at once, for example, gasoline vapors and carbon monoxide from the exhaust gases of a carburetor engine. Some substances increase the effect of other toxic substances (for example, alcohol enhances the toxic properties of gasoline vapors, etc.).

There is a misconception among machine operators that one can get used to a poisonous substance. The imaginary addiction of the body to a particular substance leads to a belated adoption of measures to stop the action of the toxic substance. Once in the human body, toxic substances cause acute or chronic poisoning. Acute poisoning develops when a large amount of toxic substances of high concentration is inhaled (for example, when opening the hatch of a container with gasoline, acetone and similar liquids). Chronic poisoning develops when small concentrations of toxic substances are inhaled for several hours or days.

Solvents account for the largest number of cases of poisoning with vapors and mists of technical fluids, which is explained by their volatility or volatility. The volatility of solvents is evaluated by conditional values ​​indicating the rate of evaporation of solvents compared with the rate of evaporation of ethyl ether, conventionally taken as a unit (Table 1).

According to volatility, solvents are divided into three groups: the first includes solvents with a volatility number of less than 7 (highly volatile); to the second - solvents with a volatility number from 8 to 13 (medium volatile) and to the third - solvents with a volatility number of more than 15 (slowly volatile).

Consequently, the faster a particular solvent evaporates, the higher the likelihood of the formation of an unhealthy concentration of solvent vapors in the air and the risk of poisoning. Most solvents evaporate at any temperature. However, as the temperature rises, the evaporation rate increases significantly. So, for example, solvent gasoline in a room at an ambient temperature of 18-20 ° C evaporates at a rate of 400 g / h per 1 m2. Vapors of many solvents are heavier than air, so the highest percentage of them is contained in the lower layers of air.

The distribution of solvent vapors in the air is affected by air currents and their circulation. In the presence of heated surfaces, under the influence of convection currents, air flows increase, as a result of which the speed of propagation of solvent vapors increases. In enclosed spaces, the air is saturated with solvent vapors much faster, and, consequently, the likelihood of poisoning increases. Therefore, if a container with a volatile solvent is left open in a closed or poorly ventilated room or the solvent is poured and spilled; then the surrounding air is quickly saturated with vapors and in a short time their concentration in the air will become dangerous to human health.

The air of the working area is considered safe if the amount of harmful vapors in it does not exceed the maximum permissible concentration (the working area is considered to be the place of permanent or periodic stay of workers to monitor and conduct production processes). The maximum permissible concentrations of toxic fumes, dust and other aerosols in the air of the working area of ​​industrial premises should not exceed the values ​​\u200b\u200bspecified in the "Instructions for the Sanitary Maintenance of Premises and Equipment of Industrial Enterprises".

Persons who clean and repair tanks, tanks from gasoline and other solvents, as well as those who work in places where technical liquids are stored and used, are at great risk of poisoning. In these cases, in violation of the norms and safety requirements, the concentration of vapors of toxic substances in the air will exceed the maximum permissible limits.

Here are some examples:

1. In a closed, unventilated warehouse, a storekeeper left a bucket of thinner gasoline overnight. With a gasoline evaporation area of ​​0.2 m2 and an evaporation rate of 400 g/h, about 800 g of gasoline will go into the vapor state from 1 m2 in 10 hours. If the internal volume of the warehouse is 1000 m3, then by morning the concentration of solvent gasoline vapors in the air will be: 800,000 mg: 1000 m3 = 800 mg/m3 of air, which is almost 2.7 times higher than the maximum allowable concentration of solvent gasoline. Therefore, before starting work, the storage room should be ventilated and doors and windows should be kept open during the day.

2. In the fuel equipment repair workshop, plunger pairs of fuel pumps are washed in B-70 gasoline, poured into a washing bath with an area of ​​0.8 m2. What will be the concentration of gasoline vapors in the air of the working room by the end of the shift, if you do not make a local suction from the washing bath and do not equip ventilation? Calculations show that for 8 hours of work about 2.56 kg of gasoline (2,560,000 mg) will go into a vapor state. Dividing the resulting weight of gasoline vapors by the internal volume of the room 2250 m3, we get the concentration of gasoline vapors in the air 1100 mg/m3, which is 3.5 times higher than the maximum allowable concentration of B-70 gasoline. This means that at the end of the working day, everyone working in this room will have a headache or other signs of poisoning. Consequently, parts and parts of machines cannot be washed in gasoline, but less toxic solvents and detergents must be used.

Toxic substances in liquid state enter the human body through the digestive organs with food and water, as well as through the skin in contact with them and using overalls moistened with these substances. Signs of poisoning with liquid toxic substances are the same as with vapor poisoning.

The ingress of liquid toxic substances through the digestive organs is possible if personal hygiene is not observed. Often, a car driver, having lowered a rubber tube into the gas tank, sucks gasoline in his mouth to create a siphon and pour gasoline from the tank into another container. This harmless technique leads to serious consequences - poisoning or inflammation of the lungs. Poisonous substances, penetrating through the skin, enter the systemic circulation, bypassing the protective barrier, and, accumulating in the body, lead to poisoning.

When working with acetone, ethyl acetate, gasoline and similar solvents, you may notice that liquids quickly evaporate from the surface of the skin and the hand turns white, i.e. liquids dissolve sebum, degrease and dry the skin. Cracks form on dry skin, and infection penetrates through them. With frequent contact with solvents, eczema and other skin diseases develop. Some technical liquids, when they get on the unprotected surface of the skin, lead to chemical burns up to the charring of the affected areas.

State budget educational institution

Higher professional education

"NORTH OSSETIAN STATE MEDICAL ACADEMY"

Ministry of Health and Social Development of Russia

DEPARTMENT OF GENERAL HYGIENE AND

PHYSICAL CULTURE

EVALUATION OF THE TOXICITY OF INDUSTRIAL POISONS ON THE ORGANISM

Study guide for students studying

specialty "Dentistry"

VLADIKAVKAZ 2012

Compiled by:

Ø assistant F.K. Khudalova,

Ø assistant A.R. Naniev

Reviewers:

Ø Kallagova F.V. - head. Department of Chemistry and Physics, Professor, MD;

Ø I.F. Botsiev - Associate Professor of the Department of Chemistry and Physics, Ph.D./M. n.

Approved by TsKUMS GBOU VPO SOGMA of the Ministry of Health and Social Development of Russia

G., protocol no.

Purpose of the lesson: to familiarize students with the main parameters characterizing the degree of toxicity and danger of chemicals in production conditions, with the basic principles of sanitary and epidemiological rules, with the principles of primary prevention in relation to industrial poisons.

The student must know:

Methods for assessing the toxicity and danger of industrial poisons; Familiarize yourself with the rules of protection against the action of industrial poisons.

The student must be able to:

1. Give a toxicological characterization of substances based on physicochemical constants.

2. List the principles of primary prevention at enterprises with industrial poisons.

3. Determine the role of the doctor in maintaining the health of workers.

Main literature:

Ø Rumyantsev G.I. Hygiene XXI century, M.: GEOTAR, 2009.

Ø Pivovarov Yu.P., Korolik V.V., Zinevich L.S. Hygiene and fundamentals of human ecology. Moscow: Academy, 2004, 2010.

Ø Lakshin A.M., Kataeva V.A. General hygiene with the basics of human ecology: Textbook. - M .: Medicine, 2004 (Textbook for students of medical universities).

Additional literature:

Ø Pivovarov Yu.P. Guide to laboratory studies and fundamentals of human ecology, 2006.

Ø Kataeva V.A., Lakshin A.M. Guide to practical and self-study in general hygiene and the basics of human ecology. M.: Medicine, 2005.

Ø "Guidelines for practical exercises in occupational health". Ed. N.F. Kirilov. Publishing house GEOTAR-Media, M., 2008

Ø GN 2.2.5.1313-03 "Maximum Permissible Concentrations (MPC) of harmful substances in the air of the working area".

Ø GN 2.2.5.1314-03 "Indicative safe levels of exposure (SHL) of harmful substances in the air of the working area."

Ø R 2.2.755-99 "Methodology for monitoring the content of harmful substances in the air of the working area"

Chemical substances that, penetrating the body under production conditions, even in relatively small quantities, cause various disturbances in its normal functioning, are called industrial poisons.

ROUTES OF POISONS INTO THE BODY

Poisons can enter the body in three ways: through the lungs, the gastrointestinal tract, and intact skin. Through the respiratory tract, poisons enter the body in the form of vapors, gases and dust, through the gastrointestinal tract - most often from contaminated hands, but also due to the ingestion of dust, vapors, gases; through the skin penetrate organic chemicals predominantly liquid, oily and pasty consistency.

The intake of poisons through the respiratory system is the main and most dangerous route, because. lungs create favorable conditions for the penetration of gases, vapors and dust into the blood.

Non-reactive gases and vapors enter the blood through the lungs on the basis of the law of diffusion, i.e. due to the difference in partial pressure of gases or vapors in the alveolar air and blood. At the beginning, the saturation of blood with gases or vapors occurs rapidly due to the large difference in partial pressure, then it slows down, and finally, when the partial pressure of gases or vapors in the alveolar air and blood equalizes, the saturation of the blood with gases or vapors stops. After the victim is removed from the polluted atmosphere, desorption of gases and vapors begins and their removal through the lungs. Desorption also occurs based on the laws of diffusion.

If the substances are highly soluble in water, then they are highly soluble in the blood. A different pattern is inherent in sorption during inhalation reacting gases, those. such that in the body quickly react when these gases are inhaled, saturation never occurs. The danger of acute poisoning is the greater, the longer a person stays in a polluted atmosphere.

The intake of poisons through the gastrointestinal tract. Poisons most often enter the oral cavity from contaminated hands. A classic example of such a route is the intake of lead. It is a soft metal, it can be easily washed off, soils hands, does not wash off with water, and can get into the oral cavity when eating and smoking. It is possible to swallow toxic substances from the air when they are retained on the mucous membranes of the nasopharynx and oral cavity. The absorption of poisons occurs mainly in the small intestine and only to a small extent in the stomach. Most of the toxic substances absorbed through the gastrointestinal wall enter the liver through the portal vein system, where they are retained and neutralized.

Entry of poisons through the skin. Through intact skin, chemicals can penetrate that are highly soluble in fats and lipoids, i.e. non-electrolytes; electrolytes, i.e., substances that dissociate into ions, do not penetrate the skin.

The amount of toxic substances that can penetrate the skin is directly dependent on their solubility in water, the size of the surface of contact with the skin and the speed of blood flow in it. The latter explains the fact that when working in conditions of high air temperature, when blood circulation in the skin is significantly increased, the number of poisoning through the skin increases. Of great importance for the entry of poisons through the skin is the consistency and volatility of the substance. Liquid organic substances with high volatility quickly evaporate from the surface of the skin and do not enter the body. Under certain conditions, volatile substances can cause poisoning through the skin, for example, if they are part of ointments, pastes, adhesives that linger on the skin for a long time. In practical work, knowledge of the ways in which poisons enter the body determines measures to prevent poisoning.

DISTRIBUTION, TRANSFORMATION

AND EXTRACTION OF POISONS FROM THE BODY

Distribution of poisons in the body. According to distribution in tissues and penetration into cells, chemicals can be divided into two main groups: non-electrolytes and electrolytes.

non-electrolytes, soluble in fats and lipoids, the substance penetrates into the cell the sooner and in greater quantity, the greater its solubility in fats. This is due to the fact that the cell membrane contains many lipoids. For this group of chemicals, there are no barriers in the body: the distribution of non-electrolytes in the body during their dynamic intake is determined mainly by the conditions of blood supply to organs and tissues. This is confirmed by the following examples.

The brain, which contains many lipoids and has a rich circulatory system, is saturated with ethyl ether very quickly, while other tissues containing a lot of fat, but with a poor blood supply, are saturated with ether very slowly. The saturation of the brain with aniline occurs very quickly, while the perirenal fat, which has a poor blood supply, is saturated very slowly. The removal of non-electrolytes from tissues also depends mainly on the blood supply: after the cessation of the entry of poison into the body, tissue organs rich in blood vessels are most quickly released from it. From the brain, for example, the removal of aniline occurs much faster than from the perirenal fat. Ultimately, non-electrolytes, after the cessation of their entry into the body, are distributed evenly in all tissues.

Ability electrolytes penetration into the cell is sharply limited and depends on the charge of its surface layer. If the cell surface is negatively charged, it does not allow anions to pass through, and if it is positively charged, it does not allow cations to pass through. The distribution of electrolytes in tissues is very uneven. The largest amount of lead, for example, accumulates in the bones, then in the liver, kidneys, muscles, and 16 days after the cessation of its entry into the body, all lead passes into the bones. Fluoride accumulates in bones, teeth, and in small amounts in the liver and skin. Manganese is mainly deposited in the liver and in small amounts in the bones and heart, even less - in the brain, kidneys, etc. Mercury is mainly deposited in the excretory organs - the kidneys and large intestine.

The fate of poisons in the body. Poisons that enter the body undergo various transformations. Almost all organic substances undergo transformations through various chemical reactions: oxidation, reduction of hydrolysis, deamination, methylation, acetylation, etc. Only chemically inert substances, such as gasoline, which is excreted from the body in unchanged form, do not undergo transformations.

Excretion of poisons from the body. Poisons are excreted through the lungs, kidneys, gastrointestinal tract, and skin. Volatile substances that do not change or change slowly in the body are released through the lungs. Water-soluble substances and products of the transformation of poisons in the body are excreted through the kidneys. Poorly soluble substances, such as heavy metals - lead, mercury, as well as manganese, arsenic, are excreted slowly through the kidneys. Poorly soluble or insoluble substances are excreted through the gastrointestinal tract: lead, mercury, manganese, antimony, etc. Some substances (lead, mercury) are excreted along with saliva in the oral cavity. All fat-soluble substances are secreted through the skin by the sebaceous glands. Sweat glands secrete mercury, copper, arsenic, hydrogen sulfide, etc.

concentrations and doses. The maximum permissible concentration (MPC) of harmful substances in the air of the working area, i.e. such concentrations that, during daily work within 8 hours during the entire working experience, cannot cause any deviations from the normal state or diseases detected by modern research methods directly in the process of work or in the long term. Maximum allowable concentrations are very important for the hygienic assessment of sanitary working conditions.

1.4. Protection of the population in areas of chemically hazardous facilities

1.4.1. General information about emergency - chemically hazardous substances and chemically hazardous objects

1.4.1.1. Emergency chemical hazardous substances

In modern conditions, in order to solve the problems of protecting personnel and the public at chemically hazardous facilities (CHOO), it is necessary to know what the main emergency chemically hazardous substances are at these facilities. So, according to the latest classification, the following terminology of emergency chemically hazardous substances is used:

Hazardous Chemical Substance (HCS)- a chemical substance, the direct or indirect effect of which on a person can cause acute and chronic diseases of people or their death.

Emergency chemically hazardous substance (AHOV)- OHV used in industry and agriculture, in the event of an accidental release (outflow) of which environmental contamination can occur with concentrations affecting a living organism (toxic doses).

Emergency chemically hazardous substance of inhalation action (AHOVID)- AHOV, during the release (pouring) of which mass injuries of people can occur by inhalation.

Of all the harmful substances currently used in industry (more than 600 thousand items), only a little more than 100 can be attributed to AHOV, 34 of which are most widespread.

The ability of any substance to easily pass into the atmosphere and cause massive damage is determined by its basic physicochemical and toxic properties. Of the physical and chemical properties, the state of aggregation, solubility, density, volatility, boiling point, hydrolysis, saturated vapor pressure, diffusion coefficient, heat of evaporation, freezing point, viscosity, corrosivity, flash point and ignition point, etc., are of the greatest importance.

The main physico-chemical characteristics of the most common AHOV are given in Table 1.3.

The mechanism of the toxic action of AHOV is as follows. Inside the human body, as well as between it and the external environment, there is an intensive metabolism. The most important role in this exchange belongs to enzymes (biological catalysts). Enzymes are chemical (biochemical) substances or compounds capable of controlling chemical and biological reactions in the body in negligible amounts.

The toxicity of certain AHOVs lies in the chemical interaction between them and enzymes, which leads to inhibition or cessation of a number of vital body functions. Complete suppression of certain enzyme systems causes a general damage to the body, and in some cases its death.

To assess the toxicity of hazardous chemical substances, a number of characteristics are used, the main of which are: concentration, threshold concentration, maximum permissible concentration (MPC), average lethal concentration and toxic dose.

Concentration- the amount of substance (AHOV) per unit volume, mass (mg / l, g / kg, g / m 3, etc.).

Threshold concentration is the minimum concentration that can cause a measurable physiological effect. At the same time, the affected feel only the primary signs of damage and remain functional.

Maximum Permissible Concentration in the air of the working area - the concentration of a harmful substance in the air, which, during daily work for 8 hours a day (41 hours a week) during the entire length of service, cannot cause diseases or deviations in the state of health of workers detected by modern research methods, in

in the process of work or in the remote periods of life of the present and subsequent generations.

Mean lethal concentration in the air - the concentration of a substance in the air, causing the death of 50% of those affected during 2, 4-hour inhalation exposure.

Toxic dose is the amount of a substance that causes a certain toxic effect.

The toxic dose is taken equal to:

with inhalation lesions - the product of the time-average concentration of hazardous chemicals in the air by the time of inhalation intake into the body (measured in g × min / m 3, g × s / m 3, mg × min / l, etc.);

with skin-resorptive lesions - the mass of hazardous chemicals, causing a certain effect of the lesion when it comes into contact with the skin (units of measurement - mg / cm 2, mg / m 3, g / m 2, kg / cm 2, mg / kg, etc.) .

To characterize the toxicity of substances when they enter the human body by inhalation, the following toxodoses are distinguished.

Average lethal toxodose ( LCt 50 ) - leads to death of 50% of those affected.

Average, excreting toxodose ( ICt 50 ) - leads to the failure of 50% of those affected.

Average threshold toksodoz ( RCt 50 ) - causes the initial symptoms of the lesion in 50% of those affected.

The average lethal dose when injected into the stomach - leads to the death of 50% of those affected with a single injection into the stomach (mg / kg).

To assess the degree of toxicity of AHOV skin-resorptive action, the values ​​\u200b\u200bof the average lethal toxodose are used ( LD 50 ), average incapacitating toxodose ( ID 50 ) and average threshold toxodose ( RD 50 ). Units of measurement - g/person, mg/person, ml/kg, etc.

The average lethal dose when applied to the skin - leads to the death of 50% of those affected with a single application to the skin.

There are a large number of ways to classify hazardous chemicals depending on the chosen base, for example, according to the ability to disperse, biological effects on the human body, storage methods, etc.

The most important are the classifications:

according to the degree of impact on the human body (see Table 1.4);

according to the predominant syndrome that develops during acute intoxication (see Table 1.5);

Table 1.4

Classification of hazardous chemicals according to the degree of impact on the human body

Index	Norms for the hazard class
Maximum allowable concentration of harmful substances in the air of the working area, mg / m 3
Mean lethal dose when injected into the stomach, mg/kg
Mean lethal dose when applied to the skin, mg/kg
Average lethal concentration in the air, mg / m 3				more than 50000
Possibility factor for inhalation poisoning
Acute zone
Zone of chronic action
Notes: 1. Each specific AHOV belongs to the hazard class according to the indicator, the value of which corresponds to the highest hazard class. 2. The coefficient of the possibility of inhalation poisoning is equal to the ratio of the maximum allowable concentration of a harmful substance in the air at 20 ° C to the average lethal concentration of a substance for mice during a two-hour exposure. 3. The zone of acute action is the ratio of the average lethal concentration of hazardous chemicals to the minimum (threshold) concentration that causes a change in biological parameters at the level of the whole organism, beyond the limits of adaptive physiological reactions. 4. The zone of chronic action is the ratio of the minimum threshold concentration that causes changes in biological parameters at the level of the whole organism, which go beyond the limits of adaptive physiological reactions, to the minimum (threshold) concentration that causes a harmful effect in a chronic experiment for 4 hours 5 times a week for for at least 4 months. According to the degree of impact on the human body, harmful substances are divided into four hazard classes: 1 - substances are extremely dangerous; 2 - highly dangerous substances; 3 - moderately dangerous substances; 4 - substances of low hazard. The hazard class is established depending on the norms and indicators given in this table.

Table 1.5

Classification of AHOV according to the predominant syndrome that develops during acute intoxication

Name	Character actions	Name
Substances with a predominantly asphyxiating effect	Affects the human respiratory tract	Chlorine, phosgene, chloropicrin.
Substances of predominantly general poisonous action	disrupt energy metabolism	Carbon monoxide, hydrogen cyanide
Substances with suffocating and general poisonous effects	They cause pulmonary edema during inhalation exposure and disrupt energy metabolism during resorption.	Amyl, acrylonitrile, nitric acid, nitrogen oxides, sulfur dioxide, hydrogen fluoride
neurotropic poisons	Act on the generation, conduction and transmission of nerve impulses	Carbon disulfide, tetraethyl lead, organophosphorus compounds.
Substances with asphyxiating and neutronic effects	Cause toxic pulmonary edema, against which a severe lesion of the nervous system is formed	Ammonia, heptyl, hydrazine, etc.
metabolic poisons	Violate the intimate processes of the metabolism of substances in the body	Ethylene oxide, dichloroethane
Substances that disrupt metabolism	They cause diseases with an extremely sluggish course and disrupt metabolism.	Dioxin, polychlorinated benzfurans, halogenated aromatic compounds, etc.

according to the main physical and chemical properties and storage conditions (see table. 1.6);

according to the severity of the impact based on several important factors (see Table 1.7);

on the ability to burn.

Table 1.6

Classification of hazardous chemicals according to the main physical and chemical properties

and storage conditions

	Characteristics	Typical representatives
	Liquid volatiles stored in pressure vessels (compressed and liquefied gases)	Chlorine, ammonia, hydrogen sulfide, phosgene, etc.
	Liquid volatiles stored in non-pressurized containers	Hydrocyanic acid, acrylic acid nitrile, tetraethyl lead, diphosgene, chloropicrin, etc.
	fuming acids	Sulfuric (r³1.87), nitrogen (r³1.4), hydrochloric (r³1.15), etc.
	Loose and solid non-volatile during storage up to + 40 ° C	Sublimate, yellow phosphorus, arsenic anhydride, etc.
	Loose and solid volatile during storage up to + 40 ° C	Hydrocyanic acid salts, mercurans, etc.

A significant part of AHOV is flammable and explosive substances, which often leads to fires in case of destruction of containers and the formation of new toxic compounds as a result of combustion.

According to the ability to burn, all hazardous chemicals are divided into groups:

non-combustible (phosgene, dioxin, etc.); substances of this group do not burn under conditions of heating up to 900 0 C and oxygen concentration up to 21%;

non-combustible flammable substances (chlorine, nitric acid, hydrogen fluoride, carbon monoxide, sulfur dioxide, chloropicrin and other thermally unstable substances, a number of liquefied and compressed gases); substances of this group do not burn when heated to 900 ° C and oxygen concentrations up to 21%, but decompose with the release of combustible vapors;

Table 1.7

Classification of AHOV according to the severity of the impact based on

taking into account several factors

Dispersion ability
Fortitude
industrial value
How it enters the body
Degree of toxicity
The ratio of the number of injured to the number of dead
delayed effects

a large number of ways to classify hazardous chemicals depending on the chosen base, for example, according to the ability to disperse, biological effects on the human body, storage methods, etc.

slow-burning substances (liquefied ammonia, hydrogen cyanide, etc.); substances of this group are capable of igniting only when exposed to a source of fire;

combustible substances (acrylonitrile, amyl, gaseous ammonia, heptyl, hydrazine, dichloroethane, carbon disulfide, tertraethyl lead, nitrogen oxides, etc.); substances of this group are capable of spontaneous combustion and combustion even after the source of fire has been removed.

1.4.1.2. Chemically hazardous objects

Chemically hazardous facility (XOO)- this is an object where hazardous chemical substances are stored, processed, used or transported, in the event of an accident or destruction of which death or chemical contamination of people, farm animals and plants, as well as chemical contamination of the natural environment can occur.

The concept of HOO unites a large group of industrial, transport and other objects of the economy, different in purpose and technical and economic indicators, but having a common property - in case of accidents they become sources of toxic emissions.

Chemically hazardous objects include:

plants and combines of chemical industries, as well as individual installations (aggregates) and workshops that produce and consume hazardous chemicals;

plants (complexes) for the processing of oil and gas raw materials;

production of other industries using AHOV (pulp and paper, textile, metallurgical, food, etc.);

railway stations, ports, terminals and warehouses at the final (intermediate) points of movement of AHOV;

vehicles (containers and bulk trains, tank trucks, river and sea tankers, pipelines, etc.).

At the same time, hazardous chemicals can be both raw materials and intermediate and final products of industrial production.

Accidentally chemically hazardous substances at the enterprise can be located in production lines, storage facilities and basic warehouses.

An analysis of the structure of chemically hazardous objects shows that the main amount of AHOV is stored in the form of raw materials or production products.

Liquefied hazardous chemicals are contained in standard capacitive cells. These can be aluminum, reinforced concrete, steel or combined tanks, in which conditions are maintained that correspond to a given storage mode.

The generalized characteristics of the tanks and possible storage options for hazardous chemicals are given in Table. 1.8.

Above ground tanks in warehouses are usually located in groups with one reserve tank per group. Around each group of tanks along the perimeter, a closed dike or enclosing wall is provided.

Some freestanding large tanks may have pallets or underground reinforced concrete tanks.

Solid hazardous chemicals are stored in special rooms or in open areas under sheds.

At short distances, AHOV is transported by road in cylinders, containers (barrels) or tank trucks.

Of the wide range of medium-capacity cylinders for storage and transportation of liquid hazardous chemicals, cylinders with a capacity of 0.016 to 0.05 m 3 are most often used. The capacity of containers (barrels) varies from 0.1 to 0.8 m 3 . Tanker trucks are mainly used to transport ammonia, chlorine, amyl and heptyl. A standard ammonia carrier has a carrying capacity of 3.2; 10 and 16 tons. Liquid chlorine is transported in tankers with a capacity of up to 20 tons, amyl - up to 40 tons, heptyl - up to 30 tons.

By rail, AHOV is transported in cylinders, containers (barrels) and tanks.

The main characteristics of tanks are given in Table 1.9.

Cylinders are transported, as a rule, in covered wagons, and containers (barrels) - on open platforms, in gondola cars and in universal containers. In a covered wagon, cylinders are placed in rows in a horizontal position up to 250 pcs.

In an open gondola car, containers are installed in a vertical position in rows (up to 3 rows) of 13 containers in each row. On an open platform, containers are transported in a horizontal position (up to 15 pcs).

Railway tanks for the transportation of hazardous chemicals can have a boiler volume from 10 to 140 m 3 with a load capacity of 5 to 120 tons.

Table 1.9

The main characteristics of railway tanks,

used for the transportation of hazardous chemicals

Name AHOV	Useful volume of the cistern boiler, m 3	Pressure in the tank, atm.	Carrying capacity, t
Acrylonitrile
Liquefied ammonia
Nitric acid (conc.)
Nitric acid (razb.)
Hydrazine
Dichloroethane
Ethylene oxide
Sulfur dioxide
carbon disulfide
Hydrogen fluoride
Chlorine liquefied
Hydrogen cyanide

By water transport, most hazardous chemicals are transported in cylinders and containers (barrels), however, a number of ships are equipped with special tanks (tanks) with a capacity of up to 10,000 tons.

In a number of countries there is such a thing as a chemically hazardous administrative-territorial unit (ATE). This is an administrative-territorial unit, more than 10% of the population of which may be in the zone of possible chemical contamination in case of accidents at chemical weapons facilities.

Zone of chemical contamination(ZKhZ) - the territory within which are distributed or where introduced HCV in concentrations or quantities that endanger the life and health of people, farm animals and plants for a certain time.

Sanitary protection zone(SPZ) - the area around a potentially hazardous facility, established to prevent or reduce the impact of harmful factors of its functioning on people, farm animals and plants, as well as on the natural environment.

The classification of objects of the economy and ATU by chemical hazard is carried out on the basis of the criteria given in Table 1.10

Table 1.10

Criteria for classifying ATUs and objects of the economy

on chemical hazard

Classified object	Definition of object classification	Criterion (indicator) for classifying an object and ATU as a chemical	Numerical value of the criterion of the degree of chemical hazard by category of chemical hazard
Object of economics	A chemically hazardous object of the economy is an object of the economy, in the event of the destruction (accident) of which mass destruction of people, farm animals and plants can occur	The number of people entering the zone of possible chemical contamination of AHOV	More than 75 thousand people.	From 40 to 75 thousand people.	less than 40 thousand people	The VKhZ zone does not go beyond the object and its SPZ
	Chemically hazardous ATE-ATE, more than 10% of the population of which may end up in the VCP zone in case of accidents at CW facilities.	Number of population (percentage of territories) in the zone of VKhZ AHOV			10 to 30%
Notes: I. The zone of possible chemical contamination (VKhZ) is the area of ​​a circle with a radius equal to the depth of the zone with a threshold toxodose. 2. For cities and urban areas, the degree of chemical hazard is estimated by the proportion of the territory that falls into the WCS zone, while assuming that the population is distributed evenly over the area. 3. To determine the depth of the zone with a threshold toxodose, the following weather conditions are set: inversion, wind speed I m/s, air temperature 20 o C, equiprobable wind direction from 0 to 360 o.

The main sources of danger in case of accidents at chemical facilities are:

salvo emissions of hazardous chemicals into the atmosphere with subsequent contamination of air, terrain and water sources;

discharge of hazardous chemicals into water bodies;

"chemical" fire with the release of hazardous chemicals and their combustion products into the environment;

explosions of hazardous chemicals, raw materials for their production or source products;

the formation of smoke zones, followed by the precipitation of hazardous chemicals, in the form of "spots" along the trail of the spread of a cloud of contaminated air, sublimation and migration.

Schematically, the main sources of danger in the event of an accident at the HOO are shown in fig. 1.2.

Rice. 1.2. Scheme of the formation of damaging factors during an accident at the chemical weapons organization

1 - salvo release of hazardous chemicals into the atmosphere; 2 - discharge of hazardous chemicals into water bodies;

3 - "chemical" fire; 4 - explosion of AHOV;

5 - smoke zones with deposition of hazardous chemicals and sublimation

Each of the above sources of danger (damage) in place and time can manifest itself separately, sequentially or in combination with other sources, and also repeated many times in various combinations. It all depends on the physical and chemical characteristics of AHOV, the conditions of the accident, weather conditions and the topography of the area. It is important to know the definition of the following terms.

chemical accident- this is an accident at a chemically hazardous facility, accompanied by a spill or release of hazardous chemical substances, which can lead to death or chemical contamination of people, farm animals and plants, chemical contamination of food, food raw materials, feed, other material assets and the area for a certain time.

Release of OHV- release in case of depressurization in a short period of time from technological installations, containers for storage or transportation of chemical substances in an amount capable of causing a chemical accident.

Strait OHV- leakage during depressurization from technological installations, containers for storage or transportation of OHV in an amount capable of causing a chemical accident.

The focus of the defeat of AHOV- this is the territory within which, as a result of an accident at a chemically hazardous facility with the release of hazardous chemicals, mass injuries of people, farm animals, plants, destruction and damage to buildings and structures occurred.

In the event of accidents at chemical facilities with the release of hazardous chemicals, the focus of chemical damage will have the following features.

I. The formation of clouds of AHOV vapors and their distribution in the environment are complex processes that are determined by phase diagrams of AHOV, their main physical and chemical characteristics, storage conditions, weather conditions, terrain, etc., therefore, forecasting the scale of chemical contamination (pollution ) is very difficult.

2. At the height of the accident at the facility, as a rule, several damaging factors act: chemical contamination of the area, air, water bodies; high or low temperature; shock wave, and outside the object - chemical contamination of the environment.

3. The most dangerous damaging factor is the impact of AHOV vapors through the respiratory system. It acts both at the scene of the accident and at large distances from the source of the release and spreads at the speed of the wind transfer of AHOV.

4. Hazardous concentrations of hazardous chemicals in the atmosphere can exist from several hours to several days, and contamination of terrain and water for an even longer time.

5. Death depends on the properties of hazardous chemicals, the toxic dose, and can occur both instantly and some time (several days) after poisoning.

1.4.2. Basic requirements of design standards

to the placement and construction of chemically hazardous facilities

The main national engineering and technical requirements for the placement and construction of chemical facilities are set out in state documents on ITM.

In accordance with the requirements of the ITM, the territory adjacent to chemically hazardous facilities, within which, with the possible destruction of containers with hazardous chemicals, the spread of clouds of contaminated air with concentrations that cause injury to unprotected people is likely to constitute a zone of possible dangerous chemical contamination.

The removal of the boundaries of the zone of possible hazardous chemical contamination is given in Table. 1.11.

To determine the removal of the boundaries of zones of possible hazardous chemical contamination with other amounts of hazardous chemicals in containers, it is necessary to use the correction factors given in Table 1.12.

Table 1.11

Removing the boundaries of the zone of possible hazardous chemical contamination

from 50-ton containers with hazardous chemicals

bunding of the pallet (glass), m	Removal of the boundaries of the zone of possible dangerous chemical contamination, km.
		hydrogen cyanide	sulfur dioxide	Hydrogen sulfide			methyl isocyanate
Without bunding

Table 1.12

Coefficients for recalculating the number of AHOV

When designing new airports, receiving and transmitting radio centers, computer centers, as well as livestock complexes, large farms and poultry farms, their placement should be provided at a safe distance from objects with hazardous chemicals.

The construction of basic warehouses for the storage of hazardous chemicals should be envisaged in a suburban area.

When placed in categorized cities and at sites of particular importance, bases and warehouses for the storage of hazardous chemicals, the amount of hazardous chemicals is established by ministries, departments and enterprises in agreement with local authorities.

At enterprises producing or consuming hazardous chemicals, it is necessary:

to design buildings and structures of predominantly frame type with light enclosing structures;

to place control panels, as a rule, in the lower floors of buildings, and also to provide for duplication of their main elements at spare control points of the facility;

provide, if necessary, protection of containers and communications from destruction by a shock wave;

develop and carry out measures to prevent spills of hazardous liquids, as well as measures to localize accidents by shutting down the most vulnerable sections of technological schemes by installing check valves, traps and barns with directional drains.

In settlements located in areas of possible dangerous contamination with hazardous chemicals, in order to provide the population with drinking water, it is necessary to create protected centralized water supply systems based primarily on underground water sources.

Passing, processing and settling of trains with AHOV should be carried out only by detours. Sites for reloading (pumping) hazardous chemicals, railway tracks for the accumulation (settling) of wagons (tanks) with hazardous chemicals must be removed at a distance of at least 250 m from residential buildings, industrial and storage buildings, parking lots of other trains. Similar requirements are imposed on berths for loading (unloading) hazardous chemicals, railway tracks for the accumulation (settling) of wagons (cistern), as well as water areas for ships with such cargo.

Newly built and reconstructed baths, shower facilities, laundries, dry cleaning factories, car washing and cleaning posts, regardless of departmental affiliation and form of ownership, should be adapted accordingly for the sanitization of people, special processing of clothing and equipment in case of industrial accidents with the release of hazardous chemicals.

At facilities with AHOV, it is necessary to create local warning systems, in the event of accidents and chemical contamination, for workers at these facilities, as well as for the population living in areas of possible hazardous chemical contamination.

Notification of the population about the occurrence of a chemical hazard and the possibility of contamination of the atmosphere with AHOV should be carried out using all available means of communication (electric sirens, radio broadcasting network, internal telephone, television, mobile loudspeaker installations, street speakers, etc.).

At chemically hazardous facilities, local systems for detecting environmental contamination with hazardous chemicals should be created.

There are a number of increased requirements for shelters that provide protection from AHOV ID:

shelters must be kept in readiness for the immediate reception of those sheltered;

in shelters located in zones of possible dangerous chemical contamination, a regime of complete or partial isolation with regeneration of internal air should be provided.

Air regeneration can be carried out in two ways. The first - with the help of regenerative units RU-150/6, the second - with the help of a regenerative cartridge RP-100 and compressed air cylinders.

Sites for reloading (pumping) hazardous chemicals and railway tracks for the accumulation (settling) of wagons (tanks) with hazardous chemicals are equipped with systems for setting up water curtains and filling with water (degasser) in case of spills of hazardous chemicals. Similar systems are being created at the berths for loading (unloading) hazardous chemicals.

In order to timely reduce the stocks of hazardous chemicals to the standards of technological needs, it is planned:

emptying in emergency situations of especially dangerous sections of technological schemes into buried tanks in accordance with the norms, rules and taking into account the specific characteristics of the product;

discharge of hazardous chemicals into emergency tanks, as a rule, by automatically turning on drain systems with mandatory duplication by a device for manually turning on emptying;

plans for a special period of chemically hazardous facilities include measures to reduce the stocks and storage periods of hazardous chemical agents as much as possible and switch to a buffer-free production scheme.

Nationwide engineering and technical measures during the construction and reconstruction of the KhOO are supplemented by the requirements of ministries and departments set out in the relevant industry regulations and design documentation.

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