There are several ways in which SDYAV (AHOV) can enter the human body:
1) inhalation - through the respiratory tract. In this case, an emergency-chemically hazardous substance, when released (spilled) of which can cause a massive injury to people by inhalation, is called – emergency chemically hazardous substance of inhalation action (AHOVID);
2) percutaneous - through unprotected skin and mucous membranes
3) oral - with contaminated water and food.
The magnitude and structure of the sanitary losses of the population in the focus of the SDYAV lesion depends on many factors: the number, properties of the SDYAV, the scale of the contamination zone, population density, the availability of protective equipment, etc.
Individual protection is provided:
· personal skin protection (SIZK), intended for protective human skin from aerosols, vapors, drops, liquid phase of hazardous chemicals, as well as from fire and heat radiation;
· respiratory protection equipment I am(RPE), providing protection of the respiratory system, face, eyes from aerosols, vapors, drops of hazardous chemicals.
Reliability collective protection equipment only provide shelters. When people are in the focus of SDYAV in an open area without a gas mask, almost 100% of the population can receive varying degrees of severity of the lesion. With 100% provision of gas masks, losses due to untimely use or malfunction of a gas mask can reach 10%. The presence of gas masks and their timely use in the simplest shelters and buildings reduces losses to 4 - 5%.
Expected structure of losses in the focus of SDYAV lesion (in percent):
In accidents at chemically hazardous objects, SDYAV should be expected in 60 - 65% of victims, traumatic injuries - in 25%, burns - in 15%. At the same time, in 5% of victims, lesions can be combined (SDYAV + trauma; SDYAV + burn).
Ministry of Education and Science of the Russian Federation
Murom Institute (branch)
federal state budgetary educational institution
higher professional education
"Vladimir State University
named after Alexander Grigorievich and Nikolai Grigorievich Stoletovs "
(MI (branch) VlSU)
Department of Technosphere Safety
Practical lesson number 3
Methodical instructions for the implementation of practical work in the discipline "Toxicology"
for students of the direction 280700.62 "Technosphere safety"
Ways of entry of toxic substances into the body.
According to the variant of the task:
1. Describe the mechanism of chemical resorption through the skin of the body (percutaneously).
2. Describe the mechanism of chemical resorption through the mucous membranes of the body (inhalation).
3. Describe the mechanism of chemical resorption through the mucous membranes of the body (oral).
Table 1
|
Option No. |
Substance serial number according to GN 2.2.5.1313-03 |
Note |
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To determine the complete characteristics of substances, use the dataINTERNETa
Materials required for practical work.
1. Ways of entry of toxic chemicals into the body
Toxic chemicals (toxicants) can enter the body through the skin (percutaneously), respiratory tract (inhalation), gastrointestinal tract (oral). The release of a toxicant from the environment into the circulatory and lymphatic systems of the body is called resorption, and the effect of the toxicant is called resorptive (systemic) action. Toxic substances can have a local effect on the skin, mucous membranes and, at the same time, do not enter the circulatory or lymphatic systems (there is no resorption). Toxicants are capable of local and resorptive action.
The route of entry of a substance into the body is determined by its state of aggregation, location in the environment, and the area of contact with the body. So, a substance in the form of vapor has a very high probability of being absorbed in the respiratory tract, but cannot enter the body through the gastrointestinal tract and skin.
The speed and nature of the resorption of substances is determined by a number of factors: the characteristics of the organism; the amount and properties of the substance; environmental parameters. Therefore, the qualitative and quantitative characteristics of the resorption of the toxicant can vary within wide limits.
Resorption through the skin. The superficial stratum corneum of the epidermis prevents the resorption of toxicants. The skin is an electrically charged membrane, where the metabolism of toxic chemicals is carried out in an amount of 2-6% relative to the metabolic activity of the liver.
The intake of substances through the skin is carried out in three ways: through the epidermis; through the sebaceous and sweat glands; through the hair follicles. For low molecular weight and lipophilic compounds that penetrate well through the skin, the transepidermal pathway is the main one. Slowly absorbed substances enter the transfollicular and transglandular routes. For example, sulfur and nitrogen mustards, which are readily soluble in fats, penetrate the skin transepidermally.
With transepidermal penetration of substances, it is possible for them to pass through cells and through intercellular spaces. Considering the passage of substances through the skin, one should distinguish between resorption itself (entry into the blood) and local action
(deposition of substances in the skin). The penetration of xenobiotics through the skin represents
is a process of passive diffusion. The rate of resorption is influenced by the area and localization of the resorbing surface, the intensity of the blood supply to the skin, as well as the properties of the toxicant. The amount of a substance that penetrates the skin is proportional to the contact area of the substance and the skin. With an increase in the area, the amount of absorbed substance also increases. When substances act in the form of an aerosol, the area of exposure to the skin increases with a simultaneous decrease in the particle diameter.
The blood supply to the skin is less than that of other tissues and organs, for example, muscles. With increased cutaneous blood flow, the possibility of toxic substances to penetrate through the skin increases. The action of irritating substances, ultraviolet irradiation, temperature effects, accompanied by vasodilation, opening of anastomoses, enhances the resorption of toxicants.
Resorption is influenced by the physicochemical properties of toxicants, primarily the ability to dissolve in lipids (lipophilicity). There is a clear correlation between the value of the partition coefficient in the oil / water system and the rate of resorption.
Lipophilic agents (eg FOS, mustards, chlorinated carbohydrates) easily cross the skin barrier. Hydrophilic agents, especially charged molecules, hardly penetrate the skin. In this regard, the permeability of the barrier to weak acids and bases depends significantly on the degree of their dissociation. So, salicylic acid and neutral alkaloid molecules are capable of resorption, but acid anions and alkaloid cations do not penetrate into the body in this way. At the same time, the penetration of lipophilic substances into the body, which do not dissolve in water at all, is also impossible: they are deposited in the fatty lubricant and the epidermis and are not captured by the blood. Therefore, oils do not penetrate the skin. Oxygen, nitrogen, carbon dioxide, hydrogen sulfide, ammonia, helium, hydrogen are capable of skin resorption. An increase in the partial pressure of gas in the air accelerates its penetration into the body, which can lead to severe intoxication.
Damage to the stratum corneum of the epidermis and fatty lubrication of the skin by keratolytic agents and organic solvents enhances the resorption of toxicants. Mechanical damage to the skin with the formation of defects, especially extensive ones, deprives it of its barrier properties. Toxicants are absorbed better through moisturized skin than through dry skin. The resorption rate of substances applied in the form of emulsions, solutions, ointments is influenced by the properties of the carrier (solvent, emulsifier, ointment base).
Resorption through the mucous membranes. The mucous membranes do not have a stratum corneum and a fatty film on the surface. They are covered with a water film through which substances easily penetrate into the tissues of the body. Resorption of substances through the mucous membranes is mainly determined by the following factors:
a) the state of aggregation of the substance (gas, aerosol, suspension, solution);
b) the dose and concentration of the toxicant;
c) the type of mucous membrane, its thickness;
d) the duration of the contact;
e) the intensity of the blood supply to the anatomical structure;
f) additional factors (parameters of the environment, the degree of filling of the stomach).
The large surface area, small thickness of mucous membranes and good blood supply make it most likely for substances to pass through the respiratory system and the wall of the small intestine.
Many toxicants are quickly absorbed already in oral cavity ... The oral epithelium does not represent a significant obstacle to the path of xenobiotics. All parts of the oral cavity are involved in resorption. Only substances in the oral cavity in molecular form can penetrate through the mucous membranes. Therefore, solutions are better resorbed than suspensions. The solution envelops the entire surface of the oral mucosa, covering it with a film that contains toxic substances. The blood flowing from the oral mucosa enters the superior vena cava, and therefore the substance enters the heart directly, into the pulmonary circulation, and then into the general bloodstream. Unlike other methods of penetration through the mucous membranes of the gastrointestinal tract, during resorption in the oral cavity, the absorbed toxicants are distributed in the body, bypassing the liver, which affects the biological activity of rapidly disintegrating compounds.
At the heart of the resorption of substances in the stomach - mechanisms of simple diffusion. The factor that determines the characteristics of the stomach is the acidity of the gastric contents. The diffusion rate is determined by the distribution coefficient of the substances in the oil / water system. Fat-soluble (or soluble in non-polar organic solvents) compounds quite easily penetrate through the gastric mucosa into the blood.
The peculiarity of resorption in the stomach is that it is carried out from an environment with a low pH value. In this regard, the mucosal epithelium forms a kind of lipid barrier between the aqueous phases: acidic (acidity of gastric juice is approximately equal to 1) and alkaline (blood pH is 7.4). Toxicants can overcome this barrier only in the form of uncharged molecules. Many compounds are not capable of dissociation in aqueous solutions (non-electrolytes), their molecules do not carry a charge, and they easily pass through the gastric mucosa (dichloroethane, carbon tetrachloride). Strong acids and alkalis (sulfuric, hydrochloric, nitric acids, NaOH, KOH) in any solution are completely dissociated and therefore pass into the blood only in case of destruction of the mucous membrane (chemical burn).
For weak acids, an acidic environment promotes the transformation of a substance into a non-ionized form; for weak bases, low pH values (high concentrations of hydrogen ions in the medium) promote the transformation of substances into an ionized form.
Non-ionized molecules are more lipophilic and more easily penetrate the biological barrier. Therefore, weak acids are better absorbed in the stomach.
A necessary condition for the resorption of a substance in the stomach is its solubility in gastric juice. Therefore, water-insoluble substances in the stomach are not absorbed. Suspended chemical compounds must go into solution before being sucked in. Since the time spent in the stomach is limited, suspensions are weaker than solutions of the same substance.
If the toxicant enters the stomach with food, interaction with its components is possible: dissolution in fats and water, absorption by proteins. At the same time, the concentration of xenobiotic decreases, and the rate of diffusion into the blood also decreases. Substances are absorbed better from an empty stomach than from a full stomach.
Intestinal resorption. The intestine is one of the main absorption sites for chemicals. Here the mechanism of passive diffusion of substances through the epithelium operates. Passive intestinal diffusion is a dose-dependent process. With an increase in the content of the toxicant in the intestine, the rate of its absorption also increases. Ions of weak acids and bases penetrate through the intestinal mucosa, which is due to their diffusion through the pores of biological membranes.
The diffusion rate of substances through the mucous membrane of the small intestine is proportional to the value of the distribution coefficient in the oil / water system. Substances insoluble in lipids, even in the form of uncharged molecules, do not penetrate the intestinal mucosa. So, xylose - a low-molecular compound belonging to the group of non-electrolytes, but insoluble in lipids - practically does not enter the internal environment of the body when taken through the mouth. Toxic substances that are readily soluble in fats are not absorbed in the intestines due to their low solubility in water. With an increase in molecular weight, the penetration of chemical compounds through the intestinal mucosa decreases. Trivalent ions are not absorbed at all in the intestine.
Absorption occurs with the highest rate in the small intestine. Cold solutions leave the stomach faster. In this regard, cold solutions of toxicants sometimes turn out to be more toxic than warm ones. Resorption in the colon is relatively slow. This is facilitated not only by a smaller surface area of the mucous membrane of this section, but also by a lower concentration of toxicants in the intestinal lumen.
The intestine has an extensive network of blood vessels, so substances that penetrate through the mucous membrane are quickly carried away by the flowing blood. The contents of the colon can act as an inert filler in which the substance is incorporated and from which its resorption is slowed down; the amount of absorbed substance remains unchanged.
Bile acids, possessing the properties of emulsifiers, promote the absorption of fats. The intestinal microflora can cause chemical modification of toxicant molecules - for example, it promotes the reduction of nitrates to nitrites in infants. The ions of these nitrites enter the bloodstream and cause the formation of methemoglobin. E. coli contains enzymes, under the influence of which glucuronides are broken down in the intestine. Conjugates of xenobiotics with glucuronic acid (the final metabolites of substances excreted in the intestine with bile) are poorly soluble in fats and are readily soluble in water. After the cleavage of glucuronic acid, the lipophilicity of the separated molecules increases significantly, and they acquire the ability to reverse resorption into the bloodstream. This process is the basis of the phenomenon of the hepatic-intestinal circulation of the toxicant.
Resorption in the lungs. Oxygen and other gaseous substances, when exhaled, penetrate through the lungs into the bloodstream through a thin capillary-alveolar barrier. A favorable condition for the absorption of substances is a large surface area of the lungs, averaging 70 m2 in humans. The movement of gases along the respiratory tract is associated with their partial adsorption on the surface of the trachea and bronchi. The worse the substance dissolves in water, the deeper it penetrates into the lungs. By inhalation, not only gases and vapors can enter the body, but also aerosols, which are also quickly absorbed into the bloodstream.
The process of penetration and distribution of gases in the body is presented in the form of several successive stages:
inhaled gas enters through the nasopharynx and trachea into the alveoli of the lungs;
by diffusion it enters the blood and dissolves in it;
the blood stream is carried throughout the body;
by diffusion it penetrates into the intercellular fluid and tissue cells.
For resorption, the inhaled gas must come into contact with the alveolar surface of the lungs. The alveoli are located deep in the lung tissue, therefore, by simple diffusion, the gas will not be able to quickly cover the distance from the nasal cavity or oral opening to their walls. In humans and other vertebrates breathing with the lungs, there is a mechanism by which mechanical mixing (convection) of gases in the respiratory tract and lungs is carried out and a constant exchange of gases between the environment and the body is ensured. This mechanism of ventilation of the lungs is successively replacing each other with the acts of inhalation and exhalation.
Ventilation of the lungs provides rapid delivery of gas from the environment to the surface of the alveolar membranes. Simultaneously with the ventilation of the lungs, the dissolution of gas in the wall of the alveoli, its diffusion into the blood, convection in the bloodstream, diffusion in the tissue are carried out. With a decrease in the partial pressure of gas in the alveolar air relative to the blood, gas from the body rushes into the lumen of the alveoli and is removed to the external environment. With forced ventilation of the lungs, you can quickly reduce the concentration of the gaseous substance in the blood and tissues. This opportunity is used to help poisoned gaseous or volatile substances by injecting them with carbogen (air with an increased content of carbon dioxide), which stimulates ventilation of the lungs, affecting the respiratory center of the brain.
Gas passes from the alveoli to the bloodstream by diffusion. In this case, the molecule of the compound moves from the gaseous medium to the liquid phase. The intake of a substance depends on the following factors: the solubility of the gas in the blood; gas concentration gradient between alveolar air and blood; the intensity of blood flow and the state of the lung tissue.
Solubility in blood differs from solubility in water, which is associated with the presence of its constituents (salts, lipids, carbohydrates, proteins) and corpuscles (leukocytes, erythrocytes) dissolved in blood plasma. An increase in temperature reduces the solubility of gases in liquids. The amount of gas dissolved in a liquid is always proportional to the value of its partial pressure.
When gases are resorbed into the blood, the intensity of pulmonary blood flow plays an important role. It is identical to the cardiac output minute volume. The higher the minute volume, the more blood per unit time enters the alveolar capillaries, the more gas is carried away by the blood flowing from the lungs and transported to the tissues, the faster equilibrium is established in the gas distribution system between the medium and tissues. The capillary wall normally does not pose a significant obstacle to diffusing gases. The penetration of gases into the blood is difficult only in pathologically altered lungs (edema, cellular infiltration of the alveolar-capillary barrier).
The blood, saturated with gas in the lungs, spreads throughout the body. Due to the higher content in the blood, gas molecules diffuse into the tissue. The blood, released from the gas, returns to the lungs. This process is repeated until the partial pressure of the gas in the tissues is equal to the pressure in the blood, and the pressure in the blood is equal to the pressure in the alveolar air (equilibrium state).
Diffusion of gases in the tissue is determined by: the solubility of gases in the tissues, the difference in gas concentration in the blood and tissues and the intensity of the blood supply to the tissues. The epithelium of the respiratory tract and the walls of the capillary bed have the permeability of a porous membrane. Therefore, fat-soluble substances are quickly resorbed, and water-soluble substances, depending on the size of their molecules. Saturation of substances that penetrate the alveolar-capillary barrier does not occur. Even large protein molecules, for example, insulin, botulinum toxin, penetrate the barrier.
Penetration of toxicants through the mucous membrane of the eye determined by the physicochemical properties of the substance (solubility in lipids and water, charge and molecular size).
The lipid barrier of the cornea of the eye is a thin structure of stratified squamous epithelium, covered from the outside by the stratum corneum. Fat-soluble substances and even water-soluble compounds easily penetrate this barrier. When a toxicant enters the cornea, most of it is washed off by tears and spreads over the surface of the sclera and conjunctiva of the eyes. About 50% of the substance applied to the cornea is removed within 30 seconds, and more than 85% - within 3-6 minutes.
Resorption from tissues. When substances act on wound surfaces or are injected into tissue (for example, subcutaneously or intramuscularly), their entry is possible either directly into the blood, or first into the tissue, and only then into the blood. In this case, high molecular weight (protein), water-soluble and even ionized molecules can penetrate into the tissue. The resulting concentration gradient of the toxicant between the site of application, the surrounding tissue and the blood is the driving force behind the resorption of the substance into the blood and the internal environment of the body. The rate of resorption is determined by the properties of tissues and toxic substances.
Properties of fabrics. The capillary wall is a porous membrane. Its thickness in various tissues ranges from 0.1 to 1 micron. The capillaries of most human tissues are characterized by pores with a diameter of about 2 nm. The surface occupied by pores is about 0.1% of the area of the capillary bed. Pores are the spaces between endothelial cells. The pores make the capillary membrane permeable to water-soluble substances (pores with large diameters up to 80 nm are found in limited quantities). In addition, the transfer of substances through the capillary wall through the mechanism of pinocytosis (formation of vesicles on the receptor membrane) is possible.
The walls of the capillaries of mammalian muscles have pores with a diameter of 3-4 nm, so they are impermeable to hemoglobin (r = 3.2 nm) and serum albumin (r = 3.5 nm), but permeable to substances such as inulin (r = 1.5 nm) and myoglobin (r = 2 nm). In this regard, the penetration of many xenobiotics into the blood is possible when they are injected into the muscles.
Capillary and lymphatic systems. The network of capillaries and lymphatic vessels is well developed in the subcutaneous tissue and in the intermuscular connective tissue. The surface area of the capillary bed in the volume of tissues is estimated in different ways. For muscles, its value is 7000-80000 cm2 / 100 g of tissue. The degree of development of the capillary network limits the rate of resorption of the xenobiotic in the tissue.
The residence time of blood in the capillaries during the blood circulation is approximately 25 seconds, while the volume of circulating blood is turned over in 1 minute. This is considered to be the reason that the degree of resorption of a substance from tissue into blood is proportional to the degree of tissue vasculature. Resorption of substances from the subcutaneous tissue is mainly carried out through the capillaries and, to a much lesser extent, through the lymphatic vessels.
For the blood supply to tissues, the percentage of open, functioning capillaries, as well as the value of blood pressure in the tissues, are important. The intensity of blood flow depends on cardiac activity, and in tissues it is regulated by vasoactive factors. Endogenous regulators - adrenaline, norepinephrine, acetylcholine, serotonin, nitric oxide, endothelium - dependent relaxing factors, prostaglandins affect the blood flow rate in the tissue and, consequently, the resorption of toxic substances. Cooling a limb slows down blood flow in it, heating - speeds it up.
1.4. Protection of the population in areas of chemically hazardous facilities
1.4.1. General information on chemically hazardous substances and chemically hazardous facilities
1.4.1.1. Emergency chemically hazardous substances
In modern conditions, in order to solve problems of protecting personnel and the population at chemically hazardous facilities (COO), 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 (HXV)- 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)- HCV, used in industry and agriculture, in the event of an emergency release (spillage) of which the environment can be contaminated with concentrations that affect a living organism (toxic doses).
Emergency chemically hazardous substance of inhalation action (AHOVID)- AHOV, when released (poured out) of which mass destruction of people by inhalation can occur.
Of all the harmful substances currently used in industry (more than 600 thousand names), only slightly more than 100 can be attributed to hazardous chemicals, 34 of which are most widespread.
The ability of any substance to easily pass into the atmosphere and cause mass destruction is determined by its basic physicochemical and toxic properties. The most important physical and chemical properties are the state of aggregation, solubility, density, volatility, boiling point, hydrolysis, saturated vapor pressure, diffusion coefficient, heat of vaporization, freezing point, viscosity, corrosivity, flash point and flash point, etc.
The main physical and chemical characteristics of the most common hazardous chemicals are given in table 1.3.
The mechanism of the toxic action of hazardous chemicals is as follows. An intensive metabolism takes place inside the human body, as well as between it and the external environment. 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 trace amounts.
The toxicity of certain hazardous chemicals lies in the chemical interaction between them and enzymes, which leads to inhibition or termination of a number of vital functions of the body. 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 chemicals, a number of characteristics are used, the main ones of which are: concentration, threshold concentration, maximum permissible concentration (MPC), average lethal concentration and toxic dose.
Concentration- the amount of a substance (AHOV) in a unit of volume, mass (mg / l, g / kg, g / m 3, etc.).
Threshold concentration- this is the minimum concentration that can cause a noticeable physiological effect. In this case, 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 work experience, cannot cause diseases or deviations in the state of health of workers, detected by modern research methods, in
the process of work or in the remote periods of life of the present and subsequent generations.
Average lethal concentration in air - the concentration of a substance in the air, causing the death of 50% of those affected by 2, 4 hours of inhalation.
Toxic dose is the amount of a substance that causes a certain toxic effect.
The toxic dose is taken equal to:
in case of 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 lesion effect when in 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 toxic doses are distinguished.
Average lethal toxicosis ( LCt 50 ) - leads to the death of 50% of those affected.
Average, removing toxodose ( ICt 50 ) - leads to failure of 50% of the affected.
Average threshold toxodose ( RCt 50 ) - causes the initial symptoms of damage in 50% of those affected.
The average lethal dose when administered into the stomach - leads to the death of 50% of the affected with a single introduction into the stomach (mg / kg).
To assess the degree of toxicity of AHOV skin-resorptive action, the values of the average lethal toxicity are used ( LD 50 ), the average disabling toxic dose ( ID 50 ) and average threshold toxicosis ( 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 dissipate, biological effects on the human body, storage methods, etc.
The most important classifications are:
by 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 | Standards for hazard class |
|||
| Maximum permissible concentration of harmful substances in the air of the working area, mg / m 3 | ||||
| Average lethal dose when administered into the stomach, mg / kg | ||||
| Average lethal dose when applied to the skin, mg / kg | ||||
| Average lethal concentration in air, mg / m 3 | more than 50,000 |
|||
| Inhalation Poisoning Potential Ratio | ||||
| Zone of acute action | ||||
| Zone of chronic action | ||||
| Notes: 1. Each specific hazardous hazardous substances 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 permissible concentration of a harmful substance in the air at 20 ° C to the average lethal concentration of the substance for mice after 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, which causes a change in biological indicators 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, causing changes in biological parameters at the level of the whole organism, which go beyond the adaptive physiological reactions, to the minimum (threshold) concentration, causing a harmful effect in a chronic experiment, 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 hazardous substances; 3 - moderately hazardous substances; 4 - low-hazard substances. The hazard class is established depending on the standards and indicators given in this table. |
||||
Table 1.5
Classification of hazardous substances according to the predominant syndrome that develops during acute intoxication
| Name | Character actions | Name |
| Substances with a predominantly asphyxiant effect | Affect the human respiratory tract | Chlorine, phosgene, chloropicrin. |
| Substances predominantly of general toxic action | Disrupt energy metabolism | Carbon monoxide, hydrogen cyanide |
| Substances with an asphyxiant and general toxic effect | They cause pulmonary edema when inhaled and disrupt energy metabolism during resorption. | Amyl, acrylonitrile, nitric acid, nitrogen oxides, sulfur dioxide, hydrogen fluoride |
| Neurotropic poisons | Affect the generation, conduction and transmission of nerve impulses | Carbon disulfide, tetraethyl lead, organophosphorus compounds. |
| Substances with an asphyxiant and neutron effect | Cause toxic pulmonary edema, against the background of which severe damage to the nervous system is formed | Ammonia, heptyl, hydrazine, etc. |
| Metabolic poisons | Disrupt the intimate metabolic processes of a substance in the body | Ethylene oxide, dichloro-ethane |
| Substances that disturb metabolism | They cause diseases with an extremely sluggish course and disrupt metabolism. | Dioxin, polychlorinated benzofurans, halogenated aromatic compounds, etc. |
by the main physical and chemical properties and storage conditions (see table. 1.6);
by the severity of the impact on the basis of taking into account several of the most important factors (see Table 1.7);
by the ability to burn.
Table 1.6
Classification of hazardous chemicals by basic physical and chemical properties
and storage conditions
| Specifications | Typical representatives |
|
| Liquid volatiles stored in containers under pressure (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 О С | Sublimate, yellow phosphorus, arsenic anhydride, etc. |
|
| Loose and solid volatiles when stored up to + 40 О С | Hydrocyanic acid salts, mercurans, etc. |
A significant part of hazardous chemicals are flammable and explosive substances, which often leads to fires in the event of destruction of containers and the formation of new toxic compounds as a result of combustion.
According to their ability to burn, all AHOV are divided into groups:
non-flammable (phosgene, dioxin, etc.); substances of this group do not burn under conditions of heating up to 900 0 С and oxygen concentration up to 21%;
non-combustible fire hazardous 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 under conditions of heating to 900 ° C and oxygen concentration up to 21%, but decompose with the release of flammable vapors;
Table 1.7
Classification of hazardous chemicals according to the severity of exposure based on
considering several factors
| Dispersion ability | ||||
| Persistence | ||||
| Industrial value | ||||
| Way of entry into the body | ||||
| Toxicity degree | ||||
| The ratio of the number of victims to the number of deaths | ||||
| Delayed Effects | ||||
a large number of ways to classify hazardous chemicals, depending on the chosen base, for example, according to the ability to dissipate, biological effects on the human body, storage methods, etc.
hardly combustible substances (liquefied ammonia, hydrogen cyanide, etc.); substances of this group can ignite only when exposed to a fire source;
flammable 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 removing the fire source.
1.4.1.2. Chemically hazardous facilities
Chemically hazardous facility (HOO)- this is an object where HCV is 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 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 facilities include:
factories and combines of chemical industries, as well as individual installations (units) and workshops that produce and consume hazardous chemicals;
plants (complexes) for the processing of oil and gas raw materials;
production of other industries using hazardous chemicals (pulp and paper, textile, metallurgical, food, etc.);
railway stations, ports, terminals and warehouses at the terminal (intermediate) points of movement of hazardous chemicals;
vehicles (containers and tank 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.
Emergency chemically hazardous substances at the enterprise can be located in technological lines, storage facilities and basic warehouses.
Analysis of the structure of chemically hazardous objects shows that the bulk of hazardous chemicals is stored in the form of raw materials or production products.
Liquefied hazardous substances are contained in standard capacitive elements. These can be aluminum, reinforced concrete, steel or combined tanks, in which the conditions corresponding to the given storage regime are maintained.
Generalized characteristics of 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. A closed embankment or enclosing wall is provided around each group of tanks along the perimeter.
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 awnings.
At short distances, hazardous chemicals are 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. Tank trucks are mainly used to transport ammonia, chlorine, amyl and heptyl. A standard ammonia tanker has a lifting capacity of 3.2; 10 and 16 tons. Liquid chlorine is transported in tank trucks with a capacity of up to 20 tons, amyl - up to 40 tons, heptyl - up to 30 tons.
AHOV is transported by rail in cylinders, containers (barrels) and tanks.
The main characteristics of the tanks are given in table 1.9.
Cylinders are transported, as a rule, in covered wagons, and containers (barrels) - on open platforms, in open wagons 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), 13 containers in each row. On an open platform, containers are transported in a horizontal position (up to 15 pcs).
Railway tanks for transportation of hazardous chemicals can have a boiler volume from 10 to 140 m 3 with a carrying capacity of 5 to 120 tons.
Table 1.9
The main characteristics of rail tank cars,
used for transportation of hazardous substances
| Name of AHOV | Useful volume of the tank boiler, m 3 | Tank pressure, atm. | Carrying capacity, t |
| Acrylonitrile | |||
| Liquefied ammonia | |||
| Nitric acid (conc.) | |||
| Nitric acid (dil.) | |||
| Hydrazine | |||
| Dichloroethane | |||
| Ethylene oxide | |||
| Sulfurous anhydride | |||
| Carbon disulfide | |||
| Hydrogen fluoride | |||
| Chlorine liquefied | |||
| Hydrogen cyanide |
Most AHOV are transported by water transport 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 concept as a chemically hazardous administrative-territorial unit (ATU). This is an administrative-territorial unit, more than 10% of the population of which may find themselves in the zone of possible chemical contamination in case of accidents at HOO.
Chemical contamination zone(ZHZ) - the territory within which OXV is distributed or where introduced in concentrations or quantities that endanger the life and health of people, farm animals and plants for a certain period of 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 the classification of ATU and objects of the economy
on chemical hazard
| Klas-sifi-circulated object | Defining object classification | Criterion (indicator) for classifying an object and ATE as chemically | Numerical value of the criterion of the degree of chemical hazard by categories of chemical hazard |
|||
| Economy object | A chemically hazardous object of the economy is an object of the economy, in case of destruction (accident) of which mass destruction of people, farm animals and plants of hazardous chemicals can occur | The number of the population falling into the zone of possible chemical contamination of hazardous chemicals | More than 75 thousand people | From 40 to 75 thousand people | less than 40 thousand people | The VHZ zone does not go beyond the facility and its SPZ |
| Chemically hazardous ATE-ATE, more than 10% of the population of which may end up in the VHZ zone in case of accidents at CW facilities. | The number of population (share of territories) in the area of the AHOV VHZ | 10 to 30% | ||||
| Notes: I. The zone of possible chemical contamination (VHZ) is the area of a circle with a radius equal to the depth of the zone with a threshold toxic dose. 2. For cities and urban areas, the degree of chemical hazard is assessed by the share of the territory falling into the VHZ zone, assuming that the population is evenly distributed over the area. 3. To determine the depth of the zone with a threshold toxic dose, the following meteorological conditions are set: inversion, wind speed I m / s, air temperature 20 о С, wind direction equiprobable from 0 to 360 о. |
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The main sources of danger in the event of accidents at a chemical facility are:
salvo emissions of hazardous chemicals into the atmosphere with subsequent contamination of air, terrain and water sources;
discharge of hazardous substances into water bodies;
"chemical" fire with the entry of hazardous chemicals and their combustion products into the environment;
explosions of hazardous chemicals, raw materials for their production or initial products;
the formation of smoke zones with the subsequent deposition of hazardous chemicals, in the form of "spots" along the trail of the spread of a cloud of contaminated air, sublimation and migration.
The main sources of danger in the event of an accident at an industrial facility are shown schematically in Fig. 1.2.
Rice. 1.2. The scheme of the formation of damaging factors in an accident at a chemical facility
1 - volley release of hazardous chemicals into the atmosphere; 2 - discharge of hazardous substances into water bodies;
3 - "chemical" fire; 4 - explosion of hazardous substances;
5 - smoke zones with precipitation of hazardous chemicals and sublimation
Each of the above sources of danger (defeat) in place and time can manifest itself separately, sequentially or in combination with other sources, as well as repeated many times in various combinations. It all depends on the physical and chemical characteristics of hazardous chemicals, accident conditions, meteorological conditions and topography of the area. It is important to know the definition of the following concepts.
Chemical accident is an accident at a chemically hazardous facility, accompanied by a spill or release of OHV, which can lead to death or chemical contamination of people, farm animals and plants, chemical contamination of food, food raw materials, feed, other material values and terrain over a certain period of time.
OHV emission- exit during depressurization in a short period of time from technological installations, tanks for storage or transportation of waste chemicals in an amount capable of causing a chemical accident.
Strait OHV- leakage during depressurization from technological units, tanks for storage or transportation of waste chemicals in an amount capable of causing a chemical accident.
AHOV lesion focus- this is the territory within which, as a result of an accident at a chemically hazardous facility with the release of hazardous chemicals, there were massive injuries to people, farm animals, plants, destruction and damage to buildings and structures.
In the event of accidents at a HOO 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 the phase state diagrams of AHOV, their main physical and chemical characteristics, storage conditions, meteorological conditions, terrain, etc., therefore, predicting the scale of chemical contamination (pollution ) is very difficult.
2. In the midst of an 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 wind transfer of hazardous chemicals.
4. Dangerous concentrations of hazardous chemicals in the atmosphere can exist from several hours to several days, and contamination of the area and water for an even longer time.
5. Death depends on the properties of hazardous chemicals, toxic dose and can occur both instantly and after some time (several days) after poisoning.
1.4.2. Basic requirements of design codes
to the placement and construction of chemically hazardous facilities
The main national engineering and technical requirements for the location and construction of HOO 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 causing damage to unprotected people is a zone of possible hazardous 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 quantities 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
| pallet (glass) embankment, m | Removal of the boundaries of the zone of possible hazardous chemical contamination, km. |
||||||
| hydrogen cyanide | sulfur dioxide | Hydrogen sulfide-rod | methylisocyanate |
||||
| Without embankment | |||||||
Table 1.12
Coefficients for recalculating the number of hazardous chemicals
When designing new airports, receiving and transmitting radio centers, computing centers, as well as livestock complexes, large farms and poultry farms, their location should be provided at a safe distance from facilities with hazardous chemicals.
The construction of basic warehouses for storing hazardous chemicals should be provided in a suburban area.
When placed in categorized cities and at facilities of particular importance, bases and warehouses for storing hazardous chemicals, the amount of hazardous chemicals stocks is established by ministries, departments and enterprises in agreement with local authorities.
At enterprises producing or consuming hazardous chemicals, it is necessary:
design buildings and structures mainly of frame type with light enclosing structures;
place control panels, as a rule, in the lower floors of buildings, as well as provide for duplication of their main elements at spare control points of the facility;
provide, if necessary, the protection of containers and communications from destruction by a shock wave;
to develop and carry out measures to prevent the spill of hazardous liquids, as well as measures to localize accidents by shutting off the most vulnerable sections of technological schemes by installing check valves, traps and barns with directed drains.
In settlements located in areas of possible dangerous contamination of hazardous chemicals, to provide the population with drinking water, it is necessary to create protected centralized water supply systems with a predominantly based on underground water sources.
The passage, processing and layover of trains with hazardous chemicals should be carried out only by rounds. Areas for reloading (pumping) hazardous chemicals, railway tracks for accumulating (standing) wagons (tanks) with hazardous chemicals should be removed at a distance of at least 250 m from residential buildings, industrial and warehouse buildings, parking lots of other trains. Similar requirements are imposed on berths for loading (unloading) hazardous chemicals, railway tracks for accumulation (storage) of wagons (tanks), as well as water areas for ships with such cargo.
Newly built and reconstructed baths, showers of enterprises, laundries, dry cleaning factories, stations for washing and cleaning vehicles, regardless of departmental affiliation and form of ownership, should be adapted accordingly for the sanitary treatment of people, special processing of clothing and equipment in case of industrial accidents with the release of hazardous chemicals.
At facilities with hazardous chemicals, it is necessary to create local warning systems, in the event of accidents and chemical contamination, the workers of these facilities, as well as the population living in areas of possible hazardous chemical contamination.
Alerting the population about the occurrence of a chemical hazard and the possibility of contamination of the atmosphere with hazardous chemicals should be carried out using all available means of communication (electric sirens, radio broadcasting network, internal telephone communications, television, mobile loud-speaking installations, street speakers, etc.).
At chemically hazardous facilities, local systems for detecting contamination of hazardous chemicals in the environment should be created.
A number of increased requirements are imposed on shelters that provide protection against hazardous substances of the ID:
shelters should be kept ready for immediate reception of those sheltered;
in shelters located in areas of possible hazardous chemical contamination, a regime of complete or partial isolation with the regeneration of internal air should be provided.
Air regeneration can be done in two ways. The first one - with the help of the RU-150/6 regenerative installations, the second - with the help of the RP-100 regenerative cartridge and compressed air cylinders.
Areas for reloading (pumping) hazardous chemicals and railway tracks for accumulating (standing) wagons (tanks) with hazardous chemicals are equipped with systems for setting water curtains and filling with water (degasser) in case of a hazardous chemical spill. 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 norms of technological needs, it is envisaged:
emptying in emergency situations especially dangerous sections of technological schemes into buried containers in accordance with the norms, rules and taking into account the specific characteristics of the product;
drainage of hazardous substances into emergency containers, as a rule, with the help of automatic activation of drainage systems with mandatory duplication with a device for manual activation of emptying;
in the plans for a special period of chemically hazardous facilities, measures for the maximum possible reduction of stocks and storage periods of hazardous chemicals and the transition to a buffer-free production scheme.
National engineering and technical measures during the construction and reconstruction of HOO are supplemented by the requirements of ministries and departments, set out in the relevant industry regulatory documents and design documentation.
The following routes of entry of poisons into the body are distinguished:
1. oral;
2. inhalation;
3. percutaneous (through intact and damaged skin);
4. through the mucous membranes (conjunctiva of the eye);
5.parenteral.
One of the most common ways of getting toxic substances into the body is by mouth. A number of toxic fat-soluble compounds - phenols, some salts, especially cyanides - are absorbed and enter the bloodstream already in the oral cavity.
Throughout the gastrointestinal tract, there are significant pH gradients that determine different rates of absorption of toxic substances. Toxic substances in the stomach can be absorbed and diluted by food masses, as a result of which their contact with the mucous membrane decreases. In addition, the rate of absorption is influenced by the intensity of blood circulation in the gastric mucosa, peristalsis, the amount of mucus, etc. Basically, the absorption of the poisonous substance occurs in the small intestine, the contents of which have a pH of 7.5 - 8.0. Fluctuations in the pH of the intestinal medium, the presence of enzymes, a large number of compounds formed during digestion in the chyme on large protein molecules and sorption on them - all this affects the resorption of toxic compounds and their deposition in the gastrointestinal tract.
The phenomena of the deposition of toxic substances in the gastrointestinal tract in case of oral poisoning indicate the need for its thorough cleansing in the course of treatment.
Inhalation poisoning is characterized by the most rapid entry of poison into the blood. This is due to the large absorption surface of the pulmonary alveoli (100-150 m 2), the small thickness of the alveolar membranes, the intense blood flow through the pulmonary capillaries and the lack of conditions for significant deposition of poisons.
The absorption of volatile compounds begins already in the upper respiratory tract, but is most fully carried out in the lungs. It occurs according to the law of diffusion in accordance with the concentration gradient. Many volatile non-electrolytes enter the body in a similar way: hydrocarbons, halogenated hydrocarbons, alcohols, ethers, etc. The rate of intake is determined by their physicochemical properties and, to a lesser extent, by the state of the body (the intensity of respiration and blood circulation in the lungs).
The penetration of toxic substances through the skin is also of great importance, mainly in military and industrial environments.
There are at least three ways to do this:
1. through the epidermis;
2. hair follicles;
3. excretory ducts of the sebaceous and sweat glands.
The epidermis is considered as a lipoprotein barrier through which a variety of substances can diffuse in quantities proportional to their distribution coefficients in the system lipids / water... This is only the first phase of the penetration of the poison, the second phase is the transport of these compounds from the dermis into the blood. Mechanical damage to the skin (abrasions, scratches, wounds, etc.), thermal and chemical burns contribute to the penetration of toxic substances into the body.
Distribution of poisons in the body. One of the main toxicological indicators is the volume of distribution, i.e. characteristic of the space in which a given toxic substance is distributed. There are three main sectors of the distribution of foreign substances: extracellular fluid (approximately 14 liters for a person weighing 70 kg), intracellular fluid (28 liters) and adipose tissue, the volume of which varies considerably. The volume of distribution depends on the three main physical and chemical properties of a given substance:
1. water solubility;
2. fat solubility;
3. the ability to dissociate (ion formation).
Water-soluble compounds are able to spread throughout the entire water sector (extracellular and intracellular fluid) of the body - about 42 liters; fat-soluble substances accumulate (deposited) mainly in lipids.
Removal of poisons from the body... The ways and means of natural elimination of foreign compounds from the body are different. According to their practical significance, they are located as follows: kidneys - intestines - lungs - skin. The degree, rate and route of excretion depend on the physicochemical properties of the released substances. The kidneys excrete mainly non-ionized compounds that are highly hydrophilic and poorly reabsorbed in the renal tubules.
Through the intestines with feces, the following substances are removed: 1) not absorbed into the bloodstream during their oral intake; 2) isolated from the liver with bile; 3) entered the intestine through its walls (by passive diffusion along the concentration gradient).
Most volatile non-electrolytes are excreted from the body mainly unchanged with exhaled air. The lower the coefficient of solubility in water, the faster their release occurs, especially that part that is in the circulating blood. The release of their fraction, deposited in adipose tissue, is delayed and occurs much more slowly, especially since this amount can be very significant, because adipose tissue can make up more than 20% of a person's total body weight. For example, about 50% of inhaled chloroform is released during the first 8-12 hours, and the rest is in the second phase of excretion, which lasts several days.
Through the skin, in particular with sweat, many toxic substances - non-electrolytes (ethyl alcohol, acetone, phenols, chlorinated hydrocarbons, etc.) - leave the body. However, with rare exceptions (the concentration of carbon disulfide in sweat is several times higher than in urine), the total amount of toxic substance removed in this way is small.
The main pathological symptoms in acute poisoning:
1) symptoms of cardiovascular dysfunction: bradycardia or tachycardia, arterial hypotension or hypertension, exotoxic shock.
Exotoxic shock is associated with 65-70% of deaths from poisoning. Such patients are in serious condition, they have psychomotor agitation or lethargy, the skin is pale with a bluish tinge, cold to the touch, shortness of breath and tachycardia, hypotension and oliguria. In this case, the functions of almost all vital organs and systems are disrupted, but acute circulatory failure is one of the leading clinical manifestations of shock.
2) Symptoms of CNS disorders: headache, impaired coordination of movements, hallucinations, delirium, convulsions, paralysis, coma.
The most severe forms of neuropsychiatric disorders in acute poisoning are toxic coma and intoxication psychoses. Coma most often develops when poisoning with substances that inhibit the functions of the central nervous system. A characteristic feature of the neurological picture of toxic coma is the absence of persistent focal symptoms and a rapid improvement in the victim's condition in response to measures to remove the poison from the body. Intoxication psychoses can occur as a result of severe poisoning with atropine, cocaine, tubazide, ethylene glycol, carbon monoxide and manifest a variety of psychopathological symptoms (confusion, hallucinations, etc.). Alcohol abusers may develop so-called alcoholic psychoses (hallucinosis, delirium tremens). In case of poisoning with some neurotoxic substances (FOS, pachicarpin, methyl bromide), neuromuscular conduction disorders with the development of paresis and paralysis occur, and as a complication - myofibrillation.
From a diagnostic point of view, it is important to know that acute visual impairment up to blindness is possible in case of poisoning with methyl alcohol and quinine; blurred vision against the background of miosis - FOS poisoning; mydriasis - in case of poisoning with atropine, nicotine, pachikarpin; "Color vision" - with salicylate poisoning; the development of hearing impairment - with poisoning with quinine, some antibiotics (kanamycin monosulfate, neomycin sulfate, streptomycin sulfate).
After suffering severe poisoning, asthenia, a state of increased fatigue, irritability, and weakness usually persist for a long time.
3) Symptoms of respiratory organs damage: bradypnea, tachypnea, pathological types of respiration (Kussmaul), laryngospasm, bronchospasm, toxic pulmonary edema. In case of respiratory disorders of central origin, typical for poisoning with neurotoxic poisons, due to inhibition of the respiratory center or paralysis of the respiratory muscles, breathing becomes shallow, arrhythmic, until it stops completely.
Mechanical asphyxia occurs in patients in a coma, when the airways are closed as a result of tongue retraction, aspiration of vomit, hypersecretion of bronchial glands, salivation. Clinically, "mechanical asphyxia" is manifested by cyanosis, the presence of large bubbling rales over the trachea and large bronchi.
With burns of the upper respiratory tract, stenosis of the larynx is possible, which is manifested by hoarseness or disappearance of the voice, shortness of breath, cyanosis, intermittent breathing, agitation of the patient.
Toxic pulmonary edema is caused by direct damage to the lung membrane by a toxic substance, followed by inflammation and edema of the lung tissue. It is most often observed with poisoning with nitrogen oxides, phosgene, carbon monoxide and other toxic substances of a suffocating effect, with inhalation of vapors of corrosive acids and alkalis and with aspiration of these substances, accompanied by a burn of the upper respiratory tract. Toxic pulmonary edema is characterized by stages of development: reflex stage - the appearance of cramps in the eyes, soreness in the nasopharynx, chest tightness, frequent shallow breathing; the stage of imaginary well-being - the disappearance of unpleasant subjective sensations; stage of pronounced clinical manifestations - bubbling breathing, profuse foamy sputum, a lot of fine bubbling moist rales over the lungs. The skin and visible mucous membranes are cyanotic, acute cardiovascular failure (collapse) often develops, the skin acquires an earthy tint.
4) Symptoms of damage to the gastrointestinal tract: manifested in the form of dyspeptic disorders (nausea, vomiting), gastroenterocolitis, burns of the digestive tract, esophageal-gastrointestinal bleeding. Bleeding is most common when poisoning with cauterizing poisons (acids and alkalis); they can be early (on the first day) and late (2-3 weeks).
Vomiting in the early stages of poisoning in many cases can be considered a beneficial phenomenon, since it helps to remove a toxic substance from the body. However, the appearance of vomiting in the coma of the patient, in case of poisoning with cauterizing poisons in children, with stenosis of the larynx and pulmonary edema, is dangerous, since aspiration of vomit into the respiratory tract can occur.
Gastroenteritis in case of poisoning is usually accompanied by dehydration of the body and electrolyte imbalance.
5) Symptoms of liver and kidney damage have a clinic of toxic hepato- and nephropathy, can have 3 degrees of severity.
A mild degree is characterized by the absence of noticeable clinical manifestations.
Moderate degree: the liver is enlarged, painful on palpation, jaundice, hemorrhagic diathesis; with kidney damage - back pain, oliguria.
Severe degree: ARF and ARF develops.
Laboratory and instrumental studies are of great importance in the diagnosis of toxic damage to the liver and kidneys.
Consciousness disorder syndrome... It is caused by the direct effect of the poison on the cerebral cortex, as well as the disorders of cerebral circulation and oxygen deficiency caused by it. This kind of phenomenon (coma, stupor) occurs in severe poisoning with chlorinated hydrocarbons, organophosphorus compounds (FOS), alcohols, opium preparations, hypnotics.
Breathing disorder... It is often observed in coma, when the respiratory center is inhibited. Disorders of the act of breathing also arise as a result of paralysis of the respiratory muscles, which sharply complicates the course of poisoning. Severe respiratory dysfunctions are observed with toxic pulmonary edema and airway obstruction.
Blood lesion syndrome... Typical for poisoning with carbon monoxide, hemoglobin oxidants, hemolytic poisons. In this case, hemoglobin is inactivated, the oxygen capacity of the blood decreases.
Circulatory disorder... Almost always accompanies acute poisoning. The reasons for the disorder of the function 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.
Thermoregulation disorder syndrome... It is observed in many poisonings and manifests itself either by a decrease in body temperature (alcohol, sleeping pills, cyanides), or an increase in it (carbon monoxide, snake venom, acids, alkalis, FOS). These shifts in the body, on the one hand, are a consequence of a decrease in metabolic processes and an increase in heat transfer, and on the other hand, the absorption of toxic products of tissue decay into the blood, a breakdown 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 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).
Mental Disorder Syndrome... Typical for poisoning with poisons that selectively affect the central nervous system (alcohol, lysergic acid diethylamide, atropine, hashish, tetraethyl lead).
Liver and kidney syndromes... They accompany 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 decay of tissue structures on them. This especially often accompanies poisoning with dichloroethane, alcohols, vinegar essence, hydrazine, arsenic, heavy metal salts, yellow phosphorus.
Syndrome of violation of water-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, perversion of redox processes in tissues, accumulation of under-oxidized metabolic products is possible.
Dose. Concentration. Toxicity
As already noted, acting on the body in different quantities, the same substance causes a different effect. Minimum effective, or threshold dose(concentration) of a toxic substance is the smallest amount that causes obvious, but reversible changes in life. 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 customary to consider lethal (lethal) doses and the concentration of poisons, that is, those quantities that lead a person (or animal) to death in the absence of treatment. Lethal doses are determined from animal experiments. In experimental toxicology, the most commonly used average lethal dose(DL 50) or the concentration (CL 50) of the poison at which 50% of the experimental animals die. If their 100% death is observed, then such a dose or concentration is indicated 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 route 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 air - with inhalation (i.e., through the respiratory system) penetration of poison into the body in the form of gas, vapor or aerosol; mg / cm 2 of the surface - if the poison comes into contact with 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); ? - volume of ventilation of the lungs (l / min); g - body weight (kg).
With different methods of introducing poisons into the body, different amounts are required in order to cause the same toxic effect. For example, the DL 50 of diisopropyl fluorophosphate found in rabbits by different routes of administration is as follows (in mg / kg):
A significant excess of the oral dose over the parenteral (i.e., introduced into the body, bypassing the gastrointestinal tract) indicates, first of all, the destruction of most of the poison in the digestive system.
Taking into account the magnitude of the average lethal doses (concentrations) for various routes of entry into the body, poisons are divided into groups. One of these classifications developed in our country is shown 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 Hygiene 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 the phenomena of cumulation, sensitization and addiction. Under cumulation means the accumulation of a toxic substance in the body ( material cumulation) or the effects it causes ( functional cumulation). It is clear that the substance accumulates that is slowly excreted or is slowly rendered harmless, while the total effective dose increases very rapidly. As for functional cumulation, it can manifest itself as severe disorders when the poison itself is not retained in the body. This phenomenon can be observed, for example, with alcohol poisoning. It is customary to evaluate the severity of the cumulative properties of toxic substances cumulation coefficient(K), which is determined in an experiment on animals:
where a is the amount of poison reintroduced to the animal, which is 0.1–0.05 DL 50; b is the number of doses administered (a); c - single dose administered.
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 poorly 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. Currently, there is no single view of the biological essence of this phenomenon. On the basis of experimental data, it can be assumed that the sensitization effect 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 foreign 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, repeated, even significantly weaker toxic effects with the subsequent reaction of the poison with antibodies (or altered receptor protein structures) causes a perverse response of the organism in the form of sensitization phenomena.
With repeated exposure to poisons on the body, the opposite phenomenon can also be observed - a weakening of their effects due to addictive, or tolerance... The mechanisms for the development of tolerance are ambiguous. For example, it has been shown that addiction to arsenous anhydride is due to the occurrence under its influence of inflammatory processes on 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, tolerance is not 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, for example 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 excessive amount of toxic substance molecules.
In connection with the above, legislative regulation is of particular importance. maximum permissible concentrations(MPC) 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 permissible concentration of these substances during a daily eight-hour work during the entire working experience cannot cause diseases or deviations in the state of health in workers, which are detected by modern research methods directly in the process of work or in long-term periods. In comparison with other industrialized countries in the USSR, there is a more stringent approach to the establishment of 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 / m3 versus 100 mg / m3), mercury and lead vapors (0.01 mg / m3 versus 0.1 mg / 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, special toxicological and sanitary laboratories operate at enterprises and institutions, which strictly control the content of harmful substances in working rooms, the introduction of new environmentally friendly technological processes, the operation of gas and dust collectors, sewage, 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
Poisons can enter the human body through the respiratory system, digestive tract and skin. The huge surface of the pulmonary alveoli (about 80–90 m 2) provides intensive absorption and a quick effect of the action of poisonous vapors and gases present in the inhaled air. In this case, in the first place, the lungs become the "gateway" for those of them that are readily 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 the poisons in the shortest way penetrate the pulmonary circulation and then, bypassing the liver, reach the blood vessels of the large circle through the heart.
With poisoned food, water, as well as in "pure" form, toxic substances are absorbed into the bloodstream through the mucous membranes of the mouth, stomach and intestines. Most of them are absorbed into the epithelial cells of the digestive tract and further into the blood by the mechanism of simple diffusion. In this case, the leading factor for the penetration of poisons into the internal environments of the body is their solubility in lipids (fats), more precisely, the nature of the distribution between the lipid and water 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 total membrane surface, it nevertheless allows the absorption of many water-soluble and hydrophilic substances. The blood stream from the gastrointestinal tract delivers toxic substances 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 transition 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, the skin barrier is overcome by HCN, CO 2, CO, H 2 S and other gases. It is interesting to note that the passage of heavy metals through the skin is facilitated by the formation of salts with fatty acids of the fatty layer of 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 mother's fetus, on the other. Therefore, the result of the action of poisons and drugs often depends on how pronounced their ability to penetrate through the barrier structures. So, substances soluble in lipids and quickly diffusing through lipoprotein membranes, for example, alcohols, narcotics, many sulfa drugs, penetrate well into the brain and spinal cord. They relatively easily enter the fetal bloodstream through the placenta. In this regard, one cannot fail 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, it adapts to a certain dose of the drug. At the same time, some foreign substances poorly penetrate 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.
Conversion of toxic substances in the body
Poisons penetrating the body, like other foreign compounds, can undergo a variety of biochemical transformations ( biotransformation), as a result of which less toxic substances are most often formed ( neutralization, or detoxification). But there are many known cases of increased toxicity of poisons when their structure in the body changes. There are also such compounds, the characteristic properties of which begin to manifest themselves only as a result of biotransformation. At the same time, a certain part of the poison molecules is released from the body without any changes or generally remains in it for a more or less long period, being fixed by proteins of blood plasma and tissues. Depending on the strength of the "poison-protein" complex formed, the effect of the poison is slowed down or completely lost. In addition, the protein structure can only be a carrier of a toxic substance, delivering it to the corresponding 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. First, the knowledge of the molecular essence of the detoxification of poisons makes it possible to cordon off the defense mechanisms of the body and, on this basis, to outline the ways of directed action on the toxic process. Secondly, the amount of a dose of poison (medicine) that has entered the body can be judged by the amount of products of their conversion - metabolites excreted through the kidneys, intestines and lungs, which makes it possible to monitor the health of people involved in the production and use of toxic substances; in addition, 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 the induced enzymes with the help of certain substances, it is possible to accelerate or slow down the biochemical processes of the transformation of foreign compounds.
It has now been established that the processes of biotransformation of foreign substances proceed in the liver, gastrointestinal tract, lungs, and kidneys (Fig. 1). In addition, according to the research results of Professor I. D. Gadaskina, a considerable number of toxic compounds undergo irreversible transformations in adipose tissue. However, the liver is of prime importance here, or rather, the microsomal fraction of its cells. 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 rough, does not have ribosomes on its surface. It is not surprising, therefore, that with liver diseases, the body's sensitivity to many foreign substances increases sharply. 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 has been proven in other organelles of the cell (for example, in mitochondria), as well as in blood plasma and in intestinal microorganisms.
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 to glycogen; 10 - smooth endonlasmic 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 elimination 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, more and more importance has been attached to the so-called monooxygenase enzyme system with mixed function, which contains a special protein - cytochrome P-450. 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. Then this, already reduced, compound reacts with activated oxygen, resulting in the formation of an oxidized and, as a rule, 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. The processes of decomposition of poison molecules up to the irreversible transformation of their cyclic radicals are of considerable importance. But a special role among the mechanisms for neutralizing poisons is played by synthesis reactions, or conjugation, as a result of which non-toxic complexes - conjugates are formed. In this case, 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. Along the way, 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 vital activity, these processes can cause a deficiency of the latter in the body. Thus, there is a danger of a different kind - the possibility of the development of secondary disease states due to a lack of necessary metabolites. Thus, the detoxification of many foreign substances depends on the stores of glycogen 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 glucuronic acid esters (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 capable of cleaving off glucuronic acid molecules and thereby contributing to the neutralization of poisons. One of these substances turned out to be 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 elimination of toxic substances and products of their transformation from the body, the lungs, digestive organs, skin, and various glands play a certain role in this process. But the nights are of the greatest importance here. That is why, in many poisonings, with the help of special means 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 effect on the kidneys of some poisons excreted in the urine (for example, mercury). In addition, the products of the conversion of toxic substances can be retained in the kidneys, as is the case with severe poisoning with ethylene glycol. When it is oxidized in the body, oxalic acid is formed and calcium oxalate crystals are precipitated in the renal tubules, which impede urination. In general, similar 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, the formation of conjugates and the complete destruction of its molecule (rupture of the aromatic ring) 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 directions with the formation of toxic metabolites (Fig. 3). The latter are excreted through the kidneys. Benzene can be retained 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 transformation processes in the body toxic metals, exerting an ever wider influence 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, during which the transfer of electrons occurs, the valence of metals changes. In this case, the transition to the state of the lowest valence is usually associated with a decrease in the toxicity of metals. For example, hexavalent chromium ions are converted 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 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 creatures and plants, there are representatives of various classes of chemical compounds, to some extent toxic to humans: organochlorine, organophosphorus, organometallic, nitrophenol, cyanide, etc. According to available data, about 10% of all fatal poisoning currently caused by pesticides. The most significant of them, as you know, are FOS. When hydrolyzed, they usually lose their toxicity. In contrast to hydrolysis, oxidation of FOS is almost always accompanied by an increase in their toxicity. This can be seen if we compare the biotransformation of two insecticides - diisopropyl fluorophosphate, which loses its toxic properties by 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 orthophosphoric acid).
Among the widely used medicinal substances sleeping pills are the most common source of poisoning. The processes of their transformation in the body have been studied quite well. In particular, it was shown that the biotransformation of one of the common derivatives of barbituric acid, luminal (Fig. 4), proceeds slowly, and this underlies its rather long-term 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 in the body, hexobarbital, is of interest. Its hypnotic effect is much shorter, even when using significantly higher doses than luminal. It is believed that this depends on a higher rate and on a larger number of ways of inactivation of hexobarbital in the body (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 from this 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 with the simultaneous use of several drugs, due importance should 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, since it blocks an enzyme (esterase) that hydrolyzes novocaine in the body. Ephedrine manifests itself in the same way, binding oxidase, inactivating adrenaline and thereby lengthening and enhancing the effect of the latter.
Rice. 4. Modification of the luminal in the body in two directions: through oxidation and through the disintegration of the barbitur ring, followed by the transformation 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 against the background of 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 an inducer of microsomal enzymes suddenly stops, then this can lead to the toxic effect of drugs and will require a decrease 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 the genetically determined half-life in blood plasma 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, there are individual differences in the reactions to one or another pharmacological agent, depending on the interaction of many genetic factors. Thus, it was found that approximately one in 1–2 thousand people has a sharply reduced activity of serum cholinesterase, which hydrolyzes ditilin, a drug used to relax skeletal muscles for several minutes during some surgical interventions. In such people, the effect of ditilin sharply lengthens (up to 2 hours or more) and can become a source of 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 (decrease to 20% of the norm). This feature makes erythrocytes unstable to a number of medications: sulfonamides, some antibiotics, phenacetin. Due to the breakdown of erythrocytes in such persons against the background of drug treatment, hemolytic anemia and jaundice occur. 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 only gives an idea of the problem of biotransformation of toxic substances in general terms, it shows that the human body has many protective biochemical mechanisms that, to a certain extent, protect it from the unwanted effects of these substances, at least from their small doses. The functioning of such a complex barrier system is provided by numerous enzyme 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 it is necessary to understand the molecular mechanisms of their biological action.
Biological characteristics of the body that affect the toxic process
What internal factors, that is, those related to the human and animal body as an object of toxic effects, determine the onset, course and consequences of poisoning?
First of all it is necessary to 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 human dose of atropine. On the other hand, there are poisons that have a stronger effect on certain species 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, those acting mainly on the nervous system, chemical compounds. Thus, the results of the experiments given by KS Shadurskiy indicate that large identical doses of some FOS on guinea pigs are 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 primarily determined 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 biotransformation of foreign substances. This approach, for example, makes it possible to biochemically evaluate the fact of the resistance of rabbits and other animals to high 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, they are more sensitive to chemicals than warm-blooded animals. In this regard, the results of experiments on volunteers (doctors of 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 such substances as muscarine, heroin, atropine, morphine, man turned out to be ten times more sensitive than laboratory animals. The effect of some FOS 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 strong agitation and convulsions. On the other hand, benzene, inducing in rabbits, as in humans, inhibition of the hematopoietic system, in dogs does not lead to such shifts. 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 action 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 difference in the course of intoxication is determined gender characteristics... A large number of experimental and clinical observations have been devoted to the study of this issue. And although at the present time there is no impression that sexual sensitivity to poisons has any general laws, 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 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 one is significant differences between individuals of different sex in the rate of biotransformation of toxic substances in liver cells. It should not be forgotten that as a result of these processes in the body, even more toxic compounds can be formed, and it is they that can ultimately determine the speed of the onset, strength and consequences of the toxic effect. The second factor determining the unequal response of animals of different sex to the same poisons is 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 external 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 manifest themselves only when they reach puberty. This is also evidenced by the following example: if female rats are injected with the male sex hormone testosterone, and males - the female sex hormone estradiol, then females begin to react to some poisons (for example, drugs) like males, and vice versa.
Clinical and hygienic and experimental data indicate about a higher sensitivity to poisons in children than in adults, which is usually explained by the originality of the nervous and endocrine systems of the child's body, the peculiarities of ventilation of the lungs, absorption processes in the gastrointestinal tract, the permeability of barrier structures, etc. in view of the low activity of the biotransformational liver enzymes of the child's body, due to which he is less tolerant of poisons such as nicotine, alcohol, lead, carbon disulfide, as well as potent drugs (for example, strychnine, opium alkaloids) and many other substances that are mainly rendered harmless in the liver. But children (as well as young animals) are even more resistant to some toxic chemical agents than adults. For example, due to their less sensitivity to oxygen starvation, children under 1 year old are more resistant to the action of carbon monoxide - a poison that blocks oxygen - the transmitting function of blood. To this it should 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.
Consequences of exposure to poisons on the body
A lot of data have already been accumulated indicating the development of various painful conditions long after the 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 the blastomogenic, that is, 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. So, in a book recently published in Russian translation by the American researcher Ekholm, cases of the carcinogenic effect of a number of substances at industrial enterprises in the United States are cited. For example, people who work with arsenic in copper, lead and zinc smelters without adequate safety precautions have a particularly high incidence of lung cancer. Nearby residents are also more likely to develop lung cancer, presumably from inhaling arsenic and other harmful substances in the air from these factories. However, as the author notes, over the past 40 years, business owners have not introduced any precautions when workers come into contact with carcinogenic poisons. All this applies even more to the miners in uranium mines and workers in the dye industry.
Naturally, for the prevention of professional malignant neoplasms, first of all, it is necessary to remove carcinogens from production and replace them with substances that do not have blastomogenic activity. Where this is not possible, the most correct solution capable of guaranteeing the safety of their use is to establish their maximum permissible concentration. At the same time, in our country, the task is to drastically limit the content of such substances in the biosphere to quantities significantly lower than the MPC. Attempts are also made to influence carcinogens and toxic products of their transformations in the body using special pharmacological agents.
One of the dangerous long-term consequences of some intoxications are various malformations and deformities, hereditary diseases, etc., which depends both on the direct effect of the poison on the gonads (mutagenic effect), and on the disorder of intrauterine development of the fetus. To substances acting in this direction, toxicologists include benzene and its derivatives, ethyleneimine, carbon disulfide, lead, manganese and other industrial poisons, as well as certain pesticides. In this regard, the infamous drug thalidomide, which was used as a sedative in a number of Western countries by pregnant women and which caused deformities in several thousand newborns, should also be named. 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 over 300 thousand patients. Later it was discovered that long-term use of "Mer-29" led many people to severe skin diseases, baldness, decreased visual acuity and even blindness. Concern "U. Merrel & Co, the manufacturer of this drug, was fined $ 80,000, while the drug Mer-29 was sold for $ 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 compensation for numerous cases of deformities in newborns in the United States and England, whose mothers took a drug called bendectin for nausea in early pregnancy. The dangers of this drug were first raised in the medical community in early 1978, but pharmaceutical companies continue to produce bendectin, which brings great profits to their owners.
Notes:
Sanotskiy IV Prevention of harmful chemical influences on humans is a complex task of medicine, ecology, chemistry and technology. - ZhVHO, 1974, No. 2, p. 125-142.
Izmerov NF 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 V.F. Sanitary protection of atmospheric air. Moscow: Medicine, 1976.
Rudaki A. Kasydy. - In the book: Iranian-Tajik poetry / Per. from Farsi. M .: Art. lit., 1974, p. 23. (Ser. B-ka universal lit.).
(Luzhnikov 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. - Book: Fundamentals of General Industrial Toxicology / Ed. N. A. Tolokoyatsev and V. A. Filova. L .: Medicine, 1976, p. 184-197.
Pokrovsky A.A. Enzyme mechanism of some intoxications. - Advances biol. chemistry, 1962, vol. 4, p. 61-81.
Tiunov L.A. Enzymes and Poisons. - In the book: Questions of general industrial toxicology / Ed. I. V. Lazareva. L., 1983, p. 80-85.
Loktionov SI 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. Moscow: Mir, 1988.
Gadaskina I. D. Theoretical and practical value of the study. transformation of poisons in the body. - In the book: Mater. scientific. session, up to 40th anniversary of the Research Institute of Occupational Health and prof. diseases. L., 1964, p. 43-45.
E. S. Koposov. Acute poisoning. - In the book: Reanimatology. 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 toxic substances / Per. with him. under ed. I. L. Knunyants and R. N. Sterlin. Moscow: Chemistry, 1973.
Demidov A.V. Aviation toxicology. Moscow: Medicine, 1967.
Zakusav V.V., Komissarov I.V., Sinyukhin V.N. Repetition of the action of medicinal substances. - In the book: Clinical Pharmacology / Ed. V.V. Zakusov. 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. The mechanism of absorption of medicinal substances when taken orally. - Health. Kazakhstan, 1972, No. 10, p. 32-33.
The term "receptor" (or "receptor structure" we will denote the "point of application" of poisons: an 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. -pharmacological ideas about the essence of these concepts will be considered in Chapter 2.
It is also customary to understand metabolites as various biochemical products of normal metabolism (metabolism).
Gadaskina I. D. Fat 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. Sanotskiy. M., 1967, p. 59-62.
Krasovsky G. N., Avilova G. G. Species, sexual and age sensitivity to poisons. - ZhVHO, 1974, No. 2, p. 159-164.
From cancer (Latin for cancer), genos (Greek for birth).
Ekholm E. Environment and human health. Moscow: Progress, 1980.
Ogryzkov N.I. The benefits and harms of drugs. Moscow: Medicine, 1968.
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