Chemical-toxicological analysis of individual narcotic substances: cannabinoids, phenylalkylamines Department. Presentation on the topic: Introduction to toxicological chemistry. Chemical-toxicological objects Presentation on toxicological chemistry

LECTURE 1. Introduction to toxicological chemistry. Toxicological chemistry. Literature: 1. Toxicological chemistry: a textbook for universities / ed. T.V. Pleteneva.-2nd ed., revised. – M.: GEOTAR-Media, – 512 p. 2. Shvaikova M.D. Toxicological chemistry. M.: Medicine Kramarenko V.F. Toxicological chemistry. – K. High school Head publishing house, – 447 p. Subject and tasks of toxicological chemistry. Relationship with other disciplines. Features and main sections of toxicological chemistry. Main directions of chemical-toxicological analysis. Stages of formation and development of toxicological chemistry. Classification of isolation methods, analysis methods and groups of toxic substances. Organization of forensic chemical and forensic medical examinations in the Russian Federation. Legal and methodological foundations of forensic chemical examination. Classification of poisons and poisonings. General characteristics toxic effect. Formation of a toxic effect. Physico-chemical characteristics of toxic substances.

Toxicological chemistry Toxicological chemistry is the science of the chemical transformations of toxic substances and their metabolites in the body, methods of their isolation from objects of biological origin, detection and quantification. Toxicology (from the Greek toxikon - poison, logos - teaching) is a science that studies the properties of poisons and physical factors, the mechanisms of their action on the human body and develops methods for diagnosing, treating and preventing poisoning. Chemistry is a science that studies substances and the processes of their transformation, accompanied by changes in composition and structure.

Tasks of modern toxicological chemistry: 1. Development of new and improvement of already used methods for isolating toxic substances from relevant objects. 2. Development of effective methods for cleaning extracts obtained from objects of chemical and toxicological analysis. 3. Introduction into CTA practice of new sensitive and specific reactions and methods for detecting toxic substances isolated from relevant objects. 4. Development and implementation of sensitive methods for quantitative determination of toxic substances into the practice of CTA. 5. Study of the metabolism of toxic substances in the body and development of methods for analyzing metabolites. Toxicological chemistry is a special pharmaceutical discipline and is interconnected with other disciplines: - medical (pharmacology, forensic and clinical toxicology); - biological (biochemistry, biology, pharmacognosy); - chemical (pharmaceutical, analytical, inorganic, organic, physical and other chemistry)

Methods and methods of chemical analysis as applied to biological objects. Sections of toxicological chemistry Biochemical toxicology Analytical toxicology questions of the mechanisms of the toxic effect of substances on such complex system as a living organism: kinetics of absorption, distribution, excretion, mechanisms of metabolic reactions, pathways and mechanisms of transport of substances.

Ecotoxicological – issues of biomedical toxicology (assessment of the safety of drugs and excipients), - professional toxicology (assessment of the risk of working with chemicals), - toxicology environment(the effect of toxicants contained in water, air and soil on biological objects). Areas of toxicological chemistry: forensic chemistry - establishes the causes of poisoning on the basis of physical evidence (objects that served as instruments for committing a crime, preserved traces of the crime, were the object of the crime and serve as a means to solve the crime). clinical-toxicological – related to issues of providing medical care for acute and chronic poisoning; narcological – identification of narcotic substances

Chemical toxicological analysis (CTA) is a set of scientifically based methods used in practice for the isolation, detection and quantification of toxic substances. Features of CTA: 1. Diversity and diversity of research objects: biological fluids (blood, urine), vomit, internal organs of human corpses, hair, nails, food and drink residues, medicines, pesticides, household chemicals, dishes, household items, clothing, water, soil, etc. 2. The need to isolate (extract) small quantities (from mg to μg) of the desired chemical substances from relatively large quantity object of research. 3. Working with trace amounts of a substance in a mixture with accompanying (coextractive, ballast) substances that are extracted during isolation and often have a negative effect on the results of the analysis. It is necessary to remove these ballast substances by introducing additional cleaning methods. 4. Establishing the presence of a toxic substance in the body and the ability to judge its quantity requires the most sensitive and specific methods of analysis. 5. Correct assessment of the analysis results - expert opinion. The expert can only talk about the detection or non-detection of the sought-after substance. 6. Difficulties in detecting and identifying a toxic substance, especially in the organs of a corpse, are also due to the behavior of the chemical substance in the body and corpse.

Legal and methodological foundations of forensic chemical examination. The legal and methodological foundations of forensic chemical examination are currently regulated by Order of the Ministry of Health of the Russian Federation No. 161 “On approval of instructions for organizing and conducting expert research.” Previously, there was Order of the Ministry of Health of the Russian Federation 407 of December 10 “On the introduction into practice of the rules for conducting forensic medical examinations in the forensic medical examination bureau.” Removal of objects for SCN research: 1. In order to detect and quantify toxic substances for SCN, various internal organs, blood, urine are removed and sent, taking into account the nature of the poison and the routes of its introduction into the body, distribution, routes and rate of elimination, duration of intoxication and therapeutic measures. Vomit, first portions of rinsing water, remains of medicinal and chemical substances, food, drinks and other objects are also sent. 2. If poisoning with a toxic substance is suspected, a complex of internal organs is sent: the stomach with its contents, 1 m of the small intestine, 1/3 of the liver, 1 kidney, all urine and at least 200 ml of blood. 3. If there is a suspicion of the introduction of poison through the vagina or uterus, the uterus and vagina are additionally sent separately. 4. If subcutaneous or intramuscular injection is suspected, a section of skin or muscle from the area of the injection site. 5. If inhalation administration is suspected – ¼ of the lung, 1/3 of the brain. 6. If grains, crystals, or tablets are found in the stomach contents, they are also sent for examination.

In case of suspected poisoning, they are additionally sent: 1. Acids, alkalis - the pharynx, trachea and esophagus, an area of skin with traces of the action of poison. 2. Volatile organic substances (chloroform, carbon tetrachloride, dichloromethane, organochlorine pesticides and other alkyl halides) – omentum, 1/3 of the brain. 3. Methyl alcohol – 1/3 of the brain. 4. Glycosides - 1/3 of the liver with gallbladder. 5. Organophosphorus compounds – necessarily blood (to determine cholinesterase activity). 6. Mercury salts – rectum, hair. 7. Chronic poisoning with lead compounds, waist – flat bones. 8. Chronic poisoning with arsenic compounds – hair, nails, flat bones. 9. Tetraethyl lead – brain, lungs. 10. Carbon monoxide – blood, muscle tissue. 11. Ethanol - blood from large veins, urine, if impossible - about 500g of muscle tissue. 12. Methemoglobin-forming poisons (aniline, nitrobenzene, potassium permanganate, formaldehyde, chromates, acetaldehyde) - blood for methemoglobin. 13. Mushrooms and poisonous plants– undigested pieces from the contents of the stomach, vomit, washing water.

Rules for conducting a forensic chemical examination of material evidence in the SKhO LSU Bureau of Forensic Examination of Health Authorities Tasks of the forensic chemical examination: - determination of toxicologically important substances to establish the cause of death; - identification of medicinal and narcotic substances that can affect the human condition; - qualitative and quantitative analysis of narcotic substances in biological material and other samples relevant for forensic medical and forensic investigative practice; - to obtain analytical results, the subsequent interpretation of which may be useful for forensic investigative authorities, attach paramount importance the right choice, seizure and referral of objects for forensic chemical examination.

Grounds for carrying out a forensic chemical examination: - a forensic chemical examination of physical evidence is carried out on the basis of a resolution of the inquiry and investigation authorities, a court ruling; - forensic chemical studies of internal organs, tissues, biological fluids of human corpses can be carried out upon written directions from forensic experts; - forensic chemical examination of biological fluids, human secretions, swabs from the surface of the skin in cases of suspected poisoning or non-medical consumption of narcotic and other drugs is carried out on the orders of doctors from drug treatment clinics and other medical institutions. Along with the material evidence, the following documents are sent: - a resolution of the inquiry or investigative authorities on the appointment of an examination or a court ruling, which sets out the circumstances of the case, lists the items sent for examination and precisely formulates the issues requiring resolution; - an extract from the report of the forensic medical examination of the corpse, containing preliminary information, basic data of the examination of the corpse and indications of the purpose of the study, signed by the forensic expert; - a copy of a hospital patient’s card certified by a medical institution, if the victim used medical care; - during repeated examinations, a certified copy of the “Act of (primary) forensic chemical research” is sent; simultaneously with the objects of research, an act of removal of samples is sent from narcological dispensaries, indicating the persons in whose presence the objects (witnesses) were taken, the signatures of the persons being examined, as well as the persons sending objects for research and taking samples.

Responsibilities and rights of persons admitted to carry out forensic chemical examinations: - forensic chemical examinations are carried out by persons admitted to occupy the position of a doctor of a forensic medical expert of an agricultural organization, who have undergone special training in toxicological chemistry; - forensic chemical experts of agricultural organizations must improve their theoretical level and professional qualifications at refresher courses at least once every five years; responsibilities of a doctor-expert: -reception of material evidence and documents related to it; -control over the registration of examinations; -conducting forensic chemical examinations on modern level achievements of science and on time; - keeping records in the work log; -conducting advisory work within its competence with persons who sent objects and conducting investigations of criminal cases; - drawing up a forensic chemical research report; -ensuring the safety of material evidence, research objects and examination documents

Reception and storage of research objects (physical evidence) and accompanying documents 1. Research objects (material evidence) are received through the Bureau office or directly to the agricultural storage department in accordance with the rules for sending cadaveric material to the agricultural chemical storage department: - objects are registered along with accompanying documents in the agricultural agricultural organization registration journal ( the journal must be numbered, laced, sealed and signed by the head of the agricultural organization; - objects are subjected to a detailed inspection and description, noting the nature of the packaging, inscriptions, seal, checking compliance with the data specified in the direction (resolution) 2. Physical evidence before the start of the forensic chemical examination. , during the analysis and until its completion, they are stored in conditions that ensure safety: - not subject to rotting - in a closed, sealed metal cabinet; - subject to rotting (internal organs, biological fluids) - in a hermetically sealed container in a refrigerator, which is sealed at the end of the work. 3. At the end of the examination: - objects that are not subject to decay are returned along with the conclusion to the sending institution; - those subject to rotting are left for storage in the agricultural organization for 1 year after the end of the examination, after which they are destroyed in accordance with the “Rules of storage and destruction...” (objects received for examination only for the presence of ethanol are destroyed 1 month after the end of the analysis) - accompanying documents are stored in the archive along with a copy of the “forensic chemical research report.”

The procedure for conducting a forensic chemical examination. Basic rules of forensic chemical analysis (FCA) 1. FCA must begin on the day the objects are received for analysis. If this is not possible, then the objects are stored in the refrigerator. 2. When starting SCA, the expert carefully examines the objects and describes them in the work log, establishing full compliance of the received objects with their description in the accompanying document. 3. The expert carefully studies all accompanying documents and draws up a research plan. 4. To carry out SCA, 2/3 of the sent objects are used, 1/3 remains in the archive for re-analysis if necessary. However, if the quantity is limited, the entire object is consumed in agreement with the sending organization. 5. Depending on the questions posed, the study can be carried out on a specific compound, a group of substances, or on an unknown substance according to the general SCA (screening analysis) scheme. 6. For research, you should always use only those methods and procedures that the expert has previously familiarized himself with, owns them, knows all the conditions, and can take into account all the errors that may arise. All methods must be tested in advance. The main task of SCA is to choose the optimal isolation method. For qualitative detection, preliminary and confirmatory methods are used, taking into account their sensitivity and specificity. 7. Each forensic chemical study should be carried out as quantitative, which it can turn into at any stage of the work. 8. Quantitative determination is carried out in all cases where this is possible and appropriate determination methods are available. The amount of substances found refers to 100 g of a sample of the object and is expressed in weight units. 9. All methods of quantitative determination must be tested on the biological matrix that will be used for analysis (blood, urine, organ tissue) according to the scheme of model experiments. 10. It is necessary to ensure the chemical purity of the reagents used for analysis, while the purity of the reagents is checked in the maximum quantities in which they will be used for analysis and by the same methods and reactions that will be used during SCA. 11. To ensure high quality of examination, it is recommended to carry out internal and external quality control, focused on both the method and the substance being determined. The forensic chemistry department must be licensed.

Documentation during forensic chemical examination Documentation is drawn up in accordance with criminal procedural legislation and the order of the Ministry of Health of the Russian Federation. Each expert has a work journal where he enters all the data on the research being carried out. For each completed examination, a “Forensic Chemical Research Report” (“Expert Conclusion”) is drawn up. The act is drawn up in two copies: one is sent to the person who appointed the examination, the second is stored in the archives of the agricultural organization. The act must have the expert’s signature, seal, and completion date. The act is drawn up personally by the expert who conducted the research, on his own behalf, in a certain form. The act consists of main sections: introductory part, description of research objects, research part (chemical research) and conclusion (conclusions). In the water part they indicate: on the basis of which documents the examination was carried out, the department in which the research was carried out, position, full name of the expert, work experience, category, list the objects received, indicate the full name of the deceased (victim), note the start and end date of the research, list the questions, subject to decision. Then they state the circumstances of the case and provide information from the documents received. The act must bear the expert’s signature, seal, and date of execution. To ensure confidentiality in agricultural organizations, precautions must be taken (distribution of information and documentation only to an authorized person).

Stages of development of toxicological chemistry Ancient Egyptian papyrus 1500 BC. contains information on the use of opium and metal compounds - lead, copper, antimony - for poisoning. Dioscidorus, who served at the court of the Roman emperor Nero (37-68 AD), was the first to try to classify poisons, dividing them into animal, plant and mineral. In the Middle Ages, Maimonides (AD) created a treatise on the treatment of poisoning due to bites by insects, snakes and mad dogs (Poisons and their antidotes, 1198). For the first time, the reason for the decrease in the bioactivity of a toxic substance was described - a decrease in its absorption in the intestines after eating food - milk, butter. Renaissance (14th-16th centuries) During the early Renaissance, under the guise of charitable supplies for the poor, Catherine de Medici herself supervised the preparation of toxic mixtures, scrupulously recording the moment of onset of toxic effects, the effectiveness of the combination of toxicants, the response of individual organs (specificity of the effect), complaints of victims ( clinical symptoms). Paracelsus () - an alchemist, successfully coped with the description of the dose-response relationship fundamental in toxicology. A detailed study of the effects of various poisons allowed us to conclude: all substances are poisons; There is not a single substance that does not exhibit toxic properties. Only a correctly selected dose allows one to draw the line between the medicinal and toxic properties of a substance. XVIII century Peter I publishes the Military Regulations - forensic medical and forensic chemical examinations acquire a legislative character. Research after autopsy of corpses is carried out only in St. Petersburg and Moscow. M.V. Lomonosov creates the first Russian chemical laboratory. Development of methods for analyzing chemical substances. The creation of medical boards in the provinces with the position of a pharmacist, whose duties include the detection of poisons.

Stages of the development of toxicological chemistry in the 19th century Russian scientist Nelyubin A.P. develops mineralization methods for determining metal poisons, detecting arsenic by reducing it to a volatile hydride (arsine) / Published the manual “General and private forensic and police chemistry.” Iovsky A.A. publishes a “Guide to the recognition of poisons, antidotes and the most important determination of the former both in the body and outside it through chemicals, called reagents." Dragendorf G. published “Forensic chemical discovery poisons”, singled out forensic chemistry as an independent discipline. Trapp Y.K. publishes the work “Manual for forensic chemical research.” Zinin N.N. published a description of the methods he developed for determining the poor quality of wines and impurities in Chinese tea. Mendeleev D.I. performed chemical examinations for forensic investigative authorities, was a member of the highest forensic commission of Russia - the Medical Council. XX century In 1958, laws appeared regarding those chemical compounds whose carcinogenicity was proven in tests on laboratory animals. A ban on their inclusion in food products. Creation in the USSR of the State Research Institute of Forensic Medicine, on the basis of which numerous methods were developed (determination of mercury in biomaterials, isolation of alkaloids by extraction into acidic aqueous media, determination of phenothiazine derivatives, and many others). Creation of forensic chemistry departments in St. Petersburg (Petrograd), Perm, Kharkov, Moscow and other cities. Publishing textbooks: “Forensic Chemistry” - A.V. Stepanov (1951), M.D. Shvaikova (1959, 1965, 1975), “Toxicological chemistry” (1987) - V.F. Kramarenko (Ukraine). Currently, there are more than 120 journals around the world publishing materials on toxicology and related disciplines. Three specialized journals are published in Russia: “Forensic Medical Examination”, “Pharmacology and Toxicology”, “Forensic Medical and Expert Practice”.

1. Subject and tasks of toxicological chemistry The basis of toxicological chemistry is made up of two natural science disciplines: toxicology and chemistry. Toxicology (from the Greek toxikon - poison and logos - teaching) is a science that studies the mechanisms of action of toxicants of a chemical nature and physical factors on the human body and develops methods for diagnosing, treating and preventing poisoning.

Toxicological chemistry is the science of the molecular and physiological mechanisms of action of toxic substances and the products of their metabolism, chemical methods of their isolation, identification and quantification in various objects (biological materials, the environment - water, air, food, medicines, other material evidence of poisoning) .

Fundamentals of analytical toxicology. - Geneva-Moscow: WHO, 1997 State (federal) laboratory designed for a population of 2 - 4 million people. tasks of district management analytical center(for 20-100 thousand people) and regional laboratories (1-2 million people), conducting scientific research and training of specialists.

State (federal) laboratory Performs any analysis, including determination of trace amounts of chemicals. For this purpose, a director, doctors (3-6), and laboratory assistants (10-15) are located in 34 laboratories. The studies use UV and IR spectrophotometry, gas and high-performance liquid chromatography, immunochemical methods, densitometry, chromatography-mass spectrometry (HPLC-MS). The number of tests per year exceeds 1000 for poisons and 5000 for alcohol.

Structure of the organization of the forensic medical direction of analytical toxicology in the Russian Federation: Structure of the organization of the forensic medical direction of analytical toxicology in the Russian Federation: About 60 thousand various expert cases - 78% of forensic examination About 500 thousand corpses annually 70-80 thousand people a year die from poisoning (52-54% - alcohol and its substitutes)

Geological pocket (oxygen poor area) Geological pocket (oxygen poor area) Mazukus is Swahili and means "evil wind". A colorless and odorless gas accumulates in such a “pocket” very close to the ground (for example, CO2). On August 21, 1986, possibly due to a landslide, Lake Nyos emits a large cloud of CO2. As a result, 1,700 people and 3,500 heads of livestock suffocated in nearby villages. There are other lakes with similar habitat conditions: Lake Kivu Goma, Congo

3.1. Biochemical toxicology studies the toxicodynamics and toxicokinetics of xenobiotics and their metabolites. Regularities describing the mechanisms and rates of intake, distribution, elimination and excretion, the mechanisms of formation of the toxic effect and biotransformation of xenobiotics - this is the range of issues of biochemical toxicology.

As a result of a chemical toxicological study (CTI), it becomes possible to: - identify the substance or group of substances that caused poisoning, - carry out diagnostics, - determine the phase of poisoning, - effectively carry out detoxification.

Toxicological study - establishing the cause of the disease 1997 - Professor of the Department of Chemistry at Dartmouth College Karen Wetterhahn worked with dimethylmercury Hg(CH3)2: the experiment was carried out in a fume hood, she had rubber gloves on her hands. When transferring a substance from one container to another, a droplet of it fell on the glove. According to the victim, she threw away her gloves and forgot about the incident. A month later, symptoms of poisoning appeared: loss of skin sensitivity, painful sensations, difficulty speaking. Tests of mercury levels in hair, blood and secretions confirmed the suspicion of mercury poisoning. Despite intensive therapy, the patient could not be saved; she died 10 months later. The lipophilic nature (tendency to interact with fats) of dimethylmercury allows, as is now known, this substance to quickly penetrate through rubber membranes and human skin into the body.

Poisoning as a disease of chemical etiology requires emergency treatment. NB! Undirected analysis, i.e. searching for an “unknown” poison requires much more time than a targeted analysis based on the conclusion of a toxicologist about the possible nature of the toxicant.

4. History of the emergence and development of toxicological chemistry Papyrus 1500 BC. contains information on the use of opium and metal compounds - lead, copper, antimony - for poisoning. Dioscorides, who served at the court of the Roman Emperor Nero (37-68), was the first to try to classify poisons, dividing them into animal, plant and mineral (“De material medica”)

Middle Ages Maimonides (1135-1204) created a treatise on the treatment of poisoning from bites by insects, snakes and rabid dogs (Poisons and Their Antidotes, 1198). For the first time, the reason for the decrease in the bioactivity of a toxic substance was described - a decrease in its absorption in the intestines after eating food - milk, butter.

Renaissance (14th-16th centuries) During the early Renaissance, under the guise of charitable supplies to the fund of the poor, Catherine de Medici herself supervised the preparation of toxic mixtures, scrupulously recording the moment of onset of toxic effects, the effectiveness of the combination of toxicants, the response of individual organs (specificity of the effect), complaints of victims (clinical symptoms).

Paracelsus (1493-1541), an alchemist, successfully described the fundamental dose-response relationship in toxicology. A detailed study of the effects of various poisons allowed us to conclude: all substances are poisons; There is not a single substance that does not exhibit toxic properties. Only a correctly selected dose allows one to draw the line between the medicinal and toxic properties of a substance.

XVIII century Peter I publishes the Military Regulations - forensic medical and forensic chemical examinations acquire a legislative character. Research after autopsy of corpses is carried out only in St. Petersburg and Moscow. M.V. Lomonosov creates the first Russian chemical laboratory. Development of methods for analyzing chemical substances. The creation of medical boards in the provinces with the position of a pharmacist, whose duties include the detection of poisons.

XIX century Russian scientist Nelyubin A.P. develops mineralization methods for determining metal poisons, detecting arsenic by reducing it to a volatile hydride (arsine). Published the manual “General and private forensic and police chemistry.” Russian scientist Iovsky A.A. publishes a “Guide to the recognition of poisons, antidotes and the most important determination of the former both in the body and outside it through chemical means called reagents.”

Russian scientist Zinin N.N. published a description of the methods he developed for determining the poor quality of wines and impurities in Chinese tea. Russian scientist Zinin N.N. published a description of the methods he developed for determining the poor quality of wines and impurities in Chinese tea. Famous Creator Periodic table elements Mendeleev D.I. performed chemical examinations for forensic investigative authorities, was a member of the highest forensic commission of Russia - the Medical Council.

XX century The widespread use of "available" drugs has led to numerous cases of poisoning. A particular danger is counterfeit drugs. Poisoning from uncontrolled dietary supplements Cases of poisoning associated with the use of food additives eg food preservation chemicals.

In the USA in 1938, mass poisoning occurred when taking sulfa drugs. This was the impetus for the creation of the Food and Drug Administration (FDA). In the USA in 1938, mass poisoning occurred when taking sulfa drugs. This was the impetus for the creation of the Food and Drug Administration (FDA). In 1947, a law was passed on the need to test the safety of pesticides. The reason for this was the improper use of pesticides in agriculture USA, which led to mass poisonings. In 1958, laws appeared regarding those chemical compounds whose carcinogenicity was proven in tests on laboratory animals. A ban on their inclusion in food products.

Creation in the USSR of the State Research Institute of Forensic Medicine, on the basis of which numerous methods were developed (determination of mercury in biomaterials, isolation of alkaloids by extraction into acidic aqueous media, determination of phenothiazine derivatives, and many others.) Creation of the State Research Institute of Forensic Medicine in the USSR, on the basis of which numerous methods have been developed (determination of mercury in biomaterials, isolation of alkaloids by extraction into acidic aqueous media, determination of phenothiazine derivatives, and many others). Creation of departments of forensic chemistry in St. Petersburg (Petrograd), Perm, Kharkov, Moscow and other cities. Publishing textbooks: “Forensic Chemistry” - A.V. Stepanov (1951), M.D. Shvaikova (1959, 1965, 1975), “Toxicological chemistry” (1987) - V.F. Kramarenko (Ukraine).

Currently, there are more than 120 journals around the world publishing materials on toxicology and related disciplines. “Archiv fur Toxikologie” began to be published in Europe in 1930. “Toxicology and Applied Pharmacology” began to be published in the mid-twentieth century. The International Association of Forensic Toxicologists (TIAFT) publishes the journal Bulletin of the International association of forensic toxicologists. In Russia, three specialized journals are published: “Forensic Medical Expertise” and “Pharmacology and Toxicology”, “Forensic Medical and Expert Practice”.

Poison is a substance that causes poisoning or death when ingested in small quantities. Poisons can include not only chemical compounds, but also other materials of various natures, for example, asbestos fibers, animal hair, zootoxins, various microorganisms

Toxin is a substance of bacterial, plant or animal origin that, when it enters the body of humans or animals, can cause disease or death. Toxin is a substance of bacterial, plant or animal origin that, when it enters the body of humans or animals, can cause disease or death.

Tolerance (lat. tolerantia ability to endure, patience; portability) is the body’s ability to tolerate the effects of poison without developing a toxic effect. Thus, tolerance manifests itself as a decrease in the body's response to the action of a toxic substance compared to previous exposure.

Cumulation (lat. cumulo, cumulatum to add up, accumulate) is the accumulation of a biologically active substance (material cumulation) or the effects it causes (functional cumulation) during repeated exposure to poisons. Cumulation is typical for compounds of mercury, arsenic, many alkaloids (for example, atropine), cardiac glycosides, and sulfonamides.

Types of toxic doses and concentrations A toxic dose is a dose that causes pathological changes in the body that do not lead to death. Toxic doses occupy a range of doses from minimally toxic to minimally lethal.

The minimum toxic dose is the threshold dose for an effect that goes beyond the limits of normal physiological reactions. The minimum toxic dose is the threshold dose for an effect that goes beyond the limits of normal physiological reactions. Minimum lethal dose - a dose that causes the death of single, most sensitive experimental animals over a fixed period of time; is taken as the lower limit of lethal dose (MLD).

An absolute lethal dose is a dose that causes the death of no less than 99% of experimental animals over a fixed period of time (LD100). An absolute lethal dose is a dose that causes the death of no less than 99% of experimental animals over a fixed period of time (LD100). An average lethal dose is a dose that causes the death of 50% of experimental animals over a fixed period of time (LD50).

The degree of toxicity of a substance depends on many factors: allotropic modification (for example, yellow and red phosphorus); oxidation states of elements (mercury(I) in calomel Hg2Cl2 and mercury(II) in sublimate HgCl2), phase state (liquid mercury and mercury vapor); degree of dispersion (silica gel SiO2 in the form of highly dispersed powder, talc); the solubility of the substance and its ability to dissociate with the formation of ionic forms of elements (slightly soluble barium sulfate and highly soluble barium chloride; molecular tetraethyl lead and lead cations in body fluids).

For intravenous, intramuscular, subcutaneous and oral administration, as well as for cutaneous application, toxic doses have dimensions of mg/kg, mcg/kg, mol/kg. But only the latter method corresponds to the international system of SI units of measurement and unambiguously reflects the toxic dose, since it takes into account the value molar mass toxic substance (n = m/M). For intravenous, intramuscular, subcutaneous and oral administration, as well as for cutaneous application, toxic doses have dimensions of mg/kg, mcg/kg, mol/kg. But only the latter method corresponds to the international system of SI units of measurement and unambiguously reflects the toxic dose, since it takes into account the molar mass of the toxic substance (n = m/M).

For toxic gases, vapors and aerosols, the dose can be presented in the form of volumetric concentrations - mg/l, mg/m3, mol/m3. Only the last method is systemic, allowing one to compare the toxicity of different substances. Sometimes so-called parts per million are used, expressed in parts per million [ppm, parts per million] or in cubic centimeters per cubic meter [cm3/m3]). For toxic gases, vapors and aerosols, the dose can be presented in the form of volumetric concentrations - mg/l, mg/m3, mol/m3. Only the last method is systematic, allowing one to compare the toxicity of different substances. Sometimes so-called parts per million are used, expressed in parts per million [ppm, parts per million] or in cubic centimeters per cubic meter [cm3/m3]).

When presenting toxicity results, the duration of inhalation and time of death must be indicated. When presenting toxicity results, the duration of inhalation and time of death must be indicated. For example, when inhaled for 4 hours, 50% of individuals died 48 hours after cessation of exposure to the toxicant. A quantitative characteristic of toxicity during inhalation action of a substance is also the product of concentration and exposure duration (C t).

In some countries, the term "acceptable daily intake" (ADI) is widely used to estimate the daily amount of a chemical ingested that does not pose an appreciable risk over a person's lifetime. In some countries, the term "acceptable daily intake" (ADI) is widely used to estimate the daily amount of a chemical ingested that does not pose an appreciable risk over a person's lifetime. ADI values are expressed in mg/kg body weight per day for many pesticides and food additives that enter the human body through food. For example, the Coca-Cola company provides information on the ADI values of some components contained in its drinks.

The degree of toxicity of a substance is also characterized by the maximum permissible concentration (MPC). MPC is the highest concentration harmful substance in environmental objects, which, under conditions of constant exposure to the body or in the long term after it, does not cause any diseases or deviations in the state of health in humans. The degree of toxicity of a substance is also characterized by the maximum permissible concentration (MPC). MPC is the highest concentration of a harmful substance in environmental objects, which, under conditions of constant exposure to the body or in the long term after it, does not cause any diseases or health problems in humans.

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Toxicological chemistry Gorchakov Eduard Vladimirovich St. Lecturer at the Department of Therapy and Pharmacology. . Literature: 1. Toxicological chemistry: a textbook for universities / ed. T.V. Pleteneva.-2nd ed., revised. – M.: GEOTAR-Media, 2005. – 512 p. 2. Toxicological chemistry. Metabolism and analysis of toxicants: training manual/ Ed. prof. N.I. Kaletina. – M.: 2008. 3. Vergeichik T.Kh. Toxicological chemistry. Textbook for pharmacy students. Universities and faculties., 2012 4. Khabrieva R.U., Kaletina N.I. Toxicological chemistry. - M.: Geotar - Media, 2010. LECTURE No. 1. Introduction to toxicological chemistry. 1. Introduction to the discipline. 2. Contents and objectives. 3. Chemical toxicological analysis (CTA). Toxicological chemistry Toxicology (from the Greek toxikon - poison, logos - teaching) is a science that studies the properties of poisons and physical factors, the mechanisms of their action on the human body and develops methods for diagnosing, treating and preventing poisoning. Chemistry is a science that studies substances and the processes of their transformation, accompanied by changes in composition and structure. Toxicological chemistry (TC) is a science that studies methods for isolating toxicological substances from various objects, as well as methods for detecting and quantifying these substances. Sources of poisoning Wastewater industrial enterprises that pollute water bodies whose water is consumed by the population. The use of pesticides (pesticides) to control pests of agricultural crops. Pesticides washed off from the surface of plants by rainwater enter the soil, then into water bodies and cause poisoning. Pharmaceutical industry. Industries related to the synthesis, production and processing of natural resources. and others. The importance of toxicological chemistry. is of great importance in the diagnosis of poisoning and in the fight against crime (forensic medical examination) has a preventive focus. The conclusions of toxicological chemists are the basis for raising the question of removing these substances from use or changing the storage conditions and the procedure for distributing them to the population. The results of studies of air and wastewater from industrial enterprises are necessary to initiate a petition for the need to build or reconstruct treatment facilities. Using toxicological chemistry methods, they establish and control the maximum permissible concentrations of toxic substances in the air. Objectives of modern toxicological chemistry: 1. Development of new and improvement of existing methods for isolating toxic substances. 2. Development of effective methods for cleaning extracts obtained from objects of chemical toxicological analysis (CTA). 3. Introduction into CTA practice of new sensitive and specific reactions, as well as methods for detecting toxic substances from the objects under study. 4. Development and implementation of sensitive methods for quantitative determination of toxic substances into the practice of CTA. 5. Study of the metabolism of toxic substances in the body and development effective ways metabolite analysis. Relationship of toxicological chemistry with other sciences Toxicological chemistry is a special discipline and is interconnected with pharmaceutical chemistry through other disciplines: - medical (pharmacology, forensic and clinical toxicology); - biological (biochemistry, biology, pharmacognosy); - chemical (pharmaceutical, analytical, inorganic, organic, physical and other chemistry); physical (the laws of physics underlie the development of instruments and apparatus). Chemical toxicological analysis (CTA) is a set of scientifically based methods used in practice for the isolation, detection and quantification of toxic substances. CTA is used to solve problems in two main areas: Forensic chemical examination. Can be carried out in the forensic chemical departments of the forensic medical examination bureau of health authorities, or in special forensic laboratories of the Ministries of Justice and Internal Affairs. Analytical diagnosis of acute poisoning and substance abuse. Similar studies are carried out in chemical and toxicological laboratories of centers for the treatment of acute poisoning, drug treatment clinics and other health care institutions. Objects of chemical and toxicological analysis. Organs of corpses, urine, blood of corpses Vomit Excrement Hair, nails Gastric lavage water, leftover food, drinks Pesticides, plant parts treated with pesticides Water from reservoirs Air samples Soil Household items, clothing, etc. Drug addiction is a serious illness leading to mental disorder and physical exhaustion of the body. Chemical-toxicological analysis in veterinary medicine Research is carried out both in veterinary laboratories and in other special institutions. Removal of objects for SCN research: 1. In order to detect and quantify toxic substances for SCN, various internal organs, blood, urine are removed and sent, taking into account the nature of the poison and the routes of its introduction into the body, distribution, routes and rate of elimination, duration of intoxication and therapeutic measures. Vomit, first portions of rinsing water, remains of medicinal and chemical substances, food, drinks and other objects are also sent. 2. If poisoning with a toxic substance is suspected, a complex of internal organs is sent: the stomach with its contents, 1 m of the small intestine, 1/3 of the liver, 1 kidney, all urine and at least 200 ml of blood. 3. If there is a suspicion of the introduction of poison through the vagina or uterus, the uterus and vagina are additionally sent separately. 4. If subcutaneous or intramuscular injection is suspected, a section of skin or muscle from the area of the injection site. 5. If inhalation administration is suspected – ¼ of the lung, 1/3 of the brain. 6. If grains, crystals, or tablets are found in the stomach contents, they are also sent for examination. In case of suspected poisoning, they are additionally sent: 1. Acids, alkalis - the pharynx, trachea and esophagus, an area of skin with traces of the action of poison. 2. Volatile organic substances (chloroform, carbon tetrachloride, dichloromethane, organochlorine pesticides and other alkyl halides) – omentum, 1/3 of the brain. 3. Methyl alcohol – 1/3 of the brain. 4. Glycosides - 1/3 of the liver with gall bladder. 5. Organophosphorus compounds – necessarily blood (to determine cholinesterase activity). 6. Mercury salts – rectum, hair. 7. Chronic poisoning with lead compounds, waist – flat bones. 8. Chronic poisoning with arsenic compounds – hair, nails, flat bones. 9. Tetraethyl lead – brain, lungs. 10. Carbon monoxide – blood, muscle tissue. 11. Ethanol - blood from large veins, urine, if impossible - about 500g of muscle tissue. 12. Methemoglobin-forming poisons (aniline, nitrobenzene, potassium permanganate, formaldehyde, chromates, acetaldehyde) - blood for methemoglobin. 13. Mushrooms and poisonous plants - undigested pieces from the contents of the stomach, vomit, rinsing water. Tasks of forensic chemical examination: - determination of toxicologically important substances to establish the cause of death; - identification of medicinal and narcotic substances that can affect the human condition; - qualitative and quantitative analysis of narcotic substances in biological material and other samples relevant for forensic and forensic practice; To obtain analytical results, the subsequent interpretation of which can be useful for forensic investigative authorities, paramount importance is attached to the correct selection, seizure and direction of objects for forensic chemical examination. Documentation for conducting research 1. A written statement indicating what is being sent, from whom and what exactly needs to be examined 2. Accompanying materials: - a decision of the court, investigative authorities on the examination with the exact wording of the questions posed to the researcher, a copy of the forensic veterinary autopsy report , -copy of the medical history Requirements for received material 1. The material must be packaged in clean containers. 2. Sealed with the drawing up of a simultaneous special act or entering into the protocol of the forensic veterinary autopsy instructions on the selection of pathological material. 3. All containers are provided with labels and an accompanying description of the contents. 4. Patent material is fixed. If it is not possible to fix it, freeze it. 5. Bulk and grain feed is sent in quantities of about 1 kg, the approximate weight or volume, storage conditions, smell, color, etc. are indicated. 6. Upon acceptance of the material by the laboratory, a receipt is issued, and the results of the analysis are reported in writing.

Chemical-toxicological analysis of individual narcotic substances: cannabinoids, phenylalkylamines department. Presentation on the topic: Introduction to toxicological chemistry. Objects of chemical-toxicological Presentation on toxicological chemistry

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