Occupational hazards at pharmaceutical enterprises. Occupational health in the chemical and pharmaceutical industry Features of the chemical and pharmaceutical industry
Distinctive features of the chemical and pharmaceutical industry
from "Chemistry and technology of chemical pharmaceuticals"
The chemical-pharmaceutical industry is characterized by a number of technological and economic features that distinguish it from other branches of the chemical industry and determine the ways of organizing production and its further development.For example, to obtain 1 ton of the synthetic antibiotic synthomycin, it is necessary to process 40 tons of raw materials.
An even larger amount of raw materials has to be processed when isolating alkaloids from low-percentage plant materials. For example, when isolating ephedrine from mountain ephedra, the material index is 112 g per 1 ton of product.
To produce 1 kg of tropine, 1800 kg of thousand-headed fish must be consumed. This determines the significant share of raw material costs in the cost of production, amounting to about 75%.
The above distinctive features of the chemical and pharmaceutical industry determine the need for highly qualified service personnel, primarily engineers, as well as operator operators.
These features urgently require further specialization of chemical and pharmaceutical plants based on common raw materials and technological processes. To quickly produce new low-tonnage drugs, pilot development workshops have been organized that produce drugs according to combined standard schemes. The production of large-scale drugs such as glucose, sulfatanabazine, caffeine, santonin (from plant materials), sulfonamide drugs, anesthetic and acetoacetic esters is being transferred to semi-continuous and continuous production schemes. Production lines for final operations of drying, crushing, sifting, weighing and packaging of large-scale chemical and pharmaceutical preparations are organized.
Ganichev L. On Aptekarsky Island. L., 1957.
Gvozdev N.V. and Kondratyev M.T. The beginning of the chemical and pharmaceutical industry in Russia. Sat. anniversary of materials. meeting, dedicated 250th anniversary of Leningrad. L., 1957.
Gusenkov P.V. Chemical and pharmaceutical industry today and tomorrow. Dokl. at the XIX session of the USSR Academy of Medical Sciences. Medical newspaper, 1964, M 11 (2278).
Volfkovich s. I. Chemical technology as a science and its tasks. M., 1961. Kalashnikov V.P. Materials on the organization of a chemical and pharmaceutical plant in Petrograd, 1915-1916. Pharmacy business, 1957, 3. Korzhenevsky E. With. Results of the implementation of the fifth five-year plan and the main tasks of the development of the chemical and pharmaceutical industry in the sixth five-year plan. Materials on the exchange of best practices and scientific achievements in the chemical and pharmaceutical industry. M., 1957, 1/11, 3-24.
Lukyanov P. M. History of chemical industries and the chemical industry of Russia until the end of the 19th century. L. - M., 1948.
Natradze A. G. Production of medicines and medical equipment in 1959-1965. Medgiz, 1961.
Natradze A.G., Yakovleva G.V. Chemical and pharmaceutical industry of the USSR and some foreign countries. Chemical science and industry, 1956, 1, 4, 461.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES There are several groups of enterprises in the chemical and pharmaceutical industry. The leading ones are factories for the production of synthetic drugs, factories for the production of antibiotics and enterprises for the production of drugs and finished dosage forms. The industrial production of synthetic drugs is based on the widespread use of organic synthesis, which brings these enterprises closer to the basic chemistry industry.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES Antibiotic enterprises are included in a special group. This is due to the fact that the basis of the technological process for obtaining these drugs is biological synthesis. A characteristic feature of factories for the production of herbal pharmaceutical and finished dosage forms is the production of a large number of various medicines in the form of liquid extracts and tinctures, injection solutions in ampoules, tablets, dragees, patches, etc.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES In the industrial production of chemical and pharmaceutical preparations, a variety of raw materials are widely used, obtained both from plant and animal products and by chemical synthesis. The most common is chemical raw materials. Mineral raw materials are used for the production of inorganic salts, and also as ingredients for various synthesis of organic compounds. A large number of mineral acids and alkalis are used. The initial organic raw materials are supplied by the coke-chemical, petrochemical, aniline dye industries and basic organic synthesis enterprises.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES Animal raw materials are also widely used in the production of medicinal products, in particular, histidine is obtained from animal blood, adrenaline - from the adrenal glands, insulin - from the pancreas, thyroidin - from the thyroid gland, etc.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES All types of technological operations in the production of medicinal products can be divided into Preparatory operations - storage, movement of solid, liquid and gaseous materials, their transformation: grinding and crushing of solid raw materials, separation of solids, removal of liquids and gases from them using methods of sedimentation, filtration, centrifugation, crystallization cooling, vacuum, etc. The actual processes of obtaining medicines are metabolic, thermal, electrochemical, biological processes, electrolysis, etc. At this stage of the technological process, the reactions of sulfation, nitration and halogenation, amination and oxidation reduction and oxidation, etc. The final stage - drugs are dried, crushed, tableted, ampuled, packaged and packaged. Additional operations
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS A significant part of the initial raw materials for the production of herbal and synthetic drugs is in a solid state and is subjected to crushing and grinding. The need for this operation often arises when obtaining dosage forms (tablets, dragees, etc.). Crushing is carried out using jaw, roller, cone, hammer and other crushers. Grinding is carried out using ball and porcelain mills and disintegrators. Small quantities of the medicinal product are crushed in mechanically driven mortars, Islamgulov, Excelsior mills, etc.
HYGIENIC CHARACTERISTICS OF BASIC TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS Occupational hazards during crushing, grinding and separation of initial drug products are dust, intense noise and general vibration. Dust is emitted at the point of entry of medicinal raw materials or finished product into crushers and mills and at the point of exit of the crushed substance. A hygienically unfavorable operation is the separation of materials into fractions. The air separators and mechanical sieves used in this process are significant sources of dust emissions. In the production of small-scale medicinal products (for example, hormonal drugs), manual rubbing on sieves is often used, which is associated with the release of dust and contamination of the skin and work clothes of workers.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS To combat dust emission, it is necessary to: § correct organization of the technological process and equipment, § covering places of dust emission with aspiration of dust-laden air.
HYGIENIC CHARACTERISTICS OF BASIC TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS Since noise and vibration in crushing and grinding plants may exceed permissible values, this equipment must be located in separate production rooms, and the foundations under them should not be connected to the building structures. In the fight against noise and vibration, it is necessary to use anti-noise and vibration-damping devices and materials. It is advisable to control the grinding and crushing processes remotely.
HYGIENIC CHARACTERISTICS OF BASIC TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS Transportation of starting components has a significant impact on the level of air pollution in the working area with harmful substances at the preparatory stage. This is due to the heavy load on communication structures, the presence of mechanisms and devices intended for moving substances that do not have effective exhaust devices and the necessary tightness. During transportation, workers may come into contact not only with vapors and gases, but also with liquid and bulk harmful substances. In some cases, manual transportation, loading and unloading of medicinal raw materials (for example, of plant origin) are still used.
HYGIENIC CHARACTERISTICS OF BASIC TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS Liquid substances are moved through pipelines using pumps, air or steam pressure, gravity and vacuum. Gaseous substances are transported using compression and vacuum. Supplying raw products with compressed air is associated with an increase in pressure in communication networks, which can lead to the release of harmful vapors and gases through leaks in pipelines, apparatus and containers.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS It should be noted that the transportation of liquid products using pumps, which is an additional factor contributing to air pollution with chemicals, is hygienically imperfect. From this point of view, transportation of liquid products by gravity or using vacuum is most favorable. The main hygienic requirements for equipment are the resistance of pipelines, gaskets and packing materials to the action of liquids, the replacement of gland pumps with sealless and submersible ones.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES PREPARATORY OPERATIONS The supply of solid medicinal raw materials (products of plant origin, organic and mineral substances) from raw material warehouses to preparatory workshops, from one equipment to another is carried out using belt conveyors, elevators, augers, as well as pneumatic and hydraulic systems. The method of transportation is determined by the aggregate state of the substances, their toxicity, the nature of production, etc. Transportation using belt conveyors, augers, etc. is associated with significant dust emissions. The most hygienic solution is to supply dry raw materials using pneumatic transport.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. This technological stage of drug production is characterized by a wide variety of technological processes and operations, equipment and chemicals used. A significant share in the industrial synthesis of intermediates and medicinal substances is occupied by processes associated with the reactions of substitution of hydrogen atoms in the nucleus of aromatic compounds by one or another group of atoms, transformation of substituents already existing in the molecule of an organic compound into others in order to give it new properties and, finally, change carbon structure of the molecule. These are reactions of nitration, sulfonation, halogenation, reduction, alkylation, etc. These processes are carried out in reactors of various types, which got their name depending on the chemical reactions carried out in them (chlorinator, nitrator, sulfator, etc.).
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Reactors can operate under conditions of high and normal atmospheric pressure or under vacuum. They can be periodic or continuous. These are steel, lead or cast iron containers with or without stirrers, heated or cooled. Depending on the processes occurring in the reactors, various types of mixers are used: blade, screw, frame, anchor, etc.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. The main harmful factor in the reactor compartment is chemical. Places where toxic substances are released from reactors can be stirrer seals, hatches through which products are loaded and unloaded, measuring glasses, inspection windows, and flange connections. At the same time, the composition and level of harmful substances in the air of the working area depend on the perfection of the equipment used, the type of medicinal intermediate or finished drug obtained, operating mode and other factors. Unfavorable hygienic conditions can be caused by manual operations, for example, when measuring the level of liquids, taking samples.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. The release of harmful substances into the air of working areas is significantly reduced by switching equipment to a vacuum process, using closed reactors with shielded stirrer motors, and using automatic control.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. The processes of separation of chemical components occupy a large share at this stage. The main equipment for carrying out such operations is a distillation apparatus and distillation units. Maintenance of this equipment is associated with the possibility of contact of workers with harmful substances that can enter the air through communication systems, hatches, taps, sampling points, etc.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Filtration and centrifugation processes are widely used to separate suspensions into solid and liquid phases. Filtration is carried out using periodic and continuous filters. The former include nutsch filters, filter presses, sheet filters, and the latter include drum, disk and belt filters. The operation of nutsch filters and filter presses is often accompanied by the release of toxic substances into the air of the working area, is associated with the use of manual labor, and the possibility of intense contamination of the skin and work clothes. From a hygienic point of view, drum filters that are sealed and equipped with exhaust ventilation are more favorable.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. For rapid separation of medicinal intermediates, batch and continuous centrifuges are used. Batch centrifuges are less advanced and have a number of disadvantages, the main ones being the inconvenience of removing the pressed material, the use of manual labor, and the lack of reliable tightness. These shortcomings cause the release of harmful substances into the air of the working area and contamination of the skin.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Mechanized and closed filters, self-unloading centrifuges with bottom discharge, drum vacuum filters, and automatic filter presses are hygienically reliable.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. A significant part of semi-products and finished medicines is dried. This process is necessary when obtaining herbal, synthetic drugs, antibiotics, vitamins, etc. Moisture is removed by mechanical (filtration, pressing, centrifugation), physicochemical (absorption by hygroscopic materials), thermal (evaporation, evaporation and condensation) methods. In the production of medicines, chamber, drum, spray, shaft and other dryers are most widely used.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Servicing most dryers is accompanied by increased heat generation directly at the workplace and the release of toxic substances. A significant disadvantage of dryers is the insufficient mechanization and sealing of the processes of loading and unloading substances undergoing drying, which causes air pollution in the working area with dust from the finished product. Significantly less harmful substances are released when using continuous dryers (rakes, sprayers, drying drums, etc.), provided with complete sealing and mechanization of loading and unloading processes.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Evaporation and crystallization processes have become widespread in the production of medicinal products. The former are used to obtain more concentrated solutions from less concentrated ones (synthetic and herbal preparations, antibiotics, vitamins, etc.). For this purpose, in most cases, multi-effect evaporators are used. Unfavorable hygienic operations when working with them are the supply of solutions and unloading of the finished product, since they are accompanied by the release of harmful compounds into the air of the working area.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. Crystallization processes are used to purify medicinal substances from impurities or isolate them from liquids. These processes are carried out in open and closed crystallizers. The main disadvantage of this equipment is the insufficient sealing and mechanization of the loading and unloading processes of medicinal substances. More favorable sanitary conditions in the workplace are created when servicing vacuum crystallizers.
HYGIENIC CHARACTERISTICS OF THE MAIN TECHNOLOGICAL PROCESSES THE ACTIVE PROCESSES OF PRODUCING MEDICINAL SUBSTANCES. The production of finished dosage forms in the form of tablets, dragees, ampoules consists of many preparatory and basic processes and operations carried out in a certain sequence on the appropriate equipment
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES FINAL OPERATIONS At the final stage of the technological process, medicinal substances are labeled, packaged and packaged. Dosage forms are packaged in plastic, paper and glass containers. Most operations at this stage are mechanized. At the same time, manual operations at individual enterprises still constitute a significant part.
HYGIENIC CHARACTERISTICS OF MAIN TECHNOLOGICAL PROCESSES FINAL OPERATIONS The main unfavorable hygienic factor at this stage of the production of medicinal products is dust. Workers, as a rule, are exposed to complex dust, since several types of medicines can be filled and packaged simultaneously. Working with a semi-mechanized and especially manual method of packaging and packing tablets, ampoules, dragees, as well as sealing boxes and coins with strips of cellophane and a number of other operations are associated with a forced position of the body.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION Chemical factor. The main unfavorable factor in the working environment at enterprises of the chemical and pharmaceutical industry is pollution of the air of the working area, clothing and skin with harmful organic and inorganic substances.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION Dust. Air pollution of working premises by dust is observed mainly at the preparatory and final stages of obtaining medicinal substances. The main sources at the preparatory stage are the delivery of raw materials from warehouses to production shops, as well as operations associated with crushing, grinding, sifting, transportation, loading, etc. Thus, a significant amount of dust is observed at workplaces when grinding plant raw materials, crushing raw materials components of synthetic products. In this case, the dust level can be 3-5 times higher than permissible.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION Dust. The final stage of drug production includes the processes of tableting, panning, drying, grinding, sifting mixtures, packaging and packaging of finished drugs. Under these conditions, medicinal dust should be considered industrial and considered an industrial poison. The dust content in the air of the working area when working on vibrating sieves and especially during manual sifting can exceed the permissible values by 5 times or more. Thus, during manual packaging, the dust concentration in the breathing zone of workers can reach 100 mg/m3 or more.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION Dust. It is known that the nature of the effect of dust on the body and the degree of severity of biological changes are largely determined by its dispersion. The dust of some medications consists of 85-98% particles less than 5 microns in size (Table 1. 1). This facilitates the penetration of a large number of medicinal substances into the body through the respiratory tract and digestive organs (with saliva).
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION Microclimate. If the thermal insulation of the heated surfaces of devices and communication heating networks is insufficient, workers may be exposed to both the chemical factor and the microclimate. Increased air temperature occurs mainly in drying departments and in devices in which the reaction occurs with the release of heat or at high temperatures (crystallizers, solvents, hydrolyzers, etc.). Thus, in the warm season, the air temperature in these areas can reach 34-38 °C with a relative humidity of 40-60%. Thus, the thermal microclimate at individual workplaces in the chemical and pharmaceutical industry is an additional factor that aggravates the effect of the chemical factor.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION NOISE. The source of industrial noise in workplaces during the manufacture of medicinal products are many technological devices. These include compressors, vacuum filters, drum dryers, centrifuges, crushers, vibrating screens, vacuum pumps, etc.
GENERAL CHARACTERISTICS OF INDUSTRIAL FACTORS DETERMINING WORKING CONDITIONS IN DRUG PRODUCTION NOISE. The noise level in some cases may exceed the permissible level. Thus, in workplaces, noise parameters may exceed the permissible values: for centrifuges by 5 dB, for a vacuum pump - by 5-6 dB, for a compressor - by 14-17 dB. The most unfavorable areas are engine rooms, where the total level of high-frequency noise often exceeds the permissible values by 20-25 dB. It should be noted that industrial noise, even at the permissible level, can aggravate the adverse effects of chemicals.
MEASURES TO IMPROVE WORKING CONDITIONS IMPROVEMENT OF TECHNOLOGICAL PROCESSES IN THE PRODUCTION OF MEDICINAL SUBSTANCES AND EQUIPMENT § § § replacement of harmful substances in the formulation with less harmful ones, replacement of an open process with a closed one, transfer of the process from high pressure to low pressure, mechanization of the process, thermal insulation of units, etc. . § transition to sealed continuous technological processes with remote control and monitoring § automation
MEASURES TO IMPROVE WORKING CONDITIONS VENTILATION To ensure high ventilation efficiency, it is necessary to have the correct space-planning layout of premises, finishing the internal surfaces of fences that prevent the sorption of toxic substances, etc. To remove harmful substances directly from the place of their formation, it is advisable to install local ventilation in accordance with features of the operating equipment and the nature of the operations performed.
MEASURES TO IMPROVE WORKING CONDITIONS VENTILATION An exhaust system in the form of an umbrella with a soft movable sleeve is installed above the hatches of reactors and other equipment, which are periodically opened. When taking samples, opening apparatus hatches, unloading components and other operations, significant release of harmful substances may occur, therefore PPE should be used when performing such operations.
MEASURES TO IMPROVE WORKING CONDITIONS NOISE Measures to combat noise üimprovement of technological equipment, ücorrect layout of production premises, üuse of noise-absorbing building materials (foam, felt, fiberboards, etc.). Also, timely preventive inspection and repair of equipment and systems that are a source of noise. In some cases, when it is impossible to reduce noise to acceptable levels, the use of personal protective equipment (antiphons) is recommended.
MEASURES TO IMPROVE WORKING CONDITIONS TREATMENT AND PREVENTIVE MEASURES üconducting preliminary and periodic medical examinations ücompliance with the established work and rest schedule, üorganization of a balanced diet, üsports.
TOPIC 13. HYGIENIC ASSESSMENT OF CHEMICAL AND BIOLOGICAL FACTORS OF THE PRODUCTION ENVIRONMENT, PRINCIPLES OF THEIR HYGIENIC STANDARDS. PREVENTION OF OCCUPATIONAL DISEASES CAUSED BY FACTORS OF CHEMICAL AND BIOLOGICAL NATURE
TOPIC 13. HYGIENIC ASSESSMENT OF CHEMICAL AND BIOLOGICAL FACTORS OF THE PRODUCTION ENVIRONMENT, PRINCIPLES OF THEIR HYGIENIC STANDARDS. PREVENTION OF OCCUPATIONAL DISEASES CAUSED BY FACTORS OF CHEMICAL AND BIOLOGICAL NATURE
Purpose of the work:study the main parameters characterizing the degree of toxicity and danger of chemicals in production conditions, master the methodological techniques of toxicological studies carried out during hygienic standardization of harmful substances, methods for assessing working conditions under the influence of production factors of a chemical and biological nature in the production of medicines, study the prevention of harmful the effects of these factors and corresponding health measures at enterprises of the chemical and pharmaceutical industry.
In preparation for the lesson, students must work through the following: theoretical issues.
1. Industrial hazards of a chemical nature, their pathogenic effects. Routes of entry of poisons and their removal from the body. Dependence of the toxic effect on the chemical structure, physicochemical properties, concentration and other factors. Local and general resorptive effect, acute and chronic intoxication. Allergic condition.
2. Industrial hazards of biological nature, their pathogenic effects.
3. Measures to combat chemical and biological factors in the working environment.
After mastering the topic the student must know:
Determination of the degree of toxicity and danger of chemicals;
be able to:
Use optimal and accessible methods for assessing the working conditions of workers under the influence of chemical factors in the working environment;
Use basic regulatory documents and reference information sources on creating favorable and healthy working conditions for pharmacy personnel under the influence of chemical and biological factors in the working environment.
Training material for completing the assignment
Hygienic assessment of chemical factors
Many types of professional activities related to the production and processing of raw materials, the manufacture and use of industrial products are carried out under conditions of exposure to industrial poisons.
Air pollution with toxic substances at chemical and pharmaceutical industry enterprises it is possible at almost all stages of the technological process for obtaining drugs (preparatory operations: transportation of liquid products or gaseous substances; separation of toxic substances from reactors, use of distillation apparatus and rectification devices, filtration and centrifugation processes, drying, evaporation and crystallization; final operations).
Industrial poisons - chemical substances that, as initial, intermediate, by-products or final products of the production process, enter the human body during his work activity and have a harmful effect on the worker, leading to impairment of his health or the health of his offspring.
The composition of toxic substances in the air of industrial premises at most chemical and pharmaceutical enterprises is complex. This is due to large differences in the production volume of medicines that are highly stable.
tyu, the simultaneous presence of many basic chemical ingredients included in the combination in the production of finished dosage forms, as well as auxiliary components (fillers, sweeteners, disintegrants, emulsifiers, etc.) mainly in the form of fine aerosols, vapors and gases. Based on their chemical structure, substances are classified into inorganic, organic and elemental organic.
The degree of toxicity of chemicals is determined by the level of doses or concentrations that cause the death of 50% of experimental animals through the main routes of penetration of substances into the body under production conditions: inhalation, percutaneous and oral (Table 55).
Table 55.Chemical toxicity classes
Toxic substances can have an effect on the body local irritant action at the point of contact with the skin and mucous membranes in the form of skin irritation, inflammation, burns (the biological effect develops before the poison is absorbed into the blood); general toxic action (acute, subacute, chronic poisoning); sensitizing action (industrial allergens); cause specific effects, including long-term (delayed): mutagenic, gonadotoxic, embryotropic, carcinogenic and others. Medicines, as a specific factor in air pollution in industrial premises, can have a direct effect on the generative function (hormones), cause the development of long-term effects, including an effect on the synthesis of DNA and RNA (cytostatics), and lead to mental and physical dependence (drugs).
Industrial poisons, depending on their properties and exposure conditions, can cause the development of acute, subacute and chronic intoxications. Acute poisoning occur with a short-term (7-8 hours) intake of relatively large quantities of chemicals into the body and have a short hidden (latent) period. This most often occurs at high concentrations in the air, erroneous ingestion, or severe contamination of the skin. The first signs of poisoning appear in the form of general weakness, headache, dizziness, nausea, vomiting, then specific changes may develop - pulmonary edema, damage to the organ of vision, paralysis of nerve centers, etc. Subacute poisoning often occur under the same conditions as acute ones, but develop much more slowly and have a protracted course. Chronic intoxication develop with constant long-term exposure to harmful substances in low concentrations and are characterized by a gradual increase in functional and organic disorders.
The thresholds for acute (Lim ac) and chronic (Lim cn) action of a chemical substance are considered to be the minimum dose or concentration, a single or long-term exposure to which causes statistically significant deviations from the norm in a number of functional or biochemical indicators of the body’s condition. The degree of danger of developing acute poisoning by industrial toxic substances is determined by the indicators: KVIO (inhalation poisoning coefficient) and Z ac (acute action zone); to assess the risk of developing chronic poisoning, Z ch (zone of chronic action) and (cumulation coefficient) are used. Kcum (the ratio of the total average lethal dose ΣDL50 received in an experiment with repeated administration of a substance to the same with a single administration) is an indicator of the cumulative nature of the substance. A distinction is made between material cumulation (accumulation of a substance in the body) and functional (gradual increase in the effect of exposure upon repeated intake of the substance into the body). The hazard rating is shown in table. 56.
The main routes of penetration of harmful substances into the body are the respiratory system and skin. The entry of toxic substances through the gastrointestinal tract in industrial conditions is rare and is usually associated with non-compliance with personal hygiene rules, partial ingestion of vapors and dust,
penetrating the respiratory tract, violating safety regulations.
When performing physical work or staying in conditions of high air temperature, high humidity, when the volume of breathing and blood flow speed increase sharply, the possibility of toxic substances entering the body and, as a consequence, poisoning can occur in a shorter period of time.
Table 56.Hazard classes for the development of acute and chronic poisoning by chemicals
The physicochemical properties that determine the toxicity and danger of chemically active substances in industrial conditions include: state of aggregation (solid, liquid, gas, vapor, aerosol), its dispersity, relative solubility in lipoids (equivalent to lipoids - octanol) and water ( P o/w = S octano (Appendix 1).
For chemicals that have a highly targeted effect (irritant, anti-enzyme, hemolytic, etc.) with short-term exposure, the leading regulation is the maximum permissible concentration MPCm, which can be measured for any 15-minute period of time during a work shift. During a shift, there should be no more than four short-term rises in concentrations not exceeding the MPC, with breaks between them of at least 1 hour; this should be checked by continuous automatic monitoring with an alarm for exceeding the MPC. For highly cumulative substances (hazard classes 1 and 2 based on the size of the zones of chronic and biological action), their biological effect is determined mainly by the amount of the substance that enters the body during the entire working day, and to assess their danger, average shift averages (over an 8-hour period) are used. - first work shift), maximum permissible concentrations (MPCss). Shift-average maximum permissible concentrations have been established for a number of metals (copper, mercury, lead and its inorganic compounds), as well as benzene, borophane
hydrofluoric acid, etc. In regulatory and methodological documents, the recording of standard values for a substance is as follows: MPC m / MPC ss. With the simultaneous presence in the air of the working area of harmful substances of unidirectional action with an additive effect, the sum of the ratios of the concentrations of each substance to its maximum permissible concentration should not exceed one, which corresponds to acceptable working conditions. The calculation is carried out according to the formula:
C1/MPC1 + C2/MPC2 + ...+ Cn/MPCn,<=1,
where: Q, WITH 2, S p- actual concentrations of substances in the air of the working area;
MPC1, MPC2, MPCn - MPC of the same substances in the air of the working area.
As a rule, combinations of substances with the same specific clinical manifestations have a summation effect: irritating substances (for example, acids and alkalis), allergens (for example, epichlorohydrin and formaldehyde), narcotic substances (a combination of alcohols).
When there is a potentiation effect (synergy) of a combination of harmful substances in the air of the working area, the sum of the ratios of the measured concentrations to their MPC should not exceed the coefficient established for these concentrations. When several substances of multidirectional action are simultaneously contained in the air of the working area, the hazard class of working conditions is established by the substance whose concentration corresponds to the highest class and degree of toxicity.
The frequency of monitoring the content of harmful substances in the air of the working area is established depending on the nature of the technological process, the hazard class and the characteristics of the biological action of chemicals in agreement with the sanitary and epidemiological service institutions.
Depending on the hazard class of harmful substances, the following frequency of monitoring its content in the air of the work area is recommended: for substances of the 1st hazard class - at least 1 time in 10 days, 2nd class - once a month, 3rd class - 1 time every 3 months, 4th grade - 1 time every 6 months.
Class of working conditions |
||||||
Harmful | Admission- | Harmful | Dangerous |
|||
substances | Timy | 3.1 | 3.2 | 3.3 | 3.4 |
|
Substances of hazard classes 1-2 | <=ПДК | 1,1-3,0 | 3,1-6,0 | 6,1-10,0 | 10,1-20,0 | |
Substances of 3-4 hazard classes | <=ПДК | 1,1-3,0 | 3,1-10,0 | |||
Substances acute actions | <=ПДК | 1,1-2,0 | 2,1-4,0 | 4,1-6,0 | 6,1-10,0 | |
Carcinogens | <=ПДК | 1,1-3,0 | 3,1-6,0 | 6,1-10,0 | ||
Allergens | <=ПДК | 1,1-3,0 | 3,1-10,0 | |||
The degree of harmfulness of working conditions is established taking into account the hazard class and concentrations of the substance in the air of the working area (Table 57). The concept of “hazard class” in this case includes both the toxicity class and the hazard classes of acute and chronic poisoning.
Contact with chemical and biological allergens during their production, packaging and use can lead to the development of allergic reactions. Allergens include antibiotics, sufanilamide drugs, many chlorinated hydrocarbons (dichlorethylene, dichloroethane, methylene chloride, carbon tetrachloride) and some solvents (benzene, aniline), metals (chromium, mercury, lead) and other compounds. Allergic properties usually increase with an increase in the number of active radicals and rings in the molecule, with lengthening of the side chains. Allergies are most often caused not by the substance itself, but by its complex with body proteins.
Workers in the chemical-pharmaceutical industry and pharmacy organizations with constant contact with antibiotics or producing fungi can develop occupational diseases in the form of dysbacteriosis, candidiasis of the skin and mucous membranes, and visceral candidiasis. With superficial candidiasis, yeast-like fungi of the genus Candida affect the mucous membranes
membranes, skin and nails; in the intestinal form, general weakness, weight loss, subfibril temperature, signs of enterocolitis, carbohydrate metabolism disorders, and immunodeficiency states are often noted.
Prolonged professional contact with various medicinal substances can lead to hypersensitivity, i.e. “allergic background” (90% of those working with antibiotics), which is accompanied by a more frequent manifestation of narrow professional sensitization to certain substances: to novocaine - in surgeons and a small number of therapists; for acrylates - from therapists and orthopedists; for penicillin - from therapists; for plaster - from orthopedists. Skin manifestations are highly polymorphic (dermatitis, eczema, urticaria, etc.). Changes in the internal organs are expressed in asthmatic bronchitis and bronchial asthma, chronic colitis, myocarditis, etc. Pathology of the nervous system is manifested by vegetative-vascular dystonia and sensory polyneuralgia. Immunity disorders are possible, which contributes to the development of dysbiosis and an increase in infectious morbidity.
Prevention of occupational poisoning: toxicological and hygienic assessment of chemical substances and their hygienic regulation taking into account biological activity; the degree of toxicity and danger of the main and auxiliary components used in the production of medicines; introduction of continuous technology that eliminates the release of toxic substances into the air of the working area; eliminating poison from production or using new technologies and streamlining the technological process aimed at replacing a highly toxic substance with a non-toxic one; automation and mechanization of production processes; use of remote control of mechanisms; use of pneumatic transport; installation of local mechanical exhaust ventilation in areas of probable toxic emissions in the form of fume hoods, side suction, umbrellas with an air velocity in them ranging from 0.25 to 1.5 m/s or general ventilation with a negative air balance; the use of automatically operating alarms for exceeding the established concentration levels of MPCs for hazardous aerosols, gases and vapors; use of personal protective equipment in the form of gas masks, respirators, overalls, safety glasses, pastes, ointments,
creams and other protective devices; organization of therapeutic nutrition; conducting preliminary and periodic (2 times a year) medical examinations; regulation (reduction) of the working day, use of additional leaves; planned and emergency current sanitary supervision of air pollution in the working area; Regular training of workers on safety precautions and industrial sanitation.
Hygienic assessment of biological factors
Industrial biological factors are biological objects, including micro- and microorganisms, products of their metabolism, as well as products of biological synthesis, which have the ability to have a harmful effect when exposed to the body of a worker.
The maximum permissible concentration of microorganisms is expressed in microbial cells per 1 m 3 (cells/m 3). The maximum permissible concentration of microorganisms-producers in the air of the working area is regulated at the level of 50,000 cells/m 3 [GN 2.2.6.709-98 “Maximum permissible concentrations (MPC) of microorganisms-producers, bacterial preparations and their components in the air of the working area”].
Exposure to producing microorganisms, bacterial preparations and their components at the MPC level does not exclude health problems in persons with hypersensitivity.
All microorganisms approved by the Ministry of Health of the Russian Federation as industrial strains are non-pathogenic or opportunistic and belong to the 3rd and 4th hazard classes according to GOST 12.1.007-76, which according to the WHO classification corresponds to the 2nd risk group (moderate) individual risk and limited risk for the general population). Classes of working conditions when working with substances of a biological nature are established, as for chemical substances, depending on whether they exceed (and by how many times) the maximum permissible concentrations of their content in the air of the working area (Table 58).
The production of the chemical and pharmaceutical industry is characterized by multicomponent air pollution, where dozens of chemical compounds are found in the air of the working area (chemical factor), microbial sensitization of the body of workers takes place (biological factor), and there are unfavorable physical factors (noise, vibration, ultrasound, microclimatic conditions), psychophysiological factors (monotony of the production process, tension of the visual analyzer, etc.).
In cases of illness directly related to production, we are talking about occupational diseases: for example, pneumoconiosis caused by sclerogenous dust, silicosis, which is accompanied by pulmonary tuberculosis.
At present, a final definition of the concept of a biological factor has not yet been formulated. However, based on the available materials, we can say that under biological A factor is understood as a set of biological objects, the impact of which on humans or the environment is associated with their ability to reproduce in natural or artificial conditions or produce biologically active substances. The main components of the biological factor that have a direct or indirect effect on humans are:
micro- and macroorganisms, products of the metabolic activity of microorganisms and microbiological synthesis, as well as some organic substances of natural origin. The existence of life on Earth is inextricably linked with the diverse world of microorganisms, but only a few decades ago their widespread, targeted use began tion.
The 40s of the 20th century are characterized by the rapid development of the production of a number of valuable products based on microbiological synthesis, i.e., the use of the ability of microorganisms to synthesize new structural elements (substances) or to excessive accumulation of metabolic products due to - enzyme systems existing in microbial cells. Such production includes the production of antibiotics, amino acids, proteins, enzymes, etc.
By now, biologically active substances (antibiotics, enzymes, vitamins, BVK, feed yeast) have acquired social significance.
A bacteriological study of the microflora of the mucous membrane of the oral cavity, pharynx, and nose in workers revealed a violation of the microbial biocenosis, which, as clinical studies have shown, contributes to the development of subatrophic rhinitis, hyperplastic and catarrhal processes of the mucous membranes of the upper respiratory tract.
The professional nature of these changes is confirmed by the presence of a dependence of pathological changes in the mucous membranes of the respiratory tract on professions; The largest number of cases of disease is observed among workers engaged in those operations where the greatest contact with antibiotics occurs.
A decrease in the body's antimicrobial resistance (bactericidal skin, phagocytic activity of neutrophils), i.e., the influence of antibiotics on natural immunity factors, was also revealed.
Data on the specific effect of antibiotics on the normal intestinal microflora, as well as their impact on natural immunity factors and the development of allergic diseases, were taken as the basis for the specific effect when rationing antibiotics in the air of the work area. Thus, along with tests for general toxicity, studies are carried out to:
Identification of sensitizing properties;
Determination of the danger of developing sensitization when an allergen enters through the skin and respiratory organs, as well as bacteriological studies of feces to determine the degree of change in the normal intestinal microflora.
At present, a final definition of the concept of a biological factor has not yet been formulated. However, based on the available materials, it can be said that a biological factor is understood as a set of biological objects, the impact of which on humans or the environment is associated with their ability to reproduce in natural or artificial conditions or to produce biologically active substances. The main components of the biological factor that have a direct or indirect effect on humans are:
micro- and macroorganisms, products of the metabolic activity of microorganisms and microbiological synthesis, as well as some organic substances of natural origin.
In the production of the chemical and pharmaceutical industry, the air environment is polluted by a complex of various chemical substances. Their number is especially large in those synthesis processes in which the final product is obtained from a large number of different raw materials, additives, and catalysts.
Example of impact chemical factors on the human body are diseases caused by beryllium, phosphorus, chromium, arsenic, mercury, lead, manganese, carbon disulfide or their toxic compounds, halogen-containing fatty hydrocarbons (dichloroethane, etc.), benzene and its toxic compounds, toxic nitro- and amido- groups, nitrogen oxides, fluorine-containing compounds, etc. Primary skin cancer is caused by tar, tar, mineral oils, or their compounds.
Chemically hazardous and harmful production factors, according to the nature of their impact on the human body, are divided into: general toxic, irritating, sensitizing, carcinogenic, mutagenic (see lecture No. 4).
TO physically Dangerous and harmful production factors include: production microclimate conditions that do not meet hygienic requirements (see lecture No. 2), increased levels of noise and vibration, non-ionizing electromagnetic fields and radiation, ionizing radiation, ultrasound, infrasound, dust and aerosols of fibrogenic action.
Psychological Harmful production factors, according to the nature of their impact on the human body, are divided into: physical overload (static and dynamic), affecting the musculoskeletal system, cardiovascular, respiratory systems and neuropsychological (mental overstrain, monotony of work, stereotypical movements, overstrain of analyzers , emotional, sensory loads), causing overstrain of the functional systems of the body, fatigue and overwork, which leads to a decrease in human performance.
Introduction
The chemical and pharmaceutical industry in the modern world is one of the most important and highly profitable industries. Enterprises in this industry produce not only medicines, but also various physiological solutions, vitamins and mineral supplements. Every year, the inhabitants of the planet consume a huge amount of different drugs and medicines.
A modern pharmaceutical company produces various drugs not only from chemical compounds, but also produces them through biological synthesis. The constant development of industry leads to the annual emergence of new medicinal compounds that are introduced into industrial production.
During any production, various violations may occur in the technology or in the devices themselves. Violation of one of the parameters of the drug production environment can lead to severe occupational illnesses for an employee and, at the same time, harm those who will use them for treatment.
A special feature of the chemical and pharmaceutical industry is that its products are often very compact and produced in small batches. The production chains of various compounds have a large number of operations and require many different types of raw materials. The rapid change in the range of drugs produced has a significant impact on working conditions.
In this regard, the issue of ensuring the safety of pharmaceutical workers in the process of activity is one of the most important.
Dangerous and harmful factors in the workplace of pharmaceutical workers
safety pharmaceutical worker professional
In the industrial production of chemical and pharmaceutical preparations, a variety of raw materials are widely used, obtained both from plant and animal products and by chemical synthesis.
The main harmful factors are:
1. Chemical factor. As studies show, the main unfavorable factor in the working environment at chemical and pharmaceutical industry enterprises is pollution of the air of the working area, clothing and skin with harmful organic and inorganic substances.
Air pollution with toxic substances is possible at all stages of the technological process. The main reasons for the content of harmful substances in the air are imperfect equipment, violation of operating procedures, lack of mechanization of operations, and the use of leaking equipment. The composition of air pollutants in the working area at most drug production enterprises is complex. A.M. Bolshakov, I.M. Novikova. General hygiene. Educational literature for students of pharmaceutical universities and pharmaceutical faculties of medical universities. Moscow. "Medicine" 2002.
The nature of the technological process and, above all, its intermittency play a significant role in air pollution in industrial premises. The implementation of processes according to a periodic scheme is associated with repeated loading and unloading of liquids or bulk materials, and the use of various methods of transporting the processed material.
The level of air pollution with vapors and gases of harmful substances is greatly influenced by the pressure in devices and communication networks.
In such processes, the tightness of the equipment is achieved by using flanged connections of pipes and devices of a special design using fluoroplastic, asbestos-lead and other gasket materials.
The highest levels of contamination with chemicals are observed when the integrity of the process equipment is broken, for example, at the stage of hydrolysis of phenylhydrazine sulfate in the production of amidopyrine, during selection through the open hatch of the apparatus, the concentration of sulfur dioxide can be 4 times higher than the maximum permissible concentration.
2. Dust. Air pollution of working premises by dust is observed mainly at the preparatory and final stages of obtaining medicinal substances. The main sources of dust emissions at the preparatory stage are the delivery of raw materials from warehouses to production shops, as well as operations associated with crushing, grinding, sifting, transportation, loading, etc. The dust content in the air of the working area can be 5 times or more higher than the permissible values .
3. Microclimate. At chemical and pharmaceutical industry enterprises, the microclimate of production premises must comply with the requirements established by SanPiN. However, studies show that if the thermal insulation of heated surfaces is insufficient, workers may be exposed to both the chemical factor and the microclimate.
4. Noise. The source of industrial noise in workplaces during the manufacture of medicinal products are many technological devices. The noise level in some cases may exceed the permissible level.
