Preventive Toxicology Research Articles

The effect of 2,6-dimethylpyridine N-oxide on cognitive functions and emotional state of rats following ins long-term oral administration

Background. Global anthropogenic environmental pollution, intensification of production, daily physical, emotional and psychogenic stress on humans, as well as the working environment provoke a variety of diseases, fatigue, and cognitive impairment, etc. This may be attributed to a reduced nonspecific resistance of the health system and the development of stressful conditions. Therefore, one of the focal points of preventive toxicology is the development of agents with adaptogenic properties that would prevent the occurrence of harmful effects under the influence of stressors. The aim of the present study was to examine the effect of 2,6-dimethylpyridine N-oxide on cognitive functions and emotional status of rats following its long-term oral administration. Materials and Methods. The plant growth regulator (PGR) Ivin (2,6-dimethylpyridine N-oxide, 99.9%) was chosen for the study. Adaptogen Eleutherococcus was used as a reference agent. The study was conducted on Wistar Hannover rats divided into 2 cohorts. Each cohort included the following groups: 1 – intact animals, 2 – control (distilled water), 3 and 4 – Ivin at doses of 13.0 and 0.013 mg/kg (1/100 and 1/100000 LD50), respectively, 5 – Eleutherococcus at a dose of 50 mg/kg. Exposure period – 28 days, oral route of administration. The state of the central nervous system was assessed by behavioural reactions in the Morris Water Maze and the Elevated Plus Maze. Results. Ivin at doses of 13 and 0.013 mg/kg increased the ability to learn and to form short- and long-term memory in rats, as evidenced by a decrease in the average time of platform location in the Morris Water Maze test. Ivin at a dose of 0.013 mg/kg significantly increased the number of rearings in closed arms of the Elevated Plus Maze, indicating its anxiolytic effect. The anti-anxiety effect of Ivin needs to be confirmed by additional studies in the Open Field and/or Hole-board tests. The effectiveness of Ivin in terms of the studied parameters was similar or exceeded those of the known adaptogen Eleutherococcus.

Hygienic assessment of occupational risk for workers during pre- and post-emergence herbicide treatments of sunflower crops

Modern agriculture extensively uses pesticide formulations at various stages of crop growth. Sunflower cultivation accounts for 31% of the global production. Assessing the occupational risk associated with pesticide application in sunflower farming is of paramount importance. Improper handling and application of pesticide formulations can have immediate adverse effects on workers, leading to acute poisoning, long-term health consequences, and the potential for chronic illnesses, including neurotoxic effects. The aim of this study was to conduct a hygienic assessment of the professional risk faced by workers during pre- and post-emergence herbicide applications in sunflower cultivation. This assessment was carried out to establish the regulations for their safe usage. Research samples after the application of the herbicides AGAT, GARPUN, KORVUS, and PARUS (patches from overalls, gloves, skin swabs from exposed areas (face-neck, hands), air samples (atmospheric air, working zone and drift zone). The assessment of professional risk was conducted in accordance with the methodological recommendations provided by experts from the L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise). Statistical analysis of the results was carried out using the licensed statistical software packages MedStat v.5.2 (Copyright© 2003-2019) and Microsoft® Excel® for Microsoft 365 MSO (Version 2305, Build 16.0.16501.20074). It has been determined that under real conditions, during pre- and post-emergence herbicide applications in sunflower cultivation using AGAT, GARPUN, KORVUS, PARUS preparations, while adhering to recommended agrotechnical and hygiene safety regulations, the inhalation, dermal, complex, and combined (AGAT and PARUS) risks for applicators are 0.0409±0.0179, 0.0429±0.0193, 0.0838±0.0224, and 0.1557±0.1322 a.u., respectively, and for tractor operators – 0.0818±0.0358, 0.0425±0.0192, 0.1243±0.0356, and 0.2347±0.1567 a.u., respectively. There is no observed increase in hygiene standards in the workplace atmosphere and in the air of the potential drift zone. It has been proven that the professional risk of their use does not exceed permissible limits (<1). It has been determined that during the performance of techno­logical operations, the mentioned risks in applicators and tractor operators did not differ significantly (p>0.05). However, a significant difference was found in the proportion of percutaneous risk (42.7±17.4% in applicators compared to 34.8±17.0% in tractor operators; p=0.034). The regulations for the safe use of the investigated pesticide formulations have been substantiated. Statistical analysis of the obtained results revealed that the values of inhalation, dermal, and combined risks during the application of these pesticides did not significantly differ during the various technological operations (applicators and tractor operators) (p>0.05). The values of the combined comprehensive risk associated with the use of the studied preparations also did not show significant differences (p>0.05). The proportion of dermal risk was significantly higher in applicators compared to this parameter determined in tractor operators (p=0.034).

Prediction of the biodegradation of chemicals using OECD QSAR Toolbox software

Introduction. The development of integrated approaches to testing, assessment of the hazard and exposure risk of chemicals on human health and the environment is one of the priorities of preventive toxicology. An integrated approach involves various combinations of methods in silico, in chemico, in vitro, ex vivo, in vivo for hazard assessment. In the Russian Federation, in silico methods are often perceived with skepticism, mainly due to the lack of their legal status, weak methodological base and insufficient training of specialists. In order to expand the methodological base, the possibility of predicting the stability of chemicals in biotic conditions using the OECD QSAR Toolbox software was studied.
 Material and methods. The OECD QSAR Toolbox software version 4.4.1., OECD guidelines on the assessment of biodegradation of chemicals.
 Results. The world community and the OECD have developed and implemented a three-level system for chemicals biodegradation testing, which includes tests for readily biodegradation (OECD Guidelines 301 A, 301 B, 301 C, 301 D, 301 E, 301 F, 306, 310), tests to determine the potential biodegradability (OECD Guidelines 302 A, 302 B, 302 C, 304 A) and model systems tests (OECD Guidelines 303 A, 303 B).
 To test the capabilities of the program, 24 endpoints were selected. They are the determination of biodegradability (%) by BOD, DOC, CO2, CH4 releases in OECD tests 301 A, 301 B, 301 C, 301 D, 
 302 C, 302 B, biodegradability (%) in sediments and soil, bioconcentration factors for more than 100 organic chemicals of various structures.
 The parameters were calculated using the analog method, followed by mandatory interpretation of the data obtained by an expert. When predicting the biodegradability of chemicals, it is necessary to perform a series of calculations using different tests (OECD tests 301 A, 301 B, 301 C, 301 D, 301 E, 302 B are preferred) and grouping methods followed by a comprehensive assessment of the results obtained, taking into account not only the structural similarity of substances and analogues, but also the quality of the experimental data used. When predicting biodegradability by BOD values, it is advisable to use the OECD 301 C test. The proportion of tested substances whose biodegradability could be estimated by BOD values is about 50% in the OECD 301 C test, which is primarily due to the presence of a significant amount of experimental data. The calculation of bioconcentration factors seems to be promising. For about 45% of the tested substances, it was possible to calculate bioconcentration coefficients with good correlation with experimental data. Biodegradation in soil (% and half-life) can be predicted only for a very limited range of compounds (10% of the tested substances), which is due to the difficulty of selecting structurally similar analogues with experimental data. The method is not applicable for predicting the biodegradation of salts, organometallic compounds, polymer molecules and mixed products.
 Conclusion. The Russian Register of Potentially Hazardous Chemical and Biological Substances has developed a methodological guide for predicting the stability of chemicals in biotic conditions using the OECD QSAR Toolbox software. The document presents algorithms for calculating biodegradability (%) according to OECD tests 301, 302, 303; BOD, bioconcentration factors and biodegradability (%) in soil.

Оцінка небезпечності, комплексне гігієнічне нормування сульфоксафлору в сільськогосподарській продовольчій сировині, об’єктах виробничого і навколишнього середовища та обґрунтування регламентів безпечного застосування інсектициду на його основі

ABSTRACT. Sulfoxaflor is recommended for use as an insecticide on wheat, barley, rapeseed, sugar beet, apple and cabbage. In the State Enterprise “L.I. Medved’s Research Center for Preventive Toxicology, Food and Chemical Safety, The Ministry of Health of Ukraine” a study was conducted on the toxicological and hygienic assessment of sulfoxaflor and the insecticide Transform, WG based on it; PDD of sulfoxaflor for humans, hygienic standards of the substance and regulations for safe use of the drug are substantiated. Aim. Toxicological and hygienic assessment of sulfoxaflor and its insecticide, assessment of the risk of exposure to agricultural workers and the population. Methods. Expert-analytical, toxicological, physico-chemical, hygienic. Results. According to the parameters of toxicity, sulfoxaflor and the drug Transform, WG belong to pesticides of the 2nd class of danger according to the limiting criterion of harmfulness – the reproductive toxicity of sulfoxaflor. It has a polytropic effect on the body with predominant damage to the liver and reproductive organs. Mutagenic, carcinogenic and teratogenic activity and embryotoxicity of sulfoxaflor are not limiting when assessing its danger. As a result of field studies, it was established that residual amounts of sulfoxaflor were not detected in the grain of the wheat and barley crops, the seeds of the rape crop and its oil, the roots of the sugar beet crop, the apple crop and their juice, cabbage at the limit level of detection methods. The degree of possible professional risk of exposure to flupyradifurone in case of entering the body of agricultural workers by inhalation and dermal routes does not exceed the permissible level. Conclusions. The use of the insecticide Transform, WG based on sulfoxaflor in the agriculture of Ukraine on wheat, barley, rapeseeds, sugar beetroots, apples and cabbage in compliance with hygienic standards and regulations is not dangerous talking about the sulfoxaflor contamination possibility of agricultural crops and environmental objects. Keywords: insecticide, sulfoxaflor, toxicological properties, hygienic standards and regulations, hazard assessment.

Стан прооксидантної та антиоксидантної систем організму щурів за умов однократної дії деяких метильних похідних N-оксид піридину – Івіну і Потейтіну

АBSTRACT. Previously, it was shown that pyridine N-oxide based plant growth regulators (PGR) Ivin and Poteitin when combined with pesticides reduce the acute and subchronic toxicity of pesticides for mammals, have a hepatoprotective effect, contribute to the reduction of mutagenic activity, in particular, of Cyclophosphane and Dioxidin cytostatics (Vasetska O.P., 2017, Vasetska O.P. et al., 2020, 2021). It is possible that a wide range of their biological effects may be associated with the activation of the body’s protective systems, in particular the antioxidant system. The effect of these PGRs on the state of the pro-oxidant and antioxidant systems is not sufficiently clarified. Therefore, an important issue for preventive toxicology is the study of the nature of the effect of PGR on the state of the body’s pro-oxidant and antioxidant systems, which will contribute to the development of preventive measures to preclude acute and chronic intoxications with pesticides. Aim. To find out the state of the body’s pro-oxidant and antioxidant systems under a single oral exposure to some plant growth regulators –pyridine N-oxide methyl derivatives. Materials and Methods. For the aim of this research we used PGR 2.6-dimethyl- pyridine N-oxide (Ivin) and a complex of 2.6- dimethylpyridine-N-oxide with succinic acid (Poteitin). PGR in the form of an aqueous solution was administered to male Wistar Han rats orally with a probe: Ivin at doses of 650 mg/kg (1/2 LD50) and 13 mg/kg (1/100 LD50), Poteitin – at doses of 1150 mg/kg (1/2 LD50) and 23 mg/kg (1/100 LD50). The influence of Ivin and Poteitin on the lipid peroxidation (LPO) and the antioxidant system under a single oral exposure to the body of male rats was determined on days 1, 3, and 7. LPO in liver tissues was determined by the content of malondialdehyde (MDA), diene conjugates (DC), ketodienes (KD), conjugated trienes (CT) and Schiff bases (SB). MDA level was determined by the reaction with 2-thiobarbituric acid, DC, KD, CT, and SB in liver tissues – by the extraction-spectrophotometric method. The antioxidant status of the body was assessed by the activity of the catalase enzymes (CAT), glutathione peroxidase (GP), glutathione reductase (GR), the content of reduced glutathione (GSH) and total antioxidant activity (AOA). The results of the research were estimated by standard methods of variational statistics according to Student’s t-test criterion. Results. It was established that Ivin in the researched doses in the heptane fraction reduces the LPO intensity (containing MDA, DC, SB) in the liver tissues of rats, in the isopropanol fraction – DC; increases the activity of catalase and total AOA in blood serum. Poteitin in the tested doses in the heptane fraction reduces the formation of lipid products (containing MDA, DC, KD and CT) in the liver tissues of rats, in the isopropanol fraction – DC; increases the activity of catalase and the content of GSH, total AOA. Both substances do not disrupt the glutathione system. Compared to Ivin, Poteitin has a more pronounced effect on the intensity of LPO and the activity of the antioxidant system. Conclusions. 1. Plant growth regulators Ivin and Poteitin, at a single exposure to the body of male rats in doses corresponding to 1/2 and 1/100 LD50, reduce pro-oxidant activity, do not disrupt the glutathione system, increase the activity of the antioxidant system. 2. Increase in the activity of the antioxidant system and inhibition of the intensity of lipid peroxidation processes both under the influence of Ivin and Poteitin are aimed at adapting the body to the chemical factor. 3. Activation of the antioxidant system together with a decrease in the intensity of LPO can be one of the mechanisms of protection of the body from the toxic effects of pesticides when they are simultaneously introduced into the body with plant growth regulators based on methyl derivatives of pyridine N-oxide. Key words: plant growth regulators, Ivin, Poteitin, prooxidant and antioxidant systems.

Якість повітря житлових приміщень як важлива детермінанта здоров’я та пріоритетне завдання у галузі гігієни середовища життєдіяльності людини

According to WHO definition, indoor air quality is an important determinant of human health. Emissions from building materials, furniture, and consumer goods, combustion processes, and infiltration of polluted atmospheric air are considered the main sources of hazardous chemicals and solid pollutants in indoor air. Aim. To conduct an analysis of the results of comprehensive sanitary and hygienic studies of air quality in residential buildings and apartments in order to determine priority chemical pollutants and products of their transformation; justify the need to improve the air quality monitoring system of residential premises taking into account modern WHO recommendations. Materials and Methods. The study of air samples of residential premises was carried out on the basis of the L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety of the Ministry of Health of Ukraine (2000-2015) and Kyiv Center for Disease Control and Prevention of the Ministry of Health of Ukraine (2015-2019). A comprehensive toxicological and hygienic assessment of the air in residential premises was carried out based on the appeals of citizens who complained about the unpleasant smell of the air. A total of 123 residential objects (856 samples) were investigated. Applied methods of systematic and comparative analysis, cross-sectional survey method (survey of residents of residential buildings and apartments), sanitary and hygienic methods; sanitary and chemical methods (29 methods according to the institution's accreditation). Statistical data processing was performed using the IBM SPSS Statistics 29.0.0.0 program (Spearman correlation analysis), with p≤0.05. Results. A high level of chemical air pollution in residential premises, carried out based on citizen complaints, was established. Various external and internal sources of chemical air pollution were determined, in particular by marker pollutants: formaldehyde, phenol, and acetone. It has been established that the cause of their emission into the air is household items (furniture), various construction and finishing materials (polymers), which are used mainly during repair work or in new buildings. A direct positive connection was found between the level of exceeding the maximum permissible limit of marker chemical pollutants and the well-being and health of residents of settlements. Symptoms such as fatigue, cough, diseases of the upper respiratory tract, headaches and dizziness, allergic conditions were most often observed, which determines the urgency of improving the preventive work of primary care doctors ‒ family medicine in the direction of detecting pre-pathological conditions among healthy individuals and especially sensitive contingents (children, teenagers, pregnant women) living in the conditions of a "sick building". Conclusions. The unsatisfactory state of air inside residential premises determines the need to improve the existing system of monitoring the quality of air inside residential premises, in particular, improving methods of sampling and analysis of priority chemical indoor air pollutants to assess the risk of their combined action. Keywords: indoor air, "sick building syndrome", phenol, formaldehyde.

Рецензія на монографію «досвід військових формувань у ліквідації наслідків аварії на чорнобильській атомній електростанції через призму сучасних радіаційних загроз (до 35 роковин аварії на чорнобильській атомній електростанції)»

The Monograph is the result of scientific and practical cooperation of the Ministry of Defense of Ukraine, the General Staff of the Armed Forces of Ukraine, the Command of the Medical Forces, the Ukrainian Military Medical Academy, the SE “L.I. Medveds Research Center of Preventive Toxicology, Food and Chemical Safety of the Ministry of Health of Ukraine”, State University “Na-tional Scientific Center of Radiation Medicine of the National Academy of Sci-ences of Ukraine” in the field of radioprotection, namely - prevention and elimi-nation of radiation exposure, organization of radiation, chemical and biological protection of forces during elimination of the consequences of a radiation acci-dent. The main goal of the Monograph is the analysis of the practical aspects of the cooperation of servicemen of the Armed Forces, representatives of power minis-tries and agencies, and the health care system on the elimination of the conse-quences of the accident at the Chernobyl nuclear power plant. The authors note that the experience gained was the basis for the development of scientific recom-mendations for improving radioprotection, taking into account the radiation ef-fect on human health and the environment. Special attention is paid in the Monograph to the study of the key principles of prevention and elimination of radiation exposure, the peculiarities of the or-ganization of radiation, chemical and biological protection of forces during the elimination of the consequences of a radiation accident. Undoubtedly, the Monograph is a useful source of information for doctors of various specialties, scientific specialists, students of the Ukrainian Military Medi-cal Academy, students of higher medical schools and educational institutions of postgraduate education, and military specialists in the organization of radiation, chemical and biological protection of forces.

Профілактична токсикологія, радіологія та медичний захист – напрямок удосконалення для спеціальності «222 медицина», сфери знань «22 охорона здоров’я»

RESUME. In the conditions of war, the role of military toxicology, radiology and medical protection, one of the scientific and practical branches that provides individual components of national security in Ukraine. Aim. Analysis of the training system for specialty "222 Medicine", field of knowledge "22 Health Care" in the field of “Preventive toxicology, radiology and medical protection” and the search for directions for its improvement in Ukraine. Materials and Methods. Considered national regulatory documents in the field of professional-qualification and educational-qualification training, for "222 Medicine", the field of knowledge "22 Health Care" in the field of preventive toxicology, radiology and medical protection. Applied methods of scientific research: analytical, comparative and content analysis, system and information approach. Results. The need to make changes to the "Handbook of qualification characteristics of employees' professions" is substantiated. Issue 78. Health Care" and to the "List of specialties and duration of internship training"; proposals for the creation of the profession "Physician toxicologist-radiologist for medical protection" in the specialty "Preventive toxicology, radiology and medical protection" are provided. The authors developed requirements for the level of qualification, scope of knowledge and skills for specialists in military toxicology, radiology and medical protection. The proposed educational and methodological approaches, which provide for various types and stages of training for system of secondary and higher education, incl. military medical education, and the system of Continuous Professional Development. Conclusions. The existing system of training personnel of medical units, parts of the Armed Forces of Ukraine and institutions of the Ministry of Health of Ukraine, involved in the provision of medical care under the conditions of CBRN threats, needs improvement, which is possible by creating a normative field for implementation in Health Care practice of Ukraine the new profession - "Physician toxicologist-radiologist for medical protection" in the specialty "Preventive toxicology, radiology and medical protection". Key Words: military medicine, personnel training, military toxicology, military radiology, medical protection.

Функціональний стан печінки за одноразового перорального впливу на організм деяких метильних похідних n-оксид піридину

RESUME. Pesticides occupy one of the priority places among environmental pollutants. The hepatobiliary system disorder is a characteristic of most pesticides. The hepatotoxic effect of synthetic plant growth regulators (PGRs) based on pyridine N-oxide isn’t explored enough. The hepatotoxic effect PGR nature finding is an important aspect of preventive toxicology. Aim. To study the effect of some pyridine-N-oxide methyl derivatives on the liver functional state under a single oral dosage into the body. Materials and Methods. For the research were used PGRs – 2.6-dimethylpyridine-N-oxide (Ivin), 99.9 % and complex 2.6- dimethylpyridine-N-oxide with succinic acid (Poteitin), 99.9 %. During the experiment which was carried out on male Wistar Han rats, it was a single oral administration of aqueous solution form of test substances: Ivin in doses of 650 and 13 mg/kg and Poteitin in doses 1150 and 23 mg/kg. The activity of the alanineaminotransferase (ALT), aspartateaminotransferase (AST), alkaline phosphatase (ALP), the content of total proteins, glucose, triglycerides, cholesterol, urea and creatinine in the blood serum were determined on the 1st, 3rd, and 7th day using “Filisit- Diagnostics” reagent kit. EPR signals (g-2.25; g-2.14; g-2.05; g-2.03; g-2.00; g-1.97; g-1.94) were determined in liver tissue on the radio spectrophotometer “Varian E-109” (USA) at a temperature of 77 K. The results. Ivin at a dose of 13 mg/kg in particular study periods significantly increased the content of urea and glucose. At a dose of 650 mg/kg, the activity of AST, the content of urea, creatinine, and glucose significantly increased, and the activity of ALP decreased. Poteitin in a dose of 23 mg/kg in particular study times significantly increased the content of urea and creatinine, and the activity of ALP in the blood serum. At a dose of 1150 mg/kg, a significant decrease in the activity of ALP, and an increase in the content of urea, creatinine and glucose in the blood serum were revealed. The majority of liver EPR signals were reduced due to the influence of Ivin and Poteitin in both studied doses in different terms. Ivin at a dose of 13 mg/kg decreased the content of Mo7+-containing proteins and free radicals (FR) on 1st and 7th days respectively. At a dose of 650 mg/kg increased the content of iron-sulfur proteins (ISP) in 1stday of experiment and there was a decrease in the content of cytochrome P-450 (CytP-450), nitrosyl complexes, ISP and free radicals (FR) in 7 days. Poteitin at a dose of 23 mg/kg decreased the content of cyt-P-450, FR, ISP, and Mo7+–containing proteins, and increased the content of Cu2+-containing proteins. At a dose of 1150 mg/kg, there was a decrease in the content of cyt-P-450, BP, and ISP (for 1st and 3th days) and their increase for 7 days. Conclusions. With acute oral exposure, Ivin and Poteitin show a weak hepatotropic effect, characterized by a hyperglycemia, a slight decrease in the activity of alkaline phosphatase and an increase in urea and creatinine levels in the blood serum. Hyperglycemia can be associated with a stressogenic reaction to a chemical factor. This may indicate a carbohydrate metabolism disorders and various pathological conditions with long-term exposure to the studied substances. Intensification of the protein degradation and the accumulation of urea and creatinine in the blood serum can lead to a disorder of the filtering and excretory functions of the kidneys, which requires further research and clarification. Ivin and Poteitin reduce the EPR spectra of rat liver – cyt-P-450, free radicals, iron-sulfur proteins, nitrosyl complexes of non-heme iron, which indicates a decrease in the activity of the monooxygenase system, inhibition of oxidation processes, the formation disruption of iron-sulfur complexes and a decrease in the labile nitrosyl complex formation. A decrease in the content of Mo7+-containing proteins and an increase in the content of Cu2+-containing proteins may be associated with the activation of antiradical processes in the liver of rats. Key Words: plant growth regulators, Ivin, Poteitin, hepatotoxic effect, liver EPR spectra.

Будівельні композитні матеріали на основі деревини: оцінка безпеки в Україні та система технічного регулювання в ЄС

Abstract. Composite building materials based on wood (further ‒ wood plastics) remain a key object of sanitary and hygienic research as an important source of marker air pollutants in residential premises. Aim. Generalization of the results of sanitary and hygienic studies of wood plastics that are in circulation on the market of Ukraine; comparative analysis of individual provisions of the system of technical regulation of the specified products in the EU and Ukraine. Materials and Methods. Directives of EU countries in the field of technical regulation of chemically hazardous construction materials and sanitary legislation of Ukraine; data of sanitary-hygienic researches of the air of residential premises based on complaints of residents of the city of Kyiv, carried out by the "Kyiv City Center for Disease Control and Prevention of the Ministry of Health of Ukraine" (2010-2019); the results of chamber studies of samples (N=4859) of building products based on wood plastics and furniture, performed in the polymer hygiene laboratory of the State Enterprise "L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety of the Ministry of Health of Ukraine" (2010-2019). Statistical analysis ‒ Microsoft Excel 2019. Results. According to the research data of wood-plastic samples, a high level of their compliance with technical requirements and quality parameters and hygienic standards of Ukraine was established, so over the 10 years of research, the average deviations were: glued plywood, veneered panels, other laminated wood materials - 3.59% (n=1234); fiberboard boards made of wood or other wood materials with or without the addition of resins or other substances ‒ 1.36% (n=1512); chipboard boards, with oriented chips and similar boards (for example, wafer boards) ‒ 1.73% (n=1441); furniture samp-les – 1.6% (n=672). At the same time, an increase in the number of cases of exceeding the concentration of phenol and formaldehyde in relation to the MPC average daily in the air of residential premises of multi-apartment buildings during the same period was found: phenol by 2.86 times (R2=0.764), formaldehyde by 2.7 times (R2=0.529). The difference between wood-plastic samples sent for sanitary-hygienic research and those products that enter residential premises is not excluded, and cases of wood-plastic use in residential premises that are not intended are also found. Fundamental differences in the approaches of the EU and Ukraine to the assessment of the safety of composite building materials still remain unsettled. Difficulties in adapting the product safety regulatory system in the EU for introduction in Ukraine are due to the methodology of risk assessment for human health as a key tool for substantiating product and commodity safety standards. The main distinguishing feature of the EU legal framework on this issue is the recognition of product safety based on the absence of unacceptable risk, and the methodology that was implemented in the Soviet period (more than 30-40 years ago) is based on the principle of "zero risk". Conclusions. There is a need to harmonize the EU system of technical regulation and safety for construction products based on wood with the approaches that are in force in Ukraine, which will contribute to updating the national sanitary legislation, methodology, criteria, and methodical approaches to ensure the safety of a wide range of construction products for the population. An effective tool on this path can be the development and implementation of a targeted interdisciplinary state program. Key Words: wood plastics, risk assessment, technical regulation.

A Knowledge, Attitude and Practices Study on Clinical Toxicology among Internees and Registered Medical Practitioners at a Tertiary Care Hospital

The present KAP study aimed to ascertain the knowledge, attitudes, and practices on clinical toxicology amonginternees and medical doctors at ACSR Govt. Medical College & Hospital, Nellore, Andhra Pradesh, India, in thelight of implementing new National Medical Commission curriculum (Graduate Medical Regulations 2019). Thestudy also aimed at understanding the knowledge and training gaps pertaining to clinical toxicology in the targetpopulation and thereby propose interventions for proper delivery of toxicology curriculum.A semi structured questionnaire was used to elicit information wherein 120 health care providers voluntarilyparticipated in the study. The results detected significant deficits towards understanding concepts in clinicaltoxicology and implementation of evidence-based approach in providing care. Our study identified the need tostress on toxidrome based approach, use of evidence-based decontamination methods, the necessity to stabilise the patientmore than being enthusiastic in diagnosing the poisoning, increased use of multidose activated charcoal as a primary antidote,use of poison control centre helpline, material safety data sheet & toxicology databases when in doubt, employing holistic caremodels, providing education on social & preventive toxicology and role of screening in chronic paediatric poisonings.

The study of the long-term effects of industrial substances by toxicologists of the I.V. Sanotsky School

One of the areas of scientific research that deeply interested I.V. Sanotsky was the study of the long-term effects of the influence of chemical compounds on the body, which is one of the most urgent problems of modern toxicology. The study aims to analyze and evaluate the results of experimental studies of chemicals with long-term effects, on the basis of which a methodology for hygienic rationing of these substances in preventive toxicology. The researchers have conducted a literature search for the period 1975-2020 according to the data of the scientific electronic library elibrary.ru and the archive of the Izmerov Research Institute of Occupational Health by keywords: preventive toxicology, long-term effects, hygienic standardization. The results of experimental studies of chemicals with long-term effects allowed us to scientifically substantiate the basic principles of establishing MPC during hygienic rationing: - selection of an experimental model, issues of data transfer from animals to humans; - dependence of the studied effects on the dose or concentration of chemicals; - threshold of effects; - dependence of the effect on the time of exposure and observation; - selectivity of the effect of poisons on reproductive function; - sanitary standardization of the content of chemical compounds with a specific effect on reproductive function. As a result of the long-term work of the Department of Industrial Toxicology, specialists have developed methodological approaches, and also have created tested, modernized, unified guidelines for the system of institutions whose task was to obtain data for the toxicological assessment of new substances with long-term effects to determine harm thresholds.

Industrial toxicology as an important part of occupational medicine: retrospective, reality and development prospects (literature review)

Introduction. The stages of development of industrial toxicology and the contribution of the main scientific schools to the theory and practice of hygienic regulation of industrial substances in the air of the working area are considered, the main tasks for the near future are identified. Material and methods. The analysis of domestic literature, materials of scientific conferences and 25 years of experience in the section “Industrial toxicology” of the Commission “Scientific foundations of occupational health and occupational diseases” of the USSR Academy of Medical Sciences was carried out. Results. On the edge of the XX-XXI centuries, there was a significant reduction in industrial toxicology laboratories in specialized institutes, which led to a multiple decrease in the number of annual substantiation of maximum allowable concentration and indicative limit values for chemicals in the air of the working area, while maintaining a great need for this work. The lack of hygienic regulations for chemicals used in technological processes reduces the quality of a special assessment of the working conditions of workers. Against this background, due to the intensive development of the nanoindustry, in which known substances in the nanoscale acquire new properties, the chemical safety strategy becomes even more relevant. The absence of a medical specialty “preventive toxicology” complicates the quality training of relevant specialists. Limitations. The study was based on the materials of domestic publications in the open press. Conclusion. The experimental base of industrial toxicology needs to be significantly expanded, and the system of hygienic regulation of chemicals in the air of the working area needs to be optimized and transferred from initiative research to a planned distribution process.

Про результати роботи онлайн науково-практичної конференції з міжнародною участю «Досвід військових формувань у ліквідації наслідків аварії на Чорнобильській АЕС через призму сучасних радіаційних та хімічних загроз» 15-16 квітня 2021 року, Київ

The Scientific-practical conference "Experience of military formations in the aftermath of the Chernobyl accident through the prism of modern radiation and chemical threats" (hereinafter - the Conference) was organized by the Ukrainian Military Medical Academy in conjunction with the National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine and conducted on the basis of SE "Research Center of Preventive Toxicology, Food and Chemical Safety named after Academician L.I. Medved of the Ministry of Health of Ukraine" in Kyiv on April 15-16, 2021. Aim. The Conference was dedicated to the 35th anniversary of the Chernobyl disaster, current issues of CBRN medical care and generalization of experience in eliminating the radiation accident, taking into account the current structure of medical forces and troops of the CBRN protection. The main purpose of the Conference was to spread the scientific and pedagogical experience of the Ukrainian Military Medical Academy as the only medical institution in the country for the training of military medical personnel. The event was attended by representatives of the Department of Military Education and Science of the Ministry of Defense of Ukraine, Command of the Medical Forces of the Armed Forces of Ukraine, higher military primary institutions of the Ministry of Defense of Ukraine, radiation, chemical, biological protection of the Armed Forces and Defense Forces of Ukraine, higher medical primary institutions of Ukraine, health care institutions of Ukraine, representatives of the Malaysian Armed Forces and colleagues from Canada. Conclusions. The conference provided an opportunity for military medics, scientists, and civil servants to come together to share experiences on a wide range of issues. Measures to eliminate the radiation accident were discussed; measures of medical protection and rendering of medical care in the conditions of radiation infection; the role of the medical service of the Armed Forces in the elimination of radiation accidents; coordination and interaction between departments and institutions of different subordination in the field of medical care and radiation protection with the involvement of military specialists in the elimination of the consequences of a radiation accident; integration of scientific and educational activities in the system of higher military medical education; application of new scientific and technical knowledge during the training of military medics and the formation of scientific personnel potential. The conference was attended by about 90 experts in the field of theoretical and clinical medicine and CBRN defense, who presented 20 plenary and 10 section reports, prepared 39 abstracts, which were reflected in the scientific journal "Ukrainian Journal of Military Medicine" (Vol. 2. №1. 2021. Appendix). Key Words: radiation accidents, military radiology, military medicine, medical protection.

До обґрунтування переліку небезпечних високотоксичних хімічних речовин, які підлягають особливому контролю щодо обігу, зберігання, використання та утилізації. Частина ІІІ (дипіридилові гербіциди паракват і дикват)

The Aim of the Research. To identify a group of highly toxic chemicals which over the past decades are most often used in deliberate criminal and suicidal incidents, sabotage, and terrorist act; the handling, storage, use and disposal of which must be especially carefully monitored by law enforcement agencies. In this part of the article bipyridyl herbicides paraquat and diquat are considered. Materials and Methods. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Methods of systemic, comparative, and content analysis were used. Results and Conclusions. Analytical review of literature data and research carried out at the State Enterprise Scientific Centre of Preventive Toxicology, Food and Chemical Safety named after Academician L.I. Medved of the Ministry of Health of Ukraine, showed that highly toxic bipyridyl herbicides paraquat and diquat can pose a threat to human life and health. Recently, in particular for more than a quarter of a century, they have become a real weapon in the hands of criminals, delinquents, and terrorists all over the world. Suicidal incidents, which also take place along with intentional criminal, terrorist, and sabotage acts, should not be concealed. Based on the analysis of the toxicity, clinical and morphological expression of intoxication when exposed to these chemicals, considering various routes of entry into the body, the need to include them in the List of hazardous highly toxic chemicals, the handling, storage, use, and disposal of which require stricter control of law enforcement agencies, is justified. Key Words: bipyridyl herbicides, paraquat, diquat, health risk, acute poisoning.

Методи оцінки нейротоксичного впливу хімічних речовин на розвиток організму в пре- і постнатальному періодах

Aim of the research. Analysis of approaches to the assessment of neurotoxic effects of chemicals during ontogenesis. The dangerous tendency of the increase in the incidence of pathology of the nervous system in the child and the mother, who during pregnancy was exposed to neurotoxicants, necessitates the protection of the child’s body from such a negative effect of chemicals. One of the possible preventive ways to solve this problem is screening of xenobiotics before their widespread application, as well as identification of their ability to cause neurotoxic effects on the body during its development, and banning substances, neurotoxic effects of which on the development of progeny are proven. Materials and Methods. Detection of adverse effects at the stage of foetal development and then at the beginning of the functioning of a nervous system in the postnatal period requires complex experimental studies in laboratory animals, which are described in the recommendations of OECD guideline 426 (OECD Guideline for Testing of Chemicals; Guideline 426: Developmental Neurotoxicity Study, 2007). The OECD guideline 426 protocol provides for a wide range of methods for assessing sensory, motor, behavioural and cognitive functions. Conclusions. Analysis of data given in publications and methodological approaches to research and evaluation of neurotoxic effects of chemicals on the developing organism showed that to obtain representative results it is important to take into account all factors that may affect the result, select adequate informative tests and comply with all requirements. In Ukraine, international methodological approaches to the study of neurotoxic effects of pesticides on the body at the stage of development in the process of ontogenesis are applied at the L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine. Key Words: nervous system, neurotoxic effects, OECD guideline 426, neurobehavioral tests.

COMPARATIVE HYGIENIC ASSESSMENT OF WORKING CONDITIONS AND OCCUPATIONAL RISK IN THE APPLICATION OF PESTICIDES (ON THE EXAMPLE OF FUNGICIDE AMISTAR EXTRA 280, SC) USING DIFFERENT TYPES OF SPRAYERS

The aim: Was a comparative hygienic assessment of working conditions and occupational risk in the application of fungicide Amistar Extra 280, SC using slotted and injector sprayers. Materials and methods: Sprayers Super Poly 110-04 (variant №1) and Guardian Air GA110-04 (variant № 2), and certified equipment were used. The occupational risk was assessed in accordance with the methodological recommendations proposed by the L.I. Medvedia Scientific Center for Preventive Toxicology, Food and Chemical Safety specialists. Results: When using the slotted sprayer Super Poly 110-04 in the air of the working zone of the tractor driver the content of azoxystrobin was 0.0015 ± 0.0001 mg/m3, cyproconazole - 0.085 ± 0.002 mg/m3, at a distance of 10 m from the edge of the field on the leeward side - 0.003 ± 0.001 and 0.11 ± 0.02 mg/m3, respectively. Visual analysis of water-sensitive cards after using slotted sprayers showed the presence of single drops of pesticide working solution in the wear zone. When applying the pesticide using a Guardian Air GA110-04 injector sprayer in the air of the working zone of the tractor driver, areas of possible wear (10 and 100 m), theconcentration of the active substances of Amistar Extra 280, SC formulation was below the limit of quantification of the method. When assessing the complex risk for tractor drivers, a statistically significant difference was found for azoxystrobin (p = 0.002) and cyproconazole (p = 0.001) when using a slotted sprayer Super Poly 110-04 and injector Guardian Air GA110-04. Conclusions: Values of the combined complex risk of application of the Amistar Extra 280, SC formulation for tractor drivers of variant №2 application were significantly lower than those for tractor drivers of variant №1.

Референс-центр ідентифікації та контролю хімічних речовин: роль і місце в національній системі хімічної безпеки

In 2014 Ukraine accepted the OSCE proposal to develop an Integrated Chemical Safety and Security Program in Ukraine (ICSSP) aiming to develop a collaborative framework between the Ukrainian partners, the OSCE and the international partners for an effective and coordinated actions to ensure chemical safety and security. The main goal of the ICSSP program is to improve Ukraine’s ability to prevent, prepare for and respond to inappropriate handling of chemicals.Effective chemical safety will help to increase the level of protection of chemical materials, associated facilities and vehicles. ICSSP also had to ensure the implementation of modern solutions and coordinated approaches to strengthen the protection of critical infrastructure in Ukraine. A comprehensive review, conducted as the first step in the implementation of ICSSP, showed that the program should be aimed at introducing national activities in the field of chemical safety by a wide range of national authorities with a focus on the development of legislative and administrative measures for the implementation of United Nations Security Council Resolution 1540 in the chemical industry. Realization of the program objectives will provide: — creating a national (regional) Reference Centre for Identification and Control of Chemicals, able to make expert conclusions regarding hazardous chemicals and precursors quickly and reliably; — expanding opportunities to detect chemicals, conduct toxicological studies, including for the purpose of export control and forensic investigations, and the possibility to clarify the nature and characteristics of “unknown” chemicals; — improving capabilities of regional network of chemical analytical laboratories to identify toxic chemicals and ability to conduct joint research, as well as to train laboratory personnel and to exchange good laboratory practices. The National Reference Centre can serve as a model laboratory and national (regional) training platform for the dissemination of knowledge and best practices.It can help to solve regional problems, because the neighbouring countries Moldova, Georgia, Azerbaijan and even some EU countries also need such assistance. Key Words: chemical safety, Reference Centre, preventive toxicology.

Токсикодинаміка за сумісної дії хлорпірифосу та івіну при тривалому надходженні до організму

The combined action of pesticides is one of the problems of toxicology, because in comparison to individual active substances, their mixtures can increase toxicity and delayed action effects, which is a risk to human health. It is known that plant growth regulators (PGR) when applied together with pesticides help to reduce the quantitative rates of pesticides applied, the accumulation of pesticides and heavy metals in plants, reduce the acute toxicity of xenobiotics. The combined effect of the prolonged admission of PGRs and pesticides is an unexplored area, and it is an important issue in preventive toxicology. The Aim of the Research. Determination of the nature of toxic effects of Chlorpyrifos and “Ivin” combined action at subchronic oral admission. Materials and Methods. Chlorpyrifos and PGR “Ivin” (2.6-dimethyl-N-pyridine oxide) combined action was studied on male Wistar Han rats. Substances were administered orally, via a feeding tube for 13 weeks; Chlorpyrifos was administered in the form of an aqueous emulsion with an auxiliary material OP-10 at a dose of 5 mg/kg (1/15 LD50), “Ivin” — in the form of an aqueous solution at a dose of 13 mg/kg and 0.013 mg/kg (1/100 and 1/100000 LD50 respectively), the control group of rats was given water with an auxiliary material OP-10. Signs of intoxication were recorded, body weight was measured in 4, 9 and 13 weeks, biochemical indicators of blood serum were determined (the activity of ALT and AST enzymes and alkaline phosphatase; the content of crude protein, urea, cholesterol, triglycerides and glucose were determined using kits of reagents by BioSystems (Spain); cholinesterase (ChE) activity in serum, red blood cells and brain tissue was determined with the use of methodology by Hesrtin S. using a kit of reagents produced by LLC NPP Filisit-Diagnostics (Ukraine). Results. No clinical signs of intoxication were detected in the experimental groups of rats. Under the isolated use of Chlorpyrifos a significant decrease in body weight, ChE inhibition activity in all bio substrates, with the greatest effect in the brain (by 48.8%); increase (after 9 and 13 weeks) in the activity of ALT and AST by 26.7–32.6%, 12.5–12.0%; a slight but a significant increase in the level of urea and glucose in blood serum to 17.3% and 17.6 %, respectively was detected. Under the combined action of Chlorpyrifos and “Ivin” in specified doses the body weight of rats was at control level, decrease of ChE activity was observed in all biological substrates and was at nearly the same level with the isolated use of Chlorpyrifos. There was a tendency towards the decline in ChE inhibition activity in brain tissue, and under the combined action of Chlorpyrifos with “Ivin” at higher doses after 4 weeks this effect was a significant (22.15%, p < 0.05). Conclusions. Chlorpyrifos under the isolated oral admission for 13 weeks has a weak hepatotoxic effect, as evidenced by the increase in cytolysis enzymes and urea levels in serum and causes a moderate anticholinesterase effect. “Ivin” under combined with Chlorpyrifos admission to the organism eliminates the hepatotoxic effects of Chlorpyrifos and reduces its anticholinergic effects in brain, which contributes to a less severe intoxication. Key Words: Chlorpyrifos, Ivin, hepatotoxic effect, anticholinesterase effect.

Сучасна модель навчально-тренінгового центру з підготовки експертів у сфері хімічної, біологічної, радіаційної та ядерної безпеки (Результати першого тренінгу з хімічної безпеки в рамках Проекту 57: Посилення існуючих експертно-криміналістичних можливостей при розслідуванні ХБРЯ інцидентів. Україна, Київ, липень 2019 р.)

Minimizing the effects of chemical, biological, radiation and nuclear (CBRN) incidents requires the simultaneous efforts of different specialists not only within one state, so recently international projects have been chosen for the purpose of developing and implementing not only national measures to minimize CBRN threats, but also coordination at the international level. The Aim of the Research. Substantiation of the relevance of a permanent international training center organization for the training of specialists in the field of CBRN security (direction — chemical security) for the needs of the power and special structures of Ukraine. Methods. Results of the instruction and trainings conducted within the framework of the project on the establishment of a network of training centers for minimizing the risks related to the CBRN threats in the countries of the region of Southeast and Eastern Europe, held on the basis of State Enterprise “Research Centre of Preventive Toxicology, Food and Chemical Safety named after L. I. Medved”, Ministry of Healthcare of Ukraine” (Science Center) in July 2019. Results and Discussion. Project 57: Strengthening the crime scene forensics capabilities in investigating CBRN incidents in the South East and Eastern Europe Centers of Excellence Region (Ref: Europe Aid / IFS / 2016/374993) came into action in 2019. The objective of Project 57 is to introduce a system of trainings on the investigation of CBRN incidents and the gradual formation of relationships between forensic experts and organizations with experience in the field of CBRN materials at the national level. Successful fulfillment of the tasks of investigating CBRN incidents requires constant professional improvement of specialists in various fields and development of the system of communication and interaction at the interdisciplinary level. Project 57 from Ukraine involved Ukrainian experts instructed and trained in EU countries as national forensic trainers in crime scene investigations. These candidates, after conducting the relevant exercises, were involved in conducting trainings on raising the level of knowledge of law enforcement officers of Ukraine. In July 2019, a team-based training (July 5) and national exercises (July 22–25) were held under Project 57 at the Science Center. Law enforcement experts from Ukraine and Moldova participated in the team and staff training. Exercises were performed in groups, and the results of the work were demonstrated and discussed via Skype conference mode. National exercises were conducted in the form of practical exercises in a specially prepared territory of the Science Center. The participants of the training worked with imitation material evidence in protective suits using technical means in real-time situations. In addition to the acquisition of practical skills, there was an exchange of knowledge and experience between the various agencies involved in the field of chemical threat. The participants gained experience that will help to improve management skills and improve coordination and communication between the actors involved in the response to the CBRN incidents. Conclusions. The conducted trainings proved the necessity of introducing a system of continuous professional instruction and advanced training of the staff of special and security structures of Ukraine involved in the investigation of CBRN incidents. Key Words: chemical, biological, radiation and nuclear safety, continuous professional development.