До обґрунтування переліку небезпечних високотоксичних хімічних речовин, які підлягають особливому контролю щодо обігу, зберігання, використання та утилізації. Частина 1 (рицин, сполуки талію та фосфорорганічні сполуки)

Мета роботи. На підставі аналітичного огляду літературних даних виділити групу високотоксичних хімічних речовин, котрі за останні десятиліття найчастіше використовуються в умисних кримінальних та суїцидальних інцидентах, диверсійних і терористичних актах, обіг, зберігання, використання та утилізацію яких потрібно особливо прискіпливо контролювати правоохоронним органам. Матеріали та методи. Аналітичний огляд наукових публікацій виконаний з використанням реферативних баз даних наукових бібліотек Pub Med, Medline і текстових баз даних наукових видавництв Elsevier, Pub Med, Central, BMJ group та інших VIP-баз даних. Використано методи системного, порівняльного та контент-аналізу. Результати та висновки. Проаналізовано наукові публікації щодо небезпечних високотоксичних хімічних речовин, які за останню чверть сторіччя найчастіше використовуються у світі, зокрема в умисних кримінальних та суїцидальних інцидентах, диверсійних і терористичних актах. Установлено, що до них переважно відносяться: рицин, сполуки талію, фосфорорганічні сполуки та бойові отруйні речовини, миш’як і його сполуки, ціаніди та неорганічні водорозчинні сполуки ртуті (сулема, мертіолят натрію), а також пестициди паракват і дикват. На основі аналізу їхньої токсичності, клінічних та морфологічних проявів інтоксикації за різних шляхів надходження до організму обґрунтовано необхідність внесення їх до Переліку особливо небезпечних хімічних речовин, обіг яких, зберігання, використання та утилізація потребують більш жорсткого контролю правоохоронних органів. У першій частині даної статті представлені рицин, сполуки талію, фосфорорганічні сполуки та бойові отруйні речовини. Ключові слова: високотоксичні небезпечні хімічні речовини, рицин, сполуки талію, фосфорорганічні сполуки.

To substantiation of the list of hazardous highly toxic chemicals that are subject to special control regarding handling, storage, use and disposal. Part 1 (ricin, thallium compounds and organophosphorus compounds)

ABSTRACT. The Aim of the Research. Based on an analytical review of literature data, 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 traffic, storage, use and disposal of which must be especially carefully monitored by law enforcement agencies. 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. The scientific publications on hazardous highly toxic chemicals, which over the past quarter century are most often used in the world, notably in deliberate criminal and suicidal incidents, sabotage, and terrorist acts, are being analysed. It was found that these chemicals mainly include ricin, thallium compounds, organophosphorus compounds, as well as chemical warfare agents, arsenic and its compounds, cyanides, and inorganic water-soluble mercury compounds (mercury bichloride, sodium merthiolate), as well as paraquat and diquat pesticides. Based on the analysis of their toxicity, clinical and morphological expression of intoxication with various routes of entry into the body, the need to include them in the List of Highly Hazardous Chemicals, whose traffic, storage, use, and disposal require stricter control of law enforcement agencies, is justified. The first part of this article presents ricin, thallium compounds, organophosphorus compounds, and chemical warfare agents. Key Words: hazardous highly toxic chemicals, ricin, thallium compounds, organophosphorus compounds.

Методичні принципи віднесення відходів до певної класифікаційної категорії щодо небезпеки

Мета. Обґрунтувати підходи з'ясування проблеми оцінки негативного впливу відходів на здоров'я населення та навколишнє середовище, який виникає з моменту утворення і на всіх етапах поводження з відходами. Матеріали та методи. Одним з пріоритетних напрямків наближення до вимог Європейського Союзу при поводженні з відходами є гармонізація сучасного українського законодавства до європейських стандартів, адаптація положень нормативно-правових актів, у тому числі класифікація відходів за ступенем небезпеки. У статті проводиться порівняльний аналіз законодавчої бази з оцінки небезпеки відходів, існуючої в даний час в Україні, з рекомендаціями ВООЗ та Директивами ЄС. Обґрунтовані і рекомендовані для впровадження методичні принципи віднесення відходів до певної класифікаційної категорії за небезпекою. Результати та висновки. Науково обґрунтовано, що віднесення відходів до певної класифікаційної категорії за небезпекою повинно ґрунтуватися не тільки на кількісних розрахунках за хімічним складом і токсичності складових інгредієнтів, які входять до складу відходів, а й на експериментальній перевірці зразків з використанням альтернативних методів. Ключові слова: відходи, Директиви ЄС, класифікація, біотестування, токсичність, небезпека, альтернативні методи.

Methodological principles of waste hazardousness classification

The Aim of the Research. Clarification of the problem of the negative impact of waste on the environment and public health. They appear from the waste formation and at all stages of its handling. Materials and Methods. One of the priority areas of approximation to the requirements of the European Union in waste management is the harmonization of modern Ukrainian legislation with European standards, adaptation of regulations, including the classification of waste according to the degree of danger. The article provides a comparative analysis of the legal framework for waste hazardousness assessment currently existing in Ukraine with WHO recommendations and EU Directives. The methodological principles of classification of waste according to a degree of hazardousness are substantiated and recommended for implementation. Results and Conclusions. It is scientifically proven that the assignment of waste to a certain classification category of hazard should be based not only on quantitative calculations of chemical composition and toxicity of constituent ingredients that are part of the waste, but also on experimental testing of samples using alternative methods. Key Words: waste, EU Directive, classification, biological testing, toxicity, hazard, alternative methods.

To the problems of toxicity testing of nanorized objects (Literature review)

Aim of the Research. To present and summarize data on the problems of assessing the toxicity and hazards of nanosized particles due to the peculiarities of their activity and variability, which prove the need to develop a vector of research in vitro. Materials and Methods. Targeted testing can provide broad coverage of nanoproducts, reduce the cost and time of research, as well as the number of animals used in experiments. Various model test systems are proposed for use, the use of which is possible to detect harmful effects of man-made nanomaterials, and also for other chemicals: cellular and subcellular elements (mitochondria, microsomes, DNA, chorioallantoic membrane vessels), organs of laboratory animals, the simplest (unicellular) organisms, microorganisms, various aquatic organisms, plants, insects, sperm of cattle. Biotesting is one of the methods of research in the field of toxicology, used to determine the degree of toxic effects of chemical, physical and biologically unfavorable factors that are potentially dangerous to humans and components of ecosystems. 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. Results and Conclusions. Recently, publications emphasize that the manifestations of biological effects depend on changes in the characteristics and properties of nanomaterials. These facts cannot be taken into account in standard toxicological studies. One of the ways to intensify tests and reduce their cost may be the use of accelerated toxicological studies on simple biological systems (models). In this regard, the development and implementation of alternative methods in vitro has become one of the leading areas of toxicological research of nanomaterials. Key Words: nanoparticles, toxicity, testing.

Morphofunctional changes in cells of Tetrahymena pyriformis W infusoria under the influence of plant growth regulators — derivatives of pyridine-n-oxide

The aim of the Research. To identify morphological changes in Tetrahymena pyriformis W infusoria under the acute exposure to plant growth regulators (PGR) — derivatives of pyridine-N-oxide and compare them to functional disorders of cells. Materials and Methods. In the research we used the 2-methylpyridine-N-oxide, 2,6-dimethylpyridine-N-oxide and their complexes with organic acids (succinic, maleic) or metal salts (ZnCl2, ZnI 2, CoCl2, MnCl2) (a total of 15 substances), synthesized at the Institute of Bioorganic chemistry and Petrochemistry, NAS, Ukraine. Studies were performed on Tetrahymena pyriformis W infusoria in isotoxic doses — at the level of toxic concentrations — LC50, LC16 and inactive concentrations (LC0). Morphological changes in cells of infusoria were assessed visually with the use of a light microscope. Structural changes in infusoria were compared to functional changes in cells (motor activity and energy state) obtained under the same experiment. Results and Conclusions. It is demonstrated that 2-methylpyridine-N-oxide, 2,6-dimethylpyridine-N-oxide and their complexes with organic acids (succinic, maleic) or metal salts (ZnCl2, ZnI2, CoCl 2, MnCl2) cause functional and morphostructural changes in infusoria, the extent of which depends on the current concentration. Morphostructural changes in infusoria under the influence of the studied PGRs are characterized by a change of shape, growth of the contractile vacuole, vesiculation, damage to the integrity of the cytoplasmic membrane, emission of cytoplasm and structural elements of cells into the nutrient medium. Complexes of methyl derivatives of pyridine-N-oxide with metal salts in the studied concentrations reduce speed and increase energy expenditure on movement, cause changes in behavioural reactions and structure of cells to a greater extent than 2-methylpyridine-N-oxide, 2,6-dimethylpyridine-N-oxide and their complexes with organic acids. Both functional and morphological changes in infusoria are more evident under the influence of studied PGR occurring at concentrations corresponding to LC50. At lower concentrations the changes in the functional activity of infusoria were observed. Comparison of the obtained functional and morphostructural indicators of the state of infusoria shows that complexes of methyl derivatives of Pyridine-N-oxide with metal salts have more toxic effects on infusoria than complexes of methyl derivatives of pyridine-N-oxide with organic acids. Reduced motor activity and an increase in energy consumption per a unit of a path of motion, together with the morphological changes of cell structure, are the indicators of toxicity of xenobiotics for infusoria and criteria for assessing their viability. Key Words: methyl derivatives of Pyridine-N-oxide, Tetrahymena pyriformis W, morphofunctional changes.

Experimental substantiation for 2-hydroxypropanoic (lactic) acid temporary occupational exposure standard

Lactic (2-hydroxypropanoic) acid is an important metabolic component of living organisms. It is also widely used in various industries. Such a wide application of the acid in manufacturing necessitates the regulation of its content in the workplace air. Toxic effects of lactic acid are described in the literature. It was found that 2-hydroxypropanoic acid belongs to hazard level IV by the criterion of acute oral and inhalation toxicity, it causes skin irritation, severe eye damage, has no skin-resorptive or sensitizing effect, does not cause reproductive toxicity and teratogenicity. Aim of the Research. Substantiation for 2-hydroxypropanoic (lactic) acid indicative safe exposure level (ISEL) in the workplace air. Methods and Materials. Analytical, toxicological, statistical. Results. In the process of conducting toxicology study, it was found that in the conditions of inhalation experiment (intranasal modelling) 2-hydroxypropanoic acid causes changes in the state of the nervous system and affects the cellular composition of bronchoalveolar lavage of experimental animals. Therefore, after a single-dose intranasal instillation Limir = Limac, it can be classified as a substance with non-specific irritant effect. It was found that the threshold of a single-dose inhalation exposure is 20 mg/m3. Conclusions. According to the data obtained in the process of the experiment and data on toxicity parameters and health-based exposure standards of the chemical analogues, the value of ISEL for 2-hydroxypropanoic (lactic) acid in the workplace air was calculated, it is 1.0 mg/m3, aerosol. Key Words: 2-hydroxypropanoic acid, lactic acid, ISEL, workplace air.

Toxicodynamics of Chlorpyrifos and “Ivin” Combined Action under Prolonged Admission

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.

Topical Effect of Minoxidil Containing Lotion on Morphofunctional Indicators of Male Rats’ Reproductive System

The problem of alopecia, for treatment of which the use of over the counter lotions containing minoxidil is recommended, is paid considerable attention all over the world. The consumers rarely seek medical advice due to certain psychological barriers. Thus, it contributes to the uncontrolled use of the drugs, and fixation of their side effects becomes impossible. There are isolated reports on the effect of minoxidil containing lotions on male fertility. The Aim. To establish organometric parameters of testes and their paradidymis, functional parameters of spermatozoa in mature rats under topical exposure to a 10% minoxidil containing lotion. Methods. Analytical, toxicological, statistical. Results. It was established that under the conditions of 72-day percutaneous application of 10% minoxidil containing lotion some changes in the reproductive system organs can be observed, which are in particular a decrease in the mass of testes and epididymis, as well as a decrease in organs’ linear size. The total time of motor activity of gametes after exposure to a lotion containing 10% minoxidil has statistically significantly shortened, a 6-fold inhibition of the activity of redox processes occurred in the rats of the experimental group compared to the control one. Conclusions. Taking into consideration the obtained data and the uncontrolled and long-term use of 10% minoxidil containing lotions by men of reproductive age, an in-depth study of its gonadotoxic effects in experimental conditions in combination with epidemiological studies of the patients using these lotions is deemed necessary. Key Words: minoxidil, gonadotoxicity, mature rats.

Complex Therapy of Acute Poisoning by Thallium Compounds (Literature review and data from own research)

The Aim of the Research. Based on the analysis of modern literature data and our own research to substantiate the principles of rational complex therapy with acute poisoning by thallium compounds (Tl+) at different stages of intoxication. Materials and Methods. The analysis of literature data and our own researches is carried out and the principles of rational complex therapy with acute poisoning by thallium compounds at different stages of intoxication development are substantiated and the algorithm of doctors’ actions at suspicion of acute Tl+ poisoning is defined. Results and Conclusions. The principles of complex therapy of acute Tl+ poisonings substantiated, which includes antidote therapy, methods of extracorporeal treatment (plasmapheresis, hemosorption, hemodialysis), treatment of toxic encephalopolyradiculoneuropathy, neuropathic pain syndrome and toxic liver damage. The sequence of appearance of the main symptoms of intoxication at low and high doses of Tl+ is determined, which allows to assume poisoning by this toxicant. Key Words: thallium, acute poisoning, complex therapy.