The global tendency of the contemporary scientific studies is using alternative biologic models as substitutes of experimental animals. HET-CAM (The Hen's Egg Test on the Chorioallantoie Membrane Assay) is an alternative to in vivo tests involving experimental animals. This test is actively used in different biomedical studies. The aim of our work was to study the irritating potential of adhesives used in shoe making industry in experimental setting using the alternative HET-CAM method. Polyurethane, polychloroprene, rubber and styrene-butadiene adhesives that are widely used in shoe-making industry were studied . HET-CAM test was used for the evaluation of the irritating action of the aforementioned adhesives. All adhesives were applied directly onto the chorioallantoic membrane of chick embryos with reactions and changes (hemorrhages, vascular lysis and coagulation) observed and registered in 30, 120 and 300 seconds after the application of the adhesive. Irritating potential of the adhesives was evaluated according to a calculated irritating index. The most pronounced signs of irritating action were caused by polyurethane adhesives, namely hemorrhages and coagulation (30 sec) – two-component adhesive and hemorrhages (30 sec) and coagulation (120-300 sec) – one-component adhesive. Vascular reactions from application of styrene-butadiene adhesives manifested predominantly with lysis and hemorrhages (30 sec), in some samples these reactions were observed at a later time-point (120-300 sec). Irritating action of rubber adhesives manifested mostly with hemorrhages (30 sec), one observation showed lysis (120 sec). Polychloroprene adhesive caused hemorrhages (30-120 sec) and also lysis (30 sec) in one of the samples. According to the irritating index, polyurethane (one- and two-component) and styrene-butadiene adhesives were estimated to be strong irritants, while rubber and polychloroprene ones cause
moderate irritating action. НЕТ-САМ test can be used as a component in the evaluation of evidence of irritating action of shoe adhesives. 

Key words: shoe adhesives, irritating action, the hen's egg test on the chorioallantoie membrane assay, in vitro method

Глобальною тенденцією сучасних досліджень є використання альтернативних біологічних моделей на заміну чи обмеження експериментів на
тваринах. HET-CAM (The Hen's Egg Test on the Chorioallantoie Membrane Assay) тест служить альтернативою тестів in vivo на експериментальних тваринах та активно використовується в різних галузях біомедичних досліджень. Метою роботи було дослідити в експериментальних умовах подразнювальний потенціал взуттєвих адгезивів з використанням альтернативного методу HET-CAM. Досліджували поліуретанові, поліхлоропренові,
каучукові та стирол-бутадієнові адгезиви, які використовуються в технології виготовлення взуття. Для оцінки подразнювальної дії клейових сполук використано метод HET-CAM. Клей у нативному вигляді наносили безпосередньо на поверхню хоріоалантоїсної оболонки курячих ембріонів та спостерігали за змінами та реакціями: виникненнями геморагій, лізисом судин та коагуляцією. Ці ефекти відстежували через 30, 120 та 300 с від часу нанесення клею на хоріоалантоїсну оболонку. За розрахованим індексом подразнення оцінювали іритативну активність адгезивів. Найбільші прояви подразнювальної дії зафіксовані при нанесенні поліуретанових адгезивів, а саме: геморагії та коагуляція (30 с) – двокомпонентний адгезив; геморагії (30 с) і коагуляція (120-300 с) –однокомпонентний адгезив. Судинні реакції від нанесення стирол-бутадієнових клеїв проявилися переважно лізисом, геморагіями (30с), в окремих зразках ці зміни проявилися пізніше (120-300 с), коагуляцією в трьох пробах (30 с або 300 с). Подразнювальний потенціал каучукового клею проявляється переважно геморагіями (30 с), в одній пробі також і лізисом (120 с); поліхлоропренового клею – переважно геморагіями (30-120 с) та лізисом (30 с) одного зразка. За значенням індексу подразнення поліуретанові (одно- і двокомпонентні), стирол-бутадієнові адгезиви оцінено як сильні подразники, каучуковий та поліхлоропреновий – помірної подразнювальної дії. НЕТ-САМтест може використовуватися як складова оцінки доказовості подразнювальної дії взуттєвих адгезивів. 

Ключові слова: взуттєві адгезиви, подразнювальний ефект, тест на хоріоалантоїсній оболонці курячого яйця, метод in vitro

Introduction. Poor regulation of active substances in disinfectants in Ukraine holds their legalization on the national market. Cluster approach in the hygienic regulation practice is one of the ways to address this issue. The aim of the study is to establish group-based hygiene regulations for the benzalkonium chloride (BC) cluster. Materials and methods of research. The subject of research is BC homologues. The research is based on the analysis of national and international scientific publications and legislative acts regarding BC toxic effects and hygienic regulations. Results. BC is a mixture of the benzalkonium chloride compounds homologues. The homologues ratio in a mixture plays a key role in assigning CAS numbers to BC. The average lethal doses with oral administration for all BC homologues are below 500 mg/kg. BC skin and oral absorption does not exceed 10 %. BC does not affect reproductive system and does not cause neonatal development abnormalities; it has no carcinogenic and mutagenic properties. Typical adverse effects of BC are related to compound irritant activity. Pursuant to EU regulation 1907/2006, substances with similar physicochemical, toxicological and ecotoxicological properties can be considered as a cluster. The data for reference substance of the cluster make it possible to predict the impact of other substances from this group on human health and environment. In case of BC, alkyl (C12–C16) dimethylbenzylammonium chloride was chosen as the reference substance. In Ukraine, the hygienic regulation sets 0.5 mg/m3 as occupational exposure limit for this substance. Following the clusters principle, it is advisable to introduce group hygiene regulations for all BC homologues based on alkyl (C12–C16) dimethylbenzylammonium chloride.
Conclusions. The implementation of cluster approach when developing exposure limits for chemical compounds in environmental medium makes it possible to introduce group hygienic regulations of 0.5 mg/m3 as occupational exposure limit for all BC homologues.
Key words: alkylbenzyldimethylammonium chloride, benzalkonium chloride, hygiene norm, cluster approach, group hygienic regulations

UDC 616-057:613.63/.65:547

Introduction. The situation of recent years during the SARS-CoV-2 pandemic has aggravated the problem of an insufficient number of approved hygienic standards of active substances included in disinfectants. This, in turn, has become a deterrent to the introduction of such agents into practice. For the proper organization of chemical safety of the workforce new methods of substantiating hygienic standards need to be developed. One of the ways to overcome the outlined higher problem, which will significantly speed up the resolution of the situation, is the introduction of read-across as an express method of substantiating the maximum permissible concentrations for a group (cluster) of compounds.

The purpose of the research is to substantiate the possibilities of developing group regulations for this cluster of compounds in the air of the working area based on data about the physicochemical and toxicological characteristics of dialkyldimethylammonium chloride С₈-С₁₀ homologues.

Results. Similar chemical structure of dialkyldimethylammonium chloride C₈-C₁₀ homologues determines their similarity in terms of physicochemical and toxicological properties. All substances are solids in their aggregate state, dissolve well in water, have the ability to penetrate biological membranes and disrupt their integrity. According to parameters of acute oral toxicity, dialkyldimethylammonium chloride C₈-C₁₀ homologues belong to moderately hazardous substances – hazard class 3, do not cause systemic toxicity; the main negative manifestation of their influence is an irritating effect which further provokes signs of general toxicity. The substances do not have carcinogenic, mutagenic effects, they do not affect reproductive function. The most studied representative of the cluster is didecyldimethylammonium chloride (DC₁₀DAC), which is accepted as a standard (analogue) for all dialkyldimethylammonium chloride C₈-C₁₀ homologues. In Ukraine a temporary hygienic standard for didecyldimethylammonium chloride in the air of the working area (approximately safe exposure level, ASEL) has been approved at the level of 0.2 mg/m³, where the limiting criteria for harmfulness are pronounced irritating effect on the skin and mucous membranes of the eyes and an acute inhalation effect. The calculation standard for quaternary ammonium compounds proposed by Dotson G.S. et al. is 0.1 mg/m³. Both standards belong to the II class of safety.

Conclusions. The read-across method allows for accepting didecyldimethylammonium chloride (DC₁₀DAC) as a standard (analogue) for all dialkyldimethylammonium chloride C₈-C₁₀ homologues. The hygienic regulation of the permissible content of didecyldimethylammonium chloride obtained on the basis of additional experimental studies as a result of the application of the cluster approach will be legitimate for dioctyldimethylammonium chloride (DC₈DAC); octyldecyldimethylammonium chloride (DC_8-10DAC), didecyldimethylammonium chloride (DC₁₀DAC) and their mixtures with different percentage ratios.

Keywords: dialkyldimethylammonium chloride C₈-C₁₀ homologues, dialkyl(C₈-C₁₀)dimethylammonium chloride, dioctyldimethylammonium chloride, didecyldimethylammonium chloride, read-across, hygienic standard, cluster approach, group hygienic regulation.

Рatients with diabetes have more complications and higher mortality from COVID-19. This is due to the fact that diabetes impairs the immune response. Hyperglycemia causes a violation of the immune response, which in turn cannot control the spread of pathogenic microorganisms and therefore patients
with diabetes are more susceptible to infections. The purpose of the work ₋₋ analysis of bibliometric databases of literature on new developments in diabetes and COVID-19 and focused on clinical recommendations for patients with diabetes infected with COVID-19. The search methods included a literature review of scientific articles that studied diabetes and COVID-19. According to the results of the analysis of the articles obtained as a result of the search in the PubMed, SCOPUS, Web of Science, MedScape databases, a combination of the terms “diabetes and SARS-CoV-2”, “diabetes and COVID-19”, “pathogenesis of diabetes in case of COVID-19”, "pancreas", "clinical features", "diagnosis", "treatment", "clinical recommendations", we found 32 messages from 2020 to 2022. The main parameters  of the study were outpatients and inpatients with diabetes and COVID-19 of middle and elderly age starting from 46 years and up to 82 years of age in France, China, the USA, Great Britain, in which a nationwide, retrospective, populationbased study was conducted. The following concomitant diseases are included in the main studies: arterial hypertension, cardiovascular diseases, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, myocardial infarction, cerebrovascular diseases. Issues of pathogenetic mechanisms in DM and COVID-19, as well as management of patients with DM and COVID-19 are highlighted.
Key words. Diabetes mellitus, СOVID-19, SARS-CoV-2, angiotensin-converting enzyme-2, cytokines.

Aim: To study the process of hemoglobin oxidation and the enzymatic reactions associated with it.
Materials and Methods: Heparinized human blood (15 IU/ml) was obtained from the clinical department. The concentration of oxy- and methemoglobin,
auto-oxidation of hemoglobin was determined spectrophotometrically spectrophotometrically. Autooxidation of hemoglobin was recorded spectrophotometrically, and protein concentration was determined by the Lowry method. Monooxygenase activity of hemoglobin was also measured by the method described
by Lowry spectrophotometrically. The concentration of O₂ and H₂O₂ in the reaction media was determined on a biomicroanalyzer OR 210/3 (Redelkis).
Results: The obtained experimental data allow us to propose a mechanism of “spontaneous autooxidation” of oxyhemoglobin, which can be described by
the following equations:
Hb²⁺O₂ = Hb³⁺ + O₂ (1)
Hb²⁺O₂ + 2e^- + 2H⁺ = Hb³⁺ + H₂O₂ (2)
Hb²⁺O₂ + 2e ^- + 2H⁺ = Hb²⁺ + H₂O₂  (3)
Hb²⁺ + O_{2 ⁼}  Hb²⁺O2 (4)
Spectral characteristics of the process of “spontaneous auto-oxidation” indicate the formation of a metform of hemoglobin, the depletion of oxygen by the system was established, at pH 5.6, an increase in the monooxygenase activity of hemoglobin is observed 3-4 times compared to the physiological level.
Сonclusions: In addition to the main, previously known functions of hemoglobin (gas transport, peroxidase, monooxygenase), it catalyzes a two-electron
oxidase reaction in which O₂
 is reduced to H₂O₂. This is confirmed by experimental data on the formation of one of the products of “spontaneous autoxidation”
of oxyhemoglobin _ deoxyform at pH 5.6 _ 8.9.
 KEY WORDS: oxyhemoglobin, methemoglobin, autooxidation, monooxygenase activity, oxidase reaction, ligands