The environmental health impacts of Russia's war on Ukraine.

BACKGROUND: Russia's invasion of Ukraine in February 2022 ignited the largest armed conflict in Europe since World War II. Ukrainian government agencies, civil society organizations, and international agencies have gathered an unprecedented amount of data about the impact of war on the environment, which is often the silent victim of war. We review these data and highlight the limitations of international governance for protection of the environment during time of war. METHODS: We performed an integrative review of academic, institutional, and media information resources using the search terms "Ukraine", "Russia", "war", "environment", "health", "human rights", "international humanitarian law", "international human rights law", "ecocide", and "war crimes". MAIN TEXT: Nearly 500,000 military personnel have been killed or wounded during the war, and more than 30,000 civilians have been killed or injured. Indirect health effects of the war have likely accounted for an even greater amount of civilian morbidity and mortality. The war has displaced more than 11 million people. Russia's military forces have caused extensive damage to civilian infrastructure. The war has devastated Ukraine's economy and reduced food and energy security in many countries. The war has caused more than $56.4 billion in damage to the environment. There has been widespread chemical contamination of air, water, and soil, and 30% of Ukraine has been contaminated with landmines and unexploded ordnance. Landscape destruction, shelling, wildfires, deforestation, and pollution have adversely affected 30% of Ukraine's protected areas. Russia's seizure of the Zaporizhzhia Nuclear Power Plant and destruction of the Nova Kakhovka Dam have posed risks of long-term environmental catastrophe. Most of these environmental impacts threaten human health. CONCLUSION: In addition to enormous human costs, Russia's war on Ukraine has had devastating impacts on the natural environment and the built environment. International law mandates that methods of warfare must be implemented with due regard to the protection and preservation of the natural environment. A just and lasting peace necessitates, among other requirements, rebuilding and restoration of Ukraine's natural environment and built environment. The environmental consequences of all wars need to be investigated and more effective measures need to be implemented to protect the environment during war.

A battery of in silico models application for pesticides exerting reproductive health effects: Assessment of performance and prioritization of mechanistic studies.

Given the high attention to endocrine disrupting chemicals (EDC), there is an urgent need for the development of rapid and reliable approaches for the screening of large numbers of chemicals with respect to their endocrine disruption potential. This study aimed at the assessment of the correlation between the predicted results of a battery of in silico tools and the reported observed adverse effects from in vivo reproductive toxicity studies. We used VirtualToxLab (VTL) software and the EndocrineDisruptome (ED) online tool to evaluate the binding affinities to nuclear receptors of 17 pesticides, 7 of which were classified as reprotoxic substances under Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP). Then, we aligned the results of the in silico modelling with data from ToxCast assays and in vivo reproductive toxicity studies. We combined results from different in silico tools in two different ways to improve the characteristics of their predictive performance. Reproductive toxicity can be caused by various mechanisms; however, in this study, we demonstrated that the use of a battery of in silico tools for assessing the binding to nuclear receptors can be useful for identifying hazardous compounds and for prioritizing further studies.

Combined reproductive and developmental toxicity study of pesticide abamectin on male and female Wistar Hannover rats.

Abamectin is a widely used pesticide and anthelmintic for humans and animals. Previous toxicological studies showed evidence of adverse effects on reproduction, but the findings were inconclusive. Abamectin is known to exhibit teratogenic activity, causing different malformations during developmental stages in rats and rabbits. The present work aims at combining reproductive and developmental toxicological assessments in a single study to evaluate the impact of abamectin on reproductive, fertility, and developmental functions. Abamectin was administered orally to 20 male and 20 female rats at doses of 0, 0.1, 1.0, and 2.0 mg/kg body weight. Abamectin exposure was prolonged for 11 weeks for males and 10 weeks for females before mating. Females were also treated during mating and pregnancy. In this study, treated animals were mated with untreated intact animals to further assess the potential sex sensitivity effect. The results demonstrate that male rats were more susceptible to general toxic effects such as decreased body weight and showed a more toxic effect on reproductive function and fertility at doses of 1.0 and 2.0 mg/kg/day. Furthermore, stages of gametogenesis and early fetal development are the most vulnerable of the reproductive process to endocrine disruptors' action, leading to changes in the estrous cycle in females and sperm quality in males. Abamectin can produce developmental toxicity in rats at a dose of 2 mg/kg/day, which is not a maternally toxic dose. Accordingly, NOAEL for reproductive toxicity and developmental toxicity with fetotoxic effects were established at the dose level of 0.1 mg/kg/day and 1.0 mg/kg/day, respectively.

ANTIHYPOXIC ACTIVITY OF 2,6-DIMETHYLPYRIDINE-N-OXIDE.

OBJECTIVE: The aim: To study the antihypoxic activity of 2,6-dimethylpyridine-N-oxide in mice using the various experimental models of acute hypoxia under orally or intraperitoneally administration. PATIENTS AND METHODS: Materials and methods: The studies were performed on male CD-1 (SPF) mice. The antihypoxic activity of 2,6-dimethylpyridine-N-oxide was studied in three experimental models of acute hypoxia - hypercapnic hypoxia or hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia at orally administration at doses 0.07; 7.1 and 71 mg/kg (respectively 1/20000, 1/200 and 1/20 of LD50) and at intraperitoneally administration at doses 7.1 and 71 mg/kg in comparison with reference drug Armadin. RESULTS: Results: It is established, that 2,6-dimethylpyridine-N-oxide shows a antihypoxic activity in the all experimental models of acute hypoxia (hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia). Its antihypoxic activity in acute hemic hypoxia and in acute hypoxia in a closed space was significantly higher than of reference drug Armadin, but during acute histotoxic hypoxia did not differ from Armadin. Also at intraperitoneal administration of 2,6-dimethylpyridine-N-oxide demonstrates less pronounced antihypoxic activity than at oral administration in all experimental models of acute hypoxia, but the coefficient efficiency is higher than in the reference drug Armadin. CONCLUSION: Conclusions: 2,6-dimethylpyridine-N-oxide may be recommended for further detailed experimental studies as a perspective antihypoxant.

"Emerging Technologies and Medical Countermeasures to Chemical, Biological, Radiological, and Nuclear (CBRN) Agents in East Ukraine".

Since 2014, Ukraine has been beset by an armed conflict with international and internal dimensions. The nature of this conflict is multidimensional, and disaster preparedness and response in this context must be as well. Health experts from Ukraine, the United States of America, United Kingdom, Czech Republic, and Norway convened for an educational event in Dnipro, East Ukraine on November 11-15, 2019. At the event, "Emerging Technologies and Countermeasures to CBRN Agents: Advanced Training Response to Conflict and Security Challenges in East Ukraine," over 1,000 participants participated in panel discussions, didactic lectures, and an advanced training on various dimensions of disaster response. This report provides an overview of the key discussions and outcomes of the event.

The problem of acute pesticide poisonings of agricultural workers in ukraine under the conditions of the new business patterns.

OBJECTIVE: Introduction: Due to introduction of new forms of agriculture and transformation of the treatment and preventive service in recent years, there has been a false impression of a sharp decrease in the level of occupational morbidity among agricultural workers 30 % to 25 % in the structure of general occupational morbidity in the 80-90s down to 0.2-0.4 %. The aim: Summarize data on the prevalence, causes, structure of acute pesticide poisoning in agricultural workers at the current stages of its reform in order to improve preventive measures. PATIENTS AND METHODS: Materials and methods: Data on the prevalence, causes and structure of 647 cases of acute pesticide poisoning in agricultural workers over the past 25 years have been summarized; staff of the Scientific Toxicology Center took part in the sanitary-hygienic investigation and establishment of the diagnosis. RESULTS: Results: The causes for the development, aetiology and structure of 647 cases of acute pesticide poisoning, among which 522 cases of acute poisoning of field beet growers with 2,4-D-based herbicides (80.7 %), 60 cases (9.3 %) of OPC poisoning, 36 cases of beet growers poisoning with sulphonylurea-based herbicides, 14 patients with acute synthetic pyrethroid poisoning, and isolated cases (15 patients) of intoxication with aluminium phosphide, dithiocarbamates, Vitavax, and Fipronil were analysed. CONCLUSION: Conclusions: Analysis of the causes of the development and structure of poisoning has allowed to optimize the complex of preventive measures to strengthen sanitary control over the implementation of individual and public safety hygienic regulations during storage and use of pesticides.

Differences in classification for skin corrosion/irritation in EU and Ukraine: Case study of alternative (in vitro and in silico) methods application for classification of pesticide active ingredient imazamox.

In Ukraine Globally Harmonized System of classification of chemicals has not been implemented yet. In this article we analyze differences between GHS/CLP classification systems and Hygienic Classification of Pesticides by the Degree of Hazard currently in force in Ukraine in respect of approach and criteria for classification of effects on skin. As a case study, we conducted in silico modelling of herbicide imazamox using skin irritation/corrosion modules of ToxTree. The prediction of ToxTree was "Not Corrosive to skin". Then skin irritation and skin corrosion in vitro tests (OECD TGs 439, 431) were conducted. Classification of this substance based on in vitro and in vivo results according to GHS/CLP was the same, while it was not possible based on in vitro results to assign certain hazard class of Ukrainian classification due to difference in its and GHS/CLP criteria. However, ongoing process of harmonization of Ukrainian legislation with EU will give opportunity not only use alternative methods, but also adopt most recent advances and incorporate data from non-animal methods directly into classification criteria.

Disturbances of trace element metabolism in ESRD patients receiving hemodialysis and hemodiafiltration.

INTRODUCTION: Accumulation of trace elements occurs in conditions of decreased kidney function. In some conditions, increased trace elements can have toxic features. On the other hand, studies are showing that concentration of some trace elements could be decreased in ERSD patients as well. The most important factor affecting trace element concentration in ERSD patients is the degree of renal failure and the usage of replacement therapy. MATERIALS AND METHODS: We analyzed the trace elements' (boron, aluminum, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, rubidium, strontium, cadmium, cesium, barium and lead) concentration in the whole blood of 41 ESRD patients who were treated with hemodialysis and hemodiafiltration and also of 61 healthy blood donors. In addition, comparison of trace element blood levels of patients receiving hemodialysis and hemofiltration was carried out. Whole blood trace element concentration was determined using inductive coupled plasma mass-spectrometry (ICPMS). RESULTS: Levels of boron, aluminum, vanadium, chromium, manganese, zinc, strontium, cadmium, barium and lead were significantly increased in ESRD patients. Significantly decreased levels were observed for nickel, arsenic, selenium and rubidium. Blood levels of cobalt, copper, cadmium and lead in hemodialysis patients were significantly higher compared to patients receiving hemodiafiltration. CONCLUSIONS: ESRD is accompanied with serious and multidirectional changes of trace element blood levels. The highest degree of blood level increases were observed for nonessential and toxic trace elements. Disorders of essential trace elements were manifested in a minor degree. Besides this, there were observed differences of trace element concentrations between ESRD patients receiving hemodialysis and hemo-diafiltration.

Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue.

OBJECTIVES: Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments. METHODS: In vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays. RESULTS: Hydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation. CONCLUSIONS: Oxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication.