[The modification of methodological approaches for potential hazard identification of inadvertent chemicals in food].

The existing methodological approaches for hazard identification and selection of priority hazard contaminants in foodstuff for further health risk assessment and legislation (in case of need) do not represent the reasons of inclusion inadvertent chemical substances in a number of priority for health risk assessment. The absence both of complex assessment and potential hazard categories of contaminants do not allow to assess the urgency of health risk assessment. Thus, it's advisable to expand the existing methodological approaches with the criteria of selection of hazard inadvertent chemical substances in food. The criteria allow for an integral assessment and further categorizing for health risk assessment and legislation. The aim of the research was to develop the methodological approaches to selection of priority inadvertent chemical substances in foodstuff for risk analysis and legislation based on the integral assessment Results. Material and methods. Various methods of chemical analysis were applied for detection of potentially hazard chemical substances in foodstuff. The further hazard identification and selection of priority chemical substances has been based on suggested criteria and categories that complete existing methodology. The approbation of methodological approaches to integral assessment and categorizing has been carried out on milk. Results and discussion. The potential hazard identification of inadvertent chemicals has been carried out using the complex of selection criteria. It was suggested to apply scores for calculation of integral score for further categorizing and selection of priority chemical substances (taking into account substances' toxicity class and possibility of migration during cooking or formation during technological process, and from packing, and from food raw materials). 5 hazard chemicals in milk (2-furanmethanol, thallium, mevinphos, sulfotep, mephospholane) were defined as priority category as the result of approbation. Conclusion. Integral assessment and categorizing of potential hazard of inadvertent chemicals in food applying basic and additional criteria taking into account natural content of the substances and their possibility of migration in food allow to assess the priority of health risk assessment and further hygienic legislation of the substances (in case if the risk level is inappropriate). During the approbation on the example of milk, 5 unintended substances that had potential hazard category I (high priority) were recommended for further risk assessment.

[Methods for the identification and quantification of microplastics in foods (a review)].

The adverse effects of microplastics (MP) found in food on the health have recently been recognized as a new source of human health risks. In order to evaluate and minimize them, it is necessary to evaluate the exposure using sensitive and specific methods. The aim of the research was the substantiation of methodological approaches to the identification and quantification of microplastics in food based on the analysis of literature data. Material and methods. Literature selection was carried out using the PubMed international reference database for the period from 2014 to 2023 using keywords corresponding to the context of the research theme. A total of 159 sources were selected, of which 94 original and review papers were included in the review according to the criteria of their relevance to the problem under consideration, scientific reliability and completeness. Results. At present, various approaches have been developed that make it possible to isolate MPs from complex bioorganic matrices (such as, for example, seafood), classify them by chemical composition, and quantify their content through the mass or number of particles. Among the most developed physic-chemical methods for the analysis of MPs are Fourier transform IR spectrometry and Raman microspectrometry, pyrolysis gas chromatography - mass spectrometry, thermogravimetric analysis, as well as approaches based on liquid chromatography, microfluorimetry, analytical scanning and transmission electron microscopy and others. Unsolved problems in the field of MP research in food include the high laboriousness and low performance of the identification technologies used, the lack of reference and standard samples of MP, the complexity of the equipment used, which makes it difficult to use it for routine hygienic control. The issue of the influence of MP aging degree on the results of its qualitative and quantitative determination has not been sufficiently studied. Some hopes in the field of development of rapid analysis of MTs are pinned on the use of aptamers. Conclusion. Existing analytical methods make it possible to determine the content of MPs in environmental objects, but further improvement and validation of these methods is required in relation to the assessment of the content of MPs in various types of food.

[Assessment of the influence of an enzymal preparation - a complex of glucoamylase and xylanase from Aspergillus awamori Xyl T-15 on the intestinal microbiom and immunological indicators of rats].

The requirements for the safety of food products obtained by microbial synthesis are including as obligation for to conduct toxicological studies - the study of various biochemical and immunological markers of toxic effects. The necessity of these studies is explained by a possible change in the structure of food ingredients produced by a microbial cell and, consequently, a change in their biological properties, as well as the possible presence of living forms and/or DNA of producer strains or of their toxic metabolites in these ingredients. At the same time, it is well known that the nutrient composition of foods has a significant impact on the composition and properties of microorganisms that make up the gut microbiome, which, in turn, determines the immune status. The purpose of the research was to justify the analyses of gut microbiocenosis composition for inclusion in the protocol of safety investigation of foods obtained by microbial synthesis [on the example of an enzyme preparation (EP) - a complex of glucoamylase and xylanase from a genetically modified strain of Aspergillus awamori Xyl T-15]. Material and methods. In experimental studies carried out for 80 days, Wistar rats (males and females) were used. The study of the effect of EP (a complex of glucoamylase and xylanase from a genetically modified Aspergillus awamori Xyl T-15 strain) in dozes 10, 100 and 1000 mg/kg body mass on the cecum microbiome and the immune status (content of cytokines and chemokines: IL-1a, IL-4, IL-6, IL-10, IL-17A, INF-γ, TNF-α, MCP-1, MIP-1a and Regulated on Activation Normal T-cell Expressed and Secreted - RANTES) was carried out. Results. It has been shown that EP - a complex of glucoamylase and xylanase from A. awamori Xyl T-15 at doses of 100 mg/kg or more causes mild disturbances in the composition of gut microbiocenosis. At the same time, these disorders have a significant immunomodulat ory and immunotoxic effect on the body, which manifests itself in a dose-dependent change in the profile of pro-inflammatory cytokines and chemokines in blood and spleen. The adverse effect of EP on the body is probably due to the formation of metabolites that are not formed during usual digestive processes in the gastrointestinal tract. The minimum effective dose (LOAEL) of EP was 100 mg/kg body weight In accordance with established requirements, the activity of the EP should not appear in ready-to-use food. Subject to this requirement, amount of EP entering the body cannot exceed the established LOAEL level. Therefore, a complex of glucoamylase and xylanase can be used in food industry, subject to the establishment of regulations «for technological purposes¼ for A. awamori Xyl T-15 strain. Conclusion. The data obtained on the relationship between the state of the microbiome and the immune status upon the introduction of EP indicate the need to include indicators of the state of gut microbiocenosis in the test protocol of safety.

[Nanocellulose in the food industry and medicine: structure, production and application].

Cellulose is the most abundant polymer in the biosphere and has many technical applications, including food production. The development of cellulose technology in the 21st century has led to the emergence of nanocellulose (NC), which has widely varying chemical and physical properties and, therefore, has fundamentally new areas of application in biomedicine and the food industry. The aim of this work is to review the literature on the structure, sources, methods for obtaining nanocelluloses, including methods for their chemical modification, current and prospective applications in the food industry, packaging materials, biomedicine, etc. Material and methods. For the analysis, sources were selected mainly for the period from 2014 to 2022, contained in the international databases PubMed, WoS and Scopus and meeting the requirements of scientific reliability and completeness. Results. Among the main types of NC there can be identified nanofibrous cellulose (NFC), consisting of fibers longer than 500 nm and about 10-20 nm thick, and nanocrystalline cellulose (NCC) with particles 100-500 nm long and less than 100 nm in diameter. A special group of materials includes bacterial NC (BNC) produced by microorganisms and representing entangled coils or layers of cellulose fibers with a thickness of less than 100 nm. Significant changes in the physical, chemical and functional properties of NC can be achieved by its physical and chemical modification, which leads to a change in swelling, an increase in the mechanical strength and stability of hydrogels, and compatibility with synthetic polymers. NFC, NCC and BNC are offered as food ingredients for inclusion both in mass consumption products and in specialized foods for dietary and therapeutic uses, as well as in the so-called «functional products¼, for which manufacturers declare the ability to influence actively on the state of intestinal microflora and digestive function. In biomedical applications, of great interest is the biocompatibility of BNC with various cell types in combination with biodegradability, which makes it possible to create new types of materials for reconstructive surgery, effective and safe dressings. When used as packaging materials, NC products successfully compete with synthetic polymers without causing long-term environmental pollution. Factors hindering the introduction of NC products into practice are the gaps of knowledge of NC biological action, combined with the risks caused by possible residual amounts of chemicals and biochemical reagents, bacterial toxins, enzyme preparations and microorganisms-producers in the composition of NC. Conclusion. There is an important task to develop a system for regulating NCs and products with its content, in accordance with the technical regulations of the Customs Union of the EAEU.

[Minor antibiotics residues in food: what are the risks for consumers].

The problem of contamination of foodstuffs with antibiotic residues does not lose its relevance everywhere, and the most widespread are the quantities of contaminants at the level of regulated values. This raises the concern of specialists in the field of production and processing of livestock products and initiates their appeal to scientific organizations of the hygienic profile for an explanation of the potential health risks associated with the consumption of low doses of antibiotics with food. Material and methods. Analysis and synthesis of data from scientific sources and official documents in the field of assessing health risks when consuming antibiotics with food, with an emphasis on the effects of minor amounts [at the level of sub-inhibitory values below minimum inhibitory concentrations has been carried out. Results and discussion. The issues of direct and indirect human exposure to antibiotics in low doses, including the formation of resistance of intestinal bacteria and the acceleration of the evolution of microbes, accumulation in the organism, the likelihood of allergic reactions, as well as preservation in foodstuffs during heat treatment, have been highlighted. The role of low doses of antibiotics as analogues of biologically active metabolites of bacteria is demonstrated, which, without exerting a toxic effect on the macroorganism, serve as triggers of changes in the microbial ecosystems of humans, animals and habitats through the mechanism of switching on regulation transcription in microbes and activation of horizontal transfer of genes encoding resistance and associated traits. The negativity of the disproportionately wide use of tetracyclines in agriculture, as the cause of the globalization of transferable resistance, has been emphasized, which was justified by the data on the ability of their sub-inhibitory doses to induce the expression of the largest number of mechanisms of its formation and most strongly provoke the horizontal transfer of linked genes between microbes. The need to preserve the current in the EAEU MRL for tetracyclines (0.01 mg/kg product), located in the concentration zone 0.05-0.1 minimum inhibitory concentrations for most sensitive bacteria, safe in terms of resistance induction, has been confirmed. Conclusion. Adequate rationing of antibiotics in food is recognized as a risk management measure for both direct and indirect negative consequences for human health, since the need to ensure MRLs requires manufacturers to strictly adhere to doses, duration of use and withdrawal periods of drugs. This reduce the likelihood of developing resistance in the gastrointestinal tract of animals, the load of the environment by resistant microbes and their transmission along the food chain. The underlying establishment of microbiological acceptable daily intake should be improved by including the selection of intestinal bacteria co-resistance under the influence of a regulated drug, as a marker of the induction of horizontal transfer of resistance genes, in the biological endpoints of determining.

[Risk assessment of glucoamylase and xylanase complex from Aspergillus awamori Xyl T-15].

The introduction of methods for food production using microbial synthesis, including those obtained with the help of genetically modified (GM) microorganisms, at the present stage, allows to increase production volumes and reduce the cost of food. At the same time, such products in accordance with TR CU 021/2011 "On food safety" are classified as a "novel food"¼ and can be placed on the market only after its risk estimation for health. The emergence of new data and research methods in the last years has made it necessary to improve the risk assessment system for this category of food. The aim of the research is to develope risk assessment approaches of food obtained by microbial synthesis on the example of the GM strain Aspergillus awamori Xyl T-15 and the enzyme preparation (EP) (a complex of glucoamylase and xylanase) produced by it. Material and methods. Outbred ICR mice (CD-1) and Wistar rats (males and females) were used in the experimental studies. Investigations of GM strain A. awamori Xyl T-15 virulence and its ability to disseminate internal organs have been carried out. Acute and subacute (during 80 days) toxicity of EP (a complex of glucoamylase and xylanase) have been studied. Results. The presented experimental data allow us to make a conclusion about the avirulence of the A. awamori Xyl T-15 strain, the lack of ability to disseminate internal organs (invasiveness). At the same time, the strain is characterized by the ability to produce mycotoxins (ochratoxin, fumonisin B2, T-2 and HT-2 toxins). The EP, a complex of glucoamylase and xylanase from A. awamori Xyl T-15, has a low oral acute toxicity for rats (LD50>5000 mg/kg). I ntragastric EP administration at doses of 10, 100 and 1000 mg/kg of body weight during 80 days had not revealed adversely affect on the rate of weight gain in animals, indicators of anxiety and cognitive function, and some studied biochemical indicators. At a dose of 100 mg/kg b.w. or more, there were changes in the relative mass of organs (lungs, kidneys, adrenal glands), small shifts in the parameters of erythropoiesis and leukocyte formula, at a dose of 1000 mg/kg b.w. - an increase in oxidative DNA destruction. T he most pronounced and dose-dependent was the effect of the EP on hepatocyte apoptosis. According to this indicator, the not observed adverse effect level (NOAEL) for EP is not more than 100 mg/kg b.w. in terms of protein. The main target organ for the toxic effect of EP is the liver. Conclusion. The data obtained demonstrate the necessity to conduct an additional analysis of the risks of possible negative effects of EP, namely, to study its impact on the gut microbiocenosis and the immune status of experimental animals, to analyze the presence of determinants of pathogenicity and antibiotic resistance, DNA of selective marker genes of A. awamori Xyl T-15 strain by PCR analysis and DNA sequencing methods.

[Risks associated with the consumption of inorganic and organic arsenic].

It is known that the chronic intake of arsenic (As) leads to the development of multisystem pathologies. In the case of high levels of As consumption, the risks of negative effects of exposure to inorganic and methylated forms persist for decades. The International Agency for Research on Cancer (IARC) has established that all inorganic forms of As are absolute carcinogens (group 1). Methylated forms of As are classified as substances possibly carcinogenic to humans (group 2b). Not metabolized in the human body forms of organic As are not carcinogenic to humans (group 3). The aim - assessment of health risks of various forms of As contained in food, including seafood. Material and methods. The scientific data regarding the risks associated with As contamination of food obtained by using PubMed, Web of Science, Google Scholar databases, legislative and regulatory acts of the Eurasian Economic Union, the Russian Federation, the Codex Alimentarius Commission, the European Union and other coun tries have been analyzed. Results. The analysis of the available data showed that the degree of As toxicity decreased in the following order: glutathione of dimethylarsonic acid (DMAIIIGl) > methylarsic acid (MMAIII) > dimethylarsic acid (DMAIII) > arsenic hydrocarbons (AsHC) > arsenite (AsIII) > arsenate (AsV) > trimethylarsine (TMAIII) > methylarsonic acid (MMAV) > dimethylarsonic acid (DMAV) > DMAIII-sugar glyceride > DMAV-sugar glyceride > thio compounds of DMAV > arsenosugarsIII > arsenosugarsV > tetramethylarsonium chloride (TETPA) > trimethylarsine oxide (TMAO), arsenocholine (AsC) > arsenobetaine (AB). Consequently, the toxicity of some methylated and organic forms of As (for example, DMAIIIGl, AsHC) may be higher than that of its inorganic forms. It is known that As is found in foods mainly in organic forms. When ingested with food, As organic forms are metabolized and, thus, could cause a number of negative effects in the organism. Conclusion. High levels of organic and inorganic forms of As in food, including seafood, could have a negative impact on the health of the population, which makes it necessary to conduct additional assessments of the health risks of various forms of As entering the body. The insufficient amount of data on the toxicity of organic forms of As indicates the impossibility of separate setting of safety maximum levels for organic and inorganic forms of As in foods.

[Nutriome as the direction of the "main blow": determination of physiological needs in macro- and micronutrients, minor biologically active substances].

One of the essential parts of fundamental research in Nutrition Science is the determination of the physiological requirements of humans for energy and food substances. Research that has been carried out in this area over the past 90 years, consistently develops and improves the norms of physiological requirements for energy and nutrients for various groups of the population of the Russian Federation. In the 50 years of the last century in this research field, determining the values of daily intake for macronutrients (proteins, lipids and carbohydrates), was in the first place. Then the Era of micronutrients (vitamins, minerals, trace elements) was started, and, finally, now there is the Era of minor food biologically active substances. More and more facts are accumulating about their leading role in regulating metabolism. They can be recognized as endogenous regulators, the primary vital components involved in the formation of human health. In recent years, the new definition of Nutriome is introduced into Nutrition Science. It is considered as a set of essential nutritional factors to maintain a dynamic equilibrium between human being and the environment, aimed to ensure viability, the preservation and reproduction of the species, keeping the adaptive capacity, the system of antioxidant defence, apoptosis, metabolism, and immune system function. The Nutriome is a formula for optimal nutrition, which is continually being improved and supplemented. Knowledge of this formula is the key to forming an optimal diet for a person, and, therefore, to save their health. It is evident that at the population level, the Nutriome has its characteristics, its structure for each age period of human life. The need to develop a formula for optimal nutrition and, consequently, updating nutrient-based dietary guidelines is induced by socio-economic and demographic changes in population, changes in anthropometric characteristics of children and adults, increasing prevalence of socially significant non-communicable diseases, developing studies of the significance of particular food substances and establishing the relationship between nutrition and health.

[Chemical food safety: development of methodological and regulatory base].

The review presents the results of studies carried out in the Federal Research Centre of Nutrition and Biotechnology in the direction of food toxicology, the purpose of which was to improve the risk assessment methodology, substantiate hygienic regulations for the content of chemical contaminants in foodstuffs and develop methods for their detection and quantitative determination. New challenges and problems associated with the control and regulation of chemical contaminants in foods are associated, firstly, with the identification of previously unrecognized chemical factors harmful to human health, and, secondly, are caused by the progress of technologies, accompanied by the emergence of new sources of nutrients and methods of processing foodstuffs, which, along with many benefits and advantages, creates new potential risks to consumer health. Among the priority chemical pollutants, which should be mentioned currently as objects of improved regulation and control methods, are toxic elements (organic and inorganic forms of arsenic, mercury, nickel), veterinary drugs, phycotoxins, phytotoxins, new mycotoxins, various forms of polychlorinated biphenyls and polycyclic aromatic hydrocarbons, biologically active substances of plant origin, concentrated during the production of extracts, as well as so-called technological contaminants, food additives, residual amounts of technological aids. An independent problem is the assessment of risks from nanoparticles and nanomaterials used in the production of foodstuffs, as well as enzyme preparations and food ingredients produced with the help of genetically modified microorganisms. The system of toxicological and hygienic assessment and control of chemical contaminants in foodstuffs operating in Russia is constantly being improved on the basis of new scientific data to substantiate the permissible levels of their content in products and new methods of analysis. The results obtained are reflected in the regulatory documents of the Russian Federation and the Eurasian Economic Union.

[COVID-19: new challenges for medical science and practical health].

Currently, due to the wide spread of the new coronavirus infection COVID-19 and the need for anti-epidemic measures, medical science should integrate all efforts to ensure, on the one hand, at the global level - the fight against the spread of infection, on the other hand, at the individual level - increasing the adaptive capacity and immune response of the organism to protect against COVID-19. Nutrition is the most important factor determining human health and the functioning of all mechanisms to protect a person from negative environmental factors. For the prevention and treatment of new coronavirus infection COVID-19, a significant role is played by the correction of eating disorders, including vitamin and micronutrient deficiency. Federal Research Centre of Nutrition and Biotechnology, together with Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), prepared Recommendations on nutrition for children and adults, requiring a self-isolation regime or quarantine at home in connection with COVID-19. In order to promptly inform and advise the population on nutrition optimization in the early days of anti-epidemic measures, an information reference Contact Center was created and is continuously functioning on the basis of the Federal Research Centre of Nutrition and Biotechnology. Equally important is the implementation of measures aimed at the prevention of food contamination with COVID-19 agent. In this regard, the Federal Research Centre of Nutrition and Biotechnology, together with Rospotrebnadzor prepared guidelines on measures to prevent the transmission of a new coronavirus infection through foods. Another aspect that the medical community has faced in connection with the pandemic is the need to reorient specialized medical organizations that have not previously worked with patients with infectious diseases in order to create Clinical centers for the treatment of the new coronavirus infection COVID-19. Thus, in the context of the spread of the new coronavirus infection COVID-19, many areas of medicine are involved in the process of providing anti-epidemic measures. Successful completion of the tasks will significantly reduce the negative consequences of the COVID-19 pandemic for the state and citizens.

[On the regulate tropane alkaloids in grain products].

Tropane alkaloids (TA) are metabolites of various plant species in the families Brassicaceae, Solanaceae and Erythroxylaceae. Seeds of these weeds are found in flax, soy, sorghum, millet, sunflower, buckwheat and food products obtained from them, in herbals used as a part of food supplements and herbal teas. Despite the fact that the contamination of grain seeds by various parts of weeds reduces by sorting and clean up, a certain amount of TA gets into processed foods. An analysis of the consumption of TA with all types of foods, conducted by the European food safety Agency (EFSA), showed that TA intake with ration of various population groups can exceed the established level of single safe intake (ARfD) - 0.016 µg/kg of body weight (by 11-18% for adults, and by 5-25% for children depending on the age). The aim of the research was to justify the need to introduce regulations for the safe content of TA in grain products. Material and methods. The study process used hygiene, analytical methods, expert assessments on the basis of generalization and analysis of contemporary scientific researches published in databases Scopus, Web of Science, PubMed, RISC, Russian and international regulatory and legislative documents. Results. The established risks associated with TA contamination of grain and grain-based foods, as well as food supplements based on herbs and herbal teas, make it necessary to monitor food products for it's presence. Conclusion. Due to the greater study of the risks associated with the presence of atropine and scopolamine in foods, scientific justification of safe levels of these TA in foods based on cereals, including baby foods for children under 3 years old containi ng millet, sorghum, buckwheat or products based on these cereals is required.

[Peroral toxicological assessment of bentonite nanoclay used in the food industry].

Bentonite nanoclay (NC) manufactured from the natural sedimentary mineral bentonite contains more than 90% montmorillonite. Currently, it is widely used in food industry as processed aids - adsorbents for the purification of vegetable oils and beverages. Clay minerals have also applications as food additives and components in composite package materials. In vitro studies have shown that various forms of NC exerted cytotoxicity in many cell lines, whereas in vivo evidence of NC oral toxicity is contradictory. Therefore, this study aimed to assess the acute oral toxicity of NC and to evaluate its toxicological characteristics in a subacute 92-day experiment on Wistar rats with a daily oral administration in doses of 1, 10, and 100 mg/kg body weight (bw). Material and methods. The NC acute toxicity was evaluated in 8 male and 8 female rats with the initial bw 236±10 and 203± 10 g, respectively. NC was administered as an aqueous dispersion intragastrically at a dose of 5 g/kg bw. On the 14th day (end of the experiment), an autopsy of the chest and abdominal organs was performed. The subacute experiment was carried out on 64 male rats with an average initial bw of 117±7 g. During the experiment the levels of anxiety and memory function were evaluated using the test "Conditional reflex of passive avoidance". On the 90th day of the experiment, diurnal urinary excretion of creatinine and selenium was evaluated. At the end of the experiment, the integral parameters, the state of the intestinal wall permeability were assessed. Hematological and biochemical parameters were examined in blood, the content of non-protein thiols and the number of cells in apoptosis were determined in liver, and the state of cultivated microbiome populations was studied in cecum. Results. The results of the determination of NC acute toxicity showed the absence of rat's mortality and specific pathological changes in the internal organs at a dose as large as 5000 mg/kg bw, which allowed attributing NC to the V hazard class. Nevertheless, under the conditions of the 92-day experiment, NC caused some adverse biological effects on rat's organism. So, even at an NC dose of 1 mg/kg bw, there was a sharp inhibition of the symbiotic bifidobacterium growth, an increase in platelet count, in LDL and the LDL/HDL ratio, together with the presence of hypertriglyceridemia. At a dose of 10 mg/kg bw, an increase in spleen mass and a decrease in the de Ritis coefficient (AsAT/AlAT) were established. At a dose of 100 mg/kg bw there were shifts in the leukocyte blood count, an excessive enterococci growth in the cecum, significantly increased animal bw, along with the decrease of AsAT/AlAT and the level of serum nitrogen metabolites, indirectly indicating inhibition of catabolic processes. However, at the highest dose of NC, intestinal absorption of the protein antigen - ovalbumin, was apparently completely blocked. Conclusion. The data obtained have shown that NC has potentially adverse effects on the rats mainly at a dose of 100 mg/kg bw, nevertheless, its NOAEL in the 92-day daily oral exposure experiment is probably less than 1 mg/kg bw.

[Lipoic acid: physiological role and prospects for clinical application].

α-Lipoic acid (also known as thioctic acid) is a natural vitamin-like compound. Lipoic acid contains asymmetrical carbon, which causes the presence of two possible optical isomers (enantiomers): R-lipoic acid (levogyrate isomer) and S-lipoic acid (rightspinning isomer). Lipoic acid functions as a cofactor for several important mitochondrial multienzyme complexes, enhances the uptake of glucose by the cells, and modulates the activity of various signaling molecules and transcription factors. It was shown that α-lipoic acid and its derivative, dihydrolipoic acid, have a direct antioxidant effect due to the neutralization of reactive oxygen species that are destructive to DNA, proteins and lipids of cells. Dihydrolipoic acid enhances the antioxidant properties of ascorbic acid, glutathione and ubiquinone. Available evidence suggests that supplementation with lipoic acid reduces the symptoms of peripheral diabetic neuropathy. Results from randomized controlled trials show that high doses of lipoic acid can improve the glycemic profile of subjects with metabolic disorders. Lipoic acid can be used to control body weight in people with obesity. R-Lipoic acid is synthesized in the human body and is contained in foods in a form covalently associated with lysine (lipoyllysine). Its dose in dietary supplements significantly exceeds the amount in the diet. Most dietary supplements contain a racemic mixture of R- and S-lipoic acid.

[Characteristics of the diet and nutritional status of workers at various industrial enterprises of the Sverdlovsk Region].

Alteration of food patterns leads to changes in nutritional status, thus contributing to the development of non-communicable diseases accounting for over a half of all causes of death of the population of our country. Poor working conditions and occupational hazards play an important role in inducing metabolic disorders and cardiovascular diseases. The objective of joint studies conducted by two Healthy Nutrition Centers located in the cities of Yekaterinburg and Moscow was to assess the diet and nutritional status of workers at two industrial enterprises of the Sverdlovsk Region. The total of 347 unrefined copper production workers (Plant 1) and 267 iron ore miners (Plant 2) were included in the study (the average age was 45.7±0.4 and 50.4±0.6 years, respectively). The study design envisaged a study of actual nutrition by a frequency method, anthropometric indices, total body composition by bio-impedancemetry, and nutritional status biomarkers using biochemical blood indices. The workers' diet was characterized by a high energy value (more than 2,500 kcal/day) with an excess of total and saturated fats (40.7-41.0 and 15.2-15.3% by the calorie content) as well as mono- and disaccharides (19.0-21.0% by the calorie content). Vitamins C and A consumption of the iron ore miners was 78% (p<0.01) and 27% (p<0.05) lower than that of the unrefined copper production workers, respectively. High (>1.0) waist to hip ratios were estimated in 28.5% of the workers. Obesity (BMI>25.0 kg/m2) was established in 36-42% of our subjects and the fat mass excess - in 81% of them. High serum concentrations of low-density lipoproteins were measured in 28 and 35% of the workers of both plants, respectively. The metabolic syndrome was identified in 27.0% of Plant 1 workers and in 44.2% of Plant 2 miners, whereas cardiovascular diseases were diagnosed in 25.9 and 56.5% of the workers, respectively. The effect of genetic factors (rs993609 polymorphism of FTO gene and Trp64Arg polymorphism in ADRB3 gene) on the development of obesity and metabolic disorders was demonstrated.

[Yessotoxin: risk assessment for public health. Justification of regulations of content in seafood].

Yessotoxin and its derivatives (about 90) are isolated from algae belonging to the species Protoceratium reticulatum, Gonyaulax cf. Spinifera, Lingulodinium polyedrum and from invertebrate organisms that feed on these algae. Previously yessotoxin have been associated with the group of diarrheal toxins. Later studies of the possible impact of yessotoxin on the activity of alkaline phosphatase allowed to exclude them from this group. Yessotoxin causes a violation of calcium entry in the cells, which, in turn, effects the calcium-calmodulin system and thus influences into homeostasis of the organism as a whole. It was shown that yessotoxin induces a biphasic change in the concentration of adenosine monophosphate, an initial increase with a subsequent relative decrease, within some minutes after adding the toxin to the lymphocytes cell culture. Yessotoxin has effects on immune system; which is manifested in an increase of cytokines level, by inducing the expression of the genes encoding them. Yessotoxin have impact into processes of cell adhesion via E-cadherin and, thus, could be an important factor in the development of Alzheimer's disease. It has been established that yessotoxin caused the development of apoptosis. In those cases all three mechanisms of cell death took place - apoptosis, paraptosis and autophagy. Yessotoxin's acute toxicity doses according to different data are from 100 to 500-750 µg per 1kg of body weight. Yessotoxin's acute reference dose (ARfD) - 25 µg/kg of body weight per day. The results of the analysis of yessotoxin level in shellfish meat showed that none of the studied samples contained more than 3.75 mg yessotoxin equivalents/kg shellfish meat. This level has been adopted by the European Union as the maximum acceptable level of yessotoxin in shellfish meat (EU Regulation N 786/2013). Presented data on the mechanism of action, toxicity and prevalence of yessotoxins make it necessary to establish regulations of their content in seafood, placed on the markets of the Eurasian Economic Union.

Effect of Silver Nanoparticles on Protein Composition of Rat Liver Microsomal Fraction.

We studied the effect of oral administration of metallic silver nanoparticles to rats on the proteome of the liver microsomal fraction. Nanoparticles (5-80 nm) were administered daily to growing Wistar male rats over 92 days. Controls received pure water. To control the effect of the carrier, the rats were administered aqueous solution of a stabilizer polyvinylpyrrolidone. The protein composition (proteome) of the liver microsomal fraction was analyzed by 2D-electrophoresis with identification of variable protein spots using the high-resolution nanoHPLC-MS/MS. Eight, 6, and 8 proteins absent in the control groups appeared in the microsomal fraction under the action of nanoparticles in doses of 0.1, 1, and 10 mg/kg body weight, among these, proteasome activator complex subunit 1 (Psme1 gene), and the heat shock protein HSP60 (Hspd1 gene) were reliably identified. The consumption of silver nanoparticles led to disappearance of protein of ß2a tubulin chain (Tuba1b gene) from the microsomal fraction. The expression of catalase, present in the proteome of the liver microsomal fraction in animals of all groups was significantly decreased after consumption of silver nanoparticles in doses of 0.1 and 10 mg/kg. The observed changes in the proteome are considered as manifestations of hepatotoxicity of silver nanoparticles and can be related to the antagonistic effect of silver on the status of the essential trace element selenium.

[Physiological needs and effective doses of vitamin D for deficiency correction. Current state of the problem].

In addition to classic role of vitamin D in musculoskeletal health over the last decade it was shown that low blood serum concentrations of 25(OH)D are associated with a number of non-skeletal disorders including cancer, high blood pressure, age-related cognitive decline, disorders of the immune and reproductive systems, etc. The prevention of the development of these diseases is reached under considerably higher concentrations of the vitamin in the blood serum, than is necessary to maintain the normal state of the bone tissue, to regulate calcium absorption and homeostasis. To maintain the concentration of the circulating form of vitamin D 25(OH)D in blood serum at a level ensuring optimum course of vitamin D-dependent biochemical processes (greater than 50 nmol/l), a higher intake of vitamin D is necessary. Reduced blood concentration of vitamin D (less than 30 ng/ml) occurs in 50-92% of the adult population of working age in our country, regardless of the season. The causes of vitamin D deficiency are the low efficiency of its endogenous synthesis in the skin due to insufficient sun exposure owing to the geographical position of our country, and inadequate intake of the vitamin from food as a result of rare consumption of the main source of this vitamin - oil-rich sea fishes. In the Russian Federation the current daily norm of physiological need (10 mcg) to some extent allows to maintain skeletal features, but such consumption does not allow to achieve adequate levels of the circulating form of vitamin D in the blood, which provide optimal manifestation of nonskeletal functions of this vitamin. The analysis of the available information and the prevalence of vitamin D deficiency point to the need to increase the physiological needs of vitamin D to 15 micrograms (600 IU/day). Simultaneously it should be recognized that vitamin D daily intake of 25 micrograms (1000 IU/day) is an effective dose to improve vitamin D status and at the same time is safe. Higher vitamin D intake can reliably eliminate the existing deficit of this vitamin in the population and maintain blood concentration of 25(OH)D at an optimum level, which will provide health benefits.

[Subacute oral toxicity in vivo of multi-walled carbon nanotubes].

Multiwall carbon nanotubes (MWCNTs) are regarded as environmental pollutants with increased risk. Recently MWCNTs have attracted attention as a promising component of packaging materials for food products, as carriers for agricultural plant growth stimulants, agrochemicals components and advanced pesticides, which creates the possibility of their exposure through the gastrointestinal tract. Objective of the research is assessment of sub-acute oral toxicity to rats of MWСNTs in an experiment lasting 100 days. MWCNTs preparation «Taunit-M®¼ was preliminary characterized by electron microscopy and Raman light scattering. Nanomaterial was administered to animals as sonicated dispersion in water with 1% by weight of nonionic surfactant Tween 20. The experiment was performed on 80 growing male Wistar rats with initial body weight (b.w.) 86±2 g. Rats of experimental groups (from 2nd to 5th) received MWCNTs dispersion instead of drinking water, the animals of the 1st control group - a carrier solution (Tween 20). Doses of MWCNTs consumed were, respectively, in groups 1-5: 0; 0.01; 0.1; 1.0 and 10 mg/kg b.w. Hematological and biochemical indices of blood were determined together with the activity of glutathione peroxidase of erythrocytes, the content of non-protein thiols in the liver, excretion of 8-hydroxy-2'-deoxyguanosine (8-oxo-G) and content of the main and transient components of gastrointestinal microbiocenosis in the cecum contents. Apoptosis of hepatocytes was studied by flow cytometry. As a result MWCNTs led to increase of blood glucose and creatinine in rats in group 2, a significant decrease in the number of neutrophils and monocytes by increasing the number of lymphocytes, decreased platelet volume, the most pronounced also in group 2, receiving the lowest dose of MWCNTs. There were no signs of oxidative DNA damage identified. At the lowest dose MWCNTs caused a significant decrease in the number of bifidobacteria, increase - citrate-assimilating Enterobacteriaceae, hemolytic aerobic microorganisms and yeast. These changes in the microbiota should be considered as adverse, apparently leading to disturbances in the immune function.

[Carbon nanotubes: mechanisms of the action, biological markers and evaluation of the (review of literature)].

The article contains the review and analysis of data on the mechanisms of the toxic action of carbon nanotubes (CNTs) on the body and available results of CNT toxicological evaluation after inhalation and oral routes of the action. Identification of cellular and molecular mechanisms of CNTs toxicity allows to justify the list of the most sensitive biochemical toxicity markers that could be used for monitoring the occupational effects of CNTs and serve as a promising target for the corresponding pharmacological and immunopharmacological interventions aimed on specific prophylaxis and therapy of diseases caused by CNT. A considerable amount of experimental data obtained in vivo on inhalation animal models allows to establish the hygienic standardfor CNT in the air of the working area. As to safe levels of the oral route of CNT it needs further study for their reliable assessment. The search and selection of sources for the review was executed with the use of public databases, including (in order of relevance) PubMed, Scopus, Google Scholar, and RISC, for the period from 2004 to 2017.

[Toxicological evaluation of colloidal nano-sized silver stabilized polyvinylpyrrolidone. III. Enzymological, biochemical markers, state of antioxidant defense system].

Nanosized colloidal silver (NCS) with primary nanoparticles (NPs) size in the range of 10-80 nm in aqueous suspension was administered to rats with initial weight 80±10 gfor the first 30 day intragastrically and for lasting 62 days with the diet consumed in doses of 0.1; 1.0 and 10 mg/kg of body weight b.w) per day based on silver (Ag). The control animals received deionized water and carrier of NPs - aqueous solution of stabilizer polyvinylpyrrolidone. Activity (Vmax) was determined in liver of microsomal mixed function monooxygenase isoforms CYP 1A1, 1A2 and 2B1 against their specific substrates, the activity of liver conjugating enzymes (glutathione-S-transferase and UDP-glucuronosyltransferase) in the microsomal fraction and a cytosol, and the overall and non-sedimentable activities of lysosomal hydrolases. In blood plasma there were evaluated malonic dialdehyde, PUFA diene conjugates, in erythrocytes - the activity of antioxidant enzymes. A set of standard biochemical indicators of blood serum was also determined. The studies revealed changes in a number of molecular markers of toxic action. Among them - the increase in the activity of key enzymes I and II stages of detoxification of xenobiotics, indicating its functional overvoltage; reducing the activity of glutathione peroxidase (GP), the total arylsulfatase A and B, ß-galactosidase (in the absence of changes in their non-sedimentable activity), levels of uric acid, increased alkaline phosphatase activity. These changes occurred mainly at the dose Ag of 10 mg/kg b.w., except for the GP to which the threshold dose was 1 mg/kg b.w. No significant changes in the studied markers in a dose Ag 0,1 mg/kg b.w. were identified. Possible mechanisms of the toxic action of silver NPs are discussed.