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SCIENTIFIC RELEVANCE. Studies of the inhalation administration of chemicals are associated with challenges in designing experiments. The parameters to be selected include the experimental animal species, the inhalation chamber, and the mode of inhalation (dynamic or static).AIM. This study aimed to analyse the practical application of regulatory requirements to non-clinical studies of the inhalation toxicity of chemicals.DISCUSSION. This review compares international and Russian standards for studying the inhalation toxicity of chemicals, including GOST 32542-2013, GOST 326432020, GOST 32636-2020, GOST 32383-2013, and GOST 2646-2014. The improvement of the legal and regulatory framework correlates with adopting the Good Laboratory Practice and the risk-based approach to categorising test substances into hazard classes. Hazard classes are determined in rodents without dose extrapolation to humans. The authors present the differences between the main guidelines on inhalation exposure in rodent studies of acute, subacute, subchronic, and chronic toxicity. The article describes current approaches to assessing the inhalation toxicity of chemicals, which allow researchers to replace animal studies with in vitro tests.CONCLUSIONS. According to the current regulatory standards, inhalation toxicity is studied in rats/mice, which have anatomical differences from humans. As an alternative to animal studies, researchers are developing and validating in vitro methods, which yet require regulatory review and approval.

The purpose of the study was to evaluate in vitro cytotoxicity and in vivo sub-acute toxicity of conditioned medium obtained from rat bone marrow-derived mesenchymal stem cells directed to osteogenic differentiation. Material and methods. Conditioned medium was obtained by culturing rat bone marrow-derived MSCs induced under osteogenic condition. Results and discussion. Conditioned medium from rat bone marrow-derived MSCs was shown to have no significant cytotoxic effect on Ehrlich adenocarcinoma cell culture and in vitro expanded peripheral blood mononuclear cells from healthy donors. The use of MSC-CM did not have a significant effect on the state of experimental SD rats, the total body weight and growth rate of animals. A pathomorphologic study revealed no any abnormalities associated with MSC-CM injection. Conclusion. The use of conditioned medium from rat bone marrow-derived mesenchymal stem cells stimulated under osteogenic condition was found to be safe for both in vitro studies (with respect to Ehrlich adenocarcinoma cell line and peripheral blood mononuclear cells from healthy donors) and in vivo studies (injection of MSC-CM to animals).

The object of the study was amorphous silica dioxide (SiO 2 ), which is widely used as a food additive (E551), a subsidiary component in pharmaceutical preparations, perfumery and cosmetic products etc. In the specification of JECFA silica dioxide does not have information about the size of its particles, which allows the use of fine amorphous SiO 2 , obtained by gas phase hydrolysis of tetrachlorosilane as a food additive. This material, known as the "Aerosil", is characterized by the size of the specific surface area of 300–380 m 2 /g and the size of its relatively weakly agglomerated particles of 6–30 nm, i.e., it is a nanomaterial. In the biological model the morphological changes in organs and tissue systems on oral supplementation of nanoscale particles of silica dioxide were studied. Wistar male rats were given nanosized silica dioxide with specific surface area of 300 m 2 /g and primary nanoparticle size on the basis of data of electrical, atomic-powered microscopy, and dynamic light scattering in the range of 20–60 nm during 92 days. Light microscopic morphological examination of organs of rats showed a relatively mild inflammation in the structure of parenchymal organs (liver, kidney), not showing a certain dose-dependent nanoparticles. The most pronounced changes were in ileum morphology, consisting of a massive lymph macrophage and eosinophil infiltration of villi, without any apparent violation of their epithelial layer structure, which indirectly indicates the absence of violations of the barrier function of the intestinal epithelium. At the maximum dose of 100 mg/kg bw, the increased immune response was the most significant in the wall of the ileum. The results indicate the potential risks to human health when using SiO 2 having a specific surface area of 300 m 2 /g or higher in the composition of food products as a food additive.

Abstract. The ability of petroleum products to initiate cumulative effects was assessed in experimental intragastric admission to male albino rats for one month. The analysis of skin-resorptive effects was performed using "test-tube" method on the skin of rats’ tails. It has been established that petroleum products can penetrate the intact skin and, with repeated admission, cause a general toxic effect. There were reductions bodyweights, the negative effect on the function of the kidneys and liver, changes of hematological parameters, as well as activation of the antioksidatnoy system. Repeated intragastric administration does not lead to the death of the animals testifying to the lack of accumulation capacity for petroleum products at the level of functional mortal effects, the cumulation coefficient being > 5.1. Negative impact on urinary function and hepatobiliary system, changes in hematological parameters and activation of the «lipid peroxidation – antioksidant defense» were observed.

Nano-sized colloidal silver (NCS) stabilized with polyvinylpyrrolidone (PVP) containing nanoparticles (NPs) of silver with a diameter of 10-80 nm was administered to growing male rats (body weight 80±10 g) during the first 30 days by intragastric gavage and then for 62 days with diet consumed in doses of 0.1, 1.0 and 10 mg/kg of body weight per day based on silver (Ag). The control animals received deionized water and PVP. The composition of microbiota from the cecum was studied using standard microbiological methods with determination of the main and transient components, together with antagonistic activity of symbiotic bifidobacteria. Expression of antigens CD45RA, CD3, CD4, CD8, CD161a on lymphocytes (Ly) of peripheral blood was determined by flow cytometry; blood serum levels of cytokines IL10, IL13, TNFα were examined by ELISA. It was shown that subacute administration of colloidal Ag in all studied doses did not lead to significant changes in the composition of the main components of normal microbiota, providing, however, the inhibitory effect on the growth of some transitory components probably including opportunistic species of microorganisms. Among the studied immunological parameters decreased amount of B-Ly was noticed at the highest dose of the NCS, while changes in the other parameters of the immune system were depended ambiguously on the dose of the product. The results were analyzed in conjunction with the data of previous publications concerning the impact on the NCS on integrated, morphological, hematological, biochemical and enzymological indexes of animals in the 92-day experiment. It was concluded that significant symptoms of NCS sub-acute oral toxicity manifested starting from a dose of 1 mg/kg body weight of Ag, and the maximum not observed adverse effect dose (NOAEL) can be estimated as 0.1 mg/kg body weight., (Copyright© GEOTAR-Media Publishing Group.)