No 6 (2020)

Cover Page

Full Issue

Articles

FROM THE EDITOR-IN-CHIEF

Khamidulina K.K.

Abstract

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Toxicological Review. 2020;(6):2
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MANIFESTATIONS OF SUBACUTE SYSTEMIC TOXICITY OF LEAD OXIDE NANOPARTICLES IN RATS AFTER AN INHALATION EXPOSURE

Sutunkova M.Р., Solovyeva S.N., Chernyshov I.N., Klinova S.V., Gurvich V.B., Shur V.Y., Shishkina E.V., Zubarev I.V., Privalova L.I., Katsnelson B.A.

Abstract

Outbred white female rats were exposed to an aerosol of lead oxide nanoparticles in a nose-only inhalation setup at an average concentration of 1.30 ± 0.10 mg / m3 during 5 days for 4 hours a day. In parallel, the control group of rats was subjected to sham exposure under similar conditions. The deposition of nanoparticles in the lungs and in the olfactory region of the brain was detected using transmission electron microscopy. Some disorders of the body state were detected in the exposed group, some of which can be considered as the result of a lead-specific toxic effect (an increase in the proportion of reticulocytes and in urinary excretion of δ-aminolevulinic acid), and others - the result of nanoparticles circumventing the blood-brain barrier (axon demyelination, vacuolization of the neurons’ cytoplasm).
Toxicological Review. 2020;(6):3-13
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EXPERIMENTAL EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF OXYMETHYLURACIL IN COMBINATION WITH KNOWN MEDICINES (MEXIDOL, TONAROL, ACETYLCYSTEINE)

Repina Е.F., Karimov D.O., Timasheva G.V., Khusnutdinova N.Y., Musina L.A., Gimadieva A.R., Baigildin S.S., Smolyankin D.A., Valova Y.V.

Abstract

The article presents the results of morphological changes in the liver of rats after acute liver injury induced by carbon tetrachloride and prophylactic correction of injuries by combinations of oxymethyluracil with different types of medical products: «Mexidol», «Tonarol» and Acetylcysteine. The best corrective effect was established after applying a combination of oxymethyluracil with «Tonarol». Thus, according to the results obtained, the studied drugs combinations can be arranged in the following sequence in accordance with decreasing of hepatoprotective activity: OMU / «Tonarol» > OMU / Acetylcysteine> OMU / «Mexidol».
Toxicological Review. 2020;(6):14-20
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REVISION OF MAC IN THE AIR OF THE WORKING AREA OF TEREPHTHALIC ACID

Khamidulina K.K., Radilov A.S., Dulov S.A., Zemlyanoy A.V., Beltyukov P.P., Vivulanets E.V., Kucherskoy S.A., Shishonok M.F., Tarasova E.V., Proskurina A.S., Egiazaryan A.R., Zamkova I.V., Dorofeeva E.V., Rinchindorzhieva E.A., Rabikova D.N., Shvykina S.A.

Abstract

The results of our own and foreign studies have shown the absence of sensitizing properties of terephthalic acid, and therefore there was a need to review the current hygienic standard – MAC – in the air of the working area and change the hazard class of the substance. The materials of the German Research Community (DFG) were used for substantiation of MAC. Recommended MAC in the air of working area is set at 5 mg/m3 (maximum single), a mixture of vapors and aerosol, hazard class 3.
Toxicological Review. 2020;(6):21-37
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ANALYSIS OF MT2A AND MT3 GENE EXPRESSION IN RAT'S LIVER AND KIDNEY IN RESPONSE TO CADMIUM CHLORIDE POISONING

Ziatdinova M.M., Yakupova T.G., Valova Y.V., Mukhammadieva G.F., Karimov D.O., Nazarova L.S., Smolyankin D.A.

Abstract

The aim of this study was to investigate the expression of metallothionein genes in the liver and kidneys of rats with acute cadmium poisoning.

Simulation of poisoning with cadmium chloride was carried out on white outbred female rats, divided into 4 groups depending on the dose of the injected toxicant. RNA samples isolated from rat liver and kidneys were used as research materials.

The multiplicity of expression of the MT3 gene in the kidneys increased at the lowest dose of CdCl2 , which was used in this experiment (0.029 mg / kg); with increasing dosage, the expression level decreased, but not lower than the control values. Analysis of the expression of the same gene in the liver showed a tendency towards a decrease in the content of transcripts with increasing dose. The frequency of expression of the MT2A gene at higher doses of CdCl2 increased both in the liver and in the kidneys.

In the present work, statistically significant dose-dependent changes in the expression multiplicity of metallothionein genes were detected 24 hours after CdCl2 administration. The revealed differences in the level of transcriptional activity of metallothionein genes require further investigation, since there are probably differences in the level of gene expression at earlier and later periods of toxicant action.

Toxicological Review. 2020;(6):38-42
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ROLE OF RESPIRATORY RATE IN THE TOLERABILITY OF PERSONAL RESPIRATORY PROTECTION EQUIPMENT

Byalovsky Y.Y., Rakitina I.S.

Abstract

The factor limiting the tolerance of personal respiratory protection equipment should be considered the frequency of respiratory movements, which reflexively changes when additional respiratory resistance occurs. Unfortunately, there is almost no information in the available literature about changes in the tolerability of personal respiratory protection equipment at different rates of respiratory movements. The purpose of this work was to study the tolerability of personal respiratory protection equipment when changing the frequency of respiratory movements.

The study was conducted on practically healthy persons of both sexes (78 people), aged from 20 to 36 years. To simulate the conditions for the use of personal respiratory protection equipment, inspiratory resistive respiratory loads of 20% of the maximum intraoral pressure during the Mueller test were used. The tolerance of personal respiratory protection equipment was assessed using the Borg visual analogue of dyspnea scale, which reflected the level of subjective discomfort that occurs when additional respiratory resistance is turned on. During the action of additional respiratory resistance, the persons were asked to hold the frequency of respiratory movements, which was set using a special setting.

An increase in the rate of respiratory movements against the background of additional respiratory resistance leads to a significant deterioration in the objective and subjective indicators of the functional state of the persons; replacing the inhaled air with an oxygen-rich respiratory mixture with carbon dioxide absorption did not lead to a significant improvement in the functional state. A moderate decrease (up to 70% of the initial frequency of respiratory movements) in the rate of respiration leads to an improvement in the indicators of adaptive activity in conditions of additional respiratory resistance. A significant decrease (up to 35% of the initial frequency of respiratory movements) in the rate of respiration under conditions of additional respiratory resistance leads to a deterioration of objective and subjective indicators of the functional state of the subjects.

An increase in peak respiratory flow rates caused by an increase in the rate of respiration, in accordance with the well – known Rohrer equation, significantly increases inelastic resistance and, as a result, respiratory needs. These needs can be met at some time due to a significant increase in the work of the respiratory muscles, but due to fatigue of the latter, psychoemotional tension increases quite quickly and the use of personal respiratory protection equipment is abandoned.

Toxicological Review. 2020;(6):43-48
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Main unit

ИЗМЕНЕНИЕ ЭКСПРЕССИИ ГЕНОВ РЕЦЕПТОРА NMDA ПОД ВОЗДЕЙСТВИЕМ НАНОЧАСТИЦ ОКСИДА МЕДИ

Ситников И., Шаихова Д., Амромина А., Сутункова М., Рябова Ю., Тажигулова А., Рузаков В.

Abstract

Введение. Медь играет важную роль в метаболизме мозга, однако частицы меди нанометрового диапазона могут проявлять нейротоксические свойства и вызывать нарушения работы клеток мозга.

Материал и методы. В течение 6 недель 3 раза в неделю внутрибрюшинно животным вводили суспензию НЧ оксида меди. Определение экспрессии генов GRIN1, GRIN2a и GRIN2b, кодирующих белки GluN1, GluN2a и GluN2b, соответственно проводилось методом ПЦР в реальном времени с зондами.

Результаты. Определено статистически достоверное снижение уровня экспрессии генов, кодирующих белки рецептора NMDA, при воздействии наночастиц CuO 0,5 мг/мл (ΔCt (GRIN1) = 0,813; ΔCt (GRIN2A) = 3,477; ΔCt (GRIN2B) = 1,37) в сравнении с контрольной группой (ΔCt (GRIN1) = 6,301; ΔCt (GRIN2A) = 7,823; ΔCt (GRIN2B) = 4,747).

Заключение. Оценка уровня экспрессии генов рецептора NMDA может быть использована в качестве генетического маркера для определения токсического действия наночастиц оксида меди, однако необходимы дальнейшие исследования, включающие проведение поведенческих тестов, которые позволили бы подтвердить наличие клинических проявлений нейродегенеративных растройств.

Toxicological Review. 2020;(6):
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New information on toxicity and hazard of chemical and biological substances

DOMESTIC ANTITUMOR COMPOUND 2-[3-(2-CHLOROETHYL)-3-NITROSOUREIDO]-1,3- PROPANEDIOL (CHLONISOL). ACUTE TOXICITY

Stukov A.N., Vershinina S.F., Kharitonova N.N., Filatova L.V., Latipova D.Н., Tyndyk M.L., Zmitrichenko Y.G., Semenov A.L., Bespalov V.G., Semiglazova T.Y.

Abstract

2-[3-(2-Chloroethyl)-3-nitrosoureido]-1,3-propanediol (Сhlonisol) is a representative of a separate group of derivatives of the class of nitrosoalkylureas – alkylnitrosoureidopropanediols, which are characterized by high antitumor activity on a wide range of experimental tumors. Chlonisol LD50 in male mice for intravenous administration was 35 mg/kg, intraperitoneal – 39 mg/kg, in female mice – 34 mg/kg and 36 mg/kg, respectively. In rats of males with intraperitoneal administration, LD50 was 30 mg/kg, in rats of females – 32 mg/kg. The maximum tolerated dose in mice, rats, guinea pigs and rabbits was 20 mg/kg. The tolerated dose for dogs was a dose of 2 mg/kg. Myelo-depression was a dose-limiting side effect. Lethal and sublethal doses of Chlonisol caused aplasia of the bone marrow and lymphoid organs, damage to the mucous membrane of the gastrointestinal tract, and dystrophic changes in the myocardium, lungs, liver, kidneys, pancreas, and reproductive organs. In the late stages after intraperitoneal administration of sublethal doses of Chlonisol, chylothorax and chyloperitoneum were found in some rats.
Toxicological Review. 2020;(6):49-53
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EXPERIMENTAL STUDY OF THE TOXICITY AND HAZARD OF QUETIAPINE FUMARATE

Golubeva M.I., Bidevkina М.V., Bobrineva I.A., Razumnaya I.N., Fedorova E.A., Savchenko A.Y., Ramenskaya G.V., Pozharnov I.A.

Abstract

Quetiapine is a psychotropic drug, a dibenzothiazepine derivative and a representative of the class of neuroleptics (antipsychotic drugs) of a new subgroup – atypical antipsychotic drugs («second-generation antipsychotics»). Quetiapine fumarate belongs to the 3rd hazard class in terms of DL50 when administered in the stomach according to GOST 12.1.007-76 (DL50 1380-1680 mg/kg, mice and rats), has a local irritant effect: pronounced - on the mucous membrane of the eyes and moderately pronounced - on the skin. There are no signs of skin resorptive or cumulative effects of quetiapine fumarate. When inhaled, an aerosol of quetiapine fumarate has a general toxic and irritating effect in rats. The threshold of acute inhalation action of quetiapine fumarate is set at 6,2 mg/m3 for general toxic effect (effect on the quantitative composition of peripheral blood and the cardiovascular system) and irritating effect on the mucous membranes of the upper respiratory tract. For quetiapine fumarate, the tentative safe exposure level in the air of the working area is recommended at 0,2 mg/m3 , aerosol, with «+» - special protection of the skin and eyes is required. The tentative safe exposure level in the atmospheric air of urban and rural settlements is 0,002 mg/m3.
Toxicological Review. 2020;(6):54-58
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TOXICITY UNDER A SINGLE INTRAGASTRIC ADMINISTRATION OF THE ACTIVE CLATHRATE COMPLEX OF β-CYCLODEXTRIN WITH 3-(2-PHENYLETHYL)-2-THIOXO-1,3- THIAZOLIDIN-4-ONE

Erimbetov K.T., Zemlyanoy R.A., Bondarenko E.K., Goncharova A.Y.

Abstract

The clathrate complex of 3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one with β-cyclodextrin in the form of a nanopowder with an average particle size of 40.5 nm, with a wide range of pharmacological properties, was developed for the first time. It belongs to class VI of relatively harmless drugs according to Hodge and to class 5 in accordance with GOST 32644-2014.
Toxicological Review. 2020;(6):59-62
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List of publications in the journal

LIST OF WRITTING PUBLISHED IN «TOXICOLOGICAL REVIEW» IN 2020

Editorial a.

Abstract

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Toxicological Review. 2020;(6):63-64
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