No 1 (2020)

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Articles

IN MEMORY OF LIVANOV GEORGY ALEXANDROVICH

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Toxicological Review. 2020;(1):61
pages 61 views

QUESTIONS OF DYNAMICS, FORENSIC MEDICAL AND FORENSIC CHEMICAL DIAGNOSTICS OF METHADONE POISONING IN SAINT PETERSBURG IN 2009-2018

Zarafiants G.N., Isakov V.D., Gorbacheva T.V.

Abstract

Acute poisonings occupy one of the leading places in the structure of mortality due to external causes in the Russian Federation. In Saint Petersburg, there are consistently high rates of drug poisonings (especially methadone poisoning). Reports, statistical maps and other information of the Bureau of Forensic Medical Expertise for the period 2009 – 2018 were used for this study. The research methods were a selective copy of the data, including the results of a forensic chemical study, the calculation of statistical coefficients, descriptive. The analysis showed a decrease in mortality due to external causes in Saint Petersburg in 2009-2018, indicators (per 100 thousand of the population of Saint Petersburg) decreased gradually from 99,3 to 69,8. Acute poisoning of chemical etiology was in the 2nd place (24,9%) after mechanical injury. In the structure of acute poisoning of chemical etiology, the 1st place was occupied by fatal drug poisoning (45,1%). Their share was 28,7% in 2009-2011. It increased sharply up to 52,2% in the period 2012-2018 and began to change both qualitative and quantitative. In Saint Petersburg there were 19 fatal cases of methadone poisoning (0,04 per 100 thousand people) in 2009 and 599 cases (11,19 per 100 thousand people) in 2018. The number of forensic studies on the identification of methadone sharply increased (9 times). In almost half of the poisoning’s cases ethanol, other narcotic drugs (amphetamine derivatives, morphine, cocaine, etc.), as well as drugs and psychotropic substances (derivatives of barbituric acid, benzodiazepine, phenothiazine, etc.) were revealed along with methadone.

Forensic medical diagnostics of methadone poisoning are based on the results of chromatography-mass spectrometry, morphological features (macro- and microscopic), analysis of the clinical picture (from medical documents), and consideration of the circumstances of the poisoning. The combined reception of methadone, ethanol and other narcotic and / or psychotropic drugs has a potentiating deprimative effect, aggravates the clinical and morphological picture of poisoning, which must be taken into account when diagnosing them.

Toxicological Review. 2020;(1):2-7
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CARDIOVASCULAR INDICATORS AFTER ACUTE NEUROTOXIC POISONING

Ivanov M.B., Aleksandrov M.V., Chernyi V.S.

Abstract

The aim of the study was to assess the recovery of the cardiovascular system after acute poisoning with neurotoxic substances at the time of discharge from the hospital. The results of treatment and observation of 28 cases of moderate, severe and extremely severe poisonings have been studied by the evaluation of indicators of the cardiovascular system at rest and during the orthostatic tests. It has been shown that in persons with acute poisoning with neurotoxic substances, the state of health is not fully restored by the end of the course of inpatient treatment. The indicators of the cardiovascular system showed the state of pronounced sympathicotonia in these patients at the time of discharge from the hospital. Persons with acute carbon monoxide poisoning have a pronounced tension in the mechanisms of regulation of the heart rhythm. In patients with acute oral poisoning with psychotropic drugs, an orthostatic test revealed an increased tone of the sympathetic part of the autonomic nervous system. The data of rhythmocardiography indicate a pronounced tension of the regulation mechanisms. Patients in this category require further observation and medical rehabilitation.

Toxicological Review. 2020;(1):8-12
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PECULIARITIES OF METABOLIC CHANGES IN EXPERIMENTAL ANIMALS AT EARLY TERMS OF PHARMACOLOGICAL CORRECTION OF TOXIC LIVER DISEASES

Timasheva G.V., Repina E.F., Karimov D.O., Khusnutdinova N.Y., Mukhammadieva G.F., Bakirov A.B., Smolyankin D.A., Baigildin S.S.

Abstract

The paper presents the results of studies on metabolic changes in experimental animals with acute tetrachloromethane poisoning and further damage correction using substances possessing hepatoprotective properties: oxymethyluracil, ademethionine and ethylmethylhydroxypyridine succinate. It has been revealed that oxymethyluracil exhibits heteroprotective properties at the earliest stages of acute toxic liver damage with chemical toxicants: it has membrane-stabilizing properties, normalizes the levels of antioxidant system parameters, thereby restoring the oxidative-antioxidant balance in hepatocytes. Oxymethyluracil has more pronounced hepatoprotective properties at the early stages of treatment in comparison with ademethionine and ethylmethylhydroxypyridine succinate. The results obtained are important in terms of the prospective use of oxymethyluracil for the relief of hepatotoxic effects in acute exposure to hepatropic chemicals under environmental and industrial poisoning.

Toxicological Review. 2020;(1):13-19
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BIOLOGICAL MARKERS AND MORPHOGENESIS OF ACUTE RENAL INJURY IN RAT DICHLOROETHANE POISONING

Sivak K.V., Savateeva-Lyubimova T.N., Gus’kova T.A., Kul’bitzkiy G.N., Alexandrova M.L.

Abstract

The article presents the results of an experimental study on rat poisoning with 1,2-dichloroethane (250 µl / kg, intragastric administration). The aim of this work was to find the relationship between biological markers and morphological changes in acute damage to rat kidneys with dichloroethane. The study of urine samples of experimental animals by gas-liquid chromatography (GLC) revealed 1,2-dichloroethane in the concentration range of 0,05 – 0,90 µg / ml (95% C.I. = 0,09 – 0,90 µg / ml). Daily excretion with urine was 0,60 – 4,50 µg / 16h (95% C.I. = 1,14 – 3,93 µg / ml). Levels of nephron-specific biomarkers in urine were 194,62 ± 9,02 IU / L (NAGase, p = 0,0022) and 2,93 ± 0,38 ng / ml (KIM-1, p = 0,0022), which exceeded those in the control group by 5 and 23 times, respectively. Edema, disorders of intrarenal hemodynamics, leukocyte migration in interstitium, uneven damage to various areas of the kidneys due to adipose dystrophy and necrobiotic changes in the nephrothelium of the proximal tubules mainly in the cortical layer of the kidneys have developed in the kidneys. Positive correlations between the level of 1,2-dichloroethane in the urine and the level of KIM-1 (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0,0083), -N-acetylglucosaminidase (Spearman r = 0,8248, 95% C.I. 0,4613 – 0,9512, p = 0,0019), the scores on the EGTI scale (Spearman r = 0,8064, 95% C.I. 0,7126 – 0,8719, p < 0.0001); the level of KIM-1 and the scores on the EGTI scale (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0.0083), -N-acetylglucosaminidase and the scores on the EGTI scale (Spearman R = 0,4684, 95% C.I. 0,2764 – 0,6244, p < 0,0001), the level of the low and medium molecular weight substances in the blood and the scores on the EGTI scale (Spearman R = 0,6909, 95% C.I. 0,5549 – 0,7909, p < 0,0001) were found.

Toxicological Review. 2020;(1):20-26
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TOXICITY AND HAZARD OF NEUROPARALYTIC ACTION OF FIRE-RESISTANT TURBINE OILS BASED ON TRIARYL PHOSPHATES

Sidorin G.I., Lukovnikova L.V., Dyakova L.I., Shestova G.V.

Abstract

The paper presents the results of assessing the toxicity and danger of the development of neuroparalytic effect of fire-resistant turbine oils «Turbomas», «T-94» and «T-95» based on triaryl phosphates. According to the toxicity parameters, the studied oils are low-toxic substances, exhibit weakly expressed cumulative properties, do not irritate the skin and mucous membranes, penetrate through intact skin, and increase the activity of microsomal enzymes, when injected into the stomach and abdominal cavity. The study of the neuroparalytic action of oils «Turbomas», «T-94» and «T-95» did not reveal the presence of clinical and morphological signs of disorders of the neuromuscular apparatus in animals, which makes it possible to exclude the possibility of neuroparalytic action in persons in contact with the studied oils.

Toxicological Review. 2020;(1):27-33
pages 27-33 views

EXPERIMENTAL SUBSTANTIATION OF THE MAXIMUM ALLOWABLE CONCENTRATION OF DIOCTYL TEREPHTHALATE IN THE AIR OF THE WORKING AREA

Radilov A.S., Solntseva S.A., Shkaeva I.E., Dulov S.A., Vivulanets E.V., Protasova G.A., Shabasheva L.V., Nikulina O.S.

Abstract

Toxicity and hazard assessment of dioctyl terephthalate (DOTP) was performed in acute, subacute, and chronic experiments, and its principal toxicometry parameters were determined.

It was found that on single exposure DOTP exhibits low toxicity and hazard. No resorptive and irritant effects on skin and mucous membrane of eyes were detected in animal experiments. The single inhalation exposure threshold limit value was set at 300 mg/m3, based on the results of monitoring of the functional state of the central nervous system and myocardium and hematological parameters.

Thirty-day subacute experiments (oral administration, inhalation exposure, and skin applications) revealed no accumulation of the compound.

Four-month chronic exposure to DOTP aerosols (concentration 96,8 mg/m3) caused disorder of the functional state of the central nervous system and myocardium, changes in the hematological and biochemical parameters, gas and acid-base status of the blood, and morphological changes in the lungs and heart. Embryotoxic, genotoxic and gonadotoxic effects were not detected.

The chronic inhalation exposure threshold limit value for DOTP (Limch) was set at 18,6 mg/m3, and the concentration of 3,4 mg/m3 was found to be ineffective.

The maximum allowable concentration of DOTP in the air of the working area was set at 3,0 mg/m3, hazard class 3.

Toxicological Review. 2020;(1):34-38
pages 34-38 views

JUSTIFICATION OF MAXIMUM SINGEL ALLOWABLE CONCENTRATIONS OF 1-METHYL-4-ISOPROPENYLCYCLOHEX-1-ENE (LIMONENE), 3,7,7-TRIMETHYLBICYCLO[4.1.0]HEPT-2-ENE (3-CARENE) AND 2,2-DIMETHYL-3-METHYLENEBICYCLO[2.2.1]HEPTANE (CAMPHENE) IN AMBIENT AIR

Budarina O.V., Fedotova L.A., Shipulina Z.V., Potapchenko Т.D.

Abstract

This paper presents the results of the experimental studies on justification of the maximum single allowable concentrations (MAC) of 1-methyl-4-isopropenylcyclohex-1-ene (limonene), 3,7,7-trimethylbicyclo[4.1.0]hept-2-ene (3-carene), and 2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane (camphene) in the air of urban and rural settlements. The research has been carried out in accordance with the current methodology for determining the odor thresholds of substances using modern olfactometric equipment (dynamic olfactometer) and highly sensitive methods for identifying chemical components (chromatography-mass spectrometry). According to the results obtained, the recommended maximum single allowable concentrations in the atmospheric air of urban and rural settlements are 0,08 mg/m3 (hazard class 4) for limonene; 0,2 mg/m3 (hazard class 4) for 3-carene; 0,3 mg/m3 (hazard class 3) for camphene; the limiting indicator of harmfulness for all substances is reflex. An analytical methodic based on chromatography-mass spectrometry and certified in accordance with GOST R 8.563-2009 and GOST R ISO 5725-2002 has been developed to control the concentrations of α-pinene, β-pinene, camphene, 3-carene, and limonene in the atmospheric air of urban and rural settlements.

Toxicological Review. 2020;(1):39-44
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RESEARCH AND EVALUATION OF THE TOXICITY PARAMETERS OF NANO-DISPERSED MAGNESIUM OXIDE IN REPEATED INHALATION EXPOSURE

Stepankov M.S.

Abstract

A repeated inhalation exposure of Wistar rats to an aerosol of aqueous suspension of nano-dispersed magnesium oxide (5-100 nm) with actual concentration of 0,485 ± 0,121 mg/m3 has been studied. There was a significant increase in the activity of alanine aminotransferase, as well as the number of leukocytes and platelets, thrombocrit. At the same time, a significant decrease in stab neutrophils and monocytes has been noted. In animals of the experimental group, acute plethora has been found in the tissues of the brain, heart, lungs, liver, pancreas, and kidneys. Subarachnoid hemorrhages in the brain; hemorrhagic heart attacks and hyperplasia of lung tissue; hyperplasia of the myeloid germ of hematopoietic bone marrow and lymphoid tissue of the small intestine; eosinophilia of infiltrate in the stomach and large intestine have been established. The results obtained make it possible to increase the effectiveness of substantiating preventive measures for workers and population exposed to inhalation exposure to nanoparticles of magnesium oxide.

Toxicological Review. 2020;(1):45-48
pages 45-48 views

Ecological Toxicology

IMMUNOTROPIC EFFECTS OF IVERMECTIN IN PRODUCTIVE AND LABORATORY ANIMALS

Gerunov T.V.

Abstract

The aim of this work was to identify the immunotropic effects of ivermectin in productive and laboratory animals in real and simulated conditions. The studies were carried out on hybrid pigs at the age of 144 days reared in an industrial pig complex and on Wistar rats aged 5 months with a body weight of 230 - 250 g. For the experiments there was used acaricide insecticide Ivermin (Biovet Drwalew S.A., Poland), which was administered to pigs once subcutaneously in a dose of 0,2 mg / kg and to rats in a tenfold therapeutic dose. Blood samples were taken from pigs either before the administration of Ivermin, and 1, 3, 7, 14 and 30 days after the administration. The level of immunoglobulins (IgG, IgM, IgA) was determined in serum by the method of radial immunodiffusion according to Mancini. To prepare histopreparations, samples of thymus, spleen and lymph nodes were taken from rats 14 days after the administration of the preparation. For statistical processing of experimental data, Student’s T-test for dependent samples has been used.

When studying pigs’ blood serum, a decrease in the content of IgG was established in all periods of the study. A decrease in level of IgM and IgA was marked in 7 days after the experiment started. At the end of the experiment, the IgG level remained below the background value by 16,4%; IgM - by 15,2%; IgA – by 33%. In the rat thymus, a narrowing of the cortical substance was observed when a toxic dose of Ivermin was injected, with the splenic follicles reduced, and reproduction centers faintly pronounced. Hemosiderin accumulation was detected around the follicles. In the mesenteric lymph nodes, there was found a thickening of the capsule and the expansion of trabeculae. Cortical substance was narrow and paracortical zone was wide. The results of the study indicate a high risk of immunotoxic effect of ivermectin.

Toxicological Review. 2020;(1):49-53
pages 49-53 views

INFLUENCE OF HUMIC ACIDS ON THE MODIFICATION OF THE BIOACTIVITY OF MAGNETIC NANOPARTICLES

Bondarenko L.S., Uchanov P.V., Chistyakova N.G., Terekhova V.A., Kydralieva K.A.

Abstract

The influence of iron-based magnetic nanomaterials on living systems — photosynthetic plants – have been studied in standardized test systems. The effects of magnetite and maghemite nanoparticles after stabilization of their surface with humic acids by the reactions of microalgae Scenedesmus quadricauda (Turp.) Breb. and sprouts of seeds of higher plants - white mustard Sinapis alba L. – have been compared. The dynamics of growth test functions have been evaluated by changing the fluorescence of chlorophyll in a suspension of microalgae and by changing the length of the roots of seed seedlings during incubation with the studied drugs relative to the control variants (without drugs). It has been found that the treatment with humic acids sufficient for the stability of iron nanoparticles in terms of the phase state does not reduce the toxicity of maghemite in both test systems. Possible mechanisms for changing the ecotoxicity of synthesized magnetic iron nanopreparations in interaction with living systems in their growth environment are discussed.

Toxicological Review. 2020;(1):54-60
pages 54-60 views

Congresses, conferences, meetings

60TH JOINT MEETING OF THE OECD COMMITTEE ON CHEMISTRY AND THE OECD WOKING GROUP ON CHEMISTRY, PESTICIDES AND BIOTECHNOLOGY

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Toxicological Review. 2020;(1):62-64
pages 62-64 views