The Journal “Toksikologicheskiy vestnik” (Toxicological Review)

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Download PDF-version file for magazine # 6 '2016.

Nov–Dec, 2016
# 6


SOME PRINCIPLES AND MEANS OF INCREASING THE ORGANISM’S RESISTANCE TO ADVERSE EFFECTS OF METALCONTAINING NANOPARTICLES
Authors: Privalova L. I. , Katsnelson B. A. , Gurvich V. B. , Minigalieva I. A. , Sutunkova M. P. , Makeyev O. H. , Valamina I. E. , Shur V. Y. , Grigoryeva E. V. , Klinova S. V. , Shishkina E. V.

Particularly high health risks associated with impacts of metal and metal oxide nanoparticles (Me-NPs), and their presence in the occupational environment, not only in nano-industry, but also in some long-existing technologies as well necessitates to maintain levels of hazardous exposures as low as possible and also to find ways to enhance the body’s resistance to them. The article briefly discusses the theoretical background of suсh a «bio-protection». The analysis of the most significant results of experiments with different Me-NPs, shows that against the background of properly selected combinations of certain biologically active agents used in harmless doses, it can be possible to significantly weaken integral and specific toxicity and even genotoxicity of metal-containing nanoparticles.

Keywords: nanoparticles, toxicity, genotoxicity, bioprophylaxis


EXPERIMENTAL DATA AND METHODOLOGICAL CONSIDERSATIONS FOR JUSTIFICATION OF IRON OXIDE NANOPARTICLES MAXIMUM ALLOWABLE CONCENTRATION IN OCCUPSATIONAL AIR
Authors: Sutunkova M. P.

Airborne Fe2O3 nanoparticles (NPs) with an average diameter of 14 ± 4 nm, obtained by sparking iron rods of 99.9% purity were fed to a “nose only” type exposition installation for 4 hours 5 times a week over 10 months at an average concentration of 1.14 ± 0.01 mg / m3. A very low accumulation of Fe2O3-NPs in the lung tissue gradually increasing over time was found out. As judged by the almost normal histology of lung and lung-associated lymph nodes and low content of hydroxyproline in the lungs, the intensity of the developing pneumoconiosis was not important. Functional and biochemical indices of the body’s condition mostly remained normal, but some of them made consider tested NP concentration as threshold value in the chronic systemic toxicity. In accordance with general principles of setting MAC for occupational air, it was suggested to consider justified a concentration of 0.4 mg / m3, as MAC value for iron-oxide NPs.

Keywords: nanoparticles, solubility, toxicokinetics


SOME REGULATIES OF METAL OXIDE NPs COMBINED TOXICITY
Authors: Minigalieva I. A.

Toxicity of oxides nanoparticles (NPs) of some metals was studied in outbred female rats under isolated and combined action of (NiO + Mn3O4; CuO + PbO; CuO + ZnO; PbO + ZnO; PbO + CuO + ZnO) using two experimental models: ( a) a single intratracheal instillation in small doses 24 hours prior to the bronchoalveolar lavage procedure in cytology and biochemical investigations into the fluid produced; (b) repeated intraperitoneal injections at non-lethal dosage over 6 weeks to evaluate that sub-chronic intoxication produced using a great number of functional morphometric parameters and indicators of bio-distribution and elimination of the respective metals. Combination effects were described by various mathematical models including the construction of response surface. A variety of combined toxicity types was demonstrated for the same pair of NPs according to what concrete effect the toxicity was assessed and frequently also according to dose-dependent level of that effect. It was also shown that the risk-oriented approach to the classification of three-factor toxicity, previously developed for the combined action of metals in ion-molecular form, was adequate for NPs investigated,

Keywords: combined toxicity, nanoparticles


EFFETIVE AND SAFE MODIFIED CARBON SORBENTS BASED ON NANOGLOBOLAR CARBON FOR MEDICAL AND VETERINARY PURPOSES
Authors: Pyanova L. G. , Likholobov V. A. , Sedanova A. V.

At the Institute of Hydrocarbon Processing, Siberian Branch of the Russian Academy of Sciences, technological approaches were developed to the targeted synthesis of porous carbon-carbon materials of a new class based on nanoglobular dispersed carbon (particle diameter 40-60 nm). Carbon materials for medical purposes are carbon hemosorbent in sterile saline VNIITU-1, carbon enterosorbent VNIITU-2, carbon enterosorbent Zookarb and modified materials derived from them that are safe and effective drugs for solving problems in medicine and veterinary. The article reports investigation results of effects posed by hemosorbent VNIITU-1 on blood plasma biochemical parameters in patients with peritonitis (substances with low and medium molecular weight, creatinine and ammonia). The results of the study on using enterosorbent Zookarb at chronic intoxication of animals with heavy metals – zinc and iron compounds are presented. The efficiency of samples of carbon hemosorbent and enterosorbent modified with polyarginine against pro-inflammatory cytokines (interleukin 6, interleukin 8) was assessed.

Keywords: Carbon sorbents, nanoglobular carbon, Institute of Hydrocarbons Processing, Siberian Branch of the Russian Academy of Sciences, safety requirements for drugs, carbon hemosorbent in sterile saline solution VNIITU-, carbon enterosorbent Zookarb, composite veterina


COMPARATIVE APPROACHES TO RISK ASSESSMENT AND HYGIENE REGULATION OF NANOMATERIALS IN RUSSIA AND IN THE EUROPEAN UNION (ON EXAMPLE OF NORWAY)
Authors: Glushkova A. V. , Radilov A. S. , Dulov S. A. , Khlebnikova N. S.

Approaches to risk assessment when working with nanoparticles and nanomaterials in the European Union countries and the Russian Federation are in principle similar. No specific procedures for risk assessment are provided for working with nanoparticles and nanomaterials. All approaches are based on using the same methods and techniques as for assessment of substances in the micro or macro form(except nanofibers). However approaches to hygiene regulation differ to some extent from country to country. Those differences are examined in detail in the present article.

Keywords: nanoparticles, nanomaterials, risk assessment, hygiene regulation, hygiene standards, EU countries, the Russian Federation, hygiene, toxicology


THE USE OF CARBONACEOUS NANOMATERIALS IN CASE OF LESIONS CAUSED BY HIGHLY TOXIC CHEMICAL COMPOUNDS
Authors: Zemlyanoy A. V. , Onikienko S. B. , Radilov A. S. , Baranov G. A. , Khukharev V. V. , Dulov S. A. , Varlashova M. B. , Erunova N. V.

The use of catalytic properties of reactive carbonaceous nanomaterials, their composite compounds with quartz, metal oxides and silicon for neutralization and destructive adsorption of highly toxic chemical compounds can serve as a basis to create new means of protection from highly toxic chemical lesions. The first studies on the impact of high-power CO2 laser ( = 10 μ) radiation on the structure and properties of shungite were performed at D.V. Efremov Institute of Electrophysical Apparatus. The surface of the laser-treated shungite is almost 2-fold larger than the surface of natural schungite and increases its catalytic activity. The elemental composition of shungite material does not undergo significant changes after laser treatment. The laser treatment of schungite improves its ability to clean polluted water from radical and ion-radical particles, neutralizes toxic substances in water and air. Activated shungite carbon nanoparticles have a biocidal effect, reduce animal deaths and increase animal lifespan in case of cutaneous application of mustard agent.

Keywords: laser, shungite, mustard agent


OCCUPATIONAL EXPOSURE AND MEDICO-BIOLOGICAL EFFECTS OF MULTI-WALLED CARBON NANOTUBES: OVERVIEW OF AUTHORS’ RESEARCHES
Authors: Fatkhutdinova L. M. , Khaliullin T. O. , Zalyalov R. R. , Kisin E. R. , Shvedova A. A.

Advanced studies on the behavior of nanoparticles in living systems and safety degree of new nanomaterials is one of the strategic objectives of the development of nanotechnology network. The urgency of the issue is due to the lack of sufficient information about behavior of engineered nanoparticles in living systems, including humans. Carbonaceous materials occupy one of the leading position on the market of nanomaterials. The number of enterprises, which produce or use carbon nanotubes (CNT) and other types of carbon nanomaterials is growing from year to year. The establishment of molecular cellular mechanisms of CNTs biological and toxic effects in interaction between various biological objects and the human organism is necessary for further development of approaches to technical regulation of the nanoparticles content in various objects and prevention of damaging effects on the human organism. In 2009-2015. the protocol was implemented of a joint Russian-American investigation into exposure assessment and health risk from effects of multi-walled carbon nanotubes CNT-ERA (Carbon NanoTubes Exposure and Risk Assessment), one of the first world research of human health risks associated with industrial exposure to inhaled MWCNT. The study included hygienic, toxicological and epidemiological stages. Respirable fractions concentration of aerosol in the worker’s breathing zone, averaged over an 8-hour period, were in the range of 0.54 to 6.11 g / m3 (calculated as elemental carbon). Profibrotic potential of native MWCNTs used in industry, as well as potentially increased risk of pulmonary and cardiovascular diseases and malignant lung tumors were identified. The necessity of revision of domestic approaches to assessment methods of exposures and regulation of MWCNTs in the working area, development of a system of preventive measures and health service for workers were proved..

Keywords: multi-walled carbon nanotubes (MWCNTs), fibrogenic effects, carcinogenic risk, studies in vitro and in vivo, epidemiological study, biomarkers, gene expression


FEATURES OF APOPTOSIS-REGULATORY PROTEINS EXPRESSION IN NEURONS OF WHITE RATS AT EXPOSURE TO NANOSILVER ENCAPSULATED IN A POLYMER MATRIX
Authors: Sosedova L. M. , Novikov M. A. , Titov E. A.

Results of a comparative analysis of apoptosis-regulating proteins caspase-3 and bcl-2 expression in nerve tissue cells of outbred white rats are reported. . An immunohistochemical investigation into the white rats nerve tissue was performed 9-days after administration of nano biocomposites consisting of silver nanoparticles encapsulated in a matrix of arabinogalactan, a natural biopolymer. and synthetic one – poly-1-vinyl-1,2,4-triazole. White rats were examined in 2 stages: half of the rats from each group was sacrificed immediately after exposure (early term) and the rest of rats- 6 months after the end of exposure (delayed term). It was found out that the expression activity of apoptosis regulatory protein at exposure to innovative nano biocomposites had its special features depending on a preparation administered and time of inspection. The examination immediately after subacute administration of arabinogalactan, a nano biocomposite, showed that the content of apoptotic and anti-apoptotic proteins caspase-3 and bcl-2 increased in the nerve tissue cells of white rats brain. Identified results showed activation of apoptotic processes as early as on the 10th day after the end of exposure to nano biocomposites. In a delayed examination period, a number of hyperchromic and normal cells expressing the protein caspase-3, became even higher testifying to intensification of apoptosis over time under impact of nanocomposite based on the natural matrix of arabinogalactan. A significant increase in number of neurons expressing bcl – 2 was also revealed in preparations but the protective effect of this protein was not fully realized. Thus, when comparatively assessing biological effects of polymer nano biocomposites containing nano silver in natural and synthetic matrices of arabinogalactan and poly-1-vinyl-1,2,4-triazole, it was found out that disorders in neuron subcellular organization emerge at only administration of nanobiocomposite in natural matrix of arabinogalactan . Analysis of results of expression of apoptosis-regulating proteins at administration of argentum polyvinyl triazola (PVT) to white rats did not reveal any changes as compared to administration of pure polymer matrix that could attest to activation of apoptosis in nerve cells throughout the observation period. Changes in indices had multidirectional character, an increased content of bcl-2 protein that was effectively involved in the regulation of apoptosis process was not observed , as well as increased expression of the protein caspase-3, which testified to irreversible changes in cells at apoptosis induction.

Keywords: immunohistochemistry, arabinogalactan, poly-1-vinyl-1, 2, 4-triazole, nano silver, apoptosis, laboratory animals, brain


SUB-CHRONIC TOXICITY OF NANOSIZED CERIUM DIOXIDE
Authors: Tochilkina L. P. , Khodykina N. V. , Bocharova L. Yu. , Sroslov M. S. , Klauchek V. V. , Filatov B. N.

In an experiment on white male rats, systemic toxicity of cerium dioxide nanoparticles in the form of 0.078 M hydrosol was studied. It is found out that a two-month intake of cerium nano dioxide in doses of 50, 10 and 2 mg / kg, was followed by the development of toxic dose-dependent resorptive effect. The dose of 2 mg / kg was qualified as a threshold of general toxic effect in sub-chronic experiment.

Keywords: cerium dioxide, nanoparticles, hydrosol, rats, toxicity, threshold dose


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