А program of investigational studies of new combined preparations containing known medications includes investigation into general toxic effect of a combination but does not plan investigations into toxicity of its active components. The medical application of these medications assumes that pre-clinical and clinical data proving their effectiveness and safety are sufficient. But a fragmentary and controversial nature of data about toxicity of drugs available to those involved in new drug development significantly restricts the use of literature data in characterizing a combination toxicity expected profile , predicting and identifying the interaction effects. A prognostic and experimental evaluation of active components toxicological interaction was performed using the example of the metamizole sodium and ibuprofen fixed combination. The adequacy evaluation of the program of investigational studies and interpretation results of the combined preparation toxicological assessment was carried out using a common analytical practice.

Keywords: combined medications, pre-clinicall safety evaluation, investigational studies, prediction, toxicological interaction

Stable water suspensions of copper oxide particles with the mean diameter of 20 nm and copper oxide-copper ones with the mean diameter of 340 nm were used to assess the rats pulmonary phagocytosis response to a single intratracheal instillation of 0.5 mg(1 ml) of these suspensions followed by the bronchoalveolar lavage after 24 hours with the help of optical, transmission electron, and semi-contact atomic force microscopy and a number of biochemical indices measured in the bronchoalveolar lavage fluid. It was found out that the two fractions produce an expressed toxic effect on lungs but nanoparticles appear significantly more toxic than sub-micron particles greater than 100 nm in size while the former evokes a more pronounced defense recruitment of alveolar macrophages and especially of neutrophil leukocytes at a higher phagocytosis activity of these cells. Results obtained compared to literature data show that a high cytotoxic action of nanometer copper oxide particles may be caused both by a copper ions intracellular release at solubilization and direct contact of persistent particles internalized by phagocytes with cell organelles (primarily, mitochondria) and their injuryas well.

Keywords: ultrafine copper-containing particles, bronchoalveolar lavage, cytotoxicity

The association of Bche gene polymorphisms with butyrylcholinesterase activity was investigated on a model of rats poisoned with malathion at a dose of 1 LD50.. The genotype distribution of six polymorphic variants of Bche gene was studied. An authentic association (p <0.05) of variants T>C (SNPID rs198598583), G>T (SNPID rs106118718), A>T (SNPID rs107226860) with butyrylcholinesterase activity in the liver tissue a day after poisoning was shown; the prevalence of those polymorphic variants is associated with linked type of inheritance. The highest linkage correlation of the enzyme activity in the liver was observed in variants A>T (rs107226860) and G>T (rs106118718). Enzyme activity in rats with a homozygous genotype was authentically higher ( by 30 %) compared to the heterozygous genotype.

Keywords: gene polymorphism, Bche gene, butyrycholinesterase activity, intoxication, malathion

Toxic properties of 3-bromo aminobenzene sulfate were studied for its hygiene regulation in workplace air. LD 50 of the substance administrated abdominally to female rats and male and female mice are respectively 1120, 2000 and 2973 mg/kg (III hazard class according to GOST 12.1.007-76). Significant differences in species and sex sensitivity of animals to the substance are not found: the coefficient of species differences is 2.7; coefficient of sex sensitivity is 1.5. It poses no local irritation to the skin and has a moderate irritant effect on the eye mucous membranes. Sensitizing effect is not revealed. It has a weak ability to cumulation: Ccum > 5. In a sub-acute experiment selective lesion of red blood cells (methemoglobinemia, sulfhemoglobinemia) with the development of hemolytic anemia of regenerative nature was observed, as well as damage to the liver and kidneys. The threshold of acute inhalation action is 22.2 mg/m3. The tentative safe exposure level in the workplace air is 1 mg/m3.

Keywords: 3-bromo aminobenzene sulfate, toxicological characteristics, hygiene regulation

The present work presents the rationale harmonization of maximum permissible concentration (MPC) of methyl mercaptan in the air with its standard values adopted in Sweden and Finland (0.006 mg/m3) in the air of areas with pulp and paper production. Based on these studies, it was found that harmonizied MPC of methyl mercaptan (0.006 mg/m3) reliably provides preventing of development of resorptive effects as well as protection of the population from “obsessive” odour. The normative was approved by the Chief State Sanitary Physician of the Russian Federation (GN 2.1.6.2326-08 - Attachment 4 to GN 2.1.6.1338-03).

Keywords: methyl mercaptan, maximum single limit permissible concentration, the reference concentration, resorptive effect, reflex action

Experimental studies of the biological action of the preparation (Hyalrepair-02) based on hyaluronic acid or its salt modified with ascorbic acid and amino acids were carried out in white rats. It was established that the drug did not produce any adverse effects on the animals organism: haemotological, biochemical and other indicators characterizing the state of systems and organs of animals exposed to test compounds had no statistically significant differences from similar control indicators . Based on the first stage of the studies, it could be said that this non-toxic compound may be used in cosmetics to treat minor facial defects to be aesthetically corrected (wrinkles, scars, etc.), in mesotherapy, biorevitalisation, bioreparation, contouring plastics and reconstructive surgery to replace soft tissues in traumatology for joint fluid replacement.

Keywords: hyaluronic acid, ascorbic acid, amino acids, Hyalrepair, toxicity

At present a large–scale oil and gas development work is carried out on the Russian sea shelf. Therefore it is necessary to know toxicity of the preparation MAX PLEX used on drilling platforms as there is a real possibility that its residual quantity could get in the soil posing harm to biological water resources. The preparation toxicity was assessed in accordance with «The Guidelines for determining toxicity of water, bottom deposits, pollutants, drilling fluid Huids using a biotesting method». Toxicity assessment was based on determining mean lethal concentrations EC50 and LC50 characterizing changes in survival (death) of standard sea test-organisms (Phytoplankton Phaedactylum tricornutum Bohin; zooplankton- Aryemia salina, fishes, one-day old fishes- Poecillia reticulate Peters) by 50% for a determined time period- 72, 48 and 96 hours (EC50/72h and LC50 /48 and 96 h). Based on toxicity assessment of the preparation for hydrobionts, it was established that the most sensitive test-object is Phaedactylum tricornutum Bohin having EC50/72h= 8.3 mg/l. According to the classification proposed by L.A. Lesnikov and K.K. Vrochinskiy, based on grading of acute toxicity to hydrobionts, the preparation MAX PLEX is classified as moderately toxic (for phytoplankton LC50 is 8.3 mg/l during 72h ).

Keywords: preparation, phytoplankton, zooplankton, fish, toxicity

The shungite effect on the culture of green chlorococcal microalga Scenedesmus quadricauda (Turp). Breb was studied based on the amount of 100 g / l potassium dichromate at a concentration of 3 mg /l. In the presence of shungite, the culture growth stimulation was observed, and in the presence of potassium dichromate the growth inhibition occurred compared to the control. It is shown that the combined action of potassium dichromate and shungite on the Scenedesmus quadricauda population eliminates toxic effect of potassium dichromate. The most rapid growth of the culture occurred when only shungite was added to the culture medium, while the photosynthesis efficiency, number of cells and proportion of living cells increased in the presence of shungite. Apparently, shungite in the culture medium acts, on one hand, as sorbent, and on the other alters the redox state of the medium. The mechanism of action of shungite is nonspecific and can be used as a universal remedy for water purification from various pollutants.

Keywords: Scenedesmus quadricauda, potassium dichromate, shungite cell viability, fluorescence, photosynthetic efficiency