No 5 (2019)

The paper retraces the development of a mechanistic multi-chamber model describing particle retention in lungs in chronic inhalation exposures. This model was first developed and experimentally tested for various conditions of exposure to polydisperse dusts of SiO₂ or TiO₂, and later successfully used as a basis for analyzing patterns in the retention of nanoparticles (NP) having different chemical compositions (Fe₂O₃, SiO₂, NiO). The most significant adaptation of this model for exposure to element oxide NPs was due to the need to take into account not only the physiological mechanisms of their elimination, but also their solubility «in vivo». It has been found that the relative contribution of the latter might be different for nanoparticles of different nature and predominant in some cases. The modeling of NiO-NPs retention also suggests that damage to the physiological pulmonary clearance mechanisms by particularly toxic nanoparticles might result in lung toxicokinetics becoming nonlinear.

The article presents the results of the study on toxicity of 3-chloropropyl and 6-chlorohexyl acrylates in acute (at the level of lethal and sublethal doses and concentrations) and subchronic experiments (dose-monotone intake at the level of 0.1 DL₅₀ per os for 45 days), which allowed to justify the value of approximately safe levels of exposure for chemicals in the air of the working area. Scientifically substantiated values of approximately safe exposure levels for 3-chloropropyl acrylate at 5 mg/m³ and for 6-chlorohexyl acrylate at 2 mg/m³ have been established.

A comprehensive assessment of the role of stromal cells in regenerative processes has been carried out on the model of diffuse toxic liver damage with carbon tetrachloride (CCl₄) and its correction with aminophthalhydrazide. It has been found that the immunomodulating effect of aminophthalhydrazide is manifested in a decrease in leukocyte infiltration, there is a sharp decrease in the level of CD45⁺ to the values of intact animals on the 7^th and 14^th days of the experiment. The number of CD3⁺ lymphocytes, mast cells and the area occupied by collagen are also reduced. Since the introduction of aminophthalhydrazide reduces the number of CD45⁺, CD₃+ lymphocytes, but the number of sinusoidal cells increases compared to group of animals treated only with CCl₄, it can be assumed that the decrease in the toxic effect of CCl₄ is associated with the change in the number and functional activity of sinusoidal cells, which is aimed at removing the inflammatory response and restoring hepatic tissue after toxic damage.

The influence of long-term effects of acute poisoning by neurotoxicants on changes in the concentration of neurotrophic factors and factors of apoptosis in laboratory animals has been experimentally investigated. Acute sodium thiopental poisoning was modeled by a single intraperitoneal injection at a dose of 85 mg / kg. In one month after the poisoning the surviving animals were euthanized to select biological material. Changes in concentration of neurotrophic markers: MBP, NSE, BDNF and PEDF in blood serum of laboratory animals and apoptotic factors in brain tissues: caspase 3, caspase 9 and protein p53 have been estimated by ELISA and immunohistochemistry, respectively. The results showed impaired homeostasis of brain neurotrophic factors studied in serum, as well as induction of apoptotic reactions studied in brain tissues of laboratory rats. These changes are one of the pathogenetic links of the mechanism of damage to the nervous system, which can be manifested in violation of higher nervous activity, including changes in behavioral reactions and cognitive functions.

The aim of this work was to evaluate the thyroid status in mouse-like rodents under the influence of synthetic pyrethroid cypermethrin.

The studies were performed on 168 male rats (Rattus norvegicus) and 112 male red voles (Myodes rutilus). When simulating acute intoxication, cypermethrin was injected once into the stomach at a dose of lA LD50 followed by observation of rats for 30 days and voles for 7 days. When studying chronic intoxication, cypermethrin was administered to rats at a dose of 1/100 LD50, the duration of the experiment was 120 days. Acaricidal treatment of the forest was carried out on a one-hectare site, and the results of the capture of voles and their thyroid status were compared with voles caught on the background site.

Synthetic pyrethroid cypermethrin in acute and chronic experiments causes a change in thyroid status in laboratory rats, which is reflected in a decrease in the level of thyroid hormones in the blood serum. Moreover, there is an increase in the level of thyroid-stimulating hormone in rats. The introduction of a high dose of cypermethrin (A LD50) into male voles under field vivarium conditions also revealed the sensitivity of representatives of this species to the action of synthetic pyrethroids, which was manifested in a decrease in the synthesis of T4 and T3 in their thyroid glands. Acaricidal forest treatment contributes to a temporary change in thyroid status in male red field vole (Myodes rutilus) caught in the treated area, which, apparently, is a consequence of adaptive changes and migration processes in the population of this species.