The dissertation is devoted to the study of changes in Wistar Hannover rats blood system under the condition of acute oral intoxication with some triazole fungicides and determination of their hematotoxic action mechanisms. Complex, in-depth hematological studies of the effects of epoxiconazole (EPO), cyproconazole (CYP) and tebuconazole (TEB) in the dynamics with the analysis of one of the main toxicological dependencies "time-effect" have been carried out. Additional methods for hematotoxicity assessment along with standard ones were used: morphological with analysis of cell structure injury, cytochemical and study of hematopoiesis in bone marrow (BM) and spleen. As a result, cytotoxic effect on peripheral blood (PB) cells was the main hematotoxic mechanism for all investigated triazole fungicides. EPO and CYP caused significant leukocytes destruction in the vascular channel, the growth of leukolysis forms and number of partially destroyed cells, mostly neutrophilic. The number of neutrophils with degenerative changes in nuclei (EPO, CYP, TEB) was increased. The appearance of morphologically modified "tailed" and villous lymphocytes (EPO) was shown. Erythrocytes membranopathy (acanthocytosis) and the presence of microspherocytes due to the weak hemolytic effect of TEB were established. Development of erythropoiesis was carried out pathologically (EPO, TEB): nucleated red blood cells with atypical structure were evidenced in blood circulation. The appearance of phagocytic macrophages with captured destroyed cells and cellular components (EPO, CYP, TEB) and destructive erythrocytes (TEB) in response to cytotoxic action were established. Monoblasts (EPO) and promonocytes output (EPO, CYP, TEB) into PB were obtained. Stimulation of monocytopoies in the BM has been occurred on 3d postexposed day (PED) in order to fully provide this protective reaction. Macrophages were transformed from this progenitors and monocytes directly in the bloodstream. Macrophages were circulated in blood to the end of experiments (14 PED) for all substances. Due to the CYP intoxication, their quantitative content in the vascular channel was the highest among all studied triazoles. Macrophages function was to clean bloodstream from destroyed and pathologically altered cells. Hypoxia (1-3 PED), erythrocytosis, polychromasia were a common response to intoxication by all studied triazoles. In addition to the main mechanism of action, other changes were established: compensatory leukocytosis, neutrophilia (after CYP intoxication - intense with left shift to metamyelocytes), hypersegmentosis from the marginal pool of neutrophils; lymphocytopenia with increase of prolymphocytes number (EPO, TEB) and weak suppression of lymphocyte precursor cells in the BM (CYP). Inhibition of succinate dehydrogenase and acid phosphatase activity in lymphocytes were noticed on the 1 PED due to the toxic effect of TEB. Naphthol-AS-D-chloracetateterase activity in neutrophils, succinate dehydrogenase, acid phosphatase activity in lymphocytes increased (EPO, CYP, TEB). Quantitative changes of immunocompetent cells ammount (by the reaction type to acid phosphatase) were observed. An anemic effect was detected by EPO and TEB intoxication. As a result of BM and the spleen hemopoiesis studies, several additional mechanisms of TEB hematotoxic action were identified: disturbance of hemoglobin formation, dyserythropoiesis with pathological regeneration and the development of substitute extramedullary erythropoiesis in the spleen, suppressive action on eosinophilopoiesis and basophilopoiesis have been established.
