The combined action of pesticides is one of the problems of toxicology, because in comparison to individual active substances, their mixtures can increase toxicity and delayed action effects, which is a risk to human health. It is known that plant growth regulators (PGR) when applied together with pesticides help to reduce the quantitative rates of pesticides applied, the accumulation of pesticides and heavy metals in plants, reduce the acute toxicity of xenobiotics. The combined effect of the prolonged admission of PGRs and pesticides is an unexplored area, and it is an important issue in preventive toxicology. The Aim of the Research. Determination of the nature of toxic effects of Chlorpyrifos and “Ivin” combined action at subchronic oral admission. Materials and Methods. Chlorpyrifos and PGR “Ivin” (2.6-dimethyl-N-pyridine oxide) combined action was studied on male Wistar Han rats. Substances were administered orally, via a feeding tube for 13 weeks; Chlorpyrifos was administered in the form of an aqueous emulsion with an auxiliary material OP-10 at a dose of 5 mg/kg (1/15 LD50), “Ivin” — in the form of an aqueous solution at a dose of 13 mg/kg and 0.013 mg/kg (1/100 and 1/100000 LD50 respectively), the control group of rats was given water with an auxiliary material OP-10. Signs of intoxication were recorded, body weight was measured in 4, 9 and 13 weeks, biochemical indicators of blood serum were determined (the activity of ALT and AST enzymes and alkaline phosphatase; the content of crude protein, urea, cholesterol, triglycerides and glucose were determined using kits of reagents by BioSystems (Spain); cholinesterase (ChE) activity in serum, red blood cells and brain tissue was determined with the use of methodology by Hesrtin S. using a kit of reagents produced by LLC NPP Filisit-Diagnostics (Ukraine). Results. No clinical signs of intoxication were detected in the experimental groups of rats. Under the isolated use of Chlorpyrifos a significant decrease in body weight, ChE inhibition activity in all bio substrates, with the greatest effect in the brain (by 48.8%); increase (after 9 and 13 weeks) in the activity of ALT and AST by 26.7–32.6%, 12.5–12.0%; a slight but a significant increase in the level of urea and glucose in blood serum to 17.3% and 17.6 %, respectively was detected. Under the combined action of Chlorpyrifos and “Ivin” in specified doses the body weight of rats was at control level, decrease of ChE activity was observed in all biological substrates and was at nearly the same level with the isolated use of Chlorpyrifos. There was a tendency towards the decline in ChE inhibition activity in brain tissue, and under the combined action of Chlorpyrifos with “Ivin” at higher doses after 4 weeks this effect was a significant (22.15%, p < 0.05). Conclusions. Chlorpyrifos under the isolated oral admission for 13 weeks has a weak hepatotoxic effect, as evidenced by the increase in cytolysis enzymes and urea levels in serum and causes a moderate anticholinesterase effect. “Ivin” under combined with Chlorpyrifos admission to the organism eliminates the hepatotoxic effects of Chlorpyrifos and reduces its anticholinergic effects in brain, which contributes to a less severe intoxication. Key Words: Chlorpyrifos, Ivin, hepatotoxic effect, anticholinesterase effect.

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The aim: To study the antihypoxic activity of 2,6-dimethylpyridine-N-oxide in mice using the various experimental models of acute hypoxia under orally or intraperitoneally administration. Materials and methods: The studies were performed on male CD-1 (SPF) mice. The antihypoxic activity of 2,6-dimethylpyridine-N-oxide was studied in three experimental models of acute hypoxia - hypercapnic hypoxia or hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia at orally administration at doses 0.07; 7.1 and 71 mg/kg (respectively 1/20000, 1/200 and 1/20 of LD50) and at intraperitoneally administration at doses 7.1 and 71 mg/kg in comparison with reference drug Armadin. Results: It is established, that 2,6-dimethylpyridine-N-oxide shows a antihypoxic activity in the all experimental models of acute hypoxia (hypoxia in a closed space, hemic hypoxia and histotoxic hypoxia). Its antihypoxic activity in acute hemic hypoxia and in acute hypoxia in a closed space was significantly higher than of reference drug Armadin, but during acute histotoxic hypoxia did not differ from Armadin. Also at intraperitoneal administration of 2,6-dimethylpyridine-N-oxide demonstrates less pronounced antihypoxic activity than at oral administration in all experimental models of acute hypoxia, but the coefficient efficiency is higher than in the reference drug Armadin. Conclusions: 2,6-dimethylpyridine-N-oxide may be recommended for further detailed experimental studies as a perspective antihypoxant.

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The study objective was to determine the functional state of infusoria Tetrahymena pyriformis W by parameters of motor activity and energy consumption for movements under acute effects of plant growth regulators — N-oxide pyridine derivatives, their complexes with organic acids and metal salts. Materials and methods. 2,6-dimethylpyridine-N-oxide, 2-methylpyridine-N-oxide and their complexes with organic acids (succinic, maleic) or metal salts (ZnCl2, ZnI2, CoCl2, MnCl2) — in total, 13 substances, synthesized at the Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine have been used in the work. Studies have been carried out on the infusoria Tetrahymena pyriformis W in isotoxic doses — at the level of toxic concentrations — LC50, LC16 and inactive concentrations (LC0). Motor activity and energy state of infusoria using an automated laser Doppler spectrometer were evaluated. Results and conclusion. It was shown that the studied N-oxide pyridine derivatives and their complexes with organic acids or metal salts inhibit the motor activity of the infusoria and increase energy consumption for movements with the greatest effect in the concentrations of the corresponding LC50. 2,6-dimethylpyridine-N-oxide, 2-methylpyridine-N-oxide, and their complexes with succinic acid and metal salts of CoCl2 and ZnCl2 were the most toxic for the viability of infusoria. Therefore in order to assess the toxicity ofxenobiotics and viability of infusoria Tetrahymena pyriformis W, it is reasonable to recommend parameters of motor activity and energy consumption per unit of the rout that have the highest criterial significance. Key words: toxicity, plant growth regulators, N-oxide pyridine derivatives, Tetrahymena pyriformis W.