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Chronic toxicity of new pyridine-n-oxide derivatives for tetrahymena pyriformis w, determination of “structure-toxicity”, “concentration-time-effect” correlation

There is a considerable amount of work in the scientific literature on nonlinear (“paradoxical”) effects, but their toxicological significance for the body is still poorly understood. Plant growth regulators are biologically active substances at the level of low and ultra-low doses and concentrations, they are widely used in agriculture. To date, the mechanisms of their toxic and specific effects on the body, the presence of “paradoxical” effects at low doses have not been sufficiently studied. Thus, it is important to further indepth study of the “concentration-time-effect” relationship under chronic exposure to the body, which will be important for understanding the general biological processes, developing approaches to hygienic regulation and risk assessment for human health and non-target environmental objects.

The Aim of the Research. Determine the dependence of “structure-toxicity”, “concentration-time-effect” of plant growth regulators – pyridine-N-oxide derivatives under conditions of chronic effects on the body of ciliates Tetrahymena pyriformis W.

Materials and Methods. The object of research was complexes of methyl derivatives of pyridine-N-oxide with organic acids and metal salts. Studies were performed on ciliates of Tetrahymena pyriformis W in the stationary phase of growth. The chronic effect of plant growth regulators on ciliates was studied in a 96-hour experiment in the concentration range from 1×10 -2 M to 1×10-28 M. The initial number of ciliates in the sample was 20,000 cells/ml of culture medium. The samples were incubated in a dry air thermostat at 25°C. After 24, 48, 72, 96 hours, the number of ciliates in different growth phases was determined. The experiments were performed in four replicates. The results of the research were subjected to mathematical processing by methods of variation statistics using the standard software package Microsoft® Office Excel 2010.

Results. It is shown that at a concentration of 1×10-2 M investigated complexes of methyl derivatives of N-oxidepyridine with metal salts are more toxic than with organic acids. In the range of concentrations from 1×10-4 M to 1×10-28 M dependence "concentration-timeeffect" was not detected. Regardless of the concentration and duration of action, both inhibition and induction of ciliate population growth were observed. The change in the direction of the effect was observed at the level of high, low and ultralow concentrations.

Conclusions. 1. Under conditions of chronic exposure to the population of ciliates Tetrahymena pyriformis W, the rate of growth inhibition at a concentration of 1×10-2 M, studied complexes DG-377 (Di-2,6-dimethylpyridine-N-oxide with ZnCl2), DG-380 (Di-2,6-dimethylpyridine-N-oxide with ZnI2), DG-387 (Di-2,6-dimethylpyridine-N-oxide with CoCl2), DG-480 (2-methylpyridineN-oxide with CoCl2), DG-471 (Di-2-methylpyridine-N-oxide with CoI2) are more toxic than similar complexes with organic acids – DG-361a (2,6-dimethylpyridine-N-oxide with succinic acid), DG-361 (Di-2,6-dimethylpyridine-N- with succinic acid), DG-362 (2,6-dimethylpyridine-N-oxide with maleic acid), DG-349a (2-methylpyridine-N-oxide with succinic acid).

2. In the range of concentrations from 1×10-4 M to 1×10 -28 M, regardless of the concentration and time of action, there is both inhibition and induction of growth of the ciliate population. The change in the direction of the effect was observed at the level of high, low and ultralow concentrations. The growth of the ciliate population, depending on the concentrations of the studied substances and the time of exposure, was polymodal in nature.

3. According to the direction and severity of the effect on the growth of the ciliate population for DG-361a, DG-361, DG-377, DG-387, DG-349a and DG-480 is characterized mainly by an inhibitory effect. The stimulating effect was observed in some phases of growth and was moderate or weak. For DG-362, DG-380 and DG-471 is characterized by a pronounced stimulation of population growth of ciliates.

Key Words: methyl derivatives of pyridine-N-oxide, ciliates, “structure-toxicity”, “concentration-time-effect”.