Toxicodynamics of Chlorpyrifos and “Ivin” Combined Action under Prolonged Admission

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.