In the dissertation work, a theoretical generalization and practical solution of one of the current scientific problems of preventive medicine was carried out regarding the substantiation of methodical approaches to the risk assessment of the combined effect of the active substances (a.s.) of pesticides on human health when they enter the body with food products of plant origin based on the grouping of dr. according to the general mechanism of toxicity (GMT), the creation of cumulative assessment groups (CAG), the use of the concept of the hazard index (HI) and the relative potency factor (RPF), in order to determine the total margin of exposure (MOET) and development of preventive measures to eliminate or reduce risk aimed at protecting public health.
Based on the results of a hygienic assessment of the range of active substances of mixed preparations used in Ukraine to protect grain crops, apple orchards and potatoes, the identification of 85 a.s. was carried out for the first time according to clearly established criteria of danger (toxicological end points) reflecting the specific effect and their distribution in CAG according to the effect on the nervous system (NS), thyroid gland (TG) and liver. It was established that 20 a.s. capable of causing acute effects of functional changes in three departments of the nervous system (motor, sensory and vegetative), 3 a.s. are characterized by a specific neurotoxic effect – inhibition of acetylcholinesterase (AChE) activity, 4 a.s. with chronic exposure can cause pathological changes in the nervous system due to degeneration of axons and myelin. 27 a.s. have an effect on the thyroid gland, which is mainly mediated through the induction of liver enzymes. 48 a.s. were included in CAG for hepatotoxic effects. For these substances, the no observed adverse effect level (NOAEL) turned out to be the lowest and was used in the justification of the acceptable daily intake (ADI) for humans.
Using HI and RPF, the hazard characterization of combined exposure of 10 a.s. was conducted for the first time (acetamiprid, imidacloprid, lambda-cyhalothrin, myclobutanil, pyraclostrobin, tebuconazole, thiamethoxam, trifloxystrobin, fluopyram and cypermethrin), which are widely used in the integrated system of chemical protection of grain crops, apples and potatoes, which increases the probability of their multi-residues appearing in one sample final products. For the index compound (IC) in the group of studied a.s. lambda-cyhalothrin was chosen, which is characterized by the most complete toxicological database. Relative to IS, PRFs for other substances and their total cumulative exposure (Etotal) were also calculated for children aged 2 to 6 years and adults. The conducted studies showed that the combined effect of the active substance per unit of body weight of children, calculated according to the scenario of using the maximum residue level (MRL), is higher. The risk of exposure to residual quantities of a.s. of pesticides when they enter the body of children together exceeds the permissible limit both with the use of HI and RPF.
For a comparative assessment, a ranking of the contribution of the active substances to the total combined risk of combined exposure was carried out. Among the studied a.s. the largest contribution to the Etotal with bread products is given by cypermethrin, which is due to its high MRL (0.1 mg/kg) compared to the fairly low ADI (0.003 mg/kg), despite compliance with the principle of complex hygienic rationing. Fluopyram (68.80-70.06) % is characterized by the largest contribution to Etotal with apples at reference values: ADI – 0.01 mg/kg, MRL – 0.5 mg/kg. Cypermethrin (20.16-20.43) % is characterized by the largest contribution to Etotal with potatoes. Thus, the obtained results can be used in the justification of management decisions regarding the revision of the MRL for those years with the greatest exposure impact.
At the next stage of research, a comparative toxicological and hygienic evaluation of the new fungicidal drugs "Miravis 200 SC" (adepidynTM (pydiflumetofen), 200 g/l), "Miravis Ace 275 SE" (adepidynTM (pydiflumetofen), 150 g/l) was carried out + propiconazole, 125 g/l), "Miravis Neo 300 SE" (adepidynTM (pydiflumetofen), 75 g/l + azoxystrobin, 100 g/l + propiconazole, 125 g/l).
It was established that the combined fungicides "Miravis Neo 300 SE" and "Miravis Ace 275 SE" are more toxic in the mode of single oral exposure compared to the single-component fungicide "Miravis 200 SC". The type of combined action of adepidyn™ (pydiflumetofen), azoxystrobin and propiconazole was determined and the potentiation coefficient (CP) was calculated at the level of 1.9 for "Miravis Ace 275 SE" and 6.9 for "Miravis Neo 300 SE", which indicates increased toxicity (potentiation), which can be considered as a consequence of simultaneous exposure to these substances.
