The aim: The toxicological-hygienic assessment of dermal absorption of diquat in terms of potential risk of its bioavailability in professional use. Materials and methods: The object of the study was cutaneous exposure of diquat, determined in toxicological experiments of different duration (data of scientific literature) and at the stage of state testing of pesticide preparations based on diquat dibromide (data of a full-scale hygiene experiment, prognostic model of risk assessment), the technical concentrate of diquat dibromide (active substance content not less than 377 g / kg) contains relevant supplements, the content of which is regulated by the Food and Agriculture Organization. Results and conclusions: Due to the high risk of the diquat adverse effects affecting the personnel, general public and environment, the European Union has introduced administrative decisions to forbid plant protection products containing the diquat. Fulfillment of the conditions of the Association Agreement between Ukraine and the European Union indicates the need to develop common regulations and risk assessment methods aimed at ensuring high level of protection of human health and the environment.

The aim: Hazard characterization and assessment of combined exposure to several pesticides when they simultaneously get to the human body with bakery products. Materials and methods: Methods of analytical analysis of the range of pesticide active substances, which are registered and used in modern systems of grain crop protection in Ukraine, were used in the study. Normative documents of national legislation on hygienic regulation of pesticides and methodological approaches to assessing the combined e!ects of pesticide mixtures in food products serve as materials for assessment. Results: It is established that the total risk of exposure to residual amounts of pesticides in bread products (wheat and rye bread) during its comparable getting into the body was 0.59 for children 2-6 years and 0.36 - for adults, with an allowable value of ≤ 1.0. The combined e!ect of pesticides per unit of children’s body weight is higher, but also lies within acceptable limits. The largest contribution to the overall risk of combined exposure to triazoles is made by flutriafol (38.5-47.0%), which in the future may be the basis for substantiating measures to reduce such exposure and make appropriate management decisions. Conclusions: Safety of consumption of agricultural products is ensured by strict following hygienic regulations for the pesticide application (application rates, frequency of treatments, pre-harvest intervals), which makes it impossible to accumulate their residual amounts in food. Triazole pesticides, widely used in almost all crop protection systems, pose a potential risk of adverse health e!ects due to additive or synergistic effects.

Background: The quality and safety of agricultural product, grown with the application of chemical plant protection products, is an urgent problem of preventive medicine. The occurrence of multiple pesticide residues in the foodstuffs is of concern to the general public and is engaging scientists in the search for approaches to the assessment and control of multi-residues. Objective: We analyzed a range of the active substances of combined pesticides used in Ukraine in modern apple orchard protection systems, characterized a hazard and assessed the combined exposure to several pesticides at their joint ingress with apples into the human body. Materials and methods: In the work, we applied the methods of analytical research of the range of active substances of pesticides, registered and used in Ukraine in modern systems of apple orchard protection, by functional purpose (herbicides, insecticides, acaricides, fungicides); used the normative documents of national legislation on hygienic regulation of pesticides and methodological approaches to the assessment of the combined effects of pesticide mixtures in the foodstuffs. Results: According to the results of the analysis of the residues of active substances of pesticides in apples, the conclusion about the low level of short-term (acute) risk for health consumers has been made. However, it is impossible to ignore a presence of many pesticides with a similar mechanism of biological action in food, and hence, a possibility of their additive or synergistic effect on health. Conclusions: Further research should be aimed at assessing the exposure and identifying the health hazards of the consumers from the combined effect of pesticides, applied for vegetables and cereals, by established groups of substances with a general effect mode / mechanism.

Annotation. The creation of combined pesticide formulations for the purpose of more effective protection of agricultural crops is a significant factor in the importance of assessing their synergistic effects. Substances that produce a similar pesticidal effect, in combination with each other, can enhance the toxic effect and, therefore, show dose additivity. The aim is toxicological and hygienic evaluation and determination of the type of combined action of pydiflumetofen, azoxystrobin and propiconazole – the active substances of the mixed formulations “Miravis Ace 275 SE” and “Miravis Neo 300 SE” according to toxicity indicators. Analytical review of scientific publications was carried out using data from EFSA, FAO, ECHA, PPDB, Internet sites. According to the literature, a comparative toxicological-hygienic evaluation of fungicidal preparations and their active substances was carried out. The general mechanism of fungicidal action was evaluated according to the classification developed by the Fungicide Resistance Action Committee (FRAC). The hazard class according to the toxic metric parameters of the substances under study was determined in accordance with the Hygienic classification of pesticides according to the degree of hazard (DSanPiN 8.8.1.002-98). The nature and type of combined action was carried out according to the Finney method with evaluation according to the criteria of acute toxicity. Systematization of data, their structuring for the purpose of further toxicological assessment of substances at the level of their inactive and threshold doses was carried out in the table editor Microsoft Excel 2019 (Microsoft Office 2019, Microsoft). As a result of the conducted research, the most toxic mixed fungicide “Miravis Neo 300 SE” based on three active substances was determined (the average lethal dose (LD50) is 550 mg/kg). It has been established that in cases of combinations of active substances to obtain a lethal effect, a dose of substances that does not exceed 100% in total is required, which indicates the strengthening (potentiation) of toxicity. It was pointed out that the share of propiconazole in the potentiation of the toxic effect in both mixed preparations is the highest compared to other active substances and is 0.87 for “Miravis Neo 300 SE” and 0.88 for “Miravis Ace 275 SE”. It was observed that the adverse effects of simultaneous exposure to several pesticides may change during the transition from acute to chronic exposure. Therefore, it is important to continue the research of the active substances of pesticides with the determination of limiting criteria for harmfulness, taking into account the remote effects of exposure. Thus, the toxicological and hygienic assessment made it possible to establish that the combined fungicides “Miravis Neo 300 SE” and “Miravis Ace 275 SE” are more toxic in the mode of single oral exposure in comparison with the single-component fungicide “Miravis 200 SC”. Increased toxicity (potentiation) can be considered as a consequence of the simultaneous exposure of several active substances. The active substance propiconazole poses the main danger of adverse effects on the body at the level of lethal doses. The obtained values of the potentiation coefficients will be taken into account in further studies of the risk assessment of complex and combined effects of pesticides on workers and their potential danger when entering the human body with food products.