Toxicological and hygienic assessment of Sivanto Prime 200 SL and its active ingredient — flupyradifurone, justification of ADD of flupyradifurone was performed as per the results of studies conducted by the manufacturer and according to the literature data [1,2] in line with guidelines [3] and current Ukrainian hygienic classification [4]. Changes in the content of flupyradifurone over time in agricultural crops, justification of its maximum allowable level (MAL) in grapes, apples, pears and juices made of them, cabbage were studied as per [3] and fundamental principles laid down in the guidelines of UN Food and Agricultural Organization (FАО) [5]. Sampling and transportation of samples for the studies were performed according to the unified rules [6].

Content of flupyradifurone in the study objects was measured using recommended guidelines [7–9]. Limit of quantification (LoQ) — by high-performance liquid chromatography (HPLC), in particular in grapes, apples, pears — 0.02 mg/kg; grape, apple and pear juices, cabbage — 0.01 mg/kg.

For justification of the tentative safe exposure level (TSEL) of flupyradifurone in working and atmospheric air, guidelines were followed [10–12].

Development and justification of maximum allowable concentration (MAC) of flupyradifurone in water of water bodies was performed as per guidelines [3] and fundamental provisions [13,14]. According to the developed guidelines on detection of flupyradifurone in water of water bodies [15], LoQ of a substance by HPLC — 0.002 mg/dm³.

Justification of tentative allowable concentration (TAC) of flupyradifurone in soil was performed as per the guidelines [16]. LoQ of flupyradifurone in the soil — by HPLC as per developed guidelines [17] — 0.02 mg/kg.

For prediction of hazard exposure of flupyradifurone on rural labourers, calculation of the coefficients of selectivity (CoS) that are the ratio between efficient consumption rate and median lethal dermal dose (CoSd) and concentrations of inhalation exposure (CoSi) was performed. The results were evaluated according to the scale: CoS < 1 — very poor selectivity, CoS from 1 to 99 — poor selectivity, CoS ≥ 100 — sufficient selectivity [18].

Study and assessment of hazard exposure of Sivanto Prime 200 SL on rural labourers who applied it and during processing of areas after application of insecticide, as well as potential exposure to the population at the boundary of sanitary protection zone during spraying with the product was performed as per guidelines [3] and recommendations [19].

Measurement of flupyradifurone content in the production and environmental objects was performed as per requirements in the guidelines [17, 20]. Limits of quantification of the active substance by HPLC in working air — 0.1 mg/m³, in atmospheric air — 0.005 mg/m³, and in soil — 0.02 mg/kg.

Results and their discussion. According to the Hygienic Classification of Pesticides by Hazard Level (DSanPiN (State Sanitary Regulations and Rules) 8.8.1.002-98) [4], technical flupyradifurone by the parameters of acute oral and dermal toxicity belongs to hazard class 4, acute inhalation toxicity — to hazard class 2, by skin irritation action — to hazard class 4, and on eye mucous membranes — to hazard class 3, by allergenic action — to hazard class 3. By the limiting toxicity parameter, flupyradifurone belongs to hazard class 2 pesticides.

Sivanto Prime 200 SL, according to the DSanPiN 8.8.1.002-98) [4], by the parameters of acute oral toxicity belongs to hazard class 4, acute dermal — to hazard class 3, acute inhalation toxicity — to hazard class 2, by skin irritation action — to hazard class 4, and on eye mucous membranes — to hazard class 3, by allergenic action — to hazard class 3. By the limiting harmful index, Sivanto Prime 200 SL belongs to hazard class 2 pesticides.

Toxicokinetics and metabolism of flupyradifurone were studied in rats after 3 mg/kg single oral doses of the radiolabeled substance. It was shown that flupyradifurone is rapidly absorbed and eliminated from the body. The highest concentration of radioactive tracer was registered in bone tissue in 1 hour (males — 38.3 %, females — 51.2 %), however, it rapidly decreases and amounted to 3–4 % of a higher dose in 24 hours, respectively. Plasma concentration of labelled flupyradifurone was low (1.27 to 0.1 %). Elimination of radioactivity was predominantly with urine — within the first 24 hours after administration 71.8 % in males and 85.88 % in females.

The main biotransformation pathways — hydroxylation with further glucuronization, cleavage of difluoroethyl group with formation of difluoroacetic acid, breaking in pyridine methyl bond with formation of flupyradifurone-difluoroethyl aminofuranone.

Urine predominantly contains flupyradifurone (47.7 %) and main metabolites — difluoroacetic acid, flupyradifurone-difluoroethyl aminofuranone (1–5 %).

Cumulation, retention and persistence in the body are not typical to flupyradifurone.

Toxicokinetics of flupyradifurone in blood plasma was studied in rats receiving this substance with feed in the concentration of 400 ppm (22.6 mg/kg — males and 32.4 mg/kg — females) during 7 days. Plasma concentration of the substance did not significantly differ in males and females (7.8–8.3 mg/mL and 8.8–9.4 mg/mL, respectively).

Chronic intoxication in rats was characterised by mild anaemia and hepatotoxic effects (reduced glucose and bilirubin concentration, raised serum concentration of cholesterol, hypertrophy of hepatocytes, reduced glycogen stocks in hepatocytes). Also, thyroid gland of males demonstrated hypertrophy and pigmentation of follicular cells, cases of involved colloid. These changes in the thyroid gland are not significant in terms of toxicity since their severity was minimal, they were found only in males and reported in control animals. NOAEL for rats — 400 ppm (15.8 mg/kg for males and 22.5 mg/kg for females).

Chronic exposure to flupyradifurone to mice body resulted in mild hepatotoxicity and nephrotoxicity (reduced absolute and relative weight of the liver and kidneys, liver of some animals showed macrosocio-economic of hepatocytes in males; and in kidneys — cortical mineralization, basophily of tubular cells). NOAEL for mice — 300 ppm (43 mg/kg for males and 53 mg/kg for females).

The main parameter of flupyradifurone toxicity in dogs was bodyweight reduction and minimal degeneration of muscular fibres in calves and biceps muscles of thighs. NOAEL for dogs — 300 ppm (7.8 mg/kg for males and females).

The main target organs of flupyradifurone toxicity in rats is the liver and thyroid gland, in mice — liver and kidneys, in dogs — skeletal muscles, kidneys and liver. Flupyradifurone is the inducer of cytochrome P450.

The selectivity of flupyradifurone in terms of the nervous system was not reported.

Acute single action resulted in flupyradifurone NOAEL by the toxicity action in rats at the level of 50 mg/kg. NOAEL by neurotoxicity in the subchronic experiment for rats — 2,500 ppm (143 mg/kg for males and 173 mg/kg for females). Upon neurotoxicity study for the development of rats offspring, NOAEL was established at the level of 500 ppm (42.4 mg/kg).

Flupyradifurone has no mutagenic and carcinogenic action. Flupyradifurone NOEL for pregnant female rats is 15 mg/kg and NOАEL for foetal development — 15 mg/kg, NOEL for pregnant female rabbits is 15 mg/kg and NOАEL for foetal development — 7.5 mg/kg. NOAEL by reproductive and systemic toxicity for rats in two-generation tests was 100 ppm (6.4 mg/kg for males and 7.7 mg/kg for females). By its teratogenicity, embryo- and reproductive toxicity, flupyradifurone belongs to hazard class 3. By its mutagenicity and carcinogenicity — to hazard class 4.

Flupyradifurone metabolites — difluoroacetic acid, f lupyradifurone-difluoroethyl aminofuranone, (6-chloro-3-pyridyl)methanol, 6-chloronicotinic acid, flupyradifurone-aminofuranone, and flupyradifurone acetic acid are moderate- to low-toxic substances. Nature of their toxic action after repeated administrations is similar to flupyradifurone, and they have no mutagenicity.

Considering limiting NOAEL of flupyradifurone based on reproductive and systemic toxicity for rats in two-generation test 6.4 mg/kg in males and safety factor 300, the recommended and approved ADD for human in Ukraine is 0.02 mg/kg.

Flupyradifurone metabolism was studied in target plants (apple trees, cotton, rice, tomatoes and potatoes) under different technological applications (spraying of plants and soil, processing of bulbs and introduction to the soil in the form of granules), as well as in further rotation crops. The studies were performed using ¹⁴ C-labelled flupyradifurone by pyridinyl or furanone unit. Also, label by difluoroacetic acid was used upon introduction of flupyradifurone to the soil.

Metabolism of the substance was similar for all plant groups. The main component of distribution of pyridinyl unit of the molecule was flupyradifurone (25–88 % from the introduced concentration). Metabolites containing furanone unit were virtually undetectable, and the main components were natural glucosides and carbohydrate components that specify wide degradation of furanone analogue.

Laboratory studies of aerobic degradation of flupyradifurone under the standard conditions at 20 ⁰С in different soils have established that average Т₅₀ of substance is 73 days. The main metabolites are difluoroaceticacid (maximum 33.9 %) and 6-chloronicotinic acid (maximum 17.1 %). Т₅₀ of which is 45–75 days and 2–37 days, respectively. Then СО₂ (maximum 59 %) and non-extractable residues (maximum 34 %) are formed. Under anaerobic conditions in the soil, flupyradifurone is stable, and its degradation predominantly develops due to photolysis.

Estimated values of flupyradifurone T₅₀ in the soil under field conditions: Germany — 39–43 days, Italy — 8 days, Spain — 23 days.

Thus, according to the stability in the soil as per DSanPiN 8.8.1.002-98, flupyradifurone may be classified as hazard class 2 pesticides (stable in soil).

Studies of desorption and adsorption of flupyradifurone in soils have shown that flupyradifurone belongs to substances with moderate mobility in the soil, its metabolite difluoroacetic acid — to the substances with high mobility in the soil, and metabolite 6-chloronicotinic acid — to the substances with moderate mobility in the soil. Calculations of the possibility of migration of flupyradifurone and its two metabolites to the groundwaters have shown that their migration is expected at the level below 0.0001 mg/dm³.

Flupyradifurone is stable to hydrolysis within the entire range of pH. Its degradation is faster due to photolysis. Degradation in the buffer solution and sterile natural water — Т₅₀ — 2.7 days. In an anaerobic system “water/sludge”, the substance is predominantly in the aquatic phase and degrades poorly. Overall Т₅₀ in the system is 190–250 days.

According to DSanPiN 8.8.1.002-98, the above data allow classifying flupyradifurone by the stability in water to hazard class 1 pesticides (highly-stable in water).

Difluoroacetic acid is formed in the aquatic system (6 %) with further mineralization to СО₂ (8.5 % over 120 days). Non-extractable residues are accumulated in the sludge (up to 25 %). In the aquatic phase, metabolite poorly degrades to СО₂ (25 %) and non-extractable residues (16 %).

Insecticide Sivanto Prime 200 SL (a. i. – flupyradifurone, 200 g/L) was tested in Ukraine for protection of vineyards with the maximum consumption rate of 0.5 L/ha (consumption rate of a. i. is 100 g/ha) two times, apple and pear trees with the maximum consumption rate of 1.0 L/ha (consumption rate of a. i. is 200 g/ha) two times, cabbages with the maximum consumption rate of 0.7 L/ha (consumption rate of a. i. 140 g/L) three times. One of the tasks of the study was the justification of MAL for residual amounts of flupyradifurone in apples, pears and juices made of them, cabbage. Preliminary calculation of the no observed effect level of flupyradifurone in the diet was performed based on its ADD.

Upon ADD equal to 0.02 mg/kg, allowable daily intake of flupyradifurone for the human body is 1.2 mg/daily. According to the principles of complex hygienic rationing, it is allowable that 70 % of the substance measured in all environments may be consumed by a human with diet [3]. Considering this fact, the estimated no-observed effect intake of flupyradifurone from the diet is 0.84 mg/daily.

Studies (Region of Odesa) of the actual content of flupyradifurone in Izabella variety grapes have shown that residual amounts of the active ingredient were 0.083 mg/kg at the day after the second processing, at Day 6 — 0.043 mg/kg, at Day 14 — 0.034 mg/kg, at Day 28 — less than 0.02 mg/kg. In grapes yield (Day 48 after the last processing), flupyradifurone was not detected at the level of the limit of detection (LoD) by HPLC — 0.07 mg/kg. In the yield of grapes from other areas at Day 77 after processing and juice made of them, flupyradifurone was undetectable. In the yield of grapes of Muskat Odeskyi variety (Day 77 after the second processing), flupyradifurone was not detected at the level of LoD by HPLC. In the grape juice made of grapes yield, flupyradifurone was not detected at the level of LoD by HPLC — 0.003 mg/kg.

The obtained study results in the region of Kyiv and Odesa suggest that Aidared apple variety, flupyradifurone was found at the day after the second processing in the amount of 0.41 mg/kg, at Day 7 — 0.029 mg/kg, at Day 14 — 0.02 mg/kg, at Day 28 — 0.019 mg/kg. Yield from Aidared apple variety (Day 103 after the last processing) and Golden Delicious (Day 128 after the last processing), flupyradifurone was not detected at the level of LoD by HPLC — 0.007 mg/kg. In the apple juice made of apple yield, flupyradifurone was not detected at the level of LoD by HPLC — 0.003 mg/kg.

Changes in flupyradifurone decomposition in apples and grapes over time are provided in Fig. 1.

Fig. 1. Changes in flupyradifurone decomposition in apples and grapes over time

In the yield of Star Krymson variety (Day 42 after the second processing) and juice made of them, flupyradifurone was not detected at the level of LoD by HPLC — 0.007 mg/kg and 0.003 mg/kg, respectively.

Conducted studies in the region of Kyiv using Aggressor cabbage have shown that the content of flupyradifurone in leaves at the day after the third processing was 3.3 mg/kg, at Day 8 — 0.38 mg/kg, at Day 14 — 0.052 mg/kg, at Day 28 — 0.011 mg/kg. In the cabbage heads at Day 50 after processing (yield), flupyradifurone was not detected at the level of LoD by HPLC — 0.003 mg/kg.

In the leaves of Express cabbage in the region of Kyiv, flupyradifurone was detected at the day after the third processing at the level of 3.8 mg/kg, at Day 7 — 0.05 mg/kg, at Day 14 — 0.025 mg/kg. In the cabbage heads during yield (Day 28 after processing), the active ingredient of insecticide was not detected at the level of LoD by HPLC.

Changes in flupyradifurone decomposition in cabbages over time are provided in Fig. 2.

Fig. 2. Changes in flupyradifurone decomposition in cabbages over time

In EU, the following flupyradifurone maximum residual levels (MRL), mg/kg, were set: grapes — 0.8, apples — 0.4, pears — 0.4, cabbage — 0.01 (at the level of LoQ).

Based on the toxicological and hygienic assessment of Sivanto Prime 200 SL and its active ingredient, results of the study of flupyradifurone content in grapes, apples, pears and juices made of them, cabbage, and guided by generally established methodological approaches in hygienic rationing, considering MRL in apples and pears for EU member states, recommended and approved flupyradifurone MALs are provided in Table 2.

Table 2

Maximum allowable levels (MALs) of residual amounts and limits of quantification (LoQ) of flupyradifurone in grapes, apples, pears, and juices made of them, cabbage

If the above hygienic standards are complied with [3], possible daily intake of flupyradifurone by the human body with grapes, apples, pears, and juices made of them, cabbage is 5.9% from the level of no adverse effect intake of the substance with diet (4.2% from its allowable daily intake). Safety interval before harvesting of grapes, apples, pears were set as 14 days, cabbage — 28 days.

Using the obtained data of natural research and first-order equation [15–17], constant of decomposition rate (k) and half-life (Т ₅₀) of flupyradifurone was calculated for apples, grapes and cabbage, and it was evaluated by stability in vegetating crops and agricultural raw materials according to DSanPiN 8.8.1.002-98 (Table 3).

Table 3

Decomposition rate and hazard class

Calculated half-lives (Т₅₀) are as follows: for apples — 5 days, grapes — 15 days, cabbage — 2–3 days. The obtained data, according to the Hygienic Classification of Pesticides by Hazard Level (DSanPiN 8.8.1.002-98) under the parameter “stability in vegetating crops and agricultural raw materials” allow classifying stability flupyradifurone in the grapes to hazard class 2, in apples — to hazard class 3, in cabbage — to hazard class 4.

Possible concentration of flupyradifuronein crops after safety interval before harvesting was calculated as follows, and compared with actual value:

where С_t — content of substance at a period of time, mg/kg

С₀ — initial concentration of a substance in the soil, mg/kg

k — constant of decomposition rate

t — time, day

l — base of the natural logarithm (2.73)

According to the estimated data, amount of flupyradifurone that may be contained in grapes at Day 14 after processing (set safe interval before harvesting) is 0.04 mg/kg, at the same time field results give the following — 0.034 mg/kg). These values do not exceed the set hygienic standard for grapes — 0.4 mg/kg.

For apples, possible amount of flupyradifurone at Day 14 (safe interval before harvesting), is 0.02 mg/kg (by the results of field studies — 0.02 mg/kg), for cabbages at Day 28 — 0.001 mg/kg to 0.01 mg/kg (by the results of field studies — 0.011 mg/kg and at the level of LoQ by HPLC 0.003 mg/kg).

Therefore, estimated residual amounts of the active ingredient in the grapes, apples and cabbage completely comply with the appropriate obtained experimental findings and meet set safe intervals before harvesting.

Value of TSEL of flupyradifurone in working and atmospheric air of populated places were justified [3, 10–12]. To calculate TSEL of flupyradifurone in working air, its acute toxicity parameters upon oral, dermal and inhalation exposure, and estimated limit concentration for experimental animals under chronic inhalation exposure were used. Recommended and approved TSEL of flupyradifurone in working air is at the level of 1.0 mg/m³ (LoQ by HPLC — 0.1 mg/m³). To calculate TSEL of flupyradifurone in atmospheric air of populated places, correlation relationships between MAC of chemical substances for atmospheric air and MAC for working air, LD₅₀ and LC ₅₀ were used. Recommended and approved TSEL of flupyradifurone in atmospheric air of populated places is at the level of 0.01 mg/m³ (LoQ by HPLC — 0.005 mg/m³).

Justification of maximum allowable concentration of flupyradifurone in water of water bodies for drinking and household, as well as cultural and social purpose was performed by the following key directions [3,13,14] — study of the effect of active ingredient on organoleptic properties of water and general sanitary regimen of water bodies, determination of the maximum no adverse effect concentration of flupyradifurone in water by the sanitary and toxicological feature of hazard.

Limit concentration by the effect of flupyradifurone on odour is the concentration of the substance at the level of 29.34 mg/dm³. Limit concentrations of substances in terms of the effect on the colouration degree, turbidity and ability of aquatic solutions to foaming were above 3,100 mg/dm³ (limit of solubility). Therefore, limit concentration by the effect on organoleptic properties of water is the concentration of flupyradifurone at the level of 29.34 mg/dm³.

To assess the effect of flupyradifurone on the overall al sanitary regimen of water bodes, nature and intensity of the biochemical oxygen demand (BOD) as the most significant parameter of the ability of water bodies to self-purification from organic contamination, content of dissolved oxygen, condition of ammonification and nitrification of nitrogen-containing organic substances, reaction (pH) of aquatic environment, changes in the development and dieaway of aquatic saprophyte microflora over time have been studied. The studies were performed with flupyradifurone in the concentrations of 0.2 mg/dm ³, 0.02 mg/dm³, and 0.002 mg/dm³. This substance in all concentrations stimulates BOD processes. The limit concentration of flupyradifurone in terms of the effect on BOD processes was 0.002 mg/dm³. Effect of flupyradifurone on the content of dissolved oxygen in water of water bodies was insignificant. Its content at the level of 0.002 mg/dm³ may be set as the limit concentration by the effect on ammonification and nitrification. Flupyradifurone did not affect pH of the aquatic environment. Results of microbiological studies have shown that the concentration of 0.02 mg/dm³ is the limiting by the effect of flupyradifurone on changes in development and dieaway of aquatic saprophyte microflora over time.

Therefore, the limit concentration of flupyradifurone by the effect on the general sanitary regimen of water bodies is the concentration of 0.02 mg/dm³.

During calculation of the maximum no adverse effect concentration of flupyradifurone in water by the sanitary and toxicological feature of hazard, ADD of flupyradifurone - 0.02 mg/kg, human body weight - 60 kg, average daily water consumption at the level of 3 litres and 10 % from allowable daily intake of substances in the human body with water in accordance with the main provisions were taken into account [14]. As a result of calculations, maximum no observed effect concentration of flupyradifurone was obtained at the level of 0.04 mg/dm³.

Based on limit and sublimit levels set by the main hazard parameters, justification of MAC of flupyradifurone in water of water bodies of drinking and household as well as the cultural and social purpose was justified. Analysis of the obtained data allowed to conclude that the limiting feature of unfavourable action of flupyradifurone is general sanitary. As MAC of flupyradifurone in water of water bodies of drinking and household, as well as cultural and social purpose, recommended and approved concentration is 0.002 mg/dm³ (limiting hazard feature is general sanitary). The limit of its assay in water by HPLC is 0.002 mg/dm³.

Since flupyradifurone by the stability in soil belongs to hazard class 2 pesticides, estimated justification of its tentative allowable concentration in the soil was performed [16]. During calculations, MAL of flupyradifurone in cabbage of 0.02 mg/kg was used, and this allowed to recommend TAC of flupyradifurone in the soil at the level of 0.4 mg/kg. The limit of the assay by HPLC is 0.02 mg/kg. The above values were formally approved.

Previous assessment of the hazard of exposure of flupyradifurone on labourers who use it suggested that the substance has sufficient selectivity (CoSd was 617, CoSi — 230), thus, its maximum efficient consumption rate is 100-fold lower than median lethal doses and concentrations when the substance contacts with the skin and inhaled.

Studies of the hazard of exposure of Sivanto Prime 200 SL on rural workers and population during and after its use (boom spraying of cabbage with the consumption rate of 0.7 L/ha — 300 L/ha of working liquid, airborne spraying of apple trees with the consumption rate of 1.0 L/ha — 1,000 L/ha of working liquid) were performed. The obtained results have shown that in the air of respiration zone of refuelling operator and tractor operator, in the air of zone of possible spread of product aerosol at the distance of 300 m from the boundary of plot (boom spraying) and at the distance of 500 m from the boundary of plot (airborne spraying) during processing, 1 hour, 3 and 7 days after processing, flupyradifurone was not detected (LoD of flupyradifurone by HPLC in working air is 0.02 mg/m³ and in atmospheric air — 0.001 mg/m³). In the soil of the processed plot after boom spraying, the content of flupyradifurone 3 days after processing was 0.51 mg/kg at TAC of 0.4 mg/kg. Seven days after processing, the substance was not detected in soil at the level of the LoQ by HPLC — 0.005 mg/kg. The performed calculations have shown that the amount of flupyradifurone that may affect labourers in contact with the processed crop in 7 days is insignificant in terms of toxicity. After airborne spraying, the content of flupyradifurone in the soil of processed plot in 3 and 7 days did not exceed its TAC in the soil. In the soil from the boundary of the sanitary protective zone (300 m and 500 m) 1 hour after processing, the active ingredient was not detected at the level of LoD.

According to Guidelines 8.8.1.4-162-2009 [19] and study results, possible exposure inhalation (Di) and dermal (Dd) doses (mg of a. i./kg body weight) that affected refuelling operator and tractor operator during working shift (4 hours) were calculated; tentative allowable inhalation (ADi) and dermal (ADd) doses of flupyradifurone for labourers (mg a. i./kg body weight) were justified. ADi = 0.1 and Add = 0.36. Results of comparison of possible exposure and tentative allowable doses suggest that hazard (risk) coefficients and indices of complex effect of flupyradifurone on the labourers were below the allowable level.

Conclusion

1. Flupyradifurone and Sivanto Prime 200 SL belong to hazard class 2 by the limiting hazard criterion — acute inhalation toxicity. The main target organs of flupyradifurone toxicity in rats is the liver and thyroid gland, in mice — liver and kidneys, in dogs — skeletal muscles, kidneys and liver.

Flupyradifurone has no mutagenicity and carcinogenicity; by its teratogenicity, embryo- and developmental toxicity, it belongs to hazard class 3 pesticides.

2. To prevent the possibility of a negative effect on human health and quality of the environment, ADD and hygienic standards of flupyradifurone were justified, namely:

• ADD — 0.02 mg/kg body weight/day.
• MAL, mg/kg: grapes — 0.4 (LoQ by HPLC — 0.02), grape juice — 0.01 (LoQ by HPLC — 0.01), apples — 0.4 (LoQ by HPLC — 0.02), apple juice — 0.01 (LoQ by HPLC — 0.01), pears — 0.4 (LoQ by HPLC — 0.02), pear juice — 0.01 (LoQ by HPLC — 0.01), cabbage — 0.02 (LoQ by HPLC — 0.01).
• TSEL in the working air, mg/m³: 1.0 (LoQ by HPLC — 0.1).
• TSEL in the atmospheric air, mg/m³: 0.01 (LoQ by HPLC — 0005).
• MAC in the water of water bodies, mg/dm³: 0.002, general sanitary (LoQ by HPLC — 0.002).
• TAC in the soil, mg/kg: 0.4 (LoQ by HPLC — 0.02).

3. When current rules of handling pesticides are met, levels of flupyradifurone in the working environment, as well as its external inhalation and dermal exposure are sufficiently safe for rural labourers involved in the use of insecticide Sivanto Prime 200 SL. Sanitary protective zones set for agro-industrial field provide safety of ground application of the product for population and environmental objects; if mechanised works are performed on the processed areas, production environment is safe in 3 days, and for manual works — in 7 days after spraying.

Flupyradifurone was not detected in the yield of grapes, apples, pears, and juice made of them, cabbage at the level of the methods of detection. After the use of insecticide, safe intervals before harvesting are as follows: grapes, apples, pears — 14 days, cabbage — 28 days.

4. In terms of toxicological and hygienic position, there are no objections against constant registration of insecticide Sivanto Prime 200 SL in Ukraine (a. i. — flupyradifurone, 200 g/L) in vineyards with maximum consumption rate of 0.5 L/ha two times, apple and pear trees with the maximum consumption rate of 1.0 L/ha two times, cabbages with the maximum consumption rate of 0.7 L/ha three times.