Assessment of hazard and hygienic rating of flubendiamide in agricultural food products of the plant origin, industrial and environmental objects

  • Authors: O.P. Kravchuk, P.G. Zhminko, V.I. Medvedev, A.P. Grinko, S.G. Serhieiev, L.P. Ivanova, O.M. Bagatska, O.M. Kuznetsova, P.V. Aleinov, I.P. Pavlenko, V.G. Lyshavsky
  • UDC: 614.7:613.26:615.9:543.393:632.95
  • DOI: 10.33273/2663-4570-2018-82-83-2-3-13-23
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State Enterprise “L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health of Ukraine”, Kyiv, Ukraine

Abstract. Flubendiamide is recommended for use as an insecticide for corn, sunflower, soybean, cabbage, and tomatoes. The State Enterprise “L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety” of the Ministry of Health of Ukraine conducted a study on toxicological and hygienic assessment of flubendiamide and insecticide Belt 480 SC on its basis; the justification of flubendiamide PDE (permitted daily exposure) to human, hygienic rates of the substance and the rules for safe use of the drug. Objectives. Toxicological and hygienic assessment of the use of insecticide on the basis of flubendiamide, assessment of the risk of its impact on agricultural workers and population.
Methods. Expert-analytical, toxicological, physical and chemical, and hygienic.
Results. According to the toxicity parameters, flubendiamide and Belt 480 SC are pesticides of the second class of hazard. The mutagenic, carcinogenic and teratogenic activity, embryo and reproductive toxicity of flubendiamide are not limiting in assessing its hazard. The results of field studies showed that residual amounts of flubendiamide were not found in the crop of corn and soybean, sunflower seeds, cabbage and tomatoes. The degree of possible occupational risk of exposure to flubendiamide in case of intake by agricultural workers via inhalation and dermal routes does not exceed the permissible level.
Conclusion. Insecticide Belt 480 SC, based on flubendiamide in agriculture of Ukraine in corn, sunflower, soybean, cabbage and tomatoes under adherence to hygienic rates and regulations is not hazardous from the point of view of the possibility of contamination of agricultural crops and environmental objects with flubendiamide.
Key words: insecticide, flubendiamide, toxicology, hygienic rates and regulations, assessment of hazard.

In the current conditions of agricultural development, the use of new plant protection chemicals (PPCs) is expanding annually. Under certain conditions, some of them may have a negative impact on human health and the environment. In this regard, a comprehensive assessment of their potential hazard for human and environment is relevant during pre-authorization under the established criteria of harmful action. Hygienic assessment and regulation of the safe use of new active ingredients of PPCs in the agriculture are of particular importance. One of these is the new insecticide flubendiamide, which is contained in Belt 480 SC (active ingredient — flubendiamide, 480 g/L) and is recommended for use on corn, sunflower, soybean, cabbage and tomatoes. Flubendiamide is registered in EU countries, the USA, Australia, Brazil, and other countries.

Objective of the work was to assess hazard of flubendiamide and Belt 480 SC, justify permissible daily exposure (PDE) of flubendiamide for human, its hygienic rates in soybean-corn, sunflower seeds, vegetable oils, cabbage, tomatoes, tomato juice, air of the working area, atmospheric air, water of reservoirs and soil, as well as safety requirements when using insecticide Belt 480 SC, terms of backup to work and waiting periods after application of the preparation.

Materials and methods. Flubendiamide, by its chemical structure, belongs to phthalic acid diamides. Chemical name, structural formula, and physicochemical properties of flubendiamide are presented in Table 1.

Table 1. Physicochemical properties of flubendiamide.

 

Toxicological and hygienic assessment of Belt 480 SC and its active ingredient — flubendiamide, justification of flubendiamide PDE was carried out according to the results of studies of the manufacturer and literature data [1–10] in accordance with the guidance [11] and valid Ukrainian hygienic classification [12]. Research of changes in the content of flubendiamide over time in crops, justification of its maximum permissible levels (MPL) in corn grain, soybean, sunflower seeds, cabbage, tomatoes and tomato juice was conducted in accordance with [11] and the basic principles laid down in the guidelines of UN Food and Agriculture Organization (FAO) [13]. Selection and transportation of samples for the study were carried out in accordance with unified rules [14].

Determination of the content of flubendiamide in the investigated objects complied with the recommended guidelines [15–17]. The limits of quantitative (LOQ) by high-performance liquid chromatography (HPLC) in corn and soybean, sunflower seeds — 0.05 mg/kg, cabbage and tomatoes — 0.1 mg/kg, tomato juice — 0.05 mg/kg.

Justification of the approximate safety exposure levels (ASEL) of flubendiamide in the air of the working zone and the atmospheric air was guided by the guidelines [18–20].

The development and justification of the maximum permissible concentration of flubendiamide in water of reservoirs were carried out in accordance with the guidelines [11] and the main provisions [21, 22]. In accordance with the developed guidelines for the determination of flubendiamide in water of reservoirs [23], LOQ of substances by the HPLC was 0.003 mg/dm3.

The development and justification of MPC of flubendiamide in the soil were carried out in accordance with the guidelines and recommendations [11, 24]. LOQ of flubendiamide in the soil by the HPLC method according to the developed guidelines [25] was 0.05 mg/kg.

For prediction of the risk of flubendiamide exposure to agricultural workers, selective effect factors (SEF), which are the ratio of the effective rate of consumption and median lethal doses and concentrations under the application of substance on the skin (SEFd) and under the inhalation exposure (SEFi), were calculated. Results were assessed by the following scale: SEF <1 — extremely low selective effect, SEF from 1 to 99 — low selective effect, SEF ≥100 — sufficient selective effect [26].

Exploration and assessment of hazard exposure to Belt 480 SC to agricultural workers engaged in its application and during cultivation of areas after the use of the preparation, as well as the potential exposure to the population at the border of the sanitary protection zone during spraying with the preparation was carried out in accordance with the guidelines [11] and recommendations [27].

Determination of the content of flubendiamide in industrial and environmental objects was carried out in accordance with the requirements specified in the guidelines [25, 28]. The limits of the quantification of the active ingredient by the HPLC method in the air of the working zone are 0.02 mg/m3, in the atmospheric air — 0.001 mg/m3 and in the soil — 0.05 mg/kg.

Results and discussion. In accordance with the Hygienic Classification of Pesticides by Level of Hazard (DSanPiN (State Sanitary Rules and Rates) 8.8.1.002-98) [12], technical flubendiamide according to the parameters of acute oral and dermal toxicity belongs to the 4th class of hazard, acute inhalation toxicity — to the 2nd class of hazard, in case of irritating effects on the skin — to the 4th class of hazard and on the mucous membranes of the eye — to the 3rd class of hazard, by its allergenic action — to the 4th class of hazard. By limiting toxicity parameter, flubendiamide belongs to pesticides of the 2nd class of hazard.

In accordance with DSanPiN 8.8.1.002-98 [12], Belt 480 SC according to the parameters of acute oral and dermal toxicity belongs to the 4th class of hazard, acute inhalation toxicity — to the 2nd class of hazard, in case of irritating effects on the skin and on the mucous membranes of the eye — to the 4th class of hazard, by its allergenic action — to the 4th class of hazard. By limiting hazard parameter, Belt 480 SC belongs to pesticides of the 2nd class of hazard.

The kinetics and metabolism of flubendiamide have been studied in rats. Animals were given orally 14C-labelled flubendiamide in aniline or phthalate rings at doses of 2 and 200 mg/kg. It was shown that flubendiamide is weakly absorbed in the gastrointestinal tract of rats, evenly distributed in tissues and organs, does not accumulate in the body. At a dose of 2 mg/kg, the maximum concentration of radioactivity in plasma was observed in males 12 hours and in females 6 hours after administration. At a dose of 200 mg/kg, the kinetics of flubendiamide was similar. After 168 hours, the radioactivity in the tissues was minimal.

Metabolism of flubendiamide in the body of male rats is carried out by oxidation of the methyl group of the aniline ring to form metabolites: flubendiamide-benzyl alcohol; flubendiamide-benzyl aldehyde and flubendiamide-benzoic acid which are found in faeces. The main metabolite that is found in the urine is flubendiamide-benzyl alcohol. In the liver of male rats, flubendiamide-benzyl alcohol, flubendiamide-benzyl aldehyde and flubendiamide-aniline, as well as more polar metabolites are detected. In female rats, glutathione conjugation of flubendiamide predominantly occurs, and conjugates with glycine and cysteine are detected. In vitro studies showed that female rats had no isoforms of P450 cytochrome responsible for the first stage of hydroxylation of the substance found in male rats and humans.

Subchronic studies established NOAEL of flubendiamide for male and female rats — 50 ppm (2.85 mg/kg for males and 3.29 mg/kg for females) by hepatotoxic and haematotoxic effects, hypertrophy of follicular cells of the thyroid gland. NOEL for mice is 100 ppm (11.9 mg/kg for males and 14.7 mg/kg for females) based on the increase in liver weight in females and pathohistological changes in the liver of males and females. NOEL for dogs is 100 ppm (2.58 mg/kg for males and 2.82 mg/kg for females) based on a decrease in the partial thromboplastin time and increased alkaline phosphatase activity in males and females, as well as possible toxic effects on female adrenal glands.

Chronic (one-year) study established NOAEL for male and female rats — 20 ppm (0.78 mg/kg for males and 0.96 mg/kg for females) by hepatotoxic and haematotoxic effects, hypertrophy of follicular cells of the thyroid gland.

In experiments of chronic toxicity and carcinogenic activity over 2 years, NOEL was established for rats at 50 ppm (1.7 mg/kg for males by hepatotoxic and nephrotoxic activity, testicular atrophy and 2.15 mg/kg for females by hepatotoxicity and nephrotoxicity, follicular cell hypertrophy of the thyroid gland). NO(A)EL for male and female mice — 50 ppm (4.85 mg/kg and 4.44 mg/kg, respectively) based on changes in liver and thyroid tissue. NOAEL for dogs — 100 ppm (2.21 mg/kg for males and 2.51 mg/kg for females) by hepatotoxic action and reduction of activated partial thromboplastin time.

Flubendiamide has a polytropic effect on the body. The main target organs are the liver, thyroid gland, kidneys, blood system. High flubendiamide doses show a toxic effect on the adrenal glands and gonads. It has been shown that flubendiamide doses of 83 mg/kg and 812 mg/kg increase content of cytochrome P-450 and activity of enzymes of monooxygenase system of the liver, stimulate synthesis of thyroid stimulating hormone (TSG) and thyroid hormones. Pathohistological changes in the thyroid gland are regarded as secondary, caused by an increase in the pituitary production of TSG, due to an increase in the level of thyroid hormones excretion as a result of induction of microsomal liver enzymes.

Flubendiamide does not possess mutagenic and carcinogenic activity, selective neurotoxic and immunotoxic action.

NOEL for pregnant female rats — 10 mg/kg, NOAEL for foetal development — 10 mg/kg. NOEL for pregnant female rabbits — 100 mg/kg, NOAEL for foetal development — 20 mg/kg. NOEL for flubendiamide by reproductive and systemic toxicity parameters — 20 ppm (1.3 mg/kg of body weight).

Studies on the effects of flubendiamide on the nervous system and postnatal development in rats established NOAEL by a neurotoxic effect of 12,000 ppm (976.6 mg/kg). NOAEL for the maternal body — 120 ppm (9.99 mg/kg) by hepatotoxic action, NOAEL for young rats — 120 ppm (9.99 mg/kg) by reduced body weight gain, eye bulb enlargement, exophthalmos, blurred eyeball, slowing down of preputial separation.

In accordance with DSanPiN 8.8.1.002-98, flubendiamide by its mutagenic and carcinogenic activity belongs to the 4th class of hazard, by teratogenic activity, embryo and reproductive toxicity — to the 3rd class of hazard. Based on limiting NOEL of flubendiamide by reproductive toxicity — 20 ppm (1.3 mg/kg of body weight) and chronic toxicity in a one-year experiment for rats — 20 ppm (0.78 mg/kg for males and 0.96 mg/kg for females) and a safety factor of 100, PDE for flubendiamide in human will be 0.01 mg/kg. However, taking into account changes in the endocrine organs, a manifestation of foetotoxicity on 2 species of animals, effect on the eyes in the postnatal development, it is advisable to additionally introduce a modifying safety factor 3 in the calculation of PDE. Taking into account the above, PDE of flubendiamide for a human was recommended and approved at the level of 0.003 mg/kg.

Metabolism of flubendiamide in plants was studied on fruits (apples) and fruit vegetables (tomatoes, peppers), leafy vegetables (cabbage) and cereals (corn) using [14C] -labelled by phthalic acid and [14C] -anil-labelled flubendiamide.

Study data showed that flubendiamide was the main component of the total amount of radioactive residues and ranged from 50 % to 94 % in ripe crops. All metabolites were found to be low (1–6 % of total radioactivity) with the exception of the metabolite A-1 (NN1-0001-des-iodo), which amounted to more than 10 %. However, residues of the metabolite A-1 in all tested samples were always below the limits of the quantification, so it is not used to monitor the residual amounts of flubendiamide. Initial compounds were found in tomatoes at day 0 — 98.6 % (3.2 mg/kg), after 1 week — 84.3 % (2.3 mg/kg) and after 4 weeks — 63.4 % (1.27 mg/kg) of total radioactive residues, in unripe cabbage plants after 3 weeks — 91 % (0.534 mg/kg) and in ripe plants after 6 weeks — 91.2 % (0.538 mg/kg) of total radioactive residues.

Laboratory studies establishing degradation of flubendiamide in the soil in aerobic conditions without sunlight, found that the substance is very stable and, disintegrating, forms a number of metabolites, the main of which is the metabolite A-1 in the amount of 7.1 %. When simulating sunlight, the substance is also quite persistent, however, the amount of metabolite A-1 is 17.6 %. The half-life (T50) in these conditions on different types of soils (sunflower, loam, clay) is more than one year. Under anaerobic conditions, flubendiamide is a more stable substance than under aerobic conditions.

Field studies to investigate the destruction of flubendiamide in soil were conducted in Western Europe. It was established that the substance is sufficiently stable in the soil. Flubendiamide degrades in two phases. The first phase is more rapid due to photolysis and the second phase is rather slow. According to the European Food Safety Authority (EFSA), the half-life of flubendiamide in the field experiment is from 5.8 to 970 days, as per The Pesticide Manual — from 210 to 777 days [5].

Therefore, by the “stability in soil” parameter in accordance with DSanPiN 8.8.1-002-98, flubendiamide can be classified as pesticides of the 1st class of hazard (highly resistant in soil).

Study on desorption and adsorption in soils have shown that flubendiamide belongs to substances with fairly low mobility. Distribution factor in the system of organic matter-water (Kos) is 1,076–3,318–94 mg/L. When studying the migration of matter in the filtration columns, it was found that the main part concentrates in the upper horizon of 0–10 cm (67,22 %), however, it can migrate to a depth of 15–20 cm. The adsorption of flubendiamide has a positive correlation with the amount of organic matter of the soil and a negative one with pH of the soil solution.

Flubendiamide has a low potential for leaching — leaching index (GUS) is 0.59. The obtained data indicate that the substance will not migrate to the groundwater.

Therefore, according to the “depth of migration by the soil profile”, flubendiamide can be classified as pesticides of the 3rd class of hazard.

Establishing processes of degradation of flubendiamide in sterile buffer solutions showed that the substance is stable to hydrolysis at pH 5–9.

In aqueous solutions of laboratory conditions, under the influence of artificial sunlight, the flubendiamide half-life is: in distilled water (25 °C) — 5.5 days and in field water — 4.3 days. The main metabolites of flubendiamide are A-1 (up to 32 % of the substance introduced in 7 days of the study) and A-10 (NNI-0001-3-OH-hydroxy herfluoroalkyl) (up to 13 % of the substance introduced).

During the examination of the processes of photolysis of substance under the field conditions in the countries of Central Europe (mid-summer) it was found that flubendiamide half-life was from 10 to 60 days; with the half-life of des-iodo flubendiamide was more than a year in all studies conducted.

During the introduction of the substance into the laboratory model, microecosystems “water/sediment” under conditions of the laboratory model experiment, a fairly rapid transition of flubendiamide into the sedimentary phase of the system was established. Under aerobic conditions, using lake and pond water, T50 of flubenidamide for the aqueous phase was from 14 to 40 days; for the aqueous microecosystem in general — more than a year.

In the anaerobic conditions, in the system of pond water, T50 for the aqueous phase was close to 11 days and for microecosystem in general — 284 days, depending on the type of sediments (sand, loam, clay). It was concluded that ionization and anaerobic water metabolism are the main ways of degradation of this substance. Provided data allow including flubendiamide to the 1st class of hazard by the parameter “stability in the water” in accordance with DSanPiN 8.8.1.002-98.

Insecticide Belt 480 SC was tested in Ukraine for one-time protection of corn, sunflower and soybean with a maximum rate of consumption of 0.15 L/ha (rate of consumption of flubendiamide — 72 g/ha), and two times for cabbage and tomatoes with a maximum rate of consumption of 0.1 L/ha (rate of consumption of flubendiamide — 48 g/ha). One of the tasks of the study was to justify MPL of the content of residual amounts of flubendiamide in corn grain and oil, sunflower seeds and oil, soybean grain and oil, cabbage, tomatoes and tomato juice. For this purpose, a preliminary calculation of the safe level of the content of flubendiamide in the diet was carried out, based on the magnitude of its PDE. For PDE equal to 0.003 mg/kg, the daily allowance of flubendiamide for a human is 0.18 mg/daily. According to the principles of integrated hygienic rationing, it is allowed that up to 70 % of residual amounts of a substance that is determined in all media can penetrate a human body with diet [11]. Considering this fact, the estimated safe consumption of flubendiamide with diet is 0.126 mg/daily.

Conducted studies on the actual content of flubendiamide in corn grain (Region of Kyiv) showed that the residual amounts of the active ingredient in the grain were less than 0.05 mg/kg on the day of treatment and were not detected at day 8, 15, 28 and 50 (harvest) at the level of the limit of detection (LOD) by HPLC — 0.02 mg/kg.

The obtained study results (Region of Kyiv and Kherson) indicate that flubendiamide was present in the baskets of sunflower at day 0 and 3 after treatment in amounts of 1.6 mg/kg and 0.65 mg/kg, respectively. In seeds of sunflower, the content of flubendiamide at day 7 and 14 after treatment was 0.19 mg/kg and 0.09 mg/kg, respectively. At day 30, 38 (harvest) and day 44 (harvest) after treatment flubendiamide was not detected in sunflower seeds at the level of LOD by HPLC — 0.02 mg/kg.

Tests on soybean were conducted in the Region of Kyiv and Poltava. In green soybean plants, the amount of flubendiamide at day 0 and 7 after treatment was 3.6 mg/kg and 1.1 mg/kg, respectively. The content of flubendiamide in the beans of soy at day 14 after treatment was 0.61 mg/k.g In the harvest of soybean grain at day 29 and 34 after treatment, flubendiamide was not detected at the level of LOD by HPLC — 0.02 mg/kg.

The conducted studies on cabbage (Region of Kyiv) showed that the content of flubendiamide in cabbage head after the second treatment was less than 0.1 mg/kg at day 0 and 7 after treatment. At day 14, 21, 30 and 46 (harvest) after treatment, flubendiamide was not detected in cabbage heads at the level of LOD by HPLC — 0,03 mg/kg.

Tests on tomatoes (Region of Kyiv) indicate that flubendiamide was detected in tomatoes on the day of the second treatment at the level of 0.18 mg/kg, and at day 4 and 8 after treatment — less than 0.1 mg/kg. At day 14, 21 and 39 (harvest) after treatment, flubendiamide was not detected in tomatoes at the level of LOD by HPLC — 0,03 mg/kg. In tomato juice, obtained from tomatoes collected during the period of marketed ripeness, flubendiamide was not detected at the level of LOD by HPLC — 0.02 mg/kg.

In the EU, the following values for maximum residue levels (MRL) for flubendiamide are the following: corn (grain) — 0.01 mg/kg, soybean (grain) — 0.01 mg/kg, tomatoes — 0.2 mg/kg and salad — 0.01 mg/kg.

Taking into account the above, flubendiamide MPL values are recommended and approved, and they are presented in Table 2.

Table 2. Maximum permissible levels (MPL) of residual quantities and limits of quantification (LOQ) of flubendiamide in corn, soybean, sunflower, cabbage, tomatoes and tomato juice.

 

The establishment of MPL content of the residual amounts of flubendiamide in vegetable oils is considered inappropriate based on the results of studies on its content in corn grain, soybean and sunflower seeds.

In accordance with [11], if these hygienic standards are observed, the daily intake of flubendiamide into the human body may amount to 14.4 % of the level of safe intake from diet (10.1 % of its permissible daily intake).

Waiting periods till harvesting were established for corn, sunflower and soybean — 30 days, cabbage — 20 days, and tomatoes — 14 days.

The substantiation of the values of AESL of flubendiamide in the air of the working zone and the atmospheric air of inhabited places was performed [11, 18–20]. To calculate AESL of flubendiamide in the air of the working zone, parameters of its acute toxicity for oral, dermal and inhalation entrance in the body and estimated threshold concentration for the experimental animals under chronic inhalation exposure were used. The recommended and approved AESL of flubendiamide in the air of the working zone is at the level of 0.2 mg/m3 (LOQ by HPLC — 0.02 mg/m3). Correlation bonds between MPCs of chemical substances for atmospheric air and MPCs for an air of the working zone, LD50 and LC50, were used to calculate AESL of flubendiamide in atmospheric air of inhabited places. The recommended and approved AESL of flubendiamide in atmospheric air of inhabited places is at the level of 0.001 mg/m3 (LOQ by HPLC — 0.001 mg/m3).

Substantiation of the maximum permissible concentration of flubendiamide in water of reservoirs for household and drinking, cultural and household purposes was carried out according to the following main directions [11,21,22] — examination of the influence of flubendiamide on the organoleptic properties of water and general sanitary regime of reservoirs, determination of the maximum inactive concentration of flubendiamide in water under sanitary toxicological sign of harm.

Threshold concentrations of flubendiamide in relation to the effect on the organoleptic properties of water (odour at 20 and 60 °C, colour, turbidity, the foaming ability of aqueous solutions) were higher than 0.03 mg/dm3 (solubility limit). Therefore the threshold concentration by the effect on the organoleptic properties of water is the concentration of flubendiamide over 0.03 mg/dm3.

In order to assess the effect of flubendiamide on the general sanitary regimen of reservoirs, the nature and intensity of biochemical oxygen consumption (BOC) as the most significant parameter of the ability of reservoir to self-purification from organic pollution, dissolved oxygen content, the state of processes of ammonification and nitrification of nitrogen-containing organic substances, pH of aqueous medium, development and dying of water saprophytic microflora over time were studied. Studies have been conducted with flubendiamide at concentrations of 0.03 mg/dm3, 0.003 mg/dm3, and 0.0003 mg/dm3. Flubendiamide at concentrations of 0.03 mg/dm3 and 0.003 mg/dm3 suppresses the processes of BOC. The threshold concentration of flubendiamide in relation to the effect on the processes of BOC was 0.003 mg/dm3. The effect of flubendiamide on the content of dissolved oxygen in the water of reservoirs was insignificant. The content of flubendiamide at the level of 0.003 mg/dm3 can be considered as its threshold concentration by the parameters of the effects on ammonification and nitrification processes. Flubendiamide did not affect the pH of the aqueous medium. The results of microbiological studies have shown that the concentration of 0.003 mg/dm3 is a threshold under the influence of flubendiamide on the development and dying of water saprophytic microflora over time.

Therefore, the threshold concentration of flubendiamide in relation to the effect on the general sanitary regimen of reservoirs is the concentration of 0.003 mg/dm3.

When calculating the maximum inactive concentration of flubendiamide in water by sanitary toxicological sign of harm, PDE of flubendiamide of 0.003 mg/kg, human body weight of 60 kg, daily average water consumption at the level of 3 L and 10 % of the permissible daily intake of the substance to the human body from water in accordance with the main provisions were taken into account [22]. As a result, the value of the most inactive concentration of flubendiamide has been obtained — 0.006 mg/dm3.

Based on the threshold and sub-threshold levels established on the basis of the main parameters of harm, the justification of the MPC of flubendiamide in water of water reservoirs for household and drinking, cultural and household purposes was carried out. The analysis of obtained data allowed to conclude that the limiting feature of the adverse effect of flubendiamide is the general sanitary. The value of 0.003 mg/dm3 was recommended and approved as MPC of flubendiamide in water of reservoirs for household and drinking, cultural and household purposes (limiting sign of harm — general sanitary). The limit of the quantification of flubendiamide in water by HPLC is 0.003 mg/dm3.

Due to the fact that flubendiamide belongs to pesticides of the 1st class of hazard by “soil stability” parameter, experimental studies have been carried out to substantiate the maximum permissible concentration of a substance in the soil in accordance with [21, 24]. When substantiating MPC of flubendiamide in the soil, the above characteristics of the substance were taken into account by the criteria “soil stability” and “depth of migration by the soil profile” in accordance with DSanPiN 8.8.1.002-98 [12], literature data [1–10], and results of own studies. The experiment has established the values of translocation, water migration, air migration and phytotoxic parameters, as well as, the general sanitary parameter according to the literature. The limiting parameter of the safe content of flubendiamide in the soil is translocation. Taking into account this value, its MPC in the soil is 0.25 mg/kg. The value of 0.25 mg/kg is the recommended and approved MPC of flubendiamide in a soil with a translocation limiting parameter. The limit of the quantification by HPLC is 0.05 mg/kg.

The obtained study results of the hazardous effects of Belt 480 SC on agricultural workers and population during and after its application (boom spraying, a rate of consumption of 0.15 L/ha, working fluid of 250 L/ha) showed that in the air of the breathing zone of the filling attendant and tractor operator, in the air the zone of possible sweeping of drug aerosol at a distance of 300 m from the boundary of the site during spraying and at the same place 1 hour after spraying, in air above the site after 1 hour, 3 and 7 days after spraying, flubendiamide was not detected (LOD of flubendiamide by HPLC in the air of the working zone — 0.06 mg/m3 and in atmospheric air — 0.001 mg/m3). In the soil of the treated area, the content of flubendiamide in 3 and 7 days did not exceed the hygienic standards. In the soil from the border of the sanitary protection zone (300 m), 1 hour after treatment, the active ingredient was not detected (LOD by HPLC — 0.02 mg/kg).

According to the MR 8.8.1.4-162-2009 [27] and study results, possible exposure inhalation (Di) and dermal (Dd) doses, mg of active ingredient/kg body weight were calculated, which had an effect on filling attendant and tractor operator during the work shift (6 hours); approximate permissible inhalation (PDi) and dermal (PDd) doses of flubendiamide for workers, mg of active ingredient/kg body weight per day (PDi = 0.019; PDd = 0.1) were justified. The results of the comparison of possible exposure and approximate permissible doses indicate that the factor and indices of hazard (risk) of the complex effect of flubendiamide on the workers were significantly lower than the acceptable level.

Conclusion

1. Flubendiamide and Belt 480 SC belong to the pesticides of the 2nd class of hazard according to the limiting criterion of hazard — acute inhalation toxicity. Flubendiamide has a polytropic effect on the body. The main target organs in rats are liver, thyroid gland, kidneys, and blood system. Flubendiamide by its mutagenic and carcinogenic activity belongs to the pesticides of 4th class of hazard, by teratogenic activity, embryo and reproductive toxicity — to the pesticides of the 3rd class of hazard.

2. To prevent the possibility of adverse effects on human health and changes in the quality of the environment, PDE and the following hygienic standards of flubendiamide are justified:

–  PDE — 0.003 mg/kg body weight/daily.
–  MPL, mg/kg: corn (grain) — 0.05 (LOD by HPLC — 0.05); corn (oil) — does not required, sunflower (seeds) — 0.05 (LOD by HPLC — 0.05); sunflower (oil) — does not require, soybean (grain) — 0.05 (LOD by HPLC — 0.05), soybean (oil) — does not required, cabbage — 0.1 (LOD by HPLC — 0.1), tomatoes — 0.1 (LOD by HPLC — 0.1), tomato juice — 0.05 (LOD by HPLC — 0.05).
–  AESL in the air of the working zone, mg/m3: 0.2 (LOD by HPLC — 0.02).
–  AESL in atmospheric air, mg/m3: 0.001 (LOD by HPLC — 0001).
–  MPC in water of water reservoirs, mg/dm3: 0.003, general sanitary (LOD by HPLC — 0003).
–  MPC in soil, mg/kg: 0.25, translocation (LOD by HPLC — 0.05).

3. In case of compliance with the current rules of pesticide management, the levels of flubendiamide content in the production environment, as well as its external inhalation and dermal exposure, are safe for agricultural workers involved in the use of insecticide Belt 480 SC. The sanitary protection zone established under the conditions of the agro-industrial sector is safe for land use of the drug for the population and objects of the environment; at the stages of work on treated areas, the production environment is safe when works are performed 3 and 7 days after spraying.

Flubendiamide was not found in the harvest of corn and soybean, sunflower seeds, cabbage and tomatoes at the level of the limit of detection (LOD). After application of insecticide, the waiting time for harvesting is corn, sunflower and soybean — 30 days, cabbage — 20 days, and tomatoes — 14 days.

4. From toxicological and hygienic positions, there are no objections concerning the permanent registration of insecticide Belt 480 SC in Ukraine for use in corn, soybean and sunflower with a maximum rate of consumption of 0.15 L/ha, once; cabbage and tomatoes — 0,1 L/ha, twice.

 

REFERENCES

1. Registration of the New Active Ingredient Flubendiamide Contained in Belt SC Insecticide (EPA Reg. No. 264–1025) and Synapse WG Insecticide (EPA Reg. No. 264–1026): New York State Department of Environmental Conservation Division of Materials Management. Bureau of Pest Management Product Registration & Pest Management Alternatives Section.

2. Pesticide Fact Sheet. Flubendiamide Conditional Registration. – Washington: EPA. Office of Prevention, Pesticides and Toxic Substances, 2008. – 65 р.

3. Public Release Summary on Evaluation of the new active flubendiamide in the product/s Belt 480 SC Insecticide & Belt 240 WG Insecticide. –  Canberra, Australia: National Registration Authority for Agricultural and Veterinary Chemicals. – 76 р.

4. Pesticide Fact Sheet. Flubendiamide. – EPA. – 2012.

5. A World Compendium the Pesticide Manual Fifteenth Edition Editor:CDS Tomlin. Flubendiamide. – BCPS. – 2009. – P.229–230.

6. Conclusion on pesticide peer review/Conclusion on the peer review of the pesticide risk assessment of the active ingredient flubendiamide //EFSA Journal 2013. – No. 11(9):3298. – 62 р.

7. European Food Safety Authority (EFSA), Parma, Italy EFSA Journal 2013. – No. 11(9)3298.

8. Sahoo SK, Sharma RK, Battu RS, Singh B Pesticide Residue Analysis Laboratory, Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, 141004, India.Bulletin of Environmental Contamination and Toxicology. – 2009. No. 83(3). – Р. 384–387.

9. United States Environmental Protection Agency. Washington. D.C. 20460-0001. BELTTM SC Insecticide. – 2012.

10. FLUBENDIAMIDE (242) First draft prepared by Prof. Eloisa Dutra Caldas University of Brasilia Brasilia, BRAZIL – Р.1266–1392.

11. Guidelines for the Hygienic Evaluation of New Pesticides: approved by the Ministry of Health Protection of USSR as of 13.03.87 No. 4263-87 – Kyiv, 1988. – 210 p.

12. Hygienic classification of pesticides by the degree of hazard: DSanPiN 8.8.1.002-98 approved by the MoH of Ukraine under No. 2 as of 28.09.98. – Kyiv, 1998 – 20 p.

13. Guidelines on pesticide residue trials to provide data for the registration of pesticides and the establishment of maximum residue. FAO, UN. ROME. – 1986.

14. Uniform Rules of Taking Samples of Agricultural Products, Food and Environmental Objects for Pesticide Microdetermination: approved by the Ministry of Health Protection of USSR August 21, 1979 No. 2051-79. – Moscow:.Ministry of Health Protection of USSR, 1980. – 40 p.

15. Guidelines for the determination of flubendiamide in corn grain and corn oil using the method of high performance liquid chromatography: Guideline No. 1,322–2,014 as of 28.11.2014, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 383 as of 28.11.14), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 04.03-08-5523/7 as of 40.11.14).

16. Guidelines for the determination of flubendiamide in sunflower seeds and sunflower oil using the method of high performance liquid chromatography No. 1422-2015 as of 18.05.15, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 156 as of 18.05.2015), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 04.03-08-1545/17 23 as of 10.04.15).

17. Guidelines for the determination of flubendiamide in cabbage, tomatoes and tomato juice using the method of high performance liquid chromatography No. 1174–2012 as of 05.09.12, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 452 as of 05.09.2012), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 23 as of 02.08.2012).

18. Guidelines for the conduct of studies to substantiate the sanitary standards of hazardous substances in the air of the working zone: approved by the Ministry of Health Protection of USSR as of 04.04.80 No. 2163-80. – Moscow, 1981. – 20 p.

19. Guidelines for the determination of approximate safe levels of exposure to hazardous substances in the air of the working zone: approved by the Ministry of Health Protection of USSR as of 04.11.85 No. 4000-85. – Moscow, 1985. – 34 p.

20. Guidelines “Justification of the approximate safe levels of exposure (AESL) of chemical substances in the atmospheric air of inhabited places”, Guidelines 2.2.6.-111-2004, approved by the MoH of Ukraine under No. 485 as of 07.10.04. – Kyiv, 2004. – 33 p.

21. Guidelines for the development and scientific substantiation of the maximum permissible concentrations of hazardous substances in water of water reservoirs: approved by Ministry of Health Protection of USSR as of 15.04.75 No. 1296-75. – Moscow, 1976. – 78 p.

22. Guidelines for drinking-water quality. Second Edition. Geneva: WHO, 1993 – V. No. 1; 1996. – V. No. 2. – 1997. – V. No. 3.

23. Guidelines for the determination of flubendiamide in water by high performance liquid chromatography No. 1172-2012 as of 05.09.12, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 452 as of 05.09.2012), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 23 as of 02.08.2012).

24. Guidelines on hygienic substantiation of MPC of chemical substances in soil. – М., 1982. – 57 p.

25. Guidelines for the determination of flubendiamide in soil by high performance liquid chromatography No. 1173-2012 as of 05.09.12, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 452 as of 05.09.2012), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 23 as of 02.08.2012).

26. Sierhieiev S. H. Assessment of the possibility for the development of acute toxic effects during work with pesticides considering their selectivity of action /S. H. Sierhieiev, Yu. H. Chaika // Current issues of toxicology. – 2008. – No. 4. – P. 29–31.

27. Guidelines “Study, Assessment and Reduction of the Risk of Inhalation and Percutaneous Exposure to Pesticides of Persons Who Work With Them or May Be Exposed During and After Chemical Protection of Plants and Other Objects”: Guidelines 8.8.1.4-162-2009, approved by the MoH of Ukraine No. 324 as of 13.05.2009 — Kyiv, 2009. – 32 p.

28. Guidelines for the determination of flubendiamide in the air of the working zone and atmospheric air using the method of high performance liquid chromatography No. 1171-2012 as of 05.09.12, approved by the Ministry of Ecology and Natural Resources of Ukraine (Order No. 452 as of 05.09.2012), agreed by the State Sanitary Epidemiological Service of Ukraine (Letter No. 23 as of 02.08.2012).

 

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