L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety”, Ministry of Health of Ukraine, Kyiv, Ukraine
Abstract. Objectives of the work. To study the toxicity of the quizalofop-p-ethyl technical generic, toxicological and hygienic properties of the agent Astarg 125 EC (quizalofop-p-ethyl, 125 g/L) made on its basis, and to develop the regulation of the application of this herbicide in agriculture.
Methods of the study. Toxicological, hygienic, chemical and statistical.
Results and their discussion. The toxicity parameters of the quizalofop-p-ethyl generic and Astarg 125 EC herbicide made on its basis were determined using different routes of exposure to laboratory animals. The conducted studies showed that the character of the toxic effect and the non-effective level of quizalofop-p-ethyl do not significantly differ from those of compounds produced by other companies that are registered in Ukraine. According to the toxicity indicators, quizalofop-p-ethyl and Astarg 125 EC herbicide refer to pesticides of the 2nd hazard class (State Sanitary Rules and Regulations 8.8.1.002-98). Limiting harmful index is inhalation toxicity. The species sensitivity of laboratory animals to toxic effect was not observed. The results of the hygienic assessment of working conditions when using Astarg 125 EC herbicidal agent under agricultural production conditions showed that when assessing the conditions for its safe use, it is necessary to take into account the hygienic standards in the working zone air and open air of the inhabited areas of its active ingredient — quizalofop-p-ethyl.
Conclusions:
- Taking into account quizalofop-p-ethyl content level in the herbicide Astarg 125 EC, its toxicity parameters at different routes of exposure, it is possible to use it for its intended purpose provided that the regulations for safe use, as well as the usual precautions for storage and application of the agent are observed.
- Using Astarg 125 EC to protect sugar beet is safe from the standpoint of nutrition hygiene. It is recommended to use the herbicide on sugar beet with a consumption rate of 1,2 L/ha.
- Control of the aerial environment and environmental objects when applying Astarg 125 EC herbicide should be carried out according to its active ingredient — quizalofop-p-ethyl.
Key words: herbicide, Astarg 125 EC, toxicity, hygiene of application, regulatory actions.
Relevance. Introduction of modern crop cultivation technologies, an integral part of which is plant protection agents (PPA), plant growth regulators and fertilisers, is an important reserve for agricultural production increase. Development of effective and human- and environment-friendly agents is an urgent and important problem. Therefore, a range of herbicides is constantly expanding and renewing. Such new substances include the systemic herbicide Astarg 125 EC, which is recommended for use in agriculture against annual and perennial weeds in sugar beet crops [1]. Penetrating through the surface of the leaf of grass weeds and moving to the point of growth, root and rhizome, the agent disrupts the process of photosynthesis. Plants stop growing, gain on anthocyanin colour, wither and die. The herbicidal efficacy of this agent is 90–98 %. The active ingredient of Astarg 125 EC is quizalofop-p-ethyl. Physical and chemical properties of quizalofop-p-ethyl are presented in Table 1.
Table 1. Physical and chemical properties of quizalofop-p-ethyl.
The conducted information search showed that a positive feature of quizalofop-p-ethyl herbicide is low persistence in environmental objects and plants. The substance quickly degrades in the soil forming an intermediate metabolite — quizalofop-p-acid; hydrolysis proceeds more rapidly in soils with high microbial activity. Quizalofop-p-ethyl is moderately sorbate and characterized by low mobility in the soil, stable in neutral and dilute acidic solutions, not stable in alkaline solutions.
Analysis of literature data showed that quizalofop-p-ethyl can have an adverse effect on the body. According to the literature, information on the toxicity parameters of quizalofop-p-ethyl of different manufacturers in acute experiment is contradictory [2–9]. Thus, when administered orally, LD50 ranges from 1,010 to 6,600 mg/kg for male rats, and from 1,082 to 5,700 mg/kg for female rats. In case of inhalation exposure, LC50 of quizalofop-p-ethyl for rats can be 3,34 mg/L and 75 mg/L. The information on its sensitisation and irritant properties also differs. The main characteristic of quizalofop-p-ethyl toxic effect is a hepatotrophic effect that manifests in all species of animals exposed to its high concentrations. The limiting effect when assessing the herbicide’s danger is generally toxic. Quizalofop-p-ethyl rapidly metabolises in the body to quizalofop-p-acid and is excreted with urine and faeces. Given the toxicological properties, the WHO classified quizalofop-p-ethyl as a pesticide of the 2nd hazard class.
This brief review of the literature showed that the negative effect of quizalofop-ethyl on the body indicates the relevance and need for a comprehensive toxicological and hygienic study of the technical substance and the agent made on its basis. The manufacturer did not provide information on the toxicity parameters of quizalofop-p-ethyl and the herbicide agent Astarg 125 EC.
The objective of the work is to determine the toxicity of technical quizalofop-p-ethyl, the toxicological and hygienic properties of the herbicide Astarg 125 EC, to develop regulations for its application from the standpoint of safety for workers and the population. To achieve the objective, the following tasks were set: to study the toxicity parameters of the agent Astarg 125 EC and its active ingredient at different routes of exposure to laboratory animals; to conduct a hygienic assessment of the working conditions of individuals applying it; to study the dynamics of quizalofop-p-ethyl content in sugar beet, soil; to substantiate the possibility of using the previously approved hygienic standards and regulations.
Objects and methods of the study. Objects of the study: technical agent of quizalofop-p-ethyl, herbicide Astarg 125 EC, white Wistar Han rats, mice, Chinchilla rabbits, guinea pigs, working zone air, soil, sugar beet, wipe-samples from open skin areas and layers of work clothes.
Toxicological and hygienic studies were carried out in accordance with the Methodology Guidelines for the Hygienic Evaluation of New Pesticides [9]. When determining the toxicity parameters of Astarg 125 EC and quizalofop-p-ethyl in case of oral, dermal and inhalation exposure, the criterion of the substance effect on the body was the appearance of intoxication symptoms and death of animals; LD50 and LC50, sensitization and irritant properties were determined. In order to detect the species sensitivity, the studies were carried out on rats, mice and rabbits. The maintenance, care and all manipulations with laboratory animals were carried out in accordance with the provision of the General Ethical Principles for Experiments on Animals and DSTU IS0 10994-2:2004. Hygienic studies on the evaluation of working conditions were carried out based on the results of determining of quizalofop-p-ethyl concentrations in the working zone air at various workplaces, in wipe-samples from open skin areas and layers of work clothes; analysis of the content of its residues in the soil and sugar beet was performed. Sampling of air, soil and sugar beet, as well as packaging, storage, transportation and acceptance of samples to the laboratory for research, were conducted consistent with the Uniform Rules of Taking Samples of Agricultural Products, Food and Environmental Objects for Pesticide Microdetermination [10]. Measurement of quizalofop-p-ethyl concentrations in the working zone air, soil, sugar beet was carried out after appropriate sample preparation by gas-liquid chromatography, and in the atmospheric air — by high-performance liquid chromatography [11–13].
Before the start of work with the Astarg 125 EC and after its completion, a medical examination of the workers was carried out — the pulse rate was determined, the state of the skin and mucous membranes were assessed. Exposure inhalation and dermal doses of quizalofop-p-ethyl that affect the refueller and tractor operator during the work shift, as well as its approximately permissible inhalation and dermal doses and the occupational risk of substance exposure to workers were determined in accordance with methodological approaches [14].
Statistical processing of digital data was carried out using the method of variation statistics [15]. The studies corresponded with the requirements of the quality control system of the State Enterprise “L. I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety” of the Ministry of Health of Ukraine, which takes into account the requirements of ISO/IEC 17025 (accreditation certificate No. 2H375 dated May 22, 2015).
Results and their discussion. In case of inhalation intake of technical quizalofop-p-ethyl, rats developed an intoxication pattern, which manifested as a decrease in motor activity, ataxia, shallow breathing, weak reaction to tactile and noxious stimuli, as well as a decrease in body weight gain. Thus, in a week, in comparison with the initial body weight, experimental animals increased their weight by 1.9 %, while this indicator was 7.0 % in the control group; in two weeks, body weight in experimental animals increased by 7.8 %, while in the control animals body weight increased by 13.5 %. The conducted researches showed that in case of a single intake (exposure for 4 hours) through respiratory tracts of rats, LC50 of technical quizalofop-p-ethyl is 4,800 mg/m3. In case of a single administration of quizalofop-p-ethyl LD50 into the gastrointestinal canal, macroscopic studies showed that the appearance of the experimental female rats and the condition of their internal organs did not differ from those of the control animals. Behaviour and feed eating after application of the pesticide to the animal skin were at the control level. The increase in the body weight of the experimental rats during the whole experiment did not differ from the control group. LD50 of quizalofop-p-ethyl in case of dermal exposure is more than 4,000 mg/kg. Quizalofop-p-ethyl weakly irritates eye mucous membranes of rabbits. In a day, there was conjunctival hyperaemia (2 points) and a small amount of serous discharge (2 points). During the entire period of observation, there were no palpebral oedema and changes of tactile sensitivity. Symptoms of irritation were not observed after 4 days. The substance does not have skin irritant and sensitisation properties. Thus, the active ingredient of Asterg 125 EC — quizalofop-p-ethyl, manufactured by the People’s Republic of China, is classified as a substance of the 2nd hazard class due to its impact on the body in accordance with the current hygienic classification of Ukraine. Limiting harmful index is inhalation toxicity. According to the nature of the toxic effect and non-effective level, technical quizalofop-p-ethyl refers to a similar technical sample of other companies registered in Ukraine.
When studying the toxic properties of the herbicide Astarg 125 EC at different routes of exposure to laboratory animals, it was established that: In case of a single oral intake of the agent in high doses, laboratory animals developed an intoxication pattern indicative of its predominant effect on the central nervous system. Rats and mice gained less body weight compared to the initial level. Thus, a week after exposure, rats from the experimental group increased their body weight by 4.7 %, while rats from the control group increased weight by 9.8 %; in two weeks, body weight in the experimental group increased by 9.2 % compared to 12.0 % of the control group. %. The macroscopic studies carried out at the end of the experiment showed that the condition of internal organs of the animals did not differ from those of the control group. In the experiment with a single administration of the Astarg 125 EC into the stomach, it was found that LD50 for mice and rats is 2,000 mg/kg. The sensitivity of mice and rats to the agent depending on the species and sex of animals was not observed. EHF is 1.0. After applying the drug to the skin of rats and rabbits at a dose of 4,000 mg/kg, no signs of intoxication and death of animals were observed. In case of dermal exposure, LD50 of Astarg 125 EC for rats and rabbits is > 4,000 mg/kg. No macroscopically visible changes in the internal organs of the animals were observed. Animal sensitivity to the agent depending on the species and sex was not observed. Rats subjected to inhalation exposure to Astarg 125 EC at a dose of 4,000 mg/m3 within 4 hours showed decreased motor activity, impaired coordination of movements, shallow breathing. Symptoms of intoxication resolved in 10–12 hours. In the experimental group, the body weight gain was 3.5–2 times less than in the control group. Thus, in a week, in comparison with the initial body weight, experimental animals increased their weight by 1.9 %, while this indicator was 7.0 % in the control group; in two weeks, the body weight gain was 7.8 % and 13.5 % respectively. No lethal outcomes were observed. No macroscopically visible changes in the internal organs of rats were observed. LC50 of Astarg 125 EC for rats is 4,000 mg/m3. Astarg 125 EC moderately irritates the mucous membrane of the eyes, which manifested as diffuse hyperaemia and conjunctival oedema, serous discharges. These events passed in 7 days after the exposure. The herbicide does not have skin irritant properties. Studies of its sensitisation properties showed that after intradermal administration through the ear of guinea pigs, no local skin reaction was observed, no skin manifestations of the process development after herbicide application in the challenging dose were observed. Thus, on the basis of the obtained data on the parameters of acute toxic effects, the agent Astarg 125 EC refers to the 2nd hazard class according to the State Sanitary Rules and Regulations 8.8.81.002-98.
When studying the hygienic assessment of working conditions when using Astarg 125 EC, researches were carried out on the basis of LLC Khmelnytske, the Town of Khmelnyk of the Region of Vinnytsia, on sugar beet fields treated with the herbicide. The rate of herbicide consumption was 1.2 L/ha, the amount of used working fluid was 200 L/ha. The active ingredient concentration in the working solution was 150 g/L. During the treatment, the OП-2000 trailer sprayer and the UMZ tractor were used. The boom operating width was 17 m, the height above the ground was 0.5 m. The boom was operated from the tractor cab. The size of the experimental area was 68x147 m2. The working speed of the unit was 7 km/h or 1.94 m/s. The per-second coating area was 17 m . 1.94 m/s = 32.98 m2/s. The per-second working solution consumption rate was 0.66 L/s. The consumption rate of the active ingredient of Asterg 125 EC in the per-second volume of the working solution was 495 mg/s or 0.75 mg/cm3. According to the Khmelnyk meteorological station (the Region of Vinnytsia), during the spraying of the experimental area, the air temperature at an altitude of 2 m above ground level was 25.6oC; the wind speed at weather vane level was 1.5 m/s (in terms of the 2 m height — 0.99 m/s); relative humidity was 45.5 %, atmospheric pressure was 746 mm Hg; the sky was partly cloudy. From the standpoint of turbulent diffusion, the state of the atmosphere in the surface layer was practically neutral.
Calculation of the vertical air speed according to the method recommended in the work [16] showed that during the spraying period the convective air flow rate did not exceed 0.17 m/s. Preparation of the working solution and filling of the sprayer with the working solution of Astarg 125 EC were carried out in the field. About 100 litres of water were poured out of the tanker, then the preparation was added with constant stirring and the water was added to the required volume. A refueller and tractor operator were engaged in refuelling and spraying. The workers had work clothes and personal respiratory protection equipment. The results of hygienic studies on the evaluation of working conditions showed that under these conditions of Astarg 125 EC application, quizalofop-p-ethyl does not get into the working zone air. In 1 hour, 3 and 7 days after spraying the herbicide, at the sensitivity level of the chemical and analytical method, quizalofop-p-ethyl was not observed in the air of breathing zone of the refueller and tractor operator, in the zone of possible aerosol spread at a distance of 300 m from the boundary of the treated area and above this area. A study of the soil samples indicates that 3 and 7 days after a single spraying with Astarg 125 EC, the amount of quizalofop-p-ethyl was 0.7 mg/kg, which is below its exposure standard.
According to the results of the conducted studies, after refuelling and spraying, the irritant effect of the agent on the skin and mucous membranes of the eyes of the workers were not observed. The refueller and tractor operator did not have complaints of feeling unwell during and after the work. The work clothes of the refueller and tractor operator did not contain quizalofop-p-ethyl. Neither outer (fabric), nor middle and inner (gauze and filter) layers were contaminated, which indicates that there is no possibility of substance penetration through the work clothes. The content of quizalofop-p-ethyl on the face, neck and hands of the refueller was 0.009 mg and 0.01 mg on the hands of the tractor operator. Probably, this is the result of improper use of gloves when refilling a sprayer. The relative risk values of inhalation, dermal and complex exposure of workers to quizalofop-p-ethyl when using Astarg 125 EC were determined for assessing the safety indices of inhalation, dermal and complex effects of quizalofop-p-ethyl. The obtained data indicate that, at the recommended rate of agent consumption, the predicted values of the hazard (risk) index of the complex effect of quizalofop-p-ethyl on those working with Astarg 125 EC did not exceed the permissible level of 1. Thus, at the stages of sugar beet processing with the use of the herbicidal agent Astarg 125 EC, the working environment is sufficiently safe for workers.
The calculated value of the quizalofop-p-ethyl concentration in the air of the sanitary protection zone showed that the initial nominal air volume is 16.49 m3/s, its gain is 5.61 m3/s and the volume of the unsettleable fraction of the working solution is 12.94 m3/s. In this case, the herbicide initial concentration is 30.0 mg/m3.s. Calculations showed that under the described spraying conditions, 2 seconds after the working solution release into the air, only unsettleable fraction remains, which contains 9.7 mg of quizalofop-p-ethyl.
Subsequently, the herbicide concentration in the air of a fixed point was determined. The calculation results are presented in Table 2.
Table 2. The calculated values of quizalofop-p-ethyl concentrations at various distances from the treated area.
The calculations showed that under these field test conditions, the concentration of quizalofop-p-ethyl in a single wave exceeded the maximum permissible concentration in the ambient air by 11 times only at the boundary of the treated area and by 1.7 times at a distance of 25 m from the boundary. In the rest fixed points of the sanitary protection zone (50 to 300 m), the level of calculated concentrations was below the permissible norm.
According to the obtained results, the sanitary protection zone established for the conditions of the agroindustrial complex ensures the safety of the agent ground application for the population and environmental objects; at the stages of cultivation of the treated crop, the working environment is sufficiently safe for mechanical works in 3 days and for hand works in 7 days after spraying.
The results of the hygienic assessment of the working conditions when using the herbicidal agent Astarg 125 EC under agricultural production conditions showed that when assessing the conditions for its safe use, it is necessary to take into account the hygienic standards in the working zone air and ambient air of the inhabited areas of its active ingredient — quizalofop-p-ethyl. Hygienic studies on the dynamics of the residual content of quizalofop-p-ethyl in sugar beets were carried out on the basis of Shyrokostup farm, the Region of Kyiv, the District of Kaharlyk, the Village of Shubodka. Astrag 125 EC herbicidal agent was once applied at a consumption rate of 1.2 L/ha.
Organoleptic examinations observed that the experimental beet sugar samples did not have any changes in their appearance, colour and smell in comparison with the corresponding control samples. Quizalofop-p-ethyl was not found in the sugar beet top in 56 days after treatment, and also in the beet-roots in 56, 85 and 111 (harvest period) days after treatment. It should be noted that quizalofop-p-ethyl was not observed in the soil of the treated area during the harvest period.
Based on the toxicological and hygienic assessment of the properties of Astarg 125 EC and its active ingredient, the results of studies on the dynamics of quizalofop-p-ethyl content in sugar beet, and also guided by the standard methodological approaches established in hygienic rationing, a control of the herbicide use should be performed according to the previously established MRL value of quizalofop-p-ethyl in sugar beet, which is 0.05 mg/kg (limit of the quantitative determination by gas-liquid chromatography method is 0.01 mg/kg). Given the agent application technology, it is unnecessary to determine the safety interval before harvesting. The calculations of the possible daily intake of quizalofop-P-ethyl to the human body showed that, theoretically, the intake of a substance with sugar beet (in terms of sugar) can be about 1 % of the allowable daily intake. Using Astarg 125 EC to protect sugar beet is safe from the standpoint of nutrition hygiene.
Based on the results of the conducted studies, the Instruction for Safe Use of the Herbicide 125 EC in Agriculture was developed to provide measures to prevent the negative impact of the agent on workers and the environment during its storage and handling.
Conclusions
1. According to acute toxicity parameters, herbicidal agent Astarg 125 EC and its active ingredient, quizalofop-p-ethyl, belong to substances of 2nd hazard class (State Sanitary Rules and Regulations 8.8.1.2.002-98). Limiting harmful index is inhalation toxicity.
2. Control of the aerial environment and environmental objects when applying the herbicide Astarg 125 EC should be carried out according to quizalofop-p-ethyl.
3. When controlling the use of Astarg 125 EC, it is necessary to be guided by the following hygienic standards and regulations: quizalofop-p-ethyl ADD for humans is 0.01 mg/kg; MRL in beet sugar is 0.05 mg/kg; SRLI in the working zone air is 0.2 mg/m3; SRLI in the atmospheric air is 0.04 mg/m3; APC in soil is 0.8 mg/kg; MAC in reservoir water is 0.0001 mg/dm3 with a general sanitary limiting harmful index. The safety interval before sugar beet harvest is not required. The safety period for mechanical works on treated areas is 3 days, and 7 days for hand works.
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