Publications by authors named "Dragica Brkic"

8 Publications

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Effects of the technical ingredient clomazone and its two formulated products on aquatic macrophytes.

Environ Pollut 2021 May 16;277:116753. Epub 2021 Feb 16.

Institute of Pesticides and Environmental Protection, Banatska 31b, 11000, Belgrade, Serbia.

One active ingredient can be a component of different types of formulations of pesticides, while the toxicity of its formulations may vary depending on various constituents used in the mixture. The present study focuses on evaluating the effects of the active ingredient clomazone and its formulations (Rampa® EC and GAT Cenit 36 CS, both containing 360 g a.i./l of clomazone) on non-target aquatic macrophytes. The two formulation types differ in their active ingredient release and presumed environmental impact. In order to cover different ecological traits, two species of aquatic macrophytes - the floating monocot Lemna minor and the rooted dicot Myriophyllum aquaticum, were used as test models. The results of this study revealed differences in the sensitivity of tested plants to clomazone. Based on the most sensitive parameters, M. aquaticum proved to be more sensitive than L. minor to the technical ingredient and both formulations. The species sensitivity distribution (SSD) approach that was tried out in an attempt to create a higher tier step of risk assessment of clomazone for primary producers indicates that tests on rooted macrophytes can add value in risk assessment of plant protection products. The capsule formulation of clomazone was less toxic than the emulsion for L. minor, but more toxic for M. aquaticum. The most toxic for L. minor was the emulsifiable concentrate formulation Rampa® EC, followed by technical clomazone (EC 33.3 and 54.0 mg a.i./l, respectively), while the aqueous capsule suspension formulation GAT Cenit 36 CS did not cause adverse effects. On the other hand, the most toxic for M. aquaticum was the formulation GAT Cenit 36 CS, followed by technical clomazone and the formulation Rampa® EC, demonstrating a greater effect of the capsule formulation.
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http://dx.doi.org/10.1016/j.envpol.2021.116753DOI Listing
May 2021

In vitro assessment of pesticide residues bioaccessibility in conventionally grown blueberries as affected by complex food matrix.

Chemosphere 2020 Aug 19;252:126568. Epub 2020 Mar 19.

University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, P.O. Box 23, 11 010, Belgrade, Serbia.

The aim of this study was to investigate the bioaccessibility of pesticide residues in blueberries (commercial and sample from controlled field trial) from Serbia, involving the presence of a complex food matrix and to assess the potential risk to human health. The presence of nine active substances (azoxystrobin, boscalid, fludioxonil, cyprodinil, pyrimethanil, pyridaben, pyriproxyfen, acetamiprid and thiametoxam) in initial blueberry samples was determined in concentration range from 5.15 μg/kg for thiametoxam to 187 μg/kg for azoxystrobin. Clothianidin, metabolite of thiametoxam, was not detected in any blueberry sample. However, after in vitro digestion, the content of initially detected pesticides residues was significantly decreased or it was below limit of quantification resulting in the total bioaccessibility of about 15%. Azoxystrobin, pyrimethanil and fludioxonil was quantified in digestive juice at concentrations which were about 81%, 37% and 10% less than the inital concentration, respectively. The presence of food matrix during digestion of blueberries even more severely reduced concentration of pesticide residues (total bioaccessibility was about 7%) compared to digestion without the food matrix. Only azoxystrobin was quantified after digestion with food matrix in concentration of 27 μg/kg in sample from controlled field trial and detected in two commercial samples but below the limit of quantification. Furthermore, chronic risk assessment indicated that risk is acceptable for the health of different human subpopulation groups. The current study on pesticides residues, most commonly applied on blueberries, provides for the first time an insight into their bioaccessibility under conditions that mimic physiological environment of human digestive tract.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126568DOI Listing
August 2020

Comparative analyses of cellular physiological responses of non-target species to cypermethrin and its formulated product: Contribution to mode of action research.

Environ Toxicol Pharmacol 2019 Jan 23;65:31-39. Epub 2018 Nov 23.

Laboratory for Ecotoxicology - LECOTOX, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 2, 21000, Novi Sad, Serbia.

Physiological responses of bacterial, fish, rat and human hepatoma cells to the technical cypermethrin (AS), cypermethrin-based plant protection product (PPP), and the major co-formulant (solvent) were compared. The endpoints included: bioluminescence, total protein content, activity of mitochondrial dehydrogenase and cytochrome P450 (CYP) enzymes CYP1A and CYP1B, and expression of several genes encoding different CYP enzyme isoforms. Toxicity of PPP was compared with the toxicity predicted using concentration addition model. Cypermethrin disturbs the activity of mitochondrial dehydrogenase. Induction of CYP1A1-, CYP1A2- and CYP1B1-associated activity was more pronounced in PPP than in cypermethrin treatment. The predominant biotransformation pathway of cypermethrin is related to Cyp3a1 induction. Deviations between observed and predicted toxicity of PPP indicate synergistic effects of cypermethrin and a solvent. In vitro cellular assays may serve as rapid pre-screening tool and provide for a good indication of mixture effects and prompt further in vivo testing of PPPs when really needed.
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http://dx.doi.org/10.1016/j.etap.2018.11.007DOI Listing
January 2019

Environmental exposure to organophosphorus nerve agents.

Environ Toxicol Pharmacol 2017 Dec 7;56:163-171. Epub 2017 Sep 7.

Faculty of Agriculture, University of Belgrade, Institute for Phytomedicine, Serbia. Electronic address:

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems.
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http://dx.doi.org/10.1016/j.etap.2017.09.004DOI Listing
December 2017

Toxicity of clomazone and its formulations to zebrafish embryos (Danio rerio).

Aquat Toxicol 2017 Jul 19;188:54-63. Epub 2017 Apr 19.

Research Center for Toxic Compounds in Environment, Kamenice 753/5, 62500 Brno, Czech Republic. Electronic address:

Herbicides are the most widely used group of pesticides but after reaching water bodies they are able to cause adverse effects on non-target organisms. Different formulations using the same active ingredient are frequently available, which raises the issue of potential influence of different formulation types on herbicide toxicity. The present study evaluated the toxicity and teratogenic effects of the active ingredient clomazone and its two formulations (Rampa EC and GAT Cenit 36 CS, both containing 360g a.i./l of clomazone) on zebrafish embryos. The crucial difference between the two formulation types is the way of active substance release. This investigation is the first report on zebrafish embryotoxicity of both clomazone and its formulations. The technical active ingredient and formulations caused mortality and diverse teratogenic effects, showing different levels of toxicity. The LC values for the technical ingredient, Rampa EC and GAT Cenit 36 CS were 61.4, 9.6 and 92.5mg a.i./l, respectively. Spontaneous movements in 22 hpf embryos decreased under exposure to both the technical ingredient and formulations. A significant number of underdeveloped embryos was detected after exposure to clomazone and Rampa EC, while no underdevelopment was noted in embryos exposed to GAT Cenit 36 CS. Exposure to the technical ingredient and formulations led also to a series of morphological changes and interfered with the growth of zebrafish embryos. The EC based on detection of edemas, spine and tail tip deformations and gas bladder absence (120hpf) was 12.1, 10.1 and 24.1mg/l for technical clomazone, Rampa EC and GAT Cenit 36 CS, while teratogenicity index (TI) based on LC/EC ratio was 5.1, 1 and 3.8, respectively. The data in this study showed that the emulsifiable concentrate formulation (Rampa EC) caused statistically significantly higher toxicity, and the aqueous capsule suspension (GAT Cenit 36 CS) lower toxicity than technical clomazone. It indicates that different formulations with the same active ingredient may have different environmental impacts, which is why risk assessment based only on active ingredient toxicity might not be sufficient in terms of preventing formulation effects on the environment.
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http://dx.doi.org/10.1016/j.aquatox.2017.04.007DOI Listing
July 2017

Some arguments in favor of a Myriophyllum aquaticum growth inhibition test in a water-sediment system as an additional test in risk assessment of herbicides.

Environ Toxicol Chem 2015 Sep 21;34(9):2104-15. Epub 2015 Jul 21.

Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.

The present study compares the practicability, reproducibility, power, and sensitivity of a Myriophyllum aquaticum growth inhibition test in a water-sediment system with the recently accepted Myriophyllum spicatum test in an equivalent testing system and the standard Lemna sp. test. Special consideration was given to endpoints based on M. aquaticum control plant growth and variability of relative growth rate and yield: shoot length, fresh weight, dry weight, and root weight. Sensitivity analysis was based on tests performed with 3,5-dichlorophenol, atrazine, isoproturon, trifluralin, 2,4-dichlorophenoloxyacetic acid, and dicamba. Growth rates for average M. aquaticum control plants were 0.119 d(-1) and 0.112 d(-1), with average estimated doubling time 6.33 d and 6.74 d for relative growth rate fresh weight and shoot length, respectively. Intrinsic variability of M. aquaticum endpoints was low: 12.9%, 12.5%, and 17.8% for relative growth rate shoot length, relative growth rate fresh weight and yield fresh weight, respectively. The power of the test was fairly high. When the most sensitive endpoints were used for comparison, the 2 Myriophyllum species were similarly sensitive, more sensitive (in the case of auxin simulators), or at least equally sensitive as Lemna minor to other tested herbicides. The M. aquaticum 10-d test with a 7-d exposure period in a water-sediment system has acceptable sensitivity and can provide repeatable, reliable, and reproducible results; therefore, it should not be disregarded as a good and representative additional test in environmental risk assessment.
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http://dx.doi.org/10.1002/etc.3034DOI Listing
September 2015

Subacute and subchronic toxicity of Avalon(®) mixture (bentazone+dicamba) to rats.

Environ Toxicol Pharmacol 2015 May 14;39(3):1057-66. Epub 2015 Mar 14.

Institute of Pesticides and Environmental Protection, Banatska 31-b, 11080 Belgrade-Zemun, Serbia. Electronic address:

Subacute and subchronic toxicity of the herbicide Avalon(®), a mixture of bentazone and dicamba, were tested on rats. Avalon(®) was administered at dose levels of 250, 500 and 1000mg/kg body weight/day for 28 and 90 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were monitored together with biochemistry parameters. The results showed that the mixture caused increases in the activities of ALT, AST and ALP, elevated concentrations of sodium, albumin and albumin/globulin ratio in males. In females, ALT activity, cholesterol and phosphate levels were increased. The changes generally were dose related and, in most cases, females exhibited lower susceptibility than males. The effects of a mixture are, in the most cases, different from the effects of the individual substances. The effects of bentazone were not prevalent which would be expected taking the composition of the mixture into account.
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http://dx.doi.org/10.1016/j.etap.2015.03.004DOI Listing
May 2015

Carbofuran in water: Subchronic toxicity to rats.

Environ Toxicol Pharmacol 2008 May 17;25(3):334-41. Epub 2007 Nov 17.

Institute of Pesticides and Environmental Protection, Banatska 31-b, P.O. Box 163, 11080 Belgrade, Serbia.

Carbofuran toxicity on rats was studied during subchronic exposure. Female and male rats were administered carbofuran in drinking water in concentrations of 25, 100 and 400ppm for a period of 90 days. Clinical symptoms, water consumption, body weight gain, organ weight, pathological and histopathological changes in the liver and kidneys were observed and biochemical and haematological examinations were carried out. The results obtained show that carbofuran administered to rats caused a significant decrease in water consumption as well as in brain, serum and erythrocyte cholinesterase activities. Statistically significant increases in relation to the control were found in the serum enzyme activities. The haematological data showed that carbofuran had no significant effect on Hb concentration and total RBC, but total WBC showed a significant statistical decrease. The histopathological changes in liver and kidneys were observed. However, cell regeneration in the liver and kidneys was found in all test groups.
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http://dx.doi.org/10.1016/j.etap.2007.11.002DOI Listing
May 2008