A study of the genotoxic activity of fungicide carbendazim was carried out. It was demonstrated that the tested technical grade active ingredient of carbendazim in the dose range of 125-2000 mg/kg body weight induced a statistically significant dose-dependent increase in the frequency of micronucleated polychromatic (PCE) and normochromatic erythrocytes (NCE) in the bone marrow of CD-1 mice. After administration of carbendazim at doses of 250-2000 mg/kg body weight, the accumulation of cells containing two or more micronuclei was observed. According to the results of comet assay, there was no increase in the level of breaks and alkali-labile sites in the DNA of the mouse bone marrow and liver cells after administration of technical grade carbendazim at doses up to 2000 mg/kg body weight. It is therefore suggested that the observed accumulation of cells with micronuclei is due to the aneugenic effect of carbendazim. In addition, a dose-dependent increase in the proportion of macrocytes/gigantocytes and dumbbell-shaped cells with constrictions among PCEs and NCEs was observed, which might be indicative of the inhibitory effect of the test pesticide on cytokinesis. The accumulation of polychromatophiles with pyknotic nuclei after exposure to carbendazim is probably caused by the distortion of nuclear extrusion. A possible general mechanism underlying the impairment of karyokinesis, cytokinesis, and nuclear extrusion in mammalian bone marrow erythroid cells is discussed.
In order to overcome resistance to individual pesticides and improve their effectiveness, formulations containing two or more active substances are constantly being developed and put on the market over recent years. Mixtures of residual amounts of pesticides can be present in water and food and enter the human and animal bodies. However, the combined effect of pesticides on living organisms, including genetic structures in cells, has not been studied enough and it is not yet possible to predict the genotoxic effects of their mixtures based on available data. The purpose of this review was to collect and summarize literature information on the genotoxicity of pesticide combinations obtained at different objects. The results of studies conducted in different countries of the world are discussed, examples of detected synergistic, additive and antagonistic effects are given, indicating the need for testing the genotoxicity of preparative forms of pesticides containing several active substances, as well as mixtures of jointly used pesticides in order to ensure the safe use of pesticides for public health.
In the Russian Federation about 600 active ingredients of pesticides are currently registered. A large share among them is occupied by analogous pesticides (generics), which may differ in their properties from the original products due to an increased level or altered composition of impurities. Therefore, to ensure the safe use of analogous pesticides, it is necessary to evaluate their chemical and toxicological equivalence. The analysis of algorithms described in international documents and implemented in practice in some countries for determination of the equivalence of technical materials of analog pesticides is presented. Particular attention is paid to the evaluation of pesticide safety on the basis of the mutagenicity criterion. The applicability of different methods for genotoxic activity determination to confirm the equivalence of active substances of pesticides-analogues to patented products is discussed. A brief review of the results of the researches confirming the need to assess the genotoxicity of all technical materials of analogous pesticides with a view to preventing the entry of hazardous substances into the consumer market is presented.
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