Introduction. For the treatment of agricultural crops, an original herbicide of selective action was created - propisochlor, a derivative of chloroacetanilide. Its characteristics in an acute toxicological experiment didn’t reveal the features of the pathogenesis of intoxication. The identification of regularities in the manifestation of the toxic properties of propisochlor in various regimens with the oral route of exposure is necessary at the stage of production design. Moreover, it is necessary to substantiate a number of hygienic regulations for safe production and its further application in agriculture, which lies in the plane of solving the leading state tasks aimed at protecting human health and its environment, and meets the requirements of international legislation. A special role in the development of such methods and methods belongs to the sanitary-toxicological study of new xenobiotics and generic molecules, as a result of which threshold and subthreshold doses of pesticide preparations and their active substances are determined. The aim of this study was to characterize propisochlor in a chronic oral toxicology study in rats. To achieve the goal, it was necessary to solve the following tasks: to study the chronic oral effect of the chloroacetanilide derivative on the rat organism; establish a dose that does not have a visible undesirable effect (NOELch); set the lowest dose at which no adverse effects are observed (LOAELch); calculate the allowable daily intake, or allowable daily exposure (ADD, or ADI, or PDE) for a person. Material and methods. The object of testing in this work was a herbicide from the class of chloroacetanilide, propisochlor. The test system in the chronic experiment was white male rats, on which the influence of the test compound was evaluated in dynamics after 1, 3, 6 and 12 months according to the state of integral indicators. Results. The parameters of the oral toxicity of the test compound were determined and the changes in the studied integral indicators were evaluated at various stages of the experiment in a chronic experiment. Conclusion. Based on the comparative characterization of a new herbicide propisochlor in a chronic oral toxicology study in rats, a non-acting dose (NOEL), the lowest effective dose (LOAEL), and an acceptable daily dose for humans (ADI, or PDE) are justified.
In the modern world, which is on the threshold of eight billion people, the issue of food security takes one of the leading places. Due to the limited amount of agricultural land, it is necessary to increase the yield of the fields, which is almost impossible without the use of chemical plant protection products. In turn, the use of pesticides carries huge risks to public health. Application of pesticides in the cultivation of agricultural lands can lead to their transfer into the human body in different ways. Pesticides can be transported with subsurface and lateral runoff into water reservoirs, from where they can reach the centralized water supply or be withdrawn from water sources by residents of settlements close to agricultural fields. Pesticide active volatile ingredients can evaporate from the soil surface and move over long distances. In addition, translocation of pesticides from soil to plants is a source of public health risk, which may result in further transfer of active substances in concentrations exceeding maximum residue levels (MRL) into human foodstuffs. In the same time, persistent pesticides can accumulate in the soil and subsequently lead to disruption of soil functioning. Therefore, hygienic regulation of pesticides is the most important issue in ensuring public safety. In addition to MAC values, it is proposed to use values based on the MAC: maximum allowable application level (MAEL) and safe residual quantity (SRQ). These values would allow to increase the level of protection of the population from potential harms of pesticides used in agricultural practices for specific soil and climate zones.
Introduction. Neurotoxins are a class of chemicals that damage neurons. Some pesticides have a similar effect. The increase in areas with developed heavy industry and agriculture, uncontrolled use of pesticides contribute to the emergence and progression of Alzheimer’s and Parkinson’s disease (PD). The insidiousness of PD is that it is still incurable, since there is no early diagnosis: for decades it has been asymptomatic, and by the time of manifestation there are no target neurons for therapy. Considering that the diagnosis is made at the late stages of PD development, the treatment of the disease is ineffective. It follows that in order to increase the effectiveness of treatment, it should be started as early as possible - before the appearance of motor symptoms, at the preclinical stage. To do this, it is first necessary to develop an early (preclinical) diagnosis of PD based on an in-depth study of the cellular and molecular mechanisms of pathogenesis. In order to develop early diagnosis and preventive therapy of PD, proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used in this study. Material and methods. To simulate the preclinical and clinical stages of PD, inbred lines of animals were injected with MPTP according to certain schemes. The behavior of experimental animals was assessed, and after their decapitation, the content of monoamines in the structures of the brain, peripheral organs, and blood plasma was determined by HPLC, and a morphofunctional analysis of the studied tissues and organs was performed. Results. The clinical stage of PD was modeled in animals, which corresponds to the key characteristics of PD in humans. A hypothetical preclinical stage of PD was modeled in animals, on which the method of early diagnosis was successfully tested. This model shows a number of important biochemical changes in peripheral organs, indicating the systemic nature of the disease and preceding the onset of the clinical stage of PD. Research limitations. The results of this study can only be applied to humans only after similar results have been obtained in monkeys. Limitations. Only after obtaining similar results in monkeys the results of this study can be translated to humans. Conclusion. Knowledge about the mechanisms of action of some neurotoxins is expanding, which are successfully used for the needs of fundamental, medical and biological sciences.
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