Characterization of a chloroacetanilide derivative in a chronic oral toxicology study in rats

Natal’ya Sergeevna Beloedova, T. Sinitskaya, M. A. Poroshin, Khalidya Khizbulaevna Khamidulina, Vitaly Vasilyevich Safandeev
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Abstract

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.
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氯乙酰苯胺衍生物在大鼠慢性口服毒理学研究中的表征
介绍。为了处理农作物,一种具有选择性作用的除草剂——异丙氯,一种氯乙酰苯胺的衍生物被创造出来。其急性毒理学实验特征未揭示中毒发病机制的特点。在生产设计阶段,有必要确定异丙草胺在不同方案中与口服暴露途径毒性表现的规律。此外,有必要充实一些安全生产及其在农业中的进一步应用的卫生条例,这既符合解决旨在保护人类健康及其环境的国家主要任务的范围,也符合国际立法的要求。在这些方法和方法的发展中,具有特殊作用的是对新的异种生物和通用分子进行卫生毒理学研究,从而确定农药制剂及其活性物质的阈值和亚阈剂量。本研究的目的是表征异丙氯在大鼠慢性口服毒理学研究。为实现这一目标,必须解决以下问题:研究氯乙酰苯胺衍生物对大鼠机体的慢性口服作用;确定不产生明显不良影响的剂量(NOELch);设定没有观察到不良反应的最低剂量(loelch);计算一个人的允许日摄入量,或允许日暴露量(ADD, ADI或PDE)。材料和方法。本工作的试验对象为氯乙醯胺类除草剂异丙氯。慢性实验的试验系统为雄性白鼠,分别在1、3、6、12个月后,根据各项积分指标状态,动态评价试验化合物对雄性白鼠的影响。结果。在慢性实验中,测定被试化合物的口服毒性参数,并评价所研究的综合指标在实验各阶段的变化。结论。基于在大鼠慢性口服毒理学研究中对一种新型除草剂异丙氯的比较特性,证明了其无作用剂量(NOEL)、最低有效剂量(LOAEL)和人类可接受日剂量(ADI或PDE)是合理的。
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