盐酸3-甲胺丙烯酮对人体的毒性作用评价

L. G. Gorokhova, N. V. Kizichenko, M. S. Bugaeva, N. Mikhailova
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引用次数: 0

摘要

介绍。在现代医学实践中,被称为高效抗抑郁药的盐酸氟西汀(百忧解)被广泛用于治疗精神障碍。在俄罗斯,以经济上可行的生产技术管理国内的药物生产。在氟西汀的合成过程中,主要中间体-盐酸3-甲氨基丙烯酮的制备是最重要的一步。在公开出版物中,包括在国际数据库PubChem中,没有关于这种物质对人体毒性作用的数据。研究目的是研究盐酸3-甲胺丙烯酮对实验动物的毒性作用。材料和方法。在大鼠实验研究盐酸3-甲胺丙烯酮的毒性作用时,再现了单次吸入和亚急性灌胃暴露的方式。通过外周血检查、血清生化指标、肝脏、肾脏、心脏、胃、胰腺、甲状腺等脏器的形态学变化来评价该物质对动物的影响。还使用了积分参数。结果。急性吸入性中毒和亚急性胃内暴露动物的外周血和生化特征的变化类型相同。摄入盐酸3-甲胺丙烯酮后,外周血无明显变化。动物的生化特征显示AST、ALT和碱性磷酸酶活性升高。大鼠血清中总胆固醇、甘油三酯和尿素含量升高,蛋白质和胆红素含量降低。3-甲基氨基丙烯酮在形态学水平上的影响显示了所有内脏器官的血管紊乱和中重度肝脏和肾脏的脂肪变性。肝脏部分可见小灶性多腔性坏死,覆盖肝细胞群。的局限性。本研究仅限于对盐酸3-甲基氨基丙烯酮的毒理学特性的研究。根据实验动物保护的指令性文件,体内实验的数量是有限的,这与动物的危险性和公众对体内实验的伦理观点有关。结论。3-甲胺丙烯酮在急性吸入和亚急性胃内实验条件下的不同摄入方式,导致肝胆系统出现多种紊乱,对机体的共同健康状态产生负面影响。在可能接触该物质的行业,包括参与氟西汀合成的行业,作为最大限度减少急性和慢性中毒风险的一项额外预防措施,可提供血液生化检查和肝脏超声观察的扩展清单,作为工人定期体检的一部分。
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Assessment of the toxic effect of 3-methylaminopropiophenone hydrochloride on the body
Introduction. In modern medical practice, fluoxetine hydrochloride (prozac), referred to the group of highly effective antidepressants, is widely used for the treatment of mental disorders. In Russia, the domestic production of the drug with an economically feasible production technology has been managed. In the synthesis of fluoxetine, the most important stage is the preparation of the main intermediate – 3-methylaminopropiophenone hydrochloride. Data on the toxic effect of this substance on the body in the open press, including in the international database PubChem, are not available. The research aim was the study on the toxic effect of 3-methylaminopropiophenone hydrochloride on the body of laboratory animals. Materials and methods. When studying the toxic effect of 3-methylaminopropiophenone hydrochloride in experiments on rats, the modes of single inhalation and subacute intragastric methods of exposure were reproduced. The effect of the substance on the condition of animals was assessed by the results of peripheral blood studies, biochemical blood serum parameters, morphological changes in internal organs including liver, kidneys, heart, stomach, pancreas and thyroid glands. Integral parameters were also used. Results. The results of the examination of animals subjected to acute inhalation intoxication and subacute intragastric exposure showed the same type of the changes in the peripheral blood and biochemical profile. The intake of 3-methylaminopropiophenone hydrochloride did not cause significant changes in the peripheral blood. The biochemical profile of the animals showed an increased activity of AST, ALT and alkaline phosphatase. In the blood serum of the primed rats, an increased content of total cholesterol, triglycerides and urea with a reduced content of protein and bilirubin was found. The impact of 3-methylaminopropiophenone hydrochloride at the morphological level revealed vascular disorders in all internal organs and moderately severe fatty degeneration of the liver and kidneys. In some parts of the liver, there was small-focus multi-lacular necrosis which covered groups of hepatocytes. Limitations. The investigation is limited to the study on the toxicological characteristics of 3-methylaminopropiophenone hydrochloride. In accordance with the directive documents on the protection of experimental animals, the number of in vivo experiments is limited which is connected with the dangers of animals and with public ethical views on in vivo experiments. Conclusion. Different methods of intake of 3-methylaminopropiophenone hydrochloride under the conditions of acute inhalation and subacute intragastric experiments lead to a number of disorders of the hepatobiliary system with a negative impact on the common health status of the body. As an additional preventive measure to minimize the risk of acute and chronic intoxication in industries where contact with the substance is possible, including those involved in the synthesis of fluoxetine, an extended list of biochemical blood tests, ultrasound obsservation of the liver as part of periodic medical examinations of workers can be offered.
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Gigiena i sanitariia
Gigiena i sanitariia Environmental Science-Pollution
CiteScore
0.80
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0.00%
发文量
192
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