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The effect of a new technical product of the chloroacetamide class on the parameters of acute oral toxicity and long-term effects on the body of rats 氯乙酰胺类新工艺产品对大鼠急性口服毒性及长期作用参数的影响
Pub Date : 2023-08-30 DOI: 10.47470/0869-7922-2023-31-4-262-268
T. Epishina
ntroduction. The ability of pesticides to circulate in environmental objects (water, air, soil) and their presence in agricultural products cause the possibility of their chronic adverse effects on a living organism. The aim of the study was to study the effect of a new technical product of the chloroacetamide class (TPH) on the parameters of acute oral toxicity (LD50) and long–term effects of action (embryotoxicity and teratogenicity), the establishment of a hazard class. Material and methods. In accordance with the set goal in the biological testing laboratory (vivarium) of the FSUE “FNTSG named after F.F. Studies were conducted on the effect of a new technical product of the chloroacetamide class on the parameters of acute oral toxicity (LD50) in male rats, embryotoxicity and teratogenicity in pregnant rats. Hazard classes are established according to the methodological recommendations (MP No. 1.2.0235–21). Previously, studies in this volume have not been conducted. Results. Results. It was found that the acute oral toxicity (LD50) of the studied compound is at the level of > 2000 mg/kg of body weight. According to the results of the long-term effect, it was revealed that the inactive dose (NOEL) for the mother was set at the level of 1/15 LD50 and NOEL for 1/5 LD50 fetuses (embryotoxicity, teratogenicity). Limitations related to the analysis of the results of experimental data on the study of long-term effects (embryotoxicity and teratogenicity) of the pesticide without taking into account the carcinogenic effect on the body of warm-blooded (rats) as a result of exposure to a new technical product of the chloroacetamide class. Conclusion. The studied technical product of the chloroacetamide class according to the hygienic classification of pesticides and agrochemicals by the degree of dangerity1 by acute oral toxicity (LD50) and by the long-term effects of action (embryotoxicity and teratogenicity) carried out on rodents (rats, males and females) refers to low-hazard compounds (hazard class 4).
ntroduction。农药在环境物体(水、空气、土壤)中循环的能力及其在农产品中的存在可能导致它们对生物体的慢性不利影响。本研究旨在研究氯乙酰胺类新技术产品(TPH)对其急性口服毒性(LD50)和长期作用效应(胚胎毒性和致畸性)参数的影响,建立危害等级。材料和方法。按照以F.F.命名的FSUE“FNTSG”生物试验实验室(室内)的既定目标,研究氯乙酰胺类新技术产品对雄性大鼠急性口服毒性(LD50)、胚胎毒性和妊娠大鼠致畸性等参数的影响。根据方法学建议(MP No. 1.2.0235-21)建立危害等级。在此之前,本卷中的研究尚未进行。结果。结果。结果表明,所研究化合物的急性口服毒性(LD50)在> 2000 mg/kg体重水平。根据长期效应结果,母亲的无活性剂量(NOEL)设定为1/15 LD50水平,胎儿的无活性剂量(NOEL)设定为1/5 LD50水平(胚胎毒性、致畸性)。在对农药长期影响(胚胎毒性和致畸性)研究的实验数据结果进行分析时,没有考虑到温血动物(大鼠)因接触氯乙酰胺类新技术产品而对身体产生的致癌作用,这方面存在局限性。结论。根据农药和农用化学品按危险程度的卫生分类,按急性口服毒性(LD50)和对啮齿动物(大鼠、雄性和雌性)的长期作用(胚胎毒性和致畸性)进行研究的氯乙酰胺类技术产品为低危害化合物(危害等级4)。
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引用次数: 0
New opportunities for effective identification of unknown toxicological patients (a case from practice) 有效识别未知毒理学患者的新机会(来自实践的一个案例)
Pub Date : 2023-08-30 DOI: 10.47470/0869-7922-2023-31-4-255-261
S. Kuznetsov, A. H. Lodyagin, Bair Vasil’evich Batotsyrenov, V. L. Reinuk, Andrej Georgievich Sinenchenko, Bogdan Sergeevich Litvincev, Alexandra Alexandrovna Kuznetsova, Nadezhda Anatol’evna Kirsanova
Introduction. The article considers the issues of identification of unknown patients admitted to toxicological medical hospitals on the example of a case from practice. The aim of the study was to develop an effective way to solve the main problem of the lack of information about the identity of a significant part of patients with a toxicological profile during their stay in the hospital until discharge. Material and methods. Based on the described practical case, a new highly effective method of identifying unknown patients with a toxicological profile, implemented using forensic DNA analysis, is proposed and tested. Results. As promising ways to improve interdepartmental cooperation in relation to the identification of unidentified living persons who have been admitted with acute poisoning, an algorithm for transmitting selected DNA samples to the territorial bodies of the Ministry of Internal Affairs on a system streaming basis is described. Limitations. Further verification of DNA samples according to the Federal Database of Genomic Information is carried out by the Ministry of Internal Affairs independently through the regional Forensic Centers of the Ministry of Internal Affairs of the Russian Federation, followed by informing the administration of the medical institution. Conclusion. The results obtained within the framework of this study demonstrate the high efficiency of establishing the identity of toxicological patients staying in medical hospitals as unknown persons, which represents a direct economic benefit for the healthcare system in the form of an increase in the proportion of patients paid for by territorial health insurance funds.
介绍。本文以一个实际病例为例,探讨了毒理学医院收治的不明身份病人的身份识别问题。该研究的目的是开发一种有效的方法来解决在住院至出院期间缺乏关于具有毒理学档案的相当一部分患者身份的信息的主要问题。材料和方法。基于所描述的实际案例,提出了一种新的高效方法,通过法医DNA分析来识别具有毒理学特征的未知患者,并进行了测试。结果。作为改善部门间合作的有希望的方法,在鉴定因急性中毒而入院的身份不明的活着的人方面,描述了一种将选定的DNA样本以系统流式传输的方式传输给内务部属地机构的算法。的局限性。根据联邦基因组信息数据库,内务部通过俄罗斯联邦内务部的区域法医中心独立地对DNA样本进行进一步核查,然后通知医疗机构的管理部门。结论。在本研究框架内获得的结果表明,将在医院住院的毒理学患者身份确定为未知人的效率很高,这代表了医疗保健系统的直接经济效益,其形式是增加了由领土健康保险基金支付的患者比例。
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引用次数: 0
Proposals for improving the methodic and regulatory framework of the Russian Federation in the field of chemical safety 关于改进俄罗斯联邦在化学品安全领域的方法和管理框架的建议
Pub Date : 2023-08-30 DOI: 10.47470/0869-7922-2023-31-4-214-225
Khalidya Khizbulaevna Khamidulina, Elena Vladimirovna Tarasova, Andrey Konstantinovich Nazarenko, D. N. Rabikova, A. S. Proskurina
Introduction. In accordance with Decree of the President of the Russian Federation of March 11, 2019 No. 97 “On the basis of the state policy of the Russian Federation in the field of chemical and biological safety” until 2025 and beyond” the priority areas include monitoring chemical and biological risks, improving regulatory framework and public administration. In terms of improving legal regulation and public administration, development and application of documents that provide mandatory requirements for chemical products in the Russian Federation are among the priorities. Material and methods. The regulatory legal acts of the Russian Federation, EEC and the EU (in particular, Decrees, Resolutions, Technical Regulations, Directives, Regulations, etc. in the field of safe management of substances of concern), as well as domestic and international databases, scientific articles and monographs containing information on the toxic properties of chemicals are used as materials. The methodology of the work consisted in a comparative analysis of approaches to the regulation of highly hazardous chemicals by international organizations, the Russian Federation, the European Union and its states, the USA, Canada. Results and discussions. The article presents the main provisions of the concept for the replacement of highly hazardous chemicals in products with safe analogues; scientifically substantiated national list of chemicals of concern, containing 1480 items, including 630 mutagens, 320 carcinogens, 271 reprotoxicants, 502 endocrine disruptors; criteria for classifying substances as candidates for prohibition and (or) restriction. The proposals for amending the methodological and regulatory framework of the Russian Federation in the field of chemical safety are formulated. Conclusion. In order to develop effective measures to minimize the risk of exposure to chemicals and safe management, including prohibition and (or) restriction, it is advisable: introduction of a national list of chemicals of concern into the methodological and regulatory framework of the Russian Federation and the Eurasian Economic Union; creation of state monitoring of highly hazardous chemicals in products at all stages of the life cycle from raw materials to production and consumption waste with the direct involvement of manufacturers; formation and maintenance of the register of emissions and discharges; coding of waste according to hazardous properties (carcinogenicity, mutagenicity, reprotoxicity, impact on the endocrine system) and its inclusion as a classification feature in the Federal Classification Catalog of Waste; search and evaluation of alternatives for highly hazardous chemicals.
介绍。根据俄罗斯联邦总统2019年3月11日第97号法令,“根据俄罗斯联邦在化学和生物安全领域的国家政策”,直到2025年及以后,优先领域包括监测化学和生物风险,改善监管框架和公共管理。在改进法律规章和公共行政方面,制定和适用规定俄罗斯联邦化学产品强制性要求的文件是优先事项之一。材料和方法。俄罗斯联邦、欧洲经济共同体和欧盟的法规(特别是有关物质安全管理领域的法令、决议、技术条例、指令、条例等)以及国内和国际数据库、载有化学品毒性信息的科学文章和专著被用作材料。这项工作的方法包括比较分析各国际组织、俄罗斯联邦、欧洲联盟及其各国、美国、加拿大对高度危险化学品的管制办法。结果和讨论。本文介绍了用安全类似物替代产品中高度危险化学品概念的主要规定;科学依据的《国家重点关注化学品名录》,共1480项,其中诱变剂630种,致癌物320种,生殖毒物271种,内分泌干扰物502种;禁止和(或)限制候选物质分类标准。拟定了关于修改俄罗斯联邦在化学品安全领域的方法和管理框架的建议。结论。为了制定有效措施,尽量减少接触化学品的风险和安全管理,包括禁止和(或)限制,建议:在俄罗斯联邦和欧亚经济联盟的方法和监管框架中引入一份国家关注化学品清单;在制造商的直接参与下,对从原材料到生产和消费废物的产品生命周期所有阶段的高度危险化学品进行国家监测;形成和维持排放和排放登记册;根据危险特性(致癌性、诱变性、生殖毒性、对内分泌系统的影响)对废物进行编码,并将其作为分类特征纳入《联邦废物分类目录》;寻找和评价高度危险化学品的替代品。
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引用次数: 0
A clinical case of acute methadone poisoning in an infant child 婴幼儿急性美沙酮中毒1例
Pub Date : 2023-08-30 DOI: 10.47470/0869-7922-2023-31-4-237-242
R.A. Narzikulov, A. Lodyagin, A. Sinenchenko, Chimit Bairovich Batotsyrenov, Bezhan Rustamovich Rustamov, Ivan Alexandrovich Lisitsa, N.D. Zapasnikov
Introduction. The article considers a case of a favorable outcome of severe acute oral methadone poisoning complicated by the development of acute respiratory failure and toxic hypoxic encephalopathy. Clinical observation. A clinical case of acute oral (through breast milk) methadone poisoning of severe degree in a child of 9 months and 6 days with the development of toxicohypoxic encephalopathy is presented. The narcotic substance entered the body once, after breastfeeding from mother to child. Acute poisoning in the child was manifested by respiratory insufficiency with impaired consciousness (did not respond to pain stimuli, short-term apnea was noted, saturation of arterial blood with oxygen (SpO2) was 62%). Intensive therapy included infusion, antidote, detoxification therapy, correction of acid-base state disorders, water-electrolyte balance, hypoxic disorders. Conclusion. Methadone-induced respiratory failure is characterized by dose dependence and the possibility of relief after administration of naloxone. In our clinical case, a specific antidote was used at the prehospital and hospital stages and an activator of metabolic cellular processes – riboxin in combination with B vitamins: thiamine chloride (vitamin B1) and pyridoxine hydrochloride (vitamin B6). In conclusion, it should be noted that the relevance of acute methadone poisoning in childhood remains high. Taking into account the mechanisms of the toxic effect of methadone, it is possible to formulate the directions of intensive therapy: maintenance of life support systems, rational antidote therapy, the fight against hypoxia and its consequences.
介绍。本文考虑了一个严重急性口服美沙酮中毒并发急性呼吸衰竭和中毒性缺氧脑病的有利结果的病例。临床观察。本文报道1例9个月零6天急性口服(经母乳)美沙酮严重中毒并发中毒性缺氧性脑病的病例。麻醉物质一旦进入人体,在母乳喂养后由母亲传给孩子。急性中毒患儿表现为呼吸功能不全,意识受损(对疼痛刺激无反应,出现短期呼吸暂停,动脉血氧饱和度(SpO2) 62%)。强化治疗包括输液、解毒剂、排毒、纠正酸碱状态紊乱、水电解质平衡、缺氧紊乱。结论。美沙酮引起的呼吸衰竭具有剂量依赖性和服用纳洛酮后可能缓解的特点。在我们的临床病例中,在院前和医院阶段使用了一种特殊的解毒剂和代谢细胞过程的激活剂-核糖素与B族维生素:硫胺素氯化(维生素B1)和盐酸吡哆醇(维生素B6)联合使用。总之,应该指出的是,儿童急性美沙酮中毒的相关性仍然很高。考虑到美沙酮毒性作用的机制,可以制定强化治疗的方向:维持生命支持系统,合理的解毒剂治疗,对抗缺氧及其后果。
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引用次数: 0
Evaluation of bioaccumulation and toxic effect of aluminum and molybdenum oxide nanoparticles used as an active component of bactericidal agents 作为杀菌剂活性成分的氧化铝和氧化钼纳米颗粒的生物蓄积和毒性效应评价
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-169-177
M. Stepankov
Introduction. Nanoparticles (NPs) of aluminum oxide (Al2O3) and molybdenum oxide (MoO3) have the potential to be used as an active component of bactericidal agents. At the same time, there is information in the scientific literature about the negative effects of these NPs on organism. Given that, it seems relevant to perform the study and comparative analysis of the toxicity of Al2O3 and MoO3 NPs. Materials and methods. We examined physical properties of Al2O3 NPs and MoO3 NPs. In an experiment on Wistar rats, peculiarities of bioaccumulation and toxic action at multiply inhalation exposure was researched. Results. The examined samples were a nanomaterial judging by such parameters as particle size, shape, surface area and total pore volume. Under exposure to Al2O3 NPs, aluminum concentrations were statistically significant increase in the lungs, brain, liver and blood relative to the control; under exposure to MoO3 NPs – molybdenum concentration in heart, lungs, brain, kidney and blood. Under exposure to MoO3 NPs, a wider range of negative effects changed relative to the control of biochemical parameters (increased activity of ALP, LDH, concentrations of total and direct bilirubin, urea, creatinine) was established than during exposure to Al2O3 NPs (increased activity of ALT, AST, ALP, LDH, concentrations direct bilirubin). Pathomorphological changes were identified in the lungs, brain, heart and liver under exposure to Al2O3 NPs; in lungs, brain and liver under exposure to MoO3 NPs in the lungs. However, tissue changes upon exposure to MoO3 NPs are more pronounced than those upon exposure to Al2O3 NPs. Limitations. The study involved only multiple inhalation exposure to Al2O3 NPs and MoO3 NPs in an experiment on Wistar rats. Conclusion. Differences in the toxicokinetics of Al2O3 and MoO3 NPs do not make it possible to single out among them those that are more dangerous for human health, and therefore additional studies are needed.
介绍。氧化铝(Al2O3)和氧化钼(MoO3)纳米颗粒(NPs)具有作为杀菌剂活性组分的潜力。与此同时,科学文献中也有关于这些NPs对生物体的负面影响的信息。因此,对Al2O3和MoO3 NPs的毒性进行研究和比较分析似乎是有意义的。材料和方法。研究了Al2O3 NPs和MoO3 NPs的物理性质。在Wistar大鼠实验中,研究了多次吸入暴露的生物蓄积特性和毒性作用。结果。从粒径、形状、比表面积、总孔隙体积等参数判断,所检测的样品为纳米材料。暴露于Al2O3 NPs下,肺、脑、肝和血液中的铝浓度均较对照组显著升高;心脏、肺、脑、肾和血液中的MoO3 NPs -钼浓度。与暴露于Al2O3 NPs (ALT、AST、ALP、LDH活性、直接胆红素、尿素、肌酐浓度升高)相比,暴露于MoO3 NPs下,相对于生化参数控制(ALP、LDH活性升高、总胆红素和直接胆红素浓度升高)的负面影响范围更广。暴露于Al2O3 NPs下,肺、脑、心脏和肝脏发生病理形态学改变;暴露于肺部的MoO3 NPs下,肺、脑和肝脏的变化。然而,暴露于MoO3 NPs后的组织变化比暴露于Al2O3 NPs时的组织变化更明显。的局限性。在Wistar大鼠实验中,本研究仅涉及多次吸入暴露于Al2O3 NPs和MoO3 NPs。结论。Al2O3和MoO3 NPs在毒性动力学上的差异使我们无法从中挑选出对人类健康更危险的NPs,因此需要进一步的研究。
{"title":"Evaluation of bioaccumulation and toxic effect of aluminum and molybdenum oxide nanoparticles used as an active component of bactericidal agents","authors":"M. Stepankov","doi":"10.47470/0869-7922-2023-31-3-169-177","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-3-169-177","url":null,"abstract":"Introduction. Nanoparticles (NPs) of aluminum oxide (Al2O3) and molybdenum oxide (MoO3) have the potential to be used as an active component of bactericidal agents. At the same time, there is information in the scientific literature about the negative effects of these NPs on organism. Given that, it seems relevant to perform the study and comparative analysis of the toxicity of Al2O3 and MoO3 NPs. \u0000Materials and methods. We examined physical properties of Al2O3 NPs and MoO3 NPs. In an experiment on Wistar rats, peculiarities of bioaccumulation and toxic action at multiply inhalation exposure was researched. \u0000Results. The examined samples were a nanomaterial judging by such parameters as particle size, shape, surface area and total pore volume. Under exposure to Al2O3 NPs, aluminum concentrations were statistically significant increase in the lungs, brain, liver and blood relative to the control; under exposure to MoO3 NPs – molybdenum concentration in heart, lungs, brain, kidney and blood. Under exposure to MoO3 NPs, a wider range of negative effects changed relative to the control of biochemical parameters (increased activity of ALP, LDH, concentrations of total and direct bilirubin, urea, creatinine) was established than during exposure to Al2O3 NPs (increased activity of ALT, AST, ALP, LDH, concentrations direct bilirubin). \u0000Pathomorphological changes were identified in the lungs, brain, heart and liver under exposure to \u0000Al2O3 NPs; in lungs, brain and liver under exposure to MoO3 NPs in the lungs. \u0000However, tissue changes upon exposure to MoO3 NPs are more pronounced than those upon exposure to Al2O3 NPs. \u0000Limitations. The study involved only multiple inhalation exposure to Al2O3 NPs and MoO3 NPs in an experiment on Wistar rats. \u0000Conclusion. Differences in the toxicokinetics of Al2O3 and MoO3 NPs do not make it possible to single out among them those that are more dangerous for human health, and therefore additional studies are needed.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"520 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77359557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ecological and toxicological assessment of hazard of contamination of water bodies by the γ-polyoxymethylene γ-聚甲醛污染水体危害的生态毒理学评价
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-185-191
A. A. Maslennikov, Svetlana Aleksandrovna Demidova, Oksana Ivanovna Ilchenko, V. A. Antonov
Introduction. In the process of production, storage and application of the representative of new components of solid rocket fuels – γ-polyoxymethylene, its ingress into the water of reservoirs is not excluded, which determines the mandatory assessment of the danger of its single contamination of this ecosystem. Material and methods. As an object of research, γ-polyoxymethylene (γ-POM, polyformaldehyde, acetal copolymer) was used – a mixture of dimethyl esters of polyoxymethylene glycols – a fine amorphous white powder, CAS registration number 66455-31-0. The empirical formula is CH3O(CH2O)nCH3 at n = 100–300. It is practically insoluble in water. Results. It was found that the ecotoxicant content in water at a concentration of 50.0 mg/l led to a change in its transparency. The indicated concentration of γ-POM was determined as a threshold for organoleptic harmfulness. In the course of studying the effect of the toxicant on the general sanitary regime of reservoirs, in the absence of changes in the indicators of biochemical oxygen consumption, its negative impact on nitrification processes and saprophytic microflora was revealed. The threshold concentration of the substance according to the general sanitary indicator of harmfulness is 3.5 mg/l. In experiments on laboratory animals, it was noted that a single intragastric administration of the tested xenobiotic in the form of a suspension in a 2.5% solution of aqueous starch caused a significant decrease in heart rate and a change in a number of hematological parameters. The threshold of a single general toxic effect of γ-POM is 90.0 mg/kg. Limitations of the study. The revealed features of the behavior of γ-polyoxymethylene must be taken into account when it once pollutes the water of reservoirs (in case of an emergency). However, the data obtained are insufficient to substantiate the hygienic standard of the connection in the water of water bodies. Conclusion. The results of the performed experiments indicate that a single ingress of γ-polyoxymethylene into the water represents an ecological and toxicological hazard registered for all three basic signs of harmfulness, which is taken into account when justifying its maximum permissible concentration in the water of reservoirs.
介绍。固体火箭燃料新组分代表γ-聚氧亚甲基在生产、储存和应用过程中,不排除其进入水库水体,这决定了其对该生态系统的单一污染危险性的强制性评价。材料和方法。研究对象为γ-聚甲醛(γ-POM,聚甲醛,缩醛共聚物)-聚甲醛二甲酯的混合物-精细无定形白色粉末,CAS注册号66455-31-0。实验式为n = 100-300时的ch30 (CH2O)nCH3。它几乎不溶于水。结果。研究发现,在50.0 mg/l的浓度下,水中的生态毒物含量会导致其透明度的变化。测定γ-POM指示浓度作为感官损害阈值。在研究该毒物对水库一般卫生状况的影响过程中,在生化耗氧量指标未发生变化的情况下,揭示了其对硝化过程和腐生菌群的负面影响。根据一般卫生危害性指标,该物质的阈值浓度为3.5 mg/l。在实验动物的实验中,注意到单次灌胃以2.5%淀粉悬浮液的形式给药,会导致心率显著降低和一些血液学参数的变化。γ-POM单次一般毒性作用的阈值为90.0 mg/kg。本研究的局限性。γ-聚氧亚甲基一旦污染水库水(在紧急情况下),必须考虑其暴露的行为特征。然而,所获得的数据不足以证实该接头在水体中的卫生标准。结论。所进行的实验结果表明,γ-聚氧亚甲基单次进入水中代表了一种生态和毒理学危害,所有三个基本有害迹象都登记在案,这是在证明其在水库水中的最大允许浓度时考虑到的。
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引用次数: 0
The effect of zaleplon on metabolic changes in neurotransmitters and toxic effects in Danio fish 扎来普隆对达尼欧鱼神经递质代谢变化及毒性作用的影响
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-192-203
A. A. Volkova, Roman A. Kalekin, Alevtina Mikhailovna Orlova, A. Pavlova, Olga Genrikhovna Astashkina, Andrey L. Pavlov
Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce. The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics. Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid. Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained. Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.
介绍。z -drug是一类“非苯二氮卓类”药物,其主要作用方式是通过暴露于GABA受体来调节人类的睡眠行为。有报告指出,过量使用和滥用扎来普隆会产生毒性作用。然而,关于z -药物对神经递质水平的影响的信息很少。本研究的目的是利用靶向代谢组学方法研究扎来普隆暴露对达尼欧鱼幼鱼神经递质水平的影响。材料和方法。采用浓度分别为0.1、1.0、10、100和1000 μg/l的扎来普隆对达里奥鱼仔鱼进行4 h的暴露试验。将干预组与对照组进行比较。每组20尾达尼欧鱼幼鱼。采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定神经递质及其代谢物。结果。对22种与神经传递相关的代谢物进行了量化。代谢产物色氨酸、血清素、5-羟基吲哚乙酸、乙酰血清素、肾上腺素和胆碱显著增加。显著减少的代谢物有5-羟色氨酸、5-甲氧基色胺、多巴胺、去甲肾上腺素、去甲肾上腺素、犬尿氨酸、3-羟肌尿氨酸、邻氨基苯甲酸和γ -氨基丁酸。限制。在研究达尼欧鱼的神经递质代谢变化和毒性作用时,分析了一组20只幼虫的结果,这是一个足够的样本来说明所获得的结果。结论。暴露于扎来普隆引起与大多数主要神经递质系统相关的神经递质浓度的代谢变化。
{"title":"The effect of zaleplon on metabolic changes in neurotransmitters and toxic effects in Danio fish","authors":"A. A. Volkova, Roman A. Kalekin, Alevtina Mikhailovna Orlova, A. Pavlova, Olga Genrikhovna Astashkina, Andrey L. Pavlov","doi":"10.47470/0869-7922-2023-31-3-192-203","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-3-192-203","url":null,"abstract":"Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce. \u0000The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics. \u0000Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). \u0000Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid. \u0000Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained. \u0000Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73237645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Experimental study of the effectiveness of ademethionine and inosine glycyl-cysteinyl-glutamate disodium in the treatment of dichloroethane-induced toxic hepatitis 腺苷蛋氨酸和肌苷甘酰半胱氨酸谷氨酸二钠治疗二氯乙烷所致中毒性肝炎疗效的实验研究
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-163-168
Yu.V. Orlov, S. V. Gaiduk, V. G. Kuzmich
Introduction. Currently, in the search for drugs for the toxic liver damage treatment, considerable attention is paid to glutathione preparations and its metabolic precursors. There are separate reports in the literature on the hepatoprotective and antifibrotic effects of glutathione disulfide in viral liver lesions, which gives grounds for their additional study when exposed to hepatotropic substances. Material and methods. Performing a comparative assessment of the hepatoprotective effect of inosine glycyl-cysteinyl-glutamate disodium and ademetionine on the model of dichloroethane-induced toxic hepatitis in rats was carried out with the formation of the following experimental groups of animals: no treatment; with the introduction of physiological saline; with the introduction of inosine glycyl-cysteinyl-glutamate disodium; with the introduction of ademetionine, as well as a group of intact animals. The study drugs were administered intraperitoneally for 10 days. In the course of the study, biochemical indicators of cytolytic and cholestatic syndromes of liver damage were determined, the activity of its detoxification system and plastic function were assessed. Results. In groups that did not receive treatment, but received physiological saline, the lethality of experimental animals by the 20th day of observation was 40%, in the group treated with ademetionine – 10%. In the group treated with inosine glycyl-cysteinyl-glutamate disodium, no death of animals was observed. The use of inosine glycyl-cysteinyl-glutamate disodium led to a more significant decrease in the indicators of cytolytic and cholestatic syndromes, as well as normalization of the functional activity of the liver (restoration of the content of glutathione in the liver tissue) and its plastic function (restoration of the level of total blood serum protein and glycogen content in the liver parenchyma) to a greater extent than with ademetionine. limitation. The experimental study was carried out on outbred male rats weighing 180–220 g, kept under standard vivarium conditions in one cage, no more than 6 individuals, divided into groups by randomization with the exclusion of weakened and sick animals from the study. Conclusion. The study provided an experimental justification for further study of the hepatoprotective effect of inosine glycylcysteinylglutamate disodium in toxic liver damage.
介绍。目前,在寻找治疗中毒性肝损伤的药物时,谷胱甘肽制剂及其代谢前体受到了相当大的关注。文献中有关于谷胱甘肽二硫醚对病毒性肝病变的肝保护和抗纤维化作用的单独报道,这为暴露于促肝物质时进行进一步研究提供了依据。材料和方法。比较评价肌苷-甘氨酸-半胱氨酸-谷氨酸二钠和腺苷对二氯乙烷所致中毒性肝炎模型大鼠的肝保护作用,实验动物分为以下实验组:不给药;配合生理盐水的引入;引入肌苷甘氨酸半胱氨酸谷氨酸二钠;随着腺苷的引入,以及一组完整的动物。研究药物经腹腔注射10天。在研究过程中,测定肝损伤的细胞溶解综合征和胆汁淤积综合征的生化指标,评估其解毒系统的活性和可塑性功能。结果。未给予生理盐水治疗组,观察第20天实验动物死亡率为40%,给予腺苷- 10%组。肌苷-甘氨酸-半胱氨酸-谷氨酸二钠组未见动物死亡。与使用腺苷甘氨酸半胱氨酸谷氨酸二钠相比,使用肌苷甘氨酸半胱氨酸谷氨酸二钠能更显著地降低细胞溶解综合征和胆汁淤积综合征的指标,并在更大程度上恢复肝脏的功能活性(恢复肝组织中谷胱甘肽的含量)及其可塑性功能(恢复肝实质中血清总蛋白和糖原含量的水平)。限制。实验研究选用体重180 ~ 220 g的近交系雄性大鼠,在标准饲养条件下,单笼饲养,不超过6只,随机分组,体弱多病排除。结论。本研究为进一步研究肌苷甘氨酸半胱氨酸谷氨酸二钠对中毒性肝损伤的保护作用提供了实验依据。
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引用次数: 0
Toxicological and hygienic assessment of phthalate content in bottled drinking water 瓶装饮用水中邻苯二甲酸盐含量的毒理学和卫生评价
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-178-184
V. Shilov, O. Khurtsilava, O. Markova, D. S. Isaev, Alena Yuryevna Mikheeva
Introduction. One of the most common materials containing phthalate impurities is packaging made of polymer materials (bottles). Bottles made of the following material are used for packaged (bottled) drinking water - polyethylene terephthalate (PET). The toxicological properties of phthalates, the increase in consumption of bottled water and uncertainty about the effect of storage conditions on the migration of phthalates into water initiates research on the toxicological and hygienic assessment of the content of phthalates in polymer packaging for bottled drinking water.The purpose of study was the toxicological and hygienic assessment of the content of di(2-ethylhexyl)-phthalate (DEHP); di-n-butyl phthalate (DnBP); diisobutyl phthalate (DiBP) in drinking water packed in polymer material. Materials and methods. The objects of the study were bottles samples made in the Russian Federation. The obtained extracts (containers and model medium) were analyzed by gas chromatography with mass spectrometric detection. The values of daily consumption of phthalates with bottled water for adults and children were calculated, safety coefficients were determined taking into account the maximum concentrations obtained in the experiment. Results. As a result of polymer materials studies, it was found that bottle samples contain residual amounts of phthalates – DEHP 1.7–4.2 mg/kg; DnBP <2.4–31.3 mg/kg; DiBP 2.2–10.2 2 mg/kg. Migration of phthalates into aqueous model media was noted from all the samples studied.In the samples of model solutions in contact with PET material, on the 30th day at a temperature of 20 °C, the presence of 2 phthalates: DEHP 8.6–71.0 µ/l and DiBF <2.6 to 19.2 µ/l. Comparison of phthalate concentrations in model media with the values of permissible daily consumption showed that bottled water provides a limited contribution to the total daily exposure of phthalates. Conclusion. The study results showed that the packaging made of PET is a source of chemical contamination of bottled water, which is based on the processes of migration of organic components from polymer materials. At the same time, special attention should be paid to the ability to migrate di(2-ethylhexyl)-phthalate, which can lead to excess of hygienic standards for drinking water.
介绍。最常见的含有邻苯二甲酸盐杂质的材料之一是由聚合物材料(瓶子)制成的包装。以下材料制成的瓶子用于包装(瓶装)饮用水-聚对苯二甲酸乙二醇酯(PET)。邻苯二甲酸盐的毒理学特性、瓶装水消费量的增加以及储存条件对邻苯二甲酸盐向水中迁移的影响的不确定性,引发了对瓶装饮用水聚合物包装中邻苯二甲酸盐含量的毒理学和卫生评估的研究。研究目的是对邻苯二甲酸二(2-乙基己基)酯(DEHP)含量进行毒理学和卫生学评价;邻苯二甲酸二丁酯(DnBP);高分子材料包装饮用水中的邻苯二甲酸二异丁酯(DiBP)。材料和方法。研究对象是俄罗斯联邦生产的瓶子样品。所得提取物(容器和模型介质)采用气相色谱-质谱检测进行分析。计算了成人和儿童每天饮用瓶装水时邻苯二甲酸盐的摄取量,并根据实验中得到的最大浓度确定了安全系数。结果。高分子材料研究结果发现,瓶样中邻苯二甲酸酯残留量- DEHP 1.7-4.2 mg/kg;DnBP <2.4 ~ 31.3 mg/kg;DiBP 2.2-10.2 mg/kg。从所有研究的样品中都注意到邻苯二甲酸盐向水模型介质的迁移。在与PET材料接触的模型溶液样品中,在温度为20°C的条件下,第30天,存在2种邻苯二甲酸盐:DEHP 8.6-71.0µ/l和DiBF <2.6 - 19.2µ/l。将模型介质中的邻苯二甲酸盐浓度与允许的每日消费量进行比较,结果表明瓶装水对邻苯二甲酸盐每日暴露总量的贡献有限。结论。研究结果表明,PET包装是瓶装水化学污染的一个来源,这是基于聚合物材料中有机成分迁移的过程。同时,应特别注意邻苯二甲酸二(2-乙基己基)-邻苯二甲酸酯的迁移能力,这可能导致饮用水卫生标准超标。
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引用次数: 0
The role of the toxicological service in the drug situation monitoring system: problems and ways of improvement 毒理学服务在药品形势监测系统中的作用:问题及改进途径
Pub Date : 2023-06-30 DOI: 10.47470/0869-7922-2023-31-3-142-149
I. A. Shikalova, A. H. Lodyagin, Irina Mikhaylovna Barsukova, A. M. Panov, A. Sinenchenko
Introduction. The relevance of the research topic is determined by the high significance of measures aimed at combating and preventing the illegal distribution and non-medical use of narcotic substances. The aim of the study. Show the importance of toxicological monitoring in the drug situation assessment system, identify existing problems and ways to improve it. Material and methods. analiysis of the regulatory legal framework regulating the provision of toxicological care to the population and the drug situation monitoring system, analysis of the toxicological monitoring system in St. Petersburg. Statistical and analytical methods along with content analysis were used. results. The article presents the contribution of the toxicological service to the drug situation monitoring system in the Russian Federation and identifies a number of organizational problems related to the diagnosis and accounting of acute poisoning with narcotic substances. Proposed the ways of improving toxicological monitoring, which will improve the quality and efficiency of information capturing – organization and equipping with modern diagnostic equipment of toxicological centers (departments) in all subjects of Russian Federation; ensuring the availability of toxicological counseling through the development of a system of regional information and advisory toxicological centers; coordination of poisoning by new narcotic substances and their precursors with the unified coding system ICD-10; development of a control system for filling out registration form No. 58-1/у “Emergency notification of acute poisoning of chemical etiology”; supplement the group “drug poisoning” of Federal Forms of Statistical Observation No. 57 and No. 14 with nosological units - cannabis poisoning (T40.7), LSD poisoning (T40.8), poisoning with other and unspecified psychodisleptics (T40.9); organization of a stationary post of the Ministry of Internal Affairs on the basis of toxicological centers, which will allow more effective measures to prevent spread and use of drugs. Limitations. Regulatory and legal framework in the field of official statistical accounting of acute poisoning with drugs and psychosleptics. Conclusion. The data obtained in the course of the study will allow improving the system of monitoring the drug situation in the country, conducting a comparative interregional analysis, promptly and objectively evaluating the quality of work on the prevention of illegal distribution and non-medical use of narcotic substances and drug trafficking control.
介绍。旨在打击和防止非法分销和非医疗使用麻醉药品的措施具有重要意义,这就决定了本研究课题的相关性。研究的目的。说明毒理学监测在药品形势评价体系中的重要性,指出存在的问题及改进途径。材料和方法。分析了向人口提供毒理学护理的监管法律框架和药物情况监测系统,分析了圣彼得堡的毒理学监测系统。采用统计分析和内容分析相结合的方法。结果。本文介绍了毒理学服务对俄罗斯联邦药物情况监测系统的贡献,并确定了与诊断和计算麻醉药品急性中毒有关的一些组织问题。提出了改进毒理学监测的方法,这将提高信息采集的质量和效率-在俄罗斯联邦所有学科的毒理学中心(部门)组织和配备现代诊断设备;通过建立区域信息和毒理学咨询中心系统,确保提供毒理学咨询;新麻醉品及其前体中毒与统一编码系统ICD-10的协调;制定一套控制系统,以填写第58-1号登记表"化学急性中毒紧急通报";在《联邦统计观察表》第57号和第14号的“药物中毒”一组中增加分科单位——大麻中毒(T40.7)、LSD中毒(T40.8)、其他和未指明的抗精神病药物中毒(T40.9);在毒理学中心的基础上,在内务部设立一个固定职位,以便采取更有效的措施防止毒品的传播和使用。的局限性。药物和精神睡眠药物急性中毒官方统计核算领域的监管和法律框架。结论。在研究过程中获得的数据将有助于改进监测该国毒品状况的系统,进行区域间比较分析,及时和客观地评价关于防止非法分发和非医疗使用麻醉药品以及管制毒品贩运的工作质量。
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引用次数: 0
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Toxicological Review
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