Toxicological Review最新文献

{"title":"Contractile activity of isolated rat small intestine after chronic inhalation exposure to dioctyl terephthalate","authors":"Dmitrij Vladimirovich Bobkov, S. Petunov, D. S. Laptev, Olga Valeryevna Nechaykina","doi":"10.47470/0869-7922-2022-30-3-191-196","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-191-196","url":null,"abstract":"Introduction. Dioctyl terephthalate (DOTP) is an ester of 2-ethylhexanol and terephthalic acid. It is a new generation plasticizer that is used as a more environmentally friendly and safer substitute for dioctyl phthalate (DOP) and other phthalates. Despite the established low level of toxic effects on the human body, the expansion of industrial production of DOTP requires an in-depth assessment of its safety. Material and methods. The effect of DOTP on the motility of isolated segments of the small intestine of rats was assessed under chronic inhalation exposure for 120 days at concentrations of 3.4 and 18.6 mg/m3. Results. The course exposure to dioctyl terephthalate, regardless of the dose, reduces the spontaneous contractile activity and adrenoreactivity of the smooth muscle cells of the rat small intestine, and also increases their sensitivity to cholinergic effects. Limitations. The study demonstrates a change in the spontaneous contractile activity isolated segments rat small intestine under the influence of the main mediators autonomic nervous system. Additional research is required for a detailed assessment possible mechanisms for the development of the identified changes. Conclusion. As a result of the study, it was found that chronic inhalation of dioctyl terephthalate at concentrations of 3.4 and 18.6 mg/m3 equally cause a decrease in the tone and amplitude of contractions in isolated segments of the rat small intestine. Chronic exposure to DOTP leads to a change in the reactivity of small intestine myocytes to mediators of the autonomic nervous system. The results obtained indicate that DOTP, when administered by inhalation, is enterotropic.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78143506","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}

{"title":"Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical-Biological Agency — history, present, perspectives.","authors":"A. Radilov, V. R. Rembovsky","doi":"10.47470/0869-7922-2022-30-3-134-138","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-134-138","url":null,"abstract":"","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76383398","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}

{"title":"New biomarkers for 1,1-dimethylhydrazine","authors":"A. Ukolov, D. S. Laptev, Evgeny Yurievich Karmanov, G. Karakashev, D. Krivorotov, A. Bogachenkov, Olga Valeryevna Nechaikina, Dmitry Vladimirovich Bobkov, S. Petunov","doi":"10.47470/0869-7922-2022-30-3-182-190","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-182-190","url":null,"abstract":"Introduction. Despite the large-scale use of asymmetric dimethylhydrazine (UDMH) in the domestic rocket and space industry, its biomarkers of exposure in blood plasma and urine, as well as biomarkers of cardiotoxic effects, have not yet been described. Material and methods. The study of blood and urine samples of rats after a single injection of 10 mg/kg UDMH (1/16 LD50) was carried out by HPLC-MS. The determination of the non-metabolized form of UDMH was also carried out using the method of gas chromatography with mass-selective detection with preliminary derivatization with 4-pyridinecarboxyaldehyde. The cardiotoxic effect of UDMH was assessed on a model of an isolated rat heart with subchronic intragastric administration for 28 days at doses of 0,02; 0,2; 2,0 mg/kg. Results. It has been established that the main metabolites of UDMH are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). The possibility of determining the non-metabolized form of UDMH in blood and urine by HPLC-MS was shown, concentrations reach 10-60 ng/ml of blood plasma and 200-2000 ng/ml. The use of UDMH leads to an increase in the mass coefficient of the heart at a dose of 2,0 mg/kg. In ex vivo experiments on the rat heart, the cardiotoxic effect of UDMH was shown at subchronic use at a dose of 0,2 mg/kg and above, expressed in significant dilatation of the coronary bloodstream and left ventricle, the development of pronounced negative inotropic and chronotropic effects, and a decrease in the maximum rate of contraction and relaxation of the left ventricle. ventricle, reflecting the inhibition of myocardial energy metabolism. Limitations of the study. In the work, biomarkers were detected after a single intragastric injection of NDMG, the toxicokinetic characteristics of biomarkers and their retrospectivity were not evaluated. Conclusion. The main metabolites of UDMH with intravenous administration of 1/16 DL50 are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). With subchronic administration, UDMH has cardiotoxicity at a dose of 0,02 mg/kg and above.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87542247","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}

{"title":"Experimental comparing of lipophilicity of opioid antagonists","authors":"D. Krivorotov, Dmitrij Mikhajlovich Kochura, S. Dulov, Andrej Stanislavovich Radilov","doi":"10.47470/0869-7922-2022-30-3-149-157","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-149-157","url":null,"abstract":"Introduction. The high lipophilicity of synthetic opioids determines their abnormally high toxicity in comparison with natural opiates. The need to develop medical treatment of poisoning with such substances validates the task to study experimentally the logP partition coefficients of narcotic analgesics and their antagonists in standardized conditions close to the conditions of a living organism. Material and methods. The lipophilicity of pharmacological agents was determined in accordance with the principles of GOST 32474-2013. “Methods of testing chemical products that pose a threat to the environment. The determination of the n-octanol/water partition coefficient by high-performance liquid chromatography”, using the selected calibration dependence of the lipophilicity values on the logarithm of the retention factor of the substances studied. Results. The HPLC method has been proposed to determine the logP value of opioid antagonists using selected reference pharmacological agents. The method has revealed a linear dependence of the logP of CNS-active pharmacological agents on the logarithm of their retention factor in the chromatographic column, which allowed to determine the logP value of a number of opioid receptor antagonists and a model representative of synthetic opioids in one experiment. Limitations. The calibration dependence of the lipophilicity value on the logarithm of the retention factor of the studied substances has been obtained using reference logP values of a limited number of reference substances. Conclusion. When conducting pharmacological studies, using the HPLC method for the definition of logP provides high reproducibility of measurement conditions close to the conditions of a living organism and allows to compare the results obtained. Thus, the correlation of the logP values, found by the HPLC method, has showed a ten times lower lipophilicity of naloxone relative to fentanyl. The largest value of logP, among the studied opioid receptor antagonists used in clinical practice, was found for nalmefene.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80496910","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}

{"title":"Experimental substantiation of the tentatively safe level of diethyl disulfide in the air of the working area and the atmospheric air of populated areas","authors":"Semen Alexandrovich Kucherskoy, L. A. Alikbaeva, Evgenii Yrievich Karmanov, Irina Borisovna Ermakova, Diana Gaevna Oskina, Andrej Stanislavovich Radilov","doi":"10.47470/0869-7922-2022-30-3-177-181","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-177-181","url":null,"abstract":"Introduction. Diethyl disulfide belongs to the group of dialkyl disulfides, is a part of disulfide oil and a mixture of dialkyl disulfides. As a result of industrial purification of hydrocarbon raw materials from mercaptans, tens of thousands of tons of dialkyldisulfides and their mixtures are accumulated annually, the toxicity and danger of which have not been fully studied. No hygiene standards have been developed for diethyl disulfide. Materials and methods. Studies of the effects of diethyl disulfide were carried out in non-linear animals (rats and mice). The toxic properties of diethyl disulfide were studied under the conditions of single and repeated exposure to the intragastric, intraperitoneal, inhalation and cutaneous routes of entry into the body. Results. Based on the studies carried out, the toxicometric parameters of diethyl disulfide were established. Average lethal dose with intragastric administration LD50 = 1575 mg/kg, average lethal concentration CL50 = 18700 mg/m3, coefficient of possible inhalation poisoning CPIP = 1.3, limit of acute inhalation action (Limac) is set at 120 mg/m3, acute zone Zac = 156, cumulation coefficient was 3.2. Diethyl disulfide does not have a skin-resorptive toxic effect, but it has a moderately pronounced irritating effect on the mucous membrane of the eyes. Limitations of the study. The results of the diethyl disulfide exposure assessment are given for two animal species and four main routes of entry. Conclusion. The data obtained indicate that diethyl disulfide is a moderately hazardous substance with a single intragastric, inhalation and cutaneous route of entry into the body. The cumulative properties of diethyl disulfide are moderately expressed. Based on the analysis of literature data, the results of experimental studies and mathematical forecasting, a value of 4.0 mg/m3 is recommended as an approximate safe level of exposure in the air of the working area, in the atmospheric air of urban and rural settlements - 0.04 mg/m3.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89894345","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}

{"title":"The role of cytochromes CYP1A and CYP3A in the genotoxic effect of benzo(a)pyrene","authors":"D. A. Malygina, Nadezhda Yurievna Rogovskaya, P. Beltyukov, V. Babakov","doi":"10.47470/0869-7922-2022-30-3-158-166","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-158-166","url":null,"abstract":"Introduction. Benzo(a)pyrene metabolites are genotoxic compounds, the accumulation of which contributes to carcinogenesis. The main mechanism of metabolite formation is the benzo(a)pyrene oxidation by cytochromes P450 (CYP). Inhibitors of the main cytochromes can reduce the rate of metabolite formation and, as a result, to decrease the genotoxic effects of benzo(a)pyrene metabolites. In contrast, inducers of cytochromes contribute to the enhancement of genotoxicity. Objective. The aim of the work was to develop a cell model based on the HepaRG cells to study the role of cytochromes activity in the genotoxic effect of benzo (a) pyrene. Material and methods. To assess the effect of inhibitors of cytochromes CYP3A and CYP1A on the genotoxic effect of benzo(a)pyrene in HepaRG cells, the content of active forms of proteins of the DNA damage detection and repair system, phosphorylated forms of signaling cascade proteins was determined by immunoassay using Luminex xMAP technology. The cytotoxicity of benzo(a)pyrene was assessed by real-time cell analysis on xCelligence analyzer. Results. Inhibitors of CYP3A and CYP1A cytochromes, ketoconazole and α-naphthoflavone demonstrate the ability to diminish the toxic effects of benz (a) pyrene, reduce the activation of the DNA repair system, and have a multidirectional effect on the different tyrosine kinases phosphorylation in signaling pathways. Conclusion. HepaRG human hepatoma cells are a suitable cell model both to assess the contribution of cytochromes to the metabolism of xenobiotics and to study of the cell protection from the genotoxic effect of benzo (a) pyrene by cytochrome inhibitors. Limitations. The study was performed on a cell culture. To extrapolate the data to the organism, it is necessary to take into account the data of toxicodynamics and toxicokinetics.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75650566","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}

{"title":"Study of the toxicity of combustion products of polymer materials using chromatomass spectrometry","authors":"M. F. Shishonok, Evgenii Yrievich Karmanov, A. Ukolov, A. Zemlyanoi, Nataliya Viktorovna Yerunova, A. Nikolaev, V. K. Borodavko, S. Dulov, A. Radilov","doi":"10.47470/0869-7922-2022-30-3-167-176","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-3-167-176","url":null,"abstract":"Introduction. Carrying out studies of the toxicity of combustion products (HCL50) of polymer materials: epoxy glue grade EK-5T and compound ELPLAST-180 ID according to GOST with the additional use of gas chromatography with mass selective detection. Objective. Experimental study of the toxicity of combustion products (HCL50) of polymer materials in various modes of thermal oxidative degradation: epoxy glue grade EK-5T and compound ELPLAST-180 ID, as well as a survey mass spectrometric analysis of products of thermal oxidative degradation. Material and methods. The studies were carried out in accordance with GOST 12.1.044-89. Equipment: “Toxicity” unit, “Infracar M2.01” gas analyzer, Focus GC chromato-mass-spectrometric instrumental complex with DSQ II mass spectrometer (Thermo Scientific, USA), Nova Medical Stat Profile automatic analyzer of blood gases, electrolytes and oximetry Model CCX (USA). Blood sampling was carried out in capillaries “Stat Profile Critical Care Express Capillary Tube 230 µL with Na Heparin” LOT 107669, CO2 chamber. Results. In the course of studying the products of outgassing of polymer materials using an exposure chamber and a gas chromatomass spectrometer, a significant increase in toxicity (4.8 times) of a mixture of chemicals released from epoxy glue EK-5T during the transition from thermal-oxidative decomposition (smoldering) to flame combustion was established. The toxicity index of the combustion products of the ELPLAST-180 ID compound under the same conditions increases by 1.8 times. A linear dependence of the percentage of lethality of laboratory animals on the integral indicator of the toxicity of combustion products has been established. Limitations. Studies of the toxicity of combustion products were carried out on non-metallic materials: epoxy glue EK-5T, compound ELPLAST-180 ID. These materials are planned to be used in hermetically sealed objects of the Navy. Conclusion. The expediency of using gas chromatography-mass spectrometry for assessing the combined effect of combustion products is shown.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85180453","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}

{"title":"Pesticide active ingredients regulation in the European Union","authors":"","doi":"10.47470/0869-7922-2022-30-2-130","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-2-130","url":null,"abstract":"","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82190879","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}

{"title":"The impact of the novel coronavirus SARS-CoV-2 pandemic and quarantine responses on the toxic-epidemiological situation in Azerbaijan","authors":"Ismail Namik Afandiyev","doi":"10.47470/0869-7922-2022-30-2-79-84","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-2-79-84","url":null,"abstract":"Introduction. The global pandemic of the new coronavirus SARS-CoV-2 has not only been a serious stress test for healthcare systems in many countries around the world, but has also had a significant impact on the structure and number of acute chemical poisoning. The aim of this study was to study the impact of the COVID-19 pandemic and related quarantine measures on the toxic-epidemiological situation in Azerbaijan. Materials and methods. We conducted a comparative analysis of the database of the Clinical Medicine Center in Baku during the nine months of the pandemic period (March 20 - December 21, 2020) with the data of the same period in 2019 and the previous decade (2009-2018). Results. The alarming dynamics of a significant increase in the number of alcohol surrogates and primarily methyl alcohol poisoning, was revealed. If in the 10-year period of 2009-2018, the intoxication of alcohol surrogates was only 0.09% of the total poisoning cases, then during the study period of 2020 the share of such intoxications increased to 3.4%. The mortality rate in alcohol surrogate intoxication group in 2019 was 5.6% versus 50.0% in March-December 2020. All fatal cases in alcohol surrogate intoxication cohort were related to methyl alcohol poisoning, thus, the mortality rate of this pathology was 61.5%. Conclusion. The COVID-19 pandemic and related quarantine measures had a notable impact on the toxic-epidemiological situation in Azerbaijan and led to a significant increase in alcohol and methanol poisoning and fatality. Limitations. The study was conducted on the basis of the only specialized medical institution in Azerbaijan engaged for the treatment of chemical poisoning, therefore the collected database can be considered representative and relevant to the country’s overall toxic-epidemiological situation.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77885510","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}

{"title":"International approaches to reducing the risk of highly hazardous chemicals exposure on human health and to the selection criteria for substitution by safer analogues (literature review)","authors":"A. S. Proskurina, Khalidya Khizbulaevna Khamidulina, E. Tarasova","doi":"10.47470/0869-7922-2022-30-2-68-78","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-2-68-78","url":null,"abstract":"Introduction. Replacing hazardous substances with less hazardous ones is a basic principle of any good chemical risk management. At the first stage of scientific research on the development of a national concept for the replacement of highly hazardous chemicals in the composition of products (food, synthetic detergents and household chemicals, pesticides, paints and varnishes, basic chemicals) with safer analogues, the purpose of the research was: •to study international and domestic approaches to the organization of monitoring and regulation of substances highly hazardous to human health and the environment; •analysis, selection and scientific substantiation of criteria for selecting chemicals for their replacement with safer analogues. Materials and methods. materials, used for the analysis were the literature sources from the bibliographic databases Web of Science, MedLine, EMBASE, Global Health, PubMed, Scopus, RSCI. The guidelines and recommendations of the OECD, WHO, ILO, FAO, UNEP on the organization and implementation of monitoring of highly hazardous chemicals in environmental objects have been studied and analyzed. A number of international agreements are considered, which are based on criteria for prohibiting or restricting the use of substances on the market that cause an unacceptable risk. Results. An analysis of international approaches to the sound management of chemicals has shown that the identification of causal relationships between health and/or environmental conditions and exposure to a chemical factor is a trigger for the concept of substitution. In this regard, the tools and databases of socio-hygienic monitoring carried out by Rospotrebnadzor can serve as the basis for identifying highly hazardous substances that require management decisions to be made to ban, restrict circulation and replace them with safe analogues. The study of foreign and domestic materials on the selection of priority criteria for identifying substances of greatest concern for the purpose of risk assessment and further regulation showed that the following indicators are the main ones: •biological activity (carcinogens, mutagens, GHS class 1A and 1B reprotoxicants, endocrine disruptors), •stability in the environment, •bioaccumulative potential (bioconcentration factor BCF >2000, partition coefficient n-octanol/water Log Kow ≥ 4), •the possibility of cross-media transfer (air, water flows), •toxicity to representatives of aquatic biota (acute and chronic toxicity of hazard class 1 in accordance with GHS), •production volumes (volumes of emissions and discharges), •number of contacts.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91440437","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}