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编号 4 (2023)

封面

Original articles

Proposals for improving the methodic and regulatory framework of the Russian Federation in the field of chemical safety

Khamidulina K., Tarasova E., Nazarenko A., Rabikova D., Proskurina A.

摘要

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.

Author contribution:
Khamidulina Kh.Kh. — the concept and design of the study, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Tarasova E.V., Nazarenko A.K., Rabikova D.N., Proskurina A.S. — collection and processing of materials, writing the text, editing.

Conflict of interest. The authors declare no conflicts of interest.

Acknowledgment. The state program «Ensuring the chemical and biological safety of the Russian Federation» funded the study.

Received: July 07, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):214-225
pages 214-225 views

Comparative analysis of the use of various criteria for assessing individual risk at the Navy facilities

Kicha E., Kicha M.

摘要

Introduction. The objectives of the study are to develop new risk assessment criteria and analyze their advantages, compare the results obtained with different approaches to the application of the existing methodology for calculating individual risks (using the example of one of the studied hypothetical objects).

Results. New (additional) criteria for assessing individual risk with grouping of harmful substances, justified for use in calculating the individual risk of receiving a toxodose leading to mild injury (decreased performance).

Limitations. The results obtained can be used in the development of methods for assessing the chemical safety of specific facilities and performing standardization work.

Conclusion. The use of new approaches to risk calculation should provide an opportunity to more accurately assess the level of exposure for a person, predict the likelihood of adverse effects of varying severity and, accordingly, propose mechanisms to reduce exposure levels and take measures to minimize the negative impact.

Compliance with ethical standards. The study does not require the submission of the conclusion of the Biomedical ethics committee or other documents.

Author contribution: All co-authors made an equal contribution to the research and preparation of the article for publication.

Conflict of interests. Authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: March 17, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):226-231
pages 226-231 views

The development of pre-implantation mouse embryos under the influence of sublethal doses of cadmium chloride on the maternal organism

Noniashvili E.

摘要

Introduction. Cadmium (CD) is a heavy metal widely distributed in the environment, when it enters the human body, it leads to the development of various diseases.

The aim of this work was to study the effect of sublethal doses of cadmium chloride on the preimplantation development of mouse embryos in vivo.

Material and methods. During the first three days of pregnancy, female mice were injected with 10 μM cadmium chloride (CdCl2). On the fourth day of the experiment, the embryos were explanted from the uterus and assessed development by the number of morules and blastocysts in each group and the number of blastomeres in the control and exposed embryos.

Results. Embryos exposed to cadmium chloride in utero passed the initial stages of cleavage and blastocyst formation faster than the control embryos. At the blastocyst stage, the rate of cleavage of exposed and control embryos statistically did not differ.

Limitations. The influence of the toxicant was assessed only on preimplantation mice embryos with intraperitoneal administration of the drug to mothers and in a single dose. Studies of mouse embryos at the postimplantation period of development would reveal in more detail the effect of the drug on embryogenesis.

Conclusion. Injections of sublethal doses of cadmium chloride to female mice at the debut of pregnancy force the development of embryos to the blastocyst stage.

Compliance with ethical standards. The conducted studies met the requirements of the Ethical Committee for the Use of Laboratory Animals, adopted by the Local Ethical Committee of the Federal State Budgetary Scientific Institution “IEM”, protocol No. 2/21 dated May 27, 2021.

Conflict of interest. The author declare no conflict of interest.

Funding. The study was not sponsored.

Received: April 24, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):232-236
pages 232-236 views

A clinical case of acute methadone poisoning in an infant child

Narzikulov R., Lodyagin A., Sinenchenko A., Batotsyrenov C., Rustamov B., Lisitsa I., Zapasnikov N.

摘要

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.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the State Budgetary Institution "St. Petersburg Scientific Research Institute of Ambulance named after I.I. Janelidze" Protocol No. 1 of 12.02.2022.

Author contribution:
Narzikulov R.A. — concept and design of the study, collection and processing of material, writing of the text;
Lodyagin A.N. — concept and design of the study, editing;
Sinenchenko A.G., Batotsyrenov Ch.B. — collection and processing of material;
Rustamov B.R., Lisitsyna I.A., Zapadnikov N.D. — writing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. Authors declare no conflicts of interest in connection with the publication of this article.

Financing. The study had no sponsorship.

Received: April 04, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):237-242
pages 237-242 views

Application of OECD QSAR Toolbox software for predicting the reprotoxic effects of chemicals

Lastovetskiy M., Khamidulina K., Tarasova E.

摘要

Introduction. The study of chemicals for the presence of a reprotoxic effect is a complex, time-consuming and resource-intensive process, therefore, alternative screening approaches are being developed by the international community. As such screening approaches, calculation methods are actively introduced into toxicological practice using the OECD QSAR Toolbox software. Therefore, the aim of our research was to write a manual on predicting the reprotoxic effects of chemicals using the OECD QSAR Toolbox software.

Material and methods. OECD QSAR Toolbox software version 4.4.1., OECD guidelines on the assessment of the reprotoxic effect.

Results and discussion. We have developed the manual “Prediction of the reprotoxic effect of chemicals”, selected six of the most informative and used OECD testing methods for assessing the reprotoxic potential of chemicals, studied and described the component of the “DART scheme” program, which is used to predict reproductive toxicity. The parameters that need to be set in the program to perform calculations are also selected: endpoints, profilers, databases, and others. The results of calculations in the program are presented in the form of tables.

Conclusion. Prediction of reprotoxicity using software is a screening method that allows you to select analogue substances and calculate approximate NOAEL / LOAEL values for subsequent experimental determination.

The calculated data are close to the experimental ones, however, the qualified work of an expert is required to select analogues and interpret the results obtained.

Author contribution:
Khamidulina Kh.Kh. — the concept and design of the study, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Tarasova E.V. — the concept and design of the study, collection and processing of materials, writing the text, editing;
Lastovetskiy M.L. — collection and processing of materials, writing the text, editing.

Conflict of interest. The authors declare no conflicts of interest.

Acknowledgment. The state program «Ensuring the chemical and biological safety of the Russian Federation» funded the study.

Received: July 07, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):243-254
pages 243-254 views

Discussion

New opportunities for effective identification of unknown toxicological patients (a case from practice)

Kuznetsov S., Lodyagin A., Batotsyrenov B., Reinuk V., Sinenchenko A., Litvincev B., Kuznetsova A., Kirsanova N.

摘要

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.

Compliance with ethical standards. The study did not require the approval of the Ethics committee.

Author contribution:
Kuznetsov S.V. — concept and design of the study, collection and processing of material, statistical processing, writing the text, editing;
Lodyagin A.N. — concept and design of the study, writing the text, editing; 
Batotsyrenov B.V., Reinuk V.L. — concept and design of the study, editing;
Sinenchenko A.G. — concept and design of the study, writing the text;
Litvincev B.S. — concept and design of the study;
Kuznetsova A.A. — collection and processing of material, writing the text;
Kirsanova N.A. — statistical processing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version. 

Conflict of interest. Authors acknowledge that there are no known conflicts of interest related to this publication.

Acknowledgments. The study was not sponsored.

Received: January 22, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):255-261
pages 255-261 views

New information on toxicity and hazard of chemical and biological substances

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

Epishina T.

摘要

Introduction. 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 dangerity 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).

Compliance with ethical standards. The study was approved by the Ethics Committee of the FBES "F.F. Erisman Federal Scientific Center of Hygiene of Rospotrebnadzor" (minutes of the meeting No. 11 of 12.10.2021).

Conflict of interest. The author declare no conflict of interest.

Funding. The study had no sponsorship.

Received: February 15, 2023 / Accepted: July 29, 2023 / Published: August 30, 2023

Toxicological Review. 2023;31(4):262-268
pages 262-268 views

Chemical safety

Assessment and classification of the danger of endocrine disruptors

Editroial Р.

摘要

Научно-практический журнал «Токсикологический вестник» продолжает публикацию научно обоснованного списка эндокринных разрушителей, который лёг в основу методических рекомендаций МР 1.2.0313–22 «Оценка и классификация опасности эндокринных разрушителей», утверждённых Руководителем Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека А.Ю. Поповой 30 декабря 2022 г.


Продолжение. Начало см. в научно-практическом журнале «Токсикологический вестник» № 2 и № 3, том 31, 2023.

Toxicological Review. 2023;31(4):269-275
pages 269-275 views

Congresses and conferences

pages 276-276 views