No 2 (2022)

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.

Introduction. The toxic effect of amanitin-containing macromycetes, or phalloidin syndrome, is accompanied by low patient survival and it remains as one of the leading causes of urgent liver transplantation. As a result, the problems of biodiversity and the distribution of amanitin-containing fungi leading to this condition appear in a relevant light for toxicology.

Materials and methods. The study was carried out in two stages. At the first stage, a preliminary list of amanitin-containing macromycetes was compiled by means of a system search in the PubMed database. At the second stage of the study, the presence and occurrence of amanitin-containing taxa in Russia were analyzed.

Results. Based on the literature sources and data of the Laboratory of Geography and Systematics of Fungi of the Komarov Botanical Institute of the Russian Academy of Sciences, maps of the administrative-territorial occurrences in Russia of twenty-one species of amanitin-containing macromycetes were compiled: five of Amanita, one of Galerina and fifteen of Lepiota. The species concepts of some poisonous taxa and their key identification features were reviewed. The debatable ideas about the toxicity of two Conocybe species are highlighted.

Limitations. The study takes into account only the specific occurrence of poisonous fungi in various territories of Russia, without considering the density and frequency of their growth, which may make it difficult to assess the relationship between the data presented and the likelihood of poisoning by the species in question in individual administrative units.

Conclusion. As a result of the study, the boundaries of the distribution of poisonous fly agaric and Galerina species were identified, as well as the territories with the highest registered diversity of Lepiota: the Moscow Region and the Primorsky Territory.

Introduction. The active development of agriculture with the widespread use of nitrogen-containing fertilizers, increased consumption of processed meat products containing sodium nitrite as a preservative, inevitably leads to an increase in the nitrogen load on the human body and can cause the development of cardiovascular diseases.

Materials and methods. The cardiotoxic effect of sodium nitrite was evaluated on a model of an isolated rat heart with subchronic intragastric administration for 28 days at doses of 0.03; 0.3; 3.0 mg/kg.

Results. The use of sodium nitrite leads to dilation of the coronary vessels and myocardium, inhibition of the contractile activity of the heart, disruption of its electrical activity in the form of a shortening of the QT interval associated with an increased risk of ventricular fibrillation, and a tendency to increase the amplitude of the T wave, which indicates myocardial ischemia. In a stress test with total ischemia, it was revealed that the magnitude of the change in the parameters characterizing the restoration of myocardial function under reperfusion conditions is inversely proportional to the dose of sodium nitrite used.

Limitations. The study was performed only on male white rats more prone to the development of cardiovascular pathology.

Conclusion. With subchronic administration, sodium nitrite has cardiotoxicity at a dose of 0.028 mg/kg, which is twice lower than the WHO-established permissible daily intake for humans (0.06 mg/kg).

The aim. To study the effect of the rutile form of titanium dioxide upon its oral administration on the morphological and functional state of the organs of the immune system of rats.

Materials and methods. In this work, using classical morphological approaches and specific markers: proliferation — Ki-67, PCNA, apoptosis — protein p53 and macrophages — CD68, which make it possible to adequately identify not only the cells themselves, but also their functional state, a study of the spleen and thymus of rats after oral administration (10 mg/kg animal body weight, 28 days) of a nanodispersed form of TiO₂ (rutile form, 40–60 nm) obtained by diluting TiO₂ powder in distilled water was carried out. Aggregation of nanoparticles was prevented by treatment of a suspension of nanodispersed TiO₂ in an ultrasonic bath. Rats of the control group were orally administered with distilled water in the same volume.

Results. With oral administration of the rutile form of nanodispersed TiO₂, a moderate accidental involution of the thymus is observed, a reduction in the white pulp of the spleen, due to a decrease in the proliferative potential and an increase in apoptosis.

The revealed morphofunctional changes in lymphoid organs can be interpreted from the standpoint of induced secondary immunodeficiency that develops against the background of exposure to rutile TiO₂ NPs.

Limitations. When studying the effect of titanium dioxide (rutile, 40–60 nm, 10 mg/kg of animal body weight) on the morphological characteristics of the immune defense organs, the sample size was 12 Wistar rats, the maximum duration of exposure was 28 days.

Conclusion. The detected morphofunctional changes in the lymphoid organs can be interpreted from the position of induced secondary immunodeficiency, developing against the background of exposure to NPS TiO₂ of the rutile modification.

Introduction. Amiksin (tiloron) is a low molecular weight inducer of interferon, antiviral and immunomodulatory agent, used for the treatment and prevention of viral diseases, shown the effectiveness of including amixin in the complex therapy of SARS-CoV-2 infection (COVID-19) mild and moderate severity.

Materials and methods. Experimental studies to determine the parameters of amixin toxicometry were carried out using mice, rats, rabbits and guinea pigs. The substance was administered into the stomach, intraperitoneally, into the conjunctival sac of the eye, on the skin, intradermal and inhalation.

Results. It is shown that amixin belongs to the 3^rd hazard class (moderately hazardous substances) when injected into the stomach according to GOST 12.1.007-76: DL₅₀ for male mice — 500 mg/kg, for female mice — 760 mg/kg; low toxicity when injected into the abdominal cavity, DL₅₀ for male mice — 150 mg/kg. Amiksin has a weak irritant effect on the mucous membranes of the eyes, does not irritate the skin, has a skin-resorptive effect and functional cumulative activity. The threshold for acute inhalation exposure to amixin is set at 16,2 mg/m³ according to the effect on the functional state of the liver and kidneys.

Limitations. When developing and substantiating the hygienic standards for amixin in the air, various ways of the substance entering the body of several animal species in representative groups were studied.

Conclusion. For amixin aerosol, hygienic standards have been approved — 0,4 mg/m³ in the air of the working area and 0,01 mg/m³ in the atmospheric air.

Федеральной службой по надзору в сфере защиты прав потребителей и благополучия человека совместно с Секретариатом Роттердамской конвенции о процедуре предварительного обоснованного согласия в отношении отдельных опасных химических веществ и пестицидов в международной торговле 10 февраля 2022 года в режиме видеоконференцсвязи на русском и английском языках проведён вебинар «Укрепление потенциала для управления жизненным циклом химических веществ в рамках Роттердамской конвенции».

On a model of an isolated rat heart, the cardio toxic effect of sodium nitrite was revealed after subchronic intragastric administration for 28 days at doses of 0.03; 0.3; 3.0 mg/kg. The use of sodium nitrite leads to dilatation of the coronary vessels and myocardium, impairment of its electrical activity in the shortening of the QT interval, associated with an increased risk of ventricular fibrillation, and a tendency to an increase in the amplitude of the T wave, which indicates myocardial ischemia. In a load with a total ischemic test, it was found that the magnitude of the change in indicators characterizing the restoration of myocardial function under conditions of reperfusion is inversely proportional to the dose of sodium nitrite used. Thus, it was found that sodium nitrite has cardiotoxicity at a dose of 0.028 mg/kg, which is two times lower than the permissible daily intake for humans established by the WHO (0.06 mg/kg).

Регламент ЕС 1107/2009 о размещении на рынке продукции для защиты растений (с изменениями на 27.03.2021) устанавливает правила для утверждения активных веществ, антидотов и синергистов, содержащихся или входящих в состав продукции для защиты растений, а также правила для вспомогательных средств и ко-формулянтов.