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Toxicological Review

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Vol 33, No 3 (2025)
https://doi.org/10.47470/0869-7922-2025-33-3

PREVENTIVE TOXICOLOGY

149-157 13
Abstract
Introduction. Nanoparticles of various elements, including lead, are produced during high-temperature technological processes in many mining and processing facilities. Once in the atmosphere, such nanoparticles are usually oxidized to lead oxide nanoparticles. The widespread occurrence of such contamination of work premises and territories adjacent to industrial enterprises, as well as their generally recognized toxicity, determine the importance of experimental study of the toxicity of lead nanoparticles.
The aim of the study was to experimentally investigate the toxicity of lead oxide nanoparticles on rats under subacute inhalation exposure conditions.
Material and methods. Lead nanoparticles were generated by electric sparking from a pure lead rod. Their flow was mixed with air for oxidation to lead oxide and fed to the “nose only” inhalation exposure chamber. Female rats of the experimental group were exposed to lead nanoxide at a concentration of 0.215 mg/m3 for 4 hours, 5 times a week, for 3 weeks. The second group was a control group and breathed clean unfiltered air. After the experiment was completed, the rats’ body condition parameters were determined: hematological and biochemical parameters of blood and urine, as well as behavioral tests: the elevated plus maze test, open field test, and Barnes maze, and the summation threshold index was estimated. Differences between samples were assessed using the Student’s t-test. The differences were considered significant at p<0.05.
Results. Subacute inhalation exposure to lead oxide nanoparticles aerosol led to the development
of inflammatory reaction in rats, which manifested itself in the form of leukocytosis. At the same time, no changes in porphyrin metabolism and behavioral reactions were recorded in them.
Limitations. The study was limited to investigate the indices of general toxic effects in an experimental study on subacute exposure of female rats to lead oxide nanoparticles using only one dose.
Conclusion. Our findings emphasize the necessity of a comprehensive assessment of nanoparticles, especially those of industrial importance.
158-171 10
Abstract
Introduction. Microparticles of plastic (MP) pose a threat to health, but the processes of their accumulation and distribution in living organisms, especially in brain tissues, have not been sufficiently studied.
The aim of the study was to compare the accumulation of plastic microparticles of different sizes (100, 500 and 1000 nm) in the brain of rats using a descriptive and quantitative approach.
Material and methods. Female Wistar rats, 12 individuals divided into 4 groups, were intracardiacally injected with a suspension of fluorescent polystyrene microparticles (100, 500 and 1000 nm in diameter) or a saline solution (Control) with a volume of 50 µl. The accumulation of microplastics in brain tissues was assessed using fluorescence microscopy using a descriptive approach and a computer program for quantifying the content of microparticles and their conglomerates. The data was analyzed using the Bootstrap method with the Holm–Bonferroni correction, the significance of the differences was determined at p < 0.05.
Results. It was found that fluorescent microparticles of plastic accumulate mainly in the cerebral cortex, and the MP 1000 group showed a greater number of clearly defined conglomerates compared to the MP 100 and MP 500 groups. The density of plastic microparticles, estimated using an automated morphometric approach, was also higher in the experimental groups compared with the control, especially in the MP 1000 group.
Limitations. The study was limited to studying the distribution of plastic microparticles of three sizes in a toxicological experiment on a single animal species (laboratory rat). The phase of the sexual cycle of female rats was not taken into account.
Conclusion. The integration of approaches allows for a deeper understanding of the dynamics of microparticle accumulation: a descriptive approach shows the ability of particles to penetrate the blood–brain barrier (BBB), while a quantitative approach provides data on the content and distribution of particles and conglomerates.

CLINICAL TOXICOLOGY

172-181 6
Abstract
Introduction. Alcohol poisoning occupies a dominant place in the structure of all poisoning groups in the territory of the Russian Federation. Epidemiological data in Khanty-Mansi Autonomous Region – Yugra show the need for an analysis of their prevalence.
The purpose of the work is to establish the prevalence of poisoning in the territory, to determine the proportion of poisoning in nosological groups according to the severity of the course and fatal outcomes.
Material and methods. The object of the study is the cases of poisoning (12181 people) in the territory for the period 2013–2022 in groups T51–T52 (n=3952), in nosologies: T51.0 – ethanol (n=3339), T51.1 – methanol (n=52), T52.3 – glycols (n=45), distributed according to severity of the condition (mild, moderate and severe), the number of deaths. The analysis of the prevalence of poisoning, the proportion of those poisoned in groups, the distribution of patients by severity of the condition, and the rate of increase (decrease) in poisoning in 2022 compared with 2013 was carried out.
Results. The number of poisoning cases in the T51–65 group exceeds the number of poisoning cases in the
T36–T50 groups by 57.8%. The rate of decline of those poisoned in 2022 compared to 2013 was –70.2%,
in groups T36–T50: –71.4%, in groups T51–T65: –69.25%. Ethanol poisoning of mild severity amounted
to 64.2%, moderate severity – 19.7%, severe – 16.2% (methanol – 11.6, 32.7, 55.7%; ethylene glycol – 17.3, 43.5, 39.2, respectively). Deaths predominate in the T51 group – 43.9%, ethanol and methanol account for 28.9%
of deaths, and in the T52 group (33.4%). In two groups (T51–T52), the mortality rate was 46.4% (228 cases).
The generalization of the information received on the prevalence of acute poisoning of chemical etiology in Khanty-Mansi Autonomous Region – Yugra for the analyzed period (2013–2022) shows the structure of the incidence and allows predicting the volume of the possible number of poisonings, comparing the structure of poisoning with other regions of the Russian Federation.
Limitations. When studying the total number of poisonings in the territory of the Khanty-Mansiysk Autonomous Region – Yugra for 2013–2022, an assessment of 12181 poisoning was carried out.
Conclusion. The average prevalence of poisoning in the period from 2013 to 2022 in the T51 group was 22.6, in the T52 group – 1.4. The proportion of poisoning in the structure of poisoning in the T51 group was 30.5%, in the T52 group – 1.9%. The indicator of poisoning according to the severity of the course:
in the group of ethanol poisoning, there was a predominance of patients with mild severity (64.1%); ethylene glycol – moderate severity (43.5%); methanol – severe (55.7%). The analysis of deaths in nosological groups T51–T52 showed their predominance in the T51 group – 43,9%.

RESEARCH METHODS

182-188 3
Abstract
Introduction. Treatment with fungicidal active compounds based on pydiflumetofen is the most effective way to combat fungal infections of plants, the use of which reduces the content of mycotoxins. This is very important mainly when storing food products, in particular citrus fruits, susceptible to contamination with a number of mycotoxins.
Material and methods. Some types of citrus fruits (oranges, tangerines) purchased on the consumer market of the Moscow region were used as objects of study. The method is based on the determination of pydiflumetofen using reversed-phase high-performance liquid chromatography with an ultraviolet detector on a diode matrix after extracting the substance from the analyzed citrus samples with a mixture of acetonitrile and water, cleaning the extracts concentrated to an aqueous residue by solid-phase extraction using cartridges.
Results. In the developed method, the achieved lower limit of quantification of pydiflumetofen in all studied plant samples (LOQ) is 0.01 mg/kg, the range of measured concentrations is 0.01–10 mg/kg. The method was tested on tangerines and oranges imported from some foreign countries and purchased in the networks of large retail realtors in the Moscow region. The content of pydiflumetofen in the pulp and juice of tangerines and oranges supplied to the Russian Federation is below the detection limit, i.e. less than 0.01 mg/kg, in the peel no more than 0.6 mg/kg, in the whole fruit no more than 0.25 mg/kg.
Limitations. Determination of the concentration of pydiflumetofen was carried out in tangerines and oranges, which are citrus fruits. The studies used samples from a limited list of exporting countries.
Conclusion. The methodical approach used to determine the content of residual quantities of pydiflumetofen showed positive results in the analysis of citrus fruits. The obtained range of detectable concentrations of pydiflumetofen fully satisfies the existing hygienic standards in force in the territory of the Russian Federation and abroad.

NEW INFORMATION ABOUT TOXICITY AND DANGER

189-196 31
Abstract
Introduction. The previously obtained data indicate pronounced critical disturbances of enteral homeostasis (barrier, motor-evacuation, secretory-absorption and digestive disfunctions of the intestine) during sulfur mustard intoxication. Obviously, against this background, the habitat of the intestinal microbiota changes significantly, which can lead to significant changes in the content of short-chain fatty acids and aromatic microbial metabolites both at the local level and in the systemic bloodstream.
The aim of the work is to study the metabolomic profile of short-chain fatty acids and aromatic microbial metabolites in the blood serum of rats in the dynamics of sulfur mustard intoxication.
Material and methods. Four experimental groups of rats were intramuscularly administered sulfur mustard at a dose of 1.0 LD50. On days 1, 2, 3 and 4 after the introduction of the toxicant, the quantitative content of acetic, propionic, butyric, valerianic, 4-hydroxyphenylacetic, phenylpropionic, 3-phenyllactic and p-hydroxyphenyllactic acids was determined in the blood serum by High performance liquid chromatography with mass spectrometry (HPLC-MS). Similar indicators were determined in the blood serum of the control group of animals.
Results. A decrease in the content of all studied short-chain fatty acids was recorded starting from the first day after the introduction of the toxicant in comparison with similar indicators of the control group. Analysis of the quantitative content of aromatic microbial metabolites revealed an increase in serum concentrations of hydroxyphenylacetic and phenyllactic acids, most pronounced by the 3rd–4th day of sulfur mustard intoxication.
Limitations. Analytical studies of samples do not apply to environmental objects, and the methodological possibilities of their interpretation are limited by the chemical nature of analytes.
Conclusion. This paper presents for the first time the results of studying the metabolomic profile (the content of short-chain fatty acids and aromatic microbial metabolites) of rat blood serum in the dynamics of sulfur mustard intoxication. Analysis of the obtained results allows us to speak about pronounced microecological changes in the gastrointestinal tract after the introduction of sulfur mustard, and a decrease in the content of short-chain fatty acids, with a simultaneous increase in the level of hydroxyphenylacetic and phenyllactic acids, may have an important patho- and thanatogenetic significance.

FROM PRACTICE

197-205 5
Abstract
Introduction. In the contemporary world, the problem of poisoning caused by organophosphorus compounds (OPs) is of great concern, with the risk of exposure to OP nerve agents remaining a reality in military settings. Healthcare professionals can utilize clinical cases of OP intoxication to prepare for the treatment of affected individuals. This study aims to investigate the characteristics of poisoning in a patient who suffered from acute oral exposure to OPs.
Description of the clinical case. The patient was discovered in a state of unconsciousness on the staircase, with a bottle of AgranTM insecticide nearby.
It was estimated that the patient had ingested approximately 600 milligrams of the substance per kilogram of their body weight. The acetylcholinesterase (AChE) activity in their serum was significantly diminished, measuring at 12 units per liter. Furthermore, the patient was also exposed to another organophosphorus (OP) substance, cypermethrin, at an estimated dose of 50 milligrams per kilogram. Upon admission, the severity of the patient’s condition was attributed to a cholinomimetic syndrome, accompanied by acute respiratory failure of mixed origin, decompensated mixed acidosis, and toxic encephalopathy. No abnormalities in neuromuscular conduction or transmission were observed. Timely etiological therapy with atropine and detoxification measures such as gastric lavage and hemosorption contributed to the normalization of the patient’s condition. Nonetheless, fourteen days following the exposure, there was a persistent and substantial reduction in the activity of serum cholinesterases and erythrocyte acetylcholinesterase.
Conclusion. Consequently, it is reasonable to infer that acetylcholinesterase activity may not consistently correlate with the severity of OP intoxication in the prolonged post-toxic period. In the absence of comprehensive treatment for OP, extracorporeal detoxification emerges as a recommended approach.
Limitations. In the performed study, the activity of erythrocyte AChE and serum butyrylcholinesterase was not evaluated, electromyography was not performed at the time of admission and during the start of treatment, the patient did not receive antidote therapy with cholinesterase reactivators.

CHEMICAL SAFETY

206-213 11
Abstract
Introduction. The share of combined effects of mechanical, thermal and infectious damage with chemical poisoning in accidents of various chemical industries, burning of plastics and petroleum products has been significantly increased by cases of damage during combat operations in the zone of special military operation.
Material and methods. A retrospective comparative analysis of patients with isolated and combined chemical trauma admitted to a first-level hospital.
Results. Combined injuries in the flow of intoxicated patients entering first-level medical institutions account for 13.7%. The etiology of chemical injury in such victims corresponds to isolated chemical damage; at that, injuries by irritants, organic acids, alkalis and detergents form the basis. The presence of contusions or a wound process promotes early seeking of medical help and hospitalization compared to isolated poisonings. The basis of toxic injuries was the pathology of the bronchopulmonary system and laryngopharyngeal mucosa. Acid burns of the mucous membrane manifested on the second or third day postexposure. The occurrence of severe multi-focal pulmonitis after poisoning with organic and mineral alkalis and detergents aggravates the course of traumatic shock and early purulent complications of mechanical trauma. The pronounced necrotizing effect was noted during local exposure of toxicants present on the ammunition fragments.
Limitations. The results of studies of chemical injury cases do not apply to categories of civilians and workers of chemical industry enterprises and provide for events during the performance of combat and combat training missions.
Conclusion. The injuries’ variety determines the need to formulate a syndromic diagnosis for setting treatment tactics and evacuation purpose of the injured.


ISSN 0869-7922 (Print)
ISSN 3034-4611 (Online)