Poisoning with acylating pulmonary toxicants results in toxic pulmonary edema (TPE), the approaches to treatment of which are limited. The lung injury similar to poisoning with acylating pulmonary toxicants can be simulation through body’s exposure to the fluoroplastic thermal degradation products containing perfluoroisobutylene. The study was aimed to compare toxic pulmonary edema manifestations in the laboratory animals poisoned with an acylating pulmonary toxicant (carbonyl chloride) and fluoroplastic thermal degradation products. Animals (male rats, n = 78) were divided into three groups: controls; Poisoning 1, where the animals were exposed to carbonyl chloride; Poisoning 2, where the animals were exposed to the fluoroplastic thermal degradation products. The animals’ lung/body ratio was determined and the partial pressure of arterial oxygen (PaO2) and carbon dioxide (PaCO2) was assesed 10 min, 1, 3, 6, 24, and 48 h after the exposure. Histological examination of lung tissue was performed 3 and 6 h after the exposure. The increase in the lung/body ratio, decrease in PaO2, and increase in PaCO2 relative to controls were revealed 3, 6, 24, and 48 h after the exposure to carbonyl chloride and fluoroplastic thermal degradation products. The signs of the interstitial toxic pulmonary edema phase were detected 3 h after the exposure to the studied toxicants, and the signs of alveolar phase were revealed after 6 h. Similar changes were identified in animals of the experimental groups. The findings have shown that the exposure to carbonyl chloride and the fluoroplastic thermal degradation products containing perfluoroisobutylene lead to similar changes in the early post-intoxication period.

The study evaluates the dynamics of aquaporin (aquaporin-1, aquaporin-5, and epithelial sodium channel) content in the aero-hematic barrier during the latent phase of rat intoxication with carbonyl chloride (phosgene), thermal decomposition products of fluoroplast containing perfluoroisobutylene, and nitrogen dioxide. Rat intoxication was modeled using average lethal concentrations of these toxic substances. At 30 and 60 minutes post-exposure, pulmonary coefficient was measured and histological and immunohistochemical studies were performed. Western blot analysis was used to determine the aquaporin-5 content in rat lung tissues exposed to the thermal decomposition products of fluoroplast. It was found that rat intoxication with phosgene and thermal decomposition products of fluoroplast containing perfluoroisobutylene led to an increase in the relative content of aquaporin-5 and epithelial sodium channel-positive cells in lung tissues as early as 30 minutes post-exposure. At 60 minutes post-exposure, there were signs of the interstitial phase of toxic pulmonary edema and an increase in the pulmonary coefficient. Exposure to nitrogen dioxide resulted in an increase in the pulmonary coefficient and the relative content of aquaporin-5-positive cells, as well as pronounced signs of the interstitial phase of edema 30 minutes post-exposure. Western blot analysis using anti-aquaporin-5 antibodies revealed an increase in the staining intensity of complexes with molecular weights of 25 and 50 kDa, suggesting the formation of aquaporin-5 tetramers and their likely translocation from the intracellular compartment to the plasma membrane of alveolar cells. These findings indicate that aquaporin-5 plays an important role in the pathogenesis of toxic pulmonary edema induced by the studied pneumotoxicants. Targeting these molecules may be a promising approach for pathogenetic therapy of poisoning.

The effectiveness of the use of oxygen, zinc bisvinylimidazole diacetate, and ascorbic acid for the treatment of powder gas poisoning was evaluated using an intoxication model of laboratory animals (mice) with thermal destruction products of nitrocellulose. Mice were subjected to intoxication with thermal destruction products of nitrocellulose in an average lethal concentration. Oxygen therapy (proportion of inhaled oxygen: 0.3; 1 ata) was performed immediately after exposure and once for 30 min. Zinc bisvinylimidazole diacetate (9 mg/kg, intraperitoneal) and ascorbic acid (40 mg/kg, intraperitoneal) were administered to mice once after exposure. Survival rate, hemoglobin derivative concentrations, pulmonary coefficient, and histological changes in the lung tissue were determined. The effectiveness of the use (protection, antidote power, and guaranteed protection indices) of a combination of zinc bisvinylimidazole diacetate and ascorbic acid was assessed. The survival rate of mice that received oxygen after intoxication with thermal destruction products of nitrocellulose was lower (20 ± 13%; p 0.05) than that of animals that did not receive treatment (60 ± 16%); 3 h after exposure, the pulmonary coefficient was 22.5 [21.9; 23.8] rel. units and 13.1 [12.5; 13.7] rel. units respectively. The protection index of the combination of zinc bisvinylimidazole diacetate and ascorbic acid was 1.39 rel. units, antidote power indicator was 0.95 rel. units, and guaranteed protection coefficient was 0.65 rel. units. The use of the study combination resulted in decreased carboxyhemoglobin (9.3 [7.8, 12.9]%; p 0.05) and methemoglobin (2.4 [1.5, 4.1]%; p 0.05) concentrations compared to animals that did not receive treatment (24.5 [22.9; 28.3]% and 8.9 [7.3; 11.1]%, respectively). The pulmonary coefficient of mice receiving the study drug combination was lower (p 0.05) than that of animals not receiving treatment at 3 and 6 h after exposure. Moreover, 6 h after exposure, signs of the alveolar phase were determined in mice that did not receive treatment, and in animals that were administered the study drug combination, signs of the interstitial phase of toxic pulmonary edema were observed. Thus, the use of oxygen after intoxication with products of thermal destruction of nitrocellulose leads to early formation of toxic pulmonary edema. As a pathogenetically based approach to the treatment of intoxication, the use of zinc bisvinylimidazole diacetate and ascorbic acid should be considered, the mechanism of action of which is aimed at relieving hemic and respiratory hypoxia.

Inhalation intake of acylating pulmonary toxicants (phosgene and perfluoroisobutylene) leads to the formation of toxic pulmonary edema; the pharmacological approaches to its treatment are inefficient. Respiratory therapy is successfully used to treat the pulmonary edema of nontoxic genesis. Data on the efficiency of respiratory support during toxic pulmonary edema are limited. The aim of this study was to experimentally test the efficiency of protective artificial ventilation with maintenance of positive end-expiratory pressure in the early period of intoxication with the products of thermal degradation of fluoroplast-4. In the experimental study, it was established that early implementation of protective artificial ventilation with maintenance of end-expiratory pressure is an efficient approach for the correction of toxic pulmonary edema in rabbits in the early period of intoxication with the products of thermal degradation of fluoroplast-4, which have a toxic pulmonary effect. Respiratory support can be a promising approach for the treatment of toxic pulmonary edema caused by intoxication with acylating pulmonary toxicants.

Nitrogen dioxide is released by the interaction of some metals with nitric acid. Inhalation intoxication with nitrogen dioxide leads to chemical pulmonary edema. This study presents the case of a patient who had acute inhalation exposure to an unidentified brown gaseous substance (presumably nitrogen dioxide) when he etched a metal product with nitric acid. Twenty-four hours after contact with the gas, he manifested signs of intoxication, such as chest pain, tachypnea, and decreased saturation. Laboratory tests revealed hemoconcentration, hyperfermentemia, and arterial hypoxemia. The X-ray image of the entire lung surface revealed a sharp increase and deformation of the pulmonary pattern due to the vascular component. The diagnosis was T65, i.e., toxic effect of other and unspecified substances. With treatment, the patients condition improved. On day 4 after therapeutic exposure, with decreased oxygen fraction in the inhaled gas mixture to 0.3, the saturation increased to 98%, and tachypnea disappeared. On day 6, with ongoing treatment (oxygen therapy, use of antioxidants, antihypoxants, anti-inflammatory, and antibacterial drugs), the inflammatory reaction stopped, the rheological properties of the blood improved, and the gas composition of arterial blood normalized, i.e., the oxygenation index was 436, which indicated the disappearance of arterial blood oxygenation disorders. During the radiological examination, the normal radiological picture of the lungs was determined. Thus, on day 6 after the start of therapy, signs of intoxication were completely stopped. Specific changes in the lungs during radiation research techniques, hemoconcentration, inflammation, and hypoxemia during laboratory blood tests should be considered prognostic signs of chemical pulmonary edema. As a pathogenetic therapy, treatment must be supplemented with drugs that stop the cascade of free radical oxidation reactions (acetylcysteine and sodium thiosulfate). Individuals exposed to nitrogen dioxide should be considered a high-risk group for lung damage and hospitalized for dynamic observation for at least 2 days. Taking into account the genotoxic effects of nitrogen dioxide, affected patients should be classified as at risk of developing neoplasms and undergo further dynamic monitoring.

Introduction. Polyethylene and synthetic foam caoutchouc are used for thermal insulation of communications, at temperatures not exceeding 90 °C and 105 °C, respectively. Data on how these materials will behave in the appropriate temperature conditions was not be found. The purpose of the study was to conduct a toxicological and hygienic assessment of products made of polyethylene foam and synthetic foam rubber under thermal exposure. Materials and methods. The thermal effect on the studied samples was modelled in a climate chamber. The time interval during the mass loss of the samples was determined, a sanitary and chemical study of the gas-air mixture in the climatic chamber was carried out. To conduct a toxicological and hygienic study in animals, a swim-escape conditioned active avoidance response was developed. Results. Under thermal (90 °C) exposure for 72 hours to polyethylene tube, a loss of 0.77% of the initial mass of the sample occurs. Thermal exposure (105 °C) to synthetic foam caoutchouc resulted in a loss of 15.3% of the initial mass of the sample for 108 hours, while pronounced changes in the appearance of the samples were determined. When conducting a sanitary and chemical study in the climate chamber, an increase in the concentration of carbon monoxide was determined after 12, 24, and 72 hours and hydrogen chloride after 12 and 24 hours following the onset of thermal exposure compared with the values of their average daily maximum permissible concentration. Thermal exposure to the sample and synthetic foam caoutchouc led to an increase in the concentration of ammonia, carbon monoxide and hydrogen chloride 12 and 24 hours after the start of exposure compared with the average daily maximum permissible concentration. During the toxicological and hygienic study, animals exposed to thermal degradation products of the materials under study were revealed to show learning disabilities. Limitations. They are conditioned by the methodology of the study. A quantitative analysis of some gaseous thermal degradation products released into the climate chamber was performed, without taking into account the aerosols formed. Conclusion. Thermal insulation materials made of synthetic foam rubber and polyethylene foam lose their structural properties when they are operated in the maximum permissible temperature conditions (105 °C and 90 °C, respectively). When they are used in appropriate temperature conditions, the formation of toxic products occurs, the inhalation effect of which leads to a disturbances of the learning ability in laboratory animals.

We studied the content of aquaporin-5 (AQP5) and epithelial sodium channel (ENaC) in rat lungs during the development of toxic pulmonary edema (TPE) caused by intoxication with phosgene and perfluoroisobutylene (1.5 LC50). The lung body weight index (LBI) was calculated and histological examination of the lung tissues was performed. Localization and expression of AQP5 and ENaC were determined by immunohistochemistry. Intoxication led to a significant (p<0.05) increase in LBI and histological changes typical of TPE 1 and 3 h after the exposure. In 1 and 3 h after phosgene intoxication, the AQP5 and ENaC content significantly (p<0.05) increased in comparison with the control. Similar changes in the AQP5 and ENaC content were observed 1 and 3 h after exposure to perfluoroisobutylene. It was hypothesized that AQP5 plays an important role in the formation of TPE caused by intoxication with acylating pulmonotoxicants. An increase in the content of ENaC can be considered as a compensatory reaction of the body aimed at clearance of the alveolar fluid.

Determination of respiratory rate is a necessary task in assessing the state of health in humans. This review provides a description of modern devices used for recording and monitoring respiratory rate. The advantages and disadvantages of the principles of operation of these devices are discussed.

Relevance. Intoxication of acylate pulmonotoxicants causes disturbance of structure and function of air-blood barrier, the output of liquid in the interstitial and alveolar space and manifestation of lung edema. Aquaporins play an important role in the transportation of fluid through the alveolar-capillary membrane, including pathological conditions. Water permeability through aquaporins is blocked by mercury ions. Using mercury chloride may reduce severity of the acute lung edema after intoxication of the pulmonotoxicants. Intention. The goal is to evaluate the role of mercury dichloride in the development of toxic pulmonary edema in laboratory animals during intoxication with pulmonotoxicants with an acylating effect. Methodology. Laboratory animals (rats and rabbits) were exposed to inhalation intoxication of carbonic acid dichloride and perfluoroisobutylene at concentrations of 1,5LC50. In 30 minutes after exposure were administrated of 0,3LD50 mercury chloride to the animals subcutaneously. The oxygenation index, acid-base state, pulmonary coefficient, histological changes in lung was investigated in 6 hours after exposure. Results. It was found that intoxication with carbonic acid dichloride and perfluoroisobutylene at concentrations of 1,5LC50 led to the development of toxic pulmonary edema in rats and rabbits 6 hours following exposure. The administration mercury chloride to 30 minutes following exposure to the pulmonotoxicants under study, led to a decrease (p 0.05) in the pulmonary coefficient, an increase (p 0.05) in the oxygenation index and normalization of the acid-base state according to compared with animals receiving 0.9 % NaCl following intoxication. When conducting a histological examination, in animals treated with mercury chloride less pronounced changes in the histoarchitectonics of the lung tissue were noted. Conclusion. Considering the fact that the administration of mercury chloride to animals led to a decrease in the manifestations of pulmonary edema in animals, it was suggested that aquaporins play an important role in the pathogenesis of toxic pulmonary edema caused by intoxication with pulmonotoxicants with an acylating effect. The use of selective blockers of aquaporins (less toxic than mercury chloride) may be a new direction in the pathogenetic therapy of toxic pulmonary edema due to exposure to pulmonotoxicants.

Perfluoroisobutylene a is pulmonotoxic chemical generated during pyrolysis of perfluoro-nalkanes (polytetrafluoroethylene). The mechanisms of acute pulmonary toxicity induced by perfluoroisobutylene have not been studied yet. The analysis of tissues of brown frogs showed that the products of polytetrafluoroethylene pyrolysis induce typical inflammatory response in the lungs (fluid accumulation, erythrocyte stasis, desquamation of the epithelium, and capillary plethora in lung septa) and oropharyngeal cavity (degeneration of ciliated epithelium, hyperemia of underlying vessels with plasmatic imbibition of the connective tissue, and margination of segmented leukocytes and monocytes). The absence of surfactant is a specific feature of the blood—air barrier of the oropharyngeal cavity in frogs compared to the lungs. It can be hypothesized that toxic effects of perfluoroisobutylene are determined by its influence on epithelial (pneumocytes and cells of nonkeratinized stratified ciliated epithelium) and endothelial cells. Even though the effects of the agent on surfactant cannot be excluded, they do not determine the probability of development of inflammatory response.

Rats were exposed to fluoroplast-4 pyrolysis products (sample weight 2.6 g, pyrolysis temperature 440-750°C, pyrolysis duration 4 min) containing perfluoroisobutylene over 15 min. Lung tissue samples for histological and electron microscopic examination were isolated in 3 and 30 min after intoxication and processed routinely. Histological examination revealed no structural changes in the lungs. In ultrathin sections of rat lungs, some changes in the structure of type I pneumocytes were detected in 3 min after the exposure: detachment of cytoplasmic processes and the appearance of transcytosis pores. These changes attested to impaired cell—cell interactions and their adhesion to the basement membrane, where structural disorganization and edema of the collagen matrix were observed. In 30 min following exposure, the signs of damage to type I pneumocytes became more pronounced. The increase in the equivalents of transcellular and paracellular permeability in the alveolar lining profile was observed. No changes in the pulmonary capillary endotheliocytes were detected, which suggest that type I pneumocytes are the primary target of the toxic effect of perfluoroisobutylene. The vulnerability of a particular cell population, in view of specific metabolism of these cells, can be the key to deciphering of the mechanisms of the toxic effect of pyrolysis products of fluorinated polymer materials.

Purpose of research – To develop an experimental model of intoxication of laboratory animals by polyacrylonitrile pyrolysis products. Materials and methods. The study was performed on the rats. Pyrolysis of polyacrylonitrile fibers was carried out at temperature of 270–350 °C. The laboratory animals were exposed to static inhalation intoxication by pyrolysis products for 15 min. Vital signs were determined in animals before and 5 minutes after intoxication. Arterial blood oxygenation index and acid-base state parameters were evaluated at 10 min after exposure. Qualitative detection of cyanides in brain and myocardial samples obtained 15 minutes after intoxication was carried out by gas chromatography. Results and discussion. It was found that the weight of the material (containing 85 % polyacrylonitrile), which pyrolysis products lead to the death of 50 % of laboratory animals within 24 hours after exposure, was 0.81 ± 0.15 g. The animals showed signs of poisoning by substances interrupting the processes of cell bioenergy when exposed to pyrolysis products obtained under specified conditions. The evident bradycardia and bradypnea (p < 0,05), and significant decrease in rectal temperature was marked. The exposed animals did not differ (p > 0,05) from the rats of the control group by the parameters of oxygenation. The signs of decompensated metabolic acidosis were detected in blood. The cyanide peak was detected by gas chromatography with a retention time of 3.78 min in brain and heart muscle biopsies. The experimental model, in which inhalation exposure of pyrolysis products of polyacrylonitrile fibers led to severe intoxication of laboratory animals, was developed. The model can be used to search for means of etiotropic and pathogenetic therapy of poisoning by combustion products of nitrogen-containing polymeric materials.

Accidents at industrial facilities that use phosgene as a feedstock for the synthesis of chemical compounds can become a source of formation of a persistent focus of chemical contamination. Phosgene has an acylating effect on the macromolecules of the components of the aerogematic barrier, which leads to the development of toxic pulmonary edema. To date, it is not known which component of the aerogematic barrier (surfactant layer, alveolocytes or endotheliocytes) serves as the primary target for this toxicant. It has been found in vitro that the action of phosgene on the surfactant (Biosurf Ltd., Russian Federation) did not lead to a decrease in the content of main phospholipids (dipalmitoylphosphatidylcholine), but contributed to an increase in the content of compounds from the group of lysophosphatidylethanolamines (proinflammatory agents). In in vivo study with intraperitoneal administration of phosgene to laboratory animals (rats), there were no signs of an inflammatory reaction of the components of the mesentery of the small intestine. Pathological changes in the lungs and liver of animals that received phosgene intraperitoneal were also not detected. The results of the study indicate that endotheliocytes located in the aerogematic barrier do not play a leading role in the initiation of a proinflammatory cascade in lung tissues after inhaled exposure to phosgene. The primary sources of proinflammatory mediators that lead to the development of toxic pulmonary edema may be alveolocytes and/or surfactant components.

Relevance.The widespread use of chlorine-containing polymer materials in the modern world is due to their various advantages over natural analogues. Given the continuing large number of fires, there is still a high risk of exposure to pyrolysis products of chlorine-containing polymer materials, primarily hydrogen chloride and carbon monoxide on the victims. The complexity of determining the toxic effect of pyrolysis products of chlorine-containing polymers makes it necessary to conduct toxicological experimental studies. Intention.The goal is to evaluate the structural and functional disorders of the respiratory system in laboratory animals when intoxicated by pyrolysis products of chlorine-containing polymer materials. Methodology.In an experimental study, pyrolysis of chlorine-containing polymer materials was performed. Thestudy was performed on 96 male rats, in which vital function indicators, pulmonary coefficient, parameters of oxygenation and acid-base state of arterial blood were determined, and histological examination of tracheal and lung tissues was performed. Results and Discussion.It was found that the pyrolysis of chlorinated paraffin (CP-70) with a mass of 7 g and sawdust with a mass of 3 g produces thermal degradation products containing hydrogen chloride at a concentration of 7325 ppm and carbon monoxide at a concentration of 1000 ppm. Exposure to pyrolysis products in laboratory animals resulted in a pronounced irritant effect during intoxication and in the early post-intoxication period. Microscopic examination of lung tissue 48 hours after exposure showed histological signs of interstitial phase of toxic pulmonary edema. We found a decrease in vital functions (heart rate, respiratory rate, rectal temperature) 24, 48 and 72 hours after exposure. Exposure to pyrolysis products led to a violation of gas exchange through the alveolar-capillary membrane, which was confirmed by a decrease in the index of oxygenation and saturation. Violation of the integrity of the alveolar-capillary membrane contributed to the penetration of fluid into the interstitial and alveolar space and the development of toxic pulmonary edema. An increase in the pulmonary coefficient (p 0.05) was observed, after 24 and 48 hours, respectively. Conclusion.As a result of the study, toxic pulmonary edema was simulated in laboratory animals by inhalation of pyrolysis products of chlorine-containing polymer materials, and structural and functional disorders of the respiratory system were determined. It was found that intoxication with pyrolysis products of chlorine-containing materials led to the development of inflammatory changes in the trachea and the manifestation of interstitial pulmonary edema. These changes were accompanied by the development of bradycardia, bradypnea, a decrease in body temperature, as well as an increase (p 0.05) in the pulmonary coefficient, and the development of decompensated respiratory acidosis. The obtained results indicate that the formation of a toxic effect when exposed to pyrolysis products is due to the combined action of hydrogen chloride and carbon monoxide.

Pulmonotoxicants are the substances causing structural and functional disorders of respiratory system. The main sources of pulmonotoxicants in the environment are thermal decomposition of synthetic polymeric materials in fires. The possibility of formation of pulmonotoxicants during the combustion of synthetic polymers of different composition with regard to the conditions of combustion (temperature, time, sufficient oxygen) was analyzed. The risk of lung damage has been considered taking into account the duration of exposure to the toxicant. In addition to general toxic carbon monoxide and cyanide, the products of thermal destruction of halogen-containing and nitrogen-containing substances pose a great danger in case of fire due to their high pulmonotoxicity. The lung damage risk is considered with account for toxicants exposure duration. The pulmonotoxicants classification has been proposed according to their hazard in relation to their concentration in the air. Main mechanisms of effect of pulmonotoxicants formed during the pyrolysis of various polymeric synthetic materials have been proposed. The description of clinical manifestations as the result of intoxication with these materials under various toxodoses effect has been shown. The hazardous risk spectrum has changed depending on the toxic exposure duration that determines the variance of treatment approaches: from possible etiotropic treatment to pathogenetic therapy of toxic pulmonary edema.

Aim. The present study was designed to determine whether medically induced hyper- and hypothyroidism effect on incidence of colon tumors induced by methylnitrosourea (MNU) burden in rats. Methods. Female rats (n = 88) were randomly divided into four groups: I (euthyroid-control), II (hyperthyroid caused by liothyronine), III (hyperthyroid caused by L-thyroxine) and IV (hypothyroid caused by propylthiouracil (PTU), also 11 rats were intact control. Colon carcinogenesis was induced with a four intrarectal instillation of MNU (4 mg in 0.5 ml saline solution) one time per week. Liothyronine (100 ± 10 µg per 100 g of animal weight 1 time per day), L-thyroxin (100 ± 10 µg per 100 g of animal weight 1 time per day) and propylthiouracil (PTU, 2,0 ± 0,15 mg per 100 g of animal weight 1 time per day) were administered intragastrically through an atraumatic probe daily, starting from the day of the last intrarectal instillation of MNU. Rats were sacrificed at 216 days after experiment beginning, and the total colon were excised, fixed for histology and analyzed. Results. Drug inhibition of thyroid hormone function by PTU resulted in a decrease in the incidence of MNU-induced colon tumors and amounted to 27.3%. The incidence of colon tumors in the hyperthyroid group caused by L-thyroxine was 70.0% (F-test – 0.012, χ2 – 7.67; p < 0.05 compared with the hypothyroid group).