scholarly journals TOXIC PULMONARY EDEMA BY INHALATION OF PYROLYSIS PRODUCTS OF CHLORINATED PARAFFIN-70 IN RATS

Author(s):  
P. G. Tolkach ◽  
V. A. Basharin ◽  
S. V. Chepur

In the study conducted on laboratory animals (rats) toxic pulmonary edema (TPE) was simulated by inhalation of pyrolysis products of chlorinated paraffin-70 (CP-70). The average-lethal dose of CP-70 burned at 280 ÷ 350 ° C for 3 minutes is 8.1 ± 0.9 g and provides a concentration of hydrogen chloride (HCl) in the chamber at the level of 7325 [5850; 8460] ppm. Under these conditions exposure for 30 minutes led to an increase in the pulmonary rate (LC) in laboratory animals 24 hours after poisoning. The diagnosis of TPE was confirmed histologically by the signs of interstitial and alveolar edema, as well as arterial hypoxemia (TI = 204.5 [180; 228]) indicating respiratory failure. The death of animals was recorded 3 days after application of the pyrolysis products of CP-70. The simulated experimental TPE model can be used to search for the means of pathogenetic therapy of pulmonary toxicants poisoning.

Author(s):  
P. G. Tolkach ◽  
V. A. Basharin ◽  
S. V. Chepur

Relevance.Thermal decomposition of various polymeric materials occur in emergency situations associated with fires, with pulmonotoxicants releasing in the environment. During pyrolysis of polytetrafluoroethylene (Teflon), a highly toxic perfluoroisobutylene is produced.Intention.To create an experimental animal model of toxic pulmonary edema due to products of thermal decomposition of polytetrafluoroethylene.Methodology.Polytetrafluoroethylene underwent pyrolysys at 440–750 0С during 6 minutes. Toxic pulmonary edema was modeled on rats via inhalation of pyrolysis products of polytetrafluoroethylene. An amount of polytetrafluoroethylene burned under these conditions with resulting death of 50 % of rats during 1 day was (2.68 ± 0.60) g. The toxic pulmonary edema diagnosis was confirmed histologically and by lung/body ratio.Results.In the pyrolysis products of polytetrafluoroethylene, highly toxic perfluoroisobutylene was found via gas chromatography with mass spectrometric detection, with relative content of 85.9 %. Such an exposure during 15 min increased (p = 0.01) lung/body ratio in laboratory animals in 3 hours. The toxic pulmonary edema diagnosis was confirmed histologically  (signs of alveolar edema). Animals started to die 7 hours after the pyrolysis products inhalation.Conclusion.In the study on rats, toxic pulmonary edema was modeled via inhalation of pyrolysis products of polytetrafluoroethylene. This model can be used for searching etiotropic and pathogenetic therapy for poisoning with pulmonotoxicants.


2020 ◽  
Vol 20 (3) ◽  
pp. 13-22
Author(s):  
P. K. Potapov ◽  
Yu. V. Dimitriev ◽  
P. G. Tolkach

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.


Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.


2019 ◽  
Vol 16 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Mohammad Aminianfar ◽  
Siavash Parvardeh ◽  
Mohsen Soleimani

Background: Clostridium botulinum causes botulism, a serious paralytic illness that results from the ingestion of a botulinum toxin. Because silver nanoparticle products exhibit strong antimicrobial activity, applications for silver nanoparticles in healthcare have expanded. Therefore, the objective of the current study was to assess a therapeutic strategy for the treatment of botulism toxicity using silver nanoparticles. Methods: A preliminary test was conducted using doses that produce illness in laboratory animals to determine the absolute lethal dose (LD100) of botulinum toxin type A (BoNT/A) in mice. Next, the test animals were divided into six groups containing six mice each. Groups I, II and III were the negative control (botulinum toxin only), positive control-1 (nano-silver only) and positive control-2 (no treatment), respectively. The remaining groups were allocated to the toxin that was supplemented with three nano-silver treatments. Results: The mortality rates of mice caused by BoNT/A significantly reduced in the treatment groups with different doses and injection intervals of nano-silver when compared to the negative control group. BoNT/A toxicity induced by intraperitoneal injection of the toxin of Clostridium botulinum causes rapid death while when coupled with nano-osilver results in delayed death in mice. Conclusion: These results, while open to future improvement, represent a preliminary step towards the satisfactory control of BoNT/A with the use of silver nanoparticles for human protection against this bioterrorism threat. Further study in this area can elucidate the underlying mechanism for detoxifying BoNT/A by silver nanoparticles.


1919 ◽  
Vol 30 (5) ◽  
pp. 417-436 ◽  
Author(s):  
Wade H. Brown ◽  
Louise Pearce

The essential facts to be gathered from these studies of the toxicologic action of N-phenylglycineamide-p-arsonic acid may be summarized very briefly. The substance is one which lends itself well to almost any method of administration and can be given to animals in very large doses. The tolerance of different animal species varies rather widely but with one exception the reaction of laboratory animals to toxic doses of the drug is of favorable character. That is, toxic effects are confined to doses relatively close to the minimum lethal dose and the recovery of animals from sublethal intoxications is remarkably rapid and complete. This feature of the action of the drug makes possible the repeated administration of even very large doses at comparatively short intervals of time without incurring the dangers incident to cumulative action or to superposition of toxic effects. On the contrary, by taking advantage of this peculiarity of action, it is possible to develop such a degree of tolerance on the part of animals that the dose of the drug administered can be progressively increased to a point well above that which is fatal to the normal animal, and this stands out as the feature of the toxicologic action of N-phenylglycineamide-p-arsonic acid which is of greatest significance in the use of the drug for therapeutic purposes.


CHEST Journal ◽  
1994 ◽  
Vol 105 (1) ◽  
pp. 229-231 ◽  
Author(s):  
Stephen E. Lapinsky ◽  
David B. Mount ◽  
Dale Mackey ◽  
Ronald F. Grossman

1993 ◽  
Vol 2 (1) ◽  
pp. 65-67 ◽  
Author(s):  
PJ Papadakos ◽  
DS Johnson ◽  
JS Abramowicz ◽  
DM Sherer

Adult respiratory distress syndrome, presenting as rapid respiratory decompensation in the setting of preeclampsia at 36 weeks of gestation, was managed by early hemodynamic monitoring with pulmonary artery catheterization. With confirmation of the diagnosis of preeclampsia the patient was delivered promptly; improvement of her respiratory failure was observed within 48 hours. Consideration of adult respiratory distress syndrome in the setting of preeclampsia is discussed, with emphasis on early confirmation of the diagnosis and determination of the precise mechanisms of pulmonary edema.


Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 795
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Alexander A. Sergeev ◽  
Alexei S. Kabanov ◽  
Tatiana V. Bauer ◽  
...  

The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.


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