Pathomorphological changes in laboratory animals exposed to lethal doses of disinfec-tants
Keywords:
disinfectant; LD50; toxicity; laboratory animals; pathological changes; histology; internal organs
Abstract
The use of disinfectants is a crucial aspect of preventive and health improvement measures for infectious diseases in farm and domestic animals. Regulatory documents require the determination of toxicity to macroorganisms, including the establishment of lethal doses and toxicity groups, during the development and registration of antimicrobial agents. This study aimed to investigate the histological changes in the internal organs of laboratory animals when determining lethal doses of innovative disinfectants. The experiments used domestic disinfectants containing glutaraldehyde as the active ingredient. Histological studies were conducted on the internal organs (kidney, liver, stomach, intestines, and spleen) of 75 laboratory animals using an Axioskop 40/40FL microscope (Carl Zeiss, Germany) with video microscopic photography. The methods used were under current standards. Hemodynamic disorders were observed in the renal tissue under the influence of lethal doses of aldehyde disinfectants. These disorders were characterized by capillary dilation and blood filling. Glomerular capillary dilation and overflow with blood cells were also detected. Additionally, stasis was observed in the lumen of the microcirculatory vessels throughout the entire length. The examination of histological sections from animal liver samples revealed a significant expansion of Dissé spaces, variations in the size of hepatocyte nuclei, beam decomposition and fragmentation, small acute perivascular hemorrhages, leukostasis in sinusoids, and hemodynamic disorders. The structure of the organ's beams was also disturbed, and a significant number of venous vessels were dilated and excessively filled with blood cells. Minor changes were detected in the stomach, including desquamation of the epithelial cells of the glands and their exfoliation into the gastric lumen, as well as circulatory disorders. Epithelial desquamation, blood vessel dilation, and signs of connective tissue edema were observed in the intestine. The kidneys exhibited signs of acute venous hemorrhage and stasis in vessels of various calibers, with the development of small acute parenchymal hemorrhages and localized lymphoid cell death in the white pulp. The prospect of further research is to investigate the histomorphological changes in the internal organs of laboratory animals when exposed to modern complex disinfectants with different active ingredients.References
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Ambrosino, A., Pironti, C., Dell’Annunziata, F., Giugliano, R., Chianese, A., Moccia, G., DeCaro, F., Galdiero, M., Franci, G., & Motta, O. (2022). Investigation of biocidal efficacy of commercial disinfectants used in public, private and workplaces during the pandemic event of SARS-CoV-2. Scientific Reports, 12, 5468.
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Laingam, S., Froscio, S. M., Bull, R. J., & Humpage, A. R. (2012). In vitro toxicity and genotoxicity assessment of disinfection by-products, organic N-chloramines. Environmental and Molecular Mutagenesis, 53(2), 83–93.
Lee, H., & Park, K. (2019). Acute toxicity of benzalkonium chloride in Balb/c mice following intratracheal instillation and oral administration. Environmental Anal-ysis, Health and Toxicology, 34(3), e2019009.
Liao, C., Tian, L., Wang, Z., Zhu, X., Han, Y., Li, T., & Wang, X. (2023). Toxicity warning and online monitoring of disinfection by-products in water by elec-troautotrophic biocathode sensors. Biosensors and Bioelectronics, 219, 114799.
Lieshchova, M., & Brygadyrenko, V. (2022). Effects of Origanum vulgare and Scutellaria baicalensis on the physiological activity and biochemical parameters of the blood in rats on a high-fat diet. Scientia Pharmaceutica, 90(3), 49.
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Marxfeld, H. A., Küttler, K., Dammann, M., Gröters, S., & van Ravenzwaay, B. (2019). Body and organ weight data in 28-day toxicological studies in two mouse strains. Data in Brief, 27, 104632.
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Musee, N., Ngwenya, P., Motaung, L. K., Moshuhla, K., & Nomngongo, P. (2023). Occurrence, effects, and ecological risks of chemicals in sanitizers and disinfec-tants: A review. Environmental Chemistry and Ecotoxicology, 5, 62–78.
Paliy, A. P. (2018). Differential sensitivity of mycobacterium to chlorine disinfec-tants. Mikrobiolohichnyi Zhurnal, 80(2), 104–116.
Park, K. (2016). An analysis of a humidifier disinfectant case from a toxicological perspective. Environmental Health and Toxicology, 31, e2016013.
Ren, Z., Yu, Y., Ramesh, M., Li, B., & Poopal, R. K. (2022). Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: An early-warning biomarker approach. Environmental Science and Pollution Research International, 29(27), 41849–41862.
Rhee, C. H., Lee, H. S., Yun, H. J., Lee, G. H., Kim, S. J., Song, S., Lee, M. H., Her, M., & Jeong, W. (2023). Chemical stability of active ingredients in diluted vete-rinary disinfectant solutions under simulated storage conditions. Frontiers in Chemistry, 11, 1204477.
Rodionova, K., Paliy, A., & Кhimych, M. (2021). Veterinary and sanitary assess-ment and disinfection of refrigerator chambers of meat processing enterprises. Potravinarstvo, 15, 616–626.
Rozman, U., Pušnik, M., Kmetec, S., Duh, D., & Šostar Turk, S. (2021). Reduced susceptibility and increased resistance of bacteria against disinfectants: A syste-matic review. Microorganisms, 9(12), 2550.
Sagripanti, J. L., & Bonifacino, A. (2000). Cytotoxicity of liquid disinfectants. Sur-gical Infections, 1(1), 3–14.
Sehmi, S. K., Allan, E., MacRobert, A. J., & Parkin, I. (2016). The bactericidal activity of glutaraldehyde-impregnated polyurethane. Microbiology Open, 5(5), 891–897.
Seo, S. Y., Park, Y. H., Jung, S. K., & Kim, J. (2022). Acute toxicity evaluation of the disinfectant containing percarbonate and tetraacetylethylenediamine by measuring behavioral responses of small fish using image analysis. Biotechnology and Bioprocess Engineering, 27(4), 687–696.
Simmonds, R. C. (2017). Chapter 4. Bioethics and animal use in programs of research, teaching, and testing. In: Weichbrod, R. H., Thompson, G. A. H., Norton, J. N. (Eds.). Management of animal care and use programs in research, education, and testing. 2nd ed. CRC Press, Taylor & Francis, Boca Raton. Pp. 1–28.
Szunyogova, E., & Parson, S. H. (2016). Histological and histochemical methods, theory and practice. 5th ed. Journal of Anatomy, 228(5), 887.
Takigawa, T., & Endo, Y. (2006). Effects of glutaraldehyde exposure on human health. Journal of Occupational Health, 48(2), 75–87.
Thumtecho, S., Sriapha, C., Tongpoo, A., Udomsubpayakul, U., Wananukul, W., & Trakulsrichai, S. (2021). Poisoning of glutaraldehyde-containing products: Clinical characteristics and outcomes. Clinical Toxicology, 59(6), 480–487.
Tong, C., Hu, H., Chen, G., Li, Z., Li, A., & Zhang, J. (2021). Disinfectant resistance in bacteria: Mechanisms, spread, and resolution strategies. Environmental Re-search, 195, 110897.
Wang, J., & Hu, X. (2023). Factors influencing disease prevention and control behaviours of hog farmers. Animals, 13(5), 787.
Wang, Y., Wu, Q., Ren, B., Muskhelishvili, L., Davis, K., Wynne, R., Rua, D., & Cao, X. (2022). Subacute pulmonary toxicity of glutaraldehyde aerosols in a human in vitro airway tissue model. International Journal of Molecular Sciences, 23(20), 12118.
Yang, H., Li, X., Cao, X., Lu, S., & Zheng, X. (2023). The toxicity assessment of 14 biocides for industrial circulating cooling water system by damage/repair path-way profiling analysis. Environmental Toxicology and Pharmacology, 100, 104156.
Zhang, M., Jin, J., Liu, Y., Ben, C., Li, H., Cheng, D., Sun, Y., Guang-Yi, W., & Zhu, S. (2023). Analysis of povidone iodine, chlorhexidine acetate and poly-hexamethylene biguanide as wound disinfectants: In vitro cytotoxicity and anti-bacterial activity. BMJ Nutrition, Prevention and Health, 6(1), 21–27.
Alajlan, A. A., Mukhtar, L. E., Almussallam, A. S., Alnuqaydan, A. M., Albakiri, N. S., Almutari, T. F., Bin Shehail, K. M., Aldawsari, F. S., & Alajel, S. M. (2022). Assessment of disinfectant efficacy in reducing microbial growth. PLoS One, 17(6), e0269850.
Alturkistani, H. A., Tashkandi, F. M., & Mohammedsaleh, Z. M. (2015). Histologi-cal stains: A literature review and case study. Global Journal of Health Science, 8(3), 72–79.
AlZain, S. (2019). Effect of 0.5% glutaraldehyde disinfection on surface wettability of elastomeric impression materials. The Saudi Dental Journal, 31(1), 122–128.
Ambrosino, A., Pironti, C., Dell’Annunziata, F., Giugliano, R., Chianese, A., Moccia, G., DeCaro, F., Galdiero, M., Franci, G., & Motta, O. (2022). Investigation of biocidal efficacy of commercial disinfectants used in public, private and workplaces during the pandemic event of SARS-CoV-2. Scientific Reports, 12, 5468.
Ballantyne, B., & Myers, R. C. (2001). The acute toxicity and primary irritancy of glutaraldehyde solutions. Veterinary and Human Toxicology, 43(4), 193–202.
Beauchamp Jr., R. O., St Clair, M. B., Fennell, T. R., Clarke, D. O., Morgan, K. T., & Kari, F. W. (1992). A critical review of the toxicology of glutaraldehyde. Critical Reviews in Toxicology, 22(3–4), 143–174.
Brill, F. H. H., Becker, B., Todt, D., Steinmann, E., Steinmann, J., Paulmann, D., Bischoff, B., & Steinmann, J. (2020). Virucidal efficacy of glutaraldehyde for instrument disinfection. GMS GMS Hygiene and Infection Control, 15, 1–5.
Burgess, W., Margolis, A., Gibbs, S., Duarte, R. S., & Jackson, M. (2017). Disinfec-tant susceptibility profiling of glutaraldehyde-resistant nontuberculous myco-bacteria. Infection Control and Hospital Epidemiology, 38(7), 784–791.
Buzun, A. I., Stegniy, B. T., Paliy, A. P., Spivak, M. Y., Bogach, M. V., Stegniy, M. Y., Kuzminov, A. V., & Pavlichenko, O. V. (2023). Experimental epizotol-ogy of low virulent variants of African swine fever virus. Microbiological Jour-nal, 3, 71–87.
Chhetri, R. K., Baun, A., & Andersen, H. R. (2019). Acute toxicity and risk evalua-tion of the CSO disinfectants performic acid, peracetic acid, chlorine dioxide and their by-products hydrogen peroxide and chlorite. The Science of the Total Environment, 677, 1–8.
Dong, F., Chen, J., Li, C., Ma, X., Jiang, J., Lin, Q., Lin, C., & Diao, H. (2019). Evidence-based analysis on the toxicity of disinfection byproducts in vivo and in vitro for disinfection selection. Water Research, 165, 114976.
Francis, M. J. (2020). A veterinary vaccine development process map to assist in the development of new vaccines. Vaccine, 38(29), 4512–4515.
Frost, L., Tully, M., Dixon, L., Hicks, H. M., Bennett, J., Stokes, I., Marsella, L., Gubbins, S., & Batten, C. (2023). Evaluation of the efficacy of commercial dis-infectants against African swine fever virus. Pathogens, 12(7), 855.
Jantawong, C., Priprem, A., Intuyod, K., Pairojkul, C., Pinlaor, P., Waraasawapati, S., Mongkon, I., Chamgramol, Y., & Pinlaor, S. (2021). Curcumin-loaded nano-complexes: Acute and chronic toxicity studies in mice and hamsters. Toxicology Reports, 8, 1346–1357.
Karpenko, Y., Hunchak, Y., Gutyj, B., Hunchak, A., Parchenko, M., & Parchenko, V. (2022). Advanced research for physico-chemical properties and parameters of toxicity piperazinium 2-((5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio) acetate. ScienceRise: Pharmaceutical Science, 36, 18–25.
Kim, J., Park, C. M., Choi, S. H., Yang, M. J., Lee, J. Y., Jeon, B. S., Ku, H. O., & Kim, M. S. (2023). Assessment of acute inhalation toxicity of citric acid and sodium hypochlorite in rats. Journal of Veterinary Science, 24(2), e22.
Laingam, S., Froscio, S. M., Bull, R. J., & Humpage, A. R. (2012). In vitro toxicity and genotoxicity assessment of disinfection by-products, organic N-chloramines. Environmental and Molecular Mutagenesis, 53(2), 83–93.
Lee, H., & Park, K. (2019). Acute toxicity of benzalkonium chloride in Balb/c mice following intratracheal instillation and oral administration. Environmental Anal-ysis, Health and Toxicology, 34(3), e2019009.
Liao, C., Tian, L., Wang, Z., Zhu, X., Han, Y., Li, T., & Wang, X. (2023). Toxicity warning and online monitoring of disinfection by-products in water by elec-troautotrophic biocathode sensors. Biosensors and Bioelectronics, 219, 114799.
Lieshchova, M., & Brygadyrenko, V. (2022). Effects of Origanum vulgare and Scutellaria baicalensis on the physiological activity and biochemical parameters of the blood in rats on a high-fat diet. Scientia Pharmaceutica, 90(3), 49.
Lin, W., Niu, B., Yi, J., Deng, Z., Song, J., & Chen, Q. (2018). Toxicity and metal corrosion of glutaraldehyde-didecyldimethylammonium bromide as a disinfectant agent. BioMed Research International, 2018, 9814209.
Marxfeld, H. A., Küttler, K., Dammann, M., Gröters, S., & van Ravenzwaay, B. (2019). Body and organ weight data in 28-day toxicological studies in two mouse strains. Data in Brief, 27, 104632.
Montagna, M. T., Triggiano, F., Barbuti, G., Bartolomeo, N., De Giglio, O., Diella, G., Lopuzzo, M., Rutigliano, S., Serio, G., & Caggiano, G. (2019). Study on the in vitro activity of five disinfectants against nosocomial bacteria. International Journal of Environmental Research and Public Health, 16(11), 1895.
Musee, N., Ngwenya, P., Motaung, L. K., Moshuhla, K., & Nomngongo, P. (2023). Occurrence, effects, and ecological risks of chemicals in sanitizers and disinfec-tants: A review. Environmental Chemistry and Ecotoxicology, 5, 62–78.
Paliy, A. P. (2018). Differential sensitivity of mycobacterium to chlorine disinfec-tants. Mikrobiolohichnyi Zhurnal, 80(2), 104–116.
Park, K. (2016). An analysis of a humidifier disinfectant case from a toxicological perspective. Environmental Health and Toxicology, 31, e2016013.
Ren, Z., Yu, Y., Ramesh, M., Li, B., & Poopal, R. K. (2022). Assessment of eco-toxic effects of commonly used water disinfectant on zebrafish (Danio rerio) swimming behaviour and recovery responses: An early-warning biomarker approach. Environmental Science and Pollution Research International, 29(27), 41849–41862.
Rhee, C. H., Lee, H. S., Yun, H. J., Lee, G. H., Kim, S. J., Song, S., Lee, M. H., Her, M., & Jeong, W. (2023). Chemical stability of active ingredients in diluted vete-rinary disinfectant solutions under simulated storage conditions. Frontiers in Chemistry, 11, 1204477.
Rodionova, K., Paliy, A., & Кhimych, M. (2021). Veterinary and sanitary assess-ment and disinfection of refrigerator chambers of meat processing enterprises. Potravinarstvo, 15, 616–626.
Rozman, U., Pušnik, M., Kmetec, S., Duh, D., & Šostar Turk, S. (2021). Reduced susceptibility and increased resistance of bacteria against disinfectants: A syste-matic review. Microorganisms, 9(12), 2550.
Sagripanti, J. L., & Bonifacino, A. (2000). Cytotoxicity of liquid disinfectants. Sur-gical Infections, 1(1), 3–14.
Sehmi, S. K., Allan, E., MacRobert, A. J., & Parkin, I. (2016). The bactericidal activity of glutaraldehyde-impregnated polyurethane. Microbiology Open, 5(5), 891–897.
Seo, S. Y., Park, Y. H., Jung, S. K., & Kim, J. (2022). Acute toxicity evaluation of the disinfectant containing percarbonate and tetraacetylethylenediamine by measuring behavioral responses of small fish using image analysis. Biotechnology and Bioprocess Engineering, 27(4), 687–696.
Simmonds, R. C. (2017). Chapter 4. Bioethics and animal use in programs of research, teaching, and testing. In: Weichbrod, R. H., Thompson, G. A. H., Norton, J. N. (Eds.). Management of animal care and use programs in research, education, and testing. 2nd ed. CRC Press, Taylor & Francis, Boca Raton. Pp. 1–28.
Szunyogova, E., & Parson, S. H. (2016). Histological and histochemical methods, theory and practice. 5th ed. Journal of Anatomy, 228(5), 887.
Takigawa, T., & Endo, Y. (2006). Effects of glutaraldehyde exposure on human health. Journal of Occupational Health, 48(2), 75–87.
Thumtecho, S., Sriapha, C., Tongpoo, A., Udomsubpayakul, U., Wananukul, W., & Trakulsrichai, S. (2021). Poisoning of glutaraldehyde-containing products: Clinical characteristics and outcomes. Clinical Toxicology, 59(6), 480–487.
Tong, C., Hu, H., Chen, G., Li, Z., Li, A., & Zhang, J. (2021). Disinfectant resistance in bacteria: Mechanisms, spread, and resolution strategies. Environmental Re-search, 195, 110897.
Wang, J., & Hu, X. (2023). Factors influencing disease prevention and control behaviours of hog farmers. Animals, 13(5), 787.
Wang, Y., Wu, Q., Ren, B., Muskhelishvili, L., Davis, K., Wynne, R., Rua, D., & Cao, X. (2022). Subacute pulmonary toxicity of glutaraldehyde aerosols in a human in vitro airway tissue model. International Journal of Molecular Sciences, 23(20), 12118.
Yang, H., Li, X., Cao, X., Lu, S., & Zheng, X. (2023). The toxicity assessment of 14 biocides for industrial circulating cooling water system by damage/repair path-way profiling analysis. Environmental Toxicology and Pharmacology, 100, 104156.
Zhang, M., Jin, J., Liu, Y., Ben, C., Li, H., Cheng, D., Sun, Y., Guang-Yi, W., & Zhu, S. (2023). Analysis of povidone iodine, chlorhexidine acetate and poly-hexamethylene biguanide as wound disinfectants: In vitro cytotoxicity and anti-bacterial activity. BMJ Nutrition, Prevention and Health, 6(1), 21–27.
Published
2024-02-24
How to Cite
Paliy, A. P., Kovalenko, L. V., Rodionova, K. O., Pavlichenko, O. V., КhimychM. S., & Balta, M. P. (2024). Pathomorphological changes in laboratory animals exposed to lethal doses of disinfec-tants . Regulatory Mechanisms in Biosystems, 15(1), 107-112. https://doi.org/10.15421/022416
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