Assessment of the toxicity of benzoic acid derivatives in the intragastric intake

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Abstract

Introduction. Benzoic acid and its numerous derivatives are widely used in all areas of chemical production. However, there is no information about the toxic properties of a large number of benzoic acid derivatives. The purpose of the study was to study the toxic properties of several derivatives of benzoic acids in intragastric intake in an experiment.

Material and methods. The following derivatives of benzoic acid were studied: 4-chlorobenzoic, 4-methoxybenzoic, p-acetoxybenzoic and 2-methoxy-5-sulfamoylbenzoic acids. The studies were performed on white laboratory rats; toxicity was studied in repeated experiments with the oral administration of substances. The condition of the animals was assessed by integrated parameters, indices of biochemical analyzes of blood serum, morphological data from a study of the liver, kidneys, heart, stomach, pancreas and thyroid glands.\

Results. According to toxicometric data, 4-chlorobenzoic acid is classified as moderately hazardous, hazard class III, 4-methoxybenzoic, p-acetoxybenzoic and 2-methoxy-5-sulfamoylbenzoic acids belong to hazard class IV (low hazard). Under the subchronic administration of all the studied compounds, there was a significant increase in urea concentration, aminotransferase activity, and a decrease in catalase activity, most pronounced in poisoning with 4-chlorobenzoic and 4-methoxybenzoic acids. Morphohistological studies confirmed the predominant effect of benzoic acid derivatives on the functioning of the hepatorenal system in the animals exposed to poisoning. Microscopically fatty liver dystrophy was observed, there was a diffuse proliferation of Kupffer cells. In the kidneys, the glomeruli were enlarged in size; the lumen of the Shumlyansky-Bowman’s capsule was narrowed as a result of swelling of the capillary endothelium.

Conclusion. Subchronic oral intake of 4-chlorobenzoic, 4-methoxybenzoic, p-acetoxybenzoic, and 2-methoxy-5-sulfamoylbenzoic acids leads to many disorders in the body, which are mainly of a common toxic nature with a predominant effect on the state of the hepatorenal system. The most pronounced organotoxic effect is manifested in the chlorine-containing derivative of benzoic acid - 4-chlorobenzoic acid. Due to the low toxicity of benzoic acids, chronic poisoning in the workplace is unlikely; it is possible only if the technological processes are disrupted.

About the authors

Larisa G. Gorokhova

Research Institute for Complex Problems of Hygiene and Occupational Diseases; Novokuznetsk Institute (Branch Campus) of the Kemerovo State University

Author for correspondence.
Email: ponomarikova@mail.ru
ORCID iD: 0000-0002-0545-631X
MD, Ph.D., leading researcher of the laboratory for molecular-genetic and experimental researches, Research Institue for
Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk, 654041, Russian Federation. Russian Federation

Nadezhda N. Mikhailova

Research Institute for Complex Problems of Hygiene and Occupational Diseases; Novokuznetsk Institute (Branch Campus) of the Kemerovo State University

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1127-6980
Russian Federation

Evgeniya V. Ulanova

Research Institute for Complex Problems of Hygiene and Occupational Diseases

Email: noemail@neicon.ru
ORCID iD: 0000-0003-2657-3862
Russian Federation

Tatyana K. Yadykina

Research Institute for Complex Problems of Hygiene and Occupational Diseases

Email: noemail@neicon.ru
ORCID iD: 0000-0001-7008-1035
Russian Federation

References

  1. Anurova M.N., Bakhrushina E.O., Demina N.B., Panteleeva E.S. Modern preservatives of microbiological stability (a review). Khimiko-farmatsevticheskiy zhurnal. 2019; 53(6): 54–61. (in Russian)
  2. Kolosova L.V., Gunar O.V. Efficacies of antimicrobial conservants of various nonsterile medicines for oral use. Khimiko-farmatsevticheskiy zhurnal. 2015; 49(9): 47–50. (in Russian)
  3. Abdukhakimov Zh.N.U., Akhatov Zh.Zh., Dzhuraev A.D. Amino derivatives of benzoic acid in the synthesis of derivatives of 1,2,3-triazoles. Molodezhnyy nauchnyy forum: estestvennye i meditsinskie nauki. 2017; (10): 30–3. (in Russian)
  4. Kumar A., Bansal D., Bajaj K., Sharma S., Srivastava V.K. Synthesis of some never derivatives of 2-amino benzoic acid as potent anti-inflammatory and analgesic agents. Bioorg Med Chem. 2003; 11(23): 5281–91. https://doi.org/10.1016/s0968-0896(03)00529-7
  5. Ivkin D.Yu., Karpov A.A., Dracheva A.V., Pitukhina N.N., Ivkina A.S., Buryakina A.V., et al. Effect of a benzoic acid derivative on the development of experimental chronic heart failure. Farmatsiya. 2016; 65(4): 49–52. (in Russian)
  6. Ukrainets I.V., Petrushova L.A., Dzyubenko S.P., Grinevich L.A., Sim G. Synthesis and Biological Properties of {[(4-Hydroxy-1-Methyl-2,2-Dioxido-1H-2,1-Benzothiazin-3-YL)Carbonyl]Amino}-Benzoic Acids and Their Derivatives. Khimiko-farmatsevticheskiy zhurnal. 2017; 51(7): 30–3. (in Russian)
  7. Rembovskiy V.R., Mogilenkova L.A. Classification of health state in workers subjected to chemical factor. Meditsina truda i promyshlennaya ekologiya. 2006; (11): 25–31. (in Russian)
  8. Rakhmanin Yu.A. Actualization of methodological problems of reglamentation of chemical pollutions on the environment. Gigiena i sanitariya. 2016; 95(8): 701–7. https://doi.org/10.18821/0016-9900-2016-95-8-701-707 (in Russian)
  9. Onishchenko G.G., Nikolaeva N.I., Khamidulina Kh.Kh., Filin A.S., Korolev A.A., Nikitenko E.I. Problems and prospects of training specialists in preventive toxicology. Gigiena i sanitariya. 2019; 98(8): 799–803. https://doi.org/10.18821/0016-9900-2019-98-8-799-803 (in Russian)
  10. Gorokhova L.G., Sosedova L.M., Martynova N.A. Preclinical study as a basis for hygienic regulation of benzofuran derivatives. Meditsina truda i promyshlennaya ekologiya. 2011; (7): 30–3. (in Russian)
  11. Sosedova L.M., Filippova T.M. The role of biosimulation in human chemical safety system. Ekologiya cheloveka. 2017; (7): 46–52. (in Russian)
  12. Gus’kova T.A., Khokhlov A.L., Romanov B.K. Safety of Drugs: from Pre-Clinic to Clinic. Monograph [Bezopasnost’ lekarstv: ot dokliniki k klinike. Monografiya]. Moscow–Yaroslavl’: Fotolayf; 2018. (in Russian)
  13. Gorokhova L.G., Bondarev O.I., Bugaeva M.S. Pathological aspects of chronic poisoning with fluoxetine. Vestnik sudebnoy meditsiny. 2013; 2(3): 35–8. (in Russian)
  14. Orlov A.I. Statistical models in medicine. Nauchnyy zhurnal KubGAU. 2016; 124(10): 1–30. (in Russian)
  15. Avdeeva O.I., Makarenko I.E., Makarova M.N., Shekunova E.V., Kashkin V.A., Makarov V.G. Harmonization studies of the acute toxicity in accordance with Russian and international requirements. Mezhdunarodnyy vestnik veterinarii. 2015; (1): 103–9. (in Russian)
  16. Karkishchenko N.N. Classic and alternative models in drug toxicology. Biomeditsina. 2006; (4): 1–23. (in Russian)
  17. Biryukova N.P., Rusakov S.V., Napalkova V.V. General principles of preclinical safety evaluation of pharmacological drugs for veterinary use. Veterinarnyy vrach. 2018; (1): 3–9. (in Russian)
  18. Gorokhova L.G., Martynova N.A. Experimental study of fluoxetine hepatotoxicity. In: Modern Problems of Occupational Medicine, Hygiene and Human Ecology: Materials of the XLVI Scientific-Practical Conference with International Participation «Hygiene, Healthcare Organization and Occupational Pathology» and the Seminar «Actual Issues of Modern Occupational Pathology» [Sovremennye problemy meditsiny truda, gigieny i ekologii cheloveka: Materialy XLVI nauchno-prakticheskoy konferentsii s mezhdunarodnym uchastiem «Gigiena, organizatsiya zdravookhraneniya i profpatologiya» i seminara «Aktual’nye voprosy sovremennoy profpatologii»]. Kemerovo: Primula; 2011: 24–7. (in Russian)
  19. Voloshchuk O.N., Kopyl’chuk G.P., Buchkovskaya I.M. Activity of the marker liver enzymes under the conditions of toxic hepatitis and alimentary deprivation of protein. Eksperimental’naya i klinicheskaya gastroenterologiya. 2014; (8): 96–100. (in Russian)
  20. Galatenko A.G. Simulation of toxic liver damage in small laboratory animals. Sovremennye aspekty sanatorno-kurortnogo lecheniya i reabilitatsii na etapakh okazaniya meditsinskoy pomoshchi detskomu i vzroslomu naseleniyu. 2017; (1): 158-70. (in Russian)
  21. Akbarkhodzhaeva Kh.N., Alimkhodzhaeva N.T., Tashkhodzhaeva A.A. Changes in the intensity of lipid peroxidation and the activity of antioxidant enzymes (SOD, catalase) in experimental rats with xenobiotic intoxication. Molodoy uchenyy. 2016; (10): 389-92. (in Russian)
  22. Solov’eva A.G., Peretyagin S.P. The effect of subchronic inhalations of nitric oxide on metabolic processes in blood of experimental animals. Biomeditsinskaya khimiya. 2016; 62(2): 212-4. (in Russian)
  23. Bakanov M.I. Liver. Biochemistry: physiology and pathology. Voprosy diagnostiki v pediatrii. 2010; 2(2): 12-9. (in Russian)
  24. Roslyy I.M., Vodolazhskaya M.G. Comparative approaches in assessing the state of humans and animals: a way to identify a common adaptive mechanism. Vestnik veterinarii. 2008; 2(45): 38-52. (in Russian)
  25. Medetkhanov F.A., Galimzyanov I.G., Nikitina E.A. Study of hepatoprotective properties of normotrophin in a model of acute toxic hepatitis in rats. Adv Agr Biol Sci. 2016; 2(5): 5-12. (in Russian)
  26. Badamshina G.G., Timasheva G.V., Bakirov A.B., Gil’manov A.Zh., Salyakhova R.M., Valeeva O.V. Laboratory markers of early metabolic violations at workers of a large chemical complex. Klinicheskaya laboratornaya diagnostika. 2014; 59(9): 129-30. (in Russian)
  27. Gorokhova L.G. Toxic and hygienic characteristics of the compounds of the benzofuran series with the risk assessment for workers’ health. Meditsina v Kuzbasse. 2019; 18(2): 58-69. (in Russian)

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