Effect of azodicarbonamide on rats with a high-fat hypercaloric diet
Keywords:
blowing agent, relative mass of the organs, biochemical indicators of blood, bodyweight increase, gut microbiotaAbstract
Azodicarbonamide is an important chemical widely used in the industry as a blowing agent in the foam industry and in the food industry as a flour bleaching agent and a dough conditioner. The discussion about its biosafety is ongoing, in a number of countries, the use of azodicarbonamide is limited or even prohibited since a slightly carcinogenic effect of its by-products has been found. Despite this, many manufacturers continue to use it as a food additive. In a laboratory experiment, the effect of various doses of azodicarbonamide on the organism of laboratory animals under the background of a high-fat diet was determined by changes in their body weight, the state and mass indices of internal organs, blood parameters, the functional state of the nervous system, and changes in the intestinal microbiota. Four groups were formed from laboratory male rats, which for 21 days were consuming: a high-fat diet with the addition of 4%, 1%, 0.25%, 0% azodicarbonamide. It has been determined that azodicarbonamide did not cause a change in the organ mass index, but the addition of 4% and 1% of the substance to the diet significantly reduced the intensity of animals' body weight gain. Both excess fat in the diet and different doses of azodicarbonamide mainly caused functional disorders of the parenchymal organs, as evidenced by changes in the activity of blood enzymes (Aspartate aminotransferase, Alanine aminotransferase, De Ritis ratio (AST/ALT), Alkaline phosphatase) and protein metabolism (Total protein, Globulins, Protein coefficient, Urea). Significant changes in the physical and orientation activity and emotional status of the animals were not observed. Low concentrations of azodicarbonamide (0.25% and 1% of the feed mass) caused a pronounced decrease in the number of normal enzymatic properties of Escherichia coli strains below the control group and the reference range, and a high concentration (4%) significantly reduced the number of Lactobacillus bacteria in comparison with the control one but did not exceed references.
References
Abramsson-Zetterberg, L., & Svensson, K. (2005). Semicarbazide is not genotoxic in the flow cytometry-based micronucleus assay in vivo. Toxicology Letters, 155(2), 211–217. https://doi.org/10.1016/j.toxlet.2004.09.019
Afrc, R. F. (1989). Probiotics in man and animals. Journal of Applied Bacteriology, 66(5), 365–378. https://doi.org/10.1111/j.1365-2672.1989.tb05105.x
Arts, J., & Kimber, I. (2017). Azodicarbonamide (ADCA): A reconsideration of classification as a respiratory sensitizer. Regulatory Toxicology and Pharmacology, 89, 268–278. https://doi.org/10.1016/j.yrtph.2017.07.018
Arts, J., & Kimber, I. (2018). Azodicarbonamide (ADCA): A reconsideration of classification as a respiratory sensitiser. Regulatory Toxicology and Pharmacology, 94, 332–333. https://doi.org/10.1016/j.yrtph.2018.01.011
Barnabás, S., & Miklós, S. (2005). Az éíelmiszerben képzodo szemikarbazid- maradékanyag mint a tiltott nitrofuráncsoportú nitrofurazon nem specifikus reziduummarkere [Semicarbazide-residue formed in foods, as non-specific marker of the prohibited nitrofurazone]. Magyar Allatorvosok Lapja, 127(3), 178–183.
Becalski, A. et al. (2006). Semicarbazide in Canadian bakery products. Food Additives and Contaminants, 23(2), 107–109. https://doi.org/10.1080/02652030500395219
Becalski, A. et al. (2004). Semicarbazide formation in azodicarbonamide-treated flour: A model study. Journal of Agricultural and Food Chemistry, 52(18), 5730–5734. https://doi.org/10.1021/jf0495385
Bechtold, W. E. et al. (1989). Azodicarbonamide: Methods for the analysis in tissues of rats and inhalation disposition. Xenobiotica, 19(9), 1003–1012. https://doi.org/10.3109/00498258909043157
Bilan, M. V. et al. (2019). Combined effect of glyphosate, saccharin and sodium benzoate on the gut microbiota of rats. Regulatory Mechanisms in Biosystems, 10(2), 228–232. https://doi.org/10.15421/021934
Bonsall, J. L. (1984). Allergic contact dermatitis to azodicarbonamide. Contact Dermatitis, 10(1), 42–49. https://doi.org/10.1111/j.1600-0536.1984.tb00060.x
Brygadyrenko, V. V. et al. (2019). Effect of alcohol tincture of Aralia elata on the organism of rats and their gut microbiota against the background of excessive fat diet. Regulatory Mechanisms in Biosystems, 10(4), 497–506. https://doi.org/10.15421/021973
Cañas, B. J. et al. (1997). Ethyl carbamate levels resulting from azodicarbonamide use in bread. Food Additives and Contaminants, 14(1), 89–94. https://doi.org/10.1080/02652039709374501
Che, W. et al. (2017). Application of visible/near-infrared spectroscopy in the prediction of azodicarbonamide in wheat flour. Journal of Food Science, 82(10), 2516–2525. https://doi.org/10.1111/1750-3841.13859
Chen, F. et al. (2021). Visual determination of azodicarbonamide in flour by label-free silver nanoparticle colorimetry. Food Chemistry, 337, 127990. https://doi.org/10.1016/j.foodchem.2020.127990
Chen, L. et al. (2016). Simultaneous detection of azodicarbonamide and the metabolic product semicarbazide in flour by capillary electrophoresis. Food Analytical Methods, 9(5), 1106–1111. https://doi.org/10.1007/s12161-015-0276-6
Cooper, K. M. et al. (2007). Enzyme immunoassay for semicarbazide – the nitrofuran metabolite and food contaminant. Analytica Chimica Acta, 592(1), 64–71. https://doi.org/10.1016/j.aca.2007.04.013
Dennis, M. J. et al. (1997a). The effect of azodicarbonamide concentrations on ethyl carbamate concentrations in bread and toast. Food Additives and Contaminants, 14(1), 95–100. https://doi.org/10.1080/02652039709374502
Dennis, M. J. et al. (1997b). The contribution of azodicarbonamide to ethyl carbamate formation in bread and beer. Food Additives and Contaminants, 14(1), 101–108. https://doi.org/10.1080/02652039709374503
Fagny, C. et al. (2002). Ribonucleotide reductase and thymidine phosphorylation: Two potential targets of azodicarbonamide. Biochemical Pharmacology, 64(3), 451–456. https://doi.org/10.1016/S0006-2952(02)01185-1
Ferris, B. G. et al. (1977). Apparent effect of an azodicarbonamide on the lungs: A preliminary report. Journal of Occupational Medicine, 19(6), 424–425.
Gafford, F. H. et al. (1971). Effect of azodicarbonamide (l, l’-azobisformamide) on thyroid function. Journal of Clinical Endocrinology and Metabolism, 32(5), 659–662. https://doi.org/10.1210/jcem-32-5-659
Gao, S., & Ru, S.-G. (2013). Research progress on the toxicity of semicarbazide. Research of Environmental Sciences, 26(6), 637–644.
Gerlach, R. F. et al. (1989). Effect of four‐week repeated inhalation exposure to unconjugated azodicarbonamide on specific and non‐specific airway sensitivity of the guinea pig. Journal of Applied Toxicology, 9(3), 145–153. https://doi.org/10.1002/jat.2550090303
Hanifarianty, S., & Fathurrohman, M. (2022). Evaluation of azodicarbonamide (ADC) on density, expansion ratio and closed cell properties of natural rubber foam. IOP Conference Series: Earth and Environmental Science, 974(1), 012123. https://doi.org/10.1088/1755-1315/974/1/012123
Hartwig, A. (2018). Azodicarbonamide [MAK Value Documentation, 2017]. The MAK-Collection for Occupational Health and Safety, 1034–1074. https://doi.org/10.1002/3527600418.mb12377e6318
Hirakawa, K. et al. (2003). Carcinogenic semicarbazide induces sequence-specific DNA damage through the generation of reactive oxygen species and the derived organic radicals. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 536(1–2), 91–101. https://doi.org/10.1016/s1383-5718(03)00030-5
Jaafar, H. A. S., & Sims, G. L. A. (1993). Thermal decomposition of azodicarbonamide (ADC). Cellular Polymers, 12(4), 303–316.
Joiner, R. R. et al. (1963). A new powdered agent for flour maturing. Cereal Chemistry, 40, 539–553.
Kim, C.-W. et al. (2004). Occupational asthma due to azodicarbonamide. Yonsei Medical Journal, 45(2), 325–329. https://doi.org/10.3349/ymj.2004.45.2.325
Krutko, I. et al. (2019). Kinetics of azodicarbonamide decomposition in the presence of an initiator for obtaining solid foams. Voprosy Khimii i Khimicheskoi Tekhnologii, 1, 26–34. https://doi.org/10.32434/0321-4095-2019-122-1-26-34
Lee, J. J. et al. (2018). Development of eco-friendly polymer foam using overcoat technology of deodorant. Materials, 11(10), 1898. https://doi.org/10.3390/ma11101898
Li, M. et al. (2015). Rapid and label-free Raman detection of azodicarbonamide with asthma risk. Sensors and Actuators, B: Chemical, 216, 535–541. https://doi.org/10.1016/j.snb.2015.04.103
Licht, T. R., & Bahl, M. I. (2019). Impact of the gut microbiota on chemical risk assessment. Current Opinion in Toxicology, 15, 109–113. https://doi.org/10.1016/j.cotox.2018.09.004
Lieshchova, M. A., & Brygadyrenko, V. V. (2021). Influence of Lavandula angustifolia, Melissa officinalis and Vitex angus-castus on the organism of rats fed with excessive fat-containing diet. Regulatory Mechanisms in Biosystems, 12(1), 169–180. https://doi.org/10.15421/022125
Lieshchova, M. A. et al. (2020). Effect of succinic acid on the organism of mice and their intestinal microbiota against the background of excessive fat consumption. Regulatory Mechanisms in Biosystems, 11(2), 153–161. https://doi.org/10.15421/022023
Lieshchova, M. A. et al. (2019). Impact of polyvinyl chloride, polystyrene, and polyethylene on the organism of mice. Regulatory Mechanisms in Biosystems, 10(1), 50–55. https://doi.org/10.15421/021908
Lieshchova, M. A. et al. (2018). Combined effect of glyphosphate, saccharin and sodium benzoate on rats. Regulatory Mechanisms in Biosystems, 9(4), 591–597. https://doi.org/10.15421/021888
Maranghi, F. et al. (2010). The food contaminant semicarbazide acts as an endocrine disrupter: Evidence from an integrated in vivo/in vitro approach. Chemico-Biological Interactions, 183(1), 40–48. https://doi.org/10.1016/j.cbi.2009.09.016
Maranghi, F. et al. (2009). Effects of the food contaminant semicarbazide following oral administration in juvenile Sprague–Dawley rats. Food and Chemical Toxicology, 47(2), 472–479. https://doi.org/10.1016/j.fct.2008.12.003
Medinsky, M. A. et al. (1990). Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures. Fundamental and Applied Toxicology, 15(2), 308–319. https://doi.org/10.1016/0272-0590(90)90057-q
Mewhinney, J. A. et al. (1987). The fate of inhaled azodicarbonamide in rats. Toxicological Sciences, 8(3), 372–381. https://doi.org/10.1093/toxsci/8.3.372
Molozhavaya, O. S. et al. (2016). Vlijanie fiziologicheskogo starenija organizma na mikrofloru zheludochno-kishechnogo trakta [Influence physiological aging on gastrointestinal microflora (Review paper)]. Aktual'nі Problemi Suchasnoi Medicini, 16(1), 304–313.
Nestmann, E. R. et al. (2005). Safety assessment and risk-benefit analysis of the use of azodicarbonamide in baby food jar closure technology: Putting trace levels of semicarbazide exposure into perspective – A review. Food Additives and Contaminants, 22(9), 875–891. https://doi.org/10.1080/02652030500195312
Noonan, G. O. et al. (2008). Semicarbazide formation in flour and bread. Journal of Agricultural and Food Chemistry, 56(6), 2064–2067. https://doi.org/10.1021/jf073198g
Normand, J.-C. et al. (1989). Occupational asthma after exposure to azodicarbonamide: Report of four cases. British Journal of Industrial Medicine, 46(1), 60–62. https://doi.org/10.1136/oem.46.1.60
Olofinnade, A. T. et al. (2020). An assessment of the effects of azodicarbonamide-containing diet on neurobehaviour, brain antioxidant status and membrane lipid peroxidation status in rats. Central Nervous System Agents in Medicinal Chemistry, 20(1), 49–57. https://doi.org/10.2174/1871524919666191104154009
Olofinnade, A. T. et al. (2021). Food-added azodicarbonamide alters haematogical parameters, antioxidant status and biochemical/histomorphological indices of liver and kidney injury in rats. Journal of Basic and Clinical Physiology and Pharmacology, 32(2), 39–50. https://doi.org/10.1515/jbcpp-2019-0341
Oser, B. L. et al. (1965). Studies of the safety of azodicarbonamide as a flour-maturing agent. Toxicology and Applied Pharmacology, 7(3), 445–472. https://doi.org/10.1016/0041-008X(65)90146-8
Pereira, A. S. et al. (2004). Implications of the use of semicarbazide as a metabolic target of nitrofurazone contamination in coated products. Food Additives and Contaminants, 21(1), 63–69. https://doi.org/10.1080/02652030310001647217
Rice, W. G. et al. (1997). Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein. Nature Medicine, 3(3), 341–345. https://doi.org/10.1038/nm0397-341
Salminen, S. et al. (1995). Gut flora in normal and disordered states. Chemotherapy, 41(1), 5–15. https://doi.org/10.1159/000239391
Shopp, G. M. et al. (1987). Acute inhalation exposure of azodicarbonarnide in the guinea pig. American Industrial Hygiene Association Journal, 48(2), 127–132. https://doi.org/10.1080/15298668791384517
Sims, G. L. A., & Jaafar, H. A. S. (1994). A chemical blowing agent system (CBAS) based on azodicarbonamide. Journal of Cellular Plastics, 30(2), 175–188. https://doi.org/10.1177/0021955X9403000205
Slovak, A. J. (1981). Occupational asthma caused by a plastics blowing agent, azodicarbonamide. Thorax, 36(12), 906–909. https://doi.org/10.1136/thx.36.12.906
Stehr, J. (2016). Chemical blowing agents in the rubber industry. Past – present – and future? International Polymer Science and Technology, 43(5), 812–819. https://doi.org/10.1177/0307174x1604300501
Suojalehto, H. et al. (2018). The classification of azodicarbonamide (ADCA) as a respiratory sensitiser; adding to the weight of evidence. Regulatory Toxicology and Pharmacology, 94, 330–331. https://doi.org/10.1016/j.yrtph.2018.01.006
Szilagyi, S. et al. (2006). Semicarbazide in baby food: A European survey. European Food Research and Technology, 224(1), 141–146. https://doi.org/10.1007/s00217-006-0296-y
Tassignon, J. et al. (1999). Azodicarbonamide inhibits T-cell responses in vitro and in vivo. Nature Medicine, 5(8), 947–950. https://doi.org/10.1038/11392
Tassignon, J. et al. (2001). Azodicarbonamide as a new T cell immunosuppressant: Synergy with cyclosporin A. Clinical Immunology, 100(1), 24–30. https://doi.org/10.1006/clim.2001.5041
Tian, L. et al. (2021). Progress in analytical methods for the determination of azodicarbonamide in wheat flour and its products. Shipin Kexue / Food Science, 42(9), 347–354. https://doi.org/10.7506/spkx1002-6630-20200507-073
Topsall, J. (1992). Basic laboratory procedures in clinical bacteriology. Pathology, 24(4), 321. https://doi.org/10.1016/s0031-3025(16)35813-5
Valentino, M., & Comai, M. (1985). Asma professionale da azodicarbonamide: Caso clinico [Occupational asthma from azodicarbonamide: Case report]. Giornale Italiano di Medicina del Lavoro, 7, 97–99.
Vlastos, D. et al. (2010). Evaluation of genotoxic effects of semicarbazide on cultured human lymphocytes and rat bone marrow. Food and Chemical Toxicology, 48(1), 209–214. https://doi.org/10.1016/j.fct.2009.10.002
Wang, X., & Zhao, C. (2021). Non-destructive quantitative analysis of azodicarbonamide additives in wheat flour by high-throughput raman imaging. Polish Journal of Food and Nutrition Sciences, 71(4), 403–410. https://doi.org/10.31883/pjfns/142879
Wang, X. et al. (2018). Near-infrared hyperspectral imaging for detection and quantification of azodicarbonamide in flour. Journal of the Science of Food and Agriculture, 98(7), 2793–2800. https://doi.org/10.1002/jsfa.8776
Wang, Y., & Chan, W. (2016). Automated in-injector derivatization combined with high-performance liquid chromatography-fluorescence detection for the determination of semicarbazide in fish and bread samples. Journal of Agricultural and Food Chemistry, 64(13), 2802–2808. https://doi.org/10.1021/acs.jafc.6b00651
Whitehead, L. W. et al. (1987). Respiratory symptoms associated with the use of azodicarbonamide foaming agent in a plastics injection molding facility. American Journal of Industrial Medicine, 11(1), 83–92. https://doi.org/10.1002/ajim.4700110109
Xing, Y.-N. et al. (2012). Semicarbazide in selected bird’s nest products. Journal of Food Protection, 75(9), 1654–1659. https://doi.org/10.4315/0362-028X.12-065
Yasui, A. et al. (2016). Analysis of azodicarbonamide in wheat flour and prepared flour mixes. Journal of the Food Hygienic Society of Japan, 57(5), 133–138. https://doi.org/10.3358/shokueishi.57.133
Ye, J. et al. (2011). Assessment of the determination of azodicarbonamide and its decomposition product semicarbazide: Investigation of variation in flour and flour products. Journal of Agricultural and Food Chemistry, 59(17), 9313–9318. https://doi.org/10.1021/jf201819x
Zauzi, N. S. A. et al. (2019). Foamability of natural rubber via microwave assisted foaming with azodicarbonamide (ADC) as blowing agent. Materials Today: Proceedings, 17, 1001–1007. https://doi.org/10.1016/j.matpr.2019.06.498
Zawadzki, M., & Maksymowicz, K. (2007). Podejrzenie zatrucia azodikarbonamidem u pacjenta z ostrym krwotocznym zapaleniem trzustki [Suspected azodicarbonamide poisoning in a patient with acute hemorrhaging pancreatitis]. Archiwum Medycyny Sa̧dowej i Kryminologii, 57(4), 430–432.
Zhang, L. et al. (2021). A colorimetric sensing platform for azodicarbonamide detection in flour based on MnO2 nanosheets oxidative system. Analytical and Bioanalytical Chemistry, 413(19), 4887–4894. https://doi.org/10.1007/s00216-021-03451-z
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