In vitro and in vivo acute toxicity of an artificial butter flavoring

References

• Almeida, A. A. C., V. R. Amorim, R. W. R. Sousa, R. B. F. Carvalho, and P. M. P. Ferreira. 2020b. Neurohormonal and behavioral actions of food additives. In: Translational Aspects of the Toxicodynamics of Food Additives. P. M. P. Ferreira, and J. A. Pereira-Freire (Eds.), pp. 82–105. doi: 10.22533/at.ed.9732009045.
   Google Scholar
• Almeida, A. A. C., J. R. O. Ferreira, R. B. F. Carvalho, M. S. Rizzo, L. S. Lopes, D. Dittz, J. M. C. Sousa, and P. M. P. Ferreira. 2020a. Non-clinical toxicity of (+)-limonene epoxide and its physio-pharmacological properties on neurological disorders. Naunyn Schmiedebergs Arch. Pharmacol. 393 (12):2301–14. doi:10.1007/s00210-020-01943-w.
   PubMed Web of Science ®Google Scholar
• Ansel, H. C., L. Allen, and N. G. Popovich. 2013. Formas Farmacêuticas e Sistemas de Liberação de Fármacos. 9th ad ed. Porto Alegre: Editora Artmed.
   Google Scholar
• Araújo, E. J. F., A. A. C. Almeida, O. A. Silva, I. H. F. Costa, L. M. Rezende-Júnior, F. C. A. Lima, A. J. Cavalheiro, C. Pessoa, M. O. Moraes, and P. M. P. Ferreira. 2017. Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors. J Ethnopharmacol 198:460–67. doi:10.1016/j.jep.2017.01.006.
   PubMed Web of Science ®Google Scholar
• Arcanjo, D. D. R., A. C. M. Albuquerque, B. Melo-Neto, L. C. L. R. Santana, M. G. F. Medeiros, and A. M. G. L. Citó. 2012. Bioactivity evaluation against Artemia salina Leach of medicinal plants used in Brazilian Northeastern folk medicine. Braz. J. Biol. 72 (3):505–09. doi:10.1590/s1519-69842012000300013.
   PubMed Web of Science ®Google Scholar
• Archer, J. 1973. Tests for emotionality in rats and mice: A review. Animal. Behav 21:205–35. doi:10.1016/S0003-3472(73)80065-X.
   PubMed Web of Science ®Google Scholar
• Boylstein, R., C. Piacitelli, A. Grote, R. Kanwal, G. Kullman, and K. Kreiss. 2006. Diacetyl emissions and airborne dust from butter flavourings used in microwave popcorn production. J Occup Environ Hyg 3 (10):530–35. doi:10.1080/15459620600909708.
   PubMedGoogle Scholar
• Brass, D. M., and S. M. Palmer. 2017. Models of toxicity of diacetyl and alternative diones. Toxicology 388:15–20. doi:10.1016/j.tox.2017.02.011.
   PubMed Web of Science ®Google Scholar
• Brazil. 2007a. Resolução da Diretoria Colegiada RDC nº 05, de 15 de janeiro de 2007, Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Brasília. http://www.anvisa.gov.br/legis/resol/2007/rdc/02_170107rdc.pdf.
   Google Scholar
• Brazil. 2007b. Boas práticas no uso de aditivos alimentares. Resolução N. 05. Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Poços de Caldas. http://www.anvisa.gov.br/legis/resol/2007/rdc/02_170107rdc.pdf/.
   Google Scholar
• Brazil. 2007c. Regulamento Técnico sobre Aditivo Aromatizante. RDC Nº 2 de 15 de janeiro de 2007. Diário Oficial da República Federativa do Brasil, Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Brasília.http://portal.anvisa.gov.br/documents/33916/391619/Anexo%2BRDC%2B2.pdf/84947fce-1b8f-4a2c-978e-2e23cf67f1/
   Google Scholar
• Brazil. 2012. Informe Técnico Nº 52/2012 GPESP/GGALI/ANVISA, 28 de novembro de 2012. Ministério da Saúde. Agência Nacional de Vigilância Sanitária. http://portal.anvisa.gov.br/documents/33916/388729/Informe+T%C3%A9cnico+n%C2%BA+52%2C+de+28+de+novembro+de+2012/8e1e812b-9ed6-4fc0-bd11-186c3c9f7bdf.
   Google Scholar
• Brazil. 2013. Guia para condução de estudos não clínicos de toxicologia e segurança farmacológica necessários ao desenvolvimento de medicamentos. Agência Nacional de Vigilância Sanitária (ANVISA). Brasília. http://portal.anvisa.gov.br/resultado-de-busca?p_p_id=101&p_p_lifecycle=0&p_p_state=maximized&p_p_mode=view&p_p_col_id=coumn1&p_p_col_count=1&_101_struts_action=%2Fasset_publisher%2Fview_content&_101_assetEntryId=352648&_101_type=document.
   Google Scholar
• Bustamante-Teixeira, M. T., F. Faerstein, and M. R. Latorre. 2002. Técnicas de análise de sobrevida. Cadernos de Saúde Pública 18 (3):579–94. doi:10.1590/S0102-311X2002000300003.
   PubMedGoogle Scholar
• Carocho, M., P. Morales, and I. C. F. R. Ferreira. 2015. Natural food additives: Quo vadis?. Trends Food Sci. Technol 45 (2):284–95. doi:10.1016/j.tifs.2015.06.007.
   Web of Science ®Google Scholar
• Carvalho, F. R. S., A. G. Moura, G. F. Rodrigues, N. M. F. Nunes, D. J. B. Lima, C. Pessoa, M. P. Costa, P. M. P. Ferreira, and A. P. Peron. 2016. Are salty liquid food flavorings in vitro antitumor substances? Anais da Academia Brasileira de Ciências 88 (3):1419–30. doi:10.1590/0001-3765201620150553.
   PubMed Web of Science ®Google Scholar
• Cazarin, K. C. C., C. L. Corrêa, and F. A. D. Zambrone. 2004. Redução, refinamento e substituição do uso de animais em estudos toxicológicos: uma abordagem atual. Revista Brasileira de Ciências Farmacêuticas 40 (3):289–99. doi:10.1590/S1516-93322004000300004.
   Google Scholar
• CDC (Center for Disease control and Prevention). 2017. The National Institute for Occupational Safety and Health (NIOSH). Exposures to Flavouring Chemicals. https://www.cdc.gov/niosh/topics/flavourings/exposure.html.
   Google Scholar
• Chen, X., Z. Zhang, H. Yang, P. Qiu, H. Wang, F. Wang, Q. Zhao, J. Fang, and J. Nie. 2020. Consumption of ultra-processed foods and health outcomes: A systematic review of epidemiological studies. Nutr J 19 (1):86. doi:10.1186/s12937-020-00604-1.
   PubMed Web of Science ®Google Scholar
• Colley, J., I. F. Gaunt, A. B. Lansdown, and P. Grasso P, and S. D. Gangolli. 1969. Acute and short-term toxicity of diacetyl in rats. Food Cosmet Toxicol 7:571–80. doi:10.1016/S0015-6264(69)80460-8.
   PubMedGoogle Scholar
• Curwin, B. D., J. A. Deddens, and L. T. Mckernan. 2015. Flavouring exposure in food manufacturing. J Expo Sci Environ Epidemiol 25 (3):324–33. doi:10.1038/jes.2014.52.
   PubMed Web of Science ®Google Scholar
• Dang, D. S., L. J. Bastarrachea, S. Martini, and S. K. Matarneh. 2021. Crystallization behavior and quality of frozen meat. Foods 10:2707. doi:10.3390/foods10112707.
   PubMed Web of Science ®Google Scholar
• Dong, Y. N., and S. Karboune. 2021. A review of bread qualities and current strategies for bread bioprotection: Flavor, sensory, rheological, and textural attributes. Compr. Rev. Food Sci. Food Saf 20 (2):1937–81. doi:10.1111/1541-4337.12717.
   PubMed Web of Science ®Google Scholar
• Effah, F., B. Taiwo, D. Baines, A. Bailey, and T. Marczylo. 2022. Pulmonary effects of e-liquid flavors: A systematic review. J. Toxicol. Environ. Health B 25 (7):343–71. doi:10.1080/10937404.2022.2124563.
   PubMed Web of Science ®Google Scholar
• EFSA (European Food Safeyt Authority). 2021. Feed additive applications: Overview and procedure. https://www.efsa.europa.eu/en/applications/feedadditives/regulationsandguidance.
   Google Scholar
• Elizabeth, L., P. Machado, M. Zinöcker, P. Baker, and M. Lawrence. 2020. Ultra-processed foods and health outcomes: A narrative review. Nutrients 12 (7):1955. doi:10.3390/nu12071955.
   PubMed Web of Science ®Google Scholar
• ERC (European Research Council). 2022. The health impact of food additives. https://erc.europa.eu/projects-statistics/stories/health-impact-food-additives.
   Google Scholar
• FAO Nutrition Meetings Report Series. 1968. No. 44. World Health Org. Techn. Rep. Ser 1968:383. https://inchem.org/documents/jecfa/jecmono/v44aje10.htm
   Google Scholar
• FAO/UN (Food and Agriculture Organization of the Unite Nations). 2022. Specifications for Flavourings. https://www.fao.org/food/food-safety-quality/scientific-advice/jecfa/jecfa-flav/details/en/c/314/.
   Google Scholar
• FAO/WHO (Food and Agriculture Organization of the World Health Organization). 2021. Food Standards, Codex Alimentarius and Food Additive Index. Updated up to the 44^th Session of the Codex Alimentarius Commission. https://www.fao.org/gsfaonline/additives/index.html.
   Google Scholar
• FDA (Food and Drug Administration). 2011. Overview and evaluation of proposed association between artificial food colors and attention deficit hyperactivity disorders (ADHD) and problem behaviors in children. Interim Toxicology Review Memorandum http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/FoodAdvisoryCommittee/UCM248113.pdf.
   Google Scholar
• FDA (Food and Drug Administration). 2022. Generally Recognized as Safe (GRAS). https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras.
   Google Scholar
• Fedan, J. S., J. A. Dowdy, K. B. Fedan, and A. F. Hubbs. 2006. Popcorn worker’s lung: In vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholine. Toxicol. Appl. Pharmacol. 215 (1):17–22. doi:10.1016/j.taap.2006.02.001.
   PubMed Web of Science ®Google Scholar
• Feingold, B. F. 1975. Why your child is Hyperactive. New York: Random House.
   Google Scholar
• Ferreira, P. M. P., P. M. Costa, A. M. Costa, D. J. B. Lima, R. R. Drumond, J. N. Silva, D. R. M. Moreira, G. B. O. Filho, J. M. Ferreira, M. G. R. Queiroz, et al. 2015. Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells. Anais da Academia Brasileira de Ciências 87 (1):313–30. doi:10.1590/0001-3765201520130345.
   PubMed Web of Science ®Google Scholar
• Ferreira, J. C., and C. M. Patino. 2016. What is survival analysis, and when should I use it? J Bras Pneumol 42 (1):77. doi:10.1590/S1806-37562016000000013.
   PubMed Web of Science ®Google Scholar
• Ferreira, P. M. P., and J. A. Pereira-Freire. 2020. Translational aspects of the Toxicodynamics of food additives. Ponta Grossa: Atena Editora. doi:10.22533/at.ed.973200904.
   Google Scholar
• Ferreira, P. M. P., D. B. Santos, J. N. Silva, A. F. Goudinho, C. L. S. Ramos, P. C. Souza, R. S. C. Almeida, D. S. Moura, R. Oliveira, C. K. Grisolia, et al. 2019. Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian Unified Health System (SUS). J Ethnopharmacol 241:112004. doi:10.1016/j.jep.2019.112004.
   PubMed Web of Science ®Google Scholar
• Ferreira, P. M. P., I. J. O. Sousa, K. N. Machado, L. A. Silva Neto, M. M. Freitas, I. L. Santos, D. C. N. Rodrigues, R. W. R. Sousa, A. C. Reis, M. L. L. B. Nascimento, et al. 2022. Antimitotic and toxicogenetic action of Stevia urticifolia aerial parts on proliferating vegetal and mammalian cells: In vitro and in vivo traditional and replacement methods. J. Toxicol. Environ. Health Part A 85 (18):750–66. doi:10.1080/15287394.2022.2081640.
   PubMed Web of Science ®Google Scholar
• Gad, S. C. 2014. “LD50/LC50 (Lethal Dosage 50/Lethal Concentration 50)”. In P. Wexler. Encyclopedia of Toxicology. 3th. Academic Press, pp. 58–60.10.1016/B978-0-12-386454-3.00867-8
   Google Scholar
• Gonzalez, R. S., K. G. Ribeiro, A. A. Santos, F. V. S. Medeiros, D. C. Souza, M. M. M. Marques, and A. P. Peron. 2021. Artificial almond flavouring additive: A potential toxic compound for the environment. Res. Soc. Dev 10 (4):e51810414203. doi:10.33448/rsd-v10i4.14203.
   Google Scholar
• Harrison, A. P., K. H. Erlwanger, V. S. Elbrønd, N. K. Andersen, and M. A. Unmack. 2004. Gastrointestinal-tract models and techniques for use in safety pharmacology. J. Pharmacol. Toxicol. Meth 49 (3):187–99. doi:10.1016/j.vascn.2004.02.008.
   PubMedGoogle Scholar
• Holden, V. K., and S. E. Hines. 2016. Update on flavoring-induced lung disease. Curr Opin Pulm Med 22 (2):158–64. PMID: 26761629. doi:10.1097/MCP.0000000000000250.
   PubMed Web of Science ®Google Scholar
• Houck, K. A., and R. J. Kavlock. 2008. Understanding mechanisms of toxicity: Insights from drug discovery research. Toxicol. Appl. Pharmacol. 227 (2):163–78. doi:10.1016/j.taap.2007.10.022.
   PubMed Web of Science ®Google Scholar
• Hubbs, A. F., A. M. Cumpston, W. T. Goldsmith, L. A. Battelli, M. L. Kashon, M. C. Jackson, D. G. Frazer, J. S. Fedan, M. P. Goravanahally, V. Castranova, et al. 2012. Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats? Am. J. Pathol. 181 (3):829–44. doi:10.1016/j.ajpath.2012.05.021.
   PubMed Web of Science ®Google Scholar
• Hubbs, A. F., W. T. Goldsmith, M. L. Kashon, D. Frazer, R. R. Mercer, L. A. Battelli, G. J. Kullman, D. Schwegler-Berry, S. Friend, and V. Castranova. 2008. Respiratory toxicologic pathology of inhaled diacetyl in Sprague-Dawley rats. Toxicol Pathol 36 (2):330–44. doi:10.1177/0192623307312694.
   PubMed Web of Science ®Google Scholar
• JECFA (Joint FAO/WHO Expert Committee on Food Additives). 2022. Evaluaciones químicas y técnicas de los aditivos alimentarios. https://www.fao.org/food/food-safety-quality/scientific-advice/jecfa/technical-assessments/es/.
   Google Scholar
• Kelly, F. L., J. Sun, B. M. Fischer, J. A. Voynow, A. B. Kummarapurugu, H. L. Zhang, J. L. Nugent, R. F. Beasley, T. Martinu, W. M. Gwinn, et al. 2014. Diacetyl induces amphiregulin shedding in pulmonary epithelial cells and in experimental bronchiolitis obliterans? Am. J. Respir. Cell Mol. Biol. 51 (4):568–74. doi:10.1165/rcmb.2013-0339OC.
   PubMed Web of Science ®Google Scholar
• Konishi, Y., S. Hayashi, and S. Fukushima. 2013. Regulatory forum opinion piece: Supporting the need for international harmonization of safety assessments for food flavouring substances. Toxicol Pathol 42 (6):949–53. doi:10.1177/0192623313495603.
   PubMed Web of Science ®Google Scholar
• Kreiss, K., A. Gomaa, G. Kullman, K. Fedan, E. J. Simoes, and P. L. Enright. 2002. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N. Engl. J. Med. 347 (5):330–38. doi:10.1056/NEJMoa020300.
   PubMed Web of Science ®Google Scholar
• Lane, M. M., J. A. Davis, S. Beattie, C. Gómez-Donoso, A. Loughman, A. O’neil, F. Jacka, M. Berk, R. Page, W. Marx, et al. 2021. Ultra-processed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies. Obes Rev 22 (3):e13146. doi:10.1111/obr.13146.
   PubMed Web of Science ®Google Scholar
• Langel, S. N., F. L. Kelly, D. M. Brass, A. E. Nagler, D. Camack, J. J. Tu, T. Travieso, R. Goswami, S. R. Perman, M. Blasi, et al. 2022. E-cigarette and food flavouring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2. Cell Death Discov 8 (1):1–11. doi:10.1038/s41420-022-00855-3.
   PubMed Web of Science ®Google Scholar
• LeBouf, R. F., B. H. Blackley, A. R. Fortner, M. Stanton, M. S. B. Martin, C. P. Groth, T. L. McClelland, M. G. Duling, D. A. Burns, A. Ranpara, et al. 2020. Exposures and emissions in coffee roasting facilities and cafés: Diacetyl, 2,3-pentanedione, and other volatile organic compounds. Front Public Health 8:561740. doi:10.3389/fpubh.2020.561740.
   PubMed Web of Science ®Google Scholar
• Libralato, G., E. Prato, L. Migliore, A. M. Cícero, and L. Manfra. 2016. A review of toxicity testing protocols and endpoints with Artemia spp. Ecol. Indicators 69:35–49. doi:10.1016/j.ecolind.2016.04.017.
   Web of Science ®Google Scholar
• Lister, R. G. 1987. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92 (2):180–85. doi:10.1007/BF00177912.
   PubMed Web of Science ®Google Scholar
• Litchfield, J. J. T., and F. A. Wilcoxon. 1949. A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther. 96 (2):99–113.
   PubMed Web of Science ®Google Scholar
• Mahon, C. P. C. A. N., E. M. Colodel, S. O. Balogun, R. G. Oliveira, and D. T. O. Martins. 2014. Toxicological evaluation of the hydroethanolic extract of Dilodendron bipinnatum Radlk. J Ethnopharmacol 155 (1):665–71. doi:10.1016/j.jep.2014.06.018.
   PubMed Web of Science ®Google Scholar
• Malone, M. H., and R. C. Robichaud. 1962. A Hippocratic screen for pure or crude drug materials. Llordya 25:320–31.
   Google Scholar
• Marques, G. S., S. I. O. Silva, J. M. C. Sousa, P. M. P. Ferreira, and A. P. Peron. 2015. Cytotoxicity and mutagenic potential of liquid synthetic food flavouring evaluated individually and in association. Food Sci. Technol 35 (1):183–88. doi:10.1590/1678-457X.6596.
   Google Scholar
• Martyny, J. W., M. V. Van Dyke, S. Arbuckle, M. Towle, and C. S. Rose. 2008. Diacetyl exposures in the flavor manufacturing industry. J Occup Environ Hyg 5 (11):679–88. doi:10.1080/15459620802368463.
   PubMed Web of Science ®Google Scholar
• McCann, D., A. Barrett, A. Cooper, D. Crumpler, L. Dalen, K. Grimshaw, E. Kitchin, K. Lok, L. Porteous, E. Prince, et al. 2007. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: A randomised, double-blinded, placebo-controlled trial. Lancet 370 (9598):1560–67. doi:10.1016/S0140-6736(07)61306-3.
   PubMed Web of Science ®Google Scholar
• McLaughlin, J. L., L. L. Rogers, and J. E. Anderson. 1988. The use of biological assays to evaluate botanicals. Drug Information J 32 (2):513–24. doi:10.1177/009286159803200223.
   Google Scholar
• Meigs, L., L. Smirnova, C. Rovida, M. Leist, and T. Hartung. 2018. Animal testing and its alternatives - the most important omics is economics. ALTEX 35:275–305. doi:10.14573/altex.1807041.
   PubMedGoogle Scholar
• Meyer, B., N. R. Ferrigni, J. E. Putnam, L. B. Jacobsen, D. E. Nichols, and J. L. McLaughlin. 1982. Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med. 45 (05):31–34. doi:10.1055/s-2007-971236.
   Web of Science ®Google Scholar
• Miller, M. S., J. J. Galligan, and T. F. Burks. 1981. Accurate measurement of intestinal transit in the rat. J. Pharmacol. Meth 6 (3):211–17. doi:10.1016/0160-5402(81)90110-8.
   PubMedGoogle Scholar
• Mittelstadt, S. W., C. L. Hemenway, and R. D. Spruell. 2005. Effects of fasting on evaluation of gastrointestinal transit with charcoal meal. J. Pharmacol. Toxicol. Meth 52 (1):154. doi:10.1016/j.vascn.2005.04.017.
   PubMedGoogle Scholar
• More, S. S., A. Raza, and R. Vince. 2012. The butter flavorant diacetyl, forms a covalent adduct with 2-deoxyguanosine, uncoils DNA, and leads to cell death. J. Agric. Food Chem. 60 (12):3311–17. doi:10.1021/jf300180e.
   PubMed Web of Science ®Google Scholar
• More, S. S., A. P. Vartak, and R. Vince. 2012. The butter flavorant, Diacetyl, Exacerbates β-Amyloid Cytotoxicity. Chem. Res. Toxicol. 25 (10):2083–91. doi:10.1021/tx3001016.
   PubMed Web of Science ®Google Scholar
• Morgan, D. L., G. P. Flake, P. J. Kirby, and S. M. Palmer. 2008. Respiratory toxicity of diacetyl in C57BL/6 mice. Toxicol. Sci. 103 (1):169–80. doi:10.1093/toxsci/kfn016.
   PubMed Web of Science ®Google Scholar
• Morgan, D. L., M. P. Jokinen, H. C. Price, W. M. Gwinn, S. M. Palmer, and G. P. Flake. 2012. Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: Implications for bronchiolitis obliterans in humans. Toxicol Pathol 40 (3):448–65. doi:10.1177/0192623311431946.
   PubMed Web of Science ®Google Scholar
• Neumann, I. D., G. Wegener, J. R. Homberg, H. Cohen, D. A. Slattery, J. Zohar, J. D. A. Olivier, and A. A. Mathé. 2011. Animal models of depression and anxiety: What do they tell us about human condition? Prog Neuropsychopharmacol 35 (6):1357–75. doi:10.1016/j.pnpbp.2010.11.028.
   Google Scholar
• Niu, Y., R. Wang, Z. Xiao, J. Zhu, X. Sun, and P. Wang. 2019. Characterization of ester odorants of apple juice by gas chromatography-olfactometry, quantitative measurements, odour threshold, aroma intensity and electronic nose. Food Res. Int. 120:92–101. doi:10.1016/j.foodres.2019.01.064.
   PubMed Web of Science ®Google Scholar
• Nunes, N. M. F., J. A. Pereira-Freire, J. N. Silva, and P. M. P. Ferreira. 2020. Pharmacotoxicological profile and damages in organicsystems. In Translational aspects of the Toxicodynamics of food additivesTranslational aspects of the Toxicodynamics of food additives, ed. P. M. P. Ferreira and J. A. Pereira-Freire, pp. 32–60. doi:10.22533/at.ed.9732009043.
   Google Scholar
• Nunes, R. D. M., I. M. S. Sales, S. I. O. Silva, J. M. C. Sousa, and A. P. Peron. 2017. Antiproliferative and genotoxic effects of nature identical and artificial synthetic food additives of aroma and flavor. Braz. J. Biol. 77 (1):150–54. doi:10.1590/1519-6984.12115.
   Web of Science ®Google Scholar
• OECD (Organisation for Economic Co-operation and Development). 2001. Test No. 423: Acute Oral Toxicity – Acute Toxic Class Method. https://www.oecd-ilibrary.org/environment/test-no-423-acute-oral-toxicity-acute-toxic-class-method_9789264071001-en.
   Google Scholar
• OECD (Organization for Economic Cooperation and Development). 2022. Guidelines for the Testing of Chemicals. https://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm.
   Google Scholar
• Oliveira, V. A., V. M. A. Oliveira, T. W. N. Oliveira, A. N. C. Damasceno, C. E. O. Silva, S. R. A. Medeiros, B. M. Soares, F. C. C. Silva, R. P. S. Aguiar, M. T. Islam, et al. 2017. Evaluation of cytotoxic and mutagenic effects of two artificial sweeteners by using eukaryotic test systems. Afr. J. Biotechnol 16 (11):547–51. doi:10.5897/AJB2016.15695.
   Google Scholar
• Pagliai, G., M. Dinu, M. P. Madarena, M. Bonaccio, L. Iacoviello, and F. Sofi. 2021. Consumption of ultra-processed foods and health status: A systematic review and meta-analysis. Br. J. Nutr. 125 (3):308–18. doi:10.1017/S0007114520002688.
   PubMed Web of Science ®Google Scholar
• Paula Neto, H. A., P. Ausina, L. S. Gomez, J. G. B. Leandro, P. Zancan, and M. Sola-Penna. 2017. Effects of food additives on immune cells as contributors to body weight gain and immune metabolic dysregulation. Front Immunol 8:1–11. doi:10.3389/fimmu.2017.01478.
   PubMed Web of Science ®Google Scholar
• Qian, M., and G. A. Reineccius. 2003. Quantification of aroma compounds in Parmigiano Reggiano cheese by a dynamic headspace gas chromatography-mass spectrometry technique and calculation of odor activity value. J. Dairy Sci. 86 (3):770–76. doi:10.3168/jds.S0022-0302(03)73658-3.
   PubMed Web of Science ®Google Scholar
• Qian, Y. L., A. YueQi, C. Shuang, and M. C. Qian. 2019. Characterization of Qingke liquor aroma from Tibet. J. Agric. Food Chem. 67 (50):13870–81. doi:10.1021/acs.jafc.9b05849.
   PubMed Web of Science ®Google Scholar
• Riemenschneider, W., and H. M. Bolt. 2005. Esters, Organic. In Ullmann’s encyclopedia of industrial chemistry. John Wiley & Sons. doi:10.1002/14356007.a09_565.
   Google Scholar
• Roberts, R., R. Callander, P. Duffy, M. Jacobsen, R. Knight, and A. Boobis. 2015. Target organ profiles in toxicity studies supporting human dosing: Does severity progress with longer duration of exposure? Regul. Toxicol. Pharmacol. 73 (3):737–46. doi:10.1016/j.yrtph.2015.10.021.
   PubMed Web of Science ®Google Scholar
• Rodgers, R. J., B. J. Cao, A. Dalvi, and A. Holmes. 1997. Animal models of anxiety: An ethological perspective. Braz. J. Med. Biol. Res 30 (3):289–304. doi:10.1590/s0100-879x1997000300002.
   PubMed Web of Science ®Google Scholar
• Rodrigues, J. V. L., L. C. Bertges, C. F. M. G. Pimentel, P. O. Neves, R. L. Bormann, J. Júnior, P. R. Nardelli, and G. C. Toledo. 2014. TRÂNSITO GASTROINTESTINAL DE Rattus norvegicus (Berkenhout, 1769) (Rodentia:Muridae) APÓS ADMINISTRAÇÃO DE TEGASERODE. GE Jornal Port. de Gastrenterologia 21 (4):138–46. doi:10.1016/j.jpg.2014.02.005.
   Google Scholar
• Saatloo, N. V., P. Sadighara, G. J. Khaniki, N. Ebrahimi, and S. Nabizadeh. 2015. Evaluating the interaction effects of using common synthetic food dyes and aspartame by Artemia salina toxicity test. J. Food Saf. Hyg 1:13–17.
   Google Scholar
• Sales, I. M. S., J. S. Barbosa, F. K. S. Santos, F. C. C. Silva, P. M. P. Ferreira, J. M. C. Sousa, and A. P. Peron. 2017a. Acute toxicity of grape, plum and orange synthetic food flavourings evaluated in in vivo test systems. Food Technol. Biotechnol 55 (1):131–37. doi:10.17113/ftb.55.01.17.4770.
   PubMed Web of Science ®Google Scholar
• Sales, I. M. S., F. K. S. Santos, J. M. C. Sousa, and A. P. Peron. 2017b. Toxicidade aguda em nível celular de aromatizantes de Biscoito e Tutti-frutti em associação. Multitemas 22 (51):253–67. doi:10.20435/multi.v22i51.1434.
   Google Scholar
• Sales, I. M. S., J. M. Silva, E. S. R. Moura, F. D. S. Alves, F. C. C. Silva, J. M. C. Sousa, and A. P. Peron. 2017c. Toxicity of synthetic flavourings, nature identical and artificial, to hematopoietic tissue cells of rodents. Braz. J. Biol. 78 (2):306–10. doi:10.1590/1519-6984.07716.
   PubMed Web of Science ®Google Scholar
• Shibamoto, T. 2014. Diacetyl: Occurrence, analysis and toxicity: A review. J. Agric. Food Chem. 62 (18):4048–53. doi:10.1021/jf500615u.
   PubMed Web of Science ®Google Scholar
• Silva, J. N., N. B. N. Monção, R. R. S. Farias, A. M. G. L. Citó, M. H. Chaves, M. R. S. Araújo, D. J. B. Lima, C. Pessoa, A. Lima, E. C. C. Araújo, et al. 2020. Toxicological, chemopreventive, and cytotoxic potentialities of rare vegetal species and supporting findings for the Brazilian Unified Health System (SUS). J. Toxicol. Environ. Health Part A 83 (13–14):525–45. doi:10.1080/15287394.2020.1780658.
   PubMed Web of Science ®Google Scholar
• Sjöstedt, N., F. Deng, O. Rauvala, T. Tepponen, and H. Kidron. 2017. Interaction of food additives with intestinal efflux transporters. Mol. Pharmacol. 14 (11):3824–33. doi:10.1021/acs.molpharmaceut.7b00563.
   Google Scholar
• Stevens, L. J., J. R. Burgess, M. A. Stochelski, and T. Kuczek. 2015. Amounts of artificial food dyes and added sugars in food and sweets commonly consumed. Clin. Pediatr 54 (4):309–21. doi:10.1177/0009922814530803.
   PubMed Web of Science ®Google Scholar
• Traesel, G. K., J. C. Souza, A. L. Barros, M. A. Souza, W. O. Schmitz, R. M. Muzzi, S. A. Oesterreich, and A. C. Arena. 2014. Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats. Food Chem. Toxicol. 74:320–25. doi:10.1016/j.fct.2014.10.026.
   PubMed Web of Science ®Google Scholar
• Walf, A. A., and C. A. Frye. 2007. The use of the elevated plus maze as an assay of anxiety-related behaviour in rodents. Nat Protoc 2 (2):322–28. doi:10.1038/nprot.2007.44.
   PubMed Web of Science ®Google Scholar
• Wang, B., J. Wang, L. Y. Xu, J. H. Zhang, N. S. Ai, and Y. P. Cao. 2020. Characterization of the key odorants in kurut with aroma recombination and omission studies. J. Dairy Sci. 103 (5):4164–73. doi:10.3168/jds.2019-17521.
   PubMed Web of Science ®Google Scholar
• Waterston, R. H., K. Lindblad-Toh, E. Birney, J. Rogers, J. F. Abril, P. Agarwal P, R. Agarwala R, R. Ainscough R, M. Alexandersson, P. An P, et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–62. doi:10.1038/nature01262.
   PubMed Web of Science ®Google Scholar
• Wei, C. -B., S. H. Liu, Y. G. Liu, L. L. Lv, W. X. Yang, and G. M. Sun. 2011. Characteristic aroma compounds from different pineapple parts. Molecules 16 (6):5104–12. doi:10.3390/molecules16065104.
   PubMed Web of Science ®Google Scholar
• Yang, Y., H. Zhong, T. Yang, C. Lan, and H. Zhu. 2021. Characterization of the key aroma compounds of a sweet rice alcoholic beverage fermented with Saccharomycopsis fibuligera. J Food Sci Technol 58 (10):3752–64. doi:10.1007/s13197-020-04833-4.
   PubMed Web of Science ®Google Scholar
• Zaccone, E. J., W. T. Goldsmith, M. J. Shimko, J. R. Wells, D. Schwegler-Berry, P. A. Willard, S. L. Case, J. A. Thompson, and J. S. Fedan. 2015. Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavouring agents. Toxicol. Appl. Pharmacol. 15 (3):542–49. doi:10.1016/j.taap.2015.10.004.
   Google Scholar
• Zaccone, Z. J., J. A. Thompson, D. S. Ponnoth, A. M. Cumpston, W. T. Goldsmith, M. C. Jackson, M. L. Kashon, D. G. Frazer, A. F. Hubbs, M. J. Shimko, et al. 2013. Popcorn flavoring effects on reactivity of rat airways in vivo and in vitro. J. Toxicol. Environ. Health Part A 76 (11):669–89. doi:10.1080/15287394.2013.796302.
   PubMed Web of Science ®Google Scholar
• Zengin, N., D. Yuzbasioglu, F. Unal, S. Yilmaz, and H. Aksov. 2011. The evaluation of the genotoxicity of two food preservatives: Sodium benzoate and potassium. Food Chem. Toxicol. 49 (4):736–39. doi:10.1016/j.fct.2010.11.040.
   Web of Science ®Google Scholar