Analysis of Constituents Comprising Children's Toothpaste Products Available in Supermarkets

Abstract

Objective: Toothpaste stands as a paramount instrument in eradicating dental plaque and remains an intrinsic component of oral and dental hygiene regimens. The primary objective of this investigation is to scrutinize the constituents of children's toothpaste products accessible in the market and ascertain the prevalence of these components across various brands. Method: Five supermarkets located in Istanbul were surveyed, and children's toothpaste products displayed on the market shelves were incorporated in this research. The constituents of the toothpaste were documented in an Excel database. In order to gather relevant literature data pertaining to each component present in the toothpaste, Google Scholar, PubMed, and ScienceDirect databases were employed. The occurrence of each ingredient across all toothpaste brands was calculated as a percentage. Results: Fifteen different toothpaste products from six brands were identified on the market shelves. A total of 62 different components were found in these toothpaste products. Among these components, 47 were determined to have the potential to induce irritation, toxicity, or adverse effects on body and environmental tissues based on the literature. Sodium fluoride was found in different ppms among the toothpastes (n=3; ≥1450 ppm & n=1; 700 ppm); toothpastes also contained potentially harmful ingredients such as sodium saccharin, sodium lauryl sulfate (n=6; 40%), titanium dioxide (n=3; 20%), and paraben (n=2; 13.3%). Conclusion: The notable prevalence of diverse deleterious and unfavorable constituents in numerous toothpaste products represents a salient and disconcerting matter. Mitigating the utilization of these elements is not only imperative for oral and dental well-being but also pivotal for overall health and societal welfare.

Keywords

• Adverse effects
• Children
• Oral and dental health
• Toothpaste ingredients
• Toxicology

Marketlerden Satın Alınabilecek Çocuk Diş Macunlarını Oluşturan Bileşenlerin Analizi

Öz

Amaç: Diş macunu, diş plağını temizlemede en önemli araçlardan biridir ve ağız ve diş hijyeni uygulamalarının ayrılmaz bir parçasıdır. Bu çalışmanın amacı, piyasada bulunan çocuk diş macunlarının içeriklerini incelemek ve bu içeriklerin macunlar arasındaki yaygınlıklarını belirlemektir. Yöntem: İstanbul’daki beş süpermarket ziyaret edilerek market raflarında yer alan çocuk diş macunları bu çalışmanın kapsamına alındı. Diş macunu içerikleri bir Excel veritabanında kaydedildi. Diş macunu oluşturan her bileşene ait literatür verilerini derlemek için Google Scholar, PubMed ve ScienceDirect veritabanları kullanıldı. Her bir içeriğin tüm diş macunlarına arasındaki bulunma oranı yüzde cinsinden belirlendi. Bulgular: Market raflarında 6 diş macunu markasına ait 15 farklı isimde diş macunu tespit edildi. Bu diş macunlarını oluşturan toplamda 62 farklı bileşen belirlendi. 62 bileşenden 47 tanesinin literatüre göre vücut ve çevre dokular için iritan, toksik veya yan etki oluşturabileceği belirlendi. Sodyum florürün diş macunları arasında farklı ppmlerde bulunduğu (n=3; ≥1450 ppm & n=1; 700 ppm); sodyum sakkarin, sodyum lauril sülfat (n=6; %40), titanyum dioksit (n=3; %20) ve paraben (n=2; %13,3) gibi olumsuz etki oluşturabilecek bileşenlerin de diş macunlarının içeriğinde yer aldığı saptandı. Sonuç: Çoğu diş macununun zararlı ve olumsuz etkiler oluşturabilecek çeşitli bileşenler içermesi kayda değer ve dikkat çekici bir durum olup; bu içeriklerin kullanımının mümkün olduğunca azaltılması sadece ağız diş sağlığı değil, genel sağlık ve toplum sağlığı açısından da önem arz etmektedir.

Anahtar Kelimeler

• Ağız diş sağlığı
• Çocuk diş macunu
• Diş macunu içeriği
• Toksikoloji
• Yan etki

Kaynakça

1. 1. Wright JT, Hanson N, Ristic H, Whall CW, Estrich CG, Zentz RR. Fluoride toothpaste efficacy and safety in children younger than 6 years: a systematic review. The Journal of the American Dental Association 2014; 145(2):182–9.
2. 2. Paraskevas S. Randomized controlled clinical trials on agents used for chemical plaque control. Int J Dent Hyg 2005; 3(4):162–78.
3. 3. Löe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol 1965; 36(3):177–87.
4. 4. Üçüncü MK, Yıldız SÖ, Ulukapı H. Dental Kaygı ve Ağız Hijyeni Farkındalığı Arasındaki İlişkinin Belirlenmesi. Balıkesir Sağlık Bilimleri Dergisi 2023; 12(2):227–37.
5. 5. Bulut ÖE. Diş hekimliği pratiğini ilgilendiren infeksiyöz hastalıklar. 4. Ulusal Sterilizasyon Dezenfeksiyon Kongresi, Ankara. 2005; 154:166.
6. 6. Lippert F. An introduction to toothpaste - its purpose, history and ingredients. Monogr Oral Sci 2013; 23:1-14.
7. 7. Ghapanchi J, Kamali F, Moattari A, Poorshahidi S, Shahin E, Rezazadeh F, Khorshidi H, Jamshidi S. In vitro comparison of cytotoxic and antibacterial effects of 16 commercial toothpastes. J Int Oral Health 2015; 7(3):39–43.
8. 8. Zohoori FV, Duckworth RM, Omid N, O’Hare WT, Maguire A. Fluoridated toothpaste: usage and ingestion of fluoride by 4‐to 6‐yr‐old children in E ngland. Eur J Oral Sci 2012; 120(5):415–21.

9. 9. Ak AT, Aksoy H, Özdaş DÖ. Türk ailelerinin florlu diş macunu ve topikal flor uygulamaları hakkında bilgi ve görüşlerinin değerlendirilmesi: Pilot çalışma. Ege Üniversitesi Dişhekimliği Fakültesi Dergisi 2018; 39(3):160–4.
10. 10. Mani A, Thawani V. Are all additives of toothpastes rational? Journal of Mahatma Gandhi Institute of Medical Sciences 2019; 24(2):71-4.
11. 11. Rolo D, Assunção R, Ventura C, Alvito P, Gonçalves L, Martins C, Bettencourt A, Jordan P, Vital N, Pereira J, Pinto F, Matos P, Silva MJ, Louro H. Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review. Nanomaterials 2022; 12(19):3275.
12. 12. Radzki D, Wilhelm-Węglarz M, Pruska K, Kusiak A, Ordyniec-Kwaśnica I. A Fresh Look at Mouthwashes-What Is Inside and What Is It for? Int J Environ Res Public Health 2022; 19(7):3926.
13. 13. Kazak EÖ, Koçak İH, Özaktaş E, Kocaman E, Kurdoğlu B, Özkan N. Rekabet Kurulu,https://www.rekabet.gov.tr/Dosya/geneldosya/htmperakendeciligisektorincelemesionraporu-pdf. 2021. p. 1–144 FMCG Retail Industry Review in Türkiye, Ankara.
14. 14. Jardim JJ, Alves LS, Maltz M. The history and global market of oral home-care products. Braz Oral Res 2009; 23:17–22.
15. 15. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T, Murray CJ, Marcenes W, GBD 2015 Oral Health Collaborators. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990–2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res 2017; 96(4):380–7.
16. 16. Tadjoedin FM, Fitri AH, Kuswandani SO, Sulijaya B, Soeroso Y. The correlation between age and periodontal diseases. Journal of International Dental and Medical Research 2017; 10(2):327.
17. 17. Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. The Scientific World Journal. 2020;2020:2146160.
18. 18. Tezel A, Alkan A, Orhan AI, Orhan K. Türkiye Ağız Diş Sağlığı Profili Araştırma Raporu 2018 [Internet]. Ankara; 2021 [cited 2022 Dec 9]. Available from: https://shgm.saglik.gov.tr/Eklenti/42552/0/tadsppdf.pdf?_tag1=398CC88DDD02EA768C966A034ACC5F05F6CEB732
19. 19. Nissen M, Sander V, Vahdad MR, Thränhardt R, Tröbs RB. Toothpaste-Ingestion in a 4-Year-Old Girl–A Bagatelle Incident? Klin Padiatr 2017; 229(01):46–7.
20. 20. Bentley EM, Ellwood RP, Davies RM. Fluoride ingestion from toothpaste by young children. Br Dent J 1999; 186(9):460–2.
21. 21. Cury JA, Tenuta LMA. Evidence-based recommendation on toothpaste use. Braz Oral Res 2014; 28:1–7.
22. 22. Klein H, Palmer CE, Knutson JW. Studies on dental caries: I. Dental status and dental needs of elementary school children. Public Health Reports (1896-1970). 1938; 751–65.
23. 23. Namal N, Ertemvehid H, Vehid S, Can G. Altı-on iki yaş grubu çocukların diş sağlığını etkileyen anneye ait faktörlerin araştırılması. Çocuk Dergisi 2009; 9(3):123–6.
24. 24. İlisulu C, Hızlıoğlu Ö, Koruyucu M, Özkurt S, Bolat E, Seymen F. Diş Çürüğü Deneyimi ile Ergenler ve Anneler arasındaki Tutarlılık Duygusu İlişkisinin Saptanması. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 2020; 10(3):338–42.
25. 25. Yıldız E, Şimşek M, Gündoğar Z, Aktan AM. Oral health survey of children referring to Faculty of Dentistry in Gaziantep: Gaziantep Diş Hekimliği Fakültesi’ne başvuran çocukların ağız ve diş sağlığı düzeyi. European Journal of Therapeutics 2015; 21(2):118–24.
26. 26. Marsh PD. Microbiology of dental plaque biofilms and their role in oral health and caries. Dental Clinics 2010; 54(3):441–54.
27. 27. Brown LJ, Wall TP, Lazar V. Trends in total caries experience: permanent and primary teeth. The Journal of the American Dental Association 2000; 131(2):223–31.
28. 28. Marinho VCC. Cochrane reviews of randomized trials of fluoride therapies for preventing dental caries. European Archives of Paediatric Dentistry 2009; 10:183–91.
29. 29. Walsh T, Hv W, Am G, Appelbe P, Vcc M, Shi X. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD007868. Cochrane Database of Systematic Reviews 2010; (1):CD007868.
30. 30. Küçükeşmen Ç, Sönmez H. Dişhekimliğinde florun, insan vücudu ve dişler üzerindeki etkilerinin değerlendirilmesi. SDÜ Tıp Fakültesi Dergisi 2008; 15(3):43–53.
31. 31. Chi DL. Caregivers who refuse preventive care for their children: the relationship between immunization and topical fluoride refusal. Am J Public Health 2014; 104(7):1327–33.
32. 32. Milgrom P, Horst JA, Ludwig S, Rothen M, Chaffee BW, Lyalina S, Pollard KS, DeRisi JL, Mancl L. Topical silver diamine fluoride for dental caries arrest in preschool children: A randomized controlled trial and microbiological analysis of caries associated microbes and resistance gene expression. J Dent 2018; 68:72–8.
33. 33. Zuo H, Chen L, Kong M, Qiu L, Lü P, Wu P, Yang Y, Chen K. Toxic effects of fluoride on organisms. Life Sci 2018; 198:18–24.
34. 34. Paszynska E, Pawinska M, Gawriolek M, Kaminska I, Otulakowska-Skrzynska J, Marczuk-Kolada G, Rzatowski S, Sokolowska K, Olszewska A, Schlagenhauf U, May TW, Amaechi BT, Luczaj-Cepowicz E. Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial. Sci Rep 2021; 11(1):2650.
35. 35. American Academy of Pediatric Dentistry. Fluoride Therapy. Last Version. 2023 [cited 2023 Jul 13]. Available from: https://www.aapd.org/media/Policies_Guidelines/BP_FluorideTherapy.pdf
36. 36. Tateyama-Makino R, Abe-Yutori M, Iwamoto T, Tsutsumi K, Tsuji M, Morishita S, Kurita K, Yamamoto Y, Nishinaga E, Tsukinoki K. The inhibitory effects of toothpaste and mouthwash ingredients on the interaction between the SARS-CoV-2 spike protein and ACE2, and the protease activity of TMPRSS2 in vitro. PLoS One 2021; 16(9):e0257705.
37. 37. Jelinska A, Zagozdzon A, Recki MG, Wisniewska A, Frelek J, Holyst R. Denaturation of proteins by surfactants studied by the taylor dispersion analysis. PLoS One 2017; 12(4):e0175838.
38. 38. Ohbu K, Jona N, Miyajima N, Mizushima N, Kashiwa I. Evaluation of Denaturation Property of Surfactants onto Protein as Measured by Circular Dichroism. Journal of Japan Oil Chemists’ Society 1980; 29(11):866-71.
39. 39. Tadin A, Gavic L, Govic T, Galic N, Zorica Vladislavic N, Zeljezic D. In vivo evaluation of fluoride and sodium lauryl sulphate in toothpaste on buccal epithelial cells toxicity. Acta Odontol Scand 2019; 77(5):386-93.
40. 40. Nikolaou A, Golfinopoulos SK. The occurrence of" red" substances in" green" household products: A preliminary investigation. CEST 2017 15th International Conference on Environmental Science and Technology Rhodes, [Internet]. 2017 [cited 2022 Nov 16]; Available from: https://cest2017.gnest.org/sites/default/files/presentation_file_list/cest2017_00586_poster_paper.pdf.
41. 41. Moore C, Addy M, Moran J. Toothpaste detergents: a potential source of oral soft tissue damage? Int J Dent Hyg 2008; 6(3):193–8.
42. 42. Benassi L, Bertazzoni G, Seidenari S. In vitro testing of tensides employing monolayer cultures: a comparison with results of patch tests on human volunteers. Contact Dermatitis 1999; 40(1):38–44.
43. 43. Rantanen I, Tenovuo J, Pienihakkinen K, Soderling E. Effects of a betaine-containing toothpaste on subjective symptoms of dry mouth: a randomized clinical trial. J Contemp Dent Pract 2003; 4(2):11–23.
44. 44. Söderling E, Le Bell A, Kirstilä V, Tenovuo J. Betaine-containing toothpaste relieves subjective symptoms of dry mouth. Acta Odontol Scand 1998; 56(2):65–9.
45. 45. Cvikl B, Lussi A. Supragingival Biofilm: Toothpaste and Toothbrushes. In: Monographs in Oral Science [Internet]. 2020. p. 65–73. Available from: https://www.karger.com/DOI/10.1159/000510201.
46. 46. Anand SP, Sati N. Artificial preservatives and their harmful effects: looking toward nature for safer alternatives. Int J Pharm Sci Res 2013; 4(7):2496–501.
47. 47. Mazur M, Ndokaj A, Bietolini S, Nisii V, Duś-Ilnicka I, Ottolenghi L. Green dentistry: Organic toothpaste formulations. A literature review. Dent Med Probl 2022; 59(3):461–74.
48. 48. Ahn GS, Park YD, Yoo SM. The exposure amount of paraben from commercial toothpaste. International Journal of Clinical Preventive Dentistry 2014; 10(1):31–6.
49. 49. Soni MG, Carabin IG, Burdock GA. Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food and chemical toxicology 2005; 43(7):985–1015.
50. 50. Qiu Z, Wei F, Sun J, Niu Y, Mei Q, Wei B, An Z, Bo X, Xie J, He M. Theoretical Study of Ozonation of Methylparaben and Ethylparaben in Aqueous Solution. Journal of Physical Chemistry A 2020; 124(52):10967-76.
51. 51. Kim S, Lee S, Shin C, Lee J, Kim S, Lee A, Park J, Kho Y, Moos RK, Koch HM, Kim S, Choi K. Urinary parabens and triclosan concentrations and associated exposure characteristics in a Korean population-A comparison between night-time and first-morning urine. Int J Hyg Environ Health 2018; 221(4):632-41.
52. 52. Tabatabaei MH, Mahounak FS, Asgari N, Moradi Z. Cytotoxicity of the ingredients of commonly used toothpastes and mouthwashes on human gingival fibroblasts. Front Dent 2019; 16(6):450-57.
53. 53. Burnett CL, Heldreth B, Bergfeld WF, Belsito D V, Hill RA, Klaassen CD, Liebler DC, Marks Jr JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA. Safety Assessment of PEGylated oils as used in cosmetics. Int J Toxicol 2014; 33(4_suppl):13S-39S.
54. 54. Müller HD, Eick S, Moritz A, Lussi A, Gruber R. Cytotoxicity and Antimicrobial Activity of Oral Rinses in Vitro. Biomed Res Int 2017; 2017:4019723.
55. 55. Kojima H, Nakada T, Yagami A, Todo H, Nishimura J, Yagi M, Yamamoto K, Sugiyama M, Ikarashi Y, Sakaguchi H, Yamaguchi M, Hirota M, Aizawa S, Nakagawa S, Hagino S, Hatao M. A step-by-step approach for assessing acute oral toxicity without animal testing for additives of quasi-drugs and cosmetic ingredients. Curr Res Toxicol 2022; 4:100100.
56. 56. Di Marzio L, Esposito S, Rinaldi F, Marianecci C, Carafa M. Polysorbate 20 vesicles as oral delivery system: In vitro characterization. Colloids Surf B Biointerfaces 2013; 104:200–6.
57. 57. Dimitrijevic D, Shaw AJ, Florence AT. Effects of Some Non-ionic Surfactants on Transepithelial Permeability in Caco-2 Cells. Journal of Pharmacy and Pharmacology 2000; 52(2):157–62.
58. 58. Baan RA. Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers: Recent evaluations by an IARC Monographs Working Group. In: Inhalation Toxicology 2007; 19(Suppl 1):213-28.
59. 59. Rompelberg C, Heringa MB, van Donkersgoed G, Drijvers J, Roos A, Westenbrink S, Peters R, van Bemmel G, Brand W, Oomen AG. Oral intake of added titanium dioxide and its nanofraction from food products, food supplements and toothpaste by the Dutch population. Nanotoxicology 2016; 10(10):1404-14.
60. 60. Chung KT. Azo dyes and human health: A review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2016; 34(4):233-61.
61. 61. Karimi-Maleh H, Darabi R, Shabani-Nooshabadi M, Baghayeri M, Karimi F, Rouhi J, Alizadeh M, Karaman O, Vasseghian Y, Karaman C. Determination of D&C Red 33 and Patent Blue V Azo dyes using an impressive electrochemical sensor based on carbon paste electrode modified with ZIF-8/g-C3N4/Co and ionic liquid in mouthwash and toothpaste as real samples. Food and Chemical Toxicology 2022; 162:112907.
62. 62. Ragusa A, Svelato A, Santacroce C, Catalano P, Notarstefano V, Carnevali O, Papa F, Rongioletti MCA, Baiocco F, Draghi S, D’Amore E, Rinaldo D, Matta M, Giorgini E. Plasticenta: First evidence of microplastics in human placenta. Environ Int 2021; 146:106274.
63. 63. Hasan MA, Hashim ST, Abid SE, Bajlan JS. Determination of the concentration of food azo dyes by high performance liquid chromatography (HPLC). Curr Res Microbiol Biotechnol 2018; 6(1):1460–5.
64. 64. Field SQ. Why There’s Antifreeze in Your Toothpaste: The Chemistry of Household Ingredients. Chicago review press; 2007; 43–4.
65. 65. Timm-Knudson VL, Johnson JS, Ortiz KJ, Yiannias JA. Allergic contact dermatitis to preservatives. Dermatol Nurs 2006; 18(2):130.
66. 66. Pizzey RL, Marquis RE, Bradshaw DJ. Antimicrobial effects of o‐cymen‐5‐ol and zinc, alone & in combination in simple solutions and toothpaste formulations. Int Dent J 2011; 61:33–40.
67. 67. Andersen A. Final report on the safety assessment of sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol, Chlorothymol, Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, o-Cymen-5-ol, and Carvacrol. Int J Toxicol 2006; 25(Suppl 1):29-127.
68. 68. Lavender SA, Petrou I, Heu R, Stranick MA, Cummins D, Kilpatrick-Liverman L, Sullivan RJ, Santarpia 3rd RP. Mode of action studies of a new desensitizing dentifrice containing 8.0% arginine, a high cleaning calcium carbonate system and 1450 ppm fluoride. Am J Dent 2010; 23(Special Issue):14A-19A.
69. 69. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. In: Journal of Nutrition 2007; 137(6 Suppl 2):1693S-1701S.
70. 70. Carda-Diéguez M, Moazzez R, Mira A. Functional changes in the oral microbiome after use of fluoride and arginine containing dentifrices: a metagenomic and metatranscriptomic study. Microbiome 2022; 10(1):1–20.
71. 71. Schmidt S. Mouthwashes and gargles: oral health. SA Pharmacist’s Assistant 2015; 15(3):8–10.
72. 72. Johnson W, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA. Safety Assessment of Benzyl Alcohol, Benzoic Acid and its Salts, and Benzyl Benzoate. Int J Toxicol 2017; 36(3_suppl):5S-30S.
73. 73. Flury M, Flühler H. Brilliant Blue FCF as a Dye Tracer for Solute Transport Studies-A Toxicological Overview. J Environ Qual 1994; 23(5):1108-12.
74. 74. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020; 323(11):1061–9.
75. 75. Uddin F. Clays, nanoclays, and montmorillonite minerals. Metallurgical and Materials Transactions A 2008; 39(12):2804–14.
76. 76. Miranda-Bermudez E, Harp BP, Barrows JN. Qualitative identification of permitted and non-permitted color additives in cosmetics. J AOAC Int 2014; 97(4):1039–47.
77. 77. Sullivan RJ, Masters J, Cantore R, Roberson A, Petrou I, Stranick M, Goldman H, Guggenheim B, Gaffar A. Development of an enhanced anticaries efficacy dual component dentifrice containing sodium fluoride and dicalcium phosphate dihydrate. Am J Dent 2001; 14:3A-11A.
78. 78. Brighenti FL, Delbem ACB, Buzalaf MAR, Oliveira FAL, Ribeiro DB, Sassaki KT. In vitro evaluation of acidified toothpastes with low fluoride content. Caries Res 2006; 40(3):239–44.
79. 79. Lu Y. Humectancies of d‐tagatose and d‐sorbitol. Int J Cosmet Sci 2001; 23(3):175–81.
80. 80. Self RL. Direct analysis in real time-mass spectrometry (DART-MS) for rapid qualitative screening of toxic glycols in glycerin-containing products. J Pharm Biomed Anal 2013; 80:155-8.
81. 81. Schemehorn BR, Moore MH, Putt MS. Abrasion, polishing, and stain removal characteristics of various commercial dentifrices in vitro. Journal of Clinical Dentistry 2011; 22(1):11-8.
82. 82. Ganss C, Marten J, Hara AT, Schlueter N. Toothpastes and enamel erosion/abrasion – Impact of active ingredients and the particulate fraction. J Dent 2016; 54:62-7.
83. 83. National Center for Biotechnology Information. PubChem. 2023 [cited 2023 Jun 27]. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 6990, 2’,4’-Dihydroxyacetophenone. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/2_4_-Dihydroxyacetophenone.
84. 84. Larramendy M, Soloneski S. Toxicology: new aspects to this scientific conundrum. BoD–Books on Demand; 2016.
85. 85. Gatica‐Ortega ME, Sanz‐Sánchez T, Pastor‐Nieto MA. Allergic contact dermatitis from hydroxyacetophenone in an anti‐wrinkle facial serum with flare‐up reactions triggered by the repeated open application test. Contact Dermatitis 2023; 88(5):407–9.
86. 86. Zhang Z, Shi Y, Zheng H, Zhou Z, Wu Z, Shen D, Wang Y, Zhang Y, Wang Z, Fu B. A hydroxypropyl methylcellulose film loaded with afcp nanoparticles for inhibiting formation of enamel white spot lesions. Int J Nanomedicine 2021; 16:7623-37.
87. 87. Ghadermazi R, Hamdipour S, Sadeghi K, Ghadermazi R, Khosrowshahi Asl A. Effect of various additives on the properties of the films and coatings derived from hydroxypropyl methylcellulose-A review. Food Science and Nutrition 2019; 7(11):3363-77.
88. 88. Cavazana TP, Hosida TY, Sampaio C, de Morais LA, Monteiro DR, Pessan JP, Delbem ACB. Calcium glycerophosphate and fluoride affect the pH and inorganic composition of dual-species biofilms of Streptococcus mutans and Candida albicans. J Dent 2021; 115:103844.
89. 89. FDA. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1201. 1992. Code of Federal Regulations Title 21, Volume 3 Sec. 184.1201 Calcium glycerophosphate.
90. 90. Cury JA, Francisco SB, Simões GS, Del Bel Cury AA, Tabchoury CPM. Effect of a calcium carbonate-based dentifrice on enamel demineralization in situ. Caries Res 2003; 37(3):194–9.
91. 91. Matheson JR, Cox TF, Baylor N, Joiner A, Patil R, Karad V, Ketkar V, Bijlani NS. Effect of toothpaste with natural calcium carbonate/perlite on extrinsic tooth stain. Int Dent J 2004; 54(5 SUPPL. 1):321-5.
92. 92. Endoh M, Takayanagi A, Fujiseki M, Eda Y, Itano M, Yano Y. Effects of toothpaste containing granular calcium carbonate on oral health. Journal of International Oral Health 2019; 11(5):249.
93. 93. Picolos MK, Orlander PR. Calcium carbonate toxicity: The updated milk-alkali syndrome; report of 3 cases and review of the literature. Endocrine Practice 2005; 11(4):272-80.
94. 94. Creeth JE, Goyal C, Qaqish J, Maclure R, Holt JS. Efficacy of an occluding toothpaste on dentinal hypersensitivity over 14 days. BDJ Open 2021; 7(1):26.
95. 95. Vranić E, Lacević A, Mehmedagić A, Uzunović A. Formulation ingredients for toothpastes and mouthwashes. Bosnian journal of basic medical sciences/Udruzenje basicnih mediciniskih znanosti=Association of Basic Medical Sciences 2004: 4(4):51-8.
96. 96. Kottke MK, Rudnic EM. Tablet dosage forms, in modern pharmaceutics. New York: Marcel Dekker 2002; 437-511.
97. 97. Jacob SE, Amini S. Cocamidopropyl Betaine. DERM 2008; 19(3):157–60.
98. 98. Gavit AA, Gagrani MB, Gurav SS, Ayyanar M, Beldar VG, Tatiya AU, Surana SJ, Firke SD, Kalaskar MG. Chemical composition and biological activities of Lonicera caprifolium L. (Caprifoliaceae) essential oil. Nat Prod Res 2024; 38(5):719-26.
99. 99. Varvaresou A, Papageorgiou S, Tsirivas E, Protopapa E, Kintziou H, Kefala V, Demetzos C. Self‐preserving cosmetics. Int J Cosmet Sci 2009; 31(3):163–75.
100. 100. Kušen M, Stura L, Purgar DD, Poje M, Židovec V. Toxic and allergenic plant species in primary school yards of Zagreb’s Lower Town district. Acta Horticulturae et Regiotecturae 2022; 25(1):99–106.
101. 101. Thanabhorn S, Jaijoy K, Thamaree S, Ingkaninan K, Panthong A. Acute and subacute toxicity study of the ethanol extract from Lonicera japonica Thunb. J Ethnopharmacol 2006; 107(3):370–3.
102. 102. Mookhtiar H, Hegde V. Comparative evaluation of surface roughness of teeth after application of remineralizing toothpastes-an in vıtro study. Guident 2019; 13(1):60-63.
103. 103. Qasthari AI, Irawan B, Herda E. The influence of brushing with theobromine and sodium monofluorophosphate toothpaste on enamel surface resistance to roughness after demineralization. In: Journal of Physics: Conference Series. IOP Publishing 2018; 1073(3): 032005.
104. 104. Shete DD, Patmas MA, Patil SP. Pro-argin technology based formulation of eugenol containing toothpaste. Indian Journal Pharmaceutical Education and Research 2020; 54(2):323–8.
105. 105. de Groot A. Contact allergy to (ingredients of) toothpastes. Dermatitis 2017; 28(2):95–114.
106. 106. Jang HJ, Shin CY, Kim KB. Safety evaluation of polyethylene glycol (PEG) compounds for cosmetic use. Toxicol Res 2015; 31:105–36.
107. 107. Iqbal Z, Ahmad FJ, Jain N, Jain GK, Talegaonkar S, Ahuja A, Khar RK, Ahmad FJ. Dental therapeutic systems. Recent Pat Drug Deliv Formul 2008; 2(1):58–67.
108. 108. Carvalho GC, Araujo VHS, Fonseca-Santos B, de Araújo JTC, de Souza MPC, Duarte JL, Chorilli M. Highlights in poloxamer-based drug delivery systems as strategy at local application for vaginal infections. Int J Pharm 2021; 602:120635.
109. 109. Chowdhury BR, Bhattacharya S, Deb M, Garai A. Development of Alcohol-free Herbal Mouthwash Having Anticancer Property. Journal of Herbal 2013; 2(1):2257–78.
110. 110. Diouf PN, Stevanovic T, Cloutier A. Antioxidant properties and polyphenol contents of trembling aspen bark extracts. Wood Sci Technol 2009; 43(5):457–70.
111. 111. Aalto‐Korte K, Välimaa J, Henriks‐Eckerman M, Jolanki R. Allergic contact dermatitis from salicyl alcohol and salicylaldehyde in aspen bark (Populus tremula). Contact Dermatitis 2005; 52(2):93–5.
112. 112. Boyko O, Brygadyrenko V. Nematicidal activity of inorganic food additives. Diversity (Basel) 2022; 14(8):663.
113. 113. Landis MN. 43 - Topical and Intralesional Antiviral Agents. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy (Fourth Edition) Elsevier 2021. p. 493-503.e4.
114. 114. Bergamo VZ, Donato RK, Nemitz MC, Acasigua GAX, Selukar BS, Lopes W, Lana DFD, Teixeira ML, Teixeira HF, Schrekker HS, Fuentefria AM. Assessing an imidazolium salt’s performance as antifungal agent on a mouthwash formulation. J Appl Microbiol 2016; 121(6):1558–67.
115. 115. Morawiec T, Dziedzic A, Niedzielska I, Mertas A, Tanasiewicz M, Skaba D, Kasperski J, Machorowska-Pieniazek A, Kucharzewski M, Szaniawska K, Wieckiewicz W, Wieckiewicz M. The biological activity of propolis-containing toothpaste on oral health environment in patients who underwent implant-supported prosthodontic rehabilitation. Evidence-based complementary and alternative medicine 2013; 2013:704947.
116. 116. Vanni R, Waldner-Tomic NM, Belibasakis GN, Attin T, Schmidlin PR, Thurnheer T. Antibacterial Efficacy of a Propolis Toothpaste and Mouthrinse Against a Supragingival Multispecies Biofilm. Oral Health Prev Dent 2015; 13(6):531-5.
117. 117. Freedman J, Griggs J, De Padova MP, Tosti A. What’s the" buzz" about propolis? Propolis-induced systemic contact dermatitis. Contact Dermatitis 2019; 80(1):65–7.
118. 118. Torres CRG, Perote L, Gutierrez NC, Pucci CR, Borges AB. Efficacy of mouth rinses and toothpaste on tooth whitening. Oper Dent 2013; 38(1):57–62.
119. 119. Heidari A, Shahrabi M, Shahrabi MS. Efficacy of three toothpastes in iron stain removal from primary teeth. Int J Clin Pediatr Dent 2019; 12(1):10.
120. 120. Suppipat S, Hu AH, Trinh LTK, Kuo CH, Huang LH. A comparative life cycle assessment of toothpaste cream versus toothpaste tablets. Sustain Prod Consum 2022; 29:357–69.
121. 121. Narayanan N, Thangavelu L. Salvia officinalis in dentistry. Dent Hypotheses 2015; 6(1):27.
122. 122. Halicioglu O, Astarcioglu G, Yaprak I, Aydinlioglu H. Toxicity of Salvia officinalis in a newborn and a child: an alarming report. Pediatr Neurol 2011; 45(4):259–60.
123. 123. Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 2017; 66(8):1414–27.
124. 124. Liu H, Tu J. Reduction of extrinsic tooth stain by a toothpaste containing 10% high cleaning silica, 0.5% sodium phytate and 0.5% sodium pyrophosphate: an 8-week randomised clinical trial. BMC Oral Health 2021; 21(1):1–7.
125. 125. Taguchi Y, Hasumi Y, Hayama K, Arai R, Nishiyama Y, Abe S. Effect of Cinnamaldehyde on Hyphal Growth of C.albicans Under Various Treatment Conditions. Med Mycol J 2012; 53(3):199-204.
126. 126. McCartney MM, Thompson CJ, Klein LR, Ngo JH, Seibel JD, Fabia F, Simms LA, Borras E, Young BS, Lara J, Turnlund MW, Nguyen AP, Kenyon NJ, Davis CE. Breath carbonyl levels in a human population of seven hundred participants. J Breath Res 2020; 14(4):046005.
127. 127. Twycross RG, Lack SA. The mouth. Control of alimentary symptoms in far advanced cancer Edinburgh: Churchill Livingstone 1986; 12–39.
128. 128. Newbrun E. Xerostomia. Oral Surg Oral Med Oral Pathol 1981; 52(3):262–3.
129. 129. Manley KJ. Will mouth wash solutions of water, salt, sodiumbicarbonate or citric acid improve upper gastrointestinal symptoms in chronic kidney disease. Nephrology 2017; 22(3):213–9.
130. 130. Femiano F, Rullo R, Di Spirito F, Lanza A, Festa VM, Cirillo N. A comparison of salivary substitutes versus a natural sialogogue (citric acid) in patients complaining of dry mouth as an adverse drug reaction: A clinical, randomized controlled study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 2011; 112(1):e15-20.
131. 131. Mason S, Patil P, Karad V. A Randomised Clinical Study to Evaluate Efficacy on Gingival Health of 62% and 67% Sodium Bicarbonate Toothpastes. Oral Health Prev Dent 2021; 19:609–18.
132. 132. Ahrari F, Hasanzadeh N, Rajabi O, Forouzannejad Z. Effectiveness of sodium bicarbonate combined with hydrogen peroxide and CPP-ACPF in whitening and microhardness of enamel. J Clin Exp Dent 2017; 9(3):e344-e350.
133. 133. Hara AT, Turssi CP. Baking soda as an abrasive in toothpastes: Mechanism of action and safety and effectiveness considerations. Journal of the American Dental Association 2017; 148(11):S27-S33.
134. 134. Abhay S, Dinnimath BM, Hullatti KK. Formulation and spectral analysis of new polyherbal toothpaste. Journal of Drug Delivery and Therapeutics 2014; 4(6):68-74.
135. 135. Malvasio V, Ainoedhofer H, Ackbar R, Hoellwarth ME, Saxena AK. Effects of sodium hydroxide exposure on esophageal epithelial cells in an in vitro ovine model: Implications for esophagus tissue engineering. In: Journal of Pediatric Surgery 2012; 47(5):874-80.
136. 136. Barkvoll P. [Should toothpastes foam? Sodium lauryl sulfate--a toothpaste detergent in focus]. Nor Tannlaegeforen Tid 1989; 99(3):82–4.
137. 137. Brown RS, Smith L, Glascoe AL. Inflammatory reaction of the anterior dorsal tongue presumably to sodium lauryl sulfate within toothpastes: a triple case report. Oral Surg Oral Med Oral Pathol Oral Radiol 2018; 125(2):e17-e21.
138. 138. Bauer CW, La Sala EF. The effect of sodium N-lauroyl sarcosinate and of sodium dehydroacetate on the enzymes of the gastrointestinal tract. J Am Pharm Assoc Am Pharm Assoc (Baltim) 1956; 45(10):675-8.
139. 139. Vertuan M, de Souza BM, Machado PF, Mosquim V, Magalhães AC. The effect of commercial whitening toothpastes on erosive dentin wear in vitro. Arch Oral Biol 2020; 109:104580.
140. 140. Sun Y, Li X, Deng Y, Sun JN, Tao D, Chen H, Hu Q, Liu R, Liu W, Feng X, Wang J, Carvell M, Joiner A. Mode of action studies on the formation of enamel minerals from a novel toothpaste containing calcium silicate and sodium phosphate salts. J Dent 2014; 42:S30-8.
141. 141. Brown RB, Razzaque MS. Phosphate toxicity and tumorigenesis. Biochim Biophys Acta Rev Cancer 2018; 1869(2):303-9.
142. 142. Koutojiam P. Sugar substitutes. A publication of the House Committee on Health Care 2005; 3(2):5.
143. 143. Gimba C, Abechi S, Elizabeth O. Investigations of Sodium Lauryl Sulphate and Saccharin Concentrations in Brands of Toothpaste. Res J Chem Sci 2014; 4(6):58-61.
144. 144. Zhu Y, Guo Y, Ye M, James FS. Separation and simultaneous determination of four artificial sweeteners in food and beverages by ion chromatography. In: Journal of Chromatography A 2005; 1085(1):143-6.
145. 145. Deis RC, Kearsley MW. Sorbitol and mannitol. Sweeteners and sugar alternatives in food technology 2012; 331–46.
146. 146. Ruiz-Ruiz JC, Moguel-Ordoñez YB, Segura-Campos MR. Biological activity of Stevia rebaudiana Bertoni and their relationship to health. Crit Rev Food Sci Nutr 2017; 57(12):2680–90.
147. 147. Ferrazzano GF, Cantile T, Alcidi B, Coda M, Ingenito A, Zarrelli A, Di Fabio G, Pollio A. Is Stevia rebaudiana Bertoni a non cariogenic sweetener? A review. Molecules 2015; 21(1):38.
148. 148. Goyal SK, Samsher null, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr 2010; 61(1):1–10.
149. 149. Latarissa IR, Barliana MI, Lestari K. A Comprehensive review of Stevia rebaudiana Bertoni effects on human health and its mechanism. Journal of Advanced Pharmacy Education & Research 2020; 10:91-5.
150. 150. Yamada A, Ohgaki S, Noda T, Shimizu M. Chronic toxicity study of dietary stevia extracts in F344 rats. Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi). 1985; 26(2):169-183_1.
151. 151. Schmandke H. Sweet-tasting steviol glycoside derivatives with antihyperglycaemic and antihypertensive effects. Ernährungs Umschau 2004; 51(11):455-458+438.
152. 152. Sowinski J, Battista G, Petrone DM, Petrone ME, DeVizio W, Volpe AR, Proskin HM. A Twelve-Week Clinical Comparison of Two Tartar Control Dentifrices. Journal of Clinical Dentistry 2000; 11(3):76-9.
153. 153. NIOSH. Pocket Guide to Chemical Hazards http://www.cdc.gov/niosh/npg/npgd0606. html. 2011. Centers for Disease Control and Prevention.
154. 154. Marinescu E, Elisei AM, Aprotosoaie AC, Cioancă O, Trifan A, Miron A, Robu S, Ifrim C, Hancianuu M. Assessment of heavy metals content in some medicinal plants and spices commonly used in Romania. Farmacia 2020; 68(6):1099–105.
155. 155. Verhulst L, Goossens A. Cosmetic components causing contact urticaria: a review and update. Contact Dermatitis 2016; 75(6):333–44.
156. 156. Baig A, He T, Buisson J, Sagel L, Suszcynsky-Meister E, White DJ. Extrinsic whitening effects of sodium hexametaphosphate-a review including a dentifrice with stabilized stannous fluoride. Compend Contin Educ Dent 2005; 26(9 Suppl 1):47-53.
157. 157. Sargent E V, Adolph J, Clemmons MK, Kirk GD, Pena BM, Fedoruk MJ. Evaluation of flu-like symptoms in workers handling xanthan gum powder. Journal of occupational medicine 1990; 32(7):625–30.
158. 158. Duane B. Xylitol and caries prevention. Evid Based Dent 2015; 16(2):37–8.
159. 159. Fontana M, González-Cabezas C. Are we ready for definitive clinical guidelines on xylitol/polyol use? Adv Dent Res 2012; 24(2):123-8.
160. 160. Fried KW, DeLeo PC. Demonstrating the protective effect of a 70-year-old occupational exposure limit against pneumoconiosis caused by mica. Toxicol Ind Health 2022; 38(2):63–9.