Các túi nicotine dạng miệng với dư vị? Phần 2: độc tính in vitro trên các tế bào nguyên bào sợi nướu người

Fühner-Wieland's Sammlung von Vergiftungsfällen - Tập 97 - Trang 2343-2356 - 2023
Selina Rinaldi1,2, Elke Pieper1, Thomas Schulz1, Ralf Zimmermann2, Andreas Luch1, Peter Laux1, Nadja Mallock-Ohnesorg1
1Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
2Chair of Analytical Chemistry, Joint Mass Spectrometry Centre, University of Rostock, Rostock, Germany

Tóm tắt

Các túi nicotine chứa ít các chất độc hại đặc trưng hơn so với các sản phẩm thuốc lá thông thường. Tuy nhiên, những rủi ro liên quan đến độc tính và tiềm năng nghiện vẫn chưa được làm rõ. Do đó, các chỉ số độc tính và thành phần các chất tạo hương đã được nghiên cứu trong nghiên cứu này. Độc tính in vitro của năm loại túi nicotine khác nhau và snus tham chiếu CRP1.1 đã được nghiên cứu trên các tế bào nguyên bào sợi nướu người (HGF-1). Các tế bào đã được tiếp xúc với chiết xuất sản phẩm (nồng độ nicotine: 0.03–1.34 mg/mL) và mẫu được lấy tại các thời điểm khác nhau. Độc tính tế bào, mức độ tổng hợp các sản phẩm oxy phản ứng (ROS) và những thay đổi trong mức độ biểu hiện của các gen viêm và stress oxy đã được đánh giá. Các hợp chất tạo hương được sử dụng trong các túi nicotine đã được xác định bằng GC–MS. Độc tính tế bào đã được quan sát thấy ở hai túi nicotine. Mức độ biểu hiện của interleukin 6 (IL6) và heme oxygenase 1 (HMOX1) đã được tăng cường bởi một và ba túi tương ứng. Sản xuất ROS đã được tăng lên hoặc giảm xuống, bởi một túi mỗi loại. CRP1.1 đã gây tăng cường IL6 và sản xuất ROS gia tăng. Độc tính không phụ thuộc trực tiếp vào nồng độ nicotine và độ thẩm thấu. Tổng cộng có 56 hương liệu đã được phát hiện trong năm túi nicotine. Bảy hương liệu đã được phân loại theo hệ thống phân loại nguy hiểm hòa hợp như được quy định trong quy định phân loại, ghi nhãn và bao bì của Châu Âu. Chín hương liệu là các độc tố tế bào đã biết. Độc tính tế bào, viêm nhiễm, và phản ứng stress oxy cho thấy rằng các tác động bất lợi như tổn thương cục bộ trên niêm mạc miệng có thể xảy ra sau khi sử dụng sản phẩm mãn tính. Kết luận, các hương liệu sử dụng trong các túi nicotine có thể góp phần vào độc tính của các túi nicotine.

Từ khóa

#nicotine pouches #toxicity #flavoring substances #human gingival fibroblasts #interleukin 6 #oxidative stress

Tài liệu tham khảo

Aldeek F, McCutcheon N, Smith C, Miller JH, Danielson TL (2021) dissolution testing of nicotine release from OTDN pouches: product characterization and product-to-product comparison. Separations 8:7. https://doi.org/10.3390/separations8010007 An Q, Ren JN, Li X, Fan G, Qu SS, Song Y et al (2021) Recent updates on bioactive properties of linalool. Food Funct 12:10370–10389 Aqil M, Ahad A, Sultana Y, Ali A (2007) Status of terpenes as skin penetration enhancers. Drug Discov Today 12:1061–1067. https://doi.org/10.1016/j.drudis.2007.09.001 Azzopardi D, Liu C, Murphy J (2021) Chemical characterization of tobacco-free “modern” oral nicotine pouches and their position on the toxicant and risk continuums. Drug Chem Toxicol. https://doi.org/10.1080/01480545.2021.1925691 Behar RZ, Luo W, McWhirter KJ, Pankow JF, Talbot P (2018) Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids. Sci Rep 8:8288. https://doi.org/10.1038/s41598-018-25575-6 Binmadi N, Harere L, Mattar A, Aljohani S, Alhindi N, Ali S, Almazrooa S (2022) Oral lesions associated with smokeless tobacco users in Saudi Arabia: single center cross-sectional study Saudi. Dent J 34:114–120. https://doi.org/10.1016/j.sdentj.2021.12.002 Bishop E, East N, Bozhilova S, Santopietro S, Smart D, Taylor M et al (2020) An approach for the extract generation and toxicological assessment of tobacco-free “modern” oral nicotine pouches. Food Chem Toxicol 145:111713. https://doi.org/10.1016/j.fct.2020.111713 Caliri AW, Tommasi S, Besaratinia A (2021) Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat Res Rev Mutat Res 787:108365. https://doi.org/10.1016/j.mrrev.2021.108365 Chang YS, Wu CL, Tseng SH, Kuo PY, Tseng SY (2008) In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide. Exp Eye Res 86:942–950. https://doi.org/10.1016/j.exer.2008.03.011 Delnevo CD, Hrywna M, Miller Lo EJ, Wackowski OA (2021) Examining market trends in smokeless tobacco sales in the United States: 2011–2019. Nicotine Tob Res 23:1420–1424. https://doi.org/10.1093/ntr/ntaa239 Delvadia PR, Barr WH, Karnes HT (2012) A biorelevant in vitro release/permeation system for oral transmucosal dosage forms. Int J Pharm 430:104–113. https://doi.org/10.1016/j.ijpharm.2012.03.050 DIN ISO 53160–1 (2010) Determination of the colourfastness of articles for common use - part 1: test with artificial saliva. East N, Bishop E, Breheny D, Gaca M, Thorne D (2021) A screening approach for the evaluation of tobacco-free “modern Oral” nicotine products using real time cell analysis. Toxicol Rep 8:481–488. https://doi.org/10.1016/j.toxrep.2021.02.014 Escobar-Garcia M, Rodriguez-Contreras K, Ruiz-Rodriguez S, Pierdant-Perez M, Cerda-Cristerna B, Pozos-Guillen A (2016) Eugenol toxicity in human dental pulp fibroblasts of primary teeth. J Clin Pediatr Dent 40:312–318. https://doi.org/10.17796/1053-4628-40.4.312 European parliament and the council of the European union (2008) Regulation (EC) No 1272/2008 of the European parliament and the council of 16 december 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing directives 67/548/EEC and 1999/45/EC, and amending regulation (EC) No 1907/2006. Evans PA (1962) Smoking and health summary of a report of the royal college of physicians of London on smoking in relation to cancer of the lung and other diseases. Cent Afr J Med 8:234–236 Foundation for a smoke-free world (2021) Global trends in nicotine Frasch HF, Barbero AM (2017) In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment. J Expo Sci Environ Epidemiol 27:618–624. https://doi.org/10.1038/jes.2016.68 Hajizadeh MR, Maleki H, Barani M, Fahmidehkar MA, Mahmoodi M, Torkzadeh-Mahani M (2019) In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents. Res Pharm Sci 14:448–458. https://doi.org/10.4103/1735-5362.268206 Halme M, Pesonen M, Salo H, Söderström M, Pasanen M, Vähäkangas K, Vanninen P (2016) Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin. J Chromatogr B 1009–1010:17–24. https://doi.org/10.1016/j.jchromb.2015.11.042 Havermans A, Pennings JLA, Hegger I, Elling JM, de Vries H, Pauwels C, Talhout R (2021) Awareness, use and perceptions of cigarillos, heated tobacco products and nicotine pouches: a survey among Dutch adolescents and adults. Drug Alcohol Depend 229:109136. https://doi.org/10.1016/j.drugalcdep.2021.109136 Hoffmann D, Djordjevic MV (1997) Chemical composition and carcinogenicity of smokeless tobacco. Adv Dent Res 11:322–329. https://doi.org/10.1177/08959374970110030301 Hrywna M, Gonsalves NJ, Delnevo CD, Wackowski OA (2022) Nicotine pouch product awareness, interest and ever use among US adults who smoke, 2022. Tob Control. https://doi.org/10.1136/tobaccocontrol-2021-057156 Hua M, Omaiye EE, Luo W, McWhirter KJ, Pankow JF, Talbot P (2019) Identification of cytotoxic flavor chemicals in top-selling electronic cigarette refill fluids. Sci Rep 9:2782. https://doi.org/10.1038/s41598-019-38978-w Hutzler C, Paschke M, Kruschinski S, Henkler F, Hahn J, Luch A (2014) Chemical hazards present in liquids and vapors of electronic cigarettes. Arch Toxicol 88:1295–1308. https://doi.org/10.1007/s00204-014-1294-7 IARC (2007) Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum 89:1–592 Imperial Brands (2021) State of the science: oral nicotine pouches and their growing harm reduction opportunity. https://imperialbrandsscience.com/blog/nicotine-pouches-and-their-growing-harm-reduction-opportunity/. Accessed 20/08 2022 Kang SW, Park HJ, Ban JY, Chung JH, Chun GS, Cho JO (2011) Effects of nicotine on apoptosis in human gingival fibroblasts. Arch Oral Biol 56:1091–1097. https://doi.org/10.1016/j.archoralbio.2011.03.016 Kim YW, Kim MJ, Chung BY, Bang DY, Lim SK, Choi SM et al (2013) Safety evaluation and risk assessment of d-limonene. J Toxicol Environ Health Part B 16:17–38. https://doi.org/10.1080/10937404.2013.769418 Knopp MM, Kiil-Nielsen NK, Masser AE, Staaf M (2022) Introducing a novel biorelevant in vitro dissolution method for the assessment of nicotine release from oral tobacco-derived nicotine (OTDN) and snus products. Separations 9:52. https://doi.org/10.3390/separations8010007 Krusemann EJZ, Boesveldt S, de Graaf K, Talhout R (2019) An E-liquid flavor wheel: a shared vocabulary based on systematically reviewing E-liquid flavor classifications in literature. Nicotine Tob Res 21:1310–1319. https://doi.org/10.1093/ntr/nty101 Mallock N, Schulz T, Malke S, Dreiack N, Laux P, Luch A (2022) Levels of nicotine and tobacco-specific nitrosamines in oral nicotine pouches. Tob Control. https://doi.org/10.1136/tc-2022-057280 Mallock-Ohnesorg N, Rinaldi S, Malke S, Dreiack N, Pieper E, Laux P, Schulz T, Zimmermann R, Luch A (2023) Oral nicotine pouches with an aftertaste? Part 1: screening and initial toxicological assessment of flavorings and other ingredients. Arch Toxicol. https://doi.org/10.1007/s00204-023-03538-9 Malpass GE, Arimilli S, Prasad GL, Howlett AC (2013) Complete artificial saliva alters expression of proinflammatory cytokines in human dermal fibroblasts. Toxicol Sci 134:18–25. https://doi.org/10.1093/toxsci/kft103 Mesa-Arango AC, Montiel-Ramos J, Zapata B, Duran C, Betancur-Galvis L, Stashenko E (2009) Citral and carvone chemotypes from the essential oils of colombian lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity. Mem Inst Oswaldo Cruz 104:878–884. https://doi.org/10.1590/s0074-02762009000600010 Plurphanswat N, Hughes JR, Fagerström K, Rodu B (2020) Initial Information on a novel nicotine product. Am J Addict 29:279–286. https://doi.org/10.1111/ajad.13020 Prasad K, Shetty M, Kanitscheider C, Szentes B, Nassar R, Edward L (2022) Assessing consumer use and behaviour patterns of oral nicotine pouches in a multi-country study. Int J Sci Rep 8:4. https://doi.org/10.18203/issn.2454-2156.IntJSciRep20221344 Prashar A, Locke IC, Evans CS (2004) Cytotoxicity of lavender oil and its major components to human skin cells. Cell Prolif 37:221–229. https://doi.org/10.1111/j.1365-2184.2004.00307.x Reilly SM, Bitzer ZT, Goel R, Trushin N, Richie JP Jr (2018) Free radical, carbonyl, and nicotine levels produced by juul electronic cigarettes. Nicotine Tob Res 21:1274–1278. https://doi.org/10.1093/ntr/nty221 Robichaud MO, Seidenberg AB, Byron MJ (2020) Tobacco companies introduce “tobacco-free” nicotine pouches. Tob Control 29:e145–e146. https://doi.org/10.1136/tobaccocontrol-2019-055321 Shaikh SB, Tung WC, Pang C, Lucas J, Li D, Rahman I (2022) Flavor classification/categorization and differential toxicity of oral nicotine pouches (ONPs) in oral gingival epithelial cells and bronchial epithelial cells. Toxics 10:660. https://doi.org/10.3390/toxics10110660 Shao Y, Zou J, Xie Z, Mayne RG, Ossip DJ, Rahman I et al (2022) Perceptions of oral nicotine pouches on reddit: observational study. J Med Internet Res 24:e37071. https://doi.org/10.2196/37071 Sinha S, Jothiramajayam M, Ghosh M, Mukherjee A (2014) Evaluation of toxicity of essential oils palmarosa, citronella, lemongrass and vetiver in human lymphocytes. Food Chem Toxicol 68:71–77. https://doi.org/10.1016/j.fct.2014.02.036 Skold M, Borje A, Harambasic E, Karlberg AT (2004) Contact allergens formed on air exposure of linalool identification and quantification of primary and secondary oxidation products and the effect on skin sensitization. Chem Res Toxicol 17:1697–1705. https://doi.org/10.1021/tx049831z Souza ACS, Silva LK, Queiroz TB, Marques ES, Hiruma-Lima CA, Gaivao IOM, Maistro EL (2020) Citral presents cytotoxic and genotoxic effects in human cultured cells. Drug Chem Toxicol 43:435–440. https://doi.org/10.1080/01480545.2019.1585445 Stanfill S, Tran H, Tyx R, Fernandez C, Zhu W, Marynak K et al (2021) Characterization of total and unprotonated (Free) nicotine content of nicotine pouch products. Nicotine Tob Res 23:1590–1596. https://doi.org/10.1093/ntr/ntab030 Takeuchi-Igarashi H, Kubota S, Tachibana T, Murakashi E, Takigawa M, Okabe M, Numabe Y (2016) Matrix remodeling response of human periodontal tissue cells toward fibrosis upon nicotine exposure. Odontology 104:35–43. https://doi.org/10.1007/s10266-014-0177-y Tobacco tactics (2021) Nicotine pouches. University of Bath. https://tobaccotactics.org/wiki/nicotine-pouches. Accessed 2022/02/15 Ulker Z, Alpsoy L, Mihmanli A (2013) Assessment of cytotoxic and apoptotic effects of benzaldehyde using different assays. Hum Exp Toxicol 32:858–864. https://doi.org/10.1177/0960327112470271 World Health Organization (2021) WHO global report on trends in prevalence of tobacco use in 2000–2025, 4th edn. World Health Organization, Geneva Zhao J, Qiao L, Shang P, Hua C, Xie Y, Li X et al (2021) Effects of smokeless tobacco on cell viability, reactive oxygen species, apoptosis, and inflammatory cytokines in human umbilical vein endothelial cells. Toxicol Mech Methods 31:349–358. https://doi.org/10.1080/15376516.2021.1876800