Smokeless tobacco (ST) products are used worldwide, and consumption is increasing in the USA. Although ST products are considered to occupy a different position on the tobacco product continuum of risk compared to combusted tobacco products, they can still lead to health problems, including cancer, dental problems and changes in heart rate and blood pressure. Therefore, the determination of harmful and potentially harmful constituents released from ST products into human saliva is important. Four certified reference ST products were tested in this study: loose leaf chewing tobacco (3S1), Swedish-style snus (1S4), snus (1S5) and moist snuff (3S3). These certified reference ST products are manufactured for research purposes, not for human consumption. The reference ST products were used in this study because they have been well characterized and are intended and designed to represent commercial ST products. The reference ST products were incubated in human saliva at 37°C with a range of incubation times for the evaluation of constituents released from these products into human saliva. In this study, alkaloids (nicotine and cotinine), tobacco-specific N-nitrosamines (TSNAs) (N’-nitrosornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and benzo[α]pyrene (B[α]P) in the reference ST products and saliva samples were determined by gas chromatography-mass spectrometry (GC-MS), gas chromatography-fame ionization detection (GC-FID), or ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Our results indicate that the amounts of each constituent released from the reference ST products were altered by the tobacco cut size and product format (pouched or unpouched). The constituents (TSNAs and alkaloids) in moist snuff and loose leaf chewing tobacco were released faster compared to those in Swedish-style snus and snus. B[α]P was only detected in reference moist snuff samples, and only 3.4% of the total B[α]P was released into human saliva after incubation for 60 min, whereas higher percentages of total TSNAs and alkaloids were released at different rates from the four reference ST products.

中文翻译：

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无烟烟草制品释放到人类唾液中的成分的体外研究

无烟烟草 (ST) 产品在全球范围内使用，美国的消费量正在增加。尽管 ST 产品被认为在烟草产品风险连续体中与燃烧烟草产品相比处于不同的位置，但它们仍可能导致健康问题，包括癌症、牙齿问题以及心率和血压的变化。因此，测定从 ST 产品释放到人体唾液中的有害和潜在有害成分非常重要。本研究测试了四种经认证的参考 ST 产品：散叶咀嚼烟草 (3S1)、瑞典式鼻烟 (1S4)、鼻烟 (1S5) 和湿鼻烟 (3S3)。这些经过认证的参考 ST 产品是为研究目的而制造的，而不是供人类食用的。在本研究中使用了参考 ST 产品，因为它们已经很好地表征并且旨在和设计用于代表商业 ST 产品。参考 ST 产品在人唾液中于 37°C 孵育，孵育时间范围为评估从这些产品释放到人唾液中的成分。在这项研究中，生物碱（尼古丁和可替宁）、烟草特有的 N-亚硝胺 (TSNA)（N'-亚硝基山烟碱和 4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮）和苯并[α]芘参比 ST 产品和唾液样品中的 (B[α]P) 采用气相色谱-质谱 (GC-MS)、气相色谱-火焰电离检测 (GC-FID) 或超高效液相色谱-串联质谱 ( UPLC-MS-MS）。我们的结果表明，从参考 ST 产品中释放的每种成分的量会因烟草切割尺寸和产品形式（袋装或未装袋）而改变。与瑞典式鼻烟和鼻烟相比，湿鼻烟和散叶咀嚼烟草中的成分（TSNA 和生物碱）释放得更快。B[α]P 仅在参考湿鼻烟样品中检测到，在孵育 60 分钟后，只有 3.4% 的总 B[α]P 释放到人体唾液中，而总 TSNA 和生物碱的释放率则更高来自四个参考 ST 产品。与瑞典式鼻烟和鼻烟相比，湿鼻烟和散叶咀嚼烟草中的成分（TSNA 和生物碱）释放得更快。B[α]P 仅在参考湿鼻烟样品中检测到，在孵育 60 分钟后，只有 3.4% 的总 B[α]P 释放到人体唾液中，而总 TSNA 和生物碱的释放率则更高来自四个参考 ST 产品。与瑞典式鼻烟和鼻烟相比，湿鼻烟和散叶咀嚼烟草中的成分（TSNA 和生物碱）释放得更快。B[α]P 仅在参考湿鼻烟样品中检测到，在孵育 60 分钟后，只有 3.4% 的总 B[α]P 释放到人体唾液中，而总 TSNA 和生物碱的释放率则更高来自四个参考 ST 产品。