The green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinensePursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC-MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5-O-diglucoside chloride, kaempferol-7-O-β-d-glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat-diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients.

BACKGROUND: Part of the appeal of e-cigarettes lies in their available flavors. To achieve attractive flavors, e-liquids contain many different flavoring agents, which allow many flavoring combinations. To advance our knowledge of e-liquid flavors and compositions and to evaluate the effect of legislation, we determined whether there are ingredient combinations that are frequently used together.
METHODS: We used e-cigarette ingredient data from the European Common Entry Gate system (EU-CEG) as available on 31 December 2022.
RESULTS: In e-liquids, we found 214 ingredient pairs with a co-occurrence odds ratio greater than 10. Together, these consisted of 62 unique ingredients. Network analysis revealed that ingredients were grouped together based on their flavor and/or chemical structure. We identified two densely connected regions (clusters) in the network. One consisted of six ingredients with sweet-vanilla-creamy flavors. The second cluster consisted of 13 ingredients. While some of these have fruity flavors, others, such as alkyl carboxylic acids and dimethyl sulfide, are known to have unpleasant flavors. Additional data and literature analyses indicated that alkyl carboxylic acids can contribute to a creamy and sweet-fruity taste, whereas dimethyl sulfide can contribute to a more refined fruity taste.
CONCLUSIONS: These results exemplify that the flavor of e-liquids is not just the sum of its parts. Big data analyses on product data can be used to detect such patterns, but expert knowledge and additional data are needed for further interpretation. Monitoring of e-liquid flavors as well as ingredients will remain important to regulate e-liquid product attractiveness.

Nicotine pouches contain fewer characteristic toxicants than conventional tobacco products. However, the associated risks in terms of toxicity and addiction potential are still unclear. Therefore, endpoints of toxicity and contents of flavoring substances were investigated in this study. The in vitro toxicity of five different nicotine pouches and the reference snus CRP1.1 were studied in human gingival fibroblasts (HGF-1). Cells were exposed to product extracts (nicotine contents: 0.03-1.34 mg/mL) and sampled at different time points. Cytotoxicity, total cellular reactive oxygen species (ROS) levels, and changes in the expression levels of inflammatory and oxidative stress genes were assessed. Flavor compounds used in the nicotine pouches were identified by GC-MS. Cytotoxicity was observed in two nicotine pouches. Gene expression of interleukin 6 (IL6) and heme oxygenase 1 (HMOX1) was upregulated by one and three pouches, respectively. ROS production was either increased or decreased, by one pouch each. CRP1.1 caused an upregulation of IL6 and elevated ROS production. Toxicity was not directly dependent on nicotine concentration and osmolarity. A total of 56 flavorings were detected in the five nicotine pouches. Seven flavorings were classified according to the harmonized hazard classification system as laid down in the European Classification, Labelling and Packaging regulation. Nine flavorings are known cytotoxins. Cytotoxicity, inflammation, and oxidative stress responses indicate that adverse effects such as local lesions in the buccal mucosa may occur after chronic product use. In conclusion, flavorings used in nicotine pouches likely contribute to the toxicity of nicotine pouches.

Many flavor ingredients are often used in potentially reduced-risk tobacco products (such as e-vapor products). Although most are \"generally recognized as safe (GRAS)\" when used in food, there is limited information available on their long-term health effects when delivered by inhalation. While obtaining route-of-exposure-specific toxicological data on flavor ingredients is critical to product evaluation, the large number of individual flavor ingredients available and their potential combinations render classical toxicological assessment approaches impractical, as they may require years of preclinical investigations and thousands of laboratory animals. Therefore, we propose a pragmatic approach in which flavor ingredients are initially assigned to groups of structurally related compounds (Flavor Groups), from which flavor group representatives (FGR) are then selected and tested individually and as a mixture in vitro and in vivo. The premise is that structurally related compounds would have comparable metabolic and biological activity and that the data generated using FGRs could support the toxicological assessment of other structurally related flavor ingredients of their respective Flavor Groups. This approach is explained in a step-wise manner and exemplified by a case study, along with its strengths, limitations as well as recommendations for further confirmatory testing. Once completed, this FGR approach could significantly reduce the time and resources required for filling the data gap in understanding the health risks of many flavor ingredients while also minimizing the need for laboratory animals.

OBJECTIVE: Electronic cigarette refill solutions (e-liquids) are available in various flavor descriptions that can be categorized as fruit, tobacco, and more. Flavors increase sensory appeal, thereby stimulating e-cigarette use, and flavoring ingredients can contribute to e-cigarette toxicity. We aim to inform toxicologists, sensory scientists, and regulators by determining flavoring compounds in e-liquids with various flavors, and compare results between flavor categories.
METHODS: Gas chromatography - mass spectrometry (GC-MS) was used to identify 79 flavorings in 320 e-liquids, classified in 15 flavor categories. Ten flavorings highly prevalent in e-liquids according to information from manufacturers were quantified. Flavoring prevalence was defined as the number of e-liquids with the flavoring as percentage of the total number of e-liquids. The method was validated in terms of specificity, linearity, repeatability, recovery, and sensitivity.
RESULTS: The mean number of flavorings per e-liquid was 6 ± 4. Flavoring prevalence was highest for vanillin (creamy/vanilla flavor), ethyl butyrate (ethereal/fruity), and cis-3-hexenol (fresh/green). Based on similarities in flavoring prevalence, four clusters of categories were distinguished: (1) fruit, candy, alcohol, beverages; (2) dessert, coffee/tea, nuts, sweets; (3) menthol/mint; and (4) spices, tobacco, and unflavored. Categories from cluster 4 generally had less flavorings per e-liquid than fruit, candy, alcohol, beverages (cluster 1) and dessert (cluster 2) (p < 0.05). Flavoring concentrations varied between e-liquids within the categories.
CONCLUSIONS: We evaluated flavoring compositions of 320 e-liquids using a simple GC-MS method. Flavoring prevalence was similar within four clusters of typically fresh/sweet, warm/sweet, fresh/cooling, and non-sweet flavor categories. To compare flavoring concentrations between individual flavor categories, additional research is needed.