{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:10:38Z","timestamp":1778091038304,"version":"3.51.4"},"reference-count":30,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union\u2019s Consumers, Health and Food Executive Agency","award":["101035968\/ JA-01-2020"],"award-info":[{"award-number":["101035968\/ JA-01-2020"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Tob Control"],"accepted":{"date-parts":[[2025,12,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The tobacco industry increasingly targets youth through products such as electronic cigarettes and heated tobacco devices. In Italy, 9.6% of children aged 11\u201313 use tobacco and nicotine products, with e-cigarettes being the most prevalent, reflecting a global trend. Articles 9 and 10 of the WHO Framework Convention on Tobacco Control mandate testing and disclosure of ingredients, including flavours, highlighting the need for standardised analytical methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To develop and validate a standardised non-targeted analysis (NTA) method for the compositional assessment of e-cigarette liquids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A gas chromatography\u2013mass spectrometry based NTA method was developed and validated through an interlaboratory study involving 21 laboratories worldwide. The method enables direct analysis of e-liquids and semi-quantitative evaluation of detected compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The method was applied to 23 commercial e-liquids from different WHO regions, identifying flavouring agents, allergens, and potential skin, eye, and respiratory irritants. Predominant flavour profiles included candy-sweet, fruity, and cooling compounds, with regional variability observed. The method demonstrated robustness and reproducibility across laboratories, including those with limited instrumentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This standardised NTA approach, now adopted as a WHO Standard Operating Procedure, provides a reliable tool for regulatory monitoring, supporting compliance, detecting undeclared substances, and strengthening flavour-related regulations globally.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/tc-2025-059702","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:20:27Z","timestamp":1778088027000},"page":"tc-2025-059702","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Future-proofing chemical profiling of tobacco and nicotine products: standardised non-targeted analysis (NTA) of e-liquid flavour profiles for monitoring and regulation purposes"],"prefix":"10.1136","author":[{"given":"Alessia","family":"Turina","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy"},{"name":"National Institute of Metrological Research (INRIM), Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-5932","authenticated-orcid":false,"given":"Alice","family":"Passoni","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Liboni","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1971-2385","authenticated-orcid":false,"given":"Walther N","family":"Klerx","sequence":"additional","affiliation":[{"name":"Centre for Health Protection | Department for Chemical analysis, Tobacco & Drugs, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5310-9064","authenticated-orcid":false,"given":"Reinskje","family":"Talhout","sequence":"additional","affiliation":[{"name":"Centre for Health Protection | Department for Chemical analysis, Tobacco & Drugs, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Cremers","sequence":"additional","affiliation":[{"name":"Centre for Health Protection | Department for Chemical analysis, Tobacco & Drugs, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Van Alphen","sequence":"additional","affiliation":[{"name":"Centre for Health Protection | Department for Chemical analysis, Tobacco & Drugs, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-1047","authenticated-orcid":false,"given":"Beno\u00eet","family":"Labarbe","sequence":"additional","affiliation":[{"name":"Risk Assessment Department, Anses, Maisons-Alfort, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-1351","authenticated-orcid":false,"given":"Enrico","family":"Davoli","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026050610201555000_tc-2025-059702v1.1","unstructured":"WHO global report on trends in prevalence of tobacco use 2000\u20132030, 2024. Available: https:\/\/www.who.int\/publications\/i\/item\/9789240088283 [Accessed Jan 2024]."},{"key":"2026050610201555000_tc-2025-059702v1.2","unstructured":"Tobacco Control Playbook, 2024. Available: https:\/\/www.who.int\/europe\/publications\/i\/item\/WHO-EURO-2019-3700-43459-61071 [Accessed 19 Sep 2024]."},{"key":"2026050610201555000_tc-2025-059702v1.3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.53127\/tblg-2023-A011","article-title":"The national report on tobacco use 2023","volume":"21","author":"Mastrobattista","year":"2023","journal-title":"Tabaccologia"},{"key":"2026050610201555000_tc-2025-059702v1.4","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-020-09572-x","article-title":"E-cigarettes use in the United States: reasons for use, perceptions, and effects on health","volume":"20","author":"Sapru","year":"2020","journal-title":"BMC Public Health"},{"key":"2026050610201555000_tc-2025-059702v1.5","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph19148747","article-title":"Adolescents, Young Adults, and Adults Continue to Use E-Cigarette Devices and Flavors Two Years after FDA Discretionary Enforcement","volume":"19","author":"McCauley","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"2026050610201555000_tc-2025-059702v1.6","doi-asserted-by":"crossref","DOI":"10.1016\/j.talanta.2021.122318","article-title":"Strategy for the identification of flavor compounds in e-liquids by correlating the analysis of GCxIMS and GC-MS","volume":"230","author":"Augustini","year":"2021","journal-title":"Talanta"},{"key":"2026050610201555000_tc-2025-059702v1.7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0194145","article-title":"A systematic review of consumer preference for e-cigarette attributes: Flavor, nicotine strength, and type","volume":"13","author":"Zare","year":"2018","journal-title":"PLoS One"},{"key":"2026050610201555000_tc-2025-059702v1.8","doi-asserted-by":"publisher","DOI":"10.1136\/tc-2022-057764"},{"key":"2026050610201555000_tc-2025-059702v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2019.106077"},{"key":"2026050610201555000_tc-2025-059702v1.10","first-page":"1381","article-title":"A Method for Classifying User-Reported Electronic Cigarette Liquid Flavors","volume":"19","author":"Yingst","year":"2017","journal-title":"Nicotine Tob Res"},{"key":"2026050610201555000_tc-2025-059702v1.11","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-031598","article-title":"Impact of non-menthol flavours in e-cigarettes on perceptions and use: an updated systematic review","volume":"9","author":"Meernik","year":"2019","journal-title":"BMJ Open"},{"key":"2026050610201555000_tc-2025-059702v1.12","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph14101274","article-title":"Generally Recognized as Safe: Uncertainty Surrounding E-Cigarette Flavoring Safety","volume":"14","author":"Sears","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"2026050610201555000_tc-2025-059702v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntae123"},{"key":"2026050610201555000_tc-2025-059702v1.14","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.7b02205"},{"key":"2026050610201555000_tc-2025-059702v1.15","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph182111107","article-title":"Effects of E-Cigarette Flavoring Chemicals on Human Macrophages and Bronchial Epithelial Cells","volume":"18","author":"Morris","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"2026050610201555000_tc-2025-059702v1.16","unstructured":"WHO Framwork Convention on Tobacco Control . Partial implementation of articles 9 and 10 regulation of the contents of tobacco products and regulation of tobacco product disclosures. 2017. Available: https:\/\/fctc.who.int\/publications\/m\/item\/regulation-of-the-contents-of-tobacco-products-and-regulation-of-tobacco-product-disclosures"},{"key":"2026050610201555000_tc-2025-059702v1.17","doi-asserted-by":"publisher","DOI":"10.1136\/tobaccocontrol-2020-055769"},{"key":"2026050610201555000_tc-2025-059702v1.18","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1021\/acs.est.2c06804","article-title":"Demonstrating the Use of Non-targeted Analysis for Identification of Unknown Chemicals in Rapid Response Scenarios","volume":"57","author":"Sloop","year":"2023","journal-title":"Environ Sci Technol"},{"key":"2026050610201555000_tc-2025-059702v1.19","unstructured":"Haglund P . Cathrin veenaas and kemiska institutionen, ume\u00e5 universitet, \u201cNon-target screening and digital archiving of abiotic samples."},{"key":"2026050610201555000_tc-2025-059702v1.20","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1021\/acs.chemrestox.3c00150","article-title":"Nontargeted Analysis in Tobacco Research: Challenges and Opportunities","volume":"36","author":"Adeniji","year":"2023","journal-title":"Chem Res Toxicol"},{"key":"2026050610201555000_tc-2025-059702v1.21","unstructured":"Work Packages 5 (WP 5) . JATC2, Available: https:\/\/jaotc.eu\/work-packages-jatc2\/"},{"key":"2026050610201555000_tc-2025-059702v1.22","unstructured":"Standard operating procedure for the determination of flavouring agents in e-liquids using non-targeted analysis: gas chromatography mass spectrometry: WHO TobLabNet official method SOP 16, Available: https:\/\/www.who.int\/publications\/i\/item\/9789240111509 [Accessed 18 Jul 2025]."},{"key":"2026050610201555000_tc-2025-059702v1.23","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/38.7.270"},{"key":"2026050610201555000_tc-2025-059702v1.24","doi-asserted-by":"crossref","first-page":"16289","DOI":"10.1021\/acs.analchem.1c02660","article-title":"An Introduction to the Benchmarking and Publications for Non-Targeted Analysis Working Group","volume":"93","author":"Place","year":"2021","journal-title":"Anal Chem"},{"key":"2026050610201555000_tc-2025-059702v1.25","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-022-04203-3"},{"key":"2026050610201555000_tc-2025-059702v1.26","unstructured":"Flavor extract manufacturers association (FEMA). 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