From biomarkers to the risk index: a novel integrated model using multidimensional urinary biomarkers to quantify...

E-cigarette use is a common form of tobacco consumption; however, just like secondhand smoke, its long-term health effects remain uncertain. At present, risk assessment indicators for e-cigarettes and second-hand smoke are not sufficiently comprehensive, and robust technical methods for holistic exposure evaluation are lacking. In this study, a questionnaire survey was conducted and urine samples from 100 non-smokers and 301 e-cigarette users were collected. Urinary metabolites of nicotine, volatile organic compounds, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, 1,2-propylene glycol, and glycerol were systematically analyzed, making this study the most comprehensive investigation to date of risk assessment indicators for e-cigarettes. The results showed significant differences in multiple urinary biomarkers between non-smokers and e-cigarette users, including total nicotine equivalents, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 2-amino-1,3,4-thiadiazole-5-carboxylic acid, S-phenylmercapturic acid, N-acetyl-S-(2-cyanoethyl)-L-cysteine, 2-hydroxypropyl mercapturic acid, 3-hydroxypropyl mercapturic acid, and total hydroxylated naphthalenes. Using integrated biomarker response (IBR) calculations, a risk assessment model was established for e-cigarette exposure. The scientific validity of this model was evaluated using the cigarette consumption test for dependence and the Fagerström test for nicotine dependence scales, and it indicates that the higher the degree of addiction to tobacco products, the higher the risk of exposure. The biomarkers and IBR-based assessment model developed in this study may provide valuable tools for clinical evaluation of the health risk status of tobacco product users and second-hand smoke.