Beyond Nicotine: Toxicological Insights Into Metals, Nanoparticles, and Flavoring Agents in E‐Cigarette Aerosols

ABSTRACT

E‐cigarettes are popular as substitutes to traditional tobacco products, especially among teenagers and young people. While regulatory and scientific efforts have been centered around nicotine, mounting data points to serious health hazards associated with nonnicotine components of e‐cigarette aerosols. This study examines new toxicological, clinical, and epidemiological research to determine the overall composition of e‐cigarette aerosols, with a particular emphasis on metals, nanoparticles, flavoring ingredients, carbonyl compounds, and volatile organic compounds (VOCs). The mechanistic routes, organ‐specific toxicity, and comparative risk profiles are thoroughly examined. Growing proof suggests that nonnicotine toxicants play a significant role in oxidative stress, inflammation, mitochondrial dysfunction, and endothelial injury. Metals and ultrafine nanoparticles produced from device components show improved bioavailability and systemic distribution, whereas solvent thermal destruction produces reactive carbonyl species such as formaldehyde and acrolein. Flavoring agents, such as diacetyl and cinnamaldehyde, have been linked to cytotoxicity and decreased respiratory defense mechanisms. Such exposures have been associated to pulmonary damage, cardiovascular dysfunction, and possible neurodevelopmental consequences, especially in sensitive groups including teenagers and pregnant women. Nonnicotine elements of e‐cigarette aerosols are a substantial and underappreciated source of toxicity. The current nicotine‐focused regulatory regimes are inadequate for combating these hazards. Comprehensive toxicological assessments, standardized emission testing, and long‐term epidemiological research are critical for informing evidence‐based policy and protecting public health. However, methodological limitations across in vitro, in vivo, and epidemiological studies complicate risk interpretation and underscore the need for uniform research approaches.