Analytical investigation of metal distribution from e-cigarette aerosols to lung deposition using multi-platform mass spectrometry

E-cigarettes are promoted as a safer alternative to conventional tobacco, yet emerging evidence indicates they may expose users to harmful metals. While prior research has focused on nicotine and organic constituents, the bioaccumulation and spatial distribution of toxic metals in lung tissue remain poorly understood. In this study, a multi-platform analytical approach combining ICP-MS, GC-ICP-MS, GC-MS, and LA-ICP-MS/MS was employed to characterise the elemental and organic composition of refillable e-cigarette liquid and its corresponding aerosol, and to assess metal accumulation in murine lung tissue following short-term exposure. Balb/c mice (7 weeks, n = 8 per group) were exposed to nicotine-containing e-cigarette aerosols (8, 16, or 32 puffs; 30 min, twice daily for 4 days) or ambient air (control). Results showed that multiple toxic metals and organometallic species were detected in both e-liquid and aerosol, including species of Al, Ni, Cu, As, Br, Sn, and Hg. Elemental bioimaging of murine lungs found heterogeneous focal accumulation patterns in lung tissue, with increased Cu, significantly elevated Ni and Pb, and significantly reduced pulmonary Fe concentrations (p ≤ 0.005). Metal distribution patterns were exposure-related but not strictly dose-dependent, indicating a complex deposition and clearance mechanism. This study provides the first evidence of metal-containing (organometallic) species in e-cigarette aerosols and exposure-associated metal accumulation in murine lung tissue. These findings reinforce the need for further mechanistic and longitudinal investigations to assess the health risks associated with chronic vaping exposure.