Caffeine-mediated cytotoxicity of snortable energy powders in human nasal epithelial cells under air-liquid interface conditions.

Snortable energy powders have recently emerged, under brands such as Sniffy, raising public health and regulatory concerns because of largely unknown nasal toxicity. This study aimed to assess the cytotoxic potential of Sniffy powders on human nasal epithelial cells and identify the constituents driving the observed toxicity. RPMI 2650 nasal epithelial cells were cultured at the air-liquid interface and exposed for 24 h to graded doses of Sniffy powders (from 0.6 to 30 mg/cm2). Cell viability and membrane integrity were assessed by resazurin reduction and LDH release. To investigate the contribution of specific constituents (caffeine, creatine, and flavourings), comparative assays were conducted using individual ingredients and combinations. Sniffy induced a strong, dose-dependent cytotoxic response, with a 50% reduction in cell viability and a twofold increase in LDH at 6 mg/cm2, corresponding to localized "hotspot" deposition in the nasal cavity. Caffeine alone reproduced the cytotoxicity of the full commercial formulation, whereas creatine and flavourings showed negligible effects. These results demonstrate that intranasal exposure to snortable caffeine-based powders can cause substantial epithelial injury in vitro, primarily driven by caffeine. The findings underscore the importance of route-specific toxicological assessment and support the maintenance of regulatory restrictions on the nasal use of such products.