Erionite is a ubiquitous natural zeolite, often occurring with fibrous habit, whose strong tumorigenic activity to humans has been certified by its inclusion in the Group 1 Human-Carcinogenic list by the International Agency for Research on Cancer. To date, the reason(s) of erionite toxicity are still unclear, albeit several hypotheses have been proposed. The present work, based on the combined analysis of the chemical and structural modifications of erionite fibres following incubation in human THP-1 macrophages and evaluation of cellular response, indicates that, upon macrophage phagocytosis, a large release of cations is counterbalanced by a significant sequestration of hydronium ions from lysosomes provoking a quick pH dysregulation. This would be restored by the hyperactivation of ATP-dependent proton pumps with significant energy expenditure for the cell, ultimately causing mitochondrial suffering, leading to chronic inflammation and eventually cancer development. © 2025 The Authors

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