Hexagonal boron nitride (hBN) is a promising two-dimensional (2D) material of interest to the scientific community and industry due to its revolutionary physico-chemical features. Skin contact is one of the most feasible exposure routes both for workers, producing hBN, and consumers, using hBN-enabled nanotechnologies. Hence, the toxic potential of hBN at the cutaneous level was evaluated following an in vitro approach with different degree of complexity, using a simplified cell model (HaCaT keratinocytes), and a more predictive and complete skin tissue (a 3D model of human epidermis). Despite its significant uptake by keratinocytes, hBN exerted only weak adverse effects, such as slight alterations of cells parameters indices of cytotoxicity (cell viability, cell mass and plasma membrane integrity) and mitochondrial-related dysfunctions (mitochondrial depolarization, ATP depletion and reactive oxygen species production), detectable only at high concentrations (>25 μg/mL) and mainly after a long exposure (72 h). In addition, adoption of the OECD TG 431 and 439 on the 3D reconstructed human epidermis model demonstrated hBN as a non-corrosive and non-irritant material, with an extremely low pro-inflammatory potential. These results denote a good biocompatibility of hBN at the skin level
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