Underestimated Toxicity: UV Amplifies Low-Dose Cr(VI) Damage to Skin at Molecular and Tissue Levels

Chromium(VI) [Cr(VI)] is a well-documented environmental carcinogen linked to DNA damage, oxidative stress, and systemic toxicity. Existing risk assessments predominantly focus on single-factor high-dose occupational exposures, while it is usually overlooked that Cr(VI) exists at a low level and coexists with environmental factors in real-world scenarios; thus, assessing the synergistic toxicity of low-dose Cr(VI) with coexposure is imperative. Herein, we reveal that UV irradiation critically amplifies the toxicity of low-dose Cr(VI) at both the molecular and tissue levels. Integrated in vitro and in vivo models, we demonstrate that UV-induced redox cycling of Cr(VI) generates reactive oxygen species (ROS), inducing DNA and protein cleavage, cytotoxicity, and skin barrier damage. Notably, acute UV-Cr(VI) coexposure compromises skin barrier function, evidenced by a 50% increase in transepidermal water loss and disorganized stratum corneum ultrastructure (epidermal thickening, aberrant basal cell activation, and infiltration of inflammatory cells). These findings establish UV as a critical enhancer of Cr(VI) toxicity, revealing the synergistic toxicity of low-dose Cr(VI) and UV irradiation at molecular and tissue levels and challenging the traditional threshold-based safety Cr(VI) dosage. This work emphasizes the urgent need to re-evaluate environmental Cr(VI) risks under real-world light-exposed scenarios, with implications for sunscreen formulations, occupational safety guidelines, and ecological regulations in the face of growing environmental challenges.