Deciphering the Toxicity of Metal Tungstates and Molybdates: Effects on L929 Cell Metabolic Activity, Oxidative Stress, and Genotoxicity

The increasing development and application of metal-based materials in biomedical and environmental fields raise important concerns regarding their potential cytotoxic and genotoxic effects. Metal tungstates (M_xWO₄) and molybdates (M_xMoO₄) offer promising functional properties in health and environmental solutions but require safety validation before practical use. This study aimed to synthesize a series of these compounds based on Ag, Ca, Sr, and Zn and evaluate their behavior in both solid state and solution, focusing on their biological interactions with L929 fibroblast cells. Cell metabolic activity was assessed over 1, 3, and 7 days, revealing that Ag-based materials were toxic even at low concentrations (7.8 μg/mL), while Ca-, Sr-, and Zn-based compounds enhanced metabolic activity at lower doses. At concentrations above 62.5 μg/mL, Zn-based materials showed toxicity, accompanied by morphological cell alterations. ROS production emerged as the primary mechanism of toxicity, especially for Ag-based samples. Intracellular oxidative stress analysis confirmed elevated ROS and RNS levels over time. Apoptotic and necrotic pathways were identified only in α-Ag₂WO₄ at the lowest dose. The micronucleus assay showed genotoxic responses in Ag-based compounds comparable to positive controls, while other materials showed no significant genotoxicity. These findings indicate that Ca-, Sr-, and Zn-based tungstates and molybdates may be safely applied in biological contexts, whereas Ag-based materials, though effective, demand cautious use due to their long-term genotoxic potential.