Toxicological Evaluation of Siloxanes by In Silico Approaches

<strong>Background and Aims:</strong> Silicones are widely used in household items, personal care products, and medical devices. They are especially preferred for products used directly on humans, as they are biocompatible, biologically stable, and unlikely to cause allergic reactions. It has been estimated that the global produc tion capacity of siloxanes has reached 400,000 tons annually. Humans in all age groups are exposed to siloxanes from various products by oral, inhalation, dermal, or parenteral routes. For many years, siloxanes have been widely regarded as nontoxic substances, fostering a sense of safety in their use across various applications. However, emerging scientific research reveals a more nuanced perspective, indicating that this assumption of safety cannot be uniformly applied to all siloxanes. This study aimed to evaluate the in silico toxicological profile of sixteen different siloxanes, commonly regarded as safe, thereby questioning their potential risks and the validity of the current safety perception. <strong>Methods:</strong> This study employed in silico toxicological evaluation of sixteen cyclic and linear siloxanes using VEGA (v.1.2.3), VEGA NRMEA (v.1.1.1), US EPA TEST (v.5.1.2 and 4.2.1), US EPA CompTox Chemicals Dashboard (v.2.5.3), PanScreen, ProTox (v.3.0), and DeepPK models. <strong>Results: </strong>Our results suggested that siloxanes may affect the endocrine system through the oestrogen receptor (ER) pathway. <strong>Conclusion:</strong> There is a growing need for new toxicity models that focus on silicone compounds. As our understanding advances, it becomes evident that the diverse chemical structures and behaviours of these compounds may pose potential risks that were previously overlooked.