Toxicity Assessment of Silicon-Based Compounds With Their Permitted Daily Exposure in Pharmaceutical Packaging...

Silicon derivative materials have evolved from the earliest elemental silicon into various forms for industrial applications that are widely used in pharmaceutical packaging and medical devices. This review examines the development of silicon-containing products, from silica and silicate-based glasses to medical-grade silicones and silicone gels. However, these materials have the potential to release extractables and leachables (E&Ls), raising safety concerns that are not adequately addressed by current oversimplified toxicological assessments, which often rely solely on establishing safety limits for elemental silicon in accordance with ICH Q3D guidelines. To better evaluate these risks, this work explores the synthesis, properties, and applications of silicon-derived materials, with the aim of identifying potential E&Ls through analysis of starting materials, end-capping agents, crosslinking compounds, and degradation byproducts. The toxicological profiles of relevant silicon compounds, including inorganic forms such as silica, as well as organosilicon compounds like cyclic/linear siloxanes and their reactive derivatives, are comprehensively summarized. Furthermore, by synthesizing data from sources such as ECHA, OECD, EFSA, and other scientific literature, this review establishes permitted daily exposure (PDE) values of 10,000 μg/day for inorganic silicon and 1020 μg/day for organosilicon, along with safety thresholds for other silicon derivatives. These refined values are intended to replace earlier generalized silicon safety assessments, offering a scientifically robust basis for regulatory safety limits and supporting the responsible advancement of silicon-based medical devices and pharmaceutical packaging.