Synthetic amorphous silicon dioxide (SAS) has been widely used as a food additive as an anticaking agent, thickener and flavor carrier. With the recent development of nanotechnology, nano-sized SAS can be unintentionally used, raising concerns about potential toxicity caused by SAS nanoparticles and the necessity for re-evaluation of toxicity. Since food additive SAS, which is classified into fumed (pyrogenic) type and precipitated type according to its manufacturing method, has different physicochemical and dissolution properties, its toxicokinetics, fate, and potential toxicity may be different in biological matrices and in the body. However, few studies have been conducted to compare the differences between fumed SAS and precipitated SAS in in vitro cytotoxicity and intestinal transport properties and in vivo toxicokinetics such as oral absorption and tissue distribution.
In this study, the physicochemical and dissolution properties of fumed SAS and precipitated SAS in various biological matrices were evaluated, and intestinal transport properties were determined. Thier toxicokinetics were evaluated in terms of oral absorption and tissue distribution after single dose and repeated oral administration for 28 days, respectively. Oral toxicity was also assessed following repeated oral administration of fumed SAS and precipitated SAS for 28 days. Potential inflammation effect related to macrophage activation by SAS was also determined both in vitro and in vivo.
The results demonstrated that fumed SAS and precipitated SAS had different physicochemical and dissolution properties depending on the manufacturing method. It was showed that precipitated SAS had significantly high in vitro intracellular uptake and intestinal transport than those of fumed SAS. After oral administration of a single dose (2,000 mg/kg) of fumed SAS and precipitated SAS, oral absorptions of the former and the latter were 3.1% and 3.9%, respectively. Both SASs only slightly distributed in liver repeated oral administration for 28 days, but returned to normal levels at 29 d post-administration. The accumulated amount of precipitated SAS was significantly higher than that of fumed SAS. These results suggest that the toxicokinetics between fumed SAS and precipitated SAS in terms of oral absorption and tissue distribution are dependent on physicochemical and dissolution properties associated with manufacturing method. Inflammatory response related to activation of both SASs was also suggested, requiring further study on their potential inflammatory toxicity.
These findings will provide useful information to understand the potential toxicity of food additive SAS. Further toxicity and mechanistic study is required to ascertain the safety of food additive nanoparticles.