Oral Toxicity Study of Silicon Dioxide Nanoparticles on Fertility and Early Embryonic Development in Mice

Silicon dioxide nanoparticles (SiO₂NPs) are one of the most commonly used non-metal oxide nanomaterials because of their biocompatibility, biodegradability, and surface functionalization. However, the potential toxicological effects of SiO₂NPs have not been comprehensively investigated, and the available toxicological data are inconsistent. In particular, the toxicological effects of SiO₂NPs on reproductive and developmental functions are limited, and little information is available regarding their potential effects on fertility and early embryonic development.

In this study, we investigated the potential reproductive and developmental toxicity of SiO₂NPs in mice, in accordance with the fertility and early embryonic development study design of International Council for Harmonization (ICH) S5 (R3) guideline. SiO₂NPs were administered once daily via oral gavage at doses of 0, 60, 250, and 1000 mg/kg during the pre-mating, mating, and early gestation periods. Endpoints related to fertility and early embryonic development were evaluated, including female fertility, tubal transport, implantation, early embryonic development, and functional aspects of male fertility. Additionally, the general health of the parental animals was also investigated.

Oral administration of SiO₂NPs did not induce any SiO₂NPs-related adverse effects on female fertility indices, tubal transport, implantation outcomes, early embryonic development, and male fertility function. Additionally, no SiO₂NPs-related adverse effects were observed in clinical signs, body weight, food consumption, clinical pathology, macroscopic observations, and organ weights at any dose level.

The results demonstrated that oral exposure to SiO₂NPs at dose levels up to 1000 mg/kg did not induce any significant adverse effects on fertility, early embryonic development, or general systemic health. These findings contribute to the human health risk assessment of SiO₂NPs, and further toxicological studies should address different physicochemical properties and additional exposure routes to resolve remaining uncertainties.