A review to support the derivation of a worst-case dermal penetration value for nanoparticles.

Data on dermal penetration of nanoparticles (NPs) was reviewed with the goal to establish a worst-case dermal penetration value for NPs. To this aim, the main focus was on studies providing quantitative dermal penetration data (29 studies). In vivo dermal penetration studies and ex vivo studies based on skin explants were included. These studies used NPs with different compositions, dimensions, and shapes. The overall results showed that skin is an efficient barrier for NPs, indistinctly of their properties. However, some studies reported that a small percentage of the applied NP dose penetrated the skin surface and reached deeper skin layers. The integrity of the skin layer and the product formulation were more critical determinants of dermal penetration than the NP properties. Most quantitative studies were based on elemental analysis such that it cannot be concluded if detected levels are attributable to a dissolved fraction or to the penetration of particles as such. Results of qualitative imaging studies suggest that at least a fraction of the levels reported in quantitative studies could be due to particle penetration. Altogether, based on the data compiled, we propose that 1% could be used as a worst-case dermal penetration value for nanoparticles within the boundaries of the properties of those included in our analysis.

Short-term oral administration of non-porous and mesoporous silica did not induce local or systemic toxicity in mice.

In this study, two sets of methyl-coated non-porous and mesoporous amorphous silica materials of two target sizes (100 and 300 nm; 10-844 m2/g) were used to investigate the potential role of specific surface area (SSA) and porosity on the oral toxicity in mice. Female Swiss mice were administered by oral gavage for 5 consecutive days. Two silica dose levels (100 and 1000 mg/kg b.w.) were tested for all four materials. All dispersions were characterized by transmission electron microscopy (TEM) and Nanoparticle tracking analysis (NTA). Batch dispersions of porous silica were rather unstable due to agglomeration. Animals were sacrificed one day after the last administration or after a three-week recovery period. No relevant toxicological effects were induced by any of the silica materials tested, as evaluated by body weight, gross pathology, relative organ weights (liver, spleen, kidneys), hematology, blood biochemistry, genotoxicity (Comet assay in jejunum cells and micronucleus test in peripheral blood erythrocytes), liver and small intestine histopathology, and intestinal inflammation. The presence of silica particles in the intestine was evaluated by a hyperspectral imaging microscopy system (CytoViva) using histological samples of jejunum tissue. Silica spectral signatures were found in jejunum samples with all the treatments, but only statistically significant in one of the treatment groups.