Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form.

Background: Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery. Results: There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT. Conclusions: Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.

Synthetic amorphous silica (SAS), manufactured in pyrogenic or precipitated form, is a nanomaterial with a widespread use as food additive (E 551). Oral exposure to SAS results from its use in food and dietary supplements, pharmaceuticals and toothpaste. Recent evidence suggests that oral exposure to SAS may pose health risks and highlights the need to address the toxic potential of SAS as affected by the physicochemical characteristics of the different forms of SAS. For this aim, investigating SAS toxicokinetics is of crucial importance and an analytical strategy for such an undertaking is presented. The minimization of silicon background in tissues, control of contamination (including silicon release from equipment), high-throughput sample treatment, elimination of spectral interferences affecting inductively coupled plasma mass spectrometry (ICP-MS) silicon detection, and development of analytical quality control tools are the cornerstones of this strategy. A validated method combining sample digestion with silicon determination by reaction cell ICP-MS is presented. Silica particles are converted to soluble silicon by microwave dissolution with mixtures of HNO₃, H₂O₂ and hydrofluoric acid (HF), whereas interference-free ICP-MS detection of total silicon is achieved by ion-molecule chemistry with limits of detection (LoDs) in the range 0.2–0.5 µg Si g⁻¹ for most tissues. Deposition of particulate SiO₂ in tissues is assessed by single particle ICP-MS.

Arsenic occurs in food in both inorganic (iAs) and organic (oAs) forms. Inorganic arsenic is highly toxic and classified as carcinogenic to humans, whereas oAs species, such as arsenobetaine (AB), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), generally exhibit lower toxicity. Rice and rice-based products represent major contributors to dietary iAs exposure. Within this context, the present study provides an updated assessment of the occurrence of iAs and oAs in rice-based beverages available on the Italian market. A method for the simultaneous determination of iAs, AB, DMA, and MMA was developed and validated, and it exhibits adequate sensitivity to ensure robust occurrence data, eliminating left-censoring for iAs. A comprehensive analysis of twenty-five representative rice-based beverages was conducted, revealing that the contamination profiles exhibited a high degree of homogeneity, with iAs as the predominant species. All samples complied with the European maximum level for iAs in non-alcoholic rice-based beverages. When combined with recent Italian consumption data, these results enabled age-specific dietary exposure assessment. Although rice drinks contribute marginally to overall population exposure, estimated intakes for regular consumers in early childhood are associated with a small margin of exposure, raising potential concern for vulnerable subgroups. The increasing diversification of dietary habits and the rising consumption of plant-based beverages point to the necessity of continuous monitoring of iAs. Ongoing efforts in monitoring studies, updated food consumption surveys, and effective risk communication are essential to refine exposure assessment and thereby enhance public health protection.

Arsenic occurs in food in both inorganic (iAs) and organic (oAs) forms. Inorganic arsenic is highly toxic and classified as carcinogenic to humans, whereas oAs species, such as arsenobetaine (AB), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), generally exhibit lower toxicity. Rice and rice-based products represent major contributors to dietary iAs exposure. Within this context, the present study provides an updated assessment of the occurrence iAs and oAs in rice-based beverages available on the Italian market. A method for the simultaneous determination of iAs, AB, DMA, and MMA was developed and validated, and it exhibits adequate sensitivity to ensure robust occurrence data, eliminating left-censoring for iAs. Analysis of 25 representative rice-based drinks revealed generally homogeneous contamination profiles, with iAs as the predominant species. All samples complied with the European maximum level for iAs in non-alcoholic rice-based beverages. When combined with recent Italian consumption data, these results enabled age-specific dietary exposure assessment. Although rice drinks contribute marginally to overall population exposure, estimated intakes for regular consumers in early childhood are associated with limited margins of exposure, raising potential concern for vulnerable subgroups. The increasing diversification of dietary habits and the rising popularity of plant-based beverages point out the need for continuous monitoring of iAs. Ongoing efforts in monitoring studies, consumption database improvement, and effective risk communication are essential to refine exposure assessment and enhance public health protection.