# Batch-Dependent Hepatobiliary Toxicity of 10 nm Silver Nanoparticles After Single Intravenous Administration in Mice

## TL;DR

This study shows that slight differences in batches of 10 nm silver nanoparticles can lead to varying levels of liver and gallbladder toxicity in mice.

## Contribution

The study reveals that batch-to-batch variability in AgNP size distribution affects in vivo hepatobiliary toxicity.

## Key findings

- All AgNP batches caused hepatobiliary toxicity, but severity varied depending on the batch.
- Batches with more smaller AgNPs were more toxic, indicating size distribution impacts toxicity.
- Silver was found in multiple cell types, showing internalization and cell-specific effects.

## Abstract

Silver nanoparticles (AgNPs) are extensively employed for their antimicrobial and biomedical properties, yet concerns persist regarding their potential toxicity. While AgNPs can induce oxidative stress, membrane disruption, and DNA damage, in vivo data remain inconsistent. This study investigated whether batch-to-batch variability in nominally identical AgNPs of 10 nm size contributes to divergent in vivo toxicity outcomes. CD-1 (ICR) mice were intravenously injected with a single 10 mg/kg bw dose of spherical, citrate-coated 10 nm AgNPs from three different batches purchased from the same manufacturer. The mice were euthanized 24 h post-exposure for quantitative silver determination by inductively coupled plasma–mass spectrometry (ICP–MS) and histopathological evaluation of liver, spleen, lungs, kidneys, and brain. Autometallography and immunofluorescence were used to assess silver distribution and cellular localization in the hepatobiliary system. All the batches induced hepatobiliary toxicity, characterized by hepatocellular necrosis and gallbladder wall hemorrhage, of differing severity. The most toxic batches contained higher proportions of smaller AgNPs, suggesting that differences in size distribution influence toxicological outcomes. Silver agglomerates were localized within multiple cell types, indicating internalization and cell-specific cytotoxicity. These findings highlight that minor physicochemical variations affect in vivo results, underscoring the importance of nanoparticle characterization to improve reproducibility in nanotoxicological research.