One of the many questions in the human risk assessment of metallic engineered nanomaterials (ENM) such as silver ENM is whether these ENM dissolve in the gastrointestinal (GI) system or are absorbed and translocated to organs and tissues as intact nanoparticles. It is difficult to elucidate this question as in situ measurement of silver ENM is still hampered by technical difficulties, but also because silver nanoparticles can be formed in vivo after exposure to silver salts. To tackle these difficulties, we compared the tissue distribution of orally administered silver ENM with the tissue distribution pattern of silver ENM and a silver salt that were administered by intravenous (IV) injection.
Female rats were exposed to a single dose of NM-300K, consisting of silver nanoparticles with a mean diameter <20 nm, or to AgNO3. The rats were treated either by oral gavage or by IV injection. During a 24-hour period, urine and feces were collected. After 24 hours, selected tissues were sampled and total Ag concentrations were measured by ICP-MS.
After treatment by IV injection with the silver salt, largest Ag concentrations were found in the liver, spleen and pancreas, and Ag was largely excreted (32% of administered dose) via urine and feces. After IV injection with NM-300K, largest Ag concentrations were found in the spleen, and <1% of the administered dose was excreted via urine and feces. This demonstrates that NM-300K, once present systemically, is circulated as particles and solubilization is limited.
After treatment of the animals by oral gavage there was a low absorption of Ag, the absorption after treatment with NM-300K being 10-fold lower than after treatment with AgNO3. As there is a certain amount of soluble Ag present in the administered NM-300K dispersion (~3%), the tissue concentrations were normalized for the soluble Ag dose. After this normalization, the Ag concentrations in tissues after exposure to NM-300K were up to 17 times larger than after exposure to AgNO3. This might indicate that either an additional fraction of NM-300K has been solubilized in the GI tract, or that NM-300K is partially taken up as intact nanoparticles. The Ag distribution pattern in the tissues after treatment with NM-300K resembled, however, more that of ionic Ag after IV injection than that of NM-300K after IV injection. This suggests that it is more likely that NM-300K is partially dissolved in the GI tract and subsequently absorbed and excreted via urine and feces.