title: Brain-targeted distribution and high retention of silver by chronic intranasal instillation of silver nanoparticles and ions in Sprague-Dawley rats.
abstract: The wide applications of silver nanoparticles (AgNPs) have been concerned regarding their unintentional toxicities. Different exposure modes may cause distinct accumulation, retention and elimination profiles, which are closely related with their toxicities. Unlike silver accumulation profiles through other regular administration modes, the biodistribution, accumulation and elimination of AgNPs by intranasal instillation are not fully understood. This study conducted intranasal instillation of polyvinylpyrrolidone-coated AgNPs in neonatal Sprague-Dawley rats at doses of 1 and 0.1 mg kg(-1) day(-1) for 4 and 12 weeks, respectively. The 4-week recovery was also designed after the 12-week exposure. Silver concentrations in the main tissues or organs were periodically monitored. Parallel exposures using silver ion were performed for the comparative studies. No physiological alterations were observed in AgNP exposures. In comparison, 1 mg kg(-1) day(-1) silver ions decreased body weight gain and caused mortality of 18.2%, showing ionic silver had a relatively higher toxicity than AgNPs. A relatively higher silver accumulation was observed in silver ion groups than AgNP groups. The silver ion release could not fully explain silver accumulation in AgNP exposures, showing silver distribution caused by particulate silver occurred in vivo. The highest silver concentration was in the liver at week 4, while it shifted to the brain after a 12-week exposure. Dose-related silver accumulation occurred for both AgNP and silver ion groups. The time course revealed a uniquely high concentration and retention of brain silver, implying chronic intranasal instillation caused brain-targeted silver accumulation. These findings provided substantial evidence on the potential neuronal threat from the intranasal administration of AgNPs or silver colloid-based products.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.|School of Earth and Space Science, University of Science and Technology of China, Anhui, 230026, China.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D011205:Povidone / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012834:Silver / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D012835:Silver Nitrate / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D012834:Silver; D012835:Silver Nitrate; D011205:Povidone
keywords: brain-targeted; intranasal instillation; silver nanoparticles; silver retention; tissue distribution