Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain.

BackgroundSilver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited.ObjectivesWe determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity.MethodsMale Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks).ResultsThe highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control.ConclusionsThe results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure. Citation: Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870-1875; http://dx.doi.org/10.1289/EHP234

Nose-to-brain transport of aerosolised quantum dots following acute exposure.

Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential transport of QDs directly to the brain has not been assessed. This study evaluated whether QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1 h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualisation via fluorescent and transmission electron microscopy. We conclude that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that QDs can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation

Aerosolized Silver Nanoparticles in the Rat Lung and Pulmonary Responses over Time

Silver nanoparticle (Ag NP) production methods are being developed and refined to produce more uniform Ag NPs through chemical reactions involving silver salt solutions, solvents, and capping agents to control particle formation. These chemical reactants are often present as contaminants and/or coatings on the Ag NPs, which could alter their interactions in vivo. To determine pulmonary effects of citrate-coated Ag NPs, Sprague-Dawley rats were exposed once nose-only to aerosolized Ag NPs (20 nm [C20] or 110 nm [C110] Ag NPs) for 6 hr. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, 21, and 56 days postexposure for analyses. Inhalation of Ag NPs, versus citrate buffer control, produced significant inflammatory and cytotoxic responses that were measured in BALF cells and supernatant. At day 7, total cells, protein, and lactate dehydrogenase were significantly elevated in BALF, and peak histopathology was noted after C20 or C110 exposure versus control. At day 21, BALF polymorphonuclear cells and tissue inflammation were significantly greater after C20 versus C110 exposure. By day 56, inflammation was resolved in Ag NP-exposed animals. Overall, results suggest delayed, short-lived inflammatory and cytotoxic effects following C20 or C110 inhalation and potential for greater responses following C20 exposure

Influence of particle size on persistence and clearance of aerosolized silver nanoparticles in the rat lung.

The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days)

Aerosolized Silver Nanoparticles in the Rat Lung and Pulmonary Responses over Time

Silver nanoparticle (Ag NP) production methods are being developed and refined to produce more uniform Ag NPs through chemical reactions involving silver salt solutions, solvents, and capping agents to control particle formation. These chemical reactants are often present as contaminants and/or coatings on the Ag NPs, which could alter their interactions in vivo. To determine pulmonary effects of citrate-coated Ag NPs, Sprague-Dawley rats were exposed once nose-only to aerosolized Ag NPs (20 nm [C20] or 110 nm [C110] Ag NPs) for six hours. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, 21, and 56 days post exposure for analyses. Inhalation of Ag NPs, versus citrate buffer control, produced significant inflammatory and cytotoxic responses that were measured in BALF cells and supernatant. At Day 7, total cells, protein, and lactate dehydrogenase were significantly elevated in BALF, and peak histopathology was noted after C20 or C110 exposure versus control. At Day 21, BALF PMNs and tissue inflammation was significantly greater after C20 versus C110 exposure. By Day 56, inflammation was resolved in Ag NP-exposed animals. Overall, results suggest delayed, short-lived inflammatory and cytotoxic effects following C20 or C110 inhalation and potential for greater responses following C20 exposure

Influence of Particle Size on Persistence and Clearance of Aerosolized Silver Nanoparticles in the Rat Lung

The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days)

Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain

BACKGROUND: Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited. OBJECTIVES: We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity. METHODS: Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks). RESULTS: The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control. CONCLUSIONS: The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure. CITATION: Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP23

Why Girls? Using Routine Activities Theory to Predict Cyberbullying Experiences Between Girls and Boys

This study uses data from the Second Youth Internet Safety Survey (D. Finkelhor, K. J. Mitchell, and J. Wolak 2011) to predict the risk of cyberbullying between genders. Although much of the cyberbullying literature has considered gender in analyses, nearly all studies have lumped boys and girls together when examining risk factors. This gender lumping has led to the inaccurate perception that risk factors for cyberbullying affect both genders similarly. Therefore, this study fills that void by reviewing differences in the online behaviors of boys and girls, whether these differences affect risk for cyberbullying, and whether routine activities theory is applicable in explaining the risk of cyberbullying for both boys and girls. © 2013 Copyright Taylor and Francis Group, LLC