Kinetics and dissolution of intratracheally administered nickel oxide nanomaterials in rats

Background: the toxicokinetics of nanomaterials are an important factor in toxicity,which may be affected by slow clearance and/or distribution in the body. methods: four types of nickel oxide (nio) nanoparticles were single-administered intratracheally to male f344 rats at three doses of 0.67-6.0 mg/kg body weight. the rats were sacrificed under anesthesia and the lung,thoracic lymph nodes,bronchoalveolar lavage fluid,liver,and other organs were sampled for ni burden measurement 3,28,and 91 days post-administration; ni excretion was measured 6 and 24 h after administration. solubility of nio nanoparticles was determined using artificial lysosomal fluid,artificial interstitial fluid,hydrogen peroxide solution,pure water,and saline. in addition,macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants. results: the wire-like nio nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical nio nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4 × 10-3 and 4.9 × 10-3/h). the largest irregular-shaped nio nanoparticles hardly dissolved in any solution,including artificial lysosomal fluid (7.8 × 10-5/h). pulmonary clearance rate constants,estimated using a one-compartment model,were much higher for the nio nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped nio nanoparticles (0-0.012/day). pulmonary clearance rate constants of the largest irregular-shaped nio nanoparticles showed an inverse correlation with dose. translocation of nio from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped nio nanoparticles,but not for the wire-like nio nanoparticles. thirty-five percent of the wire-like nio nanoparticles were excreted in the first 24 h after administration; excretion was 0.33-3.6% in that time frame for the spherical and irregular-shaped nio nanoparticles. conclusion: these findings suggest that nanomaterial solubility differences can result in variations in their pulmonary clearance. nanoparticles with moderate lysosomal solubility may induce persistent pulmonary inflammation. © 2017 the author(s).