This study utilized nano-sized ZnO to better define the pharmacokinetic and translocation properties of nano-sized particles. To determine the pharmacokinetic and translocation properties of neutron activated ZnO (65Zn) particles, we utilizied two particle sizes (7-13 nm and 40-100 nm) and two routes of exposure (intravenous injection (IV) or intratracheal instillation (IT)). Male Sprague-Dawley rats were given a single dose of neutron activated 65ZnO particles at 1.5 mg/kg body weight. At varying time points, tissues (lungs, brain, heart, spleen, kidney, skeletal muscle, liver, bone marrow and gastrointestinal tract) were collected. The radioactivity in tissues was calculated as % of instilled/injected dose. Results show that at 30 minutes post-IV, the % of injected 65Zn in the liver was significantly higher for 40-100 nm than for 7-13 nm. However, 7 days later, liver uptake was the same for both particle sizes. For the IT-instilled particles, at both 1 and 7 days post-IT, tissue distribution was similar between the 2 particle sizes. At 1 day post, only 10% of the instilled 65ZnO remained in the lung for both particle sizes. At 7 days post, the amount of 65ZnO in the lung decreased to 0.1% for both particle sizes. In conclusion, for the IV-injected particles, particle size has an initial effect on 65Zn uptake in the liver. For IT instilled particles, particle size did not alter lung clearance or distribution. The lack of particle size dependence on translocation and lung clearance of 65ZnO particles may be due to the agglomerated state of the ZnO nanoparticles. Dynamic light scattering revealed that the 7-13 nm and 40-100 nm ZnO particles had a mean diameter of 83.5 nm and 88.3 respectively. Also, the high solubility of ZnO could have obscured any influence of particle size on pulmonary deposition of the particles. The 65Zn measured in collected tissues was most certainly dissolved 65Zn from the particles, especially at later time points.
Biological-effects; Cell-biology; Cellular-reactions; Chemical-hypersensitivity; Chemical-properties; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-testing; Liver; Liver-cells; Microbiology; Microscopic-analysis; Molecular-biology; Particulate-dust; Particulates; Pharmacodynamics; Statistical-analysis
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah