Dose Metrics of Lung Inflammation in Animals Exposed to Zinc Oxide Nanoparticles by Inhalation

Nano-sized zinc oxide (ZnO) was widely applied in industrial field. However, there are literatures indicating that nano-size particles may induce inflammation, thrombosis and cardiovascular diseases, or even penetrate into systemic circulation. Previous studies have shown that total surface area of nanoparticles (NPs) is the best dose metric for particle toxicity. But these studies were conducted with intratracheal instillation, in which the surface area may not be correctly estimated because of particle agglomeration. In this study, I used inhalation exposure to compare relationship of different metrics with lung inflammation induced by zinc oxide particles. I further calculated the benchmark dose to determine the reference dose of zinc oxide.nO NPs were produced in a furnace system and SMPS was used to monitor particle size and number. Healthy SD rats were exposed to 35nm NPs at 1.5×106, 2.1×106, 7.9×106 particles/cm3 and filtered air for 6 hrs. Similarly, rats were exposed to 250nm ZnO at 6.2×104, 1.5×105, 4.5×105 particles/cm3 and filtered air. The total number of cells and proportion of neutrophils in bronchoalveolar lavage (BAL) were determined. The best fit model for lung inflammation with number, mass and surface area concentrations were compared. We also used the Benchmark dose software to calculate the reference dose for ZnO NPs on this effect.he results showed that in both 35-nm and 250-nm ZnO exposed group, percentage of neutrophils, total cells and total protein in BAL fluid increased with the ZnO particles level (p<0.05, test for trend). Further, LDH and WBC in high-dose group increased significantly compared to the controls (P<0.05).s we investigated the relationship between inflammatory markers and the particle parameters, we could find that surface area concentration had the best correlation with the inflammation markers when compared with the mass and number concentration. Significant dose-response curves were also observed in BALF total cells and percentage of neutrophils. These results indicate that total surface area of particles may play an important role in ultrafine particles related toxicity. According to our results, we choose the surface area concentration as dose to present the toxicity.he BMDL of surface area-based dose of ZnO NPs was estimated at 1.1×104 mm2/m3, which is equal to a mass-based dose of 1.14 mg/m3 for 35 nm, 3.24 mg/m3 for 100 nm, and 8.11 mg/m3 for 250 nm ZnO particles. Our results suggest that current US OSHA standard for ZnO fume (PEL, 5 mg/m3) may not be sufficient to protect workers exposed to ZnO NPs against lung inflammation.