One assumption was that TiO2 translocated from compartment 1 to the thoracic lymph nodes (Eq. (7)) BTK inhibitor library and the other assumption was that TiO2 translocated from compartment 2 to the thoracic lymph nodes (Eq. (8)). equation(7) dBLymdt=kLung→LymB1 (t=0, BLym=0) equation(8) dBLymdt=kLung→LymB2 (t=0, BLym=0)Where, BLym was the total TiO2 burden in the right and left posterior mediastinal lymph nodes, and the parathymic lymph nodes (μg); B1 was the TiO2 lung burden in compartment 1 (μg); B2 was the TiO2 lung burden in compartment 2 (μg); and kLung→Lym was the translocation rate constant from lung to thoracic lymph nodes (/day). The least squares

method was used for the estimation (Eq. (9)). equation(9) Sum of square difference=∑(LnBLym_measured−LnBLym_estimated)2 Sum of square difference=∑(LnBLym_measured−LnBLym_estimated)2 Where BLym_measured was the measured thoracic lymph node TiO2 burden and BLym_estimated was the estimated thoracic lymph node TiO2 burden. The differences in tissue Ti or TiO2 concentrations between the study

groups were statistically analyzed by Student’s t test or one-way ANOVA (Welch’s test) after F-testing using SPSS 20.0. The Z-average particle sizes were 143–148 nm in the administered suspensions, with ζ potentials of −44 mV. Fig. 3 shows the TiO2 nanoparticle size distribution Stem Cell Compound Library purchase and a scanning electron micrograph of the nanoparticle in the stock suspension. The specific surface area of TiO2 nanoparticles in the administered suspension was 59 m2/g, which was very similar to that of the primary particles (50 ± 15 m2/g, catalog value). The TiO2 concentrations in the diluted suspensions, determined by ICP-AES, were >95% of the concentration estimated by weight measurement and accounting for the dilution factor. Thus, the concentration of the stock solution was confirmed. The concentrations of Ti in drinking water and feed, determined by ICP-SFMS, were <0.10 ng/mL and 2700 ng/g,

respectively. MYO10 This corresponded to TiO2-equivalent concentrations of <0.17 ng/mL and 4500 ng/g, respectively. TiO2 burdens in lung after BALF sampling, BALF, and trachea between 1 day and 26 weeks after administration of TiO2 nanoparticles were significantly higher (P < 0.01) than those of the control group ( Fig. 4). The rat TiO2 burden depended on the dose administered. TiO2 burdens in lung after BALF sampling and BALF decreased over time. One day after administration, 58% ± 16%, 70% ± 15%, 78% ± 13%, 64% ± 15%, and 77% ± 15% of the TiO2 administered was present in the lungs after BALF sampling of rats dosed with 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg, respectively, while 6.1% ± 1.7%, 6.5% ± 0.75%, 8.6% ± 1.7%, 13% ± 3.4%, and 31% ± 4.9% of administered TiO2 was present in the lungs after BALF sampling 26 weeks after administration of 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg, respectively.