9666), 31P18O (mass: 48.9729), and 32S16O1H (mass: 48.9748). Linearity of the calibration curves for 49Ti using ICP-SFMS http://www.selleckchem.com/products/ganetespib-sta-9090.html was good between 0 and 20 ng/mL of standard solution

(0, 0.01, 0.05, 0.1, 1, 5, 10, and 20 ng/mL; R2 > 0.999). Quality assurance data for the analysis were as previously described ( Shinohara et al., 2014). Both 1-compartment and 2-compartment models were employed in this study. The 1-compartment model assumed one clearance pathway from the lungs (Fig. 1). For the 2-compartment approach, two kinds of clearance pathway models were considered. Model A (Fig. 2A) assumed, direct clearance from the compartment 1, translocation from compartment 1 to 2, and clearance via compartment 2, while model B (Fig. 2B) assumed clearance from compartment 1 only, and reciprocal translocation between compartments 1 and 2. The 1-compartment model can be represented by a 1-step clearance rate constant, as shown in Eq. (1), where B

was the TiO2 lung burden; A was the amount of TiO2 administered (mg); t was the time elapsed after administration (day); r was the fraction of the administered TiO2 that reached the alveolar region; and k was the clearance rate constant for the clearance (/day). equation(1) dBdt=−kB (t=0, B=rA) The 2-compartment model A can be represented by a 2-step clearance as shown in Eqs. (2) and (3), where B1 was the TiO2 burden in lung compartment 1 (mg); B2 was the TiO2 burden in lung compartment (-)-p-Bromotetramisole Oxalate 2 (mg); A was the amount of TiO2 administered (mg); r was the fraction SB203580 datasheet of the administered TiO2 that reached the alveolar region; and k1, k12, and k2 were the rate constants for clearance from compartment

1 (/day), translocation from compartment 1 to 2 (/day), and clearance from compartment 2 (/day), respectively. equation(2) dB1dt=−k1B1−k12B1  equation(3) dB2dt=k12  B1−k2 B2 (t=0,B1 =rA ; B2=0) The 2-compartment model B can be represented by a clearance from compartment 1 and reciprocal translocation between compartment 1 and 2 as shown in Eqs. (4) and (5), where k21 was the rate constant for translocation from compartment 1 to 2 (/day). equation(4) dB1dt=−k1B1−k12B1 +k21B2 equation(5) dB2dt=k12 B1−k21 B2 (t=0,  B1=rA;B2=0)The clearance/translocation rate constants, k, k1, k12, k2, and, k21 and the fraction of the administered TiO2 that reached the alveolar region, r, of each model were estimated by fitting the decay curve to the total TiO2 burden measured in the lungs including BALF. Curve fitting was conducted using a least squares approach, in which the following sum of square difference in the logarithmic converted lung burden between the measured lung burden (Bmeasured), and the estimated lung burden (B1 + B2) was minimized (Eq. (6)), using the Solver tool in Excel 2010.