Long-Term Clearance Kinetics of Inhaled Ultrafine Insoluble Iridium Particles from the Rat Lung, Including Transient Translocation into Secondary Organs

Abstract

Recently it was speculated that ultrafine particles (UFP) may translocate from deposition sites in the lungs to systemic circulation and whether long-term clearance differs between ultrafine and micrometer-sized particles. We have studied lung retention and clearance kinetics in 12 healthy male adult WKY rats up to 6 mo after an inhalation of ¹⁹²Ir-radiolabeled, insoluble, ultrafine 15- to 20-nm iridium particles. Whole-body retention was followed by external gamma counting, and particle clearance kinetics were determined by excretion radioanalysis. Four rats each were sacrificed after 3 wk and 2 and 6 mo; all organs as well as tissues and the carcass were radioanalyzed to balance the entire deposited radioactivity of the particles. The most prominant fraction was retained in the lungs at each time point of sacrifice (26%, 15%, 6%, respectively), and clearance out of the body was solely via excretion. Extrapulmonary particle uptake did not continue to increase but decreased with time in liver, spleen, heart, and brain when compared to previous data obtained during the first 7 days after inhalation (Kreyling et al., 2002). UFP long-term lung retention derived from whole-body measurements was comparable to previously reported data using insoluble micrometer-sized particles (Bellmann et al., 1994; Lehnert et al., 1989). In addition, differential analysis including daily excretion data revealed a pattern of fractional particle clearance rate of the ultrafine iridium particles similar to that of micrometer-sized particles reported by Snipes et al. (1983) and Bailey et al. (1985).