Tissue distribution of 20nm, 100nm and 1000nm fluorescent polystyrene latex nanospheres following acute systemic or acute and repeat airway exposure in the rat

Understanding tissue distribution and clearance of nanomaterials following different routes of exposure is needed for risk assessment. F344 female rats received single or multiple exposures to 20nm, 100nm or 1000nm latex fluorospheres by intravenous (i.v.) injection or oral pharyngeal aspiration into the airways. The presence of fluorospheres in tissues was assessed up to 90–120 days after the final dose. Blood, perfusion fluid, bone marrow, brain, eyes, feces, gut, heart, kidney, liver, lung, muscle, skin, spleen, thymus, tongue, urine and uterus plus ovaries were collected for analysis. Liver, spleen and lung were the greatest tissue depots for all particles following i.v. injection. The proportion of 100nm and 1000nm but not 20nm spheres significantly increased in the spleen over time. Lung was the greatest tissue depot for all particles following single or repeat airway exposure. Greater than 95% of 1000nm spheres that were recovered were in the lung in contrast to 70–80% of 20nm spheres or 89–95% of 100nm spheres. All 3 sizes were found in gut or gut+feces 1–7 days after lung exposure. The thymus was the largest extra-pulmonary depot for the particles; up to 25% of recovered 20nm particles were in the thymus up to 4 months after exposure compared to 6% of 100nm particles and 1–3% of 1000nm particles. A small proportion of 20nm particles were detected in kidney following both acute and repeat airway exposure. Low numbers of particles were found in the circulation (blood, perfusion), bone marrow, brain, heart, liver and spleen but not in eye, muscle, skin, tongue, ovaries, uterus or urine. These data show that the tissue targets of nano- and micron-sized spheres are very similar whether exposure occurs systemically or via the airways while the proportion of particles in some tissues and tissue clearance varies based on particle size.