Subchronic systemic toxicity and bioaccumulation of Fe3O4 nano- and microparticles following repeated intraperitoneal administration to rats.

Aqueous suspensions of 10 nm, 50 nm, or 1 µm Fe(3)O(4) particles were injected intraperitoneally (ip) to rats at a dose of 500 mg/kg in 4 mL of sterile deionized water 3 times a week for 5 weeks. Following exposure, functional and biochemical indices and histopathological examinations of spleen and liver tissues of exposed rats were evaluated for signs of toxicity. The iron content of the blood was measured photometrically, and that of the liver and the spleen by atomic adsorption spectroscopy (AAS) and electron paramagnetic resonance (EPR) methods. It was found that, given equal mass doses, Fe(3)O(4) nanoparticles possess considerably higher systemic toxicity than microparticles, but within the nanometric range the relationship between particle size and resorptive toxicity is intricate and nonunique. The latter fact may be attributed to differences in different nanoparticles' toxicokinetics, which are controlled by both more or less substantial direct penetration of nanoparticles through biological barriers and their unequal solubility.

Some peculiarities of pulmonary clearance mechanisms in rats after intratracheal instillation of magnetite (Fe3O4) suspensions with different particle sizes in the nanometer and micrometer ranges: are we defenseless against nanoparticles?

We studied differences between phagocytic responses to nanoparticles (NPs) versus microparticles in the pulmonary region by synthesizing magnetite of different sizes and instilling suspensions of these particles intratracheally into rats' lungs. Ten and 50 nm particles caused a greater increase in cell counts of the bronchoalveolar lavage fluid (BALF) than the instillation of microparticles. The response to 10 nm particles was weaker than to 50 nm ones, and the smaller NPs were more cytotoxic; both were more cytotoxic than the microparticles. Phagocytic activity was also studied using optical and atomic force microscopy. Phagocytes were more "loaded" in the lungs instilled with 10 nm particles as compared with those instilled with 50 nm particles; NPs of both sizes were engulfed more avidly than microparticles. We found in a separate comparative experiment that magnetite NPs were more cytotoxic than titanium dioxide and quartz suspensions having particle size distribution typical of industrial dusts.