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The main goal of this study was to evaluate the elemental changes occurring in the main rat organs (kidneys, spleen, heart, brain) as a result of polyethylene glycol-coated magnetic iron oxide nanoparticles (PEG-IONPs) administration. For this purpose, 24 animals were divided into four equinumerous groups, and the three of them were intravenously injected with PEG-IONPs dispersed in 15% solution of mannitol in dose of 0.03 mg of Fe per 1 kg of body weight. The organs were collected 2 h, 24 h and 7 days passing from NPs administration, respectively, for the 2H, 24H, and 7D experimental groups. The forth group of animals, namely control group, was injected with 1 mL of physiological saline solution. For the analysis of subtle elemental changes occurring in the organs after nanoparticles injection, highly sensitive method of total reflection X-ray fluorescence spectroscopy was used. Obtained results showed that administration of even such low doses of PEG-IONPs may lead to statistically significant changes in the accumulation of selected elements within kidneys and heart. Two hours and 7 days from NPs injection, the Fe level in kidneys was higher compared to that of control rats. Elevated levels of Cu, possibly associated with systemic action of ceruloplasmine enzyme, were found within kidneys in 24H and 7D groups, while in heart the similar observation was done only for 24H group. The levels of Ca and Zn increased in kidneys and heart during the first 2 h from the injection and were again elevated in these organs 7 days later. The abnormalities in Ca and Zn accumulations occurring exactly in the same manner may suggest that these elements may interplay either in the mechanisms responsible for the detoxification of the PEG-IONPs or pathological processes occurring as a result of their action.