Subchronic Systemic Toxicity and Bioaccumulation of Fe₃O₄ Nano- and Microparticles Following Repeated Intraperitoneal Administration to Rats

Abstract

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 inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)

“…[1][2][3][4][5][6][7][8][9][10] We experimented with NPs of iron oxide Fe 3 O 4 (magnetite) having mean diameters 10 nm, 50 nm or 1 mcm, gold (4 nm or 50 nm), silver (4 nm, 49 nm or 1.1 mcm), copper oxide (20 nm or 340 nm), nickel oxide NiO (30 nm), and manganese oxide Mn 3 O 4 (32 nm). Keeping in mind the above mentioned theoretical premises of our research, we used purposefully prepared and accurately characterized NPs of pure metals or their oxides suspended in deionized water rather than commercial nanomaterials.…”

“…Keeping in mind the above mentioned theoretical premises of our research, we used purposefully prepared and accurately characterized NPs of pure metals or their oxides suspended in deionized water rather than commercial nanomaterials. Only iron oxide magnetite NPs were synthesized chemically [1][2][3] while in all other cases we used a technique of laser ablation of a 99.99% pure metal target in water followed by laser fragmentation for preventing particle aggregation. The main advantages of this technique are as follows: a) it provides nano-suspensions with a sufficiently narrow particle size distribution (examples are shown in Figures 1 and 2) and b) these suspensions are highly stable as a rule, maintaining their characteristics without any noticeable particle aggregation over periods sufficient for carrying out experiments described below.…”

“…During 2009-2014 our experimental work was focused on trying to find answers to these important questions. [1][2][3][4][5][6][7][8][9][10] Although in the vast nanotoxicological literature of the last decade studies concerned with the assessment of metal or metal-oxide NP toxicity are not at the top of the list, such publications are nevertheless quite numerous. To illustrate this, we may refer to several works devoted to NPs of the metals that were the subject-matter of our own studies considered below: iron oxide, [11][12][13][14][15][16][17][18][19][20] silver, gold, 24,[45][46][47][48][49][50][51][52][53][54][55][56][57][58] copper and copper oxide, 43,[59][60][61][62][63][64][65][66][67][68] nickel oxide, 65,…”

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

“…23 Size-dependent toxicity studies in vivo are less conclusive: systemic toxicity upon intraperitoneal application of 10 nm and 50 nm iron oxide particles was higher than that after dosing with 1000 nm particles. 24 When applied intraocularly however, 4000 nm magnetic iron oxide particles caused more toxicity than 50 nm particles. 25 It is also generally accepted that fiber-shaped NPs of a given material are more reactive and toxic compared with spherical particles: carbon nanotubes, for instance, are generally more toxic than fullerenes.…”

The nanotoxicology revolution

“…Relatively little data especially with respect to long-term exposures are available concerning biodistribution and toxicokinetics (Aggarwal et al 2009;Estevanato et al 2012;Menjoge et al 2010;Garza-Ocanas et al 2010;Katsnelson et al 2011). Meanwhile, some general principles have been convincingly demonstrated.…”