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A series of studies with iron oxides has been identified, in which the effects of iron oxide particles are examined in different biological systems. With one exception, iron oxide particles did not induce any cytotoxic effects when tested on different cell cultures:

Hanawa et al. (1992) examined the effects of iron(III) oxide (Fe2O3) and iron(II,III) oxide (Fe3O4) in human gingival fibroblast cells (5 g). No cytotoxicity was detected. Warswasky et al. (1994) isolated viable alveolar macrophages from hamster or rat trachea and thereafter, exposed them to iron(III) oxide particless (particle size: 98.9% ≤5 µm; 91.5% ≤ 1 µm; median 0.32 µm) at the concentrations of 0.05, 0.1 and 0.5 mg/plate, for 24 or 48 h. No effects were observed on the phagocytic activities of the alveolar macrophages.

Iron(III) oxide did not induce significantly lipid peroxidation in rabbit tracheal epithelium cells after exposure for 1 h at a concentration of 100 µg/cm2 (Guillianelli et al., 1996). However, in a previous study (Guillianelli et al., 1993) a 12% inhibition of the culture growth was observed at the concentration of 50 µg/cm2 (iron(III) oxide particles of 1 µm). Cytotoxicity occured probably via cell membrane damage. However, this effect is probably a particle effect and is not related with the chemical compositin of the particles. This is confirmed by the fact that cytotoxicity did not decrease by pretreatment with desferrioxamine (iron chelator), indicating that the oxidative stress observed is probably related to the particle itself and not to solubilized iron within the cell, i.e. to the chemical composition of the particles.


Human lung cells (A549) were exposed to Fe2O3 particles (1 µm) for 72 h at a concentration of 19.96 µg/ml (Garcon et al., 2001). Induction of oxidative stress was investigated via determination of several biochemical parameters. The results indicate that cell exposure to the iron oxide particles did not cause oxidative damage.

Peritoneal macrophages obtained from mice by lavage were exposed to Fe3O4 particles for 18 h at concentrations up to 150 µg/ml. Lactate dehydrogenase (LDH) and beta-glucuronidase (BGLU) levels were measured in the cell lysates. Iron(II,III) oxide had little effect on the release of these factors.

One in vivo study (Dorries et al., 1992) is also summarized under the present endpoint, examining the alveolar macrophage recruitment and phagocytic activities in hamsters, after inhlation or instillation of presumed non-toxic iron(III) oxide particles. The two methods are compared.