Repeated oral dose toxicity of iron oxide nanoparticles: biochemical and histopathological alterations in different tissues of rats.

Iron oxide (Fe2O3) nanoparticles are widely used in different fields of nanotechnology. However, studies on its toxicological effects in humans and the environment are scarce. Therefore in this investigation 28 days repeated dose oral toxicity studies were conducted on Fe2O3-30 nanoparticles and its counterpart Fe2O3-Bulk with special reference to target biochemical enzymes and histopathological changes in different tissues of female albino Wistar rats. The alterations observed after Fe2O3-30 treatment in various tissues of exposed rats were dose dependent. Low dose was less effective than medium and high doses with low dose demonstrating "no observed adverse effect" (NOAEL). Further, high dose treated rats showed toxic sign and symptoms but no mortality. Due to the repeated doses of Fe2O3-30 nanoparticles, significant inhibition was observed in total, Na(+)-K+, Mg2+ and Ca(2+)-ATPases in brain of exposed rats. Similarly, significant inhibition was recorded in RBC and brain acetylcholinesterase indicating that both synaptic transmission and nerve conduction were affected by this compound. Fe2O3-30 significantly increased aspartate amino transferase, alanine amino transferase and lactate dehydrogenase in serum and liver, whereas, these enzymes were significantly decreased in kidney indicating tissue necrosis and possible leakage of these enzymes into the blood stream. Increased levels of these enzymes in liver as well as in serum might be an adaptive mechanism due to the stress of iron nanoparticles. High dose treated rats of Fe2O3-30 showed dilated central vein, perivascular round cell collections in liver along with focal areas of necrosis, whereas kidney showed focal tubular damage and red pulp congestion, whereas prominent white pulp indices were observed in spleen. However, histopathological analysis of heart and brain tissues failed to show any adverse changes in their architecture exposed to repeated doses of Fe2O3-30 when compared with controls. Fe2O3-Bulk did not induce any adverse effects in either biochemical parameters or histopathology in the treated rats and the changes observed were near to controls and mostly insignificant, indicating that the counter part of nanoparticles i.e., bulk material is less potent than the nanoparticles in causing toxicity in the exposed animals. These results suggested that as particle size decreases, this iron nanoparticle showed increased toxicity, even though the same material is relatively inert in bulk form. The changes observed in these target enzyme activities could be useful as biomarkers of exposure to nanoparticles.